primidone

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

–

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.

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

Home