Lopinavir boosted with ritonavir is a potentiated protease inhibitor widely used in HIV treatment, especially in second-line regimens. Ritonavir inhibits CYP3A4, increasing lopinavir levels.
Also known as: Kaletra, LPV/r
Lopinavir/ritonavir potently inhibits CYP3A4, raising atorvastatin levels ~4-8 fold. High risk of myopathy and rhabdomyolysis. Avoid or drastically reduce dose.
Ritonavir (lopinavir booster) is a potent and irreversible CYP3A4 inhibitor, the main enzyme of atorvastatin metabolism. Pharmacokinetic studies demonstrated that coadministration with ritonavir (400 mg twice daily) elevates atorvastatin AUC by 4-8 fold and Cmax by 3-5 fold. This significant accumulation drastically increases the risk of myopathy (muscle pain, weakness, CK elevation) and rhabdomyolysis (muscle breakdown with risk of acute renal failure and potentially fatal hyperkalaemia). The lopinavir/ritonavir (Kaletra) and atorvastatin labels recommend limiting atorvastatin to 10 mg/day when coadministered with potent CYP3A4 inhibitors. Preferred alternative: pravastatin or rosuvastatin (CYP3A4-independent metabolism). If atorvastatin is unavoidable, monitor CK weekly during the first months.
Lopinavir/r + atorvastatin: CYP3A4 inhibition → atorvastatin levels elevated 4-8x. Risk of myopathy/rhabdomyolysis. Avoid or limit to 10 mg/day.
Ritonavir (booster) irreversibly inhibits CYP3A4, the main enzyme of atorvastatin metabolism. Atorvastatin AUC increases significantly.
CK (creatine kinase), transaminases, myopathy symptoms (muscle pain, weakness, dark urine).
Myopathy, rhabdomyolysis (potentially fatal), renal failure.
AVOID the combination. If unavoidable, limit atorvastatin to 10 mg/day and monitor CK. Alternative: pravastatin or rosuvastatin (CYP3A4-independent).
DailyMed/FDA (NIH/NLM) — approved Lopinavir + Ritonavir (Kaletra) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8290add3-4449-4e58-6c97-8fe1eec972e3 ; approved Atorvastatin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3143a3ff-f186-4a21-b217-ff73b0e9c85e
Food increases lopinavir absorption by 48%. Can be taken with or without food, but consistency is recommended.
Always take with food or always without food to maintain consistent levels.
DailyMed/FDA (NIH/NLM) — approved Lopinavir + Ritonavir (Kaletra) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8290add3-4449-4e58-6c97-8fe1eec972e3
No documented disease interactions.
Can be used during pregnancy with caution. Limited studies did not demonstrate significant teratogenicity.
Can be used in all trimesters when indicated. Monitor glycaemia and lipid profile.
Excreted in breast milk. Artificial feeding is recommended for HIV-positive mothers.
Reliable contraceptive methods are recommended.
DailyMed/FDA (NIH/NLM) — approved Lopinavir + Ritonavir (Kaletra) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8290add3-4449-4e58-6c97-8fe1eec972e3
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Lopinavir is a protease inhibitor boosted by ritonavir, used in first- and second-line HIV regimens.
Binds to the catalytic site of HIV-1 protease, preventing processing of viral polyproteins into structural proteins and functional enzymes. Ritonavir acts as a pharmacokinetic booster by irreversibly inhibiting CYP3A4.
Oral bioavailability increased by food presence (48%). Tmax: 4-6 hours. Plasma protein binding 98-99%. Volume of distribution: 0.17 L/kg.
Lopinavir is metabolised by CYP3A4. Ritonavir potently and irreversibly inhibits CYP3A4, increasing lopinavir plasma levels by ~100-fold. The combination allows lower dose and less frequent dosing.
Half-life: 5-6 hours (with ritonavir). Elimination: ~80% faeces, ~10% urine (metabolites). Lipid profile should be monitored.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
