Schedule H

Oral

• Capsules: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 300 mg

• Oral solution: 20 mg/mL (limited availability)

• Sustained-release tablets: 75 mg, 150 mg (limited availability)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Peripheral Neuropathic Pain (Diabetic Peripheral Neuropathy, Post herpetic Neuralgia)

Parameter Dose

Starting dose 75 mg orally twice daily (OR 50 mg three times daily)

Titration Increase to 150 mg twice daily after 3–7 days based on response and tolerability; further increase to 300 mg twice daily after 2–4 weeks if needed

Usual maintenance dose 150–300 mg/day in 2–3 divided doses

Maximum dose 600 mg/day (rarely required; increased sedation and fall risk at higher doses)

Clinical Notes:

• In frail or elderly patients, start at 25–50 mg once or twice daily

• Therapeutic effect may take 1–2 weeks to manifest

• Pain relief usually optimal at 150–300 mg/day; doses above this rarely add benefit

• Divide doses evenly (morning and evening) to maintain steady plasma levels

1. Adjunctive Therapy in Focal (Partial) Seizures with or without Secondary Generalization

Parameter Dose

Starting dose 75 mg orally twice daily (150 mg/day)

Titration Increase to 150 mg twice daily after 1 week; further increase to 200–300 mg twice daily based on response

Usual maintenance dose 300–600 mg/day in 2–3 divided doses

Maximum dose 600 mg/day

Clinical Notes:

• Not first-line monotherapy for epilepsy

• Use as adjunct when first-line anticonvulsants (levetiracetam, carbamazepine, valproate) are inadequate

• Benefit in refractory focal epilepsy

• Do not discontinue abruptly — taper over minimum 1 week

Secondary Indications – Adults (Off-label)

Indication Dose Duration Supervision Evidence Basis

Fibromyalgia (OFF-LABEL) Starting: 75 mg twice daily; Titration: increase to 150–225 mg twice daily over 2–4 weeks; Maintenance: 300–450 mg/day; Maximum: 450 mg/day Long-term as needed Rheumatology/Pain Medicine specialist recommended Multiple RCTs (Crofford et al.); used in Indian pain clinics

Generalised Anxiety Disorder (GAD) (OFF-LABEL) Starting: 75 mg twice daily; Titration: increase to 150–300 mg/day over 1–2 weeks; Maximum: 600 mg/day Short to medium term (≤12 weeks recommended); reassess need Specialist only (Psychiatrist) Meta-analyses; Indian psychiatric practice consensus; not first-line

Central Neuropathic Pain (Spinal Cord Injury, Post-stroke) (OFF-LABEL) Starting: 75 mg twice daily; Titration: as per peripheral neuropathic pain; Maintenance: 150–600 mg/day Long-term Specialist only (Neurologist/Pain specialist) RCTs in spinal cord injury; Indian rehabilitation centre protocols

Restless Legs Syndrome (OFF-LABEL) Starting: 75 mg once daily at bedtime; Titration: increase to 150–300 mg at bedtime; Maximum: 300 mg/day Long-term as needed Specialist only International RCTs; limited Indian data

PAEDIATRIC DOSING (Specialist Only)

⚠️ Not routinely approved for paediatric use in India. Use only under specialist paediatric neurology supervision.

Primary Indications

Not applicable — no approved paediatric indications in India.

Secondary Indications – Paediatrics (Off-label)

Indication Age Dose Duration Supervision Evidence Basis

Adjunctive Therapy in Focal Seizures (OFF-LABEL) ≥12 years Starting: 2.5 mg/kg/day in 2–3 divided doses; Titration: increase every 7 days based on response; Maintenance: 5–10 mg/kg/day; Maximum: 600 mg/day or 10 mg/kg/day (whichever is lower) Long-term as needed Specialist only (Paediatric Neurologist) Limited paediatric RCTs; extrapolated from adult data

Safety Monitoring:

• CNS effects (sedation, dizziness, ataxia)

• Behavioural changes, mood disturbance

• Suicidal ideation (particularly in first few weeks)

• Weight gain

• Vision changes

Age Restriction:

• Not recommended below 12 years of age except under exceptional circumstances with paediatric neurology supervision

• Use in neuropathic pain or anxiety in children is NOT SUPPORTED by Indian guidelines

Creatinine Clearance (CrCl) Starting Dose Maximum Daily Dose Dosing Frequency

≥60 mL/min 75 mg twice daily 600 mg/day 2–3 divided doses

30–59 mL/min 25–50 mg twice daily 300 mg/day 2–3 divided doses

15–29 mL/min 25–50 mg once daily 150 mg/day 1–2 divided doses

<15 mL/min 25 mg once daily 75 mg/day Once daily

Haemodialysis 25 mg once daily (base dose) 75 mg/day (base) Once daily + supplemental dose

Haemodialysis Supplementation:

• Pregabalin is effectively removed by haemodialysis

• Give supplemental dose of 25–75 mg immediately after each 4-hour dialysis session

• Supplement based on base daily dose (approximately 50% of daily dose post-dialysis)

• Known hypersensitivity to pregabalin or any excipients

• History of angioedema to pregabalin or gabapentin

• Lactose intolerance (some capsule formulations contain lactose — use oral solution if essential)

• Elderly patients (increased risk of sedation, dizziness, falls, cognitive impairment)

• History of substance use disorder or drug dependence (potential for misuse and dependence)

• Congestive heart failure (NYHA Class III–IV) — risk of peripheral oedema and weight gain; may exacerbate symptoms

• Renal impairment (mandatory dose reduction)

• Concurrent use of CNS depressants (opioids, benzodiazepines, alcohol) — additive sedation

• History of depression or suicidal ideation

• Patients requiring driving or operating heavy machinery

• Diabetic patients (weight gain may worsen glycaemic control)

• Avoid abrupt discontinuation — taper over minimum 1 week to prevent withdrawal symptoms

Parameter Information

Overall Safety Limited human data; animal studies show teratogenic effects; avoid unless clearly necessary

Risk Possible increased risk of major birth defects (based on registry data); neonatal withdrawal possible

Preferred Alternatives Gabapentin (more human pregnancy data available); for epilepsy — lamotrigine or levetiracetam preferred

When Use May Be Justified Only when no safer alternative and benefit clearly outweighs risk; requires joint neurology/obstetric decision

Monitoring Fetal anomaly scan; fetal growth monitoring; neonatal observation for withdrawal if used near term

Parameter Information

Compatibility Generally compatible at standard doses; appears in breast milk in low concentrations

Expected Drug Level in Milk Low (milk:plasma ratio approximately 0.5–0.8)

Risk to Infant Sedation, poor feeding, irritability possible but rare at therapeutic maternal doses

Preferred Alternatives Gabapentin may be preferred (more breastfeeding safety data available)

Infant Monitoring Sedation, feeding difficulties, weight gain, developmental milestones

Precautions Avoid high doses; avoid concurrent CNS depressants during breastfeeding

Parameter Recommendation

Starting dose 25–50 mg once or twice daily

Titration Increase slowly every 7–10 days (slower than general adults)

Maximum recommended 300 mg/day (lower than general adult maximum due to increased CNS sensitivity)

Increased Risks Sedation, dizziness, falls, fractures, cognitive impairment, confusion

Additional Precautions Assess renal function before dosing (age-related decline in CrCl); monitor gait and balance; counsel on fall prevention

Interacting Drug Mechanism Effect Management

Opioids (morphine, tramadol, fentanyl, oxycodone) Additive CNS depression Profound sedation, respiratory depression, increased overdose risk, death Avoid combination if possible; if essential, reduce doses of both drugs and monitor closely

Benzodiazepines (diazepam, clonazepam, lorazepam) Additive CNS depression Enhanced sedation, respiratory depression Use lowest effective doses; monitor closely; counsel patient

Alcohol Additive CNS depression Severe sedation, psychomotor impairment Avoid concurrent use; patient counselling mandatory

Thiazolidinediones (pioglitazone, rosiglitazone) Both cause fluid retention Increased peripheral oedema, weight gain; potential worsening of heart failure Avoid combination in patients with heart failure; monitor for oedema

Interacting Drug Effect Management

Other anticonvulsants (phenytoin, carbamazepine, valproate) Additive CNS effects; no significant pharmacokinetic interaction Monitor for increased sedation; no dose adjustment usually required

Antihypertensives Additive dizziness, hypotension Monitor blood pressure; counsel on postural changes

Diuretics (loop, thiazide) Additive dizziness; potential fluid/electrolyte imbalance Monitor particularly in elderly

ACE inhibitors Rare reports of increased angioedema risk Monitor for facial/airway swelling; discontinue if angioedema occurs

Antidiabetic agents (insulin, sulfonylureas) Weight gain from pregabalin may worsen glycaemic control Monitor blood glucose; adjust antidiabetic doses as needed

First-generation antihistamines (chlorpheniramine, diphenhydramine) Additive sedation Use with caution; consider non-sedating alternatives

• Dizziness (most common; dose-related)

• Somnolence, sedation

• Peripheral oedema

• Weight gain

• Dry mouth

• Blurred vision

• Fatigue, asthenia

• Ataxia, incoordination

• Headache

• Constipation

• Euphoria (may contribute to misuse potential)

• Difficulty with concentration and attention

Adverse Effect Clinical Action

Angioedema (face, tongue, larynx) Discontinue immediately; emergency management if airway compromise; do not rechallenge

Suicidal ideation and behaviour Close monitoring especially in first few weeks; psychiatric evaluation; consider discontinuation

Severe hypersensitivity reactions (anaphylaxis, skin reactions) Discontinue permanently; supportive care

Rhabdomyolysis (rare; usually with concurrent statin or after excessive physical exertion) Discontinue; check CK levels; supportive care

Respiratory depression (particularly with opioids) Reduce doses; supportive care; may require reversal agents

Heart failure exacerbation (in predisposed patients) Discontinue; manage heart failure

Withdrawal syndrome (on abrupt cessation: insomnia, nausea, headache, diarrhoea, anxiety, sweating, rarely seizures) Taper gradually over minimum 1 week; reinstitute and taper if severe withdrawal

Long-term (every 3–6 months) Weight, peripheral oedema, signs of misuse or dependence, renal function (in elderly/CKD patients), mood and behaviour, glycaemic control (in diabetics)

On discontinuation Taper over minimum 1 week; monitor for withdrawal symptoms

• Lyrica™ (Pfizer) — 25 mg, 50 mg, 75 mg, 150 mg, 300 mg

• Pregabid™ (Torrent) — 75 mg, 150 mg

• Nervijen-P™ (Jenburkt) — 75 mg, 150 mg

• Maxgalin™ (Sun Pharma) — 50 mg, 75 mg, 150 mg, 300 mg

• Pregeb™ (Glenmark) — 75 mg, 150 mg

• Pregalin™ (Alkem) — 75 mg, 150 mg

• Pregastar™ (Lupin) — 75 mg, 150 mg

Fixed-Dose Combinations (FDCs):

• Note: FDCs should be used with caution; assess need for each component individually

Regulatory: Not listed under NLEM 2022; not under NPPA price control; prices vary significantly by brand

1. Start low in special populations — Begin at 25–50 mg/day in elderly, renal impairment, or frail patients; rapid titration increases adverse effects without improving efficacy

1. Therapeutic plateau at moderate doses — Most patients achieve optimal pain relief at 150–300 mg/day; doses above 300 mg rarely add benefit but significantly increase sedation, dizziness, and fall risk

1. Never stop abruptly — Taper over minimum 1 week to avoid withdrawal symptoms (insomnia, nausea, anxiety, and rarely seizures); longer taper (2–4 weeks) if used for extended periods

1. Misuse potential — Euphoria is a recognised effect; exercise caution in patients with substance use history; regular reassessment for signs of dependence recommended

1. Renal dosing is critical — Unlike gabapentin, pregabalin has more predictable pharmacokinetics, but renal excretion means dose must be adjusted based on CrCl; use CrCl-based table for dosing

1. CHF patients at risk — Pregabalin causes fluid retention and weight gain; avoid or use with extreme caution in NYHA Class III–IV heart failure; monitor for worsening symptoms

neuropathic-pain; diabetic-neuropathy; postherpetic-neuralgia; epilepsy-adjunct; fibromyalgia-off-label; GAD-off-label; alpha-2-delta-ligand; renal-adjustment-required; elderly-caution; dependence-risk; Schedule-H

RxIndia v1.1 — 09 Apr 2025

• CDSCO Product Information

• Indian Pharmacopoeia (IP)

• API Textbook of Medicine

• AIIMS Formulary / Treatment Protocols

• ICMR Guidelines for Epilepsy Management

• Indian Association for Study of Pain — Neuropathic Pain Guidelines

• Indian Psychiatric Society Consensus Statements (GAD off-label use reference)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• Cochrane Reviews and Meta-analyses on Pregabalin in Fibromyalgia and GAD (off-label evidence only)