Carbamazepine

CLINICAL USE

All forms of epilepsy except absence seizures

Trigeminal neuralgia

Prophylaxis in manic depressive illness

DOSE IN NORMAL RENAL FUNCTION

Epilepsy: initially 100–200 mg 1–2 times daily, increased to maintenance of 0.4–1.2 g daily in divided doses; maximum 1.6–2 g daily

Rectal: maximum 1 g daily in 4 divided doses for up to 7 days use

Trigeminal neuralgia: initially 100 mg 1–2 times daily; usual dose 200 mg 3–4 times daily; maximum 1.6 g/day; reduce dose gradually as pain goes into remission

Prophylaxis in manic-depressive illness: 400–600 mg daily in divided doses, maximum 1.6 g/day

PHARMACOKINETICS

Molecular weight :236.3

%Protein binding :70–80

%Excreted unchanged in urine : 2

Volume of distribution (L/kg) :0.8–1.9

half-life – normal/ESRD (hrs) :5–26/Unchanged

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 20 : Dose as in normal renal function

<10 : Dose as in normal renal function

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Not dialysed. Dose as in normal renal function

HD :Not dialysed. Dose as in normal renal function

HDF/high flux :Unknown dialysability. Dose as in normal renal function

CAV/VVHD :Not dialysed. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Analgesics: effect enhanced by dextropropoxyphene; decreased effect of tramadol and methadone

Antibacterials: reduced effect of doxycycline; concentration increased by clarithromycin, erythromycin and isoniazid; increased risk of isoniazid hepatotoxicity; concentration reduced by rifabutin; concentration of telithromycin reduced – avoid concomitant use

Anticoagulants: metabolism of coumarins accelerated (reduced anticoagulant effect)

Antidepressants: antagonism of anticonvulsant effect; concentration increased by fluoxetine and fluvoxamine; concentration of mianserin, mirtazepine, paroxetine and tricyclics reduced; avoid concomitant use with MAOIs; concentration reduced by St John’s wort – avoid concomitant use

Antifungals: concentration possibly increased by fluconazole, ketoconazole and miconazole; concentration of itraconazole, caspofungin, posaconazole and voriconazole possibly reduced, avoid with voriconazole, consider increasing caspofungin dose

Antimalarials: chloroquine, hydroxychloroquine and mefloquine antagonise anticonvulsant effect

Antipsychotics: antagonism of anticonvulsant effect; reduced concentration of aripiprazole (increase aripiprazole dose), haloperidol, clozapine, olanzapine, quetiapine, risperidone and sertindole; avoid concomitant use with other drugs that can cause agranulocytosis

Antivirals: reduced concentration of amprenavir, darunavir, indinavir, lopinavir, nelfinavir and saquinavir; concentration possibly increased by ritonavir; concentration of both drugs reduced in combination with efavirenz

Calcium-channel blockers: effects enhanced by diltiazem and verapamil; reduced effect of felodipine, isradipine and probably dihydropyridines, nicardipine and nifedipine

Ciclosporin: metabolism accelerated (reduced ciclosporin concentration)

Corticosteroids: reduced effect of corticosteroids

Diuretics: increased risk of hyponatraemia; concentration increased by acetazolamide; reduced eplerenone concentration – avoid concomitant use

Hormone antagonists: metabolism inhibited by danazol; accelerated metabolism of gestrinone and possibly toremifene

Oestrogens and progestogens: reduced contraceptive effect

Ulcer-healing drugs: concentration increased by cimetidine

ADMINISTRATION

Reconstition

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Route

Oral, rectal

Rate of Administration

–

Comments

When switching a patient from tablets to liquid the same total dose may be used, but given in smaller more frequent doses125 mg suppository is equivalent to 100 mg of tablets

OTHER INFORMATION

Important to initiate carbamazepine therapy at a low dose and build this up over 1–2 weeks, as it autoinduces its metabolism

May cause inappropriate antidiuretic hormone secretion

Therapeutic plasma concentration range: 4–12 micrograms/mL (

20 to 50

micromol/L at steady state).

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