primidone – kdc

CLINICAL USE

Anti-epileptic agent Also used for essential tremor

DOSE IN NORMAL RENAL FUNCTION

Epilepsy: 500 mg–1.5 g daily in 2 divided dosesEssential tremor: 62.5–750 mg daily

PHARMACOKINETICS

Molecular weight :218.3

%Protein binding :20

%Excreted unchanged in urine : 40

Volume of distribution (L/kg) :0.4–1

half-life – normal/ESRD (hrs) :10–15/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, but avoid very large doses

<10 : Reduce dose by 25–50% initially, and avoid very large single doses

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Unknown dialysability. Dose as in GFR <10 mL/min

HD :Dialysed. Dose as in GFR

<10 : mL/min

HDF/high flux :Dialysed. Dose as in GFR

<10 : mL/min

CAV/VVHD :Dialysed. Dose as in GFR=10–20 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Antibacterials: reduced concentrations of chloramphenicol, doxycycline, metronidazole and telithromycin

Anticoagulants: increased metabolism of coumarins (reduced effect)

Antidepressants: antagonise anticonvulsant effect; reduces concentration of paroxetine, mianserin and tricyclics; St John’s wort reduces active primidone metabolite concentration – avoid concomitant use

Anti-epileptics: reduces concentration of carbamazepine; carbamazepine reduces primidone concentration but increases metabolite concentration; possibly reduces concentration of ethosuximide; reduces concentration of lamotrigine and tiagabine; primidone concentration possibly reduced by phenytoin, but active metabolite increased and concentration of phenytoin may be altered; primidone concentration possibly increased by valproate, valproate concentration reduced; concentration of primidone possibly reduced by vigabatrin

Antifungals: possibly reduces concentration of posaconazole and voriconazole – avoid concomitant use; reduces absorption of griseofulvin (reduced effect)

Antimalarials: possibly increased risk of convulsions with chloroquine and hydroxychloroquine; anticonvulsant effect antagonised by mefloquine

Antipsychotics: anticonvulsant effect antagonised; metabolism of haloperidol accelerated; possibly reduces aripiprazole concentration – increase aripiprazole dose

Antivirals: concentration of indinavir, lopinavir, nelfinavir and saquinavir possibly reduced

Calcium-channel blockers: effect of felodipine, isradipine and probably other dihydropyridines, diltiazem and verapamil reduced

Ciclosporin: reduces ciclosporin blood levelsCorticosteroids: metabolism of corticosteroids accelerated, reduced effectOestrogens and progestogens: metabolism accelerated, reduced contraceptive effect

ADMINISTRATION

Reconstition

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Route

Oral

Rate of Administration

–

Comments

–.PriMidonE 605

OTHER INFORMATION

Plasma concentrations of 5–12 mcg/L (23– 55 µmol/L) have been loosely correlated with optimum responsePartially converted to phenobarbital and phenylethylmalonamide with long half-lives (metabolites may accumulate in renal impairment)May cause excessive sedation and osteomalacia.

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