Introduction

Primidone is an anticonvulsant used to treat essential tremor as well as grand mal, psychomotor, and focal epileptic seizures. Primidone was developed by J Yule Bogue and H C Carrington in 1949.

Primidone was granted FDA Approval on 8 March 1954.

Uses

Primidone is an antiepileptic used to treat grand mal, psychomotor, and focal epileptic seizures.

Primidone is commonly indicated for the management of grand mal, psychomotor, and focal epileptic seizures. In addition, it has also been studied and utilized as an effective management of essential tremor.

Associated Conditions

Grand mal Generalized tonic-clonic seizure
Partial-Onset Seizures
Temporal Lobe Epilepsy (TLE)
Tremor
Essential

Pharmacodynamics

Primidone alters sodium and calcium channel transport, reducing the frequency of nerve firing, which may be responsible for its effect on convulsions and essential tremor. Primidone has a wide therapeutic window as doses of 50-1000mg/day were effective. Patients should be counselled regarding the risk of status epilepticus with abrupt cessation of primidone.

Mechanism of Action

Primidone and its metabolites, phenobarbital and phenylethylmalonamide (PEMA), are active anticonvulsants. Primidone does not directly interact with GABA-A receptors or chloride channels but phenobarbital does. Primidone alters transmembrane sodium and calcium channel transport, reducing the frequency of nerve firing, which may be responsible for the primidone’s effect on convulsions and essential tremor.

Absorption

Oral primidone is up to 80% bioavailable with a T_max if 2-4h. A 500mg oral dose of primidone Reaches a C_max of 2.7±0.4µg/mL with a T_max of 0.5-7h. Data regarding the AUC of primidone is not readily available.

Volume of Distribution

The volume of distribution of primidone is 0.5-0.8L/kg.

Protein Binding

Primidone is 10.78-13.70% protein bound in serum.

Route of Elimination

Primidone is 72.9-80.6% recovered in urine.

Half Life

The half life of primidone is 7-22h in adults, 5-11h in children, and 8-80h in newborns.

Clearance

Primidone is cleared at a rate of 30mL/min.

Toxicity

The oral LD₅₀ in rats is 1500mg/kg and in mice is 280mg/kg. The intraperitoneal LD₅₀ in rats was 240mg/kg and in mice was 332mg/kg.

Patients experiencing a primidone overdose may present with CNS depression, coma, respiratory depression, suppressed reflexes, suppressed response to pain, hypotension, and decreased urine output. Overdose should be treated with symptomatic and supportive treatment, including the removal of unabsorbed drug.

Food Interactions

Avoid alcohol.
Avoid St. John's Wort.

Dosage

Patients 8 years of age and older who have received no previous treatment may be started on primidone according to the following regimen using either 50 mg or scored 250 mg primidone tablets:

Days 1 to 3: 100 to 125 mg at bedtime.
Days 4 to 6: 100 to 125 mg. twice a day.
Days 7 to 9: 100 to 125 mg three times a day.
Day 10 to maintenance: 250 mg three times a day.

For most adults and children 8 years of age and over, the usual maintenance dosage is three to four 250 mg primidone tablets in divided doses (250 mg three times a day or four times a day). If required, an increase to five or six 250 mg tablets daily may be made, but daily doses should not exceed 500 mg four times a day.

Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations of primidone may be necessary for optimal dosage adjustment. The clinically effective serum level for primidone is between 5 to 12 mcg/mL.

Generic Name	Primidone
Bangla Name	প্রিমিডোন
Available brands	2

Primidone