Schedule H

Oral

• Tablets: 100 mg, 300 mg, 400 mg, 600 mg, 800 mg

• Capsules: 100 mg, 300 mg, 400 mg

• Oral solution: 250 mg/5 mL (limited availability)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Epilepsy — Adjunctive Therapy for Partial Seizures (with or without secondary generalisation)

Used as add-on therapy in patients with partial onset seizures not adequately controlled by other antiepileptic drugs. Not recommended as monotherapy.

Rapid Titration Schedule (for inpatients or when quick control needed):

Day Dose

Day 1 300 mg once at bedtime

Day 2 300 mg twice daily

Day 3 onwards 300 mg three times daily

Parameter Recommendation

Starting dose 300 mg once daily at bedtime (Day 1)

Titration Increase as per schedule above; thereafter increase by 300 mg/day every 2–3 days based on response and tolerability

Usual maintenance dose 900–1800 mg/day in 3 divided doses

Maximum dose 3600 mg/day (in 3 divided doses)

Clinical Notes:

• Maximum interval between doses should not exceed 12 hours to prevent breakthrough seizures

• Used only as adjunct to existing AED therapy; not effective as monotherapy

• Therapeutic response may take 2–4 weeks

1. Neuropathic Pain (Peripheral Neuropathy including Diabetic Peripheral Neuropathy)

Parameter Recommendation

Starting dose 300 mg once daily at bedtime

Titration Day 2: 300 mg twice daily; Day 3: 300 mg three times daily; thereafter increase by 300 mg/day every 3–7 days as tolerated

Usual maintenance dose 900–1800 mg/day in 2–3 divided doses

Maximum dose 3600 mg/day (in 3 divided doses)

Clinical Notes:

• Start at bedtime to minimise daytime sedation

• Slower titration recommended in elderly or those sensitive to CNS effects

• Analgesic effect may take 1–2 weeks to manifest

• Reassess after 8 weeks if no response at adequate dose

1. Post-Herpetic Neuralgia (PHN)

Parameter Recommendation

Starting dose 300 mg once daily on Day 1 (at bedtime preferred)

Titration 300 mg twice daily on Day 2; 300 mg three times daily on Day 3; thereafter titrate by 300 mg/day every 3–7 days based on response

Usual maintenance dose 1800–2400 mg/day in 3 divided doses

Maximum dose 3600 mg/day

Clinical Notes:

• Higher doses often required for PHN compared to other neuropathic pain conditions

• Continue for at least 3–6 months after adequate pain control

• Early initiation (within 6 months of acute zoster) may improve outcomes

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Fibromyalgia Starting: 300 mg at bedtime; Titration: increase by 300 mg every 5–7 days; Maintenance: 600–1200 mg/day in divided doses; Maximum: 2400 mg/day Long-term; reassess every 3 months OFF-LABEL — Specialist only. Pregabalin has better evidence for fibromyalgia; gabapentin used when pregabalin not tolerated/available. Based on international RCTs.

Restless Legs Syndrome Starting: 300 mg at bedtime; Maintenance: 300–600 mg at bedtime; Maximum: 1200 mg/day Long-term OFF-LABEL — Specialist only. Alternative when dopamine agonists contraindicated or ineffective. Based on RCT evidence.

Generalised Anxiety Disorder (refractory) Starting: 300 mg/day; Maintenance: 900–1800 mg/day in 3 divided doses; Maximum: 2400 mg/day Short-term (up to 12 weeks); taper to discontinue OFF-LABEL — Specialist only (Psychiatry). Not first-line; use when SSRIs/SNRIs contraindicated. Risk of dependence with long-term use. Limited evidence.

Chronic Pruritus (uraemic, cholestatic) 100–300 mg after each dialysis session (for uraemic pruritus) OR 300 mg at bedtime Variable OFF-LABEL — Specialist only (Nephrology/Dermatology). Based on small RCTs.

Hot Flashes (menopause, oncology) Starting: 300 mg at bedtime; Maintenance: 300 mg three times daily; Maximum: 2400 mg/day Variable OFF-LABEL — Specialist only. Alternative when hormone therapy contraindicated. Based on RCT evidence.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Epilepsy — Adjunctive Therapy for Partial Seizures

Used as add-on therapy in children with partial onset seizures. Paediatric neurologist supervision required.

Age ≥3 to 11 years — Weight-based Dosing:

Parameter Recommendation

Starting dose 10–15 mg/kg/day in 3 divided doses

Titration Increase over 3–7 days to target maintenance range

Usual maintenance dose 25–35 mg/kg/day in 3 divided doses

Maximum dose 50 mg/kg/day OR 3600 mg/day (whichever is lower)

Age ≥12 years — Adult Dosing Protocol:

Parameter Recommendation

Starting dose 300 mg once daily at bedtime

Titration As per adult schedule

Usual maintenance dose 900–1800 mg/day in 3 divided doses

Maximum dose 3600 mg/day

Clinical Notes:

• Interval between doses should not exceed 12 hours

• Monitor for behavioural changes, somnolence, and ataxia

• Not recommended as monotherapy

Minimum Age Statement: Not recommended in children below 3 years of age for epilepsy. Use in children below 3 years only under paediatric neurologist supervision in exceptional circumstances.

Safety Monitoring:

• Behavioural and mood changes (hostility, aggression, hyperactivity)

• Somnolence and cognitive effects

• Weight monitoring

• Seizure diary

Secondary Indications — Paediatrics (Off-label)

Indication Age Dose Notes

Neuropathic Pain (cancer-related, post-traumatic) ≥3 years Starting: 5–10 mg/kg/day in 3 divided doses; Titration: increase over 1–2 weeks; Maintenance: 15–30 mg/kg/day; Maximum: 50 mg/kg/day or 2400 mg/day OFF-LABEL — Paediatric pain specialist/oncologist only. Used in paediatric palliative care and oncology settings.

Chronic Pain Syndromes ≥6 years Starting: 5 mg/kg/day; Maintenance: 15–25 mg/kg/day OFF-LABEL — Specialist only. Very limited paediatric evidence.

Notes:

• Gabapentin is removed by haemodialysis; supplemental post-dialysis dosing required

• In CAPD: very low clearance; use minimal doses

• Reduce doses proportionally in elderly with age-related renal decline

• Known hypersensitivity to gabapentin or any excipient in the formulation

• Previous severe hypersensitivity reaction (anaphylaxis, angioedema, DRESS, SJS/TEN) to gabapentin

• History of psychiatric disorders — may exacerbate depression; risk of suicidal ideation and behaviour (especially in adolescents and young adults)

• History of substance abuse — potential for misuse and dependence (gabapentinoids classified as controlled substances in some countries)

• Elderly patients — increased risk of sedation, dizziness, ataxia, and falls; start with lower doses

• Renal impairment — dose reduction mandatory; accumulation leads to toxicity

• Respiratory disease — risk of respiratory depression, especially when combined with opioids or in elderly

• Myasthenia gravis — may exacerbate weakness (rare reports)

• Diabetes mellitus — weight gain may worsen glycaemic control

• Concurrent CNS depressants — additive sedation

• Abrupt discontinuation — risk of withdrawal symptoms and rebound seizures; always taper gradually

• Driving and operating machinery — warn patients about sedation and cognitive effects

Parameter Recommendation

Safety Category Limited human data; animal studies show some evidence of fetotoxicity; not formally classified in India

Preferred Alternatives For epilepsy: lamotrigine, levetiracetam (better pregnancy safety data); For neuropathic pain: consider non-pharmacological measures or topical agents

When to Use May be continued if essential for seizure control and patient was stable on gabapentin pre-conception; avoid initiation during pregnancy if possible

Monitoring Fetal anomaly scan; fetal growth monitoring; neonatal assessment for withdrawal symptoms

Additional Notes:

• Folic acid supplementation (5 mg/day) recommended pre-conception and during first trimester

• Register patients in pregnancy exposure registries if available

• Neonatal sedation, hypotonia, and poor feeding reported with late pregnancy exposure

Parameter Recommendation

Breastfeeding Compatibility Compatible with caution; gabapentin is excreted in breast milk

Drug Levels in Milk Low to moderate (relative infant dose approximately 1–4%)

Preferred Alternatives For neuropathic pain: consider topical agents, low-dose amitriptyline; For epilepsy: continue gabapentin if essential

Infant Monitoring Monitor for sedation, drowsiness, poor feeding, developmental milestones

Parameter Recommendation

Starting dose 100–300 mg once daily at bedtime (lower than younger adults)

Titration Slower titration; increase by 100–300 mg every 5–7 days

Maximum dose Often limited to 1800–2400 mg/day due to tolerability

Additional Risks Increased sensitivity to sedation, dizziness, ataxia, cognitive impairment; high falls risk; accumulation due to age-related renal decline

Monitoring Assess renal function before dosing; regular falls risk assessment; cognitive monitoring

Interacting Drug Mechanism/Effect Management

Opioids (morphine, oxycodone, hydrocodone) Morphine increases gabapentin AUC; additive CNS depression; increased risk of respiratory depression, sedation, and death Avoid combination if possible; if essential, use lowest effective doses of both; monitor respiratory status closely; FDA warning regarding respiratory depression

Aluminium/magnesium-containing antacids Reduce gabapentin bioavailability by approximately 20% Administer gabapentin at least 2 hours after antacid

CNS depressants (benzodiazepines, alcohol, sedating antihistamines) Additive CNS depression; respiratory depression risk Use with caution; reduce doses; avoid alcohol; warn patients

Interacting Drug Effect Management

Enzyme-inducing AEDs (phenytoin, carbamazepine, phenobarbital) May slightly reduce gabapentin efficacy (mechanism unclear; possibly reduced absorption) Monitor seizure control; may need higher gabapentin doses

Pregabalin Additive gabapentinoid effects; no additional efficacy benefit; increased adverse effects Avoid concurrent use; use one gabapentinoid only

Hydrocodone Decreased hydrocodone levels reported; increased gabapentin levels Monitor for pain control and gabapentin toxicity

Naproxen May increase gabapentin absorption Usually not clinically significant; monitor

Cimetidine Slight decrease in gabapentin renal clearance Usually not clinically significant

Pioglitazone Additive peripheral oedema Monitor for oedema; consider alternatives if severe

• Somnolence, drowsiness (very common)

• Dizziness

• Ataxia, gait disturbance

• Fatigue, asthenia

• Peripheral oedema

• Weight gain

• Tremor

• Nystagmus

• Blurred vision, diplopia

• Dry mouth

• Constipation

• Nausea

• Headache

• Cognitive impairment (memory difficulties, concentration problems)

• Viral infection (reported in clinical trials)

Adverse Effect Clinical Significance

Suicidal ideation and behaviour Increased risk reported with all AEDs; monitor especially during initiation and dose changes; FDA warning applies

Severe hypersensitivity reactions Angioedema (face, lips, tongue, larynx), anaphylaxis; discontinue immediately

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Rare; presents with fever, rash, lymphadenopathy, organ involvement; discontinue immediately; may be fatal

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Very rare; discontinue immediately if mucocutaneous reactions occur

Respiratory depression Risk with concomitant opioids or CNS depressants, especially in elderly; may be fatal

Rhabdomyolysis Rare; associated with severe myopathy; discontinue if unexplained muscle pain with elevated CK

Withdrawal syndrome Anxiety, insomnia, nausea, pain, sweating, seizures (in epilepsy patients); always taper gradually over minimum 1 week

Abuse and dependence Potential for misuse; euphoria reported; exercise caution in patients with substance use history

Baseline:

• Renal function (serum creatinine, eGFR) — essential for dose determination

• Psychiatric history and mental status (suicidality screening)

• Seizure history and current AED regimen (for epilepsy indication)

• Weight

• Falls risk assessment (elderly)

After Initiation/Dose Change:

• Assess for dizziness, sedation, ataxia within first 1–2 weeks

• Mental status and mood assessment

• Seizure control (for epilepsy indication)

• Pain control (for neuropathic pain indication)

• Oedema assessment

Long-term:

• Renal function every 6–12 months (more frequently in elderly or if renal disease)

• Weight monitoring every 3–6 months

• Periodic mental health screening (suicidal ideation)

• Glycaemic control in diabetic patients

• Falls risk reassessment in elderly

• Efficacy review — consider trial tapering if indication resolved

• Review for misuse potential if concerns arise

• Gabantin® (Sun Pharma) — 100 mg, 300 mg, 400 mg capsules/tablets

• Gabapin® (Intas) — 100 mg, 300 mg, 400 mg capsules; 600 mg, 800 mg tablets

• Neurontin® (Pfizer) — 100 mg, 300 mg, 400 mg capsules (limited availability)

• Gabapax® (Torrent) — 100 mg, 300 mg, 400 mg capsules

• Gabata® (Alkem) — 100 mg, 300 mg tablets

• Gabacap® (Cipla) — 100 mg, 300 mg capsules

• Gabantyl® (USV) — 100 mg, 300 mg, 400 mg capsules

Note: Fixed-dose combinations with methylcobalamin (e.g., Gabantin Plus, Gabapin NT) are widely available but should be used judiciously; FDC rationale often not evidence-based.

• Included in NLEM 2022 (for neuropathic pain and epilepsy)

• May be NPPA price-controlled for certain strengths

• Available in government hospital supply for approved indications

• Significant price variation between brands

• Titration strategy: Start at bedtime with low dose (100–300 mg) to minimise daytime sedation and dizziness; slow titration over 1–2 weeks improves tolerability

• Renal dosing critical: Always calculate eGFR before prescribing; toxicity (severe sedation, myoclonus, encephalopathy) occurs with accumulation in renal impairment

• Not effective for acute pain: Gabapentin is indicated only for chronic neuropathic pain conditions; do not use for acute nociceptive pain (musculoskeletal, post-operative)

• Opioid combination warning: FDA has issued warnings about respiratory depression deaths when gabapentinoids combined with opioids; use lowest effective doses if combination unavoidable

• Taper to discontinue: Never stop abruptly; taper over minimum 1 week (preferably 2+ weeks) to avoid withdrawal seizures, anxiety, and insomnia

• Gabapentin vs pregabalin: Pregabalin has linear pharmacokinetics and more predictable dosing; gabapentin has saturable absorption making very high doses less effective; consider pregabalin if gabapentin at 1800 mg/day is insufficient

gabapentin; anticonvulsant; neuropathic pain; epilepsy; GABA analogue; gabapentinoid; post-herpetic neuralgia; diabetic neuropathy; renal-adjustment; NLEM; suicidality-risk; opioid-interaction

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• National List of Essential Medicines (NLEM 2022)

• API Textbook of Medicine

• ICMR Guidelines for Management of Neuropathy

• Indian Epilepsy Association Recommendations

• AIIMS Drug Formulary

• IAP Drug Formulary (paediatric dosing)

• WHO Model List of Essential Medicines (supportive paediatric reference)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• FDA Drug Safety Communications (opioid interaction warning)

• International RCTs (for off-label indications — noted accordingly)