Carbamal Carbamazepine Extended Release Tablets

CARBAMAL 200-CR®/400-CR®

Carbamazepine Extended Release Tablets USP 200 mg /400 mg

 

Pharmacological Index

Anticonvulsant, antimanic agent.

 

Compositions

Carbamal-200- CR®/400-CR®

Each extended release uncoated tablet contains:

Carbamazepine USP 200mg /400mg

Excipients Q.S.

 

General Information

Carbamazepine has anticonvulsant properties which have been found useful in the treatment of psychomotor epilepsy and as an adjunct in the treatment of partial epilepsies, when administered in conjunction with other anticonvulsant drugs to prevent the possible generalization of the epileptic discharge. A mild psychotropic effect has been observed in some patients, which seems related to the effect of the carbamazepine in psychomotor or temporal lobe epilepsy.

Carbamazepine relieves or diminishes the pain associated with trigeminal neuralgia often within 24 to 48 hours.

Carbamazepine given as a monotherapy or in combination with lithium or neuroleptics has been found useful in the treatment of acute mania and the prophylactic treatment of bipolar (manic- depressive) disorders.

Like other tricyclic compounds, carbamazepine has a moderate anticholinergic action which is responsible for some of its adverse effects. A tolerance may develop to the action of carbamazepine after a few months of treatment and should be watched for.

Carbamazepine may suppress ventricular automaticity due to its membrane-depressant effect similar to that of quinidine and procainamide, associated with suppression of phase 4 depolarization of the heart muscle fibre.

A number of investigators have reported a deterioration of EEG abnormalities with regard to focal alterations and a higher incidence of records with nil beta activity during carbamazepine combined treatment.

 

Pharmaco-kinetics

The absorption of carbamazepine in man is relatively slow. When taken in a single oral dose, the carbamazepine tablets yield peak plasma concentrations of unchanged carbamazepine within 4 to 24 hours. With respect to the quantity of carbamazepine absorbed, there is no clinically relevant difference between the various dosage forms.

When the carbamazepine controlled- release tablets are administered repeatedly, they yields lower average maximal concentration of carbamazepine in the plasma, without a reduction in the average minimal concentration. This tends to result in a lower incidence of intermittent concentration-dependent adverse drug reactions. It also ensures that the plasma concentrations remain largely stable throughout the day, thereby making it possible to manage with a twice-daily dosage.

Carbamazepine is bound to serum proteins to the extent of 70 to 80%. The concentration of unchanged substance in the saliva reflects the non-protein-bound portion present in the serum (20 to 30%).

The elimination half-life of unchanged carbamazepine in the plasma averages approximately 36 hours following a single oral dose, whereas after repeated administration, which leads to autoinduction of hepatic enzymes, it averages only 16 to 24 hours, depending on the duration of the medication. In patients receiving concomitant treatment with other enzyme-inducing anti- epileptic agents, half-life values averaging 9 to 10 hours have been found.

Only 2 to 3% of the dose, whether given singly or repeatedly, is excreted in the urine in unchanged form. The primary metabolite is the pharmacologically active 1 0,11-epoxide.

In man, the main urinary metabolite of carbamazepine is the trans-diol derivative originating from the 10,11-epoxide; a small portion of the epoxide is converted into 9-hydroxymethyl-10- carbamoyl-acridan. Other important biotransformation products are various monohydroxylated compounds, as well as the N-glucuronide of carbamazepine.

The therapeutic range for the steady-state plasma concentration of carbamazepine generally lies between 4 and 10 mcg/mL.

 

Indications

Epilepsy, Trigeminal neuralgia Mania and bipolar disorders.

 

Dosage and Administrations

Epilepsy

Adults and children > 12 years initially, 100-200 mg once or twice a day; increased in divided doses until best response obtained. Optimal daily dosage: 800-1200 mg. Rarely, some adults may require 1600 mg/day. As soon as disappearance of seizures has been obtained and maintained, reduce dosage very gradually to minimum effective dose. Children 6-12 years: Initially, 100 mg in divided doses on first day; increased by 100mg/day until best response obtained. Maximum daily dosage: 1000mg.

 

Trigeminal neuralgia

Initially, 100mg twice daily; increased by 200 mg/day until pain is relieved, usually at 200-800 mg/day (occasionally, 1200 mg/day). Reduce or discontinue Tegretol, if possible, at intervals of not more than 3 months.

 

Mania and bipolar disorders

Initially, 200-400 mg/day in divided doses (400-600 mg/day may be used in acute mania); increased gradually until symptoms are controlled or a total daily dose of 1600mg is achieved. Usual dose is 400-1200 mg/day in divided doses.

With lithium, neuroleptics: start with 100-200 mg/day and increase gradually. Daily dose > 800 mg is rarely required.

 

Contraindications

AV block, hepatic disease, a history of bone marrow depression, acute intermittent porphyria or serious blood disorders. Hypersensitivity to carbamazepine or tricyclics. Not to be given with, or within 14 days of starting or stopping MAOI therapy.

 

Precautions

Pregnancy, lactation: Weigh possible risks vs. potential benefits. Elderly patients. Urinary retention, increased intraocular pressure, cardiovascular disorders, activation of behavioral disorders, exacerbation of seizures. Perform periodic ophthalmic examinations, evaluations of renal, hepatic and bone marrow function. Abrupt cessation of carbamal may precipitate seizures. Cross-hypersensitivity with phonytoin and oxcarbazepine.

 

Side effects

Drowsiness, headache, ataxia, vertigo, fatigue, diplopia, dizziness, nausea, vomiting, allergic skin reactions, edema, fluid retention, dry mouth, leucopenia, eosinophilia.

Rarely, serious hematologic, hepatic, cardiovascular and dermatologic reactions (stop therapy).

 

Drug Interactions

Plasma levels of carbamazepine increased by macrolide antibiotics, isoniazid, verapamil, danazol, fluvoxamine, grapefruit juice, azole antifungals, loratadine, ritonavir, diltiazem, fluoxetine, cimetidine. Carbamazepine may lower plasma levels of anticonvulsants, oral contraceptive, oral anticoagulants, digoxin, cyclosporine, levothyroxine, dehydropyridine calcium channel blockers, doxycycline, TCAs, estrogens/progestrogens, corticosteroids, benzodiazepines, haloperidol, protease inhibitors for HIV treatment, olanzapine, risperidone. Plasma levels of carbamazepine may be reduced by phenytoin, Phenobarbital, rifampin, oxcarbazepine, St. John’s Wort, valproic acid, phesuximide. Combined use of carbamazepine with lithium or haloperidol may increase risk of neurotoxic side effects.

 

Warning

Avoid alcoholic beverages. Call physician immediately if seizures worsen. Caution are drowsiness, dizziness (NB driving).

Keep out of reach of children.

 

Shelf Life

Indicated on Box and strip.

 

Storage Conditions

Do not store above 25oC. Store in the original pack.

 

Presentation

Carbamal 200-CR / Carbamal 400-CR.

Blister of 10 tablets, Box of 10 Blister.

PharmacyPlus

 

Manufactured In India by

STALLION LABORATORIES PVT. LTD.

C-1B, 305/2 & 3, G.I.D.C. Kerala (Bavla),

Dist.: Ahmedabad-382 220, Gujarat.

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