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Severe seasonal and perennial allergic rhinitis

RX
Drug hypersensitivity reactions
METHYLPREDNISOLONE
Serum sickness
TABLETS
4MG Allergic contact dermatitis
Bronchial asthma
1.NAME OF THE MEDICINAL PRODUCT
6. Ophthalmic diseases
Methylprednisolone 4 mg Tablets
Anterior uveitis (iritis, iridocyclitis)
2. QUALITATIVE AND QUANTITATIVE
COMPOSITION Posterior uveitis
Each tablet contains 4 mg methylprednisolone. Optic neuritis
Excipients with known effect: 7. Respiratory diseases
lactose, sucrose Pulmonary sarcoid
For the full list of excipients, see section 6.1 Fulminating or disseminated tuberculosis (with
appropriate anti-tuberculous chemotherapy)
3. PHARMACEUTICAL FORM
Aspiration of gastric contents
Tablet
8. Haematological disorders
4. CLINICAL PARTICULARS
Idiopathic thrombocytopenic purpura
4.1 Therapeutic indications
Methylprednisolone is indicated for conditions Haemolytic anaemia (autoimmune)
requiring glucocorticoid activity such as:-
9. Neoplastic diseases
1. Endocrine disorders
Leukaemia (acute and lymphatic)
Primary and secondary adrenal insufficiency
Malignant lymphoma
Congenital adrenal hyperplasia
10. Gastro-intestinal diseases
2. Rheumatic disorders
Ulcerative colitis
Rheumatoid arthritis
Crohn's disease
Juvenile chronic arthritis
11. Miscellaneous
Ankylosing spondylitis
Tuberculous meningitis (with appropriate anti-
3. Collagen diseases/arteritis tuberculous chemotherapy)
Systemic lupus erythematosus Transplantation
Systemic dermatomyositis (polymyositis) 4.2 Posology and method of administration
Rheumatic fever with severe carditis The dosage recommendations shown in the table
below are suggested initial daily doses and are
Giant cell arteritis/polymyalgia rheumatica intended as guides. The average total daily dose
4. Dermatological diseases recommended may be given either as a single
dose or in divided doses (excepting in alternate
Pemphigus vulgaris day therapy when the minimum effective daily
5. Allergic states dose is doubled and given every other day at
8.00 am).
Undesirable effects may be minimised by using dosage for the shortest period of time. If
the lowest effective dose for the minimum possible, treatment should be administered as a
period (see section 4.4). single dose on alternate days (see section 4.4).
The initial suppressive dose level may vary Dosage Recommendations:
depending on the condition being treated. This is
continued until a satisfactory clinical response is Indications Recommended initial daily
obtained, a period usually of three to seven days dosage
in the case of rheumatic diseases (except for Rheumatoid arthritis
acute rheumatic carditis), allergic conditions severe 12 - 16 mg
affecting the skin or respiratory tract and moderately severe 8 - 12 mg
ophthalmic diseases. If a satisfactory response is moderate 4 - 8 mg
not obtained in seven days, re-evaluation of the
children 4 - 8 mg
case to confirm the original diagnosis should be
made. As soon as a satisfactory clinical response Systemic dermatomyositis 48 mg
is obtained, the daily dose should be reduced Systemic lupus 20 - 100 mg
gradually, either to termination of treatment in erythematosus
the case of acute conditions (e.g. seasonal Acute rheumatic fever 48 mg until ESR normal
asthma, exfoliative dermatitis, acute ocular for one week.
inflammations) or to the minimal effective Allergic diseases 12 - 40 mg
maintenance dose level in the case of chronic Bronchial asthma up to 64 mg single
conditions (e.g. rheumatoid arthritis, systemic dose/alternate day up to
lupus erythematosus, bronchial asthma, atopic 100 mg maximum.
dermatitis). In chronic conditions, and in Ophthalmic diseases 12 - 40 mg
rheumatoid arthritis especially, it is important Haematological disorders 16 - 100 mg
that the reduction in dosage from initial to and leukaemias
maintenance dose levels be accomplished as Malignant lymphoma 16 - 100 mg
clinically appropriate. Decrements of not more
Ulcerative colitis 16 - 60 mg
than 2 mg at intervals of 7 - 10 days are
Crohn's disease up to 48 mg per day in
suggested. In rheumatoid arthritis, maintenance
acute episodes.
steroid therapy should be at the lowest possible
level. Organ transplantation up to 3.6 mg/kg/day
Pulmonary sarcoid 32 - 48 mg on alternate
In alternate-day therapy, the minimum daily days.
corticoid requirement is doubled and Giant cell 64 mg
administered as a single dose every other day at arteritis/polymyalgia
8.00 am. Dosage requirements depend on the rheumatica
condition being treated and response of the Pemphigus vulgaris 80 - 360 mg
patient.
Elderly patients: Treatment of elderly patients, 4.3 Contraindications
particularly if long-term, should be planned Methylprednisolone tablets are contraindicated:
bearing in mind the more serious consequences
of the common side-effects of corticosteroids in • in patients who have systemic fungal infections
old age, particularly osteoporosis, diabetes,
• in patients who have systemic infections unless
hypertension, susceptibility to infection and
specific anti-infective therapy is employed
thinning of skin (see section 4.4).
• in patients who have hypersensitivity to the
Paediatric population: In general, dosage for
active substance or to any of the excipients listed
children should be based upon clinical response
in section 6.1
and is at the discretion of the physician.
Treatment should be limited to the minimum
Administration of live or live, attenuated Strongyloides hyperinfection and dissemination

vaccines is contraindicated in patients receiving with widespread larval migration, often
immunosuppressive doses of corticosteroids. accompanied by severe enterocolitis and
potentially fatal gram-negative septicemia.
4.4 Special Warnings and precautions for use
Administration of live or live, attenuated
Immunosuppressant Effects/Increased vaccines is contraindicated in patients receiving
Susceptibility to Infections immunosuppressive doses of corticosteroids.
Corticosteroids may increase susceptibility to The antibody response to other vaccines may be
infection, may mask some signs of infection, and diminished.
new infections may appear during their use.
The use of corticosteroids in active tuberculosis
Suppression of the inflammatory response and
should be restricted to those cases of fulminating
immune function increases the susceptibility to or disseminated tuberculosis in which the
fungal, viral and bacterial infections and their corticosteroid is used for the management of the
severity. The clinical presentation may often be disease in conjunction with an appropriate
atypical and may reach an advanced stage before antituberculous regimen. If corticosteroids are
being recognised.
indicated in patients with latent tuberculosis or
Persons who are on drugs which suppress the tuberculin reactivity, close observation is
immune system are more susceptible to necessary as reactivation of the disease may
infections than healthy individuals. Chicken pox occur. During prolonged corticosteroid therapy,
and measles, for example, can have a more these patients should receive chemoprophylaxis.
serious or even fatal course in non-immune Kaposi's sarcoma has been reported to occur in
children or adults on corticosteroids.
patients receiving corticosteroid therapy.
Chickenpox is of serious concern since this Discontinuation of corticosteroids may result in
normally minor illness may be fatal in clinical remission.
immunosuppressed patients. Patients (or parents
The role of corticosteroids in septic shock has
of children) without a definite history of
been controversial, with early studies reporting
chickenpox should be advised to avoid close
both beneficial and detrimental effects. More
personal contact with chickenpox or herpes recently, supplemental corticosteroids have been
zoster and if exposed they should seek urgent suggested to be beneficial in patients with
medical attention. Passive immunization with established septic shock who exhibit adrenal
varicella/zoster immunoglobulin (VZIG) is insufficiency. However, their routine use in
needed by exposed non-immune patients who septic shock is not recommended. A systematic
are receiving systemic corticosteroids or who review of short-course high-dose corticosteroids
have used them within the previous 3 months;
did not support their use. However, meta-
this should be given within 10 days of exposure analyses, and a review have suggested that
to chickenpox. If a diagnosis of chickenpox is longer courses (5-11 days) of low-dose
confirmed, the illness warrants specialist care corticosteroids might reduce mortality.
and urgent treatment. Corticosteroids should not
be stopped and the dose may need to be Immune System
increased.
Because rare instances of skin reactions and
Exposure to measles should be avoided. Medical anaphylactic/anaphylactoid reactions have
advice must be sought immediately if exposure occurred in patients receiving corticosteroid
occurs. Prophylaxis with normal intramuscular therapy, appropriate precautionary measures
immunoglobulin may be needed. should be taken prior to administration,
especially when the patient has a history of
Similarly corticosteroids should be used with allergy to any drug.
great care in patients with known or suspected
parasitic infections such as Strongyloides Endocrine Effects
(threadworm) infestation, which may lead to
In patients on corticosteroid therapy subjected to • Patients receiving doses of systemic

unusual stress, increased dosage of rapidly corticosteroid greater than 32 mg daily of
acting corticosteroids before, during, and after methylprednisolone.
the stressful situation is indicated.
• Patients repeatedly taking doses in the evening.
Adrenal cortical atrophy develops during
prolonged therapy and may persist for months A steroid “withdrawal syndrome,” seemingly
after stopping treatment. In patients who have unrelated to adrenocortical insufficiency, may
received more than physiological doses of also occur following abrupt discontinuance of
glucocorticoids. This syndrome includes
systemic corticosteroids (approximately 6 mg
symptoms such as: anorexia, nausea, vomiting,
methylprednisolone) for greater than 3 weeks,
withdrawal should not be abrupt. How dose lethargy, headache, fever, joint pain,
reduction should be carried out depends largely desquamation, myalgia, weight loss, and/or
on whether the disease is likely to relapse as the hypotension. These effects are thought to be due
to the sudden change in glucocorticoid
dose of systemic corticosteroids is reduced.
Clinical assessment of disease activity may be concentration rather than to low corticosteroid
levels.
needed during withdrawal. If the disease is
unlikely to relapse on withdrawal of systemic Glucocorticoids can produce or aggravate
corticosteroids, but there is uncertainty about Cushing's syndrome, therefore glucocorticoids
HPA suppression, the dose of systemic should be avoided in patients with Cushing's
corticosteroid may be reduced rapidly to disease.
physiological doses. Once a daily dose of 6 mg
methylprednisolone is reached, dose reduction Particular care is required when considering the
should be slower to allow the HPA-axis to use of systemic corticosteroids in patients with
recover. hypothyroidism and frequent patient monitoring
is necessary.
Abrupt withdrawal of systemic corticosteroid
treatment, which has continued up to 3 weeks is Metabolism and Nutrition Disorders
appropriate if it considered that the disease is Corticosteroids, including methylprednisolone,
unlikely to relapse. Abrupt withdrawal of doses can increase blood glucose, worsen pre-existing
up to 32 mg daily of methylprednisolone for 3 diabetes, and predispose those on long-term
weeks is unlikely to lead to clinically relevant corticosteroid therapy to diabetes mellitus.
HPA-axis suppression, in the majority of
patients. In the following patient groups, gradual Particular care is required when considering the
withdrawal of systemic corticosteroid therapy use of systemic corticosteroids in patients with
should be considered even after courses lasting 3 Diabetes mellitus (or a family history of
weeks or less: diabetes) and frequent patient monitoring is
necessary.
• Patients who have had repeated courses of
systemic corticosteroids, particularly if taken for Psychiatric Effects
greater than 3 weeks. Patients and/or carers should be warned that
• When a short course has been prescribed potentially severe psychiatric adverse reactions
within one year of cessation of long-term may occur with systemic steroids (see section
therapy (months or years). 4.8). Symptoms typically emerge within a few
days or weeks of starting treatment. Risks may
• Patients who may have reasons for be higher with high doses/systemic exposure
adrenocortical insufficiency other than (see also section 4.5), although dose levels do
exogenous corticosteroid therapy. In addition, not allow prediction of the onset, type, severity
acute adrenal insufficiency leading to a fatal or duration of reactions. Most reactions recover
outcome may occur if glucocorticoids are after either dose reduction or withdrawal,
withdrawn abruptly. although specific treatment may be necessary.
Patients/carers should be encouraged to seek Prolonged use of corticosteroids may produce

medical advice if worrying psychological posterior subcapsular cataracts and nuclear
symptoms develop, especially if depressed mood cataracts (particularly in children),
or suicidal ideation is suspected. Patients/carers exophthalmos or increased intraocular pressure,
should be alert to possible psychiatric which may result in glaucoma with possible
disturbances that may occur either during or damage to the optic nerves.
immediately after dose tapering/withdrawal of
Secondary fungal and viral infections of the eye
systemic steroids, although such reactions have
been reported infrequently. may also be enhanced in patients receiving
glucocorticoids.
Particular care is required when considering the
.
use of systemic corticosteroids in patients with
existing or previous history of severe affective Cardiac Events
disorders in themselves or in their first degree
relatives. These would include depressive or Adverse effects of glucocorticoids on the
manic-depressive illness and previous steroid cardiovascular system, such as dyslipidemia and
psychosis. hypertension, may predispose treated patients
with existing cardiovascular risk factors to
Nervous System Effects additional cardiovascular effects, if high doses
Particular care is required when considering the and prolonged courses are used. Accordingly,
use of systemic corticosteroids in patients with corticosteroids should be employed judiciously
seizure disorders and myasthenia gravis (see in such patients and attention should be paid to
myopathy statement in Musculoskeletal Effects risk modification and additional cardiac
section) and frequent patient monitoring is monitoring if needed. Low dose and alternate
necessary. day therapy may reduce the incidence of
complications in corticosteroid therapy.
There have been reports of epidural lipomatosis
Systemic corticosteroids should be used with
in patients taking corticosteroids, typically with
long-term use at high doses. caution, and only if strictly necessary, in cases
of congestive heart failure.
Ocular Effects
Visual disturbance may be reported with use of systemic corticosteroids in patients with
systemic and topical corticosteroid use. If a recent myocardial infarction (myocardial rupture
patient presents with symptoms such as blurred has been reported) and frequent patient
vision or other visual disturbances, the patient monitoring is necessary.
should be considered for referral to an
ophthalmologist for evaluation of possible Care should be taken for patients receiving
causes which may include cataract, glaucoma or cardioactive drugs such as digoxin because of
rare diseases such as central serous steroid induced electrolyte
disturbance/potassium loss (see section 4.8).
chorioretinopathy (CSCR) which have been
reported after use of systemic and topical Vascular Effects
corticosteroids. Central serous
chorioretinopathy, may lead to retinal Particular care is required when considering the
detachment. use of systemic corticosteroids in patients with
the following conditions and frequent patient
Particular care is required when considering the monitoring is necessary.
glaucoma (or a family history of glaucoma) and Hypertension
ocular herpes simplex as there is a fear of Predisposition to thrombophlebitis
corneal perforation, and frequent patient
monitoring is necessary. Thrombosis including venous thromboembolism
has been reported to occur with corticosteroids.
As a result corticosteroids should be used with improvement or recovery after stopping

caution in patients who have or may be corticosteroids may require weeks to years.
predisposed to thromboembolic disorders.
Gastrointestinal Effects use of systemic corticosteroids in patients with
osteoporosis (post-menopausal females are
High doses of corticosteroids may produce acute particularly at risk) and frequent patient
pancreatitis. monitoring is necessary.
Renal and Urinary
the following conditions and frequent patient Caution is required in patients with systemic
monitoring is necessary. sclerosis because an increased incidence of
scleroderma renal crisis has been observed with
Peptic ulceration.
corticosteroids, including methylprednisolone.
Fresh intestinal anastomoses. Blood pressure and renal function (s-creatinine)
should therefore be routinely checked. When
Abscess or other pyogenic infections. renal crisis is suspected, blood pressure should
Ulcerative colitis. be carefully controlled.
Diverticulitis. Particular care is required when considering the

Glucocorticoid therapy may mask peritonitis or renal insufficiency and frequent patient
other signs or symptoms associated with monitoring is necessary.
gastrointestinal disorders such as perforation,
obstruction or pancreatitis. In combination with Injury, poisoning and procedural
NSAIDs, the risk of developing gastrointestinal complications
ulcers is increased. Systemic corticosteroids are not indicated for,
Hepatobiliary Effects and therefore should not be used to treat,
traumatic brain injury, a multicenter study
Particular care is required when considering the revealed an increased mortality at 2 weeks and 6
use of systemic corticosteroids in patients with months after injury in patients administered
liver failure or cirrhosis and frequent patient methylprednisolone sodium succinate compared
monitoring is necessary. to placebo. A causal association with
Rarely hepatobiliary disorders were reported, in methylprednisolone sodium succinate treatment
the majority of these cases, they were reversible has not been established.
after withdrawal of therapy. Therefore Other
appropriate monitoring is required.
Undesirable effects may be minimised by using
Musculoskeletal Effects the lowest effective dose for the minimum
An acute myopathy has been reported with the period, and by administering the daily
use of high doses of corticosteroids, most often requirement as a single morning dose or
occurring in patients with disorders of whenever possible as a single morning dose on
neuromuscular transmission (e.g. myasthenia alternative days. Frequent patient review is
gravis), or in patients receiving concomitant required to appropriately titrate the dose against
therapy with anticholinergics, such as disease activity (see section 4.2).
neuromuscular blocking drugs (e.g. Patients should carry 'Steroid Treatment' cards
pancuronium). This acute myopathy is which give clear guidance on the precautions to
generalized, may involve ocular and respiratory be taken to minimise risk and which provide
muscles, and may result in quadriparesis. details of prescriber, drug, dosage and the
Elevations of creatine kinase may occur. Clinical duration of treatment.
Co-treatment with CYP3A inhibitors, including glucose-galactose malabsorption should not take
cobicistat-containing products, is expected to this medicine.
increase the risk of systemic side-effects. The
combination should be avoided unless the This medicine contains sucrose. Patients with
benefit outweighs the increased risk of systemic rare hereditary problems of fructose intolerance,
corticosteroid side-effects, in which case glucose-galactose malabsorption or sucrase-
patients should be monitored for systemic isomaltase insufficiency should not take this
corticosteroid side-effects (see section 4.5). medicine.
Aspirin and non-steroidal anti-inflammatory 4.5 Interaction with other medicinal

agents should be used cautiously in conjunction products and other forms of interaction
with corticosteroids. Methylprednisolone is a cytochrome P450
Pheochromocytoma crisis, which can be fatal, enzyme (CYP) substrate and is mainly
has been reported after administration of metabolized by the CYP3A4 enzyme. CYP3A4
systemic corticosteroids. Corticosteroids should is the dominant enzyme of the most abundant
only be administered to patients with suspected CYP subfamily in the liver of adult humans. It
catalyzes 6β-hydroxylation of steroids, the
or identified pheochromocytoma after an
appropriate risk/benefit evaluation. essential Phase I metabolic step for both
endogenous and synthetic corticosteroids. Many
Paediatric population: Corticosteroids cause other compounds are also substrates of
growth retardation in infancy, childhood and CYP3A4, some of which (as well as other drugs)
adolescence. Growth and development of infants have been shown to alter glucocorticoid
and children on prolonged corticosteroid therapy metabolism by induction (upregulation) or
should be carefully observed. Treatment should inhibition of the CYP3A4 enzyme.
be limited to the minimum dosage for the
Drug Class or
shortest possible time. In order to minimise Type
Interaction Effect
suppression of the hypothalamo-pituitary- - DRUG or
adrenal axis and growth retardation, treatment SUBSTANCE
should be administered where possible as a Antibiotic, CYP3A4 INDUCERS -

Antitubercular Drugs that induce
single dose on alternate days (see section 4.2). - RIFAMPIN CYP3A4 activity
- RIFABUTIN generally increase
Infants and children on prolonged corticosteroid hepatic clearance,
therapy are at special risk from raised resulting in decreased
plasma concentration of
intracranial pressure. Anticonvulsants CYP3A4 Inducer
medications that are
- substrates for CYP3A4.
High doses of corticosteroids may produce PHENOBARBITAL Co-administration may
- PHENYTOIN
pancreatitis in children. - PRIMIDONE
require an increase in
methylprednisolone
Use in the elderly: The common adverse effects dosage to achieve the
desired result.
of systemic corticosteroids may be associated
CYP3A4 INDUCERS –
with more serious consequences in old age, see box above
especially osteoporosis, hypertension, CYP3A4 SUBSTRATES
hypokalaemia, diabetes, susceptibility to - In the presence of
another CYP3A4
infection and thinning of the skin. Close clinical substrate, the hepatic
supervision is required to avoid life-threatening clearance of
Anticonvulsant methylprednisolone may
reactions. -
CYP3A4 Inducer
be affected, with
(and Substrate)
CARBAMAZEPINE corresponding dosage
Ingredient warning adjustments required. It
is possible that adverse
This medicine contains lactose. Patients with events associated with
rare hereditary problems of galactose the use of either drug
alone may be more
intolerance, the Lapp lactase deficiency or likely to occur with co-
administration.
Macrolide CYP3A4 INHIBITORS - MIDE clearance of

Antibacterial Drugs that inhibit - TACROLIMUS methylprednisolone may
- CYP3A4 activity be affected, with
TROLEANDOMYCI generally decrease corresponding dosage
N hepatic clearance and adjustments required. It
- GRAPEFRUIT increase the plasma is possible that adverse
JUICE concentration of events associated with
CYP3A4 substrate the use of either drug
Calcium Antagonist medications, such as alone may be more
- MIBEFRADIL methylprednisolone. In likely to occur with co-
the presence of a administration.
Histamine CYP3A4 Inhibitor CYP3A4 inhibitor, the
(4) There may be
H2 receptor dose of increased incidence of
Antagonist methylprednisolone may gastrointestinal bleeding
- CIMETIDINE need to be titrated to and ulceration when
avoid steroid toxicity. corticosteroids are given
In addition, there is a with NSAIDs.
NSAIDs
potential effect of (5) Methylprednisolone
(nonsteroidal anti-
Antibacterial methylprednisolone to may increase the
inflammatory
- ISONIAZID increase the acetylation clearance of high-dose
drugs) (4)
rate and clearance of aspirin, which can lead
- high-dose
isoniazid. to decreased salicylate
ASPIRIN (5)
Antiemetic CYP3A4 INHIBITORS – serum levels.
(acetylsalicylic
- APREPITANT see box above Discontinuation of
acid)
- CYP3A4 SUBSTRATES methylprednisolone
FOSAPREPITANT - In the presence of treatment can lead to
another CYP3A4 raised salicylate serum
Antifungal levels, which could lead
- ITRACONAZOLE substrate, the hepatic
clearance of to an increased risk of
- salicylate toxicity.
KETOCONAZOLE methylprednisolone may
be affected, with (6) An acute myopathy
Calcium Channel corresponding dosage has been reported with
Blocker adjustments required. It the concomitant use of
- DILTIAZEM is possible that adverse high doses of
Contraceptives events associated with corticosteroids and
(oral) the use of either drug anticholinergics, such
- alone may be more as neuromuscular
ETHINYLESTRADI likely to occur with co- blocking drugs. (See
OL/ administration. Non-CYP3A4- section 4.4
NORETHINDRON (1) Mutual inhibition of Musculoskeletal, for
Anticholinergics (6) mediated effects
E metabolism occurs with additional information.)
-
concurrent use of (7) Antagonism of the
Immunosuppressan NEUROMUSCULA
CYP3A4 Inhibitor ciclosporin and neuromuscular blocking
t R BLOCKERS (7)
(and Substrate) methylprednisolone, effects of pancuronium
- CICLOSPORIN which may increase the and vecuronium has
(1) plasma concentrations been reported in
Macrolide of either or both drugs. patients taking
Antibacterial Therefore, it is possible corticosteroids. This
- that adverse events interaction may be
CLARITHROMYCI associated with the use expected with all
N of either drug alone may competitive
- ERYTHROMYCIN be more likely to occur neuromuscular
upon co-administration. blockers.
Antivirals
(2) Protease inhibitors, Steroids may reduce the
- HIV-PROTEASE
such as indinavir and effects of
INHIBITORS (2) (3)
ritonavir, may increase Anticholinesterases
Pharmacokinetic anticholinesterases in
plasma concentrations myasthenia gravis.
enhancers
of corticosteroids.
-COBICISTAT Because corticosteroids
(3) Corticosteroids may
induce the metabolism may increase blood
of HIV-protease glucose concentrations,
Anti-diabetics
inhibitors resulting in dosage adjustments of
reduced plasma anti-diabetic agents may
concentrations. be required.
Immunosuppressan CYP3A4 SUBSTRATES The efficacy of
t CYP3A4 - In the presence of Anticoagulants coumarin anticoagulants
- Substrate another CYP3A4 (oral) may be enhanced by
CYCLOPHOSPHA substrate, the hepatic concurrent
corticosteroid therapy carefully observed and evaluated for signs of

and close monitoring of adrenal insufficiency. Hypoadrenalism may, in
the INR or prothrombin
time is required to avoid theory, occur in the neonate following prenatal
spontaneous bleeding. exposure to corticosteroids but usually resolves
When corticosteroids spontaneously following birth and is rarely
are administered
concomitantly with
clinically important.
potassium-depleting
agents (i.e. diuretics), Since adequate human reproductive studies have
patients should be not been done with methylprednisolone, this
observed closely for medicinal product, as with all drugs, should be
Potassium- development of
depleting agents hypokalaemia. There is used in pregnancy only after a careful
also an increased risk of assessment of the benefit-risk ratio to the
hypokalaemia with
concurrent use of
mother, embryo, foetus or child. When
corticosteroids with corticosteroids are essential, however, patients
amphotericin B, with normal pregnancies may be treated as
xanthenes, or beta2
agonists. though they were in the non-gravid state.
Aminoglutethimide- Cataracts have been observed in infants born to
Aromatase induced adrenal
inhibitors suppression may mothers undergoing long-term treatment with
- exacerbate endocrine corticosteroids during pregnancy.
AMINOGLUTETHI changes caused by
MIDE prolonged glucocorticoid Breast-feeding
treatment.
Corticosteroids are excreted in small amounts in
breast milk, however, doses of up to 40 mg daily
4.6 Fertility, Pregnancy and lactation of methylprednisolone are unlikely to cause
systemic effects in the infant. Infants of mothers
Fertility
taking higher doses than this may have a degree
Corticosteroids have been shown to impair of adrenal suppression. This medicinal product
fertility in animal studies (see section 5.3). should be used during breast feeding only after a
careful assessment of the benefit-risk ratio to the
Pregnancy mother and infant.
The ability of corticosteroids to cross the 4.7 Effects on ability to drive and use
placenta varies between individual drugs, machines
however, methylprednisolone does cross the The effect of corticosteroids on the ability to
placenta. In humans, the risk of low birth weight drive or use machinery has not been
appears to be dose related and may be systematically evaluated. Undesirable effects,
minimized by administering lower corticosteroid such as dizziness, vertigo, visual disturbances
doses. and fatigue are possible after treatment with
Administration of corticosteroids to pregnant corticosteroids. If affected, patients should not
animals can cause abnormalities of foetal drive or operate machinery.
development including cleft palate, intra-uterine 4.8 Undesirable Effects
growth retardation and effects on brain growth
and development. There is no evidence that
corticosteroids result in an increased incidence MedDRA
of congenital abnormalities, such as cleft palate System Organ Frequency† Undesirable Effects
Class
in man, however, when administered for long
periods or repeatedly during pregnancy, Infections and Common Infection (including increased
infestations susceptibility and severity of
corticosteroids may increase the risk of intra- infections with suppression of
uterine growth retardation. Infants born to clinical symptoms and signs)
mothers, who have received substantial doses of
corticosteroids during pregnancy must be
Not Known Opportunistic infection; Rare Vision blurred (see also

recurrence of dormant section 4.4)
tuberculosis, Peritonitis†
Blood and Not Known Leukocytosis Not Known Glaucoma; Exophthalmos;

lymphatic system Corneal thinning; Scleral
disorders thinning; Chorioretinopathy
Immune system Not Known Drug hypersensitivity Ear and labyrinth Not Known Vertigo
disorders Anaphylactic reaction disorders
Anaphylactoid reaction
Endocrine Common Cushingoid Cardiac disorders Not Known Cardiac failure congestive (in
disorders susceptible patients);
Myocardial rupture following
myocardial infarction
Not Known Hypopituitarism
Vascular Common Hypertension
disorders
Neoplasms Not Known Kaposi's sarcoma

Not Known Hypotension; Embolism
benign, malignant
arterial; Thrombotic events
and unspecified
(including cysts
and polyps) Respiratory, Not Known Pulmonary embolism,
Metabolism and Common Sodium retention; Fluid thoracic and Hiccups
nutrition disorders retention mediastinal
disorders
Gastrointestinal Common Peptic ulcer (with possible
Not Known Metabolic acidosis ;Alkalosis
disorders Peptic ulcer perforation and
hypokalaemic; Dyslipidaemia;
Peptic ulcer haemorrhage)
Glucose tolerance impaired;
increased requirements for Not Known Intestinal perforation; Gastric
insulin (or oral hypoglycemic haemorrhage; Pancreatitis;
agents in diabetics); Oesophagitis ulcerative;
Lipomatosis;; Increased Oesophagitis; Abdominal
appetite (which may result in distension; Abdominal pain;
Weight increased); Epidural Diarrhoea; Dyspepsia;
lipomatosis Nausea
Psychiatric Common Affective disorder (including Hepatobiliary Not Known Increase of liver enzymes
disorders Depressed mood and disorders (e.g. alanine
Euphoric mood) aminotransferase increased,
aspartate aminotransferase
Not Known Psychotic disorder (including
increased)
Mania, Delusion,
Hallucination, and Skin and Common Skin atrophy; Acne
Schizophrenia; Psychotic subcutaneous
behaviour; Affective disorder tissue disorders
(including Affect lability,
Psychological dependence, Not Known Angioedema; Hirsutism;
Suicidal ideation); Mental Petechiae; Ecchymosis;
disorder; Personality change; Erythema; Hyperhidrosis;
Confusional state; Anxiety; Skin striae; Rash Pruritus;
Mood swings; Abnormal Urticaria; Telangiectasia
behaviour; Insomnia; Musculoskeletal Common Muscular weakness; Growth
Irritability and connective retardation
Nervous system Not Known Intracranial pressure tissue disorders
disorders increased (with Papilloedema
[Benign intracranial Not Known Myalgia; Myopathy; Muscle
hypertension]); Seizure; atrophy; Osteoporosis;
Amnesia; Cognitive disorder; Osteonecrosis; Pathologic
Dizziness; Headache fracture; Neuropathic
arthropathy; Arthralgia;
Eye disorders Common Cataract
Reproductive Not Known Menstruation irregular
system and breast
disorders
General disorders Common Impaired healing period of time. Appropriate action should be
and taken to alleviate the symptoms produced by any
administration site
conditions side-effect that may become apparent. It may be
Not Known Oedema peripheral; necessary to support the patient with
Fatigue;
Malaise; Withdrawal
symptoms - too rapid a corticosteroids during any further period of
reduction of corticosteroid trauma occurring within two years of
dosage following prolonged overdosage.
treatment can lead to acute
adrenal insufficiency,
hypotension and death (see
There is no clinical syndrome of acute overdose
section 4.4) with methylprednisolone. Reports of acute
Investigations Common Blood potassium decreased toxicity and/or death following overdosage of
glucocorticoids are rare. In the event of
overdosage, no specific antidote is available;
Not Known Intraocular pressure treatment is supportive and symptomatic.
increased; Carbohydrate Methylprednisolone is haemodialysable.
tolerance decreased; Urine
calcium increased Blood
alkaline phosphatase 5. PHARMACOLOGICAL PROPERTIES
increased; Blood urea
increased; Suppression of 5.1 Pharmacodynamic properties
reactions to skin tests* Pharmacotherapeutic group:
Injury, poisoning Not Known Tendon rupture (particularly Glucocorticosteroids,
and procedural of the Achilles tendon);
complications Spinal compression fracture Methylprednisolone is a synthetic glucocorticoid
and a methyl derivative of prednisolone.
Methylprednisolone is a potent anti-
* Not a MedDRA PT inflammatory agent with the capacity to
†
profoundly inhibit the immune system.
Peritonitis may be the primary presenting sign
or symptom of a gastrointestinal disorder such as Glucocorticoids act primarily by binding to and
perforation, obstruction or pancreatitis (see activating intracellular glucocorticoid receptors.
section 4.4) Activated glucocorticoid receptors bind to
promoter regions of DNA (which may activate
Common (≥1/100 to <1/10); Uncommon or suppress transcription) and activate
(≥1/1,000 to <1/100); Rare (≥1/10,000 to transcription factors resulting in inactivation of
<1/1,000); Not known (frequency cannot be genes through de-acetylation of histones.
estimated from the available data)
Following corticosteroid administration there is
The incidence of predictable undesirable side- a delay of several hours for the clinical effects
effects associated with the use of corticosteroids, resulting from changes in gene expression to be
including hypothalamic-pituitary-adrenal seen.
suppression correlates with the relative potency
of the drug, dosage, timing of administration and Other effects not related to gene expression may
duration of treatment (see section 4.4). be more immediate.
Reporting of suspected adverse reactions Corticosteroids influence the kidney and fluid
and electrolyte balance, lipid, protein, and
Reporting suspected adverse reactions after carbohydrate metabolism, skeletal muscle, the
authorisation of the medicinal product is cardiovascular system, the immune system, the
important. It allows continued monitoring of the nervous system, and the endocrine system.
benefit/risk balance of the medicinal product. Corticosteroids are also critical in the
4.9 Overdose maintenance of function during stress.
Administration of methylprednisolone should 5.2 Pharmacokinetic properties

not be discontinued abruptly but tailed off over a
Methylprednisolone pharmacokinetics is linear, Based on conventional studies of safety

independent of route of administration. pharmacology and repeated dose toxicity, no
unexpected hazards were identified. The
Absorption:
toxicities seen in repeated-dose studies were
Methylprednisolone is rapidly absorbed and the those expected to occur with continued exposure
maximum plasma methylprednisolone to exogenous adrenocortical steroids.
concentration is achieved around 1.5 to 2.3 Mutagenic potential:
hours across doses following oral administration
in normal healthy adults. The absolute Methylprednisolone has not been formally
bioavailability of methylprednisolone in normal evaluated for genotoxicity. Studies using
healthy subjects is generally high (82% to 89%) structurally related analogues of
following oral administration. methylprednisolone showed no evidence of a
potential for genetic and chromosome mutations
Distribution:
in limited studies in bacteria and mammalian
Methylprednisolone is widely distributed into cells.
the tissues, crosses the blood-brain barrier, and Carcinogenic potential:
is secreted in breast milk. Its apparent volume of
distribution is approximately 1.4 L/kg. Methylprednisolone has not been formally
evaluated in rodent carcinogenicity studies.
The plasma protein binding of Variable results have been obtained with other
methylprednisolone in humans is approximately glucocorticoids tested for carcinogenicity in
77%.
mice and rats. However, published data indicate
Metabolism: that several related glucocorticoids including
budesonide, prednisolone, and triamcinolone
Corticosteroids are metabolised mainly in the acetonide can increase the incidence of
liver but also in the kidney and are excreted in hepatocellular adenomas and carcinomas after
the urine. oral administration in drinking water to male
In humans, methylprednisolone is metabolized rats. These tumorigenic effects occurred at doses
in the liver to inactive metabolites; the major which were less than the typical clinical doses
ones are 20α-hydroxymethylprednisolone and on a mg/m2 basis. The clinical relevance of these
20β-hydroxymethylprednisolone. findings is unknown.
Metabolism in the liver occurs primarily via the Reproductive toxicity:

CYP3A4 enzyme. (For a list of drug interactions Methylprednisolone has not been evaluated in
based on CYP3A4-mediated metabolism, see animal fertility studies. Adverse effects on
section 4.5.) fertility in male rats administered corticosterone
Methylprednisolone, like many CYP3A4 were observed and were reversible. Decreased
substrates, may also be a substrate for the ATP- weights and microscopic changes in prostate and
binding cassette (ABC) transport protein p- seminal vesicles were observed. The numbers of
glycoprotein, influencing tissue distribution and implantations and live foetuses were reduced
interactions with other medicines. and these effects were not present following
mating at the end of the recovery period.
Elimination:
An increased frequency of cleft palate was
The mean elimination half-life for total observed among the offspring of mice treated
methylprednisolone is in the range of 1.8 to 5.2 during pregnancy with methylprednisolone in
hours. Total clearance is approximately 5 to 6 doses similar to those typically used for oral
mL/min/kg. therapy in humans.
5.3 Preclinical safety data An increased frequency of cardiovascular
defects and decreased body weight were
observed among the offspring of pregnant rats

treated with methylprednisolone in a dose that
was similar to that used for oral therapy in
humans but was toxic to the mothers. In Manufactured in India by:
contrast, no teratogenic effect was noted in rats TAJ PHARMACEUTICALS LTD.
with doses <1-18 times those typically used or Mumbai, India
oral therapy in humans in another study. High At: 615, GIDC, Kerala, Bavla, Dist. Ahmedabad
frequencies of foetal death and a variety of 438225, Gujarat, INDIA
central nervous system and skeletal anomalies
were reported in the offspring of pregnant This leaflet was last revised in October 2019
rabbits treated with methylprednisolone in doses
less than those used in humans. The relevance of
these findings to the risk of malformations in
human infants born to mothers treated with
methylprednisolone in pregnancy is unknown.
Safety margins for the reported teratogenic
effects are unknown.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients

Lactose
Sucrose
Maize starch
Calcium stearate
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
Bottles - 5 years.
Blister packs - 3 years.
6.4 Special precautions for storage
Store below 25°C.
6.5 Nature and contents of container
High density polyethylene bottles with tamper
evident caps. Each bottle contains 30 or 100
tablets.
20-25 micron hard tempered aluminium
foil/lacquer, 250 micron opaque polyvinyl
chloride film blister. Pack contains 30 tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and
other handling
No special requirements.
7. MANUFACTURER:

Methylprednisolone 4 MG Tablets SMPC - Taj Pharmaceuticals

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Methylprednisolone Tablets 4 mg SMPC, Taj Phar maceuticals

Severe seasonal and perennial allergic rhinitis

Administration of live or live, attenuated Strongyloides hyperinfection and dissemination

In patients on corticosteroid therapy subjected to • Patients receiving doses of systemic

Patients/carers should be encouraged to seek Prolonged use of corticosteroids may produce

As a result corticosteroids should be used with improvement or recovery after stopping

Diverticulitis. Particular care is required when considering the

Aspirin and non-steroidal anti-inflammatory 4.5 Interaction with other medicinal

should be administered where possible as a Antibiotic, CYP3A4 INDUCERS -

Macrolide CYP3A4 INHIBITORS - MIDE clearance of

corticosteroid therapy carefully observed and evaluated for signs of

Not Known Opportunistic infection; Rare Vision blurred (see also

Blood and Not Known Leukocytosis Not Known Glaucoma; Exophthalmos;

Neoplasms Not Known Kaposi's sarcoma

Administration of methylprednisolone should 5.2 Pharmacokinetic properties

Methylprednisolone pharmacokinetics is linear, Based on conventional studies of safety

Metabolism in the liver occurs primarily via the Reproductive toxicity:

observed among the offspring of pregnant rats

6.1 List of excipients

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