Schedule H

Oral

Formulation Type Available Strengths

Immediate-release tablets 25 mg, 50 mg, 100 mg, 200 mg

Dispersible/Chewable tablets 5 mg, 25 mg, 50 mg, 100 mg

Note: Extended-release (ER/XR) tablets and injectable formulations are NOT AVAILABLE in India.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Epilepsy — Monotherapy (Adults and Adolescents ≥13 years)

For focal seizures, primary generalised tonic-clonic seizures

Parameter Recommendation

Starting dose 25 mg once daily for 2 weeks

Titration Week 3–4: 50 mg once daily; then increase by 50–100 mg every 1–2 weeks

Usual maintenance dose 100–200 mg/day (once daily or in two divided doses)

Maximum dose 500 mg/day

Clinical notes:

• Slow titration is mandatory to minimise risk of serious rash

• Therapeutic effect may take 4–6 weeks to manifest

• Can be taken with or without food

1. Epilepsy — Adjunctive Therapy WITH Valproate (Adults)

Parameter Recommendation

Starting dose 25 mg every alternate day for 2 weeks

Titration Week 3–4: 25 mg once daily; then increase by 25–50 mg every 1–2 weeks

Usual maintenance dose 100–200 mg/day (once daily or in two divided doses)

Maximum dose 200 mg/day

Clinical notes:

• Valproate inhibits lamotrigine glucuronidation — approximately doubles lamotrigine half-life

• Increased risk of serious skin reactions — extra-slow titration mandatory

• Halve all doses compared to monotherapy

1. Epilepsy — Adjunctive Therapy WITHOUT Valproate (Adults)

With enzyme-inducing AEDs (carbamazepine, phenytoin, phenobarbital, primidone)

Parameter Recommendation

Starting dose 50 mg once daily for 2 weeks

Titration Week 3–4: 50 mg twice daily; then increase by 100 mg every 1–2 weeks

Usual maintenance dose 200–400 mg/day in two divided doses

Maximum dose 700 mg/day

Clinical notes:

• Enzyme inducers accelerate lamotrigine clearance — higher doses required

• If both valproate and enzyme inducers are co-administered, follow valproate dosing guidelines

1. Bipolar I Disorder — Maintenance Therapy (Adults)

For prevention of depressive episodes

Parameter Recommendation

Starting dose 25 mg once daily for 2 weeks

Titration Week 3–4: 50 mg once daily; Week 5: 100 mg once daily; Week 6 onwards: target dose

Usual maintenance dose 200 mg/day (once daily or in two divided doses)

Maximum dose 400 mg/day (without valproate); 200 mg/day (with valproate)

Clinical notes:

• NOT effective for acute mania — use adjunctive antimanic agents

• Primarily prevents depressive episodes; modest effect on manic episode prevention

• If co-administered with valproate, use half-doses and slower titration

• Titration schedule must be followed strictly regardless of urgency

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes Evidence

Bipolar depression (acute) Starting: 25 mg/day; Target: 100–200 mg/day Maintenance duration OFF-LABEL; Specialist only; onset delayed due to slow titration Meta-analyses; Indian specialist psychiatry practice

Neuropathic pain (refractory) Starting: 25 mg/day; Target: 200–400 mg/day Trial 8–12 weeks OFF-LABEL; Specialist only Limited RCT evidence; used in refractory cases

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Epilepsy — Adjunctive Therapy in Children ≥2 years

Dosing depends critically on concomitant antiepileptic drugs:

A. WITH Valproate (enzyme inhibitor)

Parameter Recommendation

Starting dose 0.15 mg/kg/day once daily for 2 weeks

Titration Week 3–4: 0.3 mg/kg/day; then increase by 0.3 mg/kg every 1–2 weeks

Usual maintenance dose 1–5 mg/kg/day (once daily or in two divided doses)

Maximum dose 200 mg/day

B. WITHOUT Valproate (with or without enzyme inducers)

Parameter Recommendation

Starting dose 0.6 mg/kg/day in two divided doses for 2 weeks

Titration Week 3–4: 1.2 mg/kg/day; then increase by 1.2 mg/kg every 1–2 weeks

Usual maintenance dose 5–15 mg/kg/day in one to two divided doses

Maximum dose 400 mg/day

Safety Monitoring in Paediatrics:

• Monitor closely for any rash during first 8 weeks — higher risk in children

• Counsel caregivers on rash recognition and need for immediate medical attention

• Dispersible tablets allow precise weight-based dosing

• Regular assessment of seizure control and developmental milestones

Secondary Indications — Paediatric (Off-label)

Indication Age Notes Evidence

Lennox-Gastaut syndrome ≥2 years OFF-LABEL for some seizure types; Specialist only Tertiary centre protocols

Bipolar disorder (adolescents) Not recommended below 18 years Use only under child psychiatry specialist Limited data; not standard practice

Important statements:

• Not recommended below 2 years of age except in exceptional circumstances under tertiary paediatric neurology care

• Strict adherence to slow titration schedule is critical in children — higher rash risk

• Dispersible formulations preferred for accurate dosing in younger children

End-stage renal disease / Haemodialysis Significant removal during dialysis (~20%); supplemental dose of approximately 50% of maintenance may be needed post-dialysis

• Known hypersensitivity to lamotrigine or any excipient

• History of lamotrigine-related severe cutaneous reactions (SJS, TEN, DRESS)

• Risk of serious skin reactions (SJS/TEN) — highest in first 8 weeks; increased with rapid titration, paediatric age group, and valproate co-administration

• Concomitant valproate therapy — requires halved doses and slower titration

• Suicidal ideation — class warning for all antiepileptic drugs; monitor mood changes

• May worsen myoclonic seizures in some patients with idiopathic generalised epilepsy

• Renal or hepatic impairment — dose adjustment required

• Aseptic meningitis — rare; consider if meningeal symptoms develop

• Abrupt withdrawal — may precipitate rebound seizures; taper gradually over at least 2 weeks

• Hormonal contraceptive use — affects lamotrigine levels (see interactions)

Parameter Recommendation

Overall safety Among the safer antiepileptics in pregnancy; lower teratogenic risk than valproate or phenytoin

Preferred alternative Levetiracetam (if suitable for seizure type)

When may be used May be continued if seizure control is essential; benefits usually outweigh risks; use lowest effective dose

What to monitor Lamotrigine clearance increases significantly during pregnancy (up to 2-fold) — monitor serum levels if available; dose increase often required; reduce dose postpartum to prevent toxicity

Note: Can be used for bipolar disorder in pregnancy if alternative mood stabilisers are contraindicated; shared decision with psychiatrist and obstetrician.

Parameter Recommendation

Compatibility Compatible with breastfeeding; commonly used in India

Preferred alternative Levetiracetam (if equally effective for seizure type)

Drug levels in milk Moderate (~30–50% of maternal serum concentration)

Infant monitoring Monitor for sedation, poor feeding, rash; check infant if symptoms suggestive of toxicity

Parameter Recommendation

Starting dose 25 mg once daily (or 25 mg alternate days if frail)

Titration Slower titration — every 2–3 weeks

Special risks Increased sensitivity to CNS effects (dizziness, somnolence); falls risk; reduced renal clearance may affect drug levels

Additional considerations Consider lower maintenance doses; monitor for hyponatraemia (rare); assess for polypharmacy interactions

Interacting Drug Effect / Risk Recommendation

Valproate Inhibits lamotrigine glucuronidation — doubles half-life; markedly increases rash risk Halve lamotrigine dose; use extra-slow titration

Carbamazepine, phenytoin, phenobarbital, primidone Enzyme induction — decreases lamotrigine levels by ~40–50% Increase lamotrigine dose; may need 2× standard maintenance

Rifampicin Potent enzyme inducer — reduces lamotrigine efficacy significantly Increase lamotrigine dose; monitor seizure control

Combined oral contraceptives (ethinylestradiol) Decrease lamotrigine levels by ~50% during active pill phase; rebound increase during pill-free week Adjust lamotrigine dose or use non-hormonal contraception; risk of breakthrough seizures or toxicity

Interacting Drug Effect / Risk Recommendation

Oxcarbazepine Mild reduction in lamotrigine levels Monitor seizure control; may need modest dose increase

Phenytoin (dose-dependent) Variable interaction depending on doses Monitor levels if available; clinical assessment

Sertraline May modestly increase lamotrigine levels Generally safe; monitor for adverse effects

Lithium Potential additive neurotoxicity at high doses Monitor for neurological symptoms; usually safe at therapeutic levels

Lopinavir/ritonavir Decreases lamotrigine levels May need dose adjustment; monitor efficacy

• Rash (benign maculopapular — most resolve; but always evaluate carefully)

• Headache

• Dizziness

• Nausea

• Insomnia

• Somnolence

• Diplopia, blurred vision

• Ataxia

• Tremor

• Fatigue

Adverse Effect Notes

Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN) Life-threatening; highest risk in first 8 weeks; discontinue immediately if mucosal involvement, blistering, or systemic symptoms

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Fever, rash, lymphadenopathy, multi-organ involvement — discontinue immediately; may require hospitalisation

Aseptic meningitis Headache, fever, neck stiffness, photophobia — recurs on rechallenge; do not re-expose

Blood dyscrasias Rare (neutropenia, thrombocytopenia) — periodic CBC in long-term use if symptomatic

Suicidal ideation/behaviour Class effect of antiepileptics — observe during early treatment and dose changes

Multi-organ hypersensitivity May involve liver, kidney, cardiac systems; requires urgent care

During titration Close observation for rash at each visit (first 8 weeks critical) — educate patient/caregiver on warning signs; any rash requires evaluation

Long-term Periodic LFTs and RFTs if chronic use or impairment present; seizure control assessment; mood monitoring in bipolar disorder

In pregnancy Serum lamotrigine levels (if available) — each trimester and postpartum; dose adjustment as needed

• Lamitor (Torrent)

• Lametec (Cipla)

• Lamosyn (Intas)

• Lamez (Sun Pharma)

• Lamogin (Alkem)

• Lamidus (Lupin)

• Multiple generic brands available

• Available through government supply under NLEM

Notes:

• Listed under NLEM 2022 — price regulated by NPPA

• Available through government supply at subsidised rates

• Generic formulations significantly cheaper than branded

1. Slow titration is non-negotiable: Rapid dose escalation dramatically increases risk of life-threatening SJS/TEN — never accelerate titration regardless of clinical urgency

1. Valproate interaction is critical: Always halve lamotrigine dose and use extra-slow titration when co-administered with valproate — this is the most common error causing serious rash

1. Rash requires immediate evaluation: Most rashes are benign, but any rash in first 8 weeks warrants clinical assessment — discontinue immediately if systemic symptoms, mucosal involvement, or blistering present

1. Bipolar use is for maintenance, not acute episodes: Lamotrigine is ineffective for acute mania and has delayed onset in depression due to mandatory slow titration — do not use as monotherapy for acute mood episodes

1. Hormonal contraception affects levels: Counsel women that oral contraceptives reduce lamotrigine levels — seizure breakthrough may occur; dose adjustments needed during pill-free intervals

1. Dispersible tablets for paediatrics: Use dispersible formulations for precise weight-based dosing in children; can be chewed, dissolved in water, or swallowed whole

lamotrigine; anticonvulsant; epilepsy; bipolar-disorder; mood-stabiliser; SJS-risk; valproate-interaction; slow-titration; pregnancy-safer; NLEM-India; neurology

RxIndia v1.0 — 18 Apr 2025

• CDSCO-approved prescribing information

• Indian Pharmacopoeia

• National Formulary of India (NFI)

• NLEM 2022

• API Textbook of Medicine

• ICMR Epilepsy Guidelines

• AIIMS Guidelines for Bipolar Disorder

• Indian Psychiatric Society Practice Guidelines

• IAP Guidelines (for paediatric dosing)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Meta-analyses (for off-label bipolar depression indication — annotated as off-label)