Makindo Medical Notes

Indinavir is a protease inhibitor (PI) used as part of combination antiretroviral therapy (cART) for HIV-1 infection. Although now less commonly used in the UK due to newer agents with better tolerability and dosing convenience, indinavir remains a key historical and mechanistic drug in understanding HIV pharmacotherapy. Always 🔗 check the BNF summary here and use only under specialist supervision.

🧬 Mode of Action

• Indinavir is a competitive inhibitor of the HIV-1 protease enzyme — an aspartyl protease that cleaves viral gag-pol polyproteins into functional structural and enzymatic components (reverse transcriptase, integrase, protease itself).
• Inhibition of this enzyme prevents the maturation of viral particles, producing non-infectious virions.
• Active against both wild-type and some resistant HIV strains, but resistance can develop rapidly if plasma concentrations fall below therapeutic levels.

📋 Indications / Dosing

• HIV infection: Used in combination therapy (HAART) with at least two other active agents from different classes to prevent resistance.
• Typical monotherapy dose: 800 mg orally every 8 hours (empty stomach — 1 hour before or 2 hours after meals).
• Boosted regimen: 400 mg BD + ritonavir 100 mg BD gives equivalent exposure and improved adherence.
• Hydration: Advise ≥1.5 L fluid daily to reduce risk of nephrolithiasis.
• Drug interactions: with itraconazole or ketoconazole → reduce indinavir dose to 600 mg every 8 hours.
• Renal / hepatic adjustment: use with caution; avoid in severe hepatic impairment.

🧪 Pharmacology

• Absorption: Reduced by high-fat meals; take on an empty stomach or with light, non-fatty food.
• Metabolism: Hepatic via CYP3A4 — both a substrate and inhibitor.
• Half-life: ~1.5–2 hours (extended with ritonavir boosting).
• Excretion: Primarily hepatic; minor renal clearance — important in nephrolithiasis risk.

⚠️ Interactions

• Indinavir (± ritonavir) inhibits CYP3A4 → raises levels of co-administered drugs with narrow therapeutic indices (e.g., amiodarone, quinidine, simvastatin, ergot alkaloids, midazolam, triazolam).
• Contraindicated combinations: pimozide, cisapride, alfuzosin, St John’s wort, rifampicin — due to risk of arrhythmia, toxicity, or virologic failure.
• Co-administration with ritonavir increases indinavir exposure but also interaction potential — always verify in BNF.
• Interactions with oral contraceptives (↓ efficacy), antacids (↓ absorption), and ketoconazole/itraconazole (↑ levels) are clinically relevant.

🔍 Cautions

• Hydration essential: Maintain urine output ≥1.5 L/day to prevent crystalluria and nephrolithiasis.
• Hepatic impairment: accumulation risk; monitor LFTs regularly.
• Hyperbilirubinaemia: benign rise due to inhibition of bilirubin conjugation (UGT1A1).
• Insulin resistance and lipodystrophy: common with protease inhibitors (metabolic syndrome risk).
• Immune reconstitution inflammatory syndrome (IRIS): may occur after initiation of cART as immune function improves.

⛔ Contraindications

• Known hypersensitivity to indinavir or excipients.
• Concurrent use of potent CYP3A4 inducers (rifampicin, St John’s wort).
• Severe hepatic impairment.
• Concurrent use with medicines highly dependent on CYP3A4 clearance and with narrow therapeutic windows (e.g., amiodarone, ergotamine, simvastatin, midazolam).

💉 Side Effects

• Renal: nephrolithiasis (up to 10% of patients) — presents with flank pain, haematuria; encourage hydration.
• Haematological: haemolytic anaemia (rare, monitor FBC if symptomatic).
• Metabolic: dyslipidaemia, insulin resistance, central adiposity, peripheral lipoatrophy (“buffalo hump”).
• Hepatic: transaminitis, hyperbilirubinaemia.
• General: fatigue, nausea, diarrhoea, dry skin/lips (xerostomia and cheilitis classic for indinavir).
• Immune reconstitution inflammatory syndrome (IRIS): inflammatory flare of latent infections after cART initiation.

🧪 Monitoring (Specialist Care)

• HIV viral load and CD4 count every 3–6 months.
• Renal function and urinalysis (for haematuria or crystals).
• LFTs and bilirubin periodically (especially with hepatic disease).
• Fasting lipids and glucose for metabolic syndrome surveillance.

🧠 Clinical Pearls (UK context)

• Now largely superseded by atazanavir, darunavir, and integrase inhibitors due to pill burden and toxicity profile.
• Remember hydration — “PI stones” (indinavir crystals) can obstruct ureters if fluid intake is low.
• Dry mouth and cheilitis are early clues of high indinavir exposure.
• Always prescribe within a specialist HIV MDT framework — interactions and resistance patterns are complex.
• Monitor for lipodystrophy and metabolic side effects, which contribute to long-term CVD risk in patients on PIs.

📚 References

• BNF: HIV infection treatment summary
• British HIV Association (BHIVA) guidelines 2024: Management of HIV in adults.
• Uptodate: Protease inhibitor pharmacology.
• NICE NG122: HIV testing and management.