Product Monograph: Humulin

PRODUCT MONOGRAPH
®
HUMULIN R
(insulin, human biosynthetic)
Solution for Injection, 100 units/mL
HUMULIN® N
(insulin isophane, human biosynthetic, rDNA origin)
Suspension for Injection, 100 units/mL
HUMULIN® 30/70
(30% insulin injection, 70% insulin isophane, human biosynthetic, rDNA origin)
THERAPEUTIC CLASSIFICATION
Anti-Diabetic Agent
 ELI LILLY CANADA INC. Date of Approval:

3650 Danforth Avenue May 10, 2016
Toronto, Ontario
M1N 2E8
Control No: 191693
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................................................................................................................ 11
ACTION AND CLINICAL PHARMACOLOGY............................................................ 12
STORAGE AND STABILITY ......................................................................................... 13
SPECIAL HANDLING INSTRUCTIONS....................................................................... 13
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).
Short-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 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.
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 strength,
timing of administration, manufacturer, type (e.g., regular, NPH, or insulin analogs), or method
of manufacture (recombinant DNA versus animal source insulin) may result in the need for a
change in dosage. Concomitant oral antidiabetic treatment may also need to be adjusted. 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
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).
Rarely, subcutaneous (SC) administration of insulin products including HUMULIN can result in
lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue).
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.
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.
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 short 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.

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

insulin with a duration of activity of 6 to 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 with a more rapid onset of action than NPH alone and a
duration of activity of up to 24 hours.
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.

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31. Galloway J. Highlights of clinical experiences with recombinant human insulin (r DNA)
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32. Gammeltoft S. Receptor binding of biosynthetic human insulin on isolated pig
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36. Halban P, Berger M, Gjinovci A, et al. Biologic activity and pharmacokinetics of
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37. Herings R, deBoer A, Stricker B, et al. Hypoglycemia associated with use of inhibitors
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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.
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45. Landgraf R, Kammerer S, Bock T, et al. Crossover study with human insulin of
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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.
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and porcine insulin in insulin-treated diabetic individuals with and without insulin
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clinical and immunologic studies on diabetic patient with insulin intolerance. Diabetes
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patients treated with continuous subcutaneous infusion of human insulin (recombinant
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insulin in the Gerritzen test. Diabetes Care 1981;4(2):180-182.
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biosynthetic human insulin on 2-deoxyglucose transport. Diabetes Care 1981;
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IMPORTANT: PLEASE READ
PART III: CONSUMER INFORMATION If HUMULIN N and HUMULIN R mixtures are prescribed,
the individual insulins should be mixed as instructed in the
HUMULIN® R CARTRIDGES amounts recommended by your doctor or purchased as
mixtures in the ratio recommended if available.
insulin injection, human biosynthetic (rDNA origin)
Solution for Injection, 100 units/mL What the medicinal ingredient is:
and HUMULIN® R KWIKPEN®  HUMULIN R contains insulin, human biosynthetic.
insulin injection, human biosynthetic (rDNA origin) What the nonmedicinal ingredients are:
Solution for Injection, 100 units/mL 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 short-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.
When you receive your insulin from the pharmacy, always
What the medication is used for:
check to see that:
HUMULIN R is a short-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
followed by the proper letter designation and name for
What it does:
the insulin formulation: R-Regular
Insulin is a hormone that decreases the amount of sugar in your
2. The carton and the cartridge or KwikPen label is correct
blood and urine by increasing the uptake of sugar from your
for your type of insulin.
blood into 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
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
the insulin before that date.
When it should not be used:
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).
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.

 Take precautions to avoid hypoglycemia while driving or

operating machinery. This is particularly important in
patients who have reduced awareness of the warning
Serious Warnings and Precautions signs of hypoglycemia or who have frequent episodes of
hypoglycemia.
Hypoglycemia (too little sugar in the blood) is the most
common adverse effect of insulin products. Glucose  Ability to concentrate and react may be impaired as a
monitoring should be performed for all patients with result of hyperglycemia or as a result of hyperglycemia-
diabetes mellitus treated with insulins. Uncorrected induced visual impairment. Take caution in situations
hypoglycemic or hyperglycemic reactions can cause loss that require these abilities such as driving or operating
of consciousness, coma or even death. machinery.
A few patients who experienced hypoglycemic reactions  Your doctor will tell you what to do if you miss a dose of
after being transferred to HUMULIN (insulin, human insulin or miss a meal because of illness. If you miss a
biosynthetic) have reported that these early warning meal, as a substitute use sugar, sugar-sweetened candy,
symptoms were less pronounced than they were with fruit juice, or sugar-sweetened beverage according to
animal-source insulin. your doctor's instructions. If a shortage of insulin
appears inevitable, a temporary reduction in the size of
Any change of insulin should be made cautiously and dose may be made, accompanied by limitation of food to
only under medical supervision. two-thirds its usual quantity and a liberal increase in
Short-acting insulins should be combined with a longer- fluids of little or no food value, such as water, tea,
acting insulin or insulin infusion pump therapy to coffee, broths, or clear soups.
maintain adequate glucose control.
 Consult your doctor if you notice anything unusual or
HUMULIN R should not be mixed with any other insulin have doubts about your condition or your use of insulin.
unless clearly indicated and done under medical
 Consult your doctor concerning adjustments in your
supervision.
insulin schedule if you travel across more than 2 time
The contents of the cartridge of HUMULIN R should be zones.
clear. Do not use if cloudy.
 Each case of diabetes is different. Your doctor has told you INTERACTIONS WITH THIS MEDICATION
which insulin to use, how much, and when and how often to There may be interactions between HUMULIN R and other
inject it. This schedule has been individualized for you. medicines. Tell your doctor if you are taking any other
Proper control of your diabetes requires close and constant medicine which has been prescribed for you or which you
cooperation with your doctor. bought without a prescription.
 You have been instructed to test your blood and/or your
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 for colds), danazol (medicine acting on ovulation), or thyroid
blood and/or urine and notify your doctor at once. 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 doctor. antidepressants (monoamine oxidase inhibitors), beta-
Changing the type, strength, source, or manufacturer of blockers, alcohol, ACE inhibitors and angiotensin II receptor
insulin can cause problems with your blood sugar control. blockers, and anabolic steroids.
 Some patients taking HUMULIN R will require a change in
Insulin requirements can be increased, decreased, or
dosage from that used with animal-source insulins. If an
unchanged in patients receiving diuretics.
adjustment is needed, it may be made with the first dose or
over a period of several weeks.

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

 An infection or illness (especially with diarrhea or

SIDE EFFECTS AND WHAT TO DO ABOUT THEM
vomiting)
 A change in the body's need for insulin. Hypoglycemia (Insulin Reaction)
Dietary Implications: Hypoglycemia (too little sugar in the blood) is one of the
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).
to avoid hypoglycemia, you should take the amount of
carbohydrate prescribed for this meal in the form of orange
Diabetic Acidosis and Coma
juice, syrup, candy, or bread and milk, without changing your
insulin dosage. If it becomes necessary to omit a meal on Diabetic acidosis may develop if your body has too little
account of nausea and vomiting, you should test your blood insulin (this is the opposite of insulin reaction, which is the
sugar level and notify your doctor. result of too much insulin in the blood). Diabetic acidosis
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
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.
mild or severe, you should notify your doctor promptly so that
any desirable change in diet or dosage can be determined.
Lipoatrophy or Lipohypertrophy:
Rarely, administration of insulin subcutaneously can result
In case of drug overdose, contact a healthcare practitioner, in lipoatrophy (depression in the skin) or lipohypertrophy
hospital emergency department or regional Poison Control (enlargement or thickening of tissue). If you notice either of
Centre immediately, even if there are no symptoms. 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 cartridges or KwikPens (prefilled
HUMULIN and KwikPen are registered trademarks owned
pens) should be stored in the refrigerator (2-8C). DO NOT
by or licensed to Eli Lilly and Company, its subsidiaries or
FREEZE. The cartridge or KwikPen of insulin that you are
affiliates.
currently using does not have to be refrigerated but should be
kept at a temperature below 25C, away from direct heat and
*The brands listed are trademarks of their respective owners
sunlight and protected from freezing. The cartridge of insulin
and are not trademarks of Eli Lilly Canada. The makers of
currently in use should be left in the pen and may be carried
these brands are not affiliated with and do not endorse Eli
with you. Cartridges or KwikPens in use or not refrigerated
Lilly Canada or its products.
should be discarded after 28 days even if they contain insulin.
The information in this document is current as of the last
Inspection of Cartridge: revision date shown below. For the most current
HUMULIN R should be clear and colourless. DO NOT USE a information please visit our website or contact us directly.
cartridge or KwikPen of HUMULIN R if it appears cloudy,
This leaflet was prepared by Eli Lilly Canada Inc., Toronto,
thickened, or slightly coloured, or if solid particles are visible.
Ontario, M1N 2E8.
A cartridge or KwikPen that is not clear and colourless or that is
cracked or broken should be returned to the place of purchase You may need to read this package insert again. Please do
for exchange. not throw it away until you have finished your medicine.
If you notice anything unusual in the appearance or effect of Last revised:
your insulin, consult your healthcare professional.
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
 Complete a Canada Vigilance Reporting Form and:
- Fax toll-free to 1-866-678-6789, or
- Mail to: Canada Vigilance Program
Health Canada
Postal Locator 0701D
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
provide medical advice.

What the medicinal ingredient is:

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

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.
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 should be made cautiously and fruit juice, or sugar-sweetened beverage according to
only under medical supervision. your doctor's instructions. If a shortage of insulin
Short-acting insulins should be combined with a longer- dose may be made, accompanied by limitation of food to
acting insulin or insulin infusion pump therapy 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.
supervision.
have doubts about your condition or your use of insulin.
The contents of the vial of HUMULIN R should be clear.
Do not use if cloudy.
 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.
Proper control of your diabetes requires close and constant INTERACTIONS WITH THIS MEDICATION
cooperation with your doctor. There may be interactions between HUMULIN R 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 tests bought without a prescription.
consistently show the presence of sugar, your diabetes is not Insulin requirements may be increased if you are taking
properly controlled and you must let your doctor know. 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
example salbutamol used to treat asthma or pseudoephedrine
 Always keep an extra supply of insulin, as well as a spare for colds), danazol (medicine acting on ovulation), or thyroid
needle and syringe . Always wear diabetic identification so replacement therapy. Insulin requirements may also be
that appropriate treatment can be given if complications affected by diphenylhydantoin (used to treat epilepsy).
occur away from home.
Insulin requirements may be decreased in the presence of
 Never change from the insulin that has been prescribed for agents such as oral medicines for the treatment of diabetes,
you to another insulin without instructions from your doctor. salicylates (Aspirin*), sulfa antibiotics, certain
Changing the type, strength, source, or manufacturer of antidepressants (monoamine oxidase inhibitors), beta-
insulin can cause problems with your 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 in patients receiving diuretics.

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.
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.
syndrome, hyperthyroidism, and pheochromocytoma complicate
the control of diabetes. Injecting the Dose:
PROPER USE OF THIS MEDICATION
professional, where the injection is to be made.
INJECTION PROCEDURES FOR VIALS 2. Inject under the skin, as you were taught. Do not inject
directly into a vein.
Correct Syringe
3. Push the plunger in as far as it will go.
Doses of insulin are measured in units. U-100 insulin contains
100 units/mL. It is important to use a syringe that is marked for 4. Pull the needle out and apply gentle pressure over the
U-100 insulin preparations. Failure to use the proper syringe injection site for several seconds. Do not rub the area.
can lead to a mistake in dosage, causing serious problems for To avoid tissue damage, give the next injection at a site
you, such as a blood glucose level that is too low or too high. at least 1.5 cm (0.5 inches) from the previous site.
Syringe Use
Usual Dose
To help avoid contamination and possible infection, follow
these instructions exactly.
the requirements of each individual patient. HUMULIN R is
Disposable syringes and needles should be used only once and for subcutaneous (under the skin) injection. Do not inject
then discarded. NEEDLES AND SYRINGES MUST NOT BE into a vein.
SHARED with anyone including family members. You may
pass on a serious infection or get a serious infection from the Use in Pregnancy
other person. Follow the package directions supplied with your
Control of the blood sugar is vital to assure the birth of a
syringe.
Preparing the Dose: occurred before conception and should continue throughout
the pregnancy. Since pregnancy may make diabetes worse
1. Wash your hands.
2. Always examine the vial of HUMULIN R after removing patients who contemplate pregnancy or who are pregnant
from the box. HUMULIN R should look clear and should seek expert medical advice.
colourless. DO NOT use HUMULIN R if it appears cloudy,
thickened, or slightly coloured or if solid particles are
visible, or if the vial is cracked or broken.
3. If using a new bottle (vial), flip off the plastic protective cap, Overdose:
but do not remove the stopper. Wipe the top of the vial with
Hypoglycemia (Insulin Reaction):
an alcohol swab.
4. If you are mixing insulins, follow the instructions for mixing
given to you by your doctor or nurse.
5. Draw air into the syringe equal to your insulin dose. Put the  Taking too much insulin
needle through the rubber top of the insulin vial and inject  Missing or delaying meals
the air into the vial.  Exercising or working too hard just before a meal
 An infection or illness (especially with diarrhea or
6. Turn the vial and syringe upside down. Hold the vial and vomiting)
syringe firmly in 1 hand.  A change in the body's need for insulin.
7. Making sure the tip of the needle is in the insulin, withdraw
the correct dose of insulin into the syringe.

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

HOW TO STORE IT MORE INFORMATION

Your unused HUMULIN R vials should be stored in the For more information, please contact your healthcare
refrigerator (2-8C). DO NOT FREEZE. The vial of insulin professionals or pharmacist first, or Eli Lilly Canada Inc at:
that you are currently using does not have to be refrigerated but
1-888-545-5972 or visit the website at www.lilly.ca
should be kept at a temperature below 25C, away from direct
heat and sunlight and protected from freezing. Vials in use or
HUMULIN is a registered trademark owned by Eli Lilly and
not refrigerated should be discarded after 28 days even if they
Company, its subsidiaries or affiliates.
contain insulin.
Inspection of the Vial: and are not trademarks of Eli Lilly Canada. The makers of
HUMULIN R should be clear and colourless. DO NOT USE a these brands are not affiliated with and do not endorse Eli
vial of HUMULIN R if it appears cloudy, thickened, or slightly Lilly Canada or its products.
coloured or if solid particles are visible. A vial that is not clear
and colourless or that is cracked or broken should be returned to
revision date shown below. For the most current
the place of purchase for exchange.
information please visit our website or contact us directly.
If you notice anything unusual in the appearance or effect of
Ontario, M1N 2E8.
DO NOT USE AFTER EXPIRY DATE. You may need to read this package insert again. Please do
not throw it away until you have finished your medicine.
REPORTING SUSPECTED SIDE EFFECTS Last revised:
------------------------------------------------------------------------
Health Canada
Ottawa, Ontario
K1A 0K9



HUMULIN N should not be given intravenously or used for

treatment of diabetic coma.
HUMULIN® N CARTRIDGES 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).
If HUMULIN N and HUMULIN R mixtures are prescribed,
and HUMULIN® N KWIKPEN® the individual insulins should be mixed as instructed in the
amounts recommended by your doctor or purchased as
insulin isophane, human biosynthetic (rDNA origin)
mixtures in the ratio recommended if available.
This leaflet is part III of a three-part "Product Monograph" What the medicinal ingredient is:
published when HUMULIN® N was approved for sale in
Canada and is designed specifically for Consumers. This  HUMULIN N contains insulin isophane, human
leaflet is a summary and will not tell you everything about biosynthetic.
HUMULIN® N. Contact your doctor or pharmacist if you
have any questions about the drug. What the nonmedicinal ingredients are:
Glycerol, m-cresol, water for injection, hydrochloric acid,
ABOUT THIS MEDICATION sodium hydroxide, phenol, zinc oxide, protamine sulfate and
dibasic sodium phosphate.
HUMULIN has been produced by recombinant DNA processes.
It differs from animal-source insulins because it is structurally What dosage forms it comes in:
identical to the insulin produced by your body's pancreas and
because of its unique manufacturing process. HUMULIN N (NPH) is a sterile suspension containing
insulin isophane, human biosynthetic (rDNA origin) for
HUMULIN N – NPH (insulin isophane, human biosynthetic, subcutaneous injection. It is available in:
rDNA origin) has been modified so that it has a different - Cartridges, 3 mL
duration of action than Regular insulin. The result is an - KwikPens, 3 mL prefilled pen
intermediate-acting insulin with a slower onset of action than
Regular insulin and a longer duration of activity of up to 24 HUMULIN N is also available in:
hours. - Vials, 3 mL
- Vials, 10 mL
HUMULIN N cartridges and HUMULIN N KwikPen (prefilled
pens) are for subcutaneous (under the skin) injection only. Other available HUMULIN products include HUMULIN R
(Regular) and HUMULIN 30/70 (mixture of 30% Regular
What the medication is used for: 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:
Insulin is a hormone that decreases the amount of sugar in your check to see that:
blood into various tissues, such as the liver, muscles, and fat. 1. The name HUMULIN appears on the carton and
cartridge or KwikPen (prefilled pen) label and is
To control your diabetes, your doctor has prescribed injections followed by the proper letter designation and name for
of insulin to keep your blood sugar at a nearly normal level and the insulin formulation: N-NPH.
2. The carton and cartridge or KwikPen label is correct for
When it should not be used: your type of insulin.
HUMULIN N should not be used if you are allergic to this drug 3. The human insulin is of rDNA origin.
or any of the ingredients used to formulate this medication. 4. The insulin strength is U-100.
HUMULIN N should not be used during episodes of 5. The expiration date on the package will allow you to use
hypoglycemia (too little sugar in the blood). the insulin before that date.

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

or over a period of several weeks.
insulin or miss a meal because of illness. If you miss a
Short-acting insulins should be combined with a longer- dose may be made, accompanied by limitation of food to
acting insulin or insulin infusion pump therapy 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 N should not be mixed with any other insulin coffee, broths, or clear soups.
supervision.
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
zones.
shaken or rotated.
 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 N and other
Proper control of your diabetes requires close and constant medicines. Tell your doctor if you are taking any other
cooperation with your doctor. medicine which has been prescribed for you or which you
bought without a prescription.
 You have been instructed to test your blood and/or your
urine regularly for sugar. If your blood tests consistently
show above or below normal sugar levels or your urine tests Insulin requirements may be increased if you are taking
consistently show the presence of sugar, your diabetes is not other drugs with hyperglycemic activity, such as oral
properly controlled and you must let your doctor 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).
given if complications occur away from home.
you to another insulin without instructions from your doctor. salicylates (Aspirin*), sulfa antibiotics, certain
Changing the type, strength, source, or manufacturer of antidepressants (monoamine oxidase inhibitors), beta-
insulin can cause problems with your blood sugar control. blockers, alcohol, ACE inhibitors and angiotensin II receptor
blockers and anabolic steroids.
 Some patients taking HUMULIN N will require a change in
dosage from that used with animal-source insulins. If an

Insulin requirements can be increased, decreased, or unchanged 5. Carefully re-suspend the HUMULIN N by rolling the
in patients receiving diuretics. cartridge and pen in your hands 10 times and inverting it
180 10 times. This must be performed each time before
The use of thiazolidinediones (such as rosiglitazone and
you give yourself an injection even after just loading the
pioglitazone), alone or in combination with other antidiabetic
pen.
and swelling of the lower extremities. Please contact your 6. Prime the pen as directed by the manufacturer. If air
physician immediately if you develop symptoms of shortness of bubbles are present, hold the pen with the needle
breath, fatigue, exercise intolerance, or swelling of the lower pointing up and tap the side of the pen until the bubbles
extremities while you are on these agents. 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
large an air bubble will affect the accuracy of the insulin
dose administered.
INSTRUCTIONS FOR USE been provided on the side of the cartridge to help you
HUMULIN N cartridges are designed for use with Lilly injector judge the amount of insulin remaining. The distance
systems (reusable pens). between each mark represents approximately 20 units for
3 mL cartridges or KwikPens.
HUMULIN N cartridges and KwikPens (prefilled pens) are not
designed to allow any other insulin to be mixed in the cartridge. Injecting the Dose:
HUMULIN N cartridges and KwikPens MUST NOT be refilled professional, where the injection is to be made. To avoid
and are not designed for use with a traditional syringe. tissue damage, always change the site for each injection
Do not reuse needles. NEEDLES, CARTRIDGES, AND PENS by at least 1.5 cm (0.5 inches) from the previous site,
MUST NOT BE SHARED with anyone including family rotating sites on the body.
members. Never share a HUMULIN KwikPen or cartridge, even 2. Insert the needle under the skin, as you were taught. Do
if the needle on the delivery device is changed. You may pass not inject directly into a vein.
on a serious infection or get a serious infection from the other
person. 3. To inject the insulin, follow the instructions of the pen's
manufacturer.
For guidance on the use of the KwikPen (prefilled, disposable
pen) or Lilly’s reusable pens, please refer to the separate 4. Pull the needle out and apply gentle pressure over the
Instructions for Use enclosed within the pen packaging. 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 or KwikPen (prefilled pen) of
HUMULIN N after removing from the box. Re-suspend the Usual Dose
insulin by rolling the cartridge or KwikPen between your
palms 10 times and inverting it 180 10 times. HUMULIN the requirements of each individual patient. HUMULIN N is
N should look uniformly cloudy or milky after mixing. If for subcutaneous (under the skin) injection only. Do not
not, repeat the re-suspension procedure as often as inject into a vein.
necessary. DO NOT USE if the white insulin particles stick
to the bottom or sides of the cartridge or KwikPen or if there
Use in Pregnancy
are clumps floating in the insulin, or if the cartridge or Control of the blood sugar is vital to assure the birth of a
KwikPen is cracked or broken. healthy child. Normalization of the blood sugar should have
3. Carefully load the cartridge into the reusable pen following occurred before conception and should continue throughout
the manufacturer’s directions. the pregnancy. Since pregnancy may make diabetes worse
4. Wipe the exposed rubber membrane on the metal cap end of patients who contemplate pregnancy or who are pregnant
the cartridge or KwikPen (prefilled pen) with an alcohol should seek expert medical advice.
swab and attach the needle.

Overdose:
In case of drug overdose, contact a healthcare practitioner,
Hypoglycemia (Insulin Reaction): hospital emergency department or regional Poison Control
Centre immediately, even if there are no symptoms.
 Taking too much insulin
 Missing or delaying meals
 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).
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.
If uncorrected, loss of consciousness, coma, or death can
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.
situations where these abilities are of special importance (e.g.
driving a car or operating machinery – see Warnings and Allergy to Insulin
Precautions).
Patients occasionally experience redness, swelling, and
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.
Less common, but potentially more serious, is generalized
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
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.
recovered. In the event of a hypoglycemic reaction, whether Lipoatrophy or Lipohypertrophy:


injection technique may help alleviate the problem. REPORTING SUSPECTED SIDE EFFECTS
This is not a complete list of side effects. For any unexpected You can report any suspected adverse reactions associated
effects while taking HUMULIN N, contact your doctor or with the use of health products to the Canada Vigilance
pharmacist. Program by one of the following 3 ways:
------------------------------------------------------------------------
HOW TO STORE IT
Your unused HUMULIN N cartridges or KwikPens (prefilled  Complete a Canada Vigilance Reporting Form and:
pens) should be stored in the refrigerator (2-8C). DO NOT - Fax toll-free to 1-866-678-6789, or
FREEZE. The cartridge or KwikPen of insulin that you are - Mail to: Canada Vigilance Program
currently using does not have to be refrigerated but should be Health Canada
kept at a temperature below 25C, away from direct heat and Postal Locator 0701D
sunlight and protected from freezing. The cartridge of insulin Ottawa, Ontario
currently in use should be left in the pen and may be carried K1A 0K9
with you. Cartridges or KwikPens in use or not refrigerated
should be discarded after 28 days even if they contain insulin. Postage paid labels, Canada Vigilance Reporting
Inspection of Cartridge/KwikPen: are available on the MedEffect™ Canada Web site at
DO NOT USE a cartridge or KwikPen of HUMULIN N if after
re-suspending, there are clumps floating in the insulin, or if NOTE: Should you require information related to the
solid white particles stick to the bottom or wall of the cartridge management of side effects, contact your health
giving it a frosted appearance (re-suspend the insulin by professional. The Canada Vigilance Program does not
following instruction 2 under Preparing the Dose). A cartridge
or KwikPen that appears frosted or contains clumps, or is
cracked or broken should be returned to the place of purchase
for exchange.
MORE INFORMATION
your insulin, consult your healthcare professional. For more information, please contact your healthcare
professionals or pharmacist first, or Eli Lilly Canada Inc at:
HUMULIN and KwikPen are registered trademarks owned

by or licensed to Eli Lilly and Company, its subsidiaries or
affiliates.

Ontario, M1N 2E8.
You may need to read this package insert again. Please do
Last revised:

If HUMULIN N and HUMULIN R mixtures are prescribed,

the individual insulins should be mixed as instructed in the
amounts recommended by your doctor or purchased as
HUMULIN® N VIALS mixtures in the ratio recommended if available.
insulin isophane, human biosynthetic (rDNA origin)
What the medicinal ingredient is:
Suspension for Injection, 100 units/mL  HUMULIN N contains insulin isophane, human
This leaflet is part III of a three-part "Product Monograph" biosynthetic.
published when HUMULIN® N was approved for sale in
Canada and is designed specifically for Consumers. This What the nonmedicinal ingredients are:
leaflet is a summary and will not tell you everything about Glycerol, m-cresol, water for injection, hydrochloric acid,
HUMULIN® N. Contact your doctor or pharmacist if you sodium hydroxide, phenol, zinc oxide, protamine sulfate and
have any questions about the drug. dibasic sodium phosphate.
ABOUT THIS MEDICATION What dosage forms it comes in:
HUMULIN has been produced by recombinant DNA processes. HUMULIN N (NPH) is a sterile suspension containing
It differs from animal-source insulins because it is structurally insulin isophane, human biosynthetic (rDNA origin) for
identical to the insulin produced by your body's pancreas and subcutaneous injection. It is available in:
because of its unique manufacturing process. - Vials, 3 mL
HUMULIN N – NPH (insulin isophane, human biosynthetic, - Vials, 10 mL
rDNA origin) has been modified so that it has a different HUMULIN N is also available in:
duration of action than Regular insulin. The result is an
intermediate-acting insulin with a slower onset of action than - Cartridges, 3 mL
Regular insulin and a longer duration of activity of up to 24 - KwikPens, 3 mL prefilled pen
hours. Other available HUMULIN products include HUMULIN R
HUMULIN N vials are for subcutaneous (under the skin) (Regular) and HUMULIN 30/70 (mixture of 30% Regular
injection only. 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 the medication is used for: action lasts. Your doctor has prescribed the type of insulin
that he/she believes is best for you. Do not use any other
HUMULIN N is an intermediate-acting insulin used to treat insulin except on your doctor's advice and direction.
patients diagnosed with diabetes mellitus.
What it does: check to see that:
Insulin is a hormone that decreases the amount of sugar in your 1. The name HUMULIN appears on the carton and vial
blood and urine by increasing the uptake of sugar from your label and is followed by the proper letter designation
blood into various tissues, such as the liver, muscles, and fat. and name for the insulin formulation: N-NPH.
To control your diabetes, your doctor has prescribed injections 2. The carton and the vial label is correct for your type of
of insulin to keep your blood sugar at a nearly normal level and insulin.
to keep your urine as free of sugar as possible. 3. The human insulin is of rDNA origin.
When it should not be used: 4. The insulin strength is U-100.
HUMULIN N should not be used if you are allergic to this drug 5. The expiration date on the package will allow you to use
or any of the ingredients used to formulate this medication. the insulin before that date.
HUMULIN N should not be used during episodes of

HUMULIN N should not be given intravenously or used for
HUMULIN N should be used only if your doctor has prescribed
NPH insulin (insulin isophane).

 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

common adverse effect of insulin products. Glucose  Take precautions to avoid hypoglycemia while driving or
monitoring should be performed for all patients with operating machinery. This is particularly important in
diabetes mellitus treated with insulins. Uncorrected patients who have reduced awareness of the warning
hypoglycemic or hyperglycemic reactions can cause loss signs of hypoglycemia or who have frequent episodes of
of consciousness, coma or even death. hypoglycemia.
A few patients who experienced hypoglycemic reactions  Ability to concentrate and react may be impaired as a
after being transferred to HUMULIN (insulin, human result of hyperglycemia or as a result of hyperglycemia-
biosynthetic) have reported that these early warning induced visual impairment. Take caution in situations
symptoms were less pronounced than they were with that require these abilities such as driving or operating
animal-source insulin. machinery.
Any change of insulin should be made cautiously and  Your doctor will tell you what to do if you miss a dose of
only under medical supervision. insulin or miss a meal because of illness. . If you miss a
meal, as a substitute use sugar, sugar-sweetened candy,
Short-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.
HUMULIN N should not be mixed with any other insulin dose may be made, accompanied by limitation of food to
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,
coffee, broths, or clear soups.
Do not use HUMULIN N if you see lumps that float or
that stick to the sides of the vial, or if the contents of the  Consult your doctor if you notice anything unusual or
vial are clear and remain clear after the bottle is shaken have doubts about your condition or your use of insulin.
or rotated.
 Each case of diabetes is different. Your doctor has told you insulin schedule if you travel across more than 2 time
which insulin to use, how much, and when and how often to zones.
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 tests bought without a prescription.
consistently show the presence of sugar, your diabetes 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
for colds), danazol (medicine acting on ovulation), or thyroid
needle and syringe. Always wear diabetic identification so
that appropriate treatment can be given if complications
affected by diphenylhydantoin (used to treat epilepsy).
occur away from home.
you to another insulin without instructions from your doctor.
salicylates (Aspirin*), sulfa antibiotics, certain
Changing the type, strength, source, or manufacturer of
antidepressants (monoamine oxidase inhibitors), beta-
insulin can cause problems with your blood sugar control.
blockers, alcohol, ACE inhibitors and angiotensin II receptor
blockers, and anabolic steroids.

Insulin requirements can be increased, decreased, or unchanged 5. Draw air into the syringe equal to your insulin dose. Put
in patients receiving diuretics. the needle through the rubber top of the insulin vial and
inject the air into the vial.
pioglitazone), alone or in combination with other antidiabetic 6. Turn the vial and syringe upside down. Hold the vial and
agents (including insulin), has been associated with heart failure syringe firmly in 1 hand.
7. Making sure the tip of the needle is in the insulin,
withdraw the correct dose of insulin into the syringe.
extremities while you are on these agents. 8. 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
correct dose.
down so that the needle does not touch anything.
INJECTION PROCEDURES FOR VIALS
Injecting the Dose:
Correct Syringe
Doses of insulin are measured in units. U-100 insulin contains professional, where the injection is to be made.
100 units/mL. It is important to use a syringe that is marked for
U-100 insulin preparations. Failure to use the proper syringe 2. Insert the needle under the skin, as you were taught. Do
can lead to a mistake in dosage, causing serious problems for not inject directly into a vein.
you, such as a blood glucose level that is too low or too high. 3. Push the plunger in as far as it will go.
Syringe Use 4. Pull the needle out and apply gentle pressure over the
To help avoid contamination and possible infection, follow injection site for several seconds. Do not rub the area.
these instructions exactly. To avoid tissue damage, give the next injection at a site
at least 1.5 cm (0.5 inches) from the previous site.
Disposable syringes and needles should be used only once and
then discarded. NEEDLES AND SYRINGES MUST NOT BE
Usual Dose
SHARED with anyone including family members. You may
pass on a serious infection or get a serious infection from the The dosage will be determined by your doctor, according to
other person. Follow the package directions supplied with your the requirements of each individual patient. HUMULIN N is
syringe. for subcutaneous (under the skin) injection only. Do not
inject into a vein.
Preparing the Dose:
1. Wash your hands. Use in Pregnancy
2. Always examine the bottle (vial) of HUMULIN N after Control of the blood sugar is vital to assure the birth of a
removing from the box. Carefully shake or rotate the insulin healthy child. Normalization of the blood sugar should have
vial several times to completely mix (or re-suspend) the occurred before conception and should continue throughout
insulin. HUMULIN N should look uniformly cloudy or the pregnancy. Since pregnancy may make diabetes worse
milky after mixing. If not, repeat the re-suspension and because of the importance of good diabetic control,
procedure as often as necessary until the contents are mixed. patients who contemplate pregnancy or who are pregnant
DO NOT USE if the white insulin particles stick to the should seek expert medical advice.
bottom or sides of the vial or if there are clumps floating in
the insulin or if the vial is cracked or broken.
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 with Overdose:
an alcohol swab.
4. If you are mixing insulins, follow the instructions for mixing
that were given to you by your doctor or nurse.


 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
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
of glucagon (either intramuscular or subcutaneous). The patient to insulin should be skin tested with each new preparation to
should be given oral carbohydrates as soon as consciousness is be used before treatment with that preparation is started.
any desirable change in diet or dosage can be determined. Rarely, administration of insulin subcutaneously can result
In case of drug overdose, contact a healthcare practitioner, these conditions, consult your doctor. A change in your
hospital emergency department or regional Poison Control injection technique may help alleviate the problem.
unexpected effects while taking HUMULIN N, contact your
doctor or pharmacist.

HOW TO STORE IT MORE INFORMATION

Your unused HUMULIN N vials should be stored in the For more information, please contact your healthcare
refrigerator (2-8C). DO NOT FREEZE. The vial of insulin professionals or pharmacist first, or Eli Lilly Canada Inc at:
that you are currently using does not have to be refrigerated but
contain insulin.
Inspection of the Vial: and are not trademarks of Eli Lilly Canada. The makers of
DO NOT USE a vial of HUMULIN N if after re-suspending, these brands are not affiliated with and do not endorse Eli
there are clumps floating in the insulin, or if solid white Lilly Canada or its products.
particles stick to the bottom or wall of the vial giving it a frosted
appearance (re-suspend the insulin by following instruction 2
under Preparing the Dose). A vial that appears frosted or
contains clumps, or is cracked or broken should be returned to
the place of purchase for exchange. This leaflet was prepared by Eli Lilly Canada Inc., Toronto,
Ontario, M1N 2E8.
your insulin, consult your healthcare professional. You may need to read this package insert again. Please do
Last revised:
REPORTING SUSPECTED SIDE EFFECTS

------------------------------------------------------------------------
Health Canada
Ottawa, Ontario
K1A 0K9




HUMULIN 30/70 should be used only if your doctor has
HUMULIN® 30/70 CARTRIDGES prescribed insulins mixed in a ratio of 30% REGULAR and
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 cartridge.
Suspension for Injection, 100 units/mL If HUMULIN N and HUMULIN R mixtures are prescribed
This leaflet is part III of a three-part "Product Monograph" in a different proportion, the individual insulins should be
published when HUMULIN® 30/70 was approved for sale in mixed as instructed in the amounts recommended by your
Canada and is designed specifically for Consumers. This doctor or purchased as mixtures in the ratio recommended if
leaflet is a summary and will not tell you everything about available.
HUMULIN® 30/70. Contact your doctor or pharmacist if
you have any questions about the drug. What the medicinal ingredient is:
ABOUT THIS MEDICATION  HUMULIN 30/70 contains 30% HUMULIN R and

70% HUMULIN N.
HUMULIN has been produced by recombinant DNA processes.
It differs from animal-source insulins because it is structurally What the nonmedicinal ingredients are:
identical to the insulin produced by your body's pancreas and
because of its unique manufacturing process. Glycerol, m-cresol, water for injection, hydrochloric acid,
sodium hydroxide, phenol, zinc oxide, protamine sulfate and
HUMULIN 30/70 is a fixed mixture of 30% HUMULIN R- dibasic sodium phosphate.
Regular (insulin injection, human biosynthetic) and 70%
HUMULIN N- NPH (insulin isophane, human biosynthetic). It What dosage forms it comes in:
is an intermediate-acting insulin with a more rapid onset of
action than NPH insulin alone. The duration of activity may last HUMULIN 30/70 is a sterile suspension containing 30%
up to 24 hours following injection. insulin injection (Regular) and 70% insulin isophane (NPH),
human biosynthetic (rDNA origin), for subcutaneous
HUMULIN 30/70 cartridges are for subcutaneous (under the injection only. It is available in:
skin) injection only.
- Cartridges, 3 mL
What the medication is used for: HUMULIN 30/70 is also available in:
HUMULIN 30/70 is a combination of an intermediate-acting - Vials, 10 mL
and a short-acting insulin used to treat patients diagnosed with
diabetes mellitus. Other available HUMULIN products include HUMULIN R
(Regular) and HUMULIN N (NPH). These types of insulin
What it does: differ mainly in the time they require to take effect and in the
length of time their action lasts. Your doctor has prescribed
Insulin is a hormone that decreases the amount of sugar in your the type of insulin that he/she believes is best for you. Do
blood and urine by increasing the uptake of sugar from your not use any other insulin except on your doctor's advice
blood into various tissues, such as the liver, muscles, and fat. and direction.
To control your diabetes, your doctor has prescribed injections When you receive your insulin from the pharmacy, always
of insulin to keep your blood sugar at a nearly normal level and check to see that:
1. The name HUMULIN appears on the carton and
When it should not be used: cartridge label and is followed by the proper letter
designation and name for the insulin formulation: 30/70:
HUMULIN 30/70 should not be used if you are allergic to this 30% insulin injection, 70% insulin isophane, human
drug or any of the ingredients used to formulate this medication. biosynthetic (rDNA) origin.
HUMULIN 30/70 should not be used during episodes of 2. The carton and the cartridge label is correct for your type
hypoglycemia (low blood sugar). of insulin.
HUMULIN 30/70 should not be given intravenously or used for 3. The human insulin is of rDNA origin.
4. The insulin strength is U-100.

5. The expiration date on the package will allow you to use the  Some patients taking HUMULIN 30/70 will require a
insulin before that date. 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.
operating machinery. This is particularly important in
Serious Warnings and Precautions patients who have reduced awareness of the warning
Hypoglycemia (too little sugar in the blood) is the most signs of hypoglycemia or who have frequent episodes of
common adverse effect of insulin products. Glucose hypoglycemia.
monitoring should be performed for all patients with
that require these abilities such as driving or operating
A few patients who experienced hypoglycemic reactions machinery.
after being transferred to HUMULIN (insulin, human
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
fruit juice, or sugar-sweetened beverage according to
Any change of insulin should be made cautiously and your doctor's instructions. If a shortage of insulin
only under medical supervision. appears inevitable, a temporary reduction in the size of
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
coffee, broths, or clear soups.
Under no circumstances should HUMULIN 30/70 be
given intravenously.  Consult your doctor if you notice anything unusual or
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  Consult your doctor concerning adjustments in your
the cartridge are clear and remain clear after the insulin schedule if you travel across more than 2 time
cartridge is shaken or rotated. zones.

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
vomiting, your insulin requirements may change. Test your
for colds), danazol (medicine acting on ovulation), or thyroid
blood and/or urine and notify your doctor at once.
 Always keep an extra supply of insulin. Always wear affected by diphenylhydantoin (used to treat epilepsy).
given if complications occur away from home.
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 doctor. antidepressants (monoamine oxidase inhibitors), beta-
Changing the type, strength, source, or manufacturer of blockers, alcohol, ACE inhibitors and angiotensin II receptor
insulin can cause problems with your blood sugar control. blockers and anabolic steroids.

Insulin requirements can be increased, decreased, or unchanged 180 10 times. This must be performed each time before
in patients receiving diuretics. you give yourself an injection even after just loading the
pen.
pioglitazone), alone or in combination with other antidiabetic 6. Prime the pen as directed by the manufacturer. If air
agents (including insulin), has been associated with heart failure bubbles are present, hold the pen with the needle
and swelling of the lower extremities. Please contact your pointing up and tap the side of the pen until the bubbles
physician immediately if you develop symptoms of shortness of float to the top. With the pen still vertical, purge the
breath, fatigue, exercise intolerance, or swelling of the lower needle with a 2 unit dose setting of the pen. Repeat until
extremities while you are on these agents. an insulin drop appears at the end of the needle. There
may be small bubbles left; the air is harmless but too
large an air bubble will affect the accuracy of the insulin
dose administered.
been provided on the side of the cartridge to help you
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
Lilly’s reusable pens, please refer to the separate Instructions for 1. Cleanse the skin, as instructed by your healthcare
Use enclosed within the pen packaging professional, where the injection is to be made. To avoid
tissue damage, always change the site for each injection
HUMULIN 30/70 cartridges are not designed to allow any other by at least 1.5 cm (0.5 inches) from the previous site,
insulin to be mixed in the cartridge. rotating sites on the body.
HUMULIN 30/70 cartridges MUST NOT be refilled and are not 2. Insert the needle under the skin, as you were taught. Do
designed for use with a traditional syringe. not inject directly into a vein.
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
members. Never share a HUMULIN KwikPen or cartridge, even 4. Pull the needle out and apply gentle pressure over the
if the needle on the delivery device is changed. You may pass injection site for several seconds. Do not rub the area.
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.
Preparing the Dose:
1. Wash your hands. Usual Dose
2. Always examine the cartridge of HUMULIN 30/70 after The dosage will be determined by your doctor, according to
removing from the box. Re-suspend the insulin by rolling the requirements of each individual patient. HUMULIN
the cartridge between your palms 10 times and inverting it 30/70 is for subcutaneous (under the skin) injection only.
180 10 times. HUMULIN 30/70 should look uniformly Do not inject into a vein.
cloudy or milky after mixing. If not, repeat the re-
suspension procedure as often as necessary. DO NOT USE Use in Pregnancy
if the white insulin particles stick to the bottom or sides of Control of the blood sugar is vital to assure the birth of a
the cartridge or if there are clumps floating in the insulin, or healthy child. Normalization of the blood sugar should have
if the cartridge is cracked or broken. occurred before conception and should continue throughout
3. Carefully load the cartridge into the reusable pen following the pregnancy. Since pregnancy may make diabetes worse
the manufacturer’s directions. and because of the importance of good diabetic control,
patients who contemplate pregnancy or who are pregnant
4. Wipe the exposed rubber membrane on the metal cap end of should seek expert medical advice.
the cartridge with an alcohol swab and attach the needle.
5. Carefully re-suspend the HUMULIN 30/70 by rolling the in insulin dose and/or diet.
cartridge and pen in your hands 10 times and inverting it

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).
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.
If uncorrected, loss of consciousness, coma, or death can
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.
situations where these abilities are of special importance (e.g.
driving a car or operating machinery – see Warnings and Allergy to Insulin
Precautions).
Patients occasionally experience redness, swelling, and
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.
Less common, but potentially more serious, is generalized
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
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.


injection technique may help alleviate the problem. REPORTING SUSPECTED SIDE EFFECTS
This is not a complete list of side effects. For any unexpected You can report any suspected adverse reactions associated
effects while taking HUMULIN 30/70, contact your doctor or with the use of health products to the Canada Vigilance
pharmacist. Program by one of the following 3 ways:
------------------------------------------------------------------------
HOW TO STORE IT
Your unused HUMULIN 30/70 cartridges should be stored in  Complete a Canada Vigilance Reporting Form and:
the refrigerator (2-8C). DO NOT FREEZE. The cartridge of - Fax toll-free to 1-866-678-6789, or
insulin that you are currently using does not have to be - Mail to: Canada Vigilance Program
refrigerated but should be kept at a temperature below 25C, Health Canada
away from direct heat and sunlight and protected from freezing. Postal Locator 0701D
The cartridge of insulin currently in use should be left in the pen Ottawa, Ontario
and may be carried with you. Cartridges in use or not K1A 0K9
refrigerated should be discarded after 28 days even if they
contain insulin. Postage paid labels, Canada Vigilance Reporting
Inspection of the Cartridge: are available on the MedEffect™ Canada Web site at
DO NOT USE a cartridge of HUMULIN 30/70 if after re-
suspending there are clumps floating in the insulin or if solid NOTE: Should you require information related to the
white particles stick to the bottom or wall of the cartridge giving management of side effects, contact your health
it a frosted appearance (re-suspend the insulin by following professional. The Canada Vigilance Program does not
instruction 2 under Preparing the Dose). A cartridge that
appears frosted or contains clumps, or is cracked or broken,
should be returned to the place of purchase for exchange.
If you notice anything unusual in the appearance or effect of MORE INFORMATION
For more information, please contact your healthcare
DO NOT USE AFTER EXPIRY DATE. professionals or pharmacist first, or Eli Lilly Canada Inc at:


Ontario, M1N 2E8.
Last revised:

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 VIALS these products by adding additional NPH or REGULAR
30% insulin injection, human biosynthetic and 70% insulin insulin to this vial.
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
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.
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® 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.
because of its unique manufacturing process.
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 for subcutaneous injection. It is available in:
action than NPH insulin alone. The duration of activity may last - Vials, 10 mL
up to 24 hours following injection.
HUMULIN 30/70 is also available in:
HUMULIN 30/70 vials are for subcutaneous (under the skin) - Cartridges, 3 mL
injection only.
Other available HUMULIN products include HUMULIN R
What the medication is used for: (Regular) and HUMULIN N (NPH).These types of insulin
differ mainly in the time they require to take effect and in the
HUMULIN 30/70 is a combination of an intermediate-acting length of time their action lasts. Your doctor has prescribed
and a short-acting insulin used to treat patients diagnosed with the type of insulin that he/she believes is best for you. Do
diabetes mellitus. not use any other insulin except on your doctor's advice
and direction.
What it does:
Insulin is a hormone that decreases the amount of sugar in your check to see that:
blood into various tissues, such as the liver, muscles, and fat. 1. The name HUMULIN appears on the carton and vial
label and is followed by the proper letter designation and
To control your diabetes, your doctor has prescribed injections name for the insulin formulation: 30/70: 30% insulin
of insulin to keep your blood sugar at a nearly normal level and injection, 70% insulin isophane, human biosynthetic
to keep your urine as free of sugar as possible. (rDNA) origin.
When it should not be used: 2. The carton and the vial label is correct for your type of
insulin.
HUMULIN 30/70 should not be used if you are allergic to this
drug or any of the ingredients used to formulate this medication. 3. The human insulin is of rDNA origin.
4. The insulin strength is U-100.
HUMULIN 30/70 should not be used during episodes of
hypoglycemia (low blood sugar). 5. The expiration date on the package will allow you to use
the insulin before that date.
HUMULIN 30/70 should not be given intravenously or used for

If an adjustment is needed, it may be made with the first

dose or over a period of several weeks.
insulin or miss a meal because of illness. . If you miss a
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
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
vial are clear and remain clear after the cartridge is
shaken or rotated.
zones.
which insulin to use, how much, and when and how often to INTERACTIONS WITH THIS MEDICATION
Proper control of your diabetes requires close and constant There may be interactions between HUMULIN 30/70 and
cooperation with your doctor. other medicines. Tell your doctor if you are taking any other
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
show above or below normal sugar levels or your urine tests Insulin requirements may be increased if you are taking
consistently show the presence of sugar, your diabetes is not other drugs with hyperglycemic activity, such as oral
properly controlled and you must let your doctor 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 fliud 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
 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
that appropriate treatment can be given if complications Insulin requirements may be decreased in the presence of
occur away from home. agents such as oral medicines for the treatment of diabetes,
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 insulins.

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.
Correct Syringe 2. Inject under the skin, as you were taught. Do not inject
Doses of insulin are measured in units. U-100 insulin contains directly into a vein.
100 units/mL. It is important to use a syringe that is marked for 3. Push the plunger in as far as it will go.
U-100 insulin preparations. Failure to use the proper syringe
can lead to a mistake in dosage, causing serious problems for 4. Pull the needle out and apply gentle pressure over the
you, such as a blood glucose level that is too low or too high. injection site for several seconds. Do not rub the area.
To avoid tissue damage, give the next injection at a site
Syringe Use at least 1.5 cm (0.5 inches) from the previous site.
To help avoid contamination and possible infection, follow
these instructions exactly. Usual Dose
Disposable syringes and needles should be used only once and The dosage will be determined by your doctor, according to
then discarded. NEEDLES AND SYRINGES MUST NOT BE the requirements of each individual patient. HUMULIN
SHARED with anyone including family members. You may 30/70 is for subcutaneous (under the skin) injection only.
pass on a serious infection or get a serious infection from the Do not inject into a vein.
other person. Follow the package directions supplied with your
syringe. Use in Pregnancy
Preparing the Dose: Control of the blood sugar is vital to assure the birth of a
1. Wash your hands.
occurred before conception and should continue throughout
2. Always examine the bottle (vial) of HUMULIN 30/70 after the pregnancy. Since pregnancy may make diabetes worse
removing from the box. Carefully shake or rotate the insulin and because of the importance of good diabetic control,
vial several times to completely mix (or re-suspend) the patients who contemplate pregnancy or who are pregnant
insulin. HUMULIN 30/70 should look uniformly cloudy or should seek expert medical advice.
milky after mixing. If not, repeat the re-suspension
procedure as often as necessary until the contents are mixed.
DO NOT USE if the white insulin particles stick to the
bottom or sides of the vial or if there are clumps floating in
Overdose:
the insulin or if the vial is cracked or broken.
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 with Insulin reaction (too little sugar in the blood, also called
an alcohol swab. "hypoglycemia") can be brought about by:
4. Draw air into the syringe equal to your insulin dose. Put the  Taking too much insulin
needle through the rubber top of the insulin vial and inject  Missing or delaying meals
the air into the vial.  Exercising or working too hard just before a meal
5. Turn the vial and syringe upside down. Hold the bottle and  An infection or illness (especially with diarrhea or
syringe firmly in 1 hand. vomiting)
 A change in the body's need for insulin.

to avoid hypoglycemia, you should take the amount of Hypoglycemia (Insulin Reaction)
carbohydrate prescribed for this meal in the form of orange Hypoglycemia (too little glucose in the blood) is one of the
juice, syrup, candy, or bread and milk, without changing your most frequent adverse events experienced by insulin users
insulin dosage. If it becomes necessary to omit a meal on (see Proper Use of this Medication - Overdose).
account of nausea and vomiting, you should test your blood
sugar level and notify your doctor. Diabetic Acidosis and Coma
Symptoms and Treatment: Diabetic acidosis may develop if your body has too little
The first symptoms of insulin reaction usually come on insulin (this is the opposite of insulin reaction, which is the
suddenly and may include vague symptoms of fatigue, result of too much insulin in the blood). Diabetic acidosis
nervousness or “shakiness”, rapid heartbeat, nausea, and a cold may be brought on if you omit your insulin or take less than
sweat. It is of utmost importance that you understand that these the doctor has prescribed, eat significantly more than your
symptoms demand immediate attention. diet calls for, or develop a fever or infection. With acidosis,
as a result of hypoglycemia. This may constitute a risk in The first symptoms of diabetic acidosis usually come on
situations where these abilities are of special importance (e.g. gradually, over a period of hours or days, and include a
driving a car or operating machinery – see Warnings and drowsy feeling, flushed face, thirst, and loss of appetite.
Precautions). Heavy breathing and a rapid pulse are more severe
symptoms.
being transferred to HUMULIN have reported that these early If uncorrected, loss of consciousness, coma, or death can
warning symptoms were less pronounced than they were with result. Therefore, it is important that you obtain medical
animal-source insulin. Some people may not recognize when assistance immediately.
Allergy to Insulin
condition and prevent more serious symptoms. Artificial Patients occasionally experience redness, swelling, and
sweeteners are not useful for the treatment of hypoglycemia. itching at the site of injection of insulin. This condition,
called local allergy, usually clears up in a few days to a few
If a diabetic becomes delirious or mentally confused, or suffers weeks. If you have local reactions, contact your doctor, who
from loss of memory or delusions, corn syrup diluted or orange may recommend a change in the type or species of insulin.
juice with sugar should be administered by mouth. More
severe hypoglycemia may require the assistance of another Less common, but potentially more serious, is generalized
person. Patients who are unable to take sugar orally or who are allergy to insulin, which may cause rash over the whole
unconscious should be treated with intravenous administration body, shortness of breath, wheezing, reduction in blood
of glucose at a medical facility or should be given an injection pressure, fast pulse, or sweating. Severe cases of
of glucagon (either intramuscular or subcutaneous). The patient generalized allergy may be life threatening. If you think you
should be given oral carbohydrates as soon as consciousness is are having a generalized allergic reaction to insulin, notify a
recovered. In the event of a hypoglycemic reaction, whether doctor immediately. Your doctor may recommend skin
mild or severe, you should notify your doctor promptly so that testing, that is, injecting small doses of other insulins into
any desirable change in diet or dosage can be determined. the skin, in order to select the best insulin for you to use.
In case of drug overdose, contact a healthcare practitioner, be used before treatment with that preparation is started.
hospital emergency department or regional Poison Control
Centre immediately, even if there are no symptoms. Lipoatrophy or Lipohypertrophy:
unexpected effects while taking HUMULIN 30/70, contact
your doctor or pharmacist.

HOW TO STORE IT
MORE INFORMATION
Your unused HUMULIN 30/70 vials should be stored in the
refrigerator (2-8C). DO NOT FREEZE. The vial of insulin For more information, please contact your healthcare
that you are currently using does not have to be refrigerated but professionals or pharmacist first, or Eli Lilly Canada Inc at:
contain insulin.
Inspection of the Vial: *The brands listed are trademarks of their respective owners
DO NOT USE a vial of HUMULIN 30/70 if after re-suspending and are not trademarks of Eli Lilly Canada. The makers of
there are clumps floating in the insulin or if solid white particles these brands are not affiliated with and do not endorse Eli
stick to the bottom or wall of the vial giving it a frosted Lilly Canada or its products.
appearance (re-suspend the insulin by following instruction 2
under Preparing the Dose). A vial that appears frosted or
contains clumps, or is cracked or broken, should be returned to
the place of purchase for exchange.
Ontario, M1N 2E8.
DO NOT USE AFTER EXPIRY DATE. REPORTING Last revised:
SUSPECTED SIDE EFFECTS
A2.0-LIN-0000-CA-PM-YYYYMMDD
------------------------------------------------------------------------
Health Canada
Ottawa, Ontario
K1A 0K9



Product Monograph: Humulin

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PRODUCT MONOGRAPH

 ELI LILLY CANADA INC. Date of Approval:

Control No: 191693

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

Transferring Patients from Other Insulins

Carcinogenesis and Mutagenesis

Endocrine and Metabolism

HUMULIN Product Monograph Page 5 of 54

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

Ability to concentrate and react may be impaired as a result of hyperglycemia or as a result of

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

HUMULIN Product Monograph Page 6 of 54

Local Allergic Reactions:

Systemic Allergic Reactions:

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

HUMULIN Product Monograph Page 7 of 54

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.

Geriatrics (>65 years of age)

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

Monitoring and Laboratory Tests

Self-Monitoring of Blood Glucose

HUMULIN Product Monograph Page 8 of 54

Body as a Whole – Allergic reaction(s)

Skin and appendages – Lipodystrophy

Metabolic – Hypoglycemia; Insulin resistance

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

HUMULIN Product Monograph Page 9 of 54

DOSAGE AND ADMINISTRATION

Patients should be monitored closely during the adjustment period.

HUMULIN Product Monograph Page 10 of 54

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

Symptoms and Treatment

HUMULIN Product Monograph Page 11 of 54

ACTION AND CLINICAL PHARMACOLOGY

HUMULIN Product Monograph Page 12 of 54

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

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