Mazemal tablets
Carbamazepine 200 mg
DESCRIPTION:
Carbamazepine USP is an anticonvulsant and specific analgesic for trigeminal neuralgia, its chemical name is 5H-dibenz (b, f) azepine-5- carboxamide.
CLINICAL PHARMACOLOGY:
Mazema~ has been shown to be effective in the treatmenl of
psychomotor and grand mal seizures, as well as trigeminal neuralgia.
Mechanism of Action:
Carbamazepine appears to act by reducing polysynaptic response and’ blocking the post-tetanic potentiation. Carbamazepine greatly reduces or abolishes pain induced by stimulation of the infraorbital nerve. The principal metabolite of carbamazepine-10, tt-epoxde, has anticonvulsant activity as demonstrated in several in vivo animal models of seizures.
Pharmacokinetics:
The bioavailability of the tablet is 69% compared to suspension. Following a twice a day dosage re.!limen, the suspension provides higher peak levels and lower trough levels than those obtained from the conventional tablet for the same dosage regimen. Carbamazepine in blood IS 76% bound to plasma proteins. Plasma levels of carbamazepine are variable and may range from 0.5-25 mcg/ml. The CSF/serum ratio is 0.22, similar to the 22% unbound
Indications and dosage:
1- Epilepsy
Adults And Children Over 12 Years Of Age
Initial: 200 mg twice a day ,Increase at weekly intervals by adding up to 200 mg per day using a twice a day regimen or three times a day or four times a day regimen until the optimal response is obtained. Dosage generally should not exceed 1000 mg daily in children 12 to 15 years of age, and 1200 mg daily in patients above 15 years of age. Doses up to 1600 mg daily have been used in adults in rare instances.
Maintenance: Adjust dosage to the minimum effective level, usually 600-
1200 mg daily.
Children 6 – 12 Years Of Age
Initial: 100 mg twice a day, Increase at weekly intervals by adding up to 100 mg per day using three times a day or four times a day regimen until the optimal response is obtained. Dosage generally should not exceed 1000 mg daily.
Maintenance: Adjust dosage to the minimum effective level, usually 400-
600 mg daily.
Combination Therapy: Mazemal ® may be used alone or with other
anticonvulsants. When added to existing anticonvulsant therapy, the drug
should be added gradually while the other anticonvulsants are-maintained or-gradually deC<&aSed,-except phenytoin, which may have to be increased.
2-Trigeminal Neuralgia
Initial: On the first day, 100 mg twice .This daily dose may be increased by up to 200 mg a day using increments of 100 mg every 12 hours, only as needed to achieve freedom from pain. Do not exceed 1200 mg/daily.
Maintenance: Control of pain can be maintained in most patients wilh 400 mg to 600 mg daily. At least once every 3 months throughout the treatment period, attempts should be made to reduce the dose to the minimum effective level or even to discontinue the drug.
SIDE EFFECTS:
If adverse reactions are of such severity that the drug must be discontinued, the physic@n must b,e aware that abrullt discontinuation of any anticonvulsant drug in a responsive epileptic patient may lead to seizures or even status epilepticus with its life-threatening hazards. The most severe adverse reactions have been observed in the hemopoietic system To minimize the possibility of such reactions, therapy should be initiated at the low dosage recommended.
The following additional adverse reactions have been reported
Hemopoietic System: Aplastic anemia, agranulocytosis, pancytopenia, bone marrow depression, thrombocytopenia, leukopenia, leukocytosis, eosinophilia, acute intermittenl porphyria
Skin: Pruritic and erythematous rashes, urticaria, toxic epidermal necrolysis (Lyell’s Syndrome) ,photosensitivity reactions, alterations in skinpigmentation, exfoliative dermatitis, erythema multiforme and nodosum, purpura, aggravation of disseminated lupus erythromatosis, alopecia, and diaphoresis. In certain cases, discontinuation of therapy may be necessary. Isolated cases of hirsutism have been reported, but a causal relationship is not clear.
Cardiovascular System: Congestive heart failure, edema, aggravation of hypertension, hypotension, syncope and collapse, aggravation of coronary artery disease, arrhythmias and AV block, primary thrombophlebitis, recurrence of thrombophlebitis, and adenopathy or lymphadenopathy. Some of these cardiovascular complications have resulted in fatalities. Myocardial infarction has been associated with other tricyclic compounds.
Liver: Abnormalities in liver function tests, cholestatic and hepatocellular
jaundice •. hepatitis. Respiratory System: Pulmonary hypersensitivity characterized by fever, dyspnea, pneumonitis or pneumonia.
Genitourinary System: Urinary frequency, acute urinary retention,
oliguria with elevated blood pressure, azotemia, renal failure, and impotence
Nervous System: Dizziness, drowsiness, disturbances of coordination,
confusion, headache, fatigue, blurred vision, visual hallucinations, and
transient diplopia.
Digestive System: Nausea, vomiting, gastric distress and abdominal pain, diarrnea, constipation, anorexia, and dryness of the mouth and pharynx, including glossitis and stomatitis.
Eyes: Scattered punctate cortical lens opacities. as well as conjunctivitis.
have been reported
Musculoskeletal System: Aching joints and muscles. and leg cramps.
Metabolism: Fever and chills. Inappropriate antidiuretic hormone (ADH)
secretion syndrome has been reported.
Drug Abuse and Dependence :No evidence of abuse potential has been associated with carbamazepine. nor is there evidence of psychological or physical dependence in humans.
DRUG INTERACTIONS:
The simultaneous administration of phenobarbital. phenytoin. or primidone. or a combination of two. produces a marked lowering of serum levels of carbamazepine. The effect of valproic acid on carbamazepine blood levels is not clearly established. although an increase in the ratio of active 10. 11-epoxide metabolite to parent compound is a consistent finding. The half-lives of phenytoin. warfarin. doxycycline. and theophylline were significantly shortened when administered concurrently with carbamazepine. Haloperidol and valproic acid serum levels may be reduced when these drugs are administered with carbamazepine. The doses of these drugs may therefore have to be increased when carbamazepine is added to the therapeutic regimen.
Concomitant administration of carbamazepine with erythromycin. cimetidine. propoxyphene. isoniazid. fluoxetine or calcium channel blockers has been reported to resulLin elevated plasma levels of carbamazepine resulting in toxicity in some cases. Also concomitant administration of carbamazepine and lithium may Increase the risk or neurotoxic side effects. Alterations of thyroid function have been reported in combination therapy with other anticonvulsant medications. Breakthrough bleeding has been reported among patients receiving concomitant oral contraceptives and their reliability may be adversely affected.
WARNINGS:
Patients with a history of adverse hematological reaction to any drug may
be particularly at risk. Carbamazepine has shown mild antichotinergic activity: therefore. patients with increased intraocular pressure should be closely observed during therapy.Because of the relationship of the drug to other tricyclic compounds. the possibility of activation of a latent psychosis and in elderly patients of confusion or agitation should be borne in mind.
PRECAUTIONS:
General Before initiating therapy. a detailed history and physical examination
should be made. Carcinogenesis. Mutagenesis and Impairment of Fertility
Carbamazepine. when administered to Sprague-Dawley rats for two years in the diet at doses of 25, 75. and 250 mglkylday. resulted in a dose-related increase in the incidence of hepatocellular lumors in females and of benign interstitial cell adenomas in the testes of males. Bacterial and mammalian mutageniCity studies using carbarnazepine produce negative results. The significance or these findings relative to the use of carbamazepine in humans is at present. unknown.
Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women
Epidemiological data suggest that there may be an association between
the use of carbamazepine during pregnancy and congenital malformations. including spina bifida. Carbamazepine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Labor and Delivery
The effect of carbamazepine on human labor and delivery is unknown.
Nursing Mothers
During lactation. concentration of carbamazepil’le in milk is approximately
60% of the maternal plasma concentration. Because of the potential of serious adverse reactions in nursing mtants from carbamazepine. a decision should be made whether to disconlinue nursing or to discontinue the drug. taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness in children below the age of 6 years have not been estabtished.
OVERDOSE :
Acute Toxicity
Lowest known lethal dose: adults. >60 g (39 year-old man). Highest
known doses survived; adults. 30 g (31 year-old woman): children. 10 g
(ELyeac..-old boy): small children5 g (3 year- old girl)
Oral L050 in animals (mg/kg): mice. 1100-3750: rats. 3850-4025; rabbits.
1500-2680; guinea pigs. 920.
CONTRAINDICATIONS :
Carbamazepine should not be used in patients with a history of previous bone marrow depression. hypersensitivity to the drug. or known sensitivity to any of the tricyclic compounds such as amitriptyline. desipramine. imipramine. protriptyiine. nortriptyline. etc. Likewise. on theoretical grounds its use with monoamine oxidase inhibitors is not recommended. Before administration of carbamazepine. MAO inhibitors should be discontinued for a minimum of fourteen days. or longer if the clinical situation penmits.
HOW SUPPLIED :
Box contains 2 strips. each strip contains 10 tablets.
Box contains 5 strips. each strip contains 10 tablets.
Storage :
Do not store above 30·C.
Produced by:
UNIVERSAL INDUSTRIAL PHARMACEUTICAL CO.
AI Obour City. Cairo. Egypt
