Schedule H

Oral

Formulation Strengths

Tablets 250 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Generalised Tonic-Clonic Seizures (Adults)

Parameter Recommendation

Starting dose 100–125 mg orally once daily at bedtime for first 3 days

Titration Increase to 100–125 mg twice daily (days 4–6), then three times daily (days 7–10); further increase by 125 mg/day every week until seizure control

Usual maintenance dose 750–1500 mg/day in 2–3 divided doses

Maximum dose 2 g/day (rarely required)

Key notes Initiate slowly to reduce sedation; measure serum phenobarbital levels after 2–3 weeks for dose optimization

1. Focal (Partial) Seizures (Adults)

Parameter Recommendation

Starting dose 100–125 mg orally once daily at bedtime for first 3 days

Titration Increase gradually over 7–10 days as for tonic-clonic seizures

Usual maintenance dose 750–1500 mg/day in 2–3 divided doses

Maximum dose 2 g/day

Key notes May be used as monotherapy or adjunct; co-administration with phenytoin or carbamazepine may require dose adjustments

Secondary Indications – Adults (Off-label, if any)

Indication Dose Duration Notes Evidence Basis

Essential tremor — OFF-LABEL Starting: 50 mg once daily; Titration: Increase gradually to 250 mg twice or three times daily as tolerated Long-term Specialist only; consider when propranolol fails or contraindicated International RCTs; occasionally used in Indian neurology practice

PAEDIATRIC DOSING (Specialist Only)

⚠️ Not recommended below 2 years of age. Use under paediatric neurologist supervision only.

Primary Indications (Approved / Standard in India)

Epilepsy (Tonic-Clonic Seizures, Focal Seizures)

Age-Based Dosing Table:

2–6 years 50 mg once daily at bedtime Increase by 50 mg every 3–5 days 125–250 mg/day in 2 divided doses 20 mg/kg/day

6–12 years 125 mg once daily at bedtime Increase by 125 mg every 3–5 days 250–500 mg/day in 2–3 divided doses 25 mg/kg/day

12 years As per adult dosing As per adult dosing 750–1500 mg/day in 2–3 divided doses 2 g/day

Key Clinical Notes:

• Start low and titrate slowly over 7–10 days to minimize sedation and behavioural effects

• Serum primidone and phenobarbital level monitoring helpful during titration

• Monitor for paradoxical hyperactivity (more common in children)

• Regular assessment of growth, cognition, and behaviour required

Secondary Indications – Paediatrics (Off-label, if any)

Not applicable.

60 No adjustment required

30–60 Use lower end of dosing range; monitor for sedation; check serum drug levels

<30 Use with caution; consider alternative AEDs; if essential, reduce dose by 25–50%

Haemodialysis Primidone is dialyzable; supplemental dose (25–50% of daily dose) may be required post-dialysis

• Known hypersensitivity to primidone, phenobarbital, or other barbiturates

• Porphyria (acute intermittent and variant forms)

• Severe hepatic dysfunction

• Severe respiratory depression

• Pre-existing sedative drug intoxication or overdose

• Concurrent use with alcohol in intoxication state

• Elderly or debilitated patients — increased sensitivity to CNS depression

• History of depression, suicidal ideation, or psychiatric disorders

• Concurrent use with other CNS depressants

• Impaired renal or hepatic function

• Respiratory disease (risk of respiratory depression)

• History of drug or alcohol dependence

• Rapid withdrawal — may precipitate status epilepticus

• May impair cognitive function — caution with driving/machinery

• Chronic use — risk of vitamin D deficiency and osteomalacia

Aspect Recommendation

Overall safety Category D — Known teratogenic risk; associated with major congenital malformations (cardiac defects, cleft lip/palate) and neonatal haemorrhage

Preferred alternatives Carbamazepine, levetiracetam (depending on seizure type); specialist input essential

When it may be used Only if seizure control is critical and no safer alternative available; continue if already established on therapy with good control

Monitoring Fetal anatomy scan (18–20 weeks); maternal folate status; coagulation parameters in third trimester

Supplementation Peri-conceptional folic acid 5 mg/day; vitamin K 10 mg/day in last month of pregnancy

Aspect Recommendation

Compatibility Compatible with breastfeeding with monitoring

Expected levels in milk Moderate (due to active metabolite phenobarbital)

Preferred alternatives Carbamazepine, levetiracetam (if switching feasible)

Recommendation Use lowest effective dose; prefer single-drug regimens

Infant monitoring Sedation, poor feeding, lethargy, inadequate weight gain

Parameter Recommendation

Starting dose 50–125 mg once daily at bedtime

Titration Slow; increase at weekly intervals based on tolerance

Maximum dose Lower end of adult range preferred

Extra risks Excessive sedation, confusion, ataxia, cognitive impairment, increased fall risk, paradoxical agitation

Key notes Consider alternatives with better safety profile (e.g., levetiracetam, lamotrigine) where feasible

Interacting Drug Effect Mechanism Management

Phenytoin Complex bidirectional interaction; altered levels of both drugs Enzyme induction/competition Monitor serum levels of both drugs

Valproate Increased primidone/phenobarbital levels; excessive sedation Inhibits primidone metabolism Reduce primidone dose; monitor closely

CNS depressants (benzodiazepines, opioids, alcohol) Potentiated sedation; risk of respiratory depression Additive CNS depression Avoid combination or use reduced doses with close monitoring

Oral contraceptives Reduced contraceptive efficacy Hepatic enzyme induction Use alternative contraception (barrier methods, IUD)

Anticoagulants (warfarin) Reduced anticoagulant effect CYP enzyme induction Monitor INR closely; adjust warfarin dose

Corticosteroids Reduced steroid efficacy CYP3A4 induction May need increased steroid dose

Interacting Drug Effect Management

Carbamazepine Mutual enzyme induction; altered levels Monitor serum levels of both; adjust doses accordingly

Theophylline Reduced theophylline levels Monitor theophylline levels; may need dose increase

Doxycycline Reduced doxycycline efficacy Consider alternative antibiotic or higher doxycycline dose

Isoniazid May increase primidone levels (weak) Monitor for increased sedation

Rifampicin Reduced primidone efficacy May need primidone dose adjustment

Antipsychotics (chlorpromazine, haloperidol) Additive CNS depression; lowered seizure threshold Monitor sedation; seizure control

Metronidazole Possible reduced metronidazole efficacy Use with caution; monitor response

• Sedation and drowsiness (most common, especially initially)

• Ataxia and unsteadiness

• Dizziness and vertigo

• Nystagmus

• Nausea and gastrointestinal upset

• Headache

• Impaired concentration and cognitive slowing

• Paradoxical hyperactivity (especially in children)

• Fatigue and lethargy

Adverse Effect Notes

Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis Rare; requires immediate drug discontinuation and hospitalization

Agranulocytosis / Aplastic anaemia Rare but life-threatening; discontinue immediately if unexplained fever, sore throat, or bruising

Megaloblastic anaemia With prolonged use (folate depletion); monitor CBC

Hepatotoxicity Monitor LFTs; discontinue if significant elevation

Suicidal ideation and behaviour Monitor psychiatric status especially in first few months

Severe hypersensitivity reactions Discontinue and avoid re-challenge

Osteomalacia With chronic use; monitor vitamin D, calcium

Timing Parameters to Monitor

Baseline CBC with differential, LFTs, renal function, mental status assessment, baseline seizure documentation

During titration (first 2–4 weeks) Sedation level, rash, behavioural changes; serum primidone and phenobarbital levels after 2–3 weeks

Every 3–6 months (chronic use) CBC, LFTs, serum drug levels (if indicated)

Annually Bone mineral density (if prolonged use); vitamin D levels

Paediatric patients Growth parameters, cognitive assessment, behaviour evaluation at each visit

Brand Name Manufacturer

Mysoline Abbott

Primidep Sun Pharma

Various generics Multiple manufacturers

• NLEM Status: Not included in NLEM 2022

• Government supply: Available under some state government epilepsy programs

• Note: Pricing unregulated; may vary significantly by brand

1. Slow initiation essential: Always titrate slowly over 7–10 days to avoid excessive sedation; patients often discontinue prematurely due to early side effects.

1. Active metabolite monitoring: Primidone is converted to phenobarbital (active) — therapeutic drug monitoring of phenobarbital levels (15–40 μg/mL) is more reliable than primidone levels for dose optimization.

1. Not first-line today: Reserve for cases where newer AEDs are unavailable, unaffordable, or ineffective; still useful in resource-limited settings due to low cost.

1. Never stop abruptly: Taper over 2–4 weeks minimum to prevent rebound seizures or status epilepticus.

1. Paradoxical reactions in children: Watch for hyperactivity and behavioural changes — may require drug switch.

1. Drug interactions: Strong CYP inducer — always review concurrent medications, especially oral contraceptives and anticoagulants.

primidone; antiepileptic; barbiturate; tonic-clonic-seizures; focal-seizures; essential-tremor; CNS-depressant; pregnancy-risk; elderly-caution; enzyme-inducer; Schedule-H

RxIndia v1.0 — 11 Jun 2025

• CDSCO product insert

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• API Textbook of Medicine

• ICMR Epilepsy Guidelines

• AIIMS Formulary — Neurology section

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• RCT evidence (for essential tremor off-label indication only)