Schedule H (Phenobarbitone is also a psychotropic substance under NDPS Act; injectable forms may require Schedule X compliance in some states)

Oral, Intravenous, Intramuscular

• Tablets: 15 mg, 30 mg, 60 mg

• Oral solution/Syrup: 20 mg/5 mL

• Injection: 200 mg/mL (1 mL ampoule)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

1. Generalised Tonic-Clonic Seizures and Focal Seizures

Parameter Dose Clinical Notes

Starting dose 60 mg/day orally (1–2 mg/kg/day) Give as single bedtime dose or in 2 divided doses

Titration Increase by 15–30 mg every 2–4 weeks Titrate based on seizure control and sedation level

Usual maintenance dose 60–180 mg/day orally Most adults controlled at 90–120 mg/day

Maximum dose 300 mg/day Higher doses rarely tolerated due to sedation

Clinical Note: Reserve as second-line or third-line agent in resource-limited settings. Long half-life (70–140 hours) allows once-daily dosing at steady state. Therapeutic drug monitoring target: 15–40 μg/mL.

1. Status Epilepticus (Second-line after benzodiazepines; if phenytoin contraindicated or ineffective)

Parameter Dose Clinical Notes

Loading dose 15–20 mg/kg IV Administer at rate ≤50–100 mg/min (≤1 mg/kg/min)

Titration Additional 5–10 mg/kg if seizures persist after 20 min Maximum total loading: 30 mg/kg

Usual maintenance dose 1–3 mg/kg/day IV or orally Begin 12–24 hours after loading

Maximum dose 5 mg/kg/day

Critical Monitoring: Continuous respiratory and cardiovascular monitoring essential. Risk of respiratory depression significantly increased when combined with benzodiazepines. Resuscitation equipment must be available. ICU/HDU setting mandatory.

1. Neonatal Seizures — see Paediatric Section

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

1. Alcohol Withdrawal (Alternative when benzodiazepines unavailable) — OFF-LABEL

Parameter Details

Indication Alcohol withdrawal syndrome in settings where benzodiazepines are not available

Starting dose 30–60 mg orally every 6–8 hours

Titration Symptom-triggered dosing based on withdrawal severity scales

Maximum dose 240 mg/day

Duration 5–7 days with gradual taper

Specialist only Yes — Psychiatry/De-addiction medicine

Evidence basis ICMR-supported protocols for rural de-addiction centres; Indian specialist practice

1. Sedation in Mechanically Ventilated Patients (ICU setting) — OFF-LABEL

Parameter Details

Indication Refractory agitation when standard sedatives inadequate

Dose 1–3 mg/kg/day IV in divided doses or continuous infusion

Duration Short-term only; taper before extubation

Specialist only Yes — Critical Care

Evidence basis Indian ICU practice; limited international data

PAEDIATRIC DOSING (Specialist Only)

Primary Indications:

1. Neonatal Seizures

Parameter Dose Comments

Loading dose 20 mg/kg IV over 15–20 minutes Maximum infusion rate: 1 mg/kg/min

Additional loading 5–10 mg/kg if seizures persist Can repeat twice; maximum cumulative loading: 40 mg/kg

Usual maintenance dose 3–5 mg/kg/day IV or orally in 1–2 divided doses Begin 12–24 hours after loading

Maximum dose 5 mg/kg/day Higher doses rarely needed

Monitoring: Continuous cardiorespiratory monitoring; observe for apnoea, hypotension, and excessive sedation. Therapeutic level: 15–40 μg/mL (if available).

1. Infantile and Childhood Epilepsy (Generalised Tonic-Clonic and Focal Seizures)

1–6 months 3 mg/kg/day in 1–2 doses 3–5 mg/kg/day 6 mg/kg/day

6 months–5 years 3 mg/kg/day in 1–2 doses 3–6 mg/kg/day 8 mg/kg/day

5–12 years 2 mg/kg/day in 1–2 doses 2–4 mg/kg/day 6 mg/kg/day

12 years 1–2 mg/kg/day 1–3 mg/kg/day 180–300 mg/day

Dosing Notes:

• Starting dose: As per age table above

• Titration: Increase by 1 mg/kg/day every 2–4 weeks based on seizure control

• Usual maintenance dose: As per table; once-daily dosing at bedtime preferred once stable

• Maximum dose: As per table; rarely exceeded due to behavioural side effects

Formulation note: Use oral solution (20 mg/5 mL) for accurate dosing in infants and young children.

1. Paediatric Status Epilepticus

Parameter Dose Comments

Loading dose 15–20 mg/kg IV Administer at ≤1 mg/kg/min (max 50 mg/min)

Additional loading 5–10 mg/kg if seizures persist Maximum cumulative: 30 mg/kg

Maintenance Begin 12–24 hours after loading Per age-based maintenance table

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

Febrile Seizure Prophylaxis (Recurrent complex febrile seizures) — OFF-LABEL

Parameter Details

Indication High-risk recurrent febrile seizures (not routine prophylaxis)

Dose 3–5 mg/kg/day orally during febrile episodes

Duration During febrile illness only (intermittent prophylaxis)

Specialist only Yes — Paediatric neurology

Evidence basis Limited evidence; not recommended routinely per IAP; Indian specialist practice in select cases

Note: Continuous prophylaxis with phenobarbitone is no longer recommended for simple febrile seizures due to cognitive adverse effects.

Not recommended below 2 weeks of age except under specialist neonatology supervision in NICU settings.

Severe impairment (eGFR <30) Loading dose unchanged; maintenance may need reduction if excessive sedation

ESRD / Dialysis Not significantly dialyzed; no supplemental dosing required post-dialysis

Peritoneal dialysis No adjustment required

Note: Half-life may be prolonged in severe renal impairment; clinical monitoring for sedation is essential.

• Known hypersensitivity to phenobarbitone or other barbiturates

• Acute intermittent porphyria (may precipitate acute attack)

• Severe respiratory depression or severe respiratory insufficiency

• Severe hepatic impairment or hepatic precoma

• Concurrent use with rilpivirine (significant CYP induction reduces antiviral efficacy — contraindicated)

• Intra-arterial injection (risk of arterial spasm, gangrene)

• Respiratory disease including COPD, asthma, obstructive sleep apnoea (respiratory depression risk)

• Depression, suicidal ideation, or psychiatric disorders (may worsen mood)

• Elderly patients (increased sensitivity, prolonged sedation, fall risk)

• History of substance abuse or dependence (abuse potential)

• Myasthenia gravis (may worsen muscle weakness)

• Hypovolaemia or shock (increased hypotension risk with IV use)

• Chronic pain patients on opioids (additive CNS/respiratory depression)

• Long-term paediatric use (cognitive and behavioural impairment)

• Abrupt discontinuation risk — taper gradually to prevent withdrawal seizures

Aspect Recommendation

Risk category Teratogenic — associated with major congenital malformations (cardiac defects, cleft lip/palate, neural tube defects)

Use in pregnancy Avoid if possible; use only when no safer alternative available and maternal benefit clearly outweighs fetal risk

Preferred alternatives Levetiracetam, lamotrigine (preferred for women of childbearing age in Indian practice)

If continued in pregnancy Use lowest effective monotherapy dose; high-dose folic acid supplementation (4–5 mg/day) preconceptionally and throughout pregnancy

Monitoring Detailed fetal anomaly scan at 18–20 weeks; monitor for neonatal withdrawal syndrome, haemorrhagic disease of newborn (give vitamin K to neonate), neonatal sedation

Aspect Recommendation

Compatibility Generally compatible with breastfeeding with monitoring

Drug levels in milk Low to moderate (milk:plasma ratio ~0.4–0.6)

Preferred alternatives Levetiracetam, carbamazepine if initiating new therapy during lactation

Recommendations Use lowest effective maternal dose; monotherapy preferred

Infant monitoring Sedation, poor feeding, poor weight gain, irritability; rarely methemoglobinaemia

Aspect Recommendation

Starting dose 30 mg/day (or 1 mg/kg/day); lower than standard adult doses

Titration Very slow titration — increase at 3–4 week intervals only if needed

Special risks Prolonged sedation due to reduced hepatic metabolism; increased fall and fracture risk; paradoxical agitation or confusion; respiratory depression

Recommendations Consider alternative agents (levetiracetam) if feasible; avoid in frail elderly unless specifically indicated

Drug Interaction Management

Warfarin CYP induction → significantly reduced anticoagulant effect Avoid combination if possible; if used, monitor INR frequently and increase warfarin dose substantially

Oral contraceptives CYP3A4 induction → reduced contraceptive efficacy → pregnancy risk Use high-dose OCP (≥50 μg ethinylestradiol) or non-hormonal contraception

Rilpivirine Marked CYP induction → subtherapeutic rilpivirine levels Contraindicated

Other HIV protease inhibitors (ritonavir, lopinavir) CYP induction → reduced antiviral efficacy Avoid; alternative AEDs preferred

Opioids (morphine, fentanyl, tramadol) Additive CNS and respiratory depression; CYP induction may reduce opioid efficacy Use with extreme caution; dose adjustment needed; monitoring essential

Benzodiazepines Additive CNS and respiratory depression Use with caution; particularly dangerous in status epilepticus — have airway management ready

Alcohol Severe additive CNS depression Avoid concurrent use

Doxycycline CYP induction → reduced doxycycline efficacy Use alternative antibiotic or double doxycycline dose

Drug Interaction Management

Phenytoin Complex bidirectional interaction — may increase or decrease levels of both drugs Monitor levels of both; clinical observation essential

Valproate Inhibits phenobarbitone metabolism → increased phenobarbitone levels and toxicity Monitor for excessive sedation; may need phenobarbitone dose reduction

Carbamazepine Mutual CYP induction → variable effects on levels Monitor levels and clinical response

Rifampicin CYP induction → may reduce phenobarbitone levels May need phenobarbitone dose increase; monitor seizure control

Isoniazid CYP inhibition → may increase phenobarbitone levels Monitor for toxicity; consider dose reduction

Corticosteroids CYP induction → reduced corticosteroid efficacy May need higher corticosteroid doses

Theophylline CYP induction → reduced theophylline levels Monitor theophylline levels

Metronidazole CYP induction → reduced metronidazole efficacy Consider alternative or higher metronidazole dose

Antidepressants (TCAs, SSRIs) Additive sedation; altered seizure threshold Monitor closely; dose adjustments may be needed

Digoxin CYP induction → reduced digoxin levels Monitor digoxin levels

• Sedation and drowsiness (dose-dependent; often diminishes with continued use)

• Impaired concentration and cognitive slowing

• Ataxia and incoordination

• Depression and mood changes

• Paradoxical hyperactivity and irritability (especially in children)

• Nausea and vomiting

• Hypotension (particularly with IV administration)

• Rash (non-serious maculopapular type)

• Folate deficiency with chronic use

• Vitamin D deficiency and osteomalacia (chronic use)

Adverse Effect Clinical Notes

Respiratory depression Especially with IV loading or combined with other CNS depressants; requires immediate airway management

Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis Discontinue immediately if severe rash develops; hospitalization required

Agranulocytosis / Aplastic anaemia Rare; discontinue and obtain haematology consultation if unexplained fever, sore throat, bruising

Hepatotoxicity Rare; monitor LFTs if symptoms develop

Drug dependence and withdrawal Risk with chronic use; gradual taper essential — abrupt cessation causes severe withdrawal seizures

Paradoxical excitation More common in children and elderly; may require drug discontinuation

Suicidal ideation Class effect with all AEDs; monitor mood

Overdose toxicity Coma, hypotension, respiratory failure, arrhythmias — requires ICU support, possibly haemodialysis

During IV loading Continuous respiratory monitoring (oxygen saturation, respiratory rate), blood pressure every 5 minutes, ECG if cardiac history

After initiation/dose change Serum phenobarbitone levels 2–3 weeks after dose change (long half-life); clinical assessment for sedation, ataxia, cognitive changes

Long-term monitoring Phenobarbitone levels every 6–12 months (target: 15–40 μg/mL); CBC, LFTs every 6–12 months; calcium, vitamin D, bone density annually with chronic use; cognitive assessment in children; dental examination

Note: Therapeutic drug monitoring often unavailable in resource-limited settings — rely on clinical titration by balancing seizure control against sedation level.

• Gardenal (Sanofi) — most recognized brand

• Luminal (Various)

• Phenobarb (Sun Pharma)

• Epibar (Intas)

• Barbit (Various)

• Phenobarbitone Sodium IP (Multiple generic manufacturers)

Note: FDCs with phenobarbitone are not commonly used and generally not recommended.

Government supply: Available free under NPHCE (National Programme for Prevention and Control of Cancer, Diabetes, CVD & Stroke — includes epilepsy) and through government hospital pharmacies.

1. Reserve for resource-limited settings — phenobarbitone causes significant cognitive impairment with chronic use; newer AEDs (levetiracetam, lamotrigine) preferred as first-line when available and affordable.

1. Long half-life advantage — once-daily dosing is effective after steady state (2–3 weeks); improves compliance in rural settings with limited access to medications.

1. Cognitive impact in children — long-term use associated with learning difficulties and behavioural problems; avoid as first-line in paediatric epilepsy unless alternatives are unavailable.

1. Never stop abruptly — taper gradually over weeks to months to prevent severe withdrawal seizures, even in patients without prior seizure history who used it for other indications.

1. Drug interaction vigilance — potent CYP inducer affecting numerous medications; always review concurrent therapy, particularly oral contraceptives, anticoagulants, and HIV drugs.

1. IV loading caution — when used after benzodiazepines for status epilepticus, risk of respiratory depression is significantly increased; ensure airway management capability before administration.

1. Neonatal seizures — remains a first-line agent in Indian NICUs due to availability and experience; newer alternatives (levetiracetam) gaining traction but phenobarbitone remains standard in most centres.

epilepsy; neonatal seizures; barbiturate; antiepileptic; status epilepticus; NLEM India; NDPS; pregnancy-caution; CNS depressant; therapeutic drug monitoring; Schedule H

RxIndia v1.0 — 02 May 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia

• NLEM 2022

• API Textbook of Medicine

• AIIMS Paediatric and Neonatology Protocols

• IAP Guidelines for Childhood Epilepsy

• ICMR Epilepsy Management Standard Operating Procedures

• WHO Model List of Essential Medicines (supportive)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (supportive)