Schedule H

Oral

• Tablets: 75 mg, 150 mg, 400 mg, 600 mg, 800 mg

• Oral suspension: 100 mg/mL (limited market availability)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. HIV-1 Infection in Treatment-Naïve Adults (as part of combination ART)

Parameter Dose

Starting dose Darunavir 800 mg + Ritonavir 100 mg once daily with food

Titration Not applicable

Usual maintenance dose Darunavir 800 mg + Ritonavir 100 mg once daily with food

Maximum dose Darunavir 800 mg/day (once daily regimen)

Key Clinical Notes:

• Darunavir must always be co-administered with a pharmacokinetic booster (ritonavir or cobicistat)

• Must be taken with food to ensure adequate absorption

• Used in combination with two NRTIs as per NACO guidelines

1. HIV-1 Infection in Treatment-Experienced Adults (as part of combination ART)

Parameter Dose

Starting dose Darunavir 600 mg + Ritonavir 100 mg twice daily with food

Titration Not applicable

Usual maintenance dose Darunavir 600 mg + Ritonavir 100 mg twice daily with food

Maximum dose Darunavir 1200 mg/day (in two divided doses)

Key Clinical Notes:

• Twice-daily dosing required in treatment-experienced patients or those with darunavir resistance-associated mutations

• Genotypic resistance testing recommended before selecting dosing regimen

• Once-daily dosing only permissible if no darunavir resistance mutations present

1. HIV-1 Infection — Alternative Boosting with Cobicistat (Treatment-Naïve or No DRV Resistance)

Parameter Dose

Starting dose Darunavir 800 mg + Cobicistat 150 mg once daily with food

Titration Not applicable

Usual maintenance dose Darunavir 800 mg + Cobicistat 150 mg once daily with food

Maximum dose Darunavir 800 mg + Cobicistat 150 mg once daily

Key Clinical Notes:

• Cobicistat-boosted darunavir is only suitable for treatment-naïve patients or those without DRV-associated resistance mutations

• Not recommended in pregnancy (cobicistat leads to reduced darunavir exposure in later trimesters)

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

Indication Dose Duration Notes

Post-Exposure Prophylaxis (PEP) for occupational HIV exposure Darunavir 800 mg + Ritonavir 100 mg once daily (with 2 NRTIs) 28 days OFF-LABEL — Specialist only; use when preferred PEP options (e.g., dolutegravir-based) are unsuitable

Evidence basis: International PEP protocols (CDC, BHIVA); limited India-specific data; not included in current NACO PEP guidelines as first-line.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

HIV-1 Infection in Children ≥3 years (as part of combination ART)

Weight-Based Dosing (with Ritonavir boosting):

Weight (kg) Darunavir Dose Ritonavir Dose Frequency

10–<15 20 mg/kg 3 mg/kg Twice daily

15–<30 375–450 mg 48–50 mg Twice daily

30–<40 450–600 mg 60–100 mg Twice daily

≥40 600 mg 100 mg Twice daily

Dosing Format for Standard Weight Bands:

Weight 10–<15 kg:

Parameter Dose

Starting dose Darunavir 20 mg/kg + Ritonavir 3 mg/kg twice daily with food

Titration Not applicable

Usual maintenance dose Darunavir 20 mg/kg + Ritonavir 3 mg/kg twice daily

Maximum dose Do not exceed adult dosing

Weight 15–<30 kg:

Parameter Dose

Starting dose Darunavir 375–450 mg + Ritonavir 48–50 mg twice daily with food

Titration Not applicable

Usual maintenance dose Darunavir 375–450 mg + Ritonavir 48–50 mg twice daily

Maximum dose Darunavir 600 mg + Ritonavir 100 mg twice daily

Weight 30–<40 kg:

Parameter Dose

Starting dose Darunavir 450–600 mg + Ritonavir 60–100 mg twice daily with food

Titration Not applicable

Usual maintenance dose Darunavir 450–600 mg + Ritonavir 60–100 mg twice daily

Maximum dose Darunavir 600 mg + Ritonavir 100 mg twice daily

Weight ≥40 kg:

Parameter Dose

Starting dose Darunavir 600 mg + Ritonavir 100 mg twice daily with food

Titration Not applicable

Usual maintenance dose Darunavir 600 mg + Ritonavir 100 mg twice daily

Maximum dose Darunavir 600 mg + Ritonavir 100 mg twice daily

Key Clinical Notes:

• Must always administer with food

• Oral suspension (100 mg/mL) available for weight-based dosing in younger children

• Once-daily dosing is not recommended in paediatric patients

• Always co-administer with ritonavir; cobicistat not approved for paediatric use in India

Safety Monitoring:

• Baseline and periodic LFTs, serum bilirubin

• Lipid profile every 6 months

• HIV viral load and CD4 count as per NACO paediatric protocols

• Monitor for rash, especially in first 4 weeks

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

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

Age Restrictions:

• Not recommended in children <3 years due to risk of toxicity (immature hepatic CYP3A4 metabolism) and lack of appropriate formulations

• Not recommended in children <10 kg — safety and efficacy not established

• Use only under specialist supervision in paediatric HIV centres

Notes:

• Darunavir is primarily hepatically metabolised; renal clearance is minimal (<8%)

• Safe to use in patients with renal impairment without dose modification

Notes:

• Patients with chronic hepatitis B or C co-infection are at increased risk of hepatotoxicity

• Discontinue if signs of hepatic decompensation develop

• Known hypersensitivity to darunavir or any excipient

• Severe hepatic impairment (Child-Pugh C)

• Concurrent use with drugs highly dependent on CYP3A4 for clearance with narrow therapeutic index:

• Alfuzosin (risk of severe hypotension)

• Amiodarone, dronedarone (risk of serious arrhythmias)

• Cisapride (risk of QT prolongation, torsades de pointes)

• Quinidine (risk of arrhythmias)

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

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

• Simvastatin, lovastatin (risk of myopathy/rhabdomyolysis)

• Rifampicin (profound reduction in darunavir levels — loss of virological efficacy)

• St John's Wort (Hypericum perforatum — reduced darunavir levels)

• Pimozide (risk of QT prolongation)

• Lurasidone (risk of serious adverse reactions)

• Haemophilia A and B — increased risk of spontaneous bleeding; monitor for bleeding episodes

• Pre-existing cardiac conduction abnormalities — rare risk of PR interval prolongation

• Patients with known sulphonamide allergy — darunavir contains a sulfonamide moiety (theoretical cross-reactivity risk; clinical significance uncertain)

• Diabetes mellitus — may exacerbate hyperglycaemia

• Dyslipidaemia — monitor lipid profile regularly

• Elderly patients — increased risk of hepatic dysfunction and polypharmacy interactions

• Chronic hepatitis B/C co-infection — higher risk of hepatotoxicity; monitor LFTs closely

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

Parameter Information

Overall safety No evidence of teratogenicity in human data; may be used when benefit outweighs risk

Preferred regimen Ritonavir-boosted darunavir (600/100 mg twice daily) — preferred among PIs in pregnancy when PI-based regimen required

Cobicistat-boosted Not recommended in pregnancy (reduced darunavir exposure in 2nd/3rd trimester)

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

When it may be used When integrase inhibitor-based regimens are contraindicated or not tolerated

Monitoring LFTs, viral load suppression, adherence, signs of hepatotoxicity, fetal growth

Parameter Information

Compatibility Not recommended due to risk of HIV transmission via breastmilk (per NACO guidelines)

Indian guidance HIV-positive mothers on effective ART may exclusively breastfeed for 6 months with proper counselling and adherence support (WHO/NACO)

Drug levels in milk Not well studied; expected to be low based on pharmacokinetic properties

Preferred alternatives Continue effective maternal ART; ensure viral suppression

Infant monitoring Monitor HIV status, growth, feeding, signs of hepatotoxicity or jaundice

Parameter Recommendation

Starting dose Same as younger adults (Darunavir 800 mg + Ritonavir 100 mg once daily, or 600/100 mg twice daily based on treatment history)

Titration Not applicable; consider slower introduction in frail patients

Extra risks Hepatic dysfunction, polypharmacy interactions, cardiac conduction abnormalities

Monitoring LFTs, renal function, lipid profile, ECG if cardiac history; review quarterly

Notes:

• Limited clinical data in patients >65 years

• Carefully review concomitant medications for potential CYP3A4 interactions

Interacting Drug Effect/Mechanism Recommendation

Rifampicin Strong CYP3A4 inducer; markedly reduces darunavir levels (loss of virological efficacy) Contraindicated

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

Amiodarone / Dronedarone CYP3A4 substrates; risk of serious cardiac arrhythmias Contraindicated

Oral Midazolam / Triazolam CYP3A4 substrates; risk of prolonged/excessive sedation Contraindicated

Ergot derivatives CYP3A4 substrates; risk of ergotism (peripheral vasospasm) Contraindicated

Alfuzosin CYP3A4 substrate; risk of severe hypotension Contraindicated

Cisapride / Pimozide QT prolongation risk Contraindicated

St John's Wort CYP3A4 inducer; reduces darunavir levels Contraindicated

Phenytoin / Carbamazepine / Phenobarbital CYP3A4 inducers; significantly reduce darunavir levels Avoid if possible; use alternative anticonvulsant

Interacting Drug Effect/Mechanism Recommendation

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

Clarithromycin Increased levels of both drugs Monitor for QT prolongation and clarithromycin toxicity; reduce clarithromycin dose by 50% if CrCl 30–60 mL/min

Oral contraceptives (ethinylestradiol/norethindrone) Reduced contraceptive efficacy Use additional/alternative contraceptive methods

Atorvastatin / Rosuvastatin Increased statin levels Use lowest effective statin dose; do not exceed atorvastatin 20 mg/day

Warfarin Altered INR possible Monitor INR closely; adjust warfarin dose as needed

Ketoconazole / Itraconazole Increased levels of both drugs Limit azole dose to 200 mg/day; monitor for toxicity

Antacids May reduce darunavir absorption Separate dosing by at least 2 hours

Methadone Reduced methadone levels Monitor for opioid withdrawal; dose adjustment may be needed

Sildenafil / Tadalafil / Vardenafil CYP3A4 substrates; increased PDE5 inhibitor levels Use reduced doses with caution (e.g., sildenafil 25 mg every 48 hours)

Calcium channel blockers (e.g., amlodipine, diltiazem) Increased CCB levels Use with caution; clinical monitoring for hypotension and oedema

Bosentan Bidirectional interaction Specialist oversight required; dose adjustment needed

• Diarrhoea

• Nausea

• Headache

• Abdominal pain

• Rash (mild to moderate, non-progressive)

• Hyperlipidaemia (elevated triglycerides, cholesterol)

• Fatigue

• Vomiting

Adverse Effect Clinical Notes

Severe skin reactions (Stevens-Johnson Syndrome, TEN) Rare; discontinue immediately if mucocutaneous involvement or systemic symptoms develop

Hepatotoxicity Including drug-induced hepatitis and fulminant hepatic failure; discontinue if jaundice develops or transaminases >5× ULN

Anaphylaxis / Severe hypersensitivity Rare; discontinue and do not rechallenge

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

Increased bleeding in haemophilia Monitor for spontaneous bleeding episodes

New-onset or worsening diabetes mellitus Monitor blood glucose; manage accordingly

PR interval prolongation Rare; use with caution in patients with pre-existing conduction abnormalities

After initiation (2–4 weeks) LFTs, rash monitoring, adherence assessment

8 weeks HIV viral load to assess treatment response

Long-term (every 3–6 months) LFTs, lipid profile, blood glucose, renal function (if on tenofovir), viral load, CD4 count

As clinically indicated ECG if cardiac symptoms; skin examination if rash history

Prezista Janssen Tablets 75 mg, 150 mg, 400 mg, 600 mg, 800 mg

Danavir Emcure Tablets 600 mg, 800 mg

Durart Cipla Tablets 600 mg, 800 mg

Dynavir Mylan/Viatris Tablets 600 mg, 800 mg

Darunavir + Ritonavir FDC Various FDC tablets (limited availability)

Darunavir + Cobicistat FDC Various FDC tablets (limited availability)

Oral suspension 100 mg/mL Market availability variable; pricing not standardised

Notes:

• Available free of cost at government ART centres under NACO programme (third-line regimen)

• Not currently listed in NLEM 2022 as a first-line essential medicine

• NPPA price control: Not applicable

1. Never use without a pharmacokinetic booster: Darunavir alone has poor bioavailability — always co-administer with ritonavir (preferred) or cobicistat.

1. Once-daily vs twice-daily dosing: Once-daily regimen (800/100 mg) is only appropriate for treatment-naïve patients or those without darunavir resistance mutations; twice-daily dosing (600/100 mg BD) is mandatory in treatment-experienced patients.

1. Food is essential: Darunavir absorption increases significantly when taken with food — instruct patients to take with a meal.

1. Rifampicin is an absolute no: Co-administration with rifampicin causes >80% reduction in darunavir levels; use rifabutin as alternative in TB co-infection (with dose adjustment).

1. Pregnancy considerations: Use ritonavir-boosted (not cobicistat-boosted) darunavir in pregnancy; twice-daily dosing preferred in third trimester due to altered pharmacokinetics.

1. Sulfonamide moiety: Although darunavir contains a sulfonamide group, cross-reactivity with sulfonamide antibiotics appears rare; use with caution in patients with severe sulfonamide allergy history.

Darunavir; HIV; protease inhibitor; antiretroviral; ART; ritonavir-boosted; cobicistat; CYP3A4; NACO; third-line ART; pregnancy-compatible; India

RxIndia v1.0 — 25 Apr 2025

• CDSCO approved product information

• Indian Pharmacopoeia / National Formulary of India

• NACO National ART Guidelines (2021–2022)

• NACO Paediatric ART Guidelines

• IAP Guidelines for Paediatric HIV Care

• API Textbook of Medicine (HIV chapter)

• AIIMS HIV Treatment Protocol

• Product inserts (Prezista, Durart, Danavir)

• WHO Consolidated HIV Guidelines (supportive, for off-label PEP reference)

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