Schedule H

Oral

• Tablets: 100 mg

• Soft gelatin capsules: 100 mg (limited availability)

• Oral solution: 80 mg/mL (contains ethanol 43% and propylene glycol; avoid in neonates and pregnant women)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. HIV-1 Infection — As Pharmacokinetic Booster (Primary Current Use)

Ritonavir is predominantly used at low doses to enhance plasma concentrations of other protease inhibitors via CYP3A4 inhibition.

A. Boosting Lopinavir (as LPV/r — co-formulated or separate):

Parameter Dose

Starting dose Ritonavir 100 mg twice daily (with Lopinavir 400 mg twice daily)

Titration Not applicable

Usual maintenance dose Ritonavir 100 mg twice daily

Maximum dose Ritonavir 100 mg twice daily (boosting dose)

B. Boosting Atazanavir:

Parameter Dose

Starting dose Ritonavir 100 mg once daily (with Atazanavir 300 mg once daily)

Titration Not applicable

Usual maintenance dose Ritonavir 100 mg once daily

Maximum dose Ritonavir 100–200 mg once daily (depending on regimen)

C. Boosting Darunavir:

Parameter Dose

Starting dose Ritonavir 100 mg once daily (with Darunavir 800 mg once daily — treatment-naïve) OR Ritonavir 100 mg twice daily (with Darunavir 600 mg twice daily — treatment-experienced)

Titration Not applicable

Usual maintenance dose As per starting dose

Maximum dose Ritonavir 100 mg twice daily

1. HIV-1 Infection — As Active Antiretroviral Agent (Rarely Used)

Parameter Dose

Starting dose 300 mg twice daily

Titration Increase by 100 mg twice daily every 2–3 days as tolerated

Usual maintenance dose 600 mg twice daily

Maximum dose 600 mg twice daily

Key Clinical Notes:

• Full-dose ritonavir (600 mg twice daily) is rarely used in current practice due to poor GI tolerability and extensive drug interactions

• Always used as part of combination ART — never as monotherapy

• Genotypic resistance testing recommended prior to initiation

• Must be administered with food to enhance absorption

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

Indication Status

COVID-19 (Lopinavir/Ritonavir combination) NOT RECOMMENDED as per ICMR 2023 guidelines; no proven efficacy in COVID-19

Not applicable — No currently recommended off-label uses in Indian practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

HIV-1 Infection — As Pharmacokinetic Booster (with Lopinavir or Darunavir)

Age ≥2 years (Weight-based boosting with Lopinavir):

Weight (kg) Ritonavir Dose (with equivalent Lopinavir) Frequency

7–<15 50 mg (as part of LPV/r) Twice daily

15–<25 100 mg (as part of LPV/r) Twice daily

25–<35 100 mg (as part of LPV/r) Twice daily

≥35 100 mg (as part of LPV/r) Twice daily

Dosing Format:

Parameter Dose

Starting dose Weight-based as above (with food)

Titration Not applicable for boosting doses

Usual maintenance dose As per weight band

Maximum dose 100 mg twice daily (boosting dose)

Age 1–2 years:

Parameter Dose

Starting dose 3–5 mg/kg twice daily (rounded to nearest measurable dose)

Titration Not applicable

Usual maintenance dose 3–5 mg/kg twice daily

Maximum dose Do not exceed weight-appropriate adult boosting dose

Key Clinical Notes:

• Use oral solution or tablets based on child's ability to swallow

• Administer with food

• Oral solution requires accurate dosing device

Age <1 year:

Parameter Recommendation

Use Specialist only — limited safety data

Oral solution Avoid due to ethanol (43%) and propylene glycol content — risk of toxicity

Monitoring Close hepatic and CNS monitoring if use essential

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

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

Age Restrictions:

• Oral solution contraindicated in neonates and infants <1 month due to propylene glycol and ethanol toxicity risk

• Not recommended in premature neonates regardless of formulation

• Children <1 year: Use only under specialist supervision with extreme caution

• Children <2 years: Higher risk of hepatotoxicity and CNS depression; monitor closely

Safety Monitoring:

• Baseline and periodic LFTs

• Blood glucose monitoring

• Lipid profile every 6 months

• Clinical monitoring for GI tolerance and adherence

Notes:

• Ritonavir is primarily hepatically metabolised; renal excretion is minimal (<4%)

• Use with caution if co-administered with other nephrotoxic antiretrovirals (e.g., tenofovir)

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 ritonavir or any excipient

• Severe hepatic impairment (Child-Pugh C)

• Neonates and infants <1 month (oral solution — due to propylene glycol and ethanol content)

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

• Amiodarone, flecainide, propafenone, quinidine (risk of serious arrhythmias)

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

• Pimozide (risk of QT prolongation)

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

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

• Simvastatin, lovastatin (risk of myopathy/rhabdomyolysis)

• Alfuzosin (risk of severe hypotension)

• Sildenafil (when used for pulmonary arterial hypertension)

• Lurasidone (risk of serious adverse reactions)

• Concurrent use with:

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

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

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

• Diabetes mellitus or glucose intolerance — may worsen glycaemic control

• Pre-existing dyslipidaemia — may exacerbate hyperlipidaemia (hypertriglyceridaemia, hypercholesterolaemia)

• History of pancreatitis or hypertriglyceridaemia — increased pancreatitis risk

• Cardiac conduction abnormalities — risk of PR interval prolongation

• Haemophilia A and B — increased risk of spontaneous bleeding

• Elderly patients — increased risk of drug interactions due to polypharmacy

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

• Lipodystrophy syndrome with long-term use

Parameter Information

Overall safety Generally considered safe; may be used when benefit outweighs risk

Preferred status Preferred PI booster in pregnancy over cobicistat (better pharmacokinetic profile in third trimester)

Oral solution Avoid due to ethanol and propylene glycol content

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

When it may be used When PI-based regimen is required (e.g., resistance, intolerance to INSTIs)

Monitoring LFTs, fasting glucose, fetal growth, viral load suppression

Parameter Information

Compatibility HIV-positive mothers on effective ART may exclusively breastfeed for 6 months with proper counselling (per NACO/WHO)

Drug levels in milk Detectable; clinical significance uncertain

Oral solution Avoid in breastfeeding mothers due to excipient content

Preferred alternatives Continue effective maternal ART; ensure viral suppression

Infant monitoring Monitor for diarrhoea, weight gain, feeding difficulties, sedation, jaundice

Parameter Recommendation

Starting dose Same as younger adults (100 mg once or twice daily for boosting)

Titration Slower titration if using full antiviral doses (rarely indicated)

Extra risks GI intolerance, hepatic dysfunction, polypharmacy interactions, cardiac conduction abnormalities

Monitoring LFTs, lipid profile, ECG if cardiac risk factors; quarterly review of concomitant medications

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 ritonavir levels Contraindicated

Amiodarone / Flecainide / Propafenone / Quinidine CYP3A4 substrates; risk of serious cardiac arrhythmias Contraindicated

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

Ergot derivatives (ergotamine, dihydroergotamine) CYP3A4 substrates; risk of ergotism Contraindicated

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

Cisapride / Pimozide QT prolongation risk Contraindicated

St John's Wort CYP3A4 inducer; reduces ritonavir levels significantly Contraindicated

Alfuzosin CYP3A4 substrate; risk of severe hypotension Contraindicated

Mechanism: Ritonavir is a potent CYP3A4 inhibitor and substrate — numerous clinically significant interactions.

Interacting Drug Effect/Mechanism Recommendation

Rifabutin Increased rifabutin levels Reduce rifabutin dose to 150 mg every other day or 3 times weekly

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

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

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

Ketoconazole / Itraconazole Increased azole levels Limit azole dose to 200 mg/day; monitor for QT prolongation and hepatotoxicity

Phenytoin / Carbamazepine / Phenobarbital CYP3A4 inducers; reduce ritonavir levels Monitor for reduced efficacy; consider alternative anticonvulsant

Digoxin Increased digoxin levels via P-gp inhibition Monitor serum digoxin levels; dose reduction may be needed

Clarithromycin Increased clarithromycin levels Reduce clarithromycin dose by 50% if CrCl 30–60 mL/min; monitor for QT prolongation

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

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

Sildenafil / Tadalafil / Vardenafil (for erectile dysfunction) Increased PDE5 inhibitor levels Use reduced doses (e.g., sildenafil 25 mg every 48 hours)

Bosentan Bidirectional interaction Specialist oversight required; dose adjustment needed

• Nausea, vomiting

• Diarrhoea

• Abdominal pain

• Taste perversion / dysgeusia (particularly with oral solution)

• Fatigue / asthenia

• Headache

• Elevated hepatic transaminases

• Hypertriglyceridaemia

• Hypercholesterolaemia

• Perioral and peripheral paraesthesia

Adverse Effect Clinical Notes

Pancreatitis May require discontinuation; monitor triglycerides; discontinue if confirmed

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

PR interval prolongation / AV block Use with caution in patients with pre-existing conduction abnormalities; ECG monitoring if symptomatic

Stevens-Johnson Syndrome / TEN Rare; discontinue immediately if mucocutaneous involvement develops

New-onset diabetes mellitus / Hyperglycaemia Monitor blood glucose; manage accordingly

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

Increased bleeding in haemophilia Monitor for spontaneous bleeding episodes

After initiation (2–4 weeks) LFTs, GI tolerance assessment, adherence check

1–3 months Fasting lipid profile, blood glucose

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

As clinically indicated ECG if cardiac symptoms or prolonged use; renal function if co-administered with nephrotoxic drugs

Brand Name Manufacturer Formulation

Ritomune Cipla Tablets 100 mg

Ritonapil Hetero Tablets 100 mg

Norvir AbbVie Tablets 100 mg (limited availability)

Lopinavir/r Various FDC tablets and oral solution

Notes:

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

• Listed in NLEM 2022 as essential medicine for HIV treatment

• NPPA price control: Applicable for NLEM-listed formulations

1. Primarily a booster, not an active agent: Ritonavir at 100 mg is used almost exclusively as a pharmacokinetic enhancer for other PIs — full antiviral dosing (600 mg BD) is rarely used due to intolerable GI side effects.

1. Oral solution is hazardous in neonates: The oral solution contains 43% ethanol and propylene glycol — absolutely avoid in neonates, premature infants, and pregnant women.

1. Food is mandatory: Always administer with food to ensure adequate absorption and reduce GI intolerance.

1. CYP3A4 interaction powerhouse: Ritonavir is one of the most potent CYP3A4 inhibitors — screen all concomitant medications meticulously before prescribing.

1. Preferred over cobicistat in pregnancy: When a PI-boosted regimen is required in pregnancy, ritonavir is preferred over cobicistat due to better pharmacokinetic profile in later trimesters.

1. Metabolic monitoring essential: Long-term use requires regular monitoring of lipids and glucose — dyslipidaemia and hyperglycaemia are common with chronic PI use.

Ritonavir; HIV; protease inhibitor; antiretroviral; pharmacokinetic booster; CYP3A4 inhibitor; lopinavir; NACO; NLEM India; pregnancy-compatible; paediatric-specialist

RxIndia v1.0 — 08 Jun 2025

• CDSCO approved product information

• Indian Pharmacopoeia / National Formulary of India

• NLEM 2022 (National List of Essential Medicines)

• NACO National ART Guidelines (2021–2022)

• NACO Paediatric ART Guidelines

• IAP Guidelines for Paediatric HIV Care

• API Textbook of Medicine (HIV chapter)

• AIIMS Antiretroviral Protocol

• ICMR Guidelines (COVID-19 management — for exclusion reference)

• WHO Consolidated HIV Guidelines (supportive)

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