Mayanmar Product

Mezacar Tablets

Mezacar Tablets

Why you have been prescribed this medicine?

You have been prescribed this medicine if you have any of the following:
Epilepsy- Generalized tonic-clonic and partial seizures.
Mezacar is not usually effective in absences (petit mal) and myoclonic seizures. Moreover, anecdotal evidence suggests that seizure exacerbation may occur in patients with atypical absences.
The paroxysmal pain of trigeminal neuralgia.
For the prophylaxis of manic-depressive psychosis in patients unresponsive to lithium therapy.

When you should consult your doctor?

You should consult your doctor if you experience any of the following:
Adverse drug reactions from clinical trials are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions rst. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category
for each adverse drug reaction is based on the following convention (CIOMS III): very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).

Blood and lymphatic system disorders

 

 

 

Very common:

leucopenia

 

 

Common:

thrombocytopenia, eosinophilia

 

 

Rare:

leucocytosis, lymphadenopathy

 

 

Very rare:

agranulocytosis, aplastic anaemia, pancytopenia, aplasia pure red cell,

 

anaemia, anaemia megaloblastic, reticulocytosis, haemolytic anaemia

 

 

Not known:

bone marrow depression

 

 

Immune system disorders

 

 

 

Rare:

a delayed multi-organ hypersensitivity disorder with fever, rashes, vas-

 

culitis,  lymphadenopathy,  pseudo  lymphoma,  arthralgia,  leucopenia,

 

eosinophilia, hepato-splenomegaly, abnormal liver function tests and

 

vanishing bile duct syndrome (destruction and disappearance of the in-

 

trahepatic bile ducts) occurring in various combinations. Other organs

 

may also be affected (e.g. liver, lungs, kidneys, pancreas, myocardium,

 

colon)

 

 

Very rare:

anaphylactic reaction, oedema angioedema, hypogammaglobulinaemia

 

 

Not known**:

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)


Infections and infestations

 

 

 

 

 

 

Not known**

 

 

reactivation of Human herpesvirus 6 infection

 

 

 

Endocrine disorders

 

 

 

 

 

 

Common

 

 

Oedema,  uid  retention,  weight  increase,  hyponatraemia  and  blood

 

 

 

 

osmolarity decreased due to an antidiuretic hormone (ADH)-like effect,

 

 

 

 

leading in rare cases to water intoxication accompanied by lethargy,

 

 

 

 

vomiting, headache, confusional state, neurological disorders

 

 

 

 

Very rare

 

 

galactorrhoea, gynaecomastia

 

 

Metabolism and nutrition disorders

 

 

 

 

 

 

Rare

 

 

 

folate deciency, decreased appetite

 

 

 

 

Very rare

 

 

porphyria acute (acute intermittent porphyria and variegate porphyria),

 

 

 

 

porphyria non-acute (porphyria cutanea tarda)

 

 

 

Psychiatric disorders

 

 

 

 

 

 

 

Rare

 

 

 

hallucinations (visual or auditory), depression, aggression, agitation,

 

 

 

 

restlessness, confusional state

 

 

 

 

Very rare

 

 

activation of psychosis

 

 

 

Nervous system disorders

 

 

 

 

 

 

Very common

 

 

ataxia, dizziness, somnolence

 

 

 

 

Common

 

 

diplopia, headache

 

 

 

 

Uncommon

 

 

abnormal involuntary movements (e.g. tremor, asterixis, dystonia, tics),

 

 

 

 

nystagmus

 

 

 

 

 

Rare

 

 

 

dyskinesia, eye movementdisorder, speech disorders (e.g. dysarthria or

 

 

 

 

slurred speech), choreoathetosis, neuropathy peripheral, paraesthesia,

 

 

 

 

and paresis

 

 

 

 

Very rare

 

 

neuroleptic malignant syndrome, aseptic meningitis with myoclonus and

 

 

 

 

peripheral eosinophilia, dysgeusia

 

 

 

 

Not known**

 

 

sedation, memory impairment

 

 

 

Eye disorders

 

 

 

 

 

 

Common

 

 

accommodation disorders (e.g. blurred vision)

 

 

 

 

Very rare

 

 

lenticular opacities, conjunctivitis

 

 

 

Ear and labyrinth disorders

 

 

 

 

 

 

Very rare

 

 

hearing disorders, e.g. tinnitus, hyperacusis, hypoacusis, change in pitch

 

 

 

 

perception

 

 

 

Cardiac disorders

 

 

 

 

 

 

 

Rare

 

 

 

cardiac conduction disorders

 

 

 

 

Very rare

 

 

arrhythmia, atrioventricular block with syncope, bradycardia, cardiac fail -

 

 

 

 

ure congestive, coronary artery disease aggravated

 

 

 

Vascular disorders

 

 

 

 

 

 

 

Rare

 

 

 

hypertension or hypotension

 

 

 

 

Very Rare

 

 

circulatory collapse, embolism (e.g. pulmonary embolism), thrombophle-

 

 

 

 

bitis

 

 

 

Respiratory,

thoracic  and  mediastinal

 

disorders

 

 

 

 

 

 

 

Very rare

 

 

pulmonary hypersensitivity characterised e.g. by fever, dyspnoea, pneu-

 

 

 

 

monitis or pneumonia

 

 

 

Gastro-intestinal disorders

 

 

 

 

 

 

Very common

 

 

vomiting, nausea

 

 

 

 

Common

 

 

dry mouth, with suppositories rectal irritation may occur.

 

 

 

 

Uncommon

 

 

diarrhoea, constipation

 

 

 

 

 

Rare

 

 

 

abdominal pain

 

 

 

 

Very rare

 

 

Pancreatitis, glossitis, stomatitis

 

 

 

 

Not known**

 

 

colitis

 

 

 

Hepatobiliary disorders

 

 

 

 

 

 

 

Rare

 

 

 

hepatitis of cholestatic, parenchymal (hepatocellular) or mixed type, van -

 

 

 

 

ishing bile duct syndrome, jaundice

 

 

 

 

Very rare

 

 

hepatic failure, granulomatous liver disease

 

 

 

 

 

Skin

and

subcutaneous

tissue

 

disorders

 

 

 

 

 

 

 

Very common

 

 

urticaria, which may be severe dermatitus allergic

 

 

 

 

Uncommon

 

 

dermatitis exfoliative

 

 

 

 

 

Rare

 

 

 

systemic lupus erythematosus, pruritus

 

 

 

 

Very rare

 

 

Stevens-Johnson syndrome*, toxic epidermal necrolysis, photosensi-

 

 

 

 

tivity reaction, erythema multiforme, erythema nodosum, pigmentation

 

 

 

 

disorder, purpura, acne, hyperhydrosis, alopecia, hirsutism

 

 

 

 

Not known**

 

 

Acute Generalized Exanthematous Pustulosis (AGEP)**, lichenoid ker-

 

 

 

 

atosis, onychomadesis

 

 

Musculoskeletal, connective tissue and

 

bone disorders

 

 

 

 

 

 

 

Rare

 

 

 

muscular weakness

 

 

 

 

Very rare

 

 

bone metabolism disorders (decrease in plasma calcium and blood

 

 

 

 

25-hydroxy-cholecalciferol)  leading  to  osteomalacia/osteoporosis, -ar

 

 

 

 

thralgia, myalgia, muscle spasms

 

 

 

 

Not known**

 

 

fracture

 

 

 

Renal and urinary disorders

 

 

 

 

 

 

Very rare

 

 

tubulointerstitial nephritis, renal failure, renal impairment (e.g. albuminu-

 

 

 

 

ria, haematuria, oliguria and blood urea/ azotaemia), urinary retention,

 

 

 

 

urinary frequency

 

 

 

Reproductive System

 

 

 

 

 

 

Very rare:

 

 

sexual  disturbances/erecticle  dysfunction  spermatogenesis  abnormal

 

 

 

 

(with decreased sperm count and/or motility)

 

 

 

General

disorders  and  administration

 

site conditions

 

 

 

 

 

 

Very common:

 

 

fatigue

 

 

 

Investigations

 

 

 

 

 

 

Very common

 

 

gamma-glutamyltransferase increased (due to hepatic enzyme induc-

 

 

 

 

tion), usually not clinically relevant

 

 

 

 

Common

 

 

blood alkaline phosphatase increased

 

 

 

 

Uncommon

 

 

transaminases increased

 

 

 

 

Very rare

 

 

intraocular pressure increased, blood cholesterol increased, high density

 

 

 

 

lipoprotein increased, blood triglycerides increased. Thyroid function test

 

 

 

 

abnormal: decreased L-Thyroxin (free thyroxine, thyroxine, tri-iodothyro-

 

 

 

 

nine) and increased blood thyroid stimulating hormone, usually without

 

 

 

 

clinical manifestations, blood prolactin increased

 

 

 

 

Not known**

 

 

bone density decreased

 

 

 

 

 


* In some Asian countries also reported as rare. See also section Special warnings and precautions for use. **Additional adverse drug reactions from spontaneous reports (frequency not known)

What to do if you miss a dose?

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise take it as soon as you remember and then go back to taking it as you would normally.

Things you MUST NOT DO while on this medicine?

CONTRAINDICATIONS:
Known hypersensitivity to carbamazepine or structurally related drugs (e.g. tricyclic antidepressants) or any other component of the formulation.
Patients with atrioventricular block, a history of bone marrow depression or a history of hepatic porphyrias (e.g. acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda).
The use of Mezacar is contraindicated in combination with monoamine oxidase inhibitors (MAOIs) .
Treatment:
There is no specifc antidote.
Management should initially be guided by the patient's clinical condition; admission to hospital. Measurement of the plasma level to conrm carbamazepine poisoning and to ascertain the size of the overdose.
Evacuation of the stomach, gastric lavage, and administration of activated charcoal. Delay in evacuating the stomach may result in delayed absorption, leading to relapse during recovery from intoxication. Supportive medical care in an intensive care unit with cardiac monitoring and careful correction of electrolyte imbalance.
Special recommendations:
Charcoal haemoperfusion has been recommended. Hemodialysis is the effective treatment modality in the management of the carbamazepine overdose.
Relapse and aggravation of symptomatology on the 2nd and 3rd day after overdose, due to delayed absorption, should be anticipated.

What to do if you accidentally take too much (overdose) of the medicine?

OVERDOSAGE:
Signs and symptoms:
The presenting signs and symptoms of overdosage involve the central nervous (CNS depression; disorientation, depressed level of consciousness, somnolence, agitation, hallucination, coma; blurred vision, slurred speech, dysarthria, nystagmus, ataxia, dyskinesia, initially hyperreexia, later hyporeexia; convulsions, psychomotor disturbances, myoclonus,hypothermia, mydriasis), cardiovascular (Tachycardia, hypotension and at times hypertension, conduction disturbance with widening of QRS complex; syncope in association with cardiac arrest), respiratory systems (Respiratory depression, pulmonary oedema) and the adverse drug reactions mentioned under section Undesirable effects.

Is it safe in pregnancy and breast-feeding?

Tell your doctor immediately if you become pregnant while taking this medication. For safety of any drug during pregnancy or breastfeeding – please consult your doctor.

Storage Conditions:

Store below 30°C. Protect from moisture.
Keep all medicines out of reach of children

Drug Description

Composition:
Each uncoated tablet contains: Carbamazepine BP……..200 mg
Excipients:
Microcrystalline cellulose, Hypromellose E5, Sodium crosscarmellose, Colloidal silicon dioxide, Magnesium stearate.

Indications and dosage.

INDICATIONS:
Epilepsy- Generalized tonic-clonic and partial seizures.
Mezacar is not usually effective in absences (petit mal) and myoclonic seizures. Moreover, anecdotal evidence suggests that seizure exacerbation may occur in patients with atypical absences.
The paroxysmal pain of trigeminal neuralgia.
For the prophylaxis of manic-depressive psychosis in patients unresponsive to lithium therapy.

ADMINISTRATION AND DOSAGE:
Mezacar is given orally, usually in two or three divided doses. Mezacar may be taken during, after or between meals, with a little liquid e.g. a glass of water.
Epilepsy:
The dose of carbamazepine should be adjusted to the needs of the individual patient to achieve adequate control of seizures. Determination of plasma levels may help in establishing the optimum dosage. In the treatment of epilepsy, the dose of carbamazepine usually requires total plasma-carbamazepine concentrations of about 4 to 12 micrograms/mL (17 to 50 micromoles/ litre).
Adults:
It is advised that with Mezacar, a gradually increasing dosage scheme is used and this should be adjusted to suit the needs of the individual patient.
Mezacar should be taken in a number of divided doses although initially 100-200 mg once or twice daily is recommended. This may be followed by a slow increase until the best response is obtained, often 800-1200 mg daily. In some instances, 1600 mg or even 2000 mg daily may be necessary.
Elderly:
Due to the potential for drug interactions, the dosage of Mezacar should be selected with caution in elderly patients.
Children and adolescents:
It is advised that a gradually increasing dosage scheme is used and this should be adjusted to suit the needs of the individual patient.
Usual dosage 10-20 mg/kg bodyweight daily taken in several divided doses.
Mezacar tablets are not recommended for very young children

5-10 years:

400 to 600 mg daily (2-3 x 200 mg tablets per day, to be taken in divided doses).

 

 

10-15 years:

600 to 1000 mg daily (3-5 x 200 mg tablets per day, to be taken in several divided doses).

 

 

>15 years of age:

800 to 1200 mg daily (same as adult dose).

 

 


Maximum recommended dose Up to 6 years of age: 35 mg/kg/day 6-15 years of age: 1000 mg/day >15 years of age: 1200 mg/day.
Wherever possible, anti-epileptic agents should be prescribed as the sole anti-epileptic agent but if used in polytherapy the same incremental dosage pattern is advised. When Mezacar is added to existing antiepileptic therapy, this should be done gradually while maintaining or, if necessary, adapting the dosage of the other antiepileptic(s).
Trigeminal neuralgia:
Slowly raise the initial dosage of 200-400 mg daily until freedom from pain is achieved (normally at 200 mg 3-4 times daily). In the majority of patients a dosage of 200 mg 3 or 4 times a day is sufcient to maintain a pain free state. In some instances, doses of 1600 mg Mezacar daily may be needed. However, once the pain is in remission, the dosage should be gradually reduced to the lowest possible maintenance level. Maximum recommended dose is 1200 mg/day. When pain relief has been obtained, attempts should be made to gradually discontinue therapy, until another attack occurs.
Elderly:
Due to drug interactions and different antiepileptic drug pharmacokinetics, the dosage of Mezacar should be selected with caution in elderly patients.
In elderly patients, an initial dose of 100 mg twice daily is recommended. The initial dosage of 100 mg twice daily should be slowly raised daily until freedom from pain is achieved (normally at 200 mg 3 to 4 times daily). The dosage should then be gradually reduced to the lowest possible maintenance level. Maximum recommended dose is 1200 mg/day. When pain relief has been obtained, attempts should be made to gradually discontinue therapy, until another attack occurs.
For the prophylaxis of manic depressive psychosis in patients unresponsive to lithium therapy:
Initial starting dose of 400 mg daily, in divided doses, increasing gradually until symptoms are controlled or a total of 1600 mg given in divided doses is reached. The usual dosage range is 400-600 mg daily, given in divided doses.

Side effects and drug interactions.

UNDESIRABLE EFFECTS:
Adverse drug reactions from clinical trials are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions rst. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category
for each adverse drug reaction is based on the following convention (CIOMS III): very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).

Blood and lymphatic system disorders

 

Very common:

leucopenia

 

 

Common:

thrombocytopenia, eosinophilia

 

 

Rare:

leucocytosis, lymphadenopathy

 

 

Very rare:

agranulocytosis, aplastic anaemia, pancytopenia, aplasia pure red cell,

 

anaemia, anaemia megaloblastic, reticulocytosis, haemolytic anaemia

 

 

Not known:

bone marrow depression

 

 

Immune system disorders

 

 

 

Rare:

a delayed multi-organ hypersensitivity disorder with fever, rashes, vas-

 

culitis,  lymphadenopathy,  pseudo  lymphoma,  arthralgia,  leucopenia,

 

eosinophilia, hepato-splenomegaly, abnormal liver function tests and

 

vanishing bile duct syndrome (destruction and disappearance of the in-

 

trahepatic bile ducts) occurring in various combinations. Other organs

 

may also be affected (e.g. liver, lungs, kidneys, pancreas, myocardium,

 

colon)

 

 

Very rare:

anaphylactic reaction, oedema angioedema, hypogammaglobulinaemia

 

 

Not known**:

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)


Infections and infestations

 

 

 

 

 

 

Not known**

 

 

reactivation of Human herpesvirus 6 infection

 

 

 

Endocrine disorders

 

 

 

 

 

 

Common

 

 

Oedema,  uid  retention,  weight  increase,  hyponatraemia  and  blood

 

 

 

 

osmolarity decreased due to an antidiuretic hormone (ADH)-like effect,

 

 

 

 

leading in rare cases to water intoxication accompanied by lethargy,

 

 

 

 

vomiting, headache, confusional state, neurological disorders

 

 

 

 

Very rare

 

 

galactorrhoea, gynaecomastia

 

 

Metabolism and nutrition disorders

 

 

 

 

 

 

Rare

 

 

 

folate deciency, decreased appetite

 

 

 

 

Very rare

 

 

porphyria acute (acute intermittent porphyria and variegate porphyria),

 

 

 

 

porphyria non-acute (porphyria cutanea tarda)

 

 

 

Psychiatric disorders

 

 

 

 

 

 

 

Rare

 

 

 

hallucinations (visual or auditory), depression, aggression, agitation,

 

 

 

 

restlessness, confusional state

 

 

 

 

Very rare

 

 

activation of psychosis

 

 

 

Nervous system disorders

 

 

 

 

 

 

Very common

 

 

ataxia, dizziness, somnolence

 

 

 

 

Common

 

 

diplopia, headache

 

 

 

 

Uncommon

 

 

abnormal involuntary movements (e.g. tremor, asterixis, dystonia, tics),

 

 

 

 

nystagmus

 

 

 

 

 

Rare

 

 

 

dyskinesia, eye movementdisorder, speech disorders (e.g. dysarthria or

 

 

 

 

slurred speech), choreoathetosis, neuropathy peripheral, paraesthesia,

 

 

 

 

and paresis

 

 

 

 

Very rare

 

 

neuroleptic malignant syndrome, aseptic meningitis with myoclonus and

 

 

 

 

peripheral eosinophilia, dysgeusia

 

 

 

 

Not known**

 

 

sedation, memory impairment

 

 

 

Eye disorders

 

 

 

 

 

 

Common

 

 

accommodation disorders (e.g. blurred vision)

 

 

 

 

Very rare

 

 

lenticular opacities, conjunctivitis

 

 

 

Ear and labyrinth disorders

 

 

 

 

 

 

Very rare

 

 

hearing disorders, e.g. tinnitus, hyperacusis, hypoacusis, change in pitch

 

 

 

 

perception

 

 

 

Cardiac disorders

 

 

 

 

 

 

 

Rare

 

 

 

cardiac conduction disorders

 

 

 

 

Very rare

 

 

arrhythmia, atrioventricular block with syncope, bradycardia, cardiac fail -

 

 

 

 

ure congestive, coronary artery disease aggravated

 

 

 

Vascular disorders

 

 

 

 

 

 

 

Rare

 

 

 

hypertension or hypotension

 

 

 

 

Very Rare

 

 

circulatory collapse, embolism (e.g. pulmonary embolism), thrombophle-

 

 

 

 

bitis

 

 

 

Respiratory,

thoracic  and  mediastinal

 

disorders

 

 

 

 

 

 

 

Very rare

 

 

pulmonary hypersensitivity characterised e.g. by fever, dyspnoea, pneu-

 

 

 

 

monitis or pneumonia

 

 

 

Gastro-intestinal disorders

 

 

 

 

 

 

Very common

 

 

vomiting, nausea

 

 

 

 

Common

 

 

dry mouth, with suppositories rectal irritation may occur.

 

 

 

 

Uncommon

 

 

diarrhoea, constipation

 

 

 

 

 

Rare

 

 

 

abdominal pain

 

 

 

 

Very rare

 

 

Pancreatitis, glossitis, stomatitis

 

 

 

 

Not known**

 

 

colitis

 

 

 

Hepatobiliary disorders

 

 

 

 

 

 

 

Rare

 

 

 

hepatitis of cholestatic, parenchymal (hepatocellular) or mixed type, van -

 

 

 

 

ishing bile duct syndrome, jaundice

 

 

 

 

Very rare

 

 

hepatic failure, granulomatous liver disease

 

 

 

 

 

Skin

and

subcutaneous

tissue

 

disorders

 

 

 

 

 

 

 

Very common

 

 

urticaria, which may be severe dermatitus allergic

 

 

 

 

Uncommon

 

 

dermatitis exfoliative

 

 

 

 

 

Rare

 

 

 

systemic lupus erythematosus, pruritus

 

 

 

 

Very rare

 

 

Stevens-Johnson syndrome*, toxic epidermal necrolysis, photosensi-

 

 

 

 

tivity reaction, erythema multiforme, erythema nodosum, pigmentation

 

 

 

 

disorder, purpura, acne, hyperhydrosis, alopecia, hirsutism

 

 

 

 

Not known**

 

 

Acute Generalized Exanthematous Pustulosis (AGEP)**, lichenoid ker-

 

 

 

 

atosis, onychomadesis

 

 

Musculoskeletal, connective tissue and

 

bone disorders

 

 

 

 

 

 

 

Rare

 

 

 

muscular weakness

 

 

 

 

Very rare

 

 

bone metabolism disorders (decrease in plasma calcium and blood

 

 

 

 

25-hydroxy-cholecalciferol)  leading  to  osteomalacia/osteoporosis, -ar

 

 

 

 

thralgia, myalgia, muscle spasms

 

 

 

 

Not known**

 

 

fracture

 

 

 

Renal and urinary disorders

 

 

 

 

 

 

Very rare

 

 

tubulointerstitial nephritis, renal failure, renal impairment (e.g. albuminu-

 

 

 

 

ria, haematuria, oliguria and blood urea/ azotaemia), urinary retention,

 

 

 

 

urinary frequency

 

 

 

Reproductive System

 

 

 

 

 

 

Very rare:

 

 

sexual  disturbances/erecticle  dysfunction  spermatogenesis  abnormal

 

 

 

 

(with decreased sperm count and/or motility)

 

 

 

General

disorders  and  administration

 

site conditions

 

 

 

 

 

 

Very common:

 

 

fatigue

 

 

 

Investigations

 

 

 

 

 

 

Very common

 

 

gamma-glutamyltransferase increased (due to hepatic enzyme induc-

 

 

 

 

tion), usually not clinically relevant

 

 

 

 

Common

 

 

blood alkaline phosphatase increased

 

 

 

 

Uncommon

 

 

transaminases increased

 

 

 

 

Very rare

 

 

intraocular pressure increased, blood cholesterol increased, high density

 

 

 

 

lipoprotein increased, blood triglycerides increased. Thyroid function test

 

 

 

 

abnormal: decreased L-Thyroxin (free thyroxine, thyroxine, tri-iodothyro-

 

 

 

 

nine) and increased blood thyroid stimulating hormone, usually without

 

 

 

 

clinical manifestations, blood prolactin increased

 

 

 

 

Not known**

 

 

bone density decreased

 

 

 

 

 


* In some Asian countries also reported as rare. See also section Special warnings and precautions for use. **Additional adverse drug reactions from spontaneous reports (frequency not known)
INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTION:
Interactions resulting in a contraindication:
The use of Mezacar is contraindicated in combination with monoamine-oxidase inhibitors (MAOIs); before administering Mezacar MAOIs should be discontinued for a minimum of 2 weeks, or longer if the clinical situation permits.
Agents that may raise carbamazepine plasma levels:
Since raised plasma carbamazepine levels may result in adverse reactions (e.g. dizziness, drowsiness, ataxia, diplopia), the dosage of Mezacar should be adjusted accordingly and/or the plasma levels monitored when used concomitantly with the substances described below:
Analgesics, anti-inflammatory drugs: dextropropoxyphene Androgens:
danazol
Antibiotics:
Macrolide antibiotics (e.g. erythromycin, clarithromycin), ciprooxacine Antidepressants: uoxetine, uvoxamine, paroxetine, trazodone
Antiepileptics:
vigabatrin
Antifungals:
Azoles (e.g. itraconazole, ketoconazole, uconazole, voriconazole). Alternative anti-convulsants may be recommended in patients treated with voriconazole or itraconazole
Antihistamines:
loratadine Antipsychotics:

Olanzapine Antituberculosis: isoniazid
Antivirals:
Protease inhibitors for HIV treatment (e.g. ritonavir)
Carbonic anhydrase inhibitors:
Acetazolamide Cardiovascular drugs:
Diltiazem, verapamil
Gastrointestinal drugs:
Possibly cimetidine, omeprazole
Other interactions: grapefruit juice, nicotinamide (only in high dosage)
Agents that may raise the active metabolite carbamazepine-10,11-epoxide plasma levels:
Since raised plasma carbamazepine-10,11-epoxide levels may result in adverse reactions (e.g. dizziness, drowsiness, ataxia, diplopia), the dosage of Mezacar should be adjusted accordingly and/or the plasma levels monitored when used concomitantly with the substances described below:
Quetiapine, primidone, progabide, valproic acid, valnoctamide and valpromide
Agents that may decrease carbamazepine plasma levels:
The dose of Mezacar may have to be adjusted when used concomitantly with the substances described below: Antiepileptics: oxcarbazepine, phenobarbital, phenytoin (to avoid phenytoin intoxication and subtherapeutic concentrations of carbamazepine it is recommended to adjust the plasma concentration of phenytoin to 13 micrograms /mL before adding carbamazepine to the treatment) and fosphenytoin, primidone, and, although the data are partly contradictory, possibly also clonazepam.
Antineoplastics
Cisplatin or doxorubicin
Antituberculosis:
Rifampicin
Bronchodilatators or anti-asthma drugs: theophylline, aminophylline Dermatological drugs:
Isotretinoin
Other interactions:
Herbal preparations containing St John's wort (Hypericum perforatum) Effect of Mezacar on plasma levels of concomitant agents:
Carbamazepine may lower the plasma level, diminish or even abolish the activity of certain drugs. The dosage of the following drugs may have to be adjusted to clinical requirement: Analgesics, anti-inflammatory agents: buprenorphine, methadone, paracetamol (long term administration of carbamazepine and paracetamol (acetaminophen) may be associated with hepatotoxicity), tramadol
Antibiotics:
doxycycline, rifabutin
Anticoagulants:
Oral anticoagulants (e.g. warfarin and acenocoumarol)
Antidepressants:
bupropion, citalopram, mianserin, sertraline, trazodone, tricyclic antidepressants (e.g. imipramine, amitriptyline, nortriptyline, clomipramine)
Antiemetics:
aprepitant
Antiepileptics:
clobazam, clonazepam, ethosuximide, lamotrigine, oxcarbazepine, primidone, tiagabine, topiramate, valproic acid, zonisamide. To avoid phenytoin intoxication and subtherapeutic concentrations of carbamazepine it is recommended to adjust the plasma concentration of phenytoin to 13 micrograms /mL before adding carbamazepine to the treatment. There have been rare reports of an increase in plasma mephenytoin levels.
Antifungals:
itraconazole, voriconazole. Alternative anti-convulsants may be recommended in patients treated with voriconazole or itraconazole.
Antihelmintics:
albendazole
Antineoplastics:
imatinib, cyclophosphamide, lapatinib, temsirolimus.
Antipsychotics: clozapine, haloperidol and bromperidol, olanzapine, quetiapine, risperidone, aripiprazole, paliperidone Antivirals: protease inhibitors for HIV treatment (e.g. indinavir, ritonavir, saquinavir)
Anxiolytics:
alprazolam
Bronchodilatators or anti-asthma drugs: theophylline
Contraceptives:
hormonal contraceptives (alternative contraceptive methods should be considered)
Cardiovascular drugs:
calcium channel blockers (dihydropyridine group) e.g. felodipine, digoxin, simvastatin, atorvastatin, lovastatin, cerivastatin, ivabradine
Corticosteroids:
corticosteroids (e.g. prednisolone, dexamethasone)
Drugs used in erectile dysfunction:
tadalal
Immunosuppressants:
ciclosporin, everolimus, tacrolimus, sirolimus
Thyroid agents:
levothyroxine
Other drug interactions: products containing oestrogens and/or progesterones
Combinations that require specific consideration:
Concomitant use of carbamazepine and levetiracetam has been reported to increase carbamazepine-induced toxicity. Concomitant use of carbamazepine and isoniazid has been reported to increase isoniazid-induced hepatotoxicity.
The combination of lithium and carbamazepine may cause enhanced neurotoxicity in spite of lithium plasma concentrations being within the therapeutic range. Combined use of carbamazepine with metoclopramide or major tranquillisers, e.g. haloperidol, thioridazine, may also result in an increase in neurological side-effects.
Concomitant medication with Mezacar and some diuretics (hydrochlorothiazide, furosemide) may lead to symptomatic hyponatraemia.
Carbamazepine may antagonise the effects of non-depolarising muscle relaxants (e.g. pancuronium). Their dosage should be raised and patients monitored closely for a more rapid recovery from neuromuscular blockade than expected. Carbamazepine, like other psychoactive drugs, may reduce alcohol tolerance. It is therefore advisable for the patient to abstain from alcohol.
Interference with serological testing:
Carbamazepine may result in false positive perphenazine concentrations in HPLC analysis due to interference. Carbamazepine and the 10,11-epoxide metabolite may result in false positive tricyclic antidepressant concentration in uorescence polarized immunoassay method.

Warnings and precautions

SPECIAL WARNINGS AND PRECAUTIONS FOR USE Warnings:

Agranulocytosis and aplastic anaemia have been associated with Mezacar; however, due to the very low incidence of these conditions, meaningful risk estimates for Mezacar are difcult to obtain.
Decreased platelet or white blood cell counts occur occasionally to frequently in association with the use of Mezacar. Nonetheless, complete pre-treatment blood counts, including platelets and possibly reticulocytes and serum iron, should be obtained as a baseline, and periodically thereafter.
Patients and their relatives should be made aware of early toxic signs and symptoms indicative of a potential haematological problem, as well as symptoms of dermatological or hepatic reactions. If reactions such as fever, sore throat, rash, ulcers in the mouth, easy bruising, petechial or purpuric haemorrhage appear, the patient should be advised to consult his physician immediately.
If the white blood cell or platelet count is denitely low or decreased during treatment, the patient and the complete blood count should be closely monitored. However, treatment with Mezacar should be discontinued if the patient develops leucopenia which is severe, progressive or accompanied by clinical manifestations, e.g. fever or sore throat. Mezacar should also be discontinued if any evidence of signicant bone marrow depression appears.
Liver function tests should also be performed before commencing treatment and periodically thereafter, particularly in patients with a history of liver disease and in elderly patients. The drug should be withdrawn immediately in cases of aggravated liver dysfunction or acute liver disease. Some liver function tests in patients receiving carbamazepine may be found to be abnormal, particularly gamma glutamyl transferase. This is probably due to hepatic enzyme induction. Enzyme induction may also produce modest elevations in alkaline phosphatase. These enhancements of hepatic metabolizing capacity are not an indication for the withdrawal of carbamazepine.
Severe hepatic reactions to carbamazepine occur very rarely. The development of signs and symptoms of liver dysfunction or active liver disease should be urgently evaluated and treatment with Mezacar suspended pending the outcome of the evaluation.
Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.
Serious dermatological reactions, including toxic epidermal necrolysis (TEN: also known as Lyell's syndrome) and Stevens Johnson syndrome (SJS) have been reported very rarely with Mezacar. Patients with serious dermatological reactions may require hospitalization, as these conditions may be life-threatening and may be fatal. Most of the SJS/TEN cases appear in the rst few months of treatment with Mezacar. These reactions are estimated to occur in 1 to 6 per 10,000 new users in countries with mainly Caucasian populations. If signs and symptoms suggestive of severe skin reactions (e.g. SJS, Lyell's syndrome/TEN) appear, Mezacar should be withdrawn at once and alternative therapy should be considered.
HLA-B*1502 allele - in Han Chinese, Thai and other Asian populations:
HLA-B*1502 in individuals of Han Chinese and Thai origin has been shown to be strongly associated with the risk of developing Stevens-Johnson syndrome (SJS) when treated with carbamazepine. The prevalence of HLA-B*1502 carrier is about 10% in Han Chinese and Thai populations. Whenever possible, these individuals should be screened for this allele before starting treatment with carbamazepine. If these individuals test positive, carbamazepine should not be started unless there is no other therapeutic option. Tested patients who are found to be negative for HLA-B*1502 have a low risk of SJS, although the reactions may still very rarely occur.
There are some data that suggest an increased risk of serious carbamazepine-associated TEN/SJS in other Asian populations. Because of the prevalence of this allele in other Asian populations (e.g. above 15% in the Philippines and Malaysia), testing genetically at risk populations for the presence of HLA-B*1502 may be considered. The prevalence of the HLA-B*1502 allele is negligible in e.g. European descent, African, Hispanic populations sampled, and in Japanese and Koreans (< 1%).
Hypersensitivity: Mezacar may trigger hypersensitivity reactions, including Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), reactivation of HHV6 associated with DRESS, a delayed multi-organ hypersensitivity disorder with fever, rash, vasculitis, lymphadenopathy, pseudo lymphoma, arthralgia, leukopenia, eosinophilia, hepato-splenomegaly, abnormal liver function tests and vanishing bile duct syndrome (destruction and disappearance of the intrahepatic bile ducts), that may occur in various combinations. Other organs may also be affected (e.g. lungs, kidneys, pancreas, myocardium, colon)
In general, if signs and symptoms suggestive of hypersensitivity reactions occur, Mezacar should be withdrawn immediately. Patients who have exhibited hypersensitivity reactions to carbamazepine should be informed that 25-30 % of these patients may experience hypersensitivity reactions with oxacarbazepine .
Cross-hypersensitivity can occur between carbamazepine and phenytoin.
Carbamazepine should be used with caution in patients with mixed seizures which include absences, either typical or atypical. In all these conditions, carbamazepine may exacerbate seizures. In case of exacerbation of seizures, carbamazepine should be discontinued.
An increase in seizure frequency may occur during switchover from an oral formulation to suppositories.
Dose reduction and withdrawal effects:
Abrupt withdrawal of carbamazepine may precipitate seizures therefore carbamazepine withdrawal should be gradual. If treatment with carbamazepine has to be withdrawn abruptly in a patient with epilepsy, the changeover to another anti-epileptic drug should if necessary be effected under the cover of a suitable drug.
Endocrinological effects:
Breakthrough bleeding has been reported in women taking carbamazepine while using hormonal contraceptives. The reliability of hormonal contraceptives may be adversely affected by carbamazepine and women of childbearing potential should be advised to consider using alternative forms of birth control while taking carbamazepine.
Patients taking carbamazepine and requiring hormonal contraception should receive a preparation containing not less than 50µg oestrogen or use of some alternative non-hormonal method of contraception should be considered.
Monitoring of plasma levels:
Although correlations between dosages and plasma levels of carbamazepine, and between plasma levels and clinical efcacy or tolerability are rather tenuous, monitoring of the plasma levels may be useful in the following conditions: dramatic increase in seizure frequency/verication of patient compliance; during pregnancy; when treating children or adolescents; in suspected absorption disorders; in suspected toxicity when more than one drug is being used.

Precautions: Mezacar should be prescribed only after a critical benet-risk appraisal and under close monitoring in patients with a history of cardiac, hepatic or renal damage, adverse haematological reactions to other drugs, or interrupted courses of therapy with carbamazepine.
Baseline and periodic complete urinalysis and BUN determinations are recommended.
Hyponatremia:
Hyponatremia is known to occur with carbamazepine. In patients with pre-existing renal conditions associated with low sodium or in patients treated concomitantly with sodium-lowering medicinal products (e.g. diuretics, medicinal products associated with inappropriate ADH secretion), serum sodium levels should be measured prior to initiating carbamazepine therapy. Thereafter, serum sodium levels should be measured after approximately two weeks and then at monthly intervals for the rst three months during therapy, or according to clinical need. These risk factors may apply especially to elderly patients. If hyponatraemia is observed, water restriction is an important counter-measurement if clinically indicated.
Hypothyroidism:
Carbamazepine may reduce serum concentrations of thyroid hormones through enzyme induction requiring an increase in dose of thyroid replacement therapy in patients with hypothyroidism. Hence thyroid function monitoring is suggested to adjust the dosage of thyroid replacement therapy.
Anticholinergic effects:
Carbamazepine has shown mild anticholinergic activity; patients with increased intraocular pressure and urinary retention should therefore be closely observed during therapy.
Psychiatric effects:
The possibility of activation of a latent psychosis and, in elderly patients, of confusion or agitation should be borne in mind.
PREGNANCY AND LACTATION:
Offspring of epileptic mothers with untreated epilepsy are known to be more prone to developmental disorders, including malformations. Developmental disorders and malformations, including spina bida, and also other congenital anomalies e.g. craniofacial defects such as clept lip/palate, cardiovascular malformations, hypospadias and anomalies involving various body systems, have been reported.
Taking these data into consideration:
- Pregnant women with epilepsy should be treated with special care.
- If women receiving Mezacar become pregnant or plan to become pregnant, or if the problem of initiating treatment with Mezacar arises during pregnancy, the drug's expected benets must be carefully weighed against its possible hazards, particularly in the rst 3 months of pregnancy.
- During pregnancy, an effective antiepileptic treatment should not be interrupted, since the aggravation of the illness is detrimental to both the mother and the fetus.
Breast-feeding:
Carbamazepine passes into the breast milk (about 25-60% of the plasma concentrations). The benets of breast-feeding should be weighed against the remote possibility of adverse effects occurring in the infant. Mothers taking Mezacar may breast-feed their infants, provided the infant is observed for possible adverse reactions (e.g. excessive somnolence, allergic skin reaction).
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
The patient's ability to react may be impaired by the medical condition resulting in seizures and adverse reactions including dizziness, drowsiness, ataxia, diplopia, impaired accommodation and blurred vision reported with Mezacar, especially at the start of treatment or in connection with dose adjustments. Patients should therefore exercise due caution when driving a vehicle or operating machinery.

Overdosage and Contraindications

OVERDOSAGE:
Signs and symptoms:
The presenting signs and symptoms of overdosage involve the central nervous (CNS depression; disorientation, depressed level of consciousness, somnolence, agitation, hallucination, coma; blurred vision, slurred speech, dysarthria, nystagmus, ataxia, dyskinesia, initially hyperreexia, later hyporeexia; convulsions, psychomotor disturbances, myoclonus,hypothermia, mydriasis), cardiovascular (Tachycardia, hypotension and at times hypertension, conduction disturbance with widening of QRS complex; syncope in association with cardiac arrest), respiratory systems (Respiratory depression, pulmonary oedema) and the adverse drug reactions mentioned under section Undesirable effects.

CONTRAINDICATIONS:
Known hypersensitivity to carbamazepine or structurally related drugs (e.g. tricyclic antidepressants) or any other component of the formulation.
Patients with atrioventricular block, a history of bone marrow depression or a history of hepatic porphyrias (e.g. acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda).
The use of Mezacar is contraindicated in combination with monoamine oxidase inhibitors (MAOIs) .
Treatment:
There is no specifc antidote.
Management should initially be guided by the patient's clinical condition; admission to hospital. Measurement of the plasma level to conrm carbamazepine poisoning and to ascertain the size of the overdose.
Evacuation of the stomach, gastric lavage, and administration of activated charcoal. Delay in evacuating the stomach may result in delayed absorption, leading to relapse during recovery from intoxication. Supportive medical care in an intensive care unit with cardiac monitoring and careful correction of electrolyte imbalance.
Special recommendations:
Charcoal haemoperfusion has been recommended. Hemodialysis is the effective treatment modality in the management of the carbamazepine overdose.
Relapse and aggravation of symptomatology on the 2nd and 3rd day after overdose, due to delayed absorption, should be anticipated.

Clinical pharmacology.

PHARMACOLOGIC PROPERTIES:
Pharmacodynamics: As an antiepileptic agent its spectrum of activity embraces: partial seizures (simple and complex) with and without secondary generalisation; generalised tonic-clonic seizures, as well as combinations of these types of seizures. The mechanism of action of carbamazepine, has only been partially elucidated. Carbamazepine stabilizes hyperexcited nerve membranes, inhibits repetitive neuronal discharges, and reduces synaptic propagation of excitatory impulses. It is conceivable that prevention of repetitive ring of sodium-dependent action potentials in depolarised neurons via use- and voltage-dependent blockade of sodium channels may be its main mechanism of action.
Whereas reduction of glutamate release and stabilisation of neuronal membranes may account for the antiepileptic effects, the depressant effect on dopamine and noradrenaline turnover could be responsible for the antimanic properties of carbamazepine.
Pharmacokinetics:
Absorption: Carbamazepine

is absorbed almost completely but relatively slowly from the tablets. The conventional tablets yield mean peak plasma concentrations of the unchanged substance within 12 hours following single oral doses.
The bioavailability of carbamazepine in various oral formulations has been shown to lie between 85-100%. Ingestion of food has no signicant inuence on the rate and extent of absorption.
Distribution:
Carbamazepine is bound to serum proteins to the extent of 70-80%. The concentration of unchanged substance in cerebrospinal uid and saliva reects the non-protein bound portion in plasma (20-30%). Concentrations in breast milk were found to be equivalent to 25-60% of the corresponding plasma levels. Carbamazepine crosses the placental barrier. Assuming complete absorption of carbamazepine, the apparent volume of distribution ranges from 0.8 to 1.9 L/kg.
Metabolism:
Carbamazepine is metabolised in the liver, where the epoxide pathway of biotransformation is the most important one, yielding the 10,11-transdiol derivative and its glucuronide as the main metabolites.
Cytochrome P450 3A4 has been identied as the major isoform responsible for the formation of carbamazepine 10,11-epoxide from carbamazepine.
Elimination: The elimination half-life of unchanged carbamazepine averages approx. 36 hours following a single oral dose, whereas after repeated administration it averages only 16-24 hours (auto-induction of the hepatic mono-oxygenase system), depending on the duration of the medication. In patients receiving concomitant treatment with other enzyme-inducing drugs (e.g. phenytoin, phenobarbitone), half-life values averaging 9-10 hours have been found.
The mean elimination half-life of the 10, 11-epoxide metabolite in the plasma is about 6 hours following single oral doses of the epoxide itself.
After administration of a single oral dose of 400mg carbamazepine, 72% is excreted in the urine and 28% in the faeces. In the urine, about 2% of the dose is recovered as unchanged drug and about 1% as the pharmacologically active 10, 11-epoxide metabolite.
Characteristics in patients:
Owing to enhanced carbamazepine elimination, children may require higher doses of carbamazepine (in mg/kg) than adults to maintain therapeutic concentrations.
There is no indication of altered pharmacokinetics of carbamazepine in elderly patients as compared with young adults. No data are available on the pharmacokinetics of carbamazepine in patients with impaired hepatic or renal function.
STORAGE CONDITIONS:
Store below 30°C. Protect from moisture.
Keep all medicines out of reach of children.
SHELF-LIFE:
36 months
DOSAGE FORMS AND PACKAGING AVAILABLE:
White opaque PVC/PVDC-Alu blister of 10 tablets, 5 or 10 blisters are in a carton.
NAME AND ADDRESS OF MANUFACTURER:
Kusum Healthcare Pvt. Ltd.
SP 289(A), RIICO Indl. Area,
Chopanki, Bhiwadi (Rajasthan), India
DATE OF REVISION OF PACKAGE INSERT:
Not Applicable
MM Reg. No.:
1812AA 7078

CERTIFICATES

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