Makindo Medical Notes

⚠️ Warning: Saquinavir can cause serious, potentially life-threatening side effects including QT and PR interval prolongation, leading to arrhythmias. 🩸 It may also worsen liver disease, particularly in those with hepatitis or alcohol-related liver injury. Monitor ECG and liver function before and during therapy.

🧠 About

• Saquinavir is a protease inhibitor (PI) used as part of combination antiretroviral therapy (cART) for HIV-1 and HIV-2 infection.
• Always used with a small “booster” dose of ritonavir or cobicistat to inhibit its metabolism and enhance plasma concentrations (“boosted PI”).
• For current dosing and interactions, always check the BNF.

⚙️ Mode of Action

• Highly specific inhibitor of the HIV-1 and HIV-2 protease enzyme, which cleaves viral polyproteins into functional proteins necessary for viral maturation.
• By preventing cleavage of the Gag-Pol polyprotein, Saquinavir produces immature, non-infectious viral particles.
• Metabolised by CYP3A4; ritonavir co-administration inhibits CYP3A4, markedly increasing Saquinavir levels (“pharmacokinetic boosting”).

💊 Indications & Dosing

• HIV infection (adults): 1000 mg twice daily (5 × 200-mg capsules or 2 × 500-mg tablets) with food, plus ritonavir 100–200 mg once daily.
• Used only in combination antiretroviral therapy (cART) — never as monotherapy due to rapid resistance.
• Must be taken with food to enhance absorption.

⚠️ Interactions

• Extensive interactions via CYP3A4 inhibition/induction. See BNF for full list.
• Contraindicated with drugs that prolong QT or PR interval (e.g. amiodarone, sotalol, pimozide, halofantrine).
• Interactions with rifampicin, carbamazepine, St John’s wort, and simvastatin — risk of loss of efficacy or toxicity.
• Always perform a comprehensive drug interaction check before prescribing.

⚕️ Cautions

• Pre-existing cardiac conduction abnormalities or hepatic impairment (risk of arrhythmia or hepatotoxicity).
• Co-infection with hepatitis B or C — increased hepatic risk; monitor LFTs regularly.
• Monitor fasting glucose and lipid profile during prolonged therapy (risk of metabolic syndrome).

🚫 Contraindications

• Severe hepatic impairment.
• Known prolonged QT or complete AV block.
• Concomitant use with drugs highly dependent on CYP3A4 for clearance (see BNF list).
• Hypersensitivity to Saquinavir or excipients.

💥 Side Effects

• Common: Gastrointestinal upset (nausea, diarrhoea, abdominal discomfort), headache, fatigue.
• Metabolic: Hyperlipidaemia, insulin resistance, hyperglycaemia, lipodystrophy (“fat redistribution”).
• Hepatic: Elevated LFTs, hepatotoxicity (monitor ALT/AST).
• Cardiac: QT/PR prolongation, arrhythmias (particularly in hepatic impairment or drug interactions).
• Rare: Pancreatitis, rash, photosensitivity, neutropenia.

📖 Educational Summary

Saquinavir was the first licensed protease inhibitor and marked a turning point in HIV therapy. It works late in the viral life cycle, preventing maturation of infectious virions — a different site of action from NRTIs and NNRTIs. Its use has declined in favour of newer agents (e.g. darunavir, atazanavir) with fewer interactions and simpler dosing, but it remains an important teaching example of pharmacokinetic boosting and multi-drug synergy. Always remember: protease inhibitors can cause metabolic complications and cardiac toxicity, so ECG and metabolic monitoring are essential.

📚 References

• Saquinavir – British National Formulary
• BHIVA Guidelines for the Treatment of HIV-1 Positive Adults (2023)
• HIV i-Base: Protease Inhibitors Factsheet (2024)
• EMA Product Information: Invirase (Saquinavir) Summary of Product Characteristics