dosage adjustment of Carbamazepine in renal failure




Carbamazepine.JPG

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

    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).