Schedule H

Oral

• Capsules: 150 mg, 200 mg, 300 mg

• Tablets: 300 mg

• Fixed-Dose Combinations (FDCs):

• Atazanavir 300 mg + Ritonavir 100 mg (capsule/tablet)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. HIV-1 Infection in Adults (as part of combination ART with ritonavir boosting)

Parameter Dose

Starting dose Atazanavir 300 mg + Ritonavir 100 mg once daily

Titration Not applicable

Usual maintenance dose Atazanavir 300 mg + Ritonavir 100 mg once daily

Maximum dose Atazanavir 300 mg + Ritonavir 100 mg once daily

Key Clinical Notes:

• Must be taken with food to ensure adequate absorption

• Used in combination with two NRTIs (e.g., Tenofovir + Lamivudine or Tenofovir + Emtricitabine)

• Ritonavir-sparing (unboosted) regimen not recommended in Indian practice — always use with ritonavir booster

• Part of second-line ART regimens as per NACO guidelines

1. HIV-1 Infection in ART-naïve Adolescents (≥13 years and ≥40 kg)

Parameter Dose

Starting dose Atazanavir 300 mg + Ritonavir 100 mg once daily

Titration Not applicable

Usual maintenance dose Atazanavir 300 mg + Ritonavir 100 mg once daily

Maximum dose Atazanavir 300 mg + Ritonavir 100 mg once daily

Key Clinical Notes:

• Administer with food

• Use in combination with two NRTIs as per NACO adolescent ART protocols

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

Not applicable — No established off-label uses with Indian consensus.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

HIV-1 Infection in Children ≥6 years (Specialist prescription only)

Weight (kg) Atazanavir Dose Ritonavir Dose Frequency

15–<20 150 mg 100 mg Once daily

20–<40 200 mg 100 mg Once daily

≥40 300 mg 100 mg Once daily

Dosing Format per Weight Band:

Weight 15–<20 kg:

Parameter Dose

Starting dose Atazanavir 150 mg + Ritonavir 100 mg once daily

Titration Not applicable

Usual maintenance dose Atazanavir 150 mg + Ritonavir 100 mg once daily

Maximum dose Atazanavir 150 mg + Ritonavir 100 mg once daily

Weight 20–<40 kg:

Parameter Dose

Starting dose Atazanavir 200 mg + Ritonavir 100 mg once daily

Titration Not applicable

Usual maintenance dose Atazanavir 200 mg + Ritonavir 100 mg once daily

Maximum dose Atazanavir 200 mg + Ritonavir 100 mg once daily

Weight ≥40 kg:

Parameter Dose

Starting dose Atazanavir 300 mg + Ritonavir 100 mg once daily

Titration Not applicable

Usual maintenance dose Atazanavir 300 mg + Ritonavir 100 mg once daily

Maximum dose Atazanavir 300 mg + Ritonavir 100 mg once daily

Key Clinical Notes:

• Must administer with food

• Monitor LFTs and bilirubin regularly

• Always use in combination with age-appropriate NRTI backbone

Safety Monitoring:

• Baseline and periodic LFTs, serum bilirubin

• CBC with differential

• Viral load and CD4 count as per NACO protocol

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

Not applicable — No established off-label uses in Indian paediatric practice.

Age Restrictions:

• Not recommended in children <6 years due to formulation limitations and increased risk of hyperbilirubinaemia

• Not recommended in children <15 kg — safety and efficacy not established

• Use only under specialist supervision in paediatric HIV centres

Notes:

• Atazanavir is primarily hepatically metabolised; renal excretion is minimal

• Ensure adequate hydration to reduce nephrolithiasis risk

Notes:

• Higher risk of hepatotoxicity in HBV/HCV co-infected patients

• Monitor for worsening jaundice or hepatic decompensation

• Known hypersensitivity to atazanavir or any excipient

• Severe hepatic impairment (Child-Pugh C)

• Concurrent use with:

• Rifampicin (strong CYP3A4 inducer — causes profound reduction in atazanavir levels)

• Proton pump inhibitors (omeprazole ≥20 mg — significantly impairs absorption)

• Oral midazolam or triazolam (risk of prolonged/excessive sedation)

• Ergot derivatives (ergotamine, dihydroergotamine — risk of ergotism)

• Alfuzosin (risk of hypotension)

• Simvastatin, lovastatin (risk of myopathy/rhabdomyolysis)

• Unboosted atazanavir in pregnancy (subtherapeutic levels)

• Unboosted atazanavir with tenofovir (reduced efficacy)

• Pre-existing hepatic disease (especially HBV/HCV co-infection) — increased hepatotoxicity risk

• Cardiac conduction abnormalities — risk of PR interval prolongation; avoid in patients with pre-existing AV block

• Concurrent use with acid-suppressing agents — reduced atazanavir absorption

• Gilbert's syndrome — exaggerated hyperbilirubinaemia

• History of nephrolithiasis or cholelithiasis — ensure adequate hydration

• Diabetes mellitus — may cause hyperglycaemia

• Haemophilia — increased bleeding risk reported with PIs

• Elderly patients — increased risk of cardiac conduction abnormalities

Parameter Information

Overall safety Use with caution; not preferred first-line agent

Risk Subtherapeutic levels possible, especially if unboosted; increased risk of neonatal hyperbilirubinaemia

When it may be used Only if benefit outweighs risk; must always be ritonavir-boosted

Preferred alternatives Dolutegravir-based regimens are now preferred first-line as per NACO guidelines

Monitoring LFTs, bilirubin, viral load suppression; neonatal bilirubin levels at birth

Parameter Information

Compatibility Not recommended due to risk of HIV transmission via breastmilk

Indian guidance WHO/NACO advises HIV-positive mothers on effective ART may exclusively breastfeed for 6 months

Drug levels in milk Low; clinical significance unknown

Preferred alternatives Continue maternal ART as per NACO; ensure viral suppression

Infant monitoring Monitor for jaundice, feeding difficulties, weight gain

Parameter Recommendation

Starting dose Standard adult dose (Atazanavir 300 mg + Ritonavir 100 mg once daily)

Titration Not applicable

Extra risks Increased risk of cardiac conduction abnormalities (PR prolongation); age-related decline in hepatic/renal function

Monitoring Regular ECG monitoring if cardiac risk factors present; LFTs and renal function periodically

Notes:

• Limited clinical data in patients >65 years

• Use with caution; monitor for ADRs more frequently

Interacting Drug Effect/Mechanism Recommendation

Rifampicin Strong CYP3A4 inducer; markedly reduces atazanavir levels Contraindicated

Proton pump inhibitors (e.g., omeprazole ≥20 mg) Increased gastric pH impairs atazanavir absorption Contraindicated

Oral midazolam / triazolam CYP3A4 substrates; prolonged sedation Contraindicated

Ergot alkaloids CYP3A4 substrates; risk of ergotism Contraindicated

Simvastatin / lovastatin CYP3A4 substrates; risk of myopathy/rhabdomyolysis Contraindicated

Alfuzosin CYP3A4 substrate; risk of severe hypotension Contraindicated

Didanosine (buffered formulation) Antacid buffer reduces atazanavir absorption Avoid; if necessary, give atazanavir 2 hours before or 1 hour after didanosine

Interacting Drug Effect/Mechanism Recommendation

Tenofovir Reduces atazanavir levels Always use ritonavir-boosted atazanavir when co-administered

H2-receptor antagonists (e.g., ranitidine, famotidine) Reduced atazanavir absorption Separate dosing: give atazanavir with food at least 2 hours before or 10 hours after H2 blocker

Antacids Reduced absorption Separate by at least 2 hours

Warfarin Altered INR possible Monitor INR closely; dose adjustment may be needed

Phenytoin / carbamazepine CYP3A4 inducers; may reduce atazanavir levels Use with caution; consider alternative anticonvulsant

Rifabutin CYP3A4 interaction; increased rifabutin toxicity Reduce rifabutin dose to 150 mg every other day or 3 times weekly

Oral contraceptives (ethinylestradiol) Altered oestrogen levels Use additional/alternative contraceptive methods

Atorvastatin CYP3A4 substrate; increased statin levels Use lowest atorvastatin dose; do not exceed 20 mg/day

Clarithromycin Bidirectional interaction Reduce clarithromycin dose by 50%; monitor for QT prolongation

Sildenafil / tadalafil / vardenafil CYP3A4 substrates; increased PDE5 inhibitor levels Use reduced doses with caution

• Hyperbilirubinaemia (indirect, unconjugated) — very common

• Jaundice, scleral icterus (cosmetic; not indicative of hepatotoxicity)

• Nausea

• Diarrhoea

• Headache

• Rash

• Abdominal pain

• Elevated hepatic transaminases (mild)

• Lipodystrophy (with long-term use)

Adverse Effect Clinical Notes

Nephrolithiasis / cholelithiasis May require drug discontinuation; ensure hydration

PR interval prolongation ECG monitoring recommended in at-risk patients; avoid in pre-existing conduction defects

AV block (first-degree, rarely higher) Discontinue if symptomatic

Acute renal failure Rare; associated with nephrolithiasis

Stevens-Johnson Syndrome / TEN Very rare; discontinue immediately if suspected

Immune Reconstitution Inflammatory Syndrome (IRIS) May occur after ART initiation; manage underlying opportunistic infection

Severe hepatotoxicity Rare; monitor LFTs, especially in HBV/HCV co-infection

After initiation (2–4 weeks) LFTs, bilirubin; ECG if on other PR/QT-affecting drugs

4–8 weeks HIV viral load to assess treatment response

Long-term (every 6 months) LFTs, renal function, fasting lipids, blood glucose, viral load, CD4 count

As clinically indicated ECG if new cardiac symptoms; urine analysis if nephrolithiasis suspected

Virataz Cipla Capsules 150 mg, 200 mg, 300 mg

Atavir Emcure Capsules 150 mg, 200 mg, 300 mg

Aztanavir Hetero Capsules 150 mg, 200 mg, 300 mg

Notes:

• Available free of cost at government ART centres under NACO programme

• Not currently listed in NLEM 2022 as an essential medicine (dolutegravir-based regimens preferred)

• NPPA price control: Not applicable

1. Always use ritonavir boosting: Unboosted atazanavir leads to subtherapeutic levels, especially when co-administered with tenofovir — ritonavir 100 mg is mandatory for pharmacokinetic enhancement.

1. Cosmetic jaundice is benign: Indirect hyperbilirubinaemia causing scleral icterus occurs in up to 40% of patients but does not indicate hepatotoxicity; reassure patients accordingly.

1. PPIs are contraindicated: Proton pump inhibitors drastically reduce atazanavir absorption; use H2 blockers if necessary with appropriate timing separation.

1. Hydration prevents stones: Nephrolithiasis risk is significant — counsel patients to maintain adequate fluid intake (≥2 L/day).

1. Not preferred in pregnancy: Dolutegravir-based regimens are now first-line for pregnant women as per NACO; reserve atazanavir for situations where alternatives are not suitable.

1. Check drug interactions rigorously: Atazanavir is a CYP3A4 inhibitor and substrate — always verify potential interactions, especially with TB drugs, antiepileptics, and cardiovascular medications.

Atazanavir; HIV; protease inhibitor; ART; ritonavir-boosted; NACO; hyperbilirubinaemia; CYP3A4; nephrolithiasis; second-line ART; India

RxIndia v1.0 — 10 Apr 2025

• CDSCO approved product information

• Indian Pharmacopoeia / National Formulary of India

• NACO National ART Guidelines (2021)

• NACO Paediatric ART Guidelines

• IAP Guidelines for Paediatric HIV Care

• API Textbook of Medicine (HIV chapter)

• AIIMS ART Centre protocols

• WHO Consolidated HIV Guidelines (supportive, aligned with NACO)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (pharmacokinetics reference)