From the FDA Drug Label
DOSAGE AND ADMINISTRATION Usual Dosage Patients 8 years of age and older who have received no previous treatment may be started on primidone tablets 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
The recommended titration protocol for primidone is as follows:
- 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 patients already receiving other anticonvulsants, primidone should be started at 100 to 125 mg at bedtime and gradually increased to maintenance level as the other drug is gradually decreased 1. Key points to consider:
- The dosage should be individualized to provide maximum benefit
- 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
From the Research
The recommended titration protocol for primidone typically begins with a low initial dose of 125 mg at bedtime for the first 3 days, followed by 125 mg twice daily for the next 3 days, then 250 mg twice daily thereafter. This gradual titration helps minimize side effects such as sedation, dizziness, and nausea that commonly occur with initial dosing. For adults with epilepsy, the maintenance dose usually ranges from 250-500 mg three times daily, with a maximum daily dose of 2000 mg. Elderly patients or those with hepatic impairment should start at lower doses (50-125 mg daily) with slower titration. Primidone is metabolized to phenobarbital and phenylethylmalonamide (PEMA), which contribute to its anticonvulsant effect, so steady state may not be reached for 2-3 weeks. Blood level monitoring is recommended during titration, with therapeutic levels of primidone ranging from 5-12 μg/mL. Patients should be advised that drowsiness is common during initiation but often improves with continued therapy, and that abrupt discontinuation should be avoided due to risk of withdrawal seizures.
Some key points to consider when titrating primidone include:
- Starting with a low dose and gradually increasing it to minimize side effects 2
- Monitoring blood levels to ensure therapeutic levels are reached 3
- Being aware of the potential for acute toxic side effects, such as nausea, vomiting, giddiness, and sedation, especially in the beginning of treatment 3
- Considering the use of lower doses in elderly patients or those with hepatic impairment 4
- Avoiding abrupt discontinuation of primidone due to the risk of withdrawal seizures 5
It's also important to note that the efficacy of primidone in essential tremor has been shown to be similar to that of propranolol, and that low doses of primidone (250 mg/day) may be equally or more effective than high doses (750 mg/day) in controlling essential tremor, with fewer undesirable effects 4.
Overall, the goal of titrating primidone is to find the lowest effective dose that minimizes side effects and maximizes therapeutic benefit, while also considering the individual patient's needs and medical history.