Humulin-Ca-Pm

PRODUCT MONOGRAPH
HUMULIN® R
(insulin, human biosynthetic)
Solution for Injection, 100 units/mL
ATC Code: A10AB01
fast-acting
HUMULIN® N
(insulin isophane, human biosynthetic, rDNA origin)
Suspension for Injection, 100 units/mL
ATC Code: A10AC01
intermediate-acting
HUMULIN® 30/70
(30% insulin injection, 70% insulin isophane, human biosynthetic, rDNA origin)
ATC Code: A10AD01
intermediate- or long-acting combined with fast-acting
THERAPEUTIC CLASSIFICATION
Anti-Diabetic Agent
 Eli Lilly Canada Inc. Date of Initial Approval:

Exchange Tower January 11, 1983
130 King Street West, Suite 900
P.O. Box 73 Date of Revision:
Toronto, Ontario May 24, 2021
M5X 1B1
Control № 245812
HUMULIN Product Monograph Page 1 of 54

Table of Contents
PART I: HEALTH PROFESSIONAL INFORMATION...................................................... 3

SUMMARY PRODUCT INFORMATION..................................................................... 3
INDICATIONS AND CLINICAL USE .......................................................................... 3
CONTRAINDICATIONS............................................................................................... 4
WARNINGS AND PRECAUTIONS.............................................................................. 4
ADVERSE REACTIONS ............................................................................................... 9
DRUG INTERACTIONS ............................................................................................... 9
DOSAGE AND ADMINISTRATION .......................................................................... 10
OVERDOSAGE ........................................................................................................... 12
ACTION AND CLINICAL PHARMACOLOGY ......................................................... 12
STORAGE AND STABILITY ..................................................................................... 13
SPECIAL HANDLING INSTRUCTIONS.................................................................... 14
DOSAGE FORMS, COMPOSITION AND PACKAGING........................................... 14
PART II: SCIENTIFIC INFORMATION ........................................................................... 15

PHARMACEUTICAL INFORMATION ...................................................................... 15
CLINICAL TRIALS ..................................................................................................... 16
DETAILED PHARMACOLOGY ................................................................................. 17
TOXICOLOGY ............................................................................................................ 18
REFERENCES ............................................................................................................. 20
PART III: CONSUMER INFORMATION.......................................................................... 25

HUMULIN® R
(insulin, human biosynthetic)
HUMULIN® N
(insulin isophane, human biosynthetic, rDNA origin)
HUMULIN® 30/70
(30% insulin injection, 70% insulin isophane, human biosynthetic, rDNA origin)
PART I: HEALTH PROFESSIONAL INFORMATION
SUMMARY PRODUCT INFORMATION
Route of Dosage Form / Nonmedicinal Ingredients

Administration Strength
Parenteral Solution for Injection/ HUMULIN R (Regular): Glycerol, m-cresol, water
100 units/mL for injection, hydrochloric acid and sodium
hydroxide.
HUMULIN-N (NPH) and HUMULIN 30/70 also
Suspension for
contain phenol, zinc oxide, protamine sulfate and
Injection/ 100 dibasic sodium phosphate.
units/mL
INDICATIONS AND CLINICAL USE
HUMULIN (insulin, human biosynthetic) is indicated for the treatment of insulin requiring
diabetic patients.
HUMULIN-R only should be used for the treatment of emergencies such as diabetic coma and
pre-coma and in diabetics undergoing surgery, but not HUMULIN-N, or HUMULIN
MIXTURES.
In switching patients from animal source insulins to HUMULIN, it is possible that the patients
will require a change in dosage; the adjustment may be made with the first dose or over a period
of several weeks. Any change of insulin should be made cautiously and only under medical
supervision.
Changes in refinement, purity, strength, brand, type and/or method of manufacture (recombinant
DNA versus animal source insulin) may result in the need for a change in dosage.

CONTRAINDICATIONS
HUMULIN (insulin, human biosynthetic) is contraindicated during episodes of hypoglycemia.
HUMULIN is contraindicated in patients with hypersensitivity to human insulin or any of its

excipients contained in the formulation (unless used as part of a desensitization program).
HUMULIN-N, HUMULIN MIXTURES, should not be given intravenously or used for treatment
of diabetic coma.
WARNINGS AND PRECAUTIONS
General
Serious Warnings and Precautions
Hypoglycemia is the most common adverse effect of insulin products. Glucose monitoring
should be performed for all patients with diabetes mellitus treated with insulins. Uncorrected
hypoglycemic or hyperglycemic reactions can cause loss of consciousness, coma or even death
(see OVERDOSAGE, Symptoms and Treatment).
Any transfer of HUMULIN or HUMULIN MIXTURES should be made cautiously and only
under medical supervision (see DOSAGE AND ADMINISTRATION).
Fast-acting insulins should be combined with a longer-acting insulin or insulin infusion pump
therapy to maintain adequate glucose control (see DOSAGE AND ADMINISTRATION).
HUMULIN and HUMULIN MIXTURES should not be mixed with any other insulin unless
clearly indicated and done under medical supervision (see DOSAGE AND
ADMINISTRATION).
Under no circumstances should any HUMULIN MIXTURE be given intravenously.

Do not use the HUMULIN-N or HUMULIN MIXTURES if you see lumps that float or that stick
to the sides of the vial, or if the contents of the vial are clear and remain clear after the bottle is
shaken or rotated. NOTE: The contents of the vial or cartridge of HUMULIN-R should be clear.
Do not use if cloudy.
A few patients who experienced hypoglycemic reactions after being transferred to HUMULIN
(insulin, human biosynthetic) have reported that these early warning symptoms were less
pronounced than they were with animal-source insulin.
As with all insulin therapies, the duration of action of HUMULIN and HUMULIN MIXTURES
may vary in different individuals or in the same individual according to dose, injection site, blood
flow, temperature and level of physical activity.

Hypokalemia is among the potential clinical adverse effects associated with the use of
HUMULIN and all other insulin therapies. This potential clinical adverse effect may be relevant
in patients who are on potassium lowering drugs or losing potassium through other means (e.g.
diarrhea).
Stress or concomitant illness, especially infectious and febrile conditions may change insulin
requirements. In these instances, patients should contact their physician and carefully control
their blood glucose (see Part III – Consumer Information).
To avoid transmission of disease, a cartridge or prefilled syringe should not be used by more than
one person.
The number and size of daily doses and the time of administration, as well as diet and exercise,
are problems that require direct and continuous medical supervision. Usually, the most
satisfactory injection time is before breakfast.
Insulin plus Thiazolidinediones (TZDs): TZDs, alone or in combination with other antidiabetic
agents (including insulin), can cause heart failure and edema. The combination of insulin with a
TZD is not indicated for the treatment of type 2 diabetes mellitus. Please refer to the respective
TZD product monograph Warnings and Precautions information when the use of these drugs in
combination with any insulin, including HUMULIN R, HUMULIN N or HUMULIN 30/70, is
contemplated.
Changes in Insulin Regimen / Transferring Patients from Other Insulins
When patients are transferred between different types of insulin products, including animal
insulins, the early warning symptoms of hypoglycemia may change or become less pronounced
than those experienced with their previous insulin. Transferring a patient to a new type or brand
of insulin should be done only under strict medical supervision.
Changes in insulin regimen, strength, timing of administration, manufacturer, type (e.g., regular,
NPH, or insulin analogs), or method of manufacture (recombinant DNA versus animal source
insulin) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Make
any changes to a patient's insulin regimen under close medical supervision with increased
frequency of glucose monitoring. Changes in insulin dose or an adjustment in concomitant oral
antidiabetic treatment may be needed. If an adjustment is needed, it may be done with the first
doses or during the first few weeks or months and under medical supervision (see WARNINGS
AND PRECAUTIONS).
Carcinogenesis and Mutagenesis
Human insulin is produced by recombinant technology. No serious events have been reported in
subchronic toxicology studies. Human insulin was not mutagenic in a battery of in vitro and in
vivo genetic toxicity assays (see TOXICOLOGY).

Endocrine and Metabolism
Hypoglycemia
Hypoglycemia is the most frequently occurring undesirable effect of insulin therapies, including
HUMULIN. Severe hypoglycemia can result in temporary or permanent impairment of brain
function and death (see ADVERSE REACTIONS).
Hypoglycemia may occur if the insulin dose is too high in relation to the insulin requirement (see
OVERDOSAGE).
Hypoglycemia can occur regardless of the type of insulin taken and may cause fatigue, sweating,
heart palpitations, disturbed behaviour, hunger, convulsions or loss of consciousness. In extreme
circumstances, even death can occur without recognizable symptoms.
In certain cases (e.g., long duration of diabetes mellitus, diabetic nerve disease, intensified
diabetes mellitus control, patients with psychiatric illness, elderly patients or use of medications
such as beta blocking agents), the nature and intensity of early warning symptoms of
hypoglycemia (pallor, sweating, anxiety, headache, tachycardia, hunger) may change or be less
pronounced.
Hypoglycemic reactions following treatment with HUMULIN are mostly mild and easily
managed.
Changes in insulin therapy or changes in life style (i.e., diet, exercise/physical activity) may
require a change in dosage to avoid hypoglycemia. Omission of a meal or unplanned strenuous
physical exercise may lead to hypoglycemia.
Glucose monitoring is recommended for all patients with diabetes mellitus who are also taking
HUMULIN or other insulin products (see Monitoring and Laboratory Tests).
The patient’s ability to concentrate and react may be impaired as a result of hypoglycemia. This
may constitute a risk in situations where these abilities are of special importance (e.g., driving a
car or operating machinery) especially in those who have reduced or absent awareness of the
warning signs of hypoglycemia or have frequent episodes of hypoglycemia.
Diabetic patients should be instructed to carry a few lumps of sugar, candies or biscuits to
prevent the progression of a hypoglycemic reaction, should one occur (see Part III, CONSUMER
INFORMATION).
Hyperglycemia
Inadequate dosing or discontinuation of HUMULIN, especially in type 1 diabetes mellitus, may

lead to hyperglycemia and when untreated, hyperglycemic events may eventually lead to diabetic
ketoacidosis or coma which are potentially fatal. Usually the first symptoms of hyperglycemia
develop gradually over a period of hours or days. They include polydipsia; polyuria; nausea;
abdominal pain, vomiting; drowsiness; blurred vision, flushed dry skin; loss of appetite, weight
loss as well as acetone odour of breath (see ADVERSE REACTIONS).

Ability to concentrate and react may be impaired as a result of hyperglycemia or as a result of
hyperglycemia-induced visual impairment. This may constitute a risk in situations where these
abilities are of special importance such as driving a car or operating machinery.
Hepatic/Biliary/Pancreatic
Insulin requirements may be decreased in the presence of hepatic impairment.
Immune
Injection Site and Local Allergic Reactions:
With insulin therapies including HUMULIN, patients may experience redness, swelling, pain,
inflammation, or itching at the site of injection (see ADVERSE REACTIONS). Prompt
recognition and appropriate management of the allergic complications of insulin therapy are
important for the safe and effective control of diabetes mellitus.
Most of these minor reactions usually resolve in a few days to a few weeks. They may occur if
the injection is not properly made (irritants in the skin cleansing agent or poor injection
technique), or if the patient is allergic to the insulin or any excipients (see
CONTRAINDICATIONS). Continuous rotation of the injection site within a given area may help
to reduce or prevent these reactions.
Lipodystrophy and Cutaneous Amyloidosis
Subcutaneous (SC) administration of insulin products including HUMULIN can result in

lipoatrophy (depression in the skin), lipohypertrophy (enlargement or thickening of tissue), or
localized cutaneous amyloidosis (skin lumps). Patients should be advised to consult their doctor
if they notice any of these conditions. Continuous rotation of the injection site within a given
area may help reduce or prevent these reactions.
Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have
been reported to result in hyperglycemia; and a sudden change in the injection site (to an
unaffected area) has been reported to result in hypoglycemia.
Systemic Allergic Reactions:
Systemic allergic reactions have rarely occurred with insulin treatments including HUMULIN.
These reactions may be characterized by a generalized rash (with pruritus), shortness of breath,
wheezing, angioneurotic edema and drop in blood pressure (see ADVERSE REACTIONS).
Severe cases of generalized allergy including anaphylactic reaction may be life threatening (see
CONTRAINDICATIONS).
Antibody Production:
Immune responses can occur with insulin products, including production of auto antibodies
(IgG). In general, glycemic control is not affected by the presence of auto antibodies. Very

rarely, auto antibodies may cause hyperglycemia (insulin resistance) or hypoglycemia
(inappropriate release). Insulin antibodies are frequently cross-reactive. Patients who have
demonstrated an allergic reaction to other insulin products may demonstrate an allergic reaction
to HUMULIN.
Renal
Insulin requirements may be decreased in the presence of renal impairment.
Reproduction Studies
There are no adequate and well-controlled studies with HUMULIN during pregnancy and
lactation (see TOXICOLOGY).
Information for Patients
Patients should be informed about potential advantages and disadvantages of HUMULIN

therapy, including possible side effects. Patients should also be offered continued education and
advice on insulin therapies, delivery device options, life-style management, self-monitoring,
complications of insulin therapy, timing of dosage, and instruction for use of injection devices,
storage of insulin, travelling and others (see PART III: CONSUMER INFORMATION).
Female patients with diabetes mellitus should be advised to inform their doctor if they are
pregnant or are contemplating pregnancy. Careful monitoring of glucose control, as well as
general health is essential in pregnant patients with diabetes (see Special Populations and PART
III: CONSUMER INFORMATION).
Special Populations
Pregnant Women
HUMULIN may be used in pregnancy, if clinically indicated. It is essential to maintain good

glucose control in both gestational diabetes and throughout pregnancy in type 1 and type 2
patients. Insulin requirements usually decrease during the first trimester and increase during the
second and third trimesters.
Patients with diabetes should be advised to inform their doctors if they are pregnant or are
contemplating pregnancy.
Nursing Women
Diabetic patients who are nursing may require adjustments in insulin dose and/or diet.
Pediatrics (<18 years of age)
HUMULIN may be used in children and adolescents, if clinically indicated.

Geriatrics (>65 years of age)
HUMULIN may be used in elderly patients, if clinically indicated.
Monitoring and Laboratory Tests
Self-Monitoring of Blood Glucose
With insulin therapy, including HUMULIN, the need for regular blood glucose self-monitoring
should be considered to obtain optimal glycemic control (see PART III: CONSUMER
INFORMATION). Glycosylated hemoglobin should be measured every 3 to 4 months in all
patients taking insulin products.
ADVERSE REACTIONS
Body as a Whole – Allergic reaction(s)
Local allergy in patients may occur as redness, swelling, or itching at the site of injection. These
minor reactions usually resolve in a few days to a few weeks. In some instances, these reactions
may be related to factors other than insulin, such as irritants in the skin cleansing agent or poor
injection technique.
Systemic allergy to insulin is less common but potentially more serious. Generalized allergy to
insulin may cause rash over the whole body, shortness of breath, wheezing, reduction in blood
pressure, rapid pulse or sweating. Severe cases of generalized allergic reaction may be life-
threatening.
Skin and appendages – Lipodystrophy
Insulin lipohypertrophy has been reported with HUMULIN. This complication has been ascribed
to the local pharmacologic effects of the subcutaneous injection of insulin. A few cases of
lipoatrophy and serum sickness have also been reported.
Metabolic – Hypoglycemia; Insulin resistance
Hypoglycemia is the most frequent undesirable effect of insulin therapy that a patient with
diabetes may suffer. Severe hypoglycemia may lead to loss of consciousness and, in extreme
cases, death.
DRUG INTERACTIONS
Drug-Drug Interactions
Insulin requirements may be decreased in the presence of agents such as oral antidiabetic
medications, salicylates, sulfa antibiotics, certain antidepressants (monoamine oxidase

inhibitors), beta-adrenergic blockers, alcohol, angiotensin converting enzyme inhibitors,
angiotensin II receptor blockers and anabolic steroids.
Drugs that may increase insulin requirements include oral contraceptives, thiazides,
glucocorticosteroids, thyroid hormones, sympathomimetics and danazol. The hypoglycemic
action of insulin may also be antagonized by diphenylhydantoin.
Insulin requirements can be increased, decreased, or unchanged in patients receiving diuretics.
Hormones that tend to counteract the hypoglycemic effects of insulin include growth hormone,
corticotropin, glucocorticoids, thyroid hormone, and glucagon. Epinephrine not only inhibits the
secretion of insulin, but also stimulates glycogen breakdown to glucose. Thus, the presence of
such diseases as acromegaly, Cushing's syndrome, hyperthyroidism, and pheochromocytoma
complicate the control of diabetes.
Insulin plus Thiazolidinediones (TZDs): To avoid the risk of developing new or worsening heart
failure, the use of TZDs in combination therapy with insulin is not indicated (see WARNINGS
AND PRECAUTIONS).
Drug-Lifestyle Interactions
Hypoglycemia may occur as a result of an excess of insulin relative to food intake, energy
expenditure, or both. Omission of a meal or unplanned strenuous physical exercise may lead to
hypoglycemia (see WARNINGS AND PRECAUTIONS and OVERDOSAGE).
DOSAGE AND ADMINISTRATION
Dosing Considerations
New Patients:
Patients receiving insulin for the first time can be started on HUMULIN (insulin, human
biosynthetic) in the same manner as they would be on animal-source insulin.
Patients should be monitored closely during the adjustment period.
Transfer Patients:
When transferring patients from animal-source insulin to HUMULIN, use the same dose and
dosage schedule.
Some patients transferring to HUMULIN will require a change in dosage from that used with
animal-source insulin. If an adjustment is needed, it may be made with the first dose or over a
period of several weeks.
Changes in total daily dosage, the number of injections per day, and/or timing of injections may
be necessary to achieve maximum glycemic control.

When a patient on high doses of animal insulin is switched to HUMULIN, it may be appropriate
to reduce the starting dosage and monitor the patient carefully.
Patients who have systemic allergy to pork or beef insulin may also react to human insulin. In
such patients, appropriate procedures (intradermal testing and, if necessary, desensitization)
should be undertaken before therapeutic doses of human insulin are administered.
A few patients who experienced hypoglycemic reactions after being transferred to HUMULIN
have reported that the early warning symptoms, i.e., nervousness, sweating, and palpitations,
were less pronounced than they were with animal-source insulin.
Formulations of HUMULIN appear to produce a slightly faster onset and slightly shorter duration
of action than the corresponding forms of animal-source insulins.
Recommended Dose and Dosage Adjustment
The dosage should be determined by the physician, according to the requirements of the patient.
HUMULIN-R is a clear, colourless solution. It may be administered by subcutaneous, intra-

muscular or intravenous injection.
HUMULIN-N and HUMULIN MIXTURES are suspensions. They should be administered by

subcutaneous injection only.
Subcutaneous administration, preferably by the patient, should be in the upper arms, thighs,
buttocks or abdomen. Injection sites should be rotated so that the same site is not used more than
approximately once a month, in order to reduce the risk of lipodystrophy and localized cutaneous
amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis.
Care should be taken to ensure that a blood vessel has not been entered. The injection site should
not be massaged.
Administration
Mixing Instructions:
The fast action of HUMULIN-R is preserved when mixed with HUMULIN-N; independent of
the time lag between mixing and administration, and independent of the proportion of regular
insulin incorporated in the mixture.
The effects of mixing HUMULIN with animal-source insulins have not been studied. This
practice is not recommended.
Instructions for Use/Handling
To prevent the possible transmission of disease, never share a HUMULIN R, HUMULIN N, or

HUMULIN 30/70, cartridge or pen, between patients even if the needle on the delivery device is
changed.

OVERDOSAGE
Hypoglycemia (low blood glucose, also called "insulin reaction") can occur if the patient takes
too much insulin, misses meals, exercises or works too hard just before a meal, or has an
infection or becomes ill (especially with diarrhea or vomiting) or if the body's need for insulin
change for other reasons.
Symptoms and Treatment
Hypoglycemia may occur in any patient receiving insulin and is most commonly manifested by
hunger, nervousness, warmth and sweating, and palpitations. Patients also may experience
headache, confusion, drowsiness, fatigue, anxiety, blurred vision, diplopia, or numbness of the
lips, nose, or fingers. The clinical manifestations of hypoglycemia can be masked by the
concomitant administration of propranolol or other beta adrenergic blockers.
If a patient is unable to take soluble carbohydrate or fruit juice orally, hypoglycemia is treated
with 10 to 20 g of dextrose intravenously or glucagon may be given subcutaneously or
intramuscularly.
For management of a suspected drug overdose, contact your regional Poison Control Centre.
ACTION AND CLINICAL PHARMACOLOGY
Insulin, human biosynthetic, is a polypeptide hormone consisting of a 21 amino acid A-chain and
a 30 amino acid B-chain linked by two disulfide bonds. HUMULIN (insulin, human
biosynthetic) is found to be chemically, physically, biologically and immunologically equivalent
to pancreatic human insulin which differs slightly from porcine or bovine insulin in amino acid
composition.
Studies indicate that immunogenicity problems with biosynthetic human insulin (BHI) produced
by recombinant DNA technology are less likely than with insulin that is derived from animal
origin. Biosynthetic human insulin is devoid of all protein contaminants of pancreatic origin
normally present in trace amounts in all insulins of pancreatic origin. The purification procedures
used in the manufacture of biosynthetic human insulin result in a product which contains an
insufficient quantity of E. coli polypeptides to be antigenic in deliberately sensitized animals. No
antibodies to E. coli polypeptides have been detected in specifically designed radioimmunoassay
methods examining patient serum samples.
Mechanism of Action
The administration of suitable doses of insulin to patients with diabetes mellitus, along with
controlled diet and exercise, temporarily restores their ability to metabolize carbohydrates, fats
and proteins; to store glycogen in the liver; and to convert glucose to fat. When given in suitable
doses at regular intervals to a patient with diabetes mellitus, the blood sugar is maintained within

a reasonable range, the urine remains relatively free of sugar and ketone bodies, and diabetic
acidosis and coma are prevented.
Pharmacodynamics
The primary activity of human insulin is the regulation of glucose metabolism. In addition,
insulin has several anabolic and anti-catabolic actions on many tissues in the body. In muscle
and other tissues (except the brain), insulin causes rapid transport of glucose and amino acids
intracellularly, promotes anabolism, and inhibits protein catabolism. In the liver, insulin
promotes the uptake and storage of glucose in the form of glycogen, inhibits gluconeogenesis,
and promotes the conversion of excess glucose into fat.
HUMULIN-R, insulin injection, human biosynthetic (rDNA Origin) REGULAR is a fast-acting

insulin. The duration of action of HUMULIN-R is between 6 and 8 hours.
HUMULIN-N, insulin isophane, human biosynthetic (rDNA Origin) NPH is an intermediate-

acting insulin with a slower onset of action than Regular insulin and a longer duration of activity
of up to 24 hours.
HUMULIN MIXTURE, insulin injection, insulin isophane, human biosynthetic (rDNA Origin)
30/70 is an intermediate-acting insulin combined with a fast-acting insulin. HUMULIN
MIXTURE has a more rapid onset of action than NPH alone and a duration of activity of up to 24
hours.
Pharmacokinetics
Insulin preparations differ in onset, peak and duration of action. Individual variations of blood
glucose response profiles are dependent upon factors such as the size of dose, site of injection and
physical activity of the patient (for all human insulin formulations). The addition of protamine to
insulin, in the presence of zinc, produces a stable complex with less intense and more prolonged
action, due to its slow dissolution.
HUMULIN-N may be mixed with HUMULIN-R to meet individual metabolic requirements of

the patient as determined by the physician.
STORAGE AND STABILITY
Prior to first use insulin should be stored in a cold place (2-8C), preferably in a refrigerator, but
not in a freezer. Do not let it freeze or leave it in direct sunlight. Expiration dates are stated on
the labels.
When in current use, vials, cartridges and prefilled pens should be stored at room temperature and
discarded after 28 days.

SPECIAL HANDLING INSTRUCTIONS
See Part III CONSUMER INFORMATION for injection procedures for vials and instructions for
use of cartridges/ pens. Also refer to the User Manual for HUMULIN KwikPen.
DOSAGE FORMS, COMPOSITION AND PACKAGING
HUMULIN is available in the following presentations:
HUMULIN R, insulin injection, human biosynthetic (rDNA Origin) REGULAR:

 Vial HI0210, 10 mL, 100 units/mL.
 Cartridge HI0219, 3.0 mL, 100 units/mL, 5 cartridges/box.
HUMULIN R KwikPen, insulin injection, human biosynthetic (rDNA Origin) REGULAR:

 Cartridge and Pen HP8804, 3.0 mL prefilled pen, 100 units/mL, 5 pens/box.
HUMULIN N, insulin isophane, human biosynthetic (rDNA Origin) NPH:

 Cartridge HI0319, 3.0 mL, 100 units /mL, 5 cartridges/box.
HUMULIN N KwikPen, insulin isophane, human biosynthetic (rDNA Origin) NPH:

 Cartridge and Pen HP8805, 3.0 mL prefilled pen, 100 units/mL, 5 pens/box.
HUMULIN 30/70, 30% insulin injection, 70% insulin isophane, human biosynthetic (rDNA
Origin):
 Cartridge HI0719, 3.0 mL, 100 units/mL, 5 cartridges/box.
HUMULIN cartridges are designed for use with Lilly injector systems.
Not all pack sizes and presentations may be marketed.

PART II: SCIENTIFIC INFORMATION
PHARMACEUTICAL INFORMATION
Drug Substance
HUMULIN (insulin, human biosynthetic) is a polypeptide hormone consisting of a 21 amino acid

A-chain and a 30 amino acid B-chain linked by two disulfide bonds. It is synthesized in a non-
disease-producing special laboratory strain of E. coli that has been genetically altered by the
addition of the human gene for insulin production.
Molecular formula: C H N O S
257 383 65 77 6
Molecular weight: 5807.72.
Structural formula:

CLINICAL TRIALS
New Patient Studies
One hundred and twenty nine (129) insulin naive patients were treated for one year. Dramatic,
albeit expected, improvement of metabolic control followed institution of biosynthetic human
insulin (BHI). Insulin antibody binding was measured and compared with results obtained from
a well-matched group of historical controls on animal insulins. BHI was less immunogenic than
modified beef pork (MBP) or purified pork insulin (PPI). The possible reasons that BHI is ever
immunogenic in humans are (1) the fact that BHI is given subcutaneously and (2) the presence of
insulin aggregates.
Transfer Patient Studies
In a double-blind, double-crossover study, patients were switched from beef-insulin to PPI or

BHI and then back again; patients on BHI had modestly higher fasting blood sugars. Moreover,
the A.M. dose of BHI could be administered closer to breakfast than was possible with animal-
sourced insulins.
In another double-blind study, patients were switched either to BHI or maintained on their PPI or
MBP insulin. Patients switched from MBP or PPI to BHI had slightly higher fasting and/or
postprandial blood sugars than control groups which were maintained on their prestudy animal
insulin programs. Patients switched from MBP to BHI demonstrated clear reductions in their
serum insulin antibody binding. Patients switched from PPI to BHI demonstrated significantly
less insulin binding at six months after transfer; at 24 months, bound insulin was essentially the
same for both groups.
The immune responses of a subset of 142 of 427 transfer patients have been statistically
analyzed. These patients had been randomly allocated to treatment with BHI, PPI or MBP.
Taking type of diabetes into account, this study confirmed that BHI was the least immunogenic.
Use of BHI in Patients with Complications of Insulin Therapy:
In isolated instances where patients were experiencing insulin allergy or resistance to insulin
therapy, BHI has been used with limited success.
There are isolated case reports in which patients with the complications of insulin therapy,
principally lipoatrophy, insulin allergy and insulin resistance, have been treated with BHI.
Overall, the clinical studies indicate that BHI is an effective, safe insulin both in patients
receiving insulin for the first time and in patients being switched from animal insulin. However,
BHI appears to be shorter acting than animal insulin. The data from these studies are not
sufficient to determine whether BHI is superior to PPI in the prevention or treatment of
complications of insulin therapy. However, HUMULIN (insulin, human biosynthetic) was
shown to be less immunogenic than mixed beef-pork insulin or purified pork insulin.

DETAILED PHARMACOLOGY
Preclinical Pharmacology
Biosynthetic human insulin (BHI) has been studied extensively. In nearly all the studies, BHI
was compared with native pancreatic human insulin as well as with purified pork insulin. The
resulting data clearly indicate that BHI is chemically, physically, biologically and
immunologically equivalent to the appropriate pancreatic insulin standards. BHI is prepared by
the proinsulin route, starting with an E. coli fermentation using recombinant DNA-containing
plasmids. The amino acid sequences of the insulin chains were found to be correct and the
disulfide bonds were shown to be in the proper configuration. Additional chemical and physical
studies verified that the normal structure of the human insulin molecule was integrally formed by
the proinsulin process.
Further confirmation that BHI is structurally identical to pancreatic human insulin was provided
by radioimmunochemical assays for insulin. BHI and pancreatic human insulin reacted
identically in the insulin radioimmunoassay, a method that is sensitive to minor structural
variations within the insulin molecule.
The biological activity of BHI was evaluated by a wide variety of in vitro techniques, all of
which demonstrated that BHI and pancreatic human insulin are equivalent within experimental
error. In addition, BHI was found to have a hypoglycemic potency equivalent to purified
pancreatic insulins as determined by the USP rabbit assay.
BHI did not elicit an antigenic response when administered to E. coli polypeptide-sensitized rats
and guinea pigs. In a clinical experiment, it was demonstrated that the anti- E. coli polypeptide
antibody levels in 20 new diabetic patients were the same regardless of whether the treatment was
with BHI or purified pork insulin.
No antibodies specific to E coli polypeptide have been detected in patient serum samples from
over 1,350 patients.
Clinical Pharmacology
Clinical pharmacologic studies with, biosynthetic human insulin (rDNA) demonstrate that
generally the pharmacokinetics and pharmacodynamics of BHI and purified pork insulin (PPI)
are the same. However, serum concentrations after BHI is administered subcutaneously may be
higher or occur sooner than after PPI. These differences are generally ascribed to the greater
solubility of BHI, which apparently is related to the presence of threonine instead of alanine on
the B-30 position of the molecule.
A 30/70 Regular/NPH mixture produced the same effect as equivalent doses of the two
formulations administered separately. Mixtures of NPH and Regular BHI have demonstrated a
slight excess of protamine in NPH BHI which binds to added Regular insulin, and that this
binding delays slightly the occurrence of the peak serum concentration. Effects of BHI on
substrates and other non-insulin and glucose parameters have been studied. Most investigators

have reported that the suppression of endogenous insulin as indicated by serum C-peptide values
was equivalent for BHI and PPI.
Growth hormone (GH) increase was also equivalent or slightly less with BHI. Prolactin response
was less after BHI than with PPI, while the cortisol response to insulin hypoglycemia may be
greater with BHI than with PPI. There was no difference in non-esterified fatty acid lowering or
blood glycerol, lactate, or 3-hydroxybutyrate levels between BHI and PPI.
While the effects of BHI on suppression of human C-peptide usually are the same as those for
PPI, BHI may affect other variables differently than PPI. Further studies will be needed to
determine the significance of differences between BHI and PPI on prolactin, GH, and glucagon
concentrations.
TOXICOLOGY
As with pork insulin, biosynthetic human insulin will be mainly used by subcutaneous injection
in humans and, therefore, the majority of studies in animals have been performed using this route
of administration. However, acute toxicity studies in monkeys and a subchronic study in dogs
were performed using intravenous administration. The experiments for acute toxicity are
presented in Table 1 and for subacute toxicity in Table 2 and are summarized as follows:
 The selection of dose levels of human insulin for the single and multiple dose studies in
animals was restricted by the potent hypoglycemic activity of this compound. The
pharmacological effects of insulin are well-known from many years of human therapy and
therefore the toxicological studies were designed to evaluate adverse effects of possible
impurities such as E. coli polypeptides.
 The minimal lethal subcutaneous dose of biosynthetic human insulin in rats and mice was
greater than 10 units/kg. This dose was a large multiple of the initial human clinical trial dose
and also much greater than the average daily therapeutic dose of insulin (0.6 units/kg/day).
 Dogs given a single subcutaneous dose of 2 units/kg or an intravenous dose of 0.1 unit/kg of
human insulin evidenced hypoglycemia and related pharmacological effects but no significant
toxicity.
 No compound-related toxic effects were observed when rats were given daily subcutaneous
injections of 2.4 units/kg of biosynthetic human insulin for one month. Similarly, beagle
dogs given daily subcutaneous injections of 2 units/kg or intravenous injections of 0.1 unit/kg
of human insulin for one month evidenced marked hypoglycemia, but no adverse effects were
seen on hematologic or serum chemistry parameters and there were no pathologic changes.
There was no evidence of tissue damage or irritation at the site of injection in the rats or dogs.
 Biosynthetic human insulin gave negative results in the Modified Ames, Rat Hepatocyte, and
Chinese Hamster mutagenicity tests.
It can be concluded that injections of pharmacologically effective doses of biosynthetic human

insulin in animals did not produce toxic effects. There were no findings that would preclude the
use of this compound in humans.

Table 1. Acute Toxicity
Species Number Route Single Duration Observations

Per Dose Dose (Days)
Rats 10 females SC 10 IU/kg 14 No mortality. Minimum lethal dose

10 males > 10 IU/kg.
Mice 10 females SC 10 IU/kg 14 No mortality. Alopecia in females on

10 males BHI. Minimum lethal dose > 10 IU/kg.
Mice 10 females SC 10 IU/kg 14 No mortality. Minimum lethal dose

10 males > 10 IU/kg
Rats 10 females SC 10 IU/kg 14 Significant tolerance of doses without

10 males signs of toxicity.
Dogs 2 females SC 2 IU/kg 14 Significant tolerance of doses without

2 males signs of toxicity.
Monkeys 2 females IV 1 IU/kg 14 Significant tolerance without signs of

2 males toxicity. Blood glucose values decreased
sharply in all animals 15-20 minutes post
administration.
Table 2. Subacute Toxicity
Species Number Route Single Daily Number of Observations

Per Dose Dose Doses
Rats 15 females SC 2.4 IU/kg/day 30 No toxicologically important

15 males changes occurred.
Dogs 3 females SC 2.0 IU/kg/day 30 One male on BHI experienced

3 males convulsions. Some ataxia and
hypoactivity.
Dogs 4 females IV 0.1 IU/kg /day 30 Decreased thrombocyte numbers.

4 males Minor changes in alanine
transaminase activities.

REFERENCES
1. Altman J, Pehuet M, Slama G, et al. Three cases of allergic reaction to human insulin.
Lancet 1983;(Aug 27):524.
2. Bachmann W, Sieger C, Lacher F, et al. Binding of biosynthetic human insulin to

erythrocytes of normal and insulin-dependent diabetic subjects: Comparison with pork and
human pancreatic insulin. Diabetes Care 1981;4(2):215-219.
3. Bachmann W, Hasche H, Mehnert H. Intradermal desensitization with human insulin

(recombinant DNA) in a patient with severe allergic skin reaction due to insulin. Diabetes
Care 1982;5(suppl 2):165-167.
4. Baker R, Ross W, Schmidtke J, et al. Preliminary studies on the immunogenicity and

amount of escherichia coli polypeptides in biosynthetic human insulin produced by
recombinant DNA Technology. Lancet 1981;2:1139-1141.
5. Bauman W, Yalow R. Immunologic Potency of recombinated A and B-chains of synthetic
human and pancreatic pork insulins. Diabetes 1981;30:265-266.
6. Beischer W, Maier V, Jonatha E, et al. Immunologic properties of biosynthetic human

insulin in vitro. Diabetes Care 1981;4(2):202-204.
7. Bell G, Pictet R, Rutter W, et al. Sequence of the human insulin gene. Nature 1980;
284:26-32.
8. Berke L, Owen J, Atkinson R. Allergies to human insulin, Diabetes Care 1984;

7(4):402-403.
9. Beyer J, Weber T, Schultz G, et al. Comparison of biosynthetic human insulin and pork
insulin during rest, food ingestion, and physical work in insulin-dependent diabetic subjects
using a glucose controlled insulin infusion system. Diabetes Care 1981;4(2):189-192.
10. Bottermann P, Gyaram H, Wahl K, et al. Pharmacokinetics of biosynthetic human insulin

and characteristics of its effect. Diabetes Care 1981;4(2):168-169.
11. Canadian Diabetes Association 2008 Clinical Practice Guidelines for the Prevention and
Management of Diabetes in Canada. Canadian J. Diabetes 2008;32(supp 1):S1-S201.
12. Carpentier J, Halban P, Renold A, et al. Internalization of 125I-insulin by IM-9 cultured
human lymphocytes: A comparison between A-14-monoiodo-pork and biosynthetic human
insulin. Diabetes Care 1981;4(2):220-222.
13. Carveth-Johnson A, Mylvaganam K, Child D. Generalised allergic reaction with synthetic
human insulin. Lancet 1982;(Dec 4):1287.
14. Chance R, Enzmann F, Galloway J, et al. Introduction to symposium on biosynthetic

human insulin, Athens, Greece (Sep 1980) and Wiesbaden, Germany (Dec 1980). Skyler J,
and Raptis S, Editors. Diabetes Care 1981;4(2):139.

15. Chance R, Kroeff E, Hoffman J, et al. Chemical, physical, and biologic properties of
biosynthetic human insulin. Diabetes Care 1981;4(2):147-154.
16. Check W. Bacterially produced human insulin given therapeutically. JAMA 1981;
245:322-323.
17. Clark A, Wiles P, Leiper J, et al. A double-blind crossover trial comparing human insulin
(recombinant DNA) with animal insulins in the treatment of previously insulin-treated
diabetic patients. Diabetes Care 1982;5(suppl 2):129-134.
18. DeLeeuw I, Delvigne C, Bekaert J. Insulin allergy treated with human insulin (recombinant
DNA). Diabetes Care 1982;5(suppl 2):168-170.
19. De Meyts P, Halban P, Hepp K. In vitro studies on biosynthetic human insulin: an

overview. Diabetes Care 1981;4(2):144-146.
20. Federlin K, Laube H, Velcovsky H. Biologic and immunologic in vivo and in vitro studies
with biosynthetic human insulin. Diabetes Care 1981;4(2):170-174.
21. Fehlmann M, Le Marchand-Brustel Y, Dolais-Kitabgi J, et al. Biologic activity and
receptor binding properties of biosynthetic human insulin in isolated rat hepatocytes and
mouse soleus muscle in vitro. Diabetes Care 1981;4(2):223-227.
22. Fineberg S, Galloway J, Fineberg N, et al. Immunologic improvement resulting from the
transfer of animal insulin-treated diabetic subjects to human insulin (recombinant DNA).
Diabetes Care 1982;5(suppl 2):107-113.
23. Fineberg S, Galloway J, Fineberg N, et al. Immunogenicity of recombinant DNA human
insulin. Diabetologia 1983;25:465-469.
24. Fussgaenger R, Ditschuneit H, Martini H, et al. Potency of biosynthetic human insulin
determined in vitro. Diabetes Care 1981;4(2):228-234.
25. Gait M. Synthetic genes for human insulin. Nature 1979;277(8):429-431.

26. Galloway J. Insulin treatment for the early 80's: facts and questions about old and new
insulins and their usage. Diabetes Care 1980;3(5):615-622.
27. Galloway J, Marsden J. Clinical trials with biosynthetic human insulin. Diabetes Care
1981;4(2):260-261.
28. Galloway J, Peck F, Fineberg S, et al. The US "new patient" and "transfer" studies.
Diabetes Care 1982;5(suppl. 2):135.
29. Galloway J, Root M, Bergstrom R, et al. Clinical pharmacologic studies with human
insulin (recombinant DNA). Diabetes Care 1982;5(suppl 2):13-22.
30. Galloway J, Spradlin C, Root M, et al. Plasma glucose response of normal fasting subjects
to neutral regular and NPH biosynthetic human and purified pork insulins. Diabetes Care
1981;4(2):183-188.

31. Galloway J. Highlights of clinical experiences with recombinant human insulin (r DNA)
and human proinsulin (r DNA). Netherland J Med 1985;28(suppl 1):37-42.
32. Gammeltoft S. Receptor binding of biosynthetic human insulin on isolated pig hepatocytes.
Diabetes Care 1981;4(2):235-237.
33. Garcia-Ortega P, Knobel H, Mirada A. Sensitization to human insulin. British Med J
1984;288:1271.
34. Gerich J. Appraisal of the role of biosynthetic human insulin in the future treatment of
diabetes mellitus. Diabetes Care 1981;4(2):262-264.
35. Goeddel D, Kleid D, Bolivar F, et al. Expression in Escherichia coli of chemically
synthesized genes for human insulin. Proc National Acad Sciences 1979;76:106-110.
36. Halban P, Berger M, Gjinovci A, et al. Biologic activity and pharmacokinetics of
biosynthetic human insulin in the rat. Diabetes Care 1981;4(2):238-243.
37. Herings R, deBoer A, Stricker B, et al. Hypoglycemia associated with use of inhibitors
Home P, Alberti K. Human insulin. Clinics Endocrin & Metabol 1982;11:543-583.
38. Howey D, Fineberg S, Nolen P, et al. The therapeutic efficacy of human insulin
(recombinant DNA) in patients with insulin-dependent diabetes mellitus: a comparative
study with purified porcine insulin. Diabetes Care 1982;5(suppl 2):73-77.
39. Johnson I. Authenticity and purity of human insulin (recombinant DNA). Diabetes Care
1982;5(suppl E2):4-12.
40. Keefer L, Piron M, De Meyts P. Human insulin prepared by DNA recombinant techniques
and native human insulin interact identically with insulin receptors. Proc National Acad
Sciences 1981;78:1391-1395.
41. Keefer L, Piron M, De Meyts P. Receptor binding properties and biologic activity in vitro
of biosynthetic human insulin. Diabetes Care 1981;4(2):209-214.
42. Keen H, Glynne A, Pickup J, et al. Human insulin produced by recombinant DNA
technology: safety and hypoglycaemic potency in healthy men. Lancet II 1980;
8191:398-401.
43. Kumar D, Alexander C, Zeidler A, et al. Immunoreactivity of human insulin of
recombinant DNA origin. Diabetes 1983;32:516-519.
44. Kurtz W, Pravenec M. Antidiabetic mechanisms of angiotensin-converting-enzyme

inhibitors and angiotensin II receptor antagonists: beyond the renin-angiotensin system.
J Hypertension 2004;22(12):2253-2261.
45. Landgraf R, Kammerer S, Bock T, et al. Crossover study with human insulin of angiotensin
converting enzyme. Lancet 1995;345:1195-98.
46. (recombinant DNA) in type 1 diabetic subjects. Diabetes Care 1982;5(suppl 2):39-42.

47. Maneschi F, Fineberg S, Kohner E. Successful treatment of immune-mediated insulin
resistance by human insulin (recombinant DNA). Diabetes Care 1982;5(suppl E2):
175-179.
48. Massi-Benedetti M, Burrin J, Capaldo B, et al. Comparative study of activity of

biosynthetic human insulin and pork insulin using glucose clamp technique in normal
subjects. Diabetes Care 1981;4(2):163-167.
49. Olefsky J. Insulin binding, biologic activity, and metabolism of biosynthetic human insulin.
Diabetes Care 1981;4(2):244-247.
50. Pedersen-Bjergaard U, Agerholm-Larsen B, Pramming S, et al. Activity of angiotensin-

converting enzyme and risk of severe hypoglycaemia in type 1 diabetes mellitus.
Lancet 2001;357:1248-1253.
51. Raptis S, Karaiskos C, Enzmann F, et al. Biologic activities of biosynthetic human insulin
in healthy volunteers and insulin-dependent diabetic patients monitored by the artificial
endocrine pancreas. Diabetes Care 1981;4(2):155-162.
52. Renner R, Vocke K, Hepp K. Search for the most practical Regular/NPH mixtures for
type 1 diabetic patients. Diabetes Care 1982;5(suppl 2):53-56.
53. Sailer D, Ludwig T, Kolb S. Comparison of the activity profiles of two fixed combinations
of Regular/NPH human insulin (recombinant DNA) of Different compositions with a fixed
Regular/NPH porcine insulin combination (PPI) in insulin-dependent diabetic individuals.
Diabetes Care 1982;5(suppl 2):57-59.
54. Schernthaner G. Affinity of IgG-insulin antibodies to human (recombinant DNA) insulin
and porcine insulin in insulin-treated diabetic individuals with and without insulin
resistance. Diabetes Care 1982;5(suppl 2):114-118.
55. Schernthaner G, Ludwig H, Jarisch R, et al. Immediate-type allergy against insulin itself:
clinical and immunologic studies on diabetic patient with insulin intolerance. Diabetes
Care 1981;4(2):196-201.
56. Schluter K, Kerp L. Receptor binding studies and clinical effects of human insulin
(recombinant DNA): studies in patients with newly diagnosed type 1 diabetes, type 2
diabetes, insulin resistance (type A and type B), insulin antibodies, insulin allergy, and
"brittle" diabetes. Diabetes Care 1982;5(suppl 2):152-160.
57. Skyler J. Human insulin of recombinant DNA origin: clinical potential. Diabetes Care
1982;5(suppl E2):181-186.
58. Skyler J. Pfeiffer E, Raptis S, et al. .Biosynthetic human insulin: progress and prospects.
Diabetes Care 1981;4(2):140-143.
59. Small P, Lerman S. Human insulin allergy. Annals Allergy 1984;53(1):39-41.

60. Spijker A, Poortman J, Thijssen J, et al. Decrease of circulating insulin antibodies in two
patients treated with continuous subcutaneous infusion of human insulin (recombinant
DNA). Diabetes Care 1982;5(suppl 2):171-174.
61. Waldhausl W, Kastner G, Komjati M, et al. Studies on the biologic actions of biosynthetic
human insulin in vitro and in diabetic man. Diabetes Care 1981;4(2):205-208.
62. Weinges K, Ehrhardt M, Enzmann F. Comparison of biosynthetic human insulin and pork
insulin in the Gerritzen test. Diabetes Care 1981;4(2):180-182.
63. Weinges K, Ehrhardt M, Nell G, et al. Pharmacodynamics of human insulin (recombinant
DNA) - Regular, NPH, and mixtures - obtained by the Gerritzen method in healthy
volunteers. Diabetes Care 1982;5(suppl 2):67-70.
64. Wieringa T, Van Putten J, Van Dijk-Besling, M, et al. Receptor binding and effect of
biosynthetic human insulin on 2-deoxyglucose transport. Diabetes Care 1981;
4(2):254-256.
65. Wiles P, Guy R, Watkins S, et al. Allergy to purified bovine, porcine, and human insulins.
British Med J 1983;287:531.

IMPORTANT: PLEASE READ
PART III: CONSUMER INFORMATION HUMULIN R should be used only if your doctor has
prescribed Regular insulin (insulin injection). You should
not attempt to add any insulin to this cartridge.
If HUMULIN N and HUMULIN R mixtures are prescribed,

HUMULIN® R CARTRIDGES
the individual insulins should be mixed as instructed in the
insulin injection, human biosynthetic (rDNA origin) amounts recommended by your doctor or purchased as
mixtures in the ratio recommended if available.
and HUMULIN® R KWIKPEN® What the medicinal ingredient is:
insulin injection, human biosynthetic (rDNA origin)  HUMULIN R contains insulin, human biosynthetic.
Solution for Injection, 100 units/mL What the nonmedicinal ingredients are:
Glycerol, m-cresol, water for injection, hydrochloric acid
This leaflet is part III of a three-part "Product Monograph" and sodium hydroxide.
published when HUMULIN® R was approved for sale in
Canada and is designed specifically for Consumers. This What dosage forms it comes in:
leaflet is a summary and will not tell you everything about HUMULIN R (Regular) is a sterile solution containing
HUMULIN® R. Contact your doctor or pharmacist if you insulin, human biosynthetic (rDNA origin) for injection. It
have any questions about the drug. is available in:
- Cartridges, 3 mL
ABOUT THIS MEDICATION - KwikPens, 3 mL prefilled pen
HUMULIN has been produced by recombinant DNA processes. HUMULIN R is also available in:
It differs from animal-source insulins because it is structurally - Vials, 3 mL
identical to the insulin produced by your body's pancreas and - Vials, 10 mL
because of its unique manufacturing process.
Other available HUMULIN products include HUMULIN N
HUMULIN R (Regular) consists of zinc-insulin crystals (NPH) and HUMULIN 30/70 (mixture of 30% Regular and
dissolved in a clear fluid. HUMULIN R is a fast-acting insulin 70% NPH). These types of insulin differ mainly in the time
with a duration of activity of 6 to 8 hours. they require to take effect and in the length of time their
action lasts. Your doctor has prescribed the type of insulin
HUMULIN R cartridges and HUMULIN R KwikPen (prefilled that he/she believes is best for you. Do not use any other
pens) are for subcutaneous (under the skin) injection. insulin except on your doctor's advice and direction.
What the medication is used for: When you receive your insulin from the pharmacy, always
check to see that:
HUMULIN R is a fast-acting insulin used to treat patients
diagnosed with diabetes mellitus. 1. The name HUMULIN appears on the carton and
cartridge or KwikPen (prefilled pen) label and is
What it does: followed by the proper letter designation and name for
the insulin formulation: R-Regular
Insulin is a hormone that decreases the amount of sugar in your
blood and urine by increasing the uptake of sugar from your 2. The carton and the cartridge or KwikPen label is correct
blood into various tissues, such as the liver, muscles, and fat. for your type of insulin.
To control your diabetes, your doctor has prescribed injections 3. The human insulin is of rDNA origin.
of insulin to keep your blood sugar at a nearly normal level and 4. The insulin strength is U-100.
to keep your urine as free of sugar as possible.
5. The expiration date on the package will allow you to use
When it should not be used: the insulin before that date.
HUMULIN R should not be used if you are allergic to this drug
or any of the ingredients used to formulate this medication.
HUMULIN R should not be used during episodes of

hypoglycemia (too little sugar in the blood).

adjustment is needed, it may be made with the first dose

or over a period of several weeks.
 Take precautions to avoid hypoglycemia while driving or
Serious Warnings and Precautions operating machinery. This is particularly important in
Hypoglycemia (too little sugar in the blood) is the most patients who have reduced awareness of the warning
common adverse effect of insulin products. Glucose signs of hypoglycemia or who have frequent episodes of
monitoring should be performed for all patients with hypoglycemia.
diabetes mellitus treated with insulins. Uncorrected  Ability to concentrate and react may be impaired as a
hypoglycemic or hyperglycemic reactions can cause loss result of hyperglycemia or as a result of hyperglycemia-
of consciousness, coma or even death. induced visual impairment. Take caution in situations
A few patients who experienced hypoglycemic reactions that require these abilities such as driving or operating
after being transferred to HUMULIN (insulin, human machinery.
biosynthetic) have reported that these early warning
 Your doctor will tell you what to do if you miss a dose of
symptoms were less pronounced than they were with
insulin or miss a meal because of illness. If you miss a
animal-source insulin.
meal, as a substitute use sugar, sugar-sweetened candy,
Any change of insulin regimen should be made cautiously fruit juice, or sugar-sweetened beverage according to
and only under medical supervision. your doctor's instructions. If a shortage of insulin
appears inevitable, a temporary reduction in the size of
Fast-acting insulins should be combined with a longer- dose may be made, accompanied by limitation of food
acting insulin or insulin infusion pump therapy to to two-thirds its usual quantity and a liberal increase in
maintain adequate glucose control. fluids of little or no food value, such as water, tea,
HUMULIN R should not be mixed with any other insulin coffee, broths, or clear soups.
unless clearly indicated and done under medical
 Consult your doctor if you notice anything unusual or
supervision.
have doubts about your condition or your use of insulin.
The contents of the cartridge of HUMULIN R should be
 Consult your doctor concerning adjustments in your
clear. Do not use if cloudy.
insulin schedule if you travel across more than 2 time
 Each case of diabetes is different. Your doctor has told you zones.
which insulin to use, how much, and when and how often to
inject it. This schedule has been individualized for you. INTERACTIONS WITH THIS MEDICATION
Proper control of your diabetes requires close and constant
cooperation with your doctor. There may be interactions between HUMULIN R and other
medicines. Tell your doctor if you are taking any other
 You have been instructed to test your blood and/or your medicine which has been prescribed for you or which you
urine regularly for sugar. If your blood tests consistently bought without a prescription.
show above or below normal sugar levels or your urine
tests consistently show the presence of sugar, your diabetes Insulin requirements may be increased if you are taking
is not properly controlled and you must let your doctor other drugs with hyperglycemic activity, such as oral
know. contraceptives (for example, birth control pills, injections
 If you become ill from any cause, especially with nausea and and patches), thiazides (for high blood pressure or excessive
vomiting, your insulin requirements may change. Test your fluid retention), corticosteroids, sympathomimetics (for
blood and/or urine and notify your doctor at once. example salbutamol used to treat asthma or pseudoephedrine
for colds), danazol (medicine acting on ovulation), or thyroid
 Always keep an extra supply of insulin. Always wear replacement therapy. Insulin requirements may also be
diabetic identification so that appropriate treatment can be affected by diphenylhydantoin (used to treat epilepsy).
given if complications occur away from home.
 Never change from the insulin that has been prescribed for Insulin requirements may be decreased in the presence of
you to another insulin without instructions from your agents such as oral medicines for the treatment of diabetes,
doctor. Changing the type, strength, source, or salicylates (Aspirin*), sulfa antibiotics, certain
manufacturer of insulin can cause problems with your antidepressants (monoamine oxidase inhibitors), beta-
blood sugar control. blockers, alcohol, ACE inhibitors and angiotensin II receptor
blockers, and anabolic steroids.
 Some patients taking HUMULIN R will require a change in
dosage from that used with animal-source insulins. If an

Insulin requirements can be increased, decreased, or unchanged dose setting of the pen. Repeat until an insulin drop
in patients receiving diuretics. appears at the end of the needle. There may be small
bubbles left; the air is harmless but too large an air
The use of thiazolidinediones (such as rosiglitazone and
bubble will affect the accuracy of the insulin dose
pioglitazone), alone or in combination with other antidiabetic
administered.
agents (including insulin), has been associated with heart failure
and swelling of the lower extremities. Please contact your 6. Set the dose as instructed by your doctor. A gauge has
physician immediately if you develop symptoms of shortness of been provided on the side of the cartridge to help you
breath, fatigue, exercise intolerance, or swelling of the lower judge the amount of insulin remaining. The distance
extremities while you are on these agents. between each mark represents approximately 20 units for
3 mL cartridges or KwikPens.
The presence of such diseases as acromegaly, Cushing’s
syndrome, hyperthyroidism, and pheochromocytoma complicate
Injecting the Dose:
the control of diabetes.
1. Cleanse the skin, as instructed by your healthcare
professional, where the injection is to be made. To avoid
PROPER USE OF THIS MEDICATION
tissue damage (skin thinning, skin thickening, or skin
INSTRUCTIONS FOR USE lumps), always change the site for each injection by at
least 1.5 cm (0.5 inches) from the previous site, rotating
HUMULIN R cartridges are designed for use with Lilly injector
sites on the body so that the same site is not used more
systems (reusable pens).
than approximately once a month. Do not inject into pits
HUMULIN R cartridges and KwikPens (prefilled pens) are not (depressions), thickened skin or lumps.
designed to allow any other insulin to be mixed in the cartridge.
2. Insert the needle under the skin, as you were taught. Do
HUMULIN R cartridges and KwikPens MUST NOT be refilled not inject directly into a vein.
and are not designed for use with a traditional syringe. 3. To inject the insulin, follow the instructions of the pen's
Do not reuse needles. NEEDLES, CARTRIDGES, AND PENS manufacturer.
MUST NOT BE SHARED with anyone including family 4. Pull the needle out and apply gentle pressure over the
members. Never share a HUMULIN KwikPen or cartridge, even injection site for several seconds. Do not rub the area.
if the needle on the delivery device is changed. You may pass
on a serious infection or get a serious infection from the other 5. Immediately after injection, remove the needle from the
person. pen. This will ensure sterility and prevent leakage, re-
entry of air and potential needle clogs.
For guidance on the use of the KwikPen (prefilled, disposable
pen) or Lilly’s reusable pens, please refer to the separate
Usual Dose
Instructions for Use enclosed within the pen packaging.
The dosage will be determined by your doctor, according to
the requirements of each individual patient. HUMULIN R is
Preparing the Dose: for subcutaneous (under the skin) injection. Do not inject
into a vein.
1. Wash your hands.
2. Always examine the cartridge or KwikPen (prefilled pen) of Use in Pregnancy
HUMULIN R after removing from the box. HUMULIN R
Control of the blood sugar is vital to assure the birth of a
should be clear and colourless. DO NOT use HUMULIN R
healthy child. Normalization of the blood sugar should have
if it appears cloudy, thickened, or slightly coloured, or if
occurred before conception and should continue throughout
solid particles are visible or if the cartridge or KwikPen is
the pregnancy. Since pregnancy may make diabetes worse
cracked or broken.
and because of the importance of good diabetic control,
3. Carefully load the cartridge into the reusable pen following patients who contemplate pregnancy or who are pregnant
the manufacturer’s directions. should seek expert medical advice.
4. Wipe the exposed rubber membrane on the metal cap end of Diabetic patients who are nursing may require adjustments
the cartridge or KwikPen (prefilled pen) with an alcohol in insulin dose and/or diet.
swab and attach the needle.
5. Prime the pen as directed by the manufacturer. If air
bubbles are present, hold the pen with the needle pointing up
and tap the side of the pen until the bubbles float to the top.
With the pen still vertical, purge the needle with a 2 unit

Overdose:
Hypoglycemia (Insulin Reaction): In case of drug overdose, contact a healthcare practitioner,
hospital emergency department or regional Poison Control
Insulin reaction (too little sugar in the blood, also called
Centre immediately, even if there are no symptoms.
"hypoglycemia") can be brought about by:
 Taking too much insulin
 Missing or delaying meals
SIDE EFFECTS AND WHAT TO DO ABOUT THEM
 Exercising or working too hard just before a meal
 An infection or illness (especially with diarrhea or Hypoglycemia (Insulin Reaction)
vomiting) Hypoglycemia (too little sugar in the blood) is one of the
 A change in the body's need for insulin. most frequent adverse events experienced by insulin users
Dietary Implications: (see Proper Use of this Medication - Overdose).
If a usual meal cannot be obtained at the appropriate time, then Diabetic Acidosis and Coma
to avoid hypoglycemia, you should take the amount of
carbohydrate prescribed for this meal in the form of orange Diabetic acidosis may develop if your body has too little
juice, syrup, candy, or bread and milk, without changing your insulin (this is the opposite of insulin reaction, which is the
insulin dosage. If it becomes necessary to omit a meal on result of too much insulin in the blood). Diabetic acidosis
account of nausea and vomiting, you should test your blood may be brought on if you omit your insulin or take less than
sugar level and notify your doctor. the doctor has prescribed, eat significantly more than your
diet calls for, or develop a fever or infection. With acidosis,
Symptoms and Treatment: urine tests show a large amount of sugar and acetone.
The first symptoms of insulin reaction usually come on The first symptoms of diabetic acidosis usually come on
suddenly and may include vague symptoms of fatigue, gradually, over a period of hours or days, and include a
nervousness or “shakiness”, rapid heartbeat, nausea, and a cold drowsy feeling, flushed face, thirst, and loss of appetite.
sweat. It is of utmost importance that you understand that these Heavy breathing and a rapid pulse are more severe
symptoms demand immediate attention. symptoms.
The patient’s ability to concentrate and to react may be impaired If uncorrected, loss of consciousness, coma, or death can
as a result of hypoglycemia. This may constitute a risk in result. Therefore, it is important that you obtain medical
situations where these abilities are of special importance (e.g. assistance immediately.
driving a car or operating machinery – see Warnings and
Precautions). Allergy to Insulin
A few patients who experienced hypoglycemic reactions after Patients occasionally experience redness, swelling, and
being transferred to HUMULIN have reported that these early itching at the site of injection of insulin. This condition,
warning symptoms were less pronounced than they were with called local allergy, usually clears up in a few days to a few
animal-source insulin. Some people may not recognize when weeks. If you have local reactions, contact your doctor, who
their blood sugar drops low. may recommend a change in the type or species of insulin.
Eating sugar or a sugar-sweetened product will often correct the Less common, but potentially more serious, is generalized
condition and prevent more serious symptoms. Artificial allergy to insulin, which may cause rash over the whole
sweeteners are not useful for the treatment of hypoglycemia. body, shortness of breath, wheezing, reduction in blood
pressure, fast pulse, or sweating. Severe cases of
If a diabetic becomes delirious or mentally confused, or suffers generalized allergy may be life threatening. If you think you
from loss of memory or delusions, corn syrup diluted or orange are having a generalized allergic reaction to insulin, notify a
juice with sugar should be administered by mouth. More severe doctor immediately. Your doctor may recommend skin
hypoglycemia may require the assistance of another person. testing, that is, injecting small doses of other insulins into
Patients who are unable to take sugar orally or who are the skin, in order to select the best insulin for you to use.
unconscious should be treated with intravenous administration Patients who have had severe generalized allergic reactions
of glucose at a medical facility or should be given an injection to insulin should be skin tested with each new preparation to
of glucagon (either intramuscular or subcutaneous). The patient be used before treatment with that preparation is started.
should be given oral carbohydrates as soon as consciousness is
recovered. In the event of a hypoglycemic reaction, whether
mild or severe, you should notify your doctor promptly so that
any desirable change in diet or dosage can be determined.

Lipoatrophy, Lipohypertrophy, or Localized Cutaneous

Amyloidosis: REPORTING SUSPECTED SIDE EFFECTS
Rarely, administration of insulin subcutaneously can result in You can report any suspected adverse reactions associated
lipoatrophy (depression in the skin), lipohypertrophy with the use of health products to the Canada Vigilance
(enlargement or thickening of tissue), or localized subcutaneous Program by one of the following 3 ways:
amyloidosis (skin lumps). If you notice any of these conditions, ------------------------------------------------------------------------
consult your doctor. A change in your injection technique may  Report online at www.healthcanada.gc.ca/medeffect
help alleviate the problem.  Call toll-free at 1-866-234-2345
 Complete a Canada Vigilance Reporting Form and:
This is not a complete list of side effects. For any unexpected - Fax toll-free to 1-866-678-6789, or
effects while taking HUMULIN R, contact your doctor or - Mail to: Canada Vigilance Program
pharmacist. Health Canada
Postal Locator 0701D
HOW TO STORE IT Ottawa, Ontario
K1A 0K9
Your unused HUMULIN R cartridges or KwikPens (prefilled
pens) should be stored in the refrigerator (2-8C). DO NOT Postage paid labels, Canada Vigilance Reporting
FREEZE. The cartridge or KwikPen of insulin that you are Form and the adverse reaction reporting guidelines
currently using does not have to be refrigerated but should be are available on the MedEffect™ Canada Web site at
kept at a temperature below 25C, away from direct heat and www.healthcanada.gc.ca/medeffect.
sunlight and protected from freezing. The cartridge of insulin
currently in use should be left in the pen and may be carried NOTE: Should you require information related to the
with you. Cartridges or KwikPens in use or not refrigerated management of side effects, contact your health
should be discarded after 28 days even if they contain insulin. professional. The Canada Vigilance Program does not
provide medical advice.
Inspection of Cartridge:
HUMULIN R should be clear and colourless. DO NOT USE a
cartridge or KwikPen of HUMULIN R if it appears cloudy, MORE INFORMATION
thickened, or slightly coloured, or if solid particles are visible.
A cartridge or KwikPen that is not clear and colourless or that is For more information, please contact your healthcare
cracked or broken should be returned to the place of purchase professionals or pharmacist first, or Eli Lilly Canada Inc at:
for exchange. 1-888-545-5972 or visit the website at www.lilly.ca
If you notice anything unusual in the appearance or effect of
your insulin, consult your healthcare professional. HUMULIN and KwikPen are registered trademarks owned
by or licensed to Eli Lilly and Company, its subsidiaries or
DO NOT USE AFTER EXPIRY DATE. affiliates.
*The brands listed are trademarks of their respective owners

and are not trademarks of Eli Lilly Canada. The makers of
these brands are not affiliated with and do not endorse Eli
Lilly Canada or its products.
The information in this document is current as of the last
revision date shown below. For the most current
information please visit our website or contact us directly.
This leaflet was prepared by: Eli Lilly Canada Inc.
You may need to read this package insert again. Please do
not throw it away until you have finished your medicine.
Last revised: May 24, 2021
LIN-0004-CA-PM-20210524


PART III: CONSUMER INFORMATION
amounts recommended by your doctor or purchased as
mixtures in the ratio recommended if available.
HUMULIN® R VIALS What the medicinal ingredient is:

insulin injection, human biosynthetic (rDNA origin)  HUMULIN R contains insulin, human biosynthetic.
What the nonmedicinal ingredients are:
Glycerol, m-cresol, water for injection, hydrochloric acid
This leaflet is part III of a three-part "Product Monograph" and sodium hydroxide.
published when HUMULIN® R was approved for sale in
Canada and is designed specifically for Consumers. This What dosage forms it comes in:
leaflet is a summary and will not tell you everything about
HUMULIN® R. Contact your doctor or pharmacist if you HUMULIN R (Regular) is a sterile solution containing
have any questions about the drug. insulin, human biosynthetic (rDNA origin) for injection. It
is available in:
- Vials, 3 mL
ABOUT THIS MEDICATION - Vials, 10 mL
HUMULIN R is also available in:
HUMULIN has been produced by recombinant DNA processes.
- Cartridges, 3 mL
It differs from animal-source insulins because it is structurally
- KwikPens, 3 mL prefilled pen
identical to the insulin produced by your body's pancreas and
because of its unique manufacturing process. Other available HUMULIN products include HUMULIN N
(NPH) and HUMULIN 30/70 (mixture of 30% Regular and
HUMULIN R (Regular) consists of zinc-insulin crystals
70% NPH). These types of insulin differ mainly in the time
dissolved in a clear fluid. It is a fast-acting insulin with a
they require to take effect and in the length of time their
duration of activity of 6 to 8 hours.
action lasts. Your doctor has prescribed the type of insulin
HUMULIN R vials are for subcutaneous (under the skin) that he/she believes is best for you. Do not use any other
injection. insulin except on your doctor's advice and direction.
When you receive your insulin from the pharmacy, always
What the medication is used for:
check to see that:
HUMULIN R is a fast-acting insulin used to treat patients
1. The name HUMULIN appears on the carton and vial and
diagnosed with diabetes mellitus.
is followed by the proper letter designation and name
for the insulin formulation: R-Regular.
What it does:
2. The carton and the vial label is correct for your type of
insulin.
blood and urine by increasing the uptake of sugar from your
blood to various tissues, such as the liver, muscles, and fat. 3. The human insulin is of rDNA origin.
To control your diabetes, your doctor has prescribed injections 4. The insulin strength is U-100.
of insulin to keep your blood sugar at a nearly normal level and
the insulin before that date.
When it should not be used:
HUMULIN R should not be used if you are allergic to this drug
HUMULIN R should not be used during episodes of
HUMULIN R should be used only if your doctor has prescribed
Regular insulin (insulin injection).

 Some patients taking HUMULIN R will require a change

in dosage from that used with animal-source insulins. If
an adjustment is needed, it may be made with the first
Serious Warnings and Precautions dose or over a period of several weeks.
Hypoglycemia (too little sugar in the blood) is the most  Take precautions to avoid hypoglycemia while driving or
common adverse effect of insulin products. Glucose operating machinery. This is particularly important in
monitoring should be performed for all patients with patients who have reduced awareness of the warning
diabetes mellitus treated with insulins. Uncorrected signs of hypoglycemia or who have frequent episodes of
hypoglycemic or hyperglycemic reactions can cause loss hypoglycemia.
of consciousness, coma or even death.
 Ability to concentrate and react may be impaired as a
A few patients who experienced hypoglycemic reactions result of hyperglycemia or as a result of hyperglycemia-
after being transferred to HUMULIN (insulin, human induced visual impairment. Take caution in situations
biosynthetic) have reported that these early warning that require these abilities such as driving or operating
symptoms were less pronounced than they were with machinery.
Any change of insulin regimen should be made cautiously insulin or miss a meal because of illness. If you miss a
and only under medical supervision. meal, as a substitute use sugar, sugar-sweetened candy,
fruit juice, or sugar-sweetened beverage according to
Fast-acting insulins should be combined with a longer-
your doctor's instructions. If a shortage of insulin
acting insulin or insulin infusion pump therapy to
maintain adequate glucose control.
dose may be made, accompanied by limitation of food
HUMULIN R should not be mixed with any other insulin to two-thirds its usual quantity and a liberal increase in
unless clearly indicated and done under medical fluids of little or no food value, such as water, tea,
supervision. coffee, broths, or clear soups.
The contents of the vial of HUMULIN R should be clear.  Consult your doctor if you notice anything unusual or
Do not use if cloudy. have doubts about your condition or your use of insulin.
 Each case of diabetes is different. Your doctor has told you  Consult your doctor concerning adjustments in your
which insulin to use, how much, and when and how often to insulin schedule if you travel across more than 2 time
inject it. This schedule has been individualized for you. zones.
cooperation with your doctor. INTERACTIONS WITH THIS MEDICATION
 You have been instructed to test your blood and/or your There may be interactions between HUMULIN R and other
urine regularly for sugar. If your blood tests consistently medicines. Tell your doctor if you are taking any other
show above or below normal sugar levels or your urine medicine which has been prescribed for you or which you
tests consistently show the presence of sugar, your diabetes bought without a prescription.
is not properly controlled and you must let your doctor
know. Insulin requirements may be increased if you are taking
other drugs with hyperglycemic activity, such as oral
 If you become ill from any cause, especially with nausea and contraceptives (for example, birth control pills, injections
vomiting, your insulin requirements may change. Test your and patches), thiazides (for high blood pressure or excessive
blood and/or urine and notify your doctor at once. fluid retention), corticosteroids, sympathomimetics (for
 Always keep an extra supply of insulin, as well as a spare example salbutamol used to treat asthma or pseudoephedrine
needle and syringe. Always wear diabetic identification so for colds), danazol (medicine acting on ovulation), or thyroid
that appropriate treatment can be given if complications replacement therapy. Insulin requirements may also be
occur away from home. affected by diphenylhydantoin (used to treat epilepsy).
manufacturer of insulin can cause problems with your antidepressants (monoamine oxidase inhibitors), beta-
blood sugar control. blockers, alcohol, ACE inhibitors and angiotensin II receptor
blockers, and anabolic steroids.

Insulin requirements can be increased, decreased, or unchanged 7. Making sure the tip of the needle is in the insulin,
in patients receiving diuretics. withdraw the correct dose of insulin into the syringe.
The use of thiazolidinediones (such as rosiglitazone and 8. Before removing the needle from the vial, check your
pioglitazone), alone or in combination with other antidiabetic syringe for air bubbles which reduce the amount of
agents (including insulin), has been associated with heart failure insulin in it. If bubbles are present, hold the syringe
and swelling of the lower extremities. Please contact your needle up and tap its side until the bubbles float to the
physician immediately if you develop symptoms of shortness of top. Push them out with the plunger and withdraw the
breath, fatigue, exercise intolerance, or swelling of the lower correct dose.
extremities while you are on these agents.
9. Remove the needle from the vial and lay the syringe
The presence of such diseases as acromegaly, Cushing’s down so that the needle does not touch anything.
the control of diabetes. Injecting the Dose:
tissue damage (skin thinning, skin thickening, or skin
INJECTION PROCEDURES FOR VIALS lumps), always change the site for each injection by at
Correct Syringe least 1.5 cm (0.5 inches) from the previous site, rotating
Doses of insulin are measured in units. U-100 insulin contains than approximately once a month. Do not inject into pits
100 units/mL. It is important to use a syringe that is marked for (depressions), thickened skin or lumps.
U-100 insulin preparations. Failure to use the proper syringe
can lead to a mistake in dosage, causing serious problems for 2. Inject under the skin, as you were taught. Do not inject
you, such as a blood glucose level that is too low or too high. directly into a vein.
Syringe Use 3. Push the plunger in as far as it will go.
To help avoid contamination and possible infection, follow 4. Pull the needle out and apply gentle pressure over the
these instructions exactly. injection site for several seconds. Do not rub the area.
Disposable syringes and needles should be used only once and
Usual Dose
then discarded. NEEDLES AND SYRINGES MUST NOT BE
SHARED with anyone including family members. You may The dosage will be determined by your doctor, according to
pass on a serious infection or get a serious infection from the the requirements of each individual patient. HUMULIN R is
other person. Follow the package directions supplied with your for subcutaneous (under the skin) injection. Do not inject
syringe. into a vein.
Preparing the Dose:
Use in Pregnancy
1. Wash your hands.
2. Always examine the vial of HUMULIN R after removing healthy child. Normalization of the blood sugar should have
from the box. HUMULIN R should look clear and occurred before conception and should continue throughout
colourless. DO NOT use HUMULIN R if it appears the pregnancy. Since pregnancy may make diabetes worse
cloudy, thickened, or slightly coloured or if solid particles and because of the importance of good diabetic control,
are visible, or if the vial is cracked or broken. patients who contemplate pregnancy or who are pregnant
should seek expert medical advice.
3. If using a new bottle (vial), flip off the plastic protective cap,
but do not remove the stopper. Wipe the top of the vial Diabetic patients who are nursing may require adjustments
with an alcohol swab. in insulin dose and/or diet.
4. If you are mixing insulins, follow the instructions for mixing
Overdose:
given to you by your doctor or nurse.
Hypoglycemia (Insulin Reaction):
5. Draw air into the syringe equal to your insulin dose. Put the
needle through the rubber top of the insulin vial and inject Insulin reaction (too little sugar in the blood, also called
the air into the vial. "hypoglycemia") can be brought about by:
6. Turn the vial and syringe upside down. Hold the vial and  Taking too much insulin
syringe firmly in 1 hand.  Missing or delaying meals


 An infection or illness (especially with diarrhea or
vomiting) Hypoglycemia (Insulin Reaction)
 A change in the body's need for insulin. Hypoglycemia (too little sugar in the blood) is one of the
Dietary Implications: most frequent adverse events experienced by insulin users
(see Proper Use of this Medication - Overdose).
If a usual meal cannot be obtained at the appropriate time, then
Diabetic Acidosis and Coma
carbohydrate prescribed for this meal in the form of orange
juice, syrup, candy, or bread and milk, without changing your Diabetic acidosis may develop if your body has too little
insulin dosage. If it becomes necessary to omit a meal on insulin (this is the opposite of insulin reaction, which is the
account of nausea and vomiting, you should test your blood result of too much insulin in the blood). Diabetic acidosis
sugar level and notify your doctor. may be brought on if you omit your insulin or take less than
the doctor has prescribed, eat significantly more than your
Symptoms and Treatment: diet calls for, or develop a fever or infection. With acidosis,
The first symptoms of insulin reaction usually come on urine tests show a large amount of sugar and acetone.
suddenly and may include vague symptoms of fatigue, The first symptoms of diabetic acidosis usually come on
nervousness or “shakiness”, rapid heartbeat, nausea, and a cold gradually, over a period of hours or days, and include a
sweat. It is of utmost importance that you understand that these drowsy feeling, flushed face, thirst, and loss of appetite.
symptoms demand immediate attention. Heavy breathing and a rapid pulse are more severe
The patient’s ability to concentrate and to react may be impaired symptoms.
as a result of hypoglycemia. This may constitute a risk in
If uncorrected, loss of consciousness, coma, or death can
situations where these abilities are of special importance (e.g.
result. Therefore, it is important that you obtain medical
driving a car or operating machinery – see Warnings and
assistance immediately.
Precautions).
A few patients who experienced hypoglycemic reactions after Allergy to Insulin
being transferred to HUMULIN have reported that these early
Patients occasionally experience redness, swelling, and
warning symptoms were less pronounced than they were with
itching at the site of injection of insulin. This condition,
animal-source insulin. Some people may not recognize when
called local allergy, usually clears up in a few days to a few
their blood sugar drops low.
weeks. If you have local reactions, contact your doctor, who
Eating sugar or a sugar-sweetened product will often correct the may recommend a change in the type or species of insulin.
condition and prevent more serious symptoms. Artificial
Less common, but potentially more serious, is generalized
sweeteners are not useful for the treatment of hypoglycemia.
allergy to insulin, which may cause rash over the whole
If a diabetic becomes delirious or mentally confused, or suffers body, shortness of breath, wheezing, reduction in blood
from loss of memory or delusions, corn syrup diluted or orange pressure, fast pulse, or sweating. Severe cases of
juice with sugar should be administered by mouth. More severe generalized allergy may be life threatening. If you think you
hypoglycemia may require the assistance of another person. are having a generalized allergic reaction to insulin, notify a
Patients who are unable to take sugar orally or who are doctor immediately. Your doctor may recommend skin
unconscious should be treated with intravenous administration testing, that is, injecting small doses of other insulins into
of glucose at a medical facility or should be given an injection the skin, in order to select the best insulin for you to use.
of glucagon (either intramuscular or subcutaneous). The patient Patients who have had severe generalized allergic reactions
should be given oral carbohydrates as soon as consciousness is to insulin should be skin tested with each new preparation to
recovered. In the event of a hypoglycemic reaction, whether be used before treatment with that preparation is started.
any desirable change in diet or dosage can be determined. Lipoatrophy, Lipohypertrophy, or Localized Cutaneous
Amyloidosis:
In case of drug overdose, contact a healthcare practitioner, Rarely, administration of insulin subcutaneously can result
hospital emergency department or regional Poison Control in lipoatrophy (depression in the skin), lipohypertrophy
Centre immediately, even if there are no symptoms. (enlargement or thickening of tissue), or localized
subcutaneous amyloidosis (skin lumps). If you notice any of
these conditions, consult your doctor. A change in your
injection technique may help alleviate the problem.

This is not a complete list of side effects. For any unexpected

effects while taking HUMULIN R, contact your doctor or MORE INFORMATION
pharmacist. For more information, please contact your healthcare
professionals or pharmacist first, or Eli Lilly Canada Inc at:
HOW TO STORE IT 1-888-545-5972 or visit the website at www.lilly.ca
Your unused HUMULIN R vials should be stored in the
HUMULIN is a registered trademark owned by Eli Lilly and
refrigerator (2-8C). DO NOT FREEZE. The vial of insulin
Company, its subsidiaries or affiliates.
that you are currently using does not have to be refrigerated but
should be kept at a temperature below 25C, away from direct
heat and sunlight and protected from freezing. Vials in use or
not refrigerated should be discarded after 28 days even if they
contain insulin.
Inspection of the Vial: The information in this document is current as of the last
HUMULIN R should be clear and colourless. DO NOT USE a information please visit our website or contact us directly.
vial of HUMULIN R if it appears cloudy, thickened, or slightly
coloured or if solid particles are visible. A vial that is not clear This leaflet was prepared by: Eli Lilly Canada Inc.
and colourless or that is cracked or broken should be returned to
the place of purchase for exchange.
your insulin, consult your healthcare professional.
LIN-0004-CA-PM-20210524
DO NOT USE AFTER EXPIRY DATE.
REPORTING SUSPECTED SIDE EFFECTS
You can report any suspected adverse reactions associated

with the use of health products to the Canada Vigilance
Program by one of the following 3 ways:
------------------------------------------------------------------------
 Report online at www.healthcanada.gc.ca/medeffect
 Call toll-free at 1-866-234-2345
- Fax toll-free to 1-866-678-6789, or
- Mail to: Canada Vigilance Program
Health Canada
Ottawa, Ontario
K1A 0K9
Postage paid labels, Canada Vigilance Reporting

Form and the adverse reaction reporting guidelines
are available on the MedEffect™ Canada Web site at
www.healthcanada.gc.ca/medeffect.
NOTE: Should you require information related to the

management of side effects, contact your health
professional. The Canada Vigilance Program does not

When it should not be used:

HUMULIN N should not be used if you are allergic to this
drug or any of the ingredients used to formulate this
medication.
HUMULIN® N CARTRIDGES HUMULIN N should not be used during episodes of
insulin isophane, human biosynthetic (rDNA origin)
HUMULIN N should not be given intravenously or used for
treatment of diabetic coma.
and HUMULIN® N KWIKPEN® HUMULIN N should be used only if your doctor has
prescribed NPH insulin (insulin isophane). You should not
insulin isophane, human biosynthetic (rDNA origin) attempt to add any insulin to this cartridge or KwikPen
Suspension for Injection, 100 units/mL (prefilled pen).
This leaflet is part III of a three-part "Product Monograph" amounts recommended by your doctor or purchased as
published when HUMULIN® N was approved for sale in mixtures in the ratio recommended if available.
Canada and is designed specifically for Consumers. This
leaflet is a summary and will not tell you everything about What the medicinal ingredient is:
HUMULIN® N. Contact your doctor or pharmacist if you
have any questions about the drug.  HUMULIN N contains insulin isophane, human
biosynthetic.
ABOUT THIS MEDICATION What the nonmedicinal ingredients are:
HUMULIN has been produced by recombinant DNA processes. Glycerol, m-cresol, water for injection, hydrochloric acid,
It differs from animal-source insulins because it is structurally sodium hydroxide, phenol, zinc oxide, protamine sulfate and
identical to the insulin produced by your body's pancreas and dibasic sodium phosphate.
HUMULIN N – NPH (insulin isophane, human biosynthetic, What dosage forms it comes in:
rDNA origin) has been modified so that it has a different HUMULIN N (NPH) is a sterile suspension containing
duration of action than Regular insulin. The result is an insulin isophane, human biosynthetic (rDNA origin) for
intermediate-acting insulin with a slower onset of action than subcutaneous injection. It is available in:
Regular insulin and a duration of activity between 16 to 18 - Cartridges, 3 mL
hours. - KwikPens, 3 mL prefilled pen
HUMULIN N cartridges and HUMULIN N KwikPen (prefilled HUMULIN N is also available in:
pens) are for subcutaneous (under the skin) injection only. - Vials, 3 mL
- Vials, 10 mL
Other available HUMULIN products include HUMULIN R
HUMULIN N is an intermediate-acting insulin used to treat (Regular) and HUMULIN 30/70 (mixture of 30% Regular
patients diagnosed with diabetes mellitus. and 70% NPH). These types of insulin differ mainly in the
time they require to take effect and in the length of time their
What it does: action lasts. Your doctor has prescribed the type of insulin
Insulin is a hormone that decreases the amount of sugar in your that he/she believes is best for you. Do not use any other
blood and urine by increasing the uptake of sugar from your insulin except on your doctor's advice and direction.
blood into various tissues, such as the liver, muscles, and fat. When you receive your insulin from the pharmacy, always
To control your diabetes, your doctor has prescribed injections check to see that:
of insulin to keep your blood sugar at a nearly normal level and 1. The name HUMULIN appears on the carton and
to keep your urine as free of sugar as possible. cartridge or KwikPen (prefilled pen) label and is
followed by the proper letter designation and name for
the insulin formulation: N-NPH.

2. The carton and cartridge or KwikPen label is correct for  Always keep an extra supply of insulin. Always wear
your type of insulin. diabetic identification so that appropriate treatment can
be given if complications occur away from home.
3. The human insulin is of rDNA origin.
4. The insulin strength is U-100.  Never change from the insulin that has been prescribed
for you to another insulin without instructions from your
5. The expiration date on the package will allow you to use the doctor. Changing the type, strength, source, or
insulin before that date. manufacturer of insulin can cause problems with your
blood sugar control.
WARNINGS AND PRECAUTIONS  Some patients taking HUMULIN N will require a change
in dosage from that used with animal-source insulins. If
an adjustment is needed, it may be made with the first
Serious Warnings and Precautions dose or over a period of several weeks.
Hypoglycemia (too little sugar in the blood) is the most  Take precautions to avoid hypoglycemia while driving or
common adverse effect of insulin products. Glucose
operating machinery. This is particularly important in
monitoring should be performed for all patients with
patients who have reduced awareness of the warning
diabetes mellitus treated with insulins. Uncorrected
signs of hypoglycemia or who have frequent episodes of
hypoglycemic or hyperglycemic reactions can cause loss hypoglycemia.
of consciousness, coma or even death.
A few patients who experienced hypoglycemic reactions
result of hyperglycemia or as a result of hyperglycemia-
after being transferred to HUMULIN (insulin, human
induced visual impairment. Take caution in situations
that require these abilities such as driving or operating
machinery.
Any change of insulin regimen should be made cautiously
and only under medical supervision.
Fast-acting insulins should be combined with a longer- fruit juice, or sugar-sweetened beverage according to
acting insulin or insulin infusion pump therapy to your doctor's instructions. If a shortage of insulin
maintain adequate glucose control. appears inevitable, a temporary reduction in the size of
HUMULIN N should not be mixed with any other insulin
to two-thirds its usual quantity and a liberal increase in
fluids of little or no food value, such as water, tea,
supervision.
coffee, broths, or clear soups.
Do not use HUMULIN N if you see lumps that float or
that stick to the sides of the cartridge, or if the contents of
the cartridge are clear and remain clear after the bottle is
shaken or rotated.  Consult your doctor concerning adjustments in your
inject it. This schedule has been individualized for you.
Proper control of your diabetes requires close and constant INTERACTIONS WITH THIS MEDICATION
cooperation with your doctor. There may be interactions between HUMULIN N and other
 You have been instructed to test your blood and/or your medicines. Tell your doctor if you are taking any other
urine regularly for sugar. If your blood tests consistently medicine which has been prescribed for you or which you
show above or below normal sugar levels or your urine bought without a prescription.
tests consistently show the presence of sugar, your diabetes
is not properly controlled and you must let your doctor Insulin requirements may be increased if you are taking
know. other drugs with hyperglycemic activity, such as oral
contraceptives (for example, birth control pills, injections
 If you become ill from any cause, especially with nausea and and patches), thiazides (for high blood pressure or excessive
vomiting, your insulin requirements may change. Test your fluid retention), corticosteroids, sympathomimetics (for
blood and/or urine and notify your doctor at once. example salbutamol used to treat asthma or pseudoephedrine

replacement therapy. Insulin requirements may also be affected there are clumps floating in the insulin, or if the cartridge
by diphenylhydantoin (used to treat epilepsy). or KwikPen is cracked or broken.
3. Carefully load the cartridge into the reusable pen
Insulin requirements may be decreased in the presence of agents
following the manufacturer’s directions.
such as oral medicines for the treatment of diabetes, salicylates
(Aspirin*), sulfa antibiotics, certain antidepressants 4. Wipe the exposed rubber membrane on the metal cap end
(monoamine oxidase inhibitors), beta-blockers, alcohol, ACE of the cartridge or KwikPen (prefilled pen) with an
inhibitors and angiotensin II receptor blockers and anabolic alcohol swab and attach the needle.
steroids.
5. Carefully re-suspend the HUMULIN N by rolling the
Insulin requirements can be increased, decreased, or unchanged cartridge and pen in your hands 10 times and inverting it
in patients receiving diuretics. 180 10 times. This must be performed each time before
you give yourself an injection even after just loading the
The use of thiazolidinediones (such as rosiglitazone and pen.
agents (including insulin), has been associated with heart failure 6. Prime the pen as directed by the manufacturer. If air
and swelling of the lower extremities. Please contact your bubbles are present, hold the pen with the needle
physician immediately if you develop symptoms of shortness of pointing up and tap the side of the pen until the bubbles
breath, fatigue, exercise intolerance, or swelling of the lower float to the top. With the pen still vertical, purge the
extremities while you are on these agents. needle with a 2 unit dose setting of the pen. Repeat until
an insulin drop appears at the end of the needle. There
The presence of such diseases as acromegaly, Cushing’s may be small bubbles left; the air is harmless but too
syndrome, hyperthyroidism, and pheochromocytoma complicate large an air bubble will affect the accuracy of the insulin
the control of diabetes. dose administered.

7. Set the dose as instructed by your doctor. A gauge has
been provided on the side of the cartridge to help you
INSTRUCTIONS FOR USE judge the amount of insulin remaining. The distance
between each mark represents approximately 20 units for
HUMULIN N cartridges are designed for use with Lilly injector
3 mL cartridges or KwikPens.
systems (reusable pens).
Injecting the Dose:
HUMULIN N cartridges and KwikPens (prefilled pens) are not
designed to allow any other insulin to be mixed in the cartridge. 1. Cleanse the skin, as instructed by your healthcare
HUMULIN N cartridges and KwikPens MUST NOT be refilled tissue damage (skin thinning, skin thickening, or skin
and are not designed for use with a traditional syringe. lumps), always change the site for each injection by at
least 1.5 cm (0.5 inches) from the previous site, rotating
Do not reuse needles. NEEDLES, CARTRIDGES, AND PENS
MUST NOT BE SHARED with anyone including family
than approximately once a month. Do not inject into pits
members. Never share a HUMULIN KwikPen or cartridge, even
(depressions), thickened skin or lumps.
if the needle on the delivery device is changed. You may pass
on a serious infection or get a serious infection from the other 2. Insert the needle under the skin, as you were taught. Do
person. not inject directly into a vein.
For guidance on the use of the KwikPen (prefilled, disposable 3. To inject the insulin, follow the instructions of the pen's
pen) or Lilly’s reusable pens, please refer to the separate manufacturer.
Instructions for Use enclosed within the pen packaging.
4. Pull the needle out and apply gentle pressure over the
Preparing the Dose: injection site for several seconds. Do not rub the area.
1. Wash your hands. 5. Immediately after injection, remove the needle from the
pen. This will ensure sterility and prevent leakage, re-
2. Always examine the cartridge or KwikPen (prefilled pen) of
entry of air and potential needle clogs.
HUMULIN N after removing from the box. Re-suspend the
insulin by rolling the cartridge or KwikPen between your
Usual Dose
palms 10 times and inverting it 180 10 times.
HUMULIN N should look uniformly cloudy or milky after The dosage will be determined by your doctor, according to
mixing. If not, repeat the re-suspension procedure as often the requirements of each individual patient. HUMULIN N is
as necessary. DO NOT USE if the white insulin particles for subcutaneous (under the skin) injection only. Do not
stick to the bottom or sides of the cartridge or KwikPen or if inject into a vein.

Use in Pregnancy If a diabetic becomes delirious or mentally confused, or

suffers from loss of memory or delusions, corn syrup diluted
Control of the blood sugar is vital to assure the birth of a healthy
or orange juice with sugar should be administered by mouth.
child. Normalization of the blood sugar should have occurred
More severe hypoglycemia may require the assistance of
before conception and should continue throughout the
another person. Patients who are unable to take sugar orally
pregnancy. Since pregnancy may make diabetes worse and
or who are unconscious should be treated with intravenous
because of the importance of good diabetic control, patients who
administration of glucose at a medical facility or should be
contemplate pregnancy or who are pregnant should seek expert
given an injection of glucagon (either intramuscular or
medical advice.
subcutaneous). The patient should be given oral
Diabetic patients who are nursing may require adjustments in carbohydrates as soon as consciousness is recovered. In the
insulin dose and/or diet. event of a hypoglycemic reaction, whether mild or severe,
you should notify your doctor promptly so that any desirable
Overdose: change in diet or dosage can be determined.
Insulin reaction (too little sugar in the blood, also called In case of drug overdose, contact a healthcare practitioner,
"hypoglycemia") can be brought about by: hospital emergency department or regional Poison Control
 An infection or illness (especially with diarrhea or SIDE EFFECTS AND WHAT TO DO ABOUT THEM
vomiting) Hypoglycemia (Insulin Reaction)
 A change in the body's need for insulin.
Hypoglycemia (too little sugar in the blood) is one of the
Dietary Implications: most frequent adverse events experienced by insulin users
If a usual meal cannot be obtained at the appropriate time, then (see Proper Use of this Medication - Overdose).
carbohydrate prescribed for this meal in the form of orange Diabetic Acidosis and Coma
juice, syrup, candy, or bread and milk, without changing your Diabetic acidosis may develop if your body has too little
insulin dosage. If it becomes necessary to omit a meal on insulin (this is the opposite of insulin reaction, which is the
account of nausea and vomiting, you should test your blood result of too much insulin in the blood). Diabetic acidosis
sugar level and notify your doctor. may be brought on if you omit your insulin or take less than
Symptoms and Treatment: the doctor has prescribed, eat significantly more than your
diet calls for, or develop a fever or infection. With acidosis,
The first symptoms of insulin reaction usually come on urine tests show a large amount of sugar and acetone.
suddenly and may include vague symptoms of fatigue,
nervousness or “shakiness”, rapid heartbeat, nausea, and a cold The first symptoms of diabetic acidosis usually come on
sweat. It is of utmost importance that you understand that these gradually, over a period of hours or days, and include a
symptoms demand immediate attention. drowsy feeling, flushed face, thirst, and loss of appetite.
Heavy breathing and a rapid pulse are more severe
The patient’s ability to concentrate and to react may be impaired symptoms.
as a result of hypoglycemia. This may constitute a risk in
situations where these abilities are of special importance (e.g. If uncorrected, loss of consciousness, coma, or death can
driving a car or operating machinery – see Warnings and result. Therefore, it is important that you obtain medical
Precautions). assistance immediately.
A few patients who experienced hypoglycemic reactions after Allergy to Insulin
being transferred to HUMULIN have reported that these early
warning symptoms were less pronounced than they were with Patients occasionally experience redness, swelling, and
animal-source insulin. Some people may not recognize when itching at the site of injection of insulin. This condition,
their blood sugar drops low. called local allergy, usually clears up in a few days to a few
weeks. If you have local reactions, contact your doctor, who
Eating sugar or a sugar-sweetened product will often correct the may recommend a change in the type or species of insulin.
condition and prevent more serious symptoms. Artificial
sweeteners are not useful for the treatment of hypoglycemia. Less common, but potentially more serious, is generalized
allergy to insulin, which may cause rash over the whole
body, shortness of breath, wheezing, reduction in blood

pressure, fast pulse, or sweating. Severe cases of generalized

allergy may be life threatening. If you think you are having a REPORTING SUSPECTED SIDE EFFECTS
generalized allergic reaction to insulin, notify a doctor
immediately. Your doctor may recommend skin testing, that is, You can report any suspected adverse reactions associated
injecting small doses of other insulins into the skin, in order to with the use of health products to the Canada Vigilance
select the best insulin for you to use. Patients who have had Program by one of the following 3 ways:
severe generalized allergic reactions to insulin should be skin ------------------------------------------------------------------------
tested with each new preparation to be used before treatment  Report online at www.healthcanada.gc.ca/medeffect
with that preparation is started.  Call toll-free at 1-866-234-2345
Lipoatrophy, Lipohypertrophy, or Localized Cutaneous - Fax toll-free to 1-866-678-6789, or
Amyloidosis: - Mail to: Canada Vigilance Program
Health Canada
Rarely, administration of insulin subcutaneously can result in Postal Locator 0701D
lipoatrophy (depression in the skin), lipohypertrophy Ottawa, Ontario
(enlargement or thickening of tissue), or localized subcutaneous K1A 0K9
amyloidosis (skin lumps). If you notice any of these conditions,
consult your doctor. A change in your injection technique may Postage paid labels, Canada Vigilance Reporting
help alleviate the problem. Form and the adverse reaction reporting guidelines
This is not a complete list of side effects. For any unexpected are available on the MedEffect™ Canada Web site at
effects while taking HUMULIN N, contact your doctor or www.healthcanada.gc.ca/medeffect.
pharmacist.
HOW TO STORE IT professional. The Canada Vigilance Program does not
Your unused HUMULIN N cartridges or KwikPens (prefilled
pens) should be stored in the refrigerator (2-8C). DO NOT
FREEZE. The cartridge or KwikPen of insulin that you are
currently using does not have to be refrigerated but should be MORE INFORMATION
kept at a temperature below 25C, away from direct heat and For more information, please contact your healthcare
sunlight and protected from freezing. The cartridge of insulin professionals or pharmacist first, or Eli Lilly Canada Inc at:
currently in use should be left in the pen and may be carried
with you. Cartridges or KwikPens in use or not refrigerated 1-888-545-5972 or visit the website at www.lilly.ca
should be discarded after 28 days even if they contain insulin.
HUMULIN and KwikPen are registered trademarks owned
Inspection of Cartridge/KwikPen: by or licensed to Eli Lilly and Company, its subsidiaries or
affiliates.
DO NOT USE a cartridge or KwikPen of HUMULIN N if after
re-suspending, there are clumps floating in the insulin, or if *The brands listed are trademarks of their respective owners
solid white particles stick to the bottom or wall of the cartridge and are not trademarks of Eli Lilly Canada. The makers of
giving it a frosted appearance (re-suspend the insulin by these brands are not affiliated with and do not endorse Eli
following instruction 2 under Preparing the Dose). A cartridge Lilly Canada or its products.
or KwikPen that appears frosted or contains clumps, or is
cracked or broken should be returned to the place of purchase The information in this document is current as of the last
for exchange. revision date shown below. For the most current
your insulin, consult your healthcare professional. This leaflet was prepared by: Eli Lilly Canada Inc.
DO NOT USE AFTER EXPIRY DATE. You may need to read this package insert again. Please do
LIN-0004-CA-PM-20210524

HUMULIN N should not be given intravenously or used for

treatment of diabetic coma.
HUMULIN N should be used only if your doctor has
prescribed NPH insulin (insulin isophane).
HUMULIN® N VIALS If HUMULIN N and HUMULIN R mixtures are prescribed,
insulin isophane, human biosynthetic (rDNA origin)
amounts recommended by your doctor or purchased as
Suspension for Injection, 100 units/mL mixtures in the ratio recommended if available.
What the medicinal ingredient is:

This leaflet is part III of a three-part "Product Monograph"
 HUMULIN N contains insulin isophane, human
published when HUMULIN® N was approved for sale in
biosynthetic.
HUMULIN® N. Contact your doctor or pharmacist if you What the nonmedicinal ingredients are:
have any questions about the drug. Glycerol, m-cresol, water for injection, hydrochloric acid,
sodium hydroxide, phenol, zinc oxide, protamine sulfate and
ABOUT THIS MEDICATION
dibasic sodium phosphate.
HUMULIN has been produced by recombinant DNA processes. What dosage forms it comes in:
identical to the insulin produced by your body's pancreas and HUMULIN N (NPH) is a sterile suspension containing
because of its unique manufacturing process. insulin isophane, human biosynthetic (rDNA origin) for
subcutaneous injection. It is available in:
HUMULIN N – NPH (insulin isophane, human biosynthetic,
rDNA origin) has been modified so that it has a different - Vials, 3 mL
duration of action than Regular insulin. The result is an - Vials, 10 mL
intermediate-acting insulin with a slower onset of action than HUMULIN N is also available in:
Regular insulin and a duration of activity between 16 to 18
hours. - Cartridges, 3 mL
- KwikPens, 3 mL prefilled pen
HUMULIN N vials are for subcutaneous (under the skin)
injection only. Other available HUMULIN products include HUMULIN R
(Regular) and HUMULIN 30/70 (mixture of 30% Regular
and 70% NPH). These types of insulin differ mainly in the
time they require to take effect and in the length of time their
HUMULIN N is an intermediate-acting insulin used to treat action lasts. Your doctor has prescribed the type of insulin
patients diagnosed with diabetes mellitus. that he/she believes is best for you. Do not use any other
insulin except on your doctor's advice and direction.
What it does:
When you receive your insulin from the pharmacy, always
Insulin is a hormone that decreases the amount of sugar in your check to see that:
blood and urine by increasing the uptake of sugar from your
1. The name HUMULIN appears on the carton and vial
blood into various tissues, such as the liver, muscles, and fat.
label and is followed by the proper letter designation
To control your diabetes, your doctor has prescribed injections and name for the insulin formulation: N-NPH.
insulin.
When it should not be used: 3. The human insulin is of rDNA origin.
HUMULIN N should not be used if you are allergic to this drug 4. The insulin strength is U-100.
the insulin before that date.
HUMULIN N should not be used during episodes of

manufacturer of insulin can cause problems with your

blood sugar control.
 Some patients taking HUMULIN N will require a change
Serious Warnings and Precautions in dosage from that used with animal-source insulins. If
Hypoglycemia (too little sugar in the blood) is the most an adjustment is needed, it may be made with the first
common adverse effect of insulin products. Glucose dose or over a period of several weeks.
monitoring should be performed for all patients with  Take precautions to avoid hypoglycemia while driving or
diabetes mellitus treated with insulins. Uncorrected operating machinery. This is particularly important in
hypoglycemic or hyperglycemic reactions can cause loss patients who have reduced awareness of the warning
of consciousness, coma or even death. signs of hypoglycemia or who have frequent episodes of
A few patients who experienced hypoglycemic reactions hypoglycemia.
after being transferred to HUMULIN (insulin, human
induced visual impairment. Take caution in situations
that require these abilities such as driving or operating
Any change of insulin regimen should be made cautiously machinery.
Fast-acting insulins should be combined with alonger- insulin or miss a meal because of illness. If you miss a
acting insulin or insulin infusion pump therapy to meal, as a substitute use sugar, sugar-sweetened candy,
maintain adequate glucose control. fruit juice, or sugar-sweetened beverage according to
your doctor's instructions. If a shortage of insulin
HUMULIN N should not be mixed with any other insulin
supervision.
Do not use HUMULIN N if you see lumps that float or fluids of little or no food value, such as water, tea,
that stick to the sides of the vial, or if the contents of the coffee, broths, or clear soups.
vial are clear and remain clear after the bottle is shaken
or rotated.
 Each case of diabetes is different. Your doctor has told you  Consult your doctor concerning adjustments in your
which insulin to use, how much, and when and how often to insulin schedule if you travel across more than 2 time
inject it. This schedule has been individualized for you. zones.
cooperation with your doctor.
INTERACTIONS WITH THIS MEDICATION
 You have been instructed to test your blood and/or your
urine regularly for sugar. If your blood tests consistently There may be interactions between HUMULIN N and other
show above or below normal sugar levels or your urine medicines. Tell your doctor if you are taking any other
tests consistently show the presence of sugar, your diabetes medicine which has been prescribed for you or which you
is not properly controlled and you must let your doctor bought without a prescription.
know. Insulin requirements may be increased if you are taking
 If you become ill from any cause, especially with nausea and other drugs with hyperglycemic activity, such as oral
vomiting, your insulin requirements may change. Test your contraceptives (for example, birth control pills, injections
blood and/or urine and notify your doctor at once. and patches), thiazides (for high blood pressure or excessive
fluid retention), corticosteroids, sympathomimetics (for
 Always keep an extra supply of insulin, as well as a spare example salbutamol used to treat asthma or pseudoephedrine
needle and syringe. Always wear diabetic identification so for colds), danazol (medicine acting on ovulation), or thyroid
that appropriate treatment can be given if complications replacement therapy. Insulin requirements may also be
occur away from home. affected by diphenylhydantoin (used to treat epilepsy).
antidepressants (monoamine oxidase inhibitors), beta-

blockers, alcohol, ACE inhibitors and angiotensin II receptor 5. Draw air into the syringe equal to your insulin dose. Put
blockers, and anabolic steroids. the needle through the rubber top of the insulin vial and
inject the air into the vial.
Insulin requirements can be increased, decreased, or unchanged
in patients receiving diuretics. 6. Turn the vial and syringe upside down. Hold the vial and
syringe firmly in 1 hand.
pioglitazone), alone or in combination with other antidiabetic 7. Making sure the tip of the needle is in the insulin,
agents (including insulin), has been associated with heart failure withdraw the correct dose of insulin into the syringe.
and swelling of the lower extremities. Please contact your
8. Before removing the needle from the vial, check your
physician immediately if you develop symptoms of shortness of
syringe for air bubbles which reduce the amount of
breath, fatigue, exercise intolerance, or swelling of the lower
insulin in it. If bubbles are present, hold the syringe
needle up and tap its side until the bubbles float to the
The presence of such diseases as acromegaly, Cushing’s top. Push them out with the plunger and withdraw the
syndrome, hyperthyroidism, and pheochromocytoma complicate correct dose.
down so that the needle does not touch anything.
Injecting the Dose:
INJECTION PROCEDURES FOR VIALS 1. Cleanse the skin, as instructed by your healthcare
Correct Syringe tissue damage (skin thinning, skin thickening, or skin
Doses of insulin are measured in units. U-100 insulin contains lumps), always change the site for each injection by at
100 units/mL. It is important to use a syringe that is marked for least 1.5 cm (0.5 inches) from the previous site, rotating
U-100 insulin preparations. Failure to use the proper syringe sites on the body so that the same site is not used more
can lead to a mistake in dosage, causing serious problems for than approximately once a month. Do not inject into pits
you, such as a blood glucose level that is too low or too high. (depressions), thickened skin or lumps.
Syringe Use 2. Insert the needle under the skin, as you were taught. Do
not inject directly into a vein.
To help avoid contamination and possible infection, follow
these instructions exactly. 3. Push the plunger in as far as it will go.
Disposable syringes and needles should be used only once and 4. Pull the needle out and apply gentle pressure over the
then discarded. NEEDLES AND SYRINGES MUST NOT BE injection site for several seconds. Do not rub the area.
SHARED with anyone including family members. You may To avoid tissue damage (skin thinning, skin thickening,
pass on a serious infection or get a serious infection from the or skin lumps), give the next injection at a site at least
other person. Follow the package directions supplied with your 1.5 cm (0.5 inches) from the previous site.
syringe.
Usual Dose
Preparing the Dose:
The dosage will be determined by your doctor, according to
1. Wash your hands. the requirements of each individual patient. HUMULIN N is
2. Always examine the bottle (vial) of HUMULIN N after for subcutaneous (under the skin) injection only. Do not
removing from the box. Carefully shake or rotate the inject into a vein.
insulin vial several times to completely mix (or re-suspend)
the insulin. HUMULIN N should look uniformly cloudy or Use in Pregnancy
milky after mixing. If not, repeat the re-suspension
procedure as often as necessary until the contents are
healthy child. Normalization of the blood sugar should have
mixed. DO NOT USE if the white insulin particles stick to
occurred before conception and should continue throughout
the bottom or sides of the vial or if there are clumps
the pregnancy. Since pregnancy may make diabetes worse
floating in the insulin or if the vial is cracked or broken.
and because of the importance of good diabetic control,
3. If using a new bottle (vial), flip off the plastic protective cap, patients who contemplate pregnancy or who are pregnant
but do not remove the stopper. Wipe the top of the vial should seek expert medical advice.
with an alcohol swab. Diabetic patients who are nursing may require adjustments
4. If you are mixing insulins, follow the instructions for mixing in insulin dose and/or diet.
that were given to you by your doctor or nurse.

Overdose:
In case of drug overdose, contact a healthcare practitioner,
Hypoglycemia (Insulin Reaction): hospital emergency department or regional Poison Control
 Exercising or working too hard just before a meal Hypoglycemia (Insulin Reaction)
 An infection or illness (especially with diarrhea or Hypoglycemia (too little sugar in the blood) is one of the
vomiting) most frequent adverse events experienced by insulin users
 A change in the body's need for insulin. (see Proper Use of this Medication - Overdose).
Dietary Implications:
to avoid hypoglycemia, you should take the amount of Diabetic acidosis may develop if your body has too little
carbohydrate prescribed for this meal in the form of orange insulin (this is the opposite of insulin reaction, which is the
juice, syrup, candy, or bread and milk, without changing your result of too much insulin in the blood). Diabetic acidosis
insulin dosage. If it becomes necessary to omit a meal on may be brought on if you omit your insulin or take less than
account of nausea and vomiting, you should test your blood the doctor has prescribed, eat significantly more than your
sugar level and notify your doctor. diet calls for, or develop a fever or infection. With acidosis,
urine tests show a large amount of sugar and acetone.
Symptoms and Treatment:
The first symptoms of diabetic acidosis usually come on
The first symptoms of insulin reaction usually come on gradually, over a period of hours or days, and include a
suddenly and may include vague symptoms of fatigue, drowsy feeling, flushed face, thirst, and loss of appetite.
nervousness or “shakiness”, rapid heartbeat, nausea, and a cold Heavy breathing and a rapid pulse are more severe
sweat. It is of utmost importance that you understand that these symptoms.
symptoms demand immediate attention.
The patient’s ability to concentrate and to react may be impaired result. Therefore, it is important that you obtain medical
as a result of hypoglycemia. This may constitute a risk in assistance immediately.
driving a car or operating machinery – see Warnings and Allergy to Insulin
Precautions).
A few patients who experienced hypoglycemic reactions after itching at the site of injection of insulin. This condition,
being transferred to HUMULIN have reported that these early called local allergy, usually clears up in a few days to a few
warning symptoms were less pronounced than they were with weeks. If you have local reactions, contact your doctor, who
animal-source insulin. Some people may not recognize when may recommend a change in the type or species of insulin.
Eating sugar or a sugar-sweetened product will often correct the allergy to insulin, which may cause rash over the whole
condition and prevent more serious symptoms. Artificial body, shortness of breath, wheezing, reduction in blood
sweeteners are not useful for the treatment of hypoglycemia. pressure, fast pulse, or sweating. Severe cases of
juice with sugar should be administered by mouth. More severe doctor immediately. Your doctor may recommend skin
hypoglycemia may require the assistance of another person. testing, that is, injecting small doses of other insulins into
Patients who are unable to take sugar orally or who are the skin, in order to select the best insulin for you to use.
should be given oral carbohydrates as soon as consciousness is Lipoatrophy, Lipohypertrophy, or Localized Cutaneous
recovered. In the event of a hypoglycemic reaction, whether Amyloidosis:
any desirable change in diet or dosage can be determined. Rarely, administration of insulin subcutaneously can result
in lipoatrophy (depression in the skin), lipohypertrophy

(enlargement or thickening of tissue), or localized subcutaneous

amyloidosis (skin lumps). If you notice any of these conditions, REPORTING SUSPECTED SIDE EFFECTS
consult your doctor. A change in your injection technique may
help alleviate the problem. You can report any suspected adverse reactions associated
------------------------------------------------------------------------
effects while taking HUMULIN N, contact your doctor or
pharmacist.  Report online at www.healthcanada.gc.ca/medeffect
HOW TO STORE IT - Fax toll-free to 1-866-678-6789, or
Your unused HUMULIN N vials should be stored in the - Mail to: Canada Vigilance Program
Health Canada
Ottawa, Ontario
K1A 0K9
contain insulin.
Inspection of the Vial: www.healthcanada.gc.ca/medeffect.
DO NOT USE a vial of HUMULIN N if after re-suspending,
there are clumps floating in the insulin, or if solid white NOTE: Should you require information related to the
particles stick to the bottom or wall of the vial giving it a frosted management of side effects, contact your health
appearance (re-suspend the insulin by following instruction 2 professional. The Canada Vigilance Program does not
under Preparing the Dose). A vial that appears frosted or provide medical advice.
contains clumps, or is cracked or broken should be returned to
If you notice anything unusual in the appearance or effect of MORE INFORMATION
your insulin, consult your healthcare professional. For more information, please contact your healthcare
DO NOT USE AFTER EXPIRY DATE. professionals or pharmacist first, or Eli Lilly Canada Inc at:
1-888-545-5972 or visit the website at www.lilly.ca


LIN-0004-CA-PM-20210524

HUMULIN 30/70 should not be given intravenously or used

for treatment of diabetic coma.
HUMULIN 30/70 should be used only if your doctor has
prescribed insulins mixed in a ratio of 30% REGULAR and
70% NPH. You should not attempt to change the ratio of
HUMULIN® 30/70 CARTRIDGES
these products by adding additional NPH or REGULAR
30% insulin injection, human biosynthetic and 70% insulin insulin to this cartridge.
isophane, human biosynthetic (rDNA origin)
If HUMULIN N and HUMULIN R mixtures are prescribed
Suspension for Injection, 100 units/mL in a different proportion, the individual insulins should be
mixed as instructed in the amounts recommended by your
doctor or purchased as mixtures in the ratio recommended if
This leaflet is part III of a three-part "Product Monograph" available.
published when HUMULIN® 30/70 was approved for sale in
Canada and is designed specifically for Consumers. This What the medicinal ingredient is:
HUMULIN® 30/70. Contact your doctor or pharmacist if  HUMULIN 30/70 contains 30% HUMULIN R and
you have any questions about the drug. 70% HUMULIN N.
ABOUT THIS MEDICATION What the nonmedicinal ingredients are:

HUMULIN has been produced by recombinant DNA processes. Glycerol, m-cresol, water for injection, hydrochloric acid,
It differs from animal-source insulins because it is structurally sodium hydroxide, phenol, zinc oxide, protamine sulfate and
identical to the insulin produced by your body's pancreas and dibasic sodium phosphate.
What dosage forms it comes in:
HUMULIN 30/70 is a fixed mixture of 30% HUMULIN R-
Regular (insulin injection, human biosynthetic) and 70% HUMULIN 30/70 is a sterile suspension containing 30%
HUMULIN N- NPH (insulin isophane, human biosynthetic). It insulin injection (Regular) and 70% insulin isophane (NPH),
is an intermediate-acting insulin with a more rapid onset of human biosynthetic (rDNA origin), for subcutaneous
action than NPH insulin alone. The duration of activity may last injection only. It is available in:
between 16 to 18 hours following injection.
- Cartridges, 3 mL
HUMULIN 30/70 cartridges are for subcutaneous (under the
HUMULIN 30/70 is also available in:
skin) injection only.
- Vials, 10 mL
What the medication is used for: Other available HUMULIN products include HUMULIN R
HUMULIN 30/70 is a combination of an intermediate-acting (Regular) and HUMULIN N (NPH). These types of insulin
and a fast-acting insulin used to treat patients diagnosed with differ mainly in the time they require to take effect and in the
diabetes mellitus. length of time their action lasts. Your doctor has prescribed
the type of insulin that he/she believes is best for you. Do
What it does: not use any other insulin except on your doctor's advice
and direction.
blood and urine by increasing the uptake of sugar from your When you receive your insulin from the pharmacy, always
blood into various tissues, such as the liver, muscles, and fat. check to see that:
To control your diabetes, your doctor has prescribed injections 1. The name HUMULIN appears on the carton and
of insulin to keep your blood sugar at a nearly normal level and cartridge label and is followed by the proper letter
to keep your urine as free of sugar as possible. designation and name for the insulin formulation:
30/70: 30% insulin injection, 70% insulin isophane,
When it should not be used: human biosynthetic (rDNA) origin.
HUMULIN 30/70 should not be used if you are allergic to this 2. The carton and the cartridge label is correct for your type
drug or any of the ingredients used to formulate this medication. of insulin.
HUMULIN 30/70 should not be used during episodes of 3. The human insulin is of rDNA origin.
hypoglycemia (low blood sugar). 4. The insulin strength is U-100.

5. The expiration date on the package will allow you to use the manufacturer of insulin can cause problems with your
insulin before that date. blood sugar control.
 Some patients taking HUMULIN 30/70 will require a
WARNINGS AND PRECAUTIONS change in dosage from that used with animal-source
insulins. If an adjustment is needed, it may be made
with the first dose or over a period of several weeks.
Serious Warnings and Precautions
Hypoglycemia (too little sugar in the blood) is the most operating machinery. This is particularly important in
common adverse effect of insulin products. Glucose patients who have reduced awareness of the warning
monitoring should be performed for all patients with signs of hypoglycemia or who have frequent episodes of
diabetes mellitus treated with insulins. Uncorrected hypoglycemia.
hypoglycemic or hyperglycemic reactions can cause loss
of consciousness, coma or even death.  Ability to concentrate and react may be impaired as a
A few patients who experienced hypoglycemic reactions induced visual impairment. Take caution in situations
after being transferred to HUMULIN (insulin, human that require these abilities such as driving or operating
biosynthetic) have reported that these early warning machinery.
animal-source insulin.  Your doctor will tell you what to do if you miss a dose of
Any change of insulin regimen should be made cautiously
fruit juice, or sugar-sweetened beverage according to
HUMULIN 30/70 should not be mixed with any other your doctor's instructions. If a shortage of insulin
insulin unless clearly indicated and done under medical appears inevitable, a temporary reduction in the size of
supervision. dose may be made, accompanied by limitation of food
Under no circumstances should HUMULIN 30/70 be
fluids of little or no food value, such as water, tea,
given intravenously.
coffee, broths, or clear soups.
Do not use HUMULIN 30/70 if you see lumps that float or
that stick to the sides of the cartridge, or if the contents of
the cartridge are clear and remain clear after the
cartridge is shaken or rotated.  Consult your doctor concerning adjustments in your
inject it. This schedule has been individualized for you. INTERACTIONS WITH THIS MEDICATION
cooperation with your doctor. There may be interactions between HUMULIN 30/70 and
other medicines. Tell your doctor if you are taking any other
 You have been instructed to test your blood and/or your medicine which has been prescribed for you or which you
urine regularly for sugar. If your blood tests consistently bought without a prescription.
show above or below normal sugar levels or your urine
tests consistently show the presence of sugar, your diabetes Insulin requirements may be increased if you are taking
is not properly controlled and you must let your doctor other drugs with hyperglycemic activity, such as oral
know. contraceptives (for example, birth control pills, injections
and patches), thiazides (for high blood pressure or excessive
 If you become ill from any cause, especially with nausea and fluid retention), corticosteroids, sympathomimetics (for
vomiting, your insulin requirements may change. Test your example salbutamol used to treat asthma or pseudoephedrine
blood and/or urine and notify your doctor at once. for colds), danazol (medicine acting on ovulation), or thyroid
replacement therapy. Insulin requirements may also be
 Always keep an extra supply of insulin. Always wear
affected by diphenylhydantoin (used to treat epilepsy).
diabetic identification so that appropriate treatment can be
given if complications occur away from home. Insulin requirements may be decreased in the presence of
agents such as oral medicines for the treatment of diabetes,
 Never change from the insulin that has been prescribed for salicylates (Aspirin*), sulfa antibiotics, certain
you to another insulin without instructions from your antidepressants (monoamine oxidase inhibitors), beta-
doctor. Changing the type, strength, source, or

blockers, alcohol, ACE inhibitors and angiotensin II receptor 5. Carefully re-suspend the HUMULIN 30/70 by rolling the
blockers and anabolic steroids. cartridge and pen in your hands 10 times and inverting it
180 10 times. This must be performed each time before
Insulin requirements can be increased, decreased, or unchanged
you give yourself an injection even after just loading the
in patients receiving diuretics.
pen.
6. Prime the pen as directed by the manufacturer. If air
bubbles are present, hold the pen with the needle
pointing up and tap the side of the pen until the bubbles
float to the top. With the pen still vertical, purge the
needle with a 2 unit dose setting of the pen. Repeat until
an insulin drop appears at the end of the needle. There
may be small bubbles left; the air is harmless but too
The presence of such diseases as acromegaly, Cushing’s large an air bubble will affect the accuracy of the insulin
syndrome, hyperthyroidism, and pheochromocytoma complicate dose administered.
7. Set the dose as instructed by your doctor. A gauge has
been provided on the side of the cartridge to help you
PROPER USE OF THIS MEDICATION judge the amount of insulin remaining. The distance
between each mark represents approximately 20 units for
INSTRUCTIONS FOR USE 3 mL cartridges.
HUMULIN 30/70 cartridges are designed for use with Lilly Injecting the Dose:
injector systems (reusable pens). For guidance on the use of 1. Cleanse the skin, as instructed by your healthcare
Lilly’s reusable pens, please refer to the separate Instructions for professional, where the injection is to be made. To avoid
Use enclosed within the pen packaging tissue damage (skin thinning, skin thickening, or skin
HUMULIN 30/70 cartridges are not designed to allow any other lumps), always change the site for each injection by at
insulin to be mixed in the cartridge. least 1.5 cm (0.5 inches) from the previous site, rotating
HUMULIN 30/70 cartridges MUST NOT be refilled and are not than approximately once a month. Do not inject into pits
designed for use with a traditional syringe. (depressions), thickened skin or lumps.
2. Insert the needle under the skin, as you were taught. Do
Do not reuse needles. NEEDLES, CARTRIDGES, AND PENS not inject directly into a vein.
MUST NOT BE SHARED with anyone including family
members. Never share a HUMULIN KwikPen or cartridge, even 3. To inject the insulin, follow the instructions of the pen's
if the needle on the delivery device is changed. You may pass manufacturer.
on a serious infection or get a serious infection from the other 4. Pull the needle out and apply gentle pressure over the
person. injection site for several seconds. Do not rub the area.
Preparing the Dose: 5. Immediately after injection, remove the needle from the
pen. This will ensure sterility and prevent leakage, re-
1. Wash your hands. entry of air and potential needle clogs.
2. Always examine the cartridge of HUMULIN 30/70 after
removing from the box. Re-suspend the insulin by rolling Usual Dose
the cartridge between your palms 10 times and inverting it The dosage will be determined by your doctor, according to
180 10 times. HUMULIN 30/70 should look uniformly the requirements of each individual patient.
cloudy or milky after mixing. If not, repeat the re- HUMULIN 30/70 is for subcutaneous (under the skin)
suspension procedure as often as necessary. DO NOT USE injection only. Do not inject into a vein.
if the white insulin particles stick to the bottom or sides of
the cartridge or if there are clumps floating in the insulin, or Use in Pregnancy
if the cartridge is cracked or broken.
3. Carefully load the cartridge into the reusable pen following healthy child. Normalization of the blood sugar should have
the manufacturer’s directions. occurred before conception and should continue throughout
4. Wipe the exposed rubber membrane on the metal cap end of the pregnancy. Since pregnancy may make diabetes worse
the cartridge with an alcohol swab and attach the needle. and because of the importance of good diabetic control,

patients who contemplate pregnancy or who are pregnant should of glucagon (either intramuscular or subcutaneous). The
seek expert medical advice. patient should be given oral carbohydrates as soon as
consciousness is recovered. In the event of a hypoglycemic
Diabetic patients who are nursing may require adjustments in
reaction, whether mild or severe, you should notify your
insulin dose and/or diet.
doctor promptly so that any desirable change in diet or
dosage can be determined.
Overdose:
Insulin reaction (too little sugar in the blood, also called hospital emergency department or regional Poison Control
"hypoglycemia") can be brought about by: Centre immediately, even if there are no symptoms.
 Exercising or working too hard just before a meal SIDE EFFECTS AND WHAT TO DO ABOUT THEM
 An infection or illness (especially with diarrhea or Hypoglycemia (Insulin Reaction)
vomiting)
 A change in the body's need for insulin. Hypoglycemia (too little sugar in the blood) is one of the
most frequent adverse events experienced by insulin users
Dietary Implications: (see Proper Use of this Medication - Overdose).
to avoid hypoglycemia, you should take the amount of Diabetic Acidosis and Coma
carbohydrate prescribed for this meal in the form of orange Diabetic acidosis may develop if your body has too little
juice, syrup, candy, or bread and milk, without changing your insulin (this is the opposite of insulin reaction, which is the
insulin dosage. If it becomes necessary to omit a meal on result of too much insulin in the blood). Diabetic acidosis
account of nausea and vomiting, you should test your blood may be brought on if you omit your insulin or take less than
sugar level and notify your doctor. the doctor has prescribed, eat significantly more than your
Symptoms and Treatment: diet calls for, or develop a fever or infection. With acidosis,
The first symptoms of insulin reaction usually come on
suddenly and may include vague symptoms of fatigue, The first symptoms of diabetic acidosis usually come on
nervousness or “shakiness”, rapid heartbeat, nausea, and a cold gradually, over a period of hours or days, and include a
sweat. It is of utmost importance that you understand that these drowsy feeling, flushed face, thirst, and loss of appetite.
symptoms demand immediate attention. Heavy breathing and a rapid pulse are more severe
symptoms.
The patient’s ability to concentrate and to react may be impaired
as a result of hypoglycemia. This may constitute a risk in If uncorrected, loss of consciousness, coma, or death can
situations where these abilities are of special importance (e.g. result. Therefore, it is important that you obtain medical
driving a car or operating machinery – see Warnings and assistance immediately.
Precautions).
Allergy to Insulin
A few patients who experienced hypoglycemic reactions after
being transferred to HUMULIN have reported that these early Patients occasionally experience redness, swelling, and
warning symptoms were less pronounced than they were with itching at the site of injection of insulin. This condition,
animal-source insulin. Some people may not recognize when called local allergy, usually clears up in a few days to a few
their blood sugar drops low. weeks. If you have local reactions, contact your doctor, who
may recommend a change in the type or species of insulin.
Eating sugar or a sugar-sweetened product will often correct the
condition and prevent more serious symptoms. Artificial Less common, but potentially more serious, is generalized
sweeteners are not useful for the treatment of hypoglycemia. allergy to insulin, which may cause rash over the whole
body, shortness of breath, wheezing, reduction in blood
If a diabetic becomes delirious or mentally confused, or suffers pressure, fast pulse, or sweating. Severe cases of
from loss of memory or delusions, corn syrup diluted or orange generalized allergy may be life threatening. If you think you
juice with sugar should be administered by mouth. More severe are having a generalized allergic reaction to insulin, notify a
hypoglycemia may require the assistance of another person. doctor immediately. Your doctor may recommend skin
Patients who are unable to take sugar orally or who are testing, that is, injecting small doses of other insulins into
unconscious should be treated with intravenous administration the skin, in order to select the best insulin for you to use.
of glucose at a medical facility or should be given an injection Patients who have had severe generalized allergic reactions

to insulin should be skin tested with each new preparation to be

used before treatment with that preparation is started. REPORTING SUSPECTED SIDE EFFECTS
Lipoatrophy, Lipohypertrophy, or Localized Cutaneous You can report any suspected adverse reactions associated
Amyloidosis: with the use of health products to the Canada Vigilance
Rarely, administration of insulin subcutaneously can result in ------------------------------------------------------------------------
lipoatrophy (depression in the skin), lipohypertrophy  Report online at www.healthcanada.gc.ca/medeffect
(enlargement or thickening of tissue), or localized subcutaneous  Call toll-free at 1-866-234-2345
amyloidosis (skin lumps). If you notice any of these conditions,  Complete a Canada Vigilance Reporting Form and:
consult your doctor. A change in your injection technique may - Fax toll-free to 1-866-678-6789, or
help alleviate the problem. - Mail to: Canada Vigilance Program
This is not a complete list of side effects. For any unexpected Health Canada
effects while taking HUMULIN 30/70, contact your doctor or Postal Locator 0701D
pharmacist. Ottawa, Ontario
K1A 0K9
HOW TO STORE IT Postage paid labels, Canada Vigilance Reporting

Your unused HUMULIN 30/70 cartridges should be stored in
the refrigerator (2-8C). DO NOT FREEZE. The cartridge of
www.healthcanada.gc.ca/medeffect.
insulin that you are currently using does not have to be
refrigerated but should be kept at a temperature below 25C,
away from direct heat and sunlight and protected from freezing.
The cartridge of insulin currently in use should be left in the pen
professional. The Canada Vigilance Program does not
and may be carried with you. Cartridges in use or not
refrigerated should be discarded after 28 days even if they
contain insulin.
Inspection of the Cartridge: MORE INFORMATION
DO NOT USE a cartridge of HUMULIN 30/70 if after re- For more information, please contact your healthcare
suspending there are clumps floating in the insulin or if solid professionals or pharmacist first, or Eli Lilly Canada Inc at:
white particles stick to the bottom or wall of the cartridge giving 1-888-545-5972 or visit the website at www.lilly.ca
it a frosted appearance (re-suspend the insulin by following
instruction 2 under Preparing the Dose). A cartridge that HUMULIN is a registered trademark owned by Eli Lilly and
appears frosted or contains clumps, or is cracked or broken, Company, its subsidiaries or affiliates.
should be returned to the place of purchase for exchange.
If you notice anything unusual in the appearance or effect of *The brands listed are trademarks of their respective owners
your insulin, consult your healthcare professional. and are not trademarks of Eli Lilly Canada. The makers of
DO NOT USE AFTER EXPIRY DATE. Lilly Canada or its products.
LIN-0004-CA-PM-20210524


HUMULIN 30/70 should not be given intravenously or used
for treatment of diabetic coma.
HUMULIN 30/70 should be used only if your doctor has
® prescribed insulins mixed in a ratio of 30% REGULAR and
HUMULIN 30/70 VIALS
70% NPH. You should not attempt to change the ratio of
30% insulin injection, human biosynthetic and 70% insulin these products by adding additional NPH or REGULAR
isophane, human biosynthetic (rDNA origin) insulin to this vial.
Suspension for Injection, 100 units/mL If HUMULIN N and HUMULIN R mixtures are prescribed
in a different proportion, the individual insulins should be
mixed as instructed in the amounts recommended by your
This leaflet is part III of a three-part "Product Monograph" doctor or purchased as mixtures in the ratio recommended if
published when HUMULIN® 30/70 was approved for sale in available.
leaflet is a summary and will not tell you everything about What the medicinal ingredient is:
HUMULIN® 30/70. Contact your doctor or pharmacist if  HUMULIN 30/70 contains 30% HUMULIN R and
you have any questions about the drug. 70% HUMULIN N.
What the nonmedicinal ingredients are:

ABOUT THIS MEDICATION
Glycerol, m-cresol, water for injection, hydrochloric acid,
HUMULIN has been produced by recombinant DNA processes.
sodium hydroxide, phenol, zinc oxide, protamine sulfate and
dibasic sodium phosphate.
identical to the insulin produced by your body's pancreas and
What dosage forms it comes in:
HUMULIN 30/70 is a fixed mixture of 30% HUMULIN R-
HUMULIN 30/70 is a sterile suspension containing 30%
Regular (insulin injection, human biosynthetic) and 70%
insulin injection (Regular) and 70% insulin isophane (NPH),
HUMULIN N- NPH (insulin isophane, human biosynthetic). It
for subcutaneous injection. It is available in:
is an intermediate-acting insulin with a more rapid onset of
action than NPH insulin alone. The duration of activity may last - Vials, 10 mL
between 16 to 18 hours following injection. HUMULIN 30/70 is also available in:
- Cartridges, 3 mL
HUMULIN 30/70 vials are for subcutaneous (under the skin)
injection only. Other available HUMULIN products include HUMULIN R
(Regular) and HUMULIN N (NPH). These types of insulin
What the medication is used for: differ mainly in the time they require to take effect and in the
length of time their action lasts. Your doctor has prescribed
HUMULIN 30/70 is a combination of an intermediate-acting
the type of insulin that he/she believes is best for you. Do
and a fast-acting insulin used to treat patients diagnosed with
not use any other insulin except on your doctor's advice
diabetes mellitus.
and direction.
What it does: When you receive your insulin from the pharmacy, always
check to see that:
blood and urine by increasing the uptake of sugar from your 1. The name HUMULIN appears on the carton and vial
blood into various tissues, such as the liver, muscles, and fat. label and is followed by the proper letter designation
and name for the insulin formulation: 30/70: 30%
To control your diabetes, your doctor has prescribed injections
insulin injection, 70% insulin isophane, human
biosynthetic (rDNA) origin.
When it should not be used: insulin.
HUMULIN 30/70 should not be used if you are allergic to this 3. The human insulin is of rDNA origin.
drug or any of the ingredients used to formulate this medication.
4. The insulin strength is U-100.
HUMULIN 30/70 should not be used during episodes of 5. The expiration date on the package will allow you to use
hypoglycemia (low blood sugar). the insulin before that date.

insulins. If an adjustment is needed, it may be made with

the first dose or over a period of several weeks.
Serious Warnings and Precautions operating machinery. This is particularly important in
Hypoglycemia (too little sugar in the blood) is the most patients who have reduced awareness of the warning
common adverse effect of insulin products. Glucose signs of hypoglycemia or who have frequent episodes of
monitoring should be performed for all patients with hypoglycemia.
diabetes mellitus treated with insulins. Uncorrected  Ability to concentrate and react may be impaired as a
hypoglycemic or hyperglycemic reactions can cause loss result of hyperglycemia or as a result of hyperglycemia-
of consciousness, coma or even death. induced visual impairment. Take caution in situations
A few patients who experienced hypoglycemic reactions that require these abilities such as driving or operating
after being transferred to HUMULIN (insulin, human machinery.
Any change of insulin regimen should be made cautiously fruit juice, or sugar-sweetened beverage according to
and only under medical supervision. your doctor's instructions. If a shortage of insulin
HUMULIN 30/70 should not be mixed with any other dose may be made, accompanied by limitation of food to
insulin unless clearly indicated and done under medical two-thirds its usual quantity and a liberal increase in
supervision. fluids of little or no food value, such as water, tea,
Under no circumstances should HUMULIN 30/70 be coffee, broths, or clear soups.
given intravenously.
Do not use HUMULIN 30/70 if you see lumps that float or have doubts about your condition or your use of insulin.
that stick to the sides of the vial, or if the contents of the
 Consult your doctor concerning adjustments in your
vial are clear and remain clear after the cartridge is
shaken or rotated.
zones.
 Each case of diabetes is different. Your doctor has told you
INTERACTIONS WITH THIS MEDICATION
inject it. This schedule has been individualized for you. There may be interactions between HUMULIN 30/70 and
Proper control of your diabetes requires close and constant other medicines. Tell your doctor if you are taking any other
cooperation with your doctor. medicine which has been prescribed for you or which you
 You have been instructed to test your blood and/or your bought without a prescription.
urine regularly for sugar. If your blood tests consistently Insulin requirements may be increased if you are taking
show above or below normal sugar levels or your urine tests other drugs with hyperglycemic activity, such as oral
consistently show the presence of sugar, your diabetes is not contraceptives (for example, birth control pills, injections
properly controlled and you must let your doctor know. and patches), thiazides (for high blood pressure or excessive
fluid retention), corticosteroids, sympathomimetics (for
 If you become ill from any cause, especially with nausea and
example salbutamol used to treat asthma or pseudoephedrine
vomiting, your insulin requirements may change. Test your
blood and/or urine and notify your doctor at once.
replacement therapy. Insulin requirements may also be
 Always keep an extra supply of insulin, as well as a spare affected by diphenylhydantoin (used to treat epilepsy).
needle and syringe. Always wear diabetic identification so
Insulin requirements may be decreased in the presence of
that appropriate treatment can be given if complications
agents such as oral medicines for the treatment of diabetes,
occur away from home.
salicylates (Aspirin*), sulfa antibiotics, certain
 Never change from the insulin that has been prescribed for antidepressants (monoamine oxidase inhibitors), beta-
you to another insulin without instructions from your doctor. blockers, alcohol, ACE inhibitors and angiotensin II receptor
Changing the type, strength, source, or manufacturer of blockers, and anabolic steroids.
insulin can cause problems with your blood sugar control. Insulin requirements can be increased, decreased, or
 Some patients taking HUMULIN 30/70 will require a unchanged in patients receiving diuretics.
change in dosage from that used with animal-source

The use of thiazolidinediones (such as rosiglitazone and 6. Making sure the tip of the needle is in the insulin,
pioglitazone), alone or in combination with other antidiabetic withdraw the correct dose of insulin into the syringe.
7. Before removing the needle from the vial, check your
syringe for air bubbles which reduce the amount of
insulin in it. If bubbles are present, hold the syringe
needle up and tap its side until the bubbles float to the
top. Push them out with the plunger and withdraw the
The presence of such diseases as acromegaly, Cushing’s correct dose.
down so that the needle does not touch anything.
PROPER USE OF THIS MEDICATION Injecting the Dose:
INJECTION PROCEDURES FOR VIALS professional, where the injection is to be made. To avoid
Correct Syringe tissue damage (skin thinning, skin thickening, or skin
lumps), always change the site for each injection by at
Doses of insulin are measured in units. U-100 insulin contains least 1.5 cm (0.5 inches) from the previous site, rotating
100 units/mL. It is important to use a syringe that is marked for sites on the body so that the same site is not used more
U-100 insulin preparations. Failure to use the proper syringe than approximately once a month. Do not inject into pits
can lead to a mistake in dosage, causing serious problems for (depressions), thickened skin or lumps.
you, such as a blood glucose level that is too low or too high.
2. Inject under the skin, as you were taught. Do not inject
Syringe Use directly into a vein.
To help avoid contamination and possible infection, follow 3. Push the plunger in as far as it will go.
these instructions exactly.
4. Pull the needle out and apply gentle pressure over the
Disposable syringes and needles should be used only once and injection site for several seconds. Do not rub the area.
then discarded. NEEDLES AND SYRINGES MUST NOT BE To avoid tissue damage (skin thinning, skin thickening,
SHARED with anyone including family members. You may or skin lumps), give the next injection at a site at least
pass on a serious infection or get a serious infection from the 1.5 cm (0.5 inches) from the previous site.
other person. Follow the package directions supplied with your
syringe.
Usual Dose
Preparing the Dose: The dosage will be determined by your doctor, according to
1. Wash your hands. the requirements of each individual patient.
HUMULIN 30/70 is for subcutaneous (under the skin)
2. Always examine the bottle (vial) of HUMULIN 30/70 after injection only. Do not inject into a vein.
removing from the box. Carefully shake or rotate the
insulin vial several times to completely mix (or re-suspend)
Use in Pregnancy
the insulin. HUMULIN 30/70 should look uniformly
cloudy or milky after mixing. If not, repeat the re- Control of the blood sugar is vital to assure the birth of a
suspension procedure as often as necessary until the healthy child. Normalization of the blood sugar should have
contents are mixed. DO NOT USE if the white insulin occurred before conception and should continue throughout
particles stick to the bottom or sides of the vial or if there the pregnancy. Since pregnancy may make diabetes worse
are clumps floating in the insulin or if the vial is cracked or and because of the importance of good diabetic control,
broken. patients who contemplate pregnancy or who are pregnant
should seek expert medical advice.
3. If using a new bottle (vial), flip off the plastic protective cap,
but do not remove the stopper. Wipe the top of the vial Diabetic patients who are nursing may require adjustments
with an alcohol swab. in insulin dose and/or diet.
4. Draw air into the syringe equal to your insulin dose. Put the
needle through the rubber top of the insulin vial and inject
the air into the vial.
5. Turn the vial and syringe upside down. Hold the bottle and
syringe firmly in 1 hand.

Overdose:
Hypoglycemia (Insulin Reaction): hospital emergency department or regional Poison Control
 Exercising or working too hard just before a meal Hypoglycemia (Insulin Reaction)
 An infection or illness (especially with diarrhea or Hypoglycemia (too little glucose in the blood) is one of the
vomiting) most frequent adverse events experienced by insulin users
 A change in the body's need for insulin. (see Proper Use of this Medication - Overdose).
Dietary Implications:
to avoid hypoglycemia, you should take the amount of Diabetic acidosis may develop if your body has too little
carbohydrate prescribed for this meal in the form of orange insulin (this is the opposite of insulin reaction, which is the
juice, syrup, candy, or bread and milk, without changing your result of too much insulin in the blood). Diabetic acidosis
insulin dosage. If it becomes necessary to omit a meal on may be brought on if you omit your insulin or take less than
account of nausea and vomiting, you should test your blood the doctor has prescribed, eat significantly more than your
sugar level and notify your doctor. diet calls for, or develop a fever or infection. With acidosis,
Symptoms and Treatment:
The first symptoms of diabetic acidosis usually come on
The first symptoms of insulin reaction usually come on gradually, over a period of hours or days, and include a
suddenly and may include vague symptoms of fatigue, drowsy feeling, flushed face, thirst, and loss of appetite.
nervousness or “shakiness”, rapid heartbeat, nausea, and a cold Heavy breathing and a rapid pulse are more severe
sweat. It is of utmost importance that you understand that these symptoms.
symptoms demand immediate attention.
The patient’s ability to concentrate and to react may be impaired result. Therefore, it is important that you obtain medical
as a result of hypoglycemia. This may constitute a risk in assistance immediately.
driving a car or operating machinery – see Warnings and Allergy to Insulin
Precautions).
A few patients who experienced hypoglycemic reactions after itching at the site of injection of insulin. This condition,
being transferred to HUMULIN have reported that these early called local allergy, usually clears up in a few days to a few
warning symptoms were less pronounced than they were with weeks. If you have local reactions, contact your doctor, who
animal-source insulin. Some people may not recognize when may recommend a change in the type or species of insulin.
Eating sugar or a sugar-sweetened product will often correct the allergy to insulin, which may cause rash over the whole
condition and prevent more serious symptoms. Artificial body, shortness of breath, wheezing, reduction in blood
sweeteners are not useful for the treatment of hypoglycemia. pressure, fast pulse, or sweating. Severe cases of
juice with sugar should be administered by mouth. More doctor immediately. Your doctor may recommend skin
severe hypoglycemia may require the assistance of another testing, that is, injecting small doses of other insulins into
person. Patients who are unable to take sugar orally or who are the skin, in order to select the best insulin for you to use.
should be given oral carbohydrates as soon as consciousness is Lipoatrophy, Lipohypertrophy, or Localized Cutaneous
recovered. In the event of a hypoglycemic reaction, whether Amyloidosis:
any desirable change in diet or dosage can be determined. Rarely, administration of insulin subcutaneously can result
in lipoatrophy (depression in the skin), lipohypertrophy

(enlargement or thickening of tissue), or localized subcutaneous

amyloidosis (skin lumps). If you notice any of these conditions, REPORTING SUSPECTED SIDE EFFECTS
consult your doctor. A change in your injection technique may
help alleviate the problem. You can report any suspected adverse reactions associated
------------------------------------------------------------------------
effects while taking HUMULIN 30/70, contact your doctor or
pharmacist.  Report online at www.healthcanada.gc.ca/medeffect
HOW TO STORE IT - Fax toll-free to 1-866-678-6789, or
Your unused HUMULIN 30/70 vials should be stored in the - Mail to: Canada Vigilance Program
Health Canada
Ottawa, Ontario
K1A 0K9
contain insulin.
Inspection of the Vial: www.healthcanada.gc.ca/medeffect.
DO NOT USE a vial of HUMULIN 30/70 if after re-suspending
there are clumps floating in the insulin or if solid white particles NOTE: Should you require information related to the
stick to the bottom or wall of the vial giving it a frosted management of side effects, contact your health
appearance (re-suspend the insulin by following instruction 2 professional. The Canada Vigilance Program does not
under Preparing the Dose). A vial that appears frosted or provide medical advice.
contains clumps, or is cracked or broken, should be returned to
If you notice anything unusual in the appearance or effect of MORE INFORMATION
your insulin, consult your healthcare professional.
For more information, please contact your healthcare
DO NOT USE AFTER EXPIRY DATE. professionals or pharmacist first, or Eli Lilly Canada Inc at:
1-888-545-5972 or visit the website at www.lilly.ca


LIN-0004-CA-PM-20210524

Humulin-Ca-Pm

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Humulin-Ca-Pm

Uploaded by

Copyright:

Available Formats

PRODUCT MONOGRAPH

 Eli Lilly Canada Inc. Date of Initial Approval:

HUMULIN Product Monograph Page 1 of 54

PART I: HEALTH PROFESSIONAL INFORMATION...................................................... 3

PART II: SCIENTIFIC INFORMATION ........................................................................... 15

PART III: CONSUMER INFORMATION.......................................................................... 25

PART III: CONSUMER INFORMATION.......................................................................... 30

PART III: CONSUMER INFORMATION.......................................................................... 35

PART III: CONSUMER INFORMATION.......................................................................... 40

PART III: CONSUMER INFORMATION.......................................................................... 45

PART III: CONSUMER INFORMATION.......................................................................... 50

HUMULIN Product Monograph Page 2 of 54

PART I: HEALTH PROFESSIONAL INFORMATION

SUMMARY PRODUCT INFORMATION

Route of Dosage Form / Nonmedicinal Ingredients

INDICATIONS AND CLINICAL USE

HUMULIN Product Monograph Page 3 of 54

HUMULIN (insulin, human biosynthetic) is contraindicated during episodes of hypoglycemia.

HUMULIN is contraindicated in patients with hypersensitivity to human insulin or any of its

WARNINGS AND PRECAUTIONS

Serious Warnings and Precautions

Under no circumstances should any HUMULIN MIXTURE be given intravenously.

HUMULIN Product Monograph Page 4 of 54

Changes in Insulin Regimen / Transferring Patients from Other Insulins

Carcinogenesis and Mutagenesis

HUMULIN Product Monograph Page 5 of 54

Inadequate dosing or discontinuation of HUMULIN, especially in type 1 diabetes mellitus, may

HUMULIN Product Monograph Page 6 of 54

Insulin requirements may be decreased in the presence of hepatic impairment.

Injection Site and Local Allergic Reactions:

Lipodystrophy and Cutaneous Amyloidosis

Subcutaneous (SC) administration of insulin products including HUMULIN can result in

Systemic Allergic Reactions:

HUMULIN Product Monograph Page 7 of 54

Insulin requirements may be decreased in the presence of renal impairment.

Information for Patients

Patients should be informed about potential advantages and disadvantages of HUMULIN

HUMULIN may be used in pregnancy, if clinically indicated. It is essential to maintain good

Pediatrics (<18 years of age)

HUMULIN may be used in children and adolescents, if clinically indicated.

HUMULIN Product Monograph Page 8 of 54

HUMULIN may be used in elderly patients, if clinically indicated.

Monitoring and Laboratory Tests

Self-Monitoring of Blood Glucose

Body as a Whole – Allergic reaction(s)

Skin and appendages – Lipodystrophy

Metabolic – Hypoglycemia; Insulin resistance

HUMULIN Product Monograph Page 9 of 54

Insulin requirements can be increased, decreased, or unchanged in patients receiving diuretics.

DOSAGE AND ADMINISTRATION

Patients should be monitored closely during the adjustment period.

HUMULIN Product Monograph Page 10 of 54

Recommended Dose and Dosage Adjustment

HUMULIN-R is a clear, colourless solution. It may be administered by subcutaneous, intra-

HUMULIN-N and HUMULIN MIXTURES are suspensions. They should be administered by

Instructions for Use/Handling

To prevent the possible transmission of disease, never share a HUMULIN R, HUMULIN N, or

HUMULIN Product Monograph Page 11 of 54

Symptoms and Treatment

ACTION AND CLINICAL PHARMACOLOGY

HUMULIN Product Monograph Page 12 of 54

HUMULIN-R, insulin injection, human biosynthetic (rDNA Origin) REGULAR is a fast-acting

HUMULIN-N, insulin isophane, human biosynthetic (rDNA Origin) NPH is an intermediate-