Schedule H

Oral

• Tablet: 50 mg

• Dispersible tablet: 10 mg (for paediatric use)

• Fixed-Dose Combinations (FDCs): Tenofovir + Lamivudine + Dolutegravir (TLD) in various strengths

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. HIV-1 Infection – Treatment-Naïve or Integrase-Inhibitor-Naïve Adults

Preferred first-line ART regimen component per NACO 2021 guidelines (as TLD: Tenofovir + Lamivudine + Dolutegravir)

Component Details

Starting dose 50 mg once daily

Titration Not applicable

Usual maintenance dose 50 mg once daily

Maximum dose 50 mg once daily (or 50 mg twice daily with enzyme inducers)

Clinical Notes:

• Administer with or without food

• Take at the same time each day for optimal adherence

• Must be combined with two NRTIs (Tenofovir + Lamivudine preferred)

1. HIV-1 Infection – With Concurrent Rifampicin Use (TB-HIV Co-infection)

Component Details

Starting dose 50 mg twice daily

Titration Not applicable

Usual maintenance dose 50 mg twice daily

Maximum dose 50 mg twice daily

Clinical Notes:

• Rifampicin induces UGT1A1 and CYP3A4, reducing dolutegravir exposure by approximately 50%

• Continue 50 mg twice daily for 2 weeks after rifampicin discontinuation, then revert to once daily

• Standard regimen per NACO TB-HIV co-infection guidelines

1. HIV-1 Infection – ART-Experienced Adults (Second-Line/Salvage Therapy)

Component Details

Starting dose 50 mg once daily (INSTI-naïve) OR 50 mg twice daily (suspected INSTI resistance)

Titration Not applicable

Usual maintenance dose As per resistance profile and specialist guidance

Maximum dose 50 mg twice daily

Clinical Notes:

• Genotypic resistance testing recommended before initiation

• Specialist supervision essential

• Twice-daily dosing required if INSTI resistance mutations suspected

Secondary Indications – Adults (Off-label)

Not applicable. No established off-label indications are routinely used in India.

PAEDIATRIC DOSING (Specialist Only)

Primary Indication: HIV-1 Infection

Minimum age/weight: ≥4 weeks of age AND ≥3 kg body weight

Weight-based dosing (as per NACO/IAP/WHO guidelines):

Weight Band Dolutegravir Dose

3 to <6 kg 5 mg twice daily (dispersible tablet)

6 to <10 kg 10 mg once daily

10 to <14 kg 15 mg once daily

14 to <20 kg 20 mg once daily

20 to <25 kg 25 mg once daily

25 to <40 kg 35 mg once daily

≥40 kg 50 mg once daily

Component Details

Starting dose As per weight band above

Titration Not applicable

Usual maintenance dose As per weight band

Maximum dose 50 mg once daily (adult dose at ≥40 kg)

With concurrent rifampicin (children >3 years and ≥20 kg):

• Double the weight-band dose (give twice daily)

Administration:

• Dispersible tablets: Dissolve in water; administer within 30 minutes of preparation

• Film-coated tablets: Swallow whole; do not crush

Safety Monitoring:

• HIV viral load at 4–8 weeks, then per NACO schedule

• Liver function tests (especially in HBV/HCV co-infection)

• Growth and developmental parameters

• Neuropsychiatric symptoms

Secondary Indications – Paediatrics (Off-label)

Not applicable. No established off-label paediatric indications in India.

Age/weight restriction: Not recommended below 4 weeks of age or <3 kg body weight except under specialist supervision in exceptional circumstances.

• Mild to moderate impairment (eGFR ≥30 mL/min): No dose adjustment required for dolutegravir itself

• Severe impairment (eGFR <30 mL/min): Dolutegravir does not require adjustment; however, use caution when given as FDC with Tenofovir (requires dose adjustment of Tenofovir component)

• Haemodialysis: No supplemental dosing required; dolutegravir is highly protein-bound and not significantly dialysed

Note: Monitor renal function regularly when using TLD fixed-dose combination

• Mild impairment (Child-Pugh A): No dose adjustment required

• Moderate impairment (Child-Pugh B): No dose adjustment required; use with caution and monitor liver function

• Severe impairment (Child-Pugh C): Avoid use — insufficient safety and efficacy data; specialist supervision only if no alternatives

• Known hypersensitivity to dolutegravir or any excipient in the formulation

• Concurrent administration with dofetilide — risk of life-threatening ventricular arrhythmias (elevated dofetilide levels via OCT2 inhibition)

• Concurrent administration with pilsicainide — increased plasma levels and arrhythmia risk

• History of INSTI resistance or prior INSTI treatment failure — resistance testing recommended

• Hepatitis B or C co-infection — increased risk of hepatotoxicity; monitor LFTs closely

• Pre-existing psychiatric disorders — may exacerbate depression, anxiety, suicidal ideation

• Women of childbearing potential not using effective contraception — counsel regarding periconceptional risk

• Concurrent use of enzyme inducers (rifampicin, carbamazepine, phenytoin) — requires dose adjustment

• Long-term use may be associated with weight gain

• Polyvalent cation-containing products (antacids, calcium, iron) — timing of administration important

Aspect Details

Overall safety Now endorsed as first-line ART in pregnancy per NACO 2021 guidelines

Historical concern Early signal of neural tube defects at periconception (Tsepamo study); subsequent data (2020 onwards) shows low absolute risk (~0.2%)

Current recommendation Can be initiated or continued throughout pregnancy; benefits outweigh risks

Preferred alternatives If patient declines dolutegravir at conception, efavirenz-based regimen may be considered

Monitoring Folic acid supplementation (5 mg daily recommended); detailed fetal anomaly scan at 18–20 weeks

Aspect Details

Compatibility Compatible with breastfeeding per NACO and WHO guidelines

Drug levels in milk Low (relative infant dose <1%)

Preferred alternatives Not routinely required

Infant monitoring Growth parameters, liver function if concern, standard ART infant prophylaxis as per NACO PMTCT protocol

• Recommended starting dose: 50 mg once daily (same as general adult population)

• Titration: Not applicable

• Extra risks:

• Age-related decline in renal function — assess eGFR before initiating TLD combination

• Increased susceptibility to neuropsychiatric effects (insomnia, headache)

• Polypharmacy common — review for drug interactions

• Monitor weight changes

Interacting Drug Effect/Mechanism Recommendation

Rifampicin Induces UGT1A1 and CYP3A4 — reduces dolutegravir AUC by ~50% Increase dose to 50 mg twice daily; continue for 2 weeks after rifampicin stopped

Dofetilide OCT2 inhibition increases dofetilide levels — life-threatening arrhythmias Contraindicated

Carbamazepine, Phenytoin, Phenobarbital Strong enzyme inducers — significantly reduce dolutegravir levels Avoid if possible; if unavoidable, use 50 mg twice daily with close viral load monitoring

Metformin OCT2 and MATE1 inhibition — increased metformin exposure by 79% Limit metformin to maximum 1000 mg/day; monitor for metformin toxicity

St. John's Wort Induces drug metabolism Avoid combination

Interacting Drug Effect/Mechanism Recommendation

Antacids (aluminium/magnesium-containing) Chelation reduces dolutegravir absorption Administer dolutegravir ≥2 hours before OR ≥6 hours after antacids

Calcium supplements Chelation reduces absorption Administer dolutegravir ≥2 hours before OR ≥6 hours after calcium

Iron supplements Chelation reduces absorption Administer dolutegravir ≥2 hours before OR ≥6 hours after iron

Sucralfate Reduces absorption Separate administration by ≥2 hours

Rifabutin Mild enzyme induction No dose adjustment usually required; monitor viral load

Efavirenz, Etravirine (without boosted PI) Reduce dolutegravir exposure Avoid combination if possible; if used, consider 50 mg twice daily

Note: Dolutegravir can be taken with food containing calcium — only separate from calcium supplements

• Insomnia and sleep disturbances

• Headache

• Nausea

• Diarrhoea

• Fatigue

• Dizziness

• Weight gain (particularly with long-term use)

• Elevated serum creatinine (inhibits tubular secretion; not indicative of true renal impairment)

• Severe hypersensitivity reactions — rash with constitutional symptoms, hepatitis, eosinophilia; discontinue immediately

• Hepatotoxicity — especially in HBV/HCV co-infection; monitor LFTs; discontinue if severe elevation

• Severe neuropsychiatric effects — depression, suicidal ideation, psychosis; requires discontinuation and psychiatric evaluation

• Neural tube defects — low risk at periconception; counsel women of childbearing potential

• Immune Reconstitution Inflammatory Syndrome (IRIS) — may occur after ART initiation

→ All serious adverse effects require immediate discontinuation and specialist referral

Phase Parameters

Baseline HIV viral load, CD4 count, serum creatinine, eGFR, LFTs (ALT, AST, bilirubin), HBsAg and anti-HCV serology, pregnancy test (women of childbearing potential), fasting glucose/HbA1c, weight

After initiation (4–8 weeks) HIV viral load, LFTs (especially if HBV/HCV co-infected), creatinine, neuropsychiatric symptoms assessment

At 6 months HIV viral load, CD4 count, renal and liver function, weight

Long-term (every 6–12 months) Viral load per NACO protocol, CD4 count annually, metabolic parameters (glucose, lipids), weight monitoring

• Instgra® (Emcure)

• Doluravir® (Hetero)

• Tivicay® (ViiV Healthcare — limited availability)

• Dolevir® (Mylan/Viatris)

• FDCs (TLD — Tenofovir + Lamivudine + Dolutegravir):

• Telura® (Emcure)

• Acriptega® (Mylan)

• Tavin-LD® (Hetero)

• TLD (Cipla)

• NACO-supplied generic TLD via government ART centres

• NLEM status: Yes (TLD combination included)

• NPPA controlled: Price ceiling applicable for NLEM formulations

• Government supply: Available free at government ART centres under NACO programme

• Preferred first-line ART in India per NACO 2021 — TLD (Tenofovir + Lamivudine + Dolutegravir) is the recommended single-tablet regimen for treatment-naïve adults

• Rifampicin co-administration requires dose doubling — always increase to 50 mg twice daily in TB-HIV co-infection

• Timing with polyvalent cations matters — separate from antacids, calcium, and iron supplements by at least 2 hours before or 6 hours after dolutegravir

• Mild creatinine rise is expected — dolutegravir inhibits OCT2-mediated tubular secretion of creatinine; this does not reflect true GFR decline

• Insomnia management — consider morning dosing if sleep disturbance is problematic

• Ensure folic acid supplementation in all women of childbearing potential — standard 5 mg daily recommended

Dolutegravir; HIV; INSTI; integrase inhibitor; ART; NACO; TLD; first-line-ART; pregnancy-compatible; TB-HIV; paediatric-HIV; NLEM India

RxIndia v1.1 — 18 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia

• NACO National Technical Guidelines on Antiretroviral Therapy (2021)

• API Textbook of Medicine (11th Edition) — HIV chapter

• IAP Guidelines for Paediatric HIV Management

• WHO Consolidated Guidelines on HIV (supportive, for paediatric weight bands)

• AIIMS HIV Management Protocols

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (13th Edition)

• National List of Essential Medicines (NLEM) 2022, India