Makindo Medical Notes

💊 About

Lopinavir–ritonavir (brand name: Kaletra®) is a combination of two protease inhibitors (PIs) used in HIV therapy. Ritonavir acts primarily as a pharmacokinetic booster, inhibiting CYP3A4 metabolism and increasing lopinavir plasma levels. Always 🔗 check the BNF entry here for current dosing, interactions, and cautions.

🧠 Mode of Action

• Lopinavir inhibits the HIV-1 protease enzyme, preventing cleavage of viral gag-pol polyproteins.
• This blocks viral maturation, leading to the formation of non-infectious viral particles.
• Ritonavir is included in a low dose to inhibit hepatic CYP3A4, thereby boosting lopinavir concentrations and extending its half-life.

📋 Indications & Dose

• Used in combination ART (HAART) for HIV-1 infection in adults and children.
• Typical adult dose: 400 mg/100 mg twice daily (lopinavir/ritonavir), or 800 mg/200 mg once daily in selected patients.
• Take with food to optimise absorption and reduce GI effects.

⚠️ Interactions

• Both drugs are potent inhibitors of CYP3A4 and P-glycoprotein.
• May increase plasma concentrations of co-administered drugs such as statins, benzodiazepines, calcium-channel blockers, and corticosteroids.
• Reduced by CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenytoin).
• Always review concomitant therapy via the BNF or Liverpool HIV interaction checker.

🚧 Cautions

• Monitor for hepatic dysfunction — particularly in hepatitis B or C co-infection.
• May cause or worsen metabolic syndrome: dyslipidaemia, insulin resistance, and central adiposity.
• Monitor for PR interval prolongation or other conduction abnormalities in at-risk patients.
• Adherence is vital to prevent viral resistance.

⛔ Contraindications

• Severe hepatic impairment.
• Concurrent use with potent CYP3A4 inducers (e.g. rifampicin, St John’s wort).
• Known hypersensitivity to either drug.

💥 Side Effects

• 😣 Gastrointestinal disturbance — nausea, diarrhoea, abdominal pain.
• 📈 Metabolic effects: hyperlipidaemia, insulin resistance, and fat redistribution (lipodystrophy).
• 🟡 Hepatotoxicity — monitor liver enzymes regularly.
• Less common: rash, headache, QT prolongation.

📚 References

• BNF: Lopinavir with Ritonavir
• British HIV Association (BHIVA) Guidelines, 2023.
• European AIDS Clinical Society (EACS) Guidelines, 2023.