Lopinavir
💊 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
