Schedule H

Oral

• Tablet: 200 mg

• Oral Suspension: 50 mg/5 mL

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. HIV-1 Infection (As Part of Combination Antiretroviral Therapy)

Lead-in Phase (Essential to Reduce Hepatotoxicity and Rash Risk):

Parameter Details

Starting dose 200 mg orally once daily

Titration After 14 days of once-daily dosing without rash or hepatotoxicity, escalate to maintenance dose

Usual maintenance dose 200 mg orally twice daily

Maximum dose 400 mg/day

CD4 Count Thresholds for Initiation (Critical for Safety):

Population CD4 Threshold Recommendation

Women (treatment-naïve) ≤250 cells/mm³ Safe to initiate nevirapine

Women (treatment-naïve) >250 cells/mm³ Avoid nevirapine — use efavirenz or dolutegravir

Men (treatment-naïve) ≤400 cells/mm³ Safe to initiate nevirapine

Men (treatment-naïve) >400 cells/mm³ Avoid nevirapine — use efavirenz or dolutegravir

Patients already on suppressive ART Any CD4 count May continue nevirapine if virologically suppressed

Clinical Notes:

• Must always be used in combination with at least two other active antiretrovirals (typically 2 NRTIs)

• Lead-in phase is mandatory — do not skip or shorten

• If therapy is interrupted for >7 days, restart with lead-in dosing (200 mg once daily for 14 days)

• Monitor LFTs intensively during first 18 weeks

• Part of NACO first-line regimens in specific populations

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

Not applicable.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. HIV-1 Infection (As Part of Combination ART)

Weight-Based and Age-Dependent Dosing:

Age/Weight Group Lead-in Phase (Once Daily × 14 days) Maintenance Dose (Twice Daily) Maximum Daily Dose

15 days to <6 months (≥3 kg) 6 mg/kg once daily 6 mg/kg twice daily Based on weight

6 months to 8 years 4 mg/kg once daily 7 mg/kg twice daily 400 mg/day

8 years 4 mg/kg once daily 4 mg/kg twice daily 400 mg/day

Alternative Fixed-Dose by Weight Band (NACO Paediatric Guidelines):

Weight Band Lead-in Dose (OD × 14 days) Maintenance Dose (BD)

3–5.9 kg 50 mg once daily 50 mg twice daily

6–9.9 kg 75 mg once daily 75 mg twice daily

10–13.9 kg 100 mg once daily 100 mg twice daily

14–19.9 kg 150 mg once daily 150 mg twice daily

20–24.9 kg 150 mg once daily 150 mg twice daily

≥25 kg 200 mg once daily 200 mg twice daily

Clinical Notes:

• Oral suspension (50 mg/5 mL) preferred for infants and young children

• Lead-in phase is mandatory in all age groups

• Always use as part of combination ART regimen under NACO/IAP/ICMR guidance

• Shake suspension well before administration

Secondary Indications — Paediatric Doses (Off-label, if any)

Not applicable.

Safety Monitoring in Children:

• Baseline and periodic LFTs (every 2 weeks for first 2 months, then monthly until 18 weeks)

• Monitor for rash (especially during first 18 weeks)

• CD4 count and viral load as per NACO paediatric ART monitoring schedule

• Weight and developmental milestones at each visit

⚠️ Not recommended in neonates <15 days of age for treatment purposes.

Note: Single-dose nevirapine for Prevention of Mother-to-Child Transmission (PMTCT) is a separate indication under NACO guidelines — refer to PMTCT protocols for dosing in neonates <15 days.

• No dose adjustment required in renal impairment

• Nevirapine is extensively metabolised hepatically; renal excretion of unchanged drug is minimal (<3%)

• Use with caution in patients with CrCl <20 mL/min if using concomitant nephrotoxic agents

• Haemodialysis: Supplemental dose of 200 mg recommended after each dialysis session (nevirapine is partially dialysable)

• Peritoneal dialysis: No specific data; use standard dosing with clinical monitoring

Note: Permanently discontinue nevirapine if clinical hepatitis or transaminase elevations with systemic symptoms occur.

• Known hypersensitivity to nevirapine or any component of the formulation

• Previous severe rash (including Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis) attributed to nevirapine

• Previous nevirapine-associated hepatotoxicity requiring discontinuation

• Moderate to severe hepatic impairment (Child-Pugh B or C)

• Treatment-naïve women with CD4 count >250 cells/mm³ (high hepatotoxicity risk)

• Treatment-naïve men with CD4 count >400 cells/mm³ (high hepatotoxicity risk)

• Concurrent use with St. John's Wort (Hypericum perforatum) — significant reduction in nevirapine levels

• Post-exposure prophylaxis (PEP) — nevirapine is not recommended due to hepatotoxicity risk in HIV-negative individuals

• First 18 weeks of therapy — highest risk period for hepatotoxicity and severe rash; intensive monitoring required

• Hepatitis B or C co-infection — increased risk of hepatotoxicity; closer LFT monitoring essential

• History of any hepatic disease — baseline LFTs mandatory; monitor more frequently

• Elevated baseline transaminases (>2.5× ULN) — initiate with extreme caution

• Women (especially with higher CD4 counts) — higher risk of symptomatic hepatic events than men

• Interruption of therapy >7 days — must restart with lead-in phase

• Concurrent use of other hepatotoxic drugs — additive hepatotoxicity risk

• Immune reconstitution inflammatory syndrome (IRIS) — may occur early after ART initiation

• Pregnancy — increased risk of hepatotoxicity; monitor LFTs frequently

Parameter Details

Risk category May be used during pregnancy; extensive safety data available from NACO PMTCT programmes

Preferred alternatives Efavirenz (after first trimester) or dolutegravir-based regimens are now preferred in Indian obstetric practice as per updated NACO guidelines

When it may be used Women already on stable, virologically suppressive nevirapine-based ART may continue; not recommended for initiation in pregnancy unless alternatives unavailable

Special considerations Increased risk of hepatotoxicity in pregnancy, especially in women with higher CD4 counts; do not initiate in treatment-naïve pregnant women with CD4 >250 cells/mm³

Monitoring LFTs every 2 weeks during first 18 weeks, then monthly; viral load and CD4 count as per schedule; fetal growth surveillance

Parameter Details

Compatible with breastfeeding Yes — compatible under NACO-approved ART protocols

Drug levels in milk Moderate; nevirapine is present in breast milk but concentrations are insufficient to treat infant HIV

Preferred alternatives Dolutegravir-based regimens are now preferred for breastfeeding mothers under updated NACO guidelines

Infant monitoring Monitor for rash, jaundice (hepatotoxicity), irritability, and feeding difficulties

Breastfeeding recommendation Exclusive breastfeeding encouraged as per Indian ART protocols unless replacement feeding is acceptable, feasible, affordable, sustainable, and safe (AFASS criteria)

Parameter Recommendation

Starting dose Standard adult dosing (200 mg once daily lead-in, then 200 mg twice daily maintenance)

Titration Lead-in phase mandatory; no faster escalation

Extra risks Increased risk of hepatotoxicity due to decreased hepatic reserve; higher likelihood of polypharmacy and drug interactions

Monitoring More frequent LFTs (every 1–2 weeks during first 18 weeks); assess for drug interactions with other medications

Interacting Drug Effect Mechanism Recommendation

Rifampicin Reduces nevirapine plasma concentrations by 20–58% CYP3A4 induction by rifampicin Avoid combination; use efavirenz-based ART for TB-HIV co-treatment as per NACO guidelines

Rifabutin Mutual interaction; variable effect on levels CYP3A4 effects Use with caution; consider efavirenz as alternative

Atazanavir (unboosted) Marked reduction in atazanavir levels Nevirapine induces CYP3A4 Avoid combination

Lopinavir/ritonavir Reduced lopinavir levels CYP3A4 induction May require increased lopinavir/ritonavir dose; avoid if possible

Ketoconazole Reduced ketoconazole levels; increased nevirapine levels Bidirectional CYP3A4 interaction Avoid combination — increased hepatotoxicity risk

St. John's Wort Marked reduction in nevirapine levels Strong CYP3A4 induction Contraindicated

Hormonal contraceptives (oestrogen/progestogen) Reduced contraceptive efficacy CYP3A4 induction Use additional or alternative contraception (barrier methods, copper IUD)

Delavirdine Mutual reduction in drug levels CYP3A4 effects Avoid combination — no clinical benefit

Interacting Drug Effect Recommendation

Fluconazole Increased nevirapine levels by ~100% Monitor for hepatotoxicity; consider dose reduction of nevirapine if prolonged fluconazole use

Itraconazole / Voriconazole Reduced azole antifungal levels Monitor antifungal efficacy; consider alternative antifungals

Clarithromycin Reduced clarithromycin levels; increased 14-OH metabolite Use azithromycin as alternative for MAC prophylaxis

Metronidazole Potential additive hepatotoxicity Monitor LFTs closely

Phenytoin / Carbamazepine / Phenobarbital May reduce nevirapine levels; variable effect on anticonvulsant levels Monitor viral load and anticonvulsant levels; dose adjustment may be needed

Methadone Reduced methadone levels Monitor for opioid withdrawal symptoms; may need methadone dose increase

Co-trimoxazole May increase risk of rash, especially early in treatment Clinical monitoring; do not discontinue co-trimoxazole prophylaxis

Warfarin Variable effect on warfarin metabolism Monitor INR closely; dose adjustment may be needed

Dexamethasone (chronic use) May reduce nevirapine levels Use with caution; monitor viral load

• Rash (maculopapular, typically in first 6 weeks; occurs in up to 15% of patients)

• Nausea and vomiting

• Headache

• Fatigue

• Diarrhoea

• Abdominal discomfort

• Elevated liver enzymes (transient, asymptomatic)

• Fever

Adverse Effect Clinical Significance

Severe hepatotoxicity Symptomatic hepatitis; may progress to fulminant hepatic failure; highest risk in first 18 weeks, women with CD4 >250, men with CD4 >400; requires immediate discontinuation

Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN) Life-threatening mucocutaneous reactions; typically occur in first 6 weeks; requires immediate discontinuation and hospitalisation

DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) Rash with fever, eosinophilia, lymphadenopathy, and multi-organ involvement; requires immediate discontinuation

Hypersensitivity reaction Rash accompanied by constitutional symptoms (fever, malaise, myalgia, arthralgia, hepatitis); requires immediate discontinuation

Granulocytopenia Rare; monitor CBC if clinical concern

Rhabdomyolysis Very rare; reported in case reports

⚠️ Any rash with systemic symptoms (fever, oral lesions, blistering, facial oedema, hepatitis, eosinophilia, myalgia) mandates immediate and permanent discontinuation of nevirapine.

Phase Parameters

Baseline (before initiation) CD4 count (mandatory — assess eligibility); LFTs (ALT, AST, bilirubin); hepatitis B and C serology; pregnancy test (if applicable); complete medication review for interactions

During lead-in phase (first 14 days) LFTs at day 7 and day 14; clinical assessment for rash and systemic symptoms

After dose escalation (weeks 2–18) LFTs every 2 weeks until week 8, then every 4 weeks until week 18; close clinical monitoring for rash, hepatitis symptoms

Long-term (after 18 weeks) LFTs every 3–6 months; viral load every 6 months; CD4 count annually (or as per NACO protocol)

If therapy interrupted >7 days Restart with lead-in dosing; repeat LFT monitoring schedule

Clinical vigilance Any rash or systemic symptoms require immediate assessment and potential discontinuation

Single-Agent Formulations:

• Nevimune® (Cipla)

• Nevipan® (Panacea Biotec)

• Neviretro® (Hetero)

• Nevirex® (Aurobindo)

Fixed-Dose Combinations (FDCs):

• Duovir-N® (Cipla) — Zidovudine + Lamivudine + Nevirapine

• Zidolam-N® (Hetero) — Zidovudine + Lamivudine + Nevirapine

• Lazid-N® (Ranbaxy) — Zidovudine + Lamivudine + Nevirapine

• Nevirapine-containing regimens are available free of cost through government ART centres under NACO programme

• FDCs are included in NLEM and are price-regulated

• Lead-in phase is non-negotiable: Always initiate with 200 mg once daily for 14 days to reduce incidence and severity of rash and hepatotoxicity. Never skip or shorten this phase.

• CD4 count determines eligibility: Do not initiate nevirapine in treatment-naïve women with CD4 >250 cells/mm³ or men with CD4 >400 cells/mm³ — risk of severe hepatotoxicity is significantly increased.

• TB co-treatment requires regimen change: Avoid nevirapine with rifampicin. Switch to efavirenz-based or dolutegravir-based ART when TB treatment is required.

• Therapy interruption protocol: If nevirapine is stopped for more than 7 days, restart with full lead-in phase to prevent hypersensitivity reactions.

• Rash + systemic symptoms = stop immediately: Any rash accompanied by fever, hepatitis, oral lesions, or constitutional symptoms warrants permanent discontinuation and specialist referral.

• LFT monitoring is intensive: Unlike many antiretrovirals, nevirapine requires frequent LFT monitoring, especially during the first 18 weeks. Document and adhere to the monitoring schedule.

Nevirapine; NNRTI; HIV; antiretroviral; ART; hepatotoxicity; rash; SJS; TEN; NACO; PMTCT; CD4 threshold; CYP3A4 inducer; NLEM India; Schedule H

RxIndia v1.0 — 05 May 2025

• CDSCO Approved Package Inserts

• Indian Pharmacopoeia / National Formulary of India

• NACO Guidelines for Antiretroviral Therapy (2021)

• NACO Guidelines for Prevention of Parent-to-Child Transmission (PMTCT)

• National List of Essential Medicines (NLEM) India 2022

• API Textbook of Medicine

• IAP Guidelines for Paediatric HIV/ART (2021)

• AIIMS ART Protocol

• WHO Consolidated Guidelines on HIV (supportive reference)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics