LOPINAVIR; RITONAVIR
Clinical safety rating: safe
Animal studies have demonstrated safety
Lopinavir is an HIV-1 protease inhibitor that prevents cleavage of viral Gag-Pol polyprotein precursors, resulting in immature, non-infectious viral particles. Ritonavir is a potent CYP3A4 inhibitor used at low doses to boost lopinavir plasma levels.
| Metabolism | Extensively metabolized in the liver via CYP3A4 isoenzyme; both lopinavir and ritonavir are substrates and inhibitors of CYP3A4. |
| Excretion | Primarily hepatic metabolism via CYP3A4; fecal excretion of metabolites (approximately 82-90%); renal excretion of unchanged drug is negligible (<3%). |
| Half-life | Lopinavir: 5-6 hours; Ritonavir: 3-5 hours. When coadministered, ritonavir inhibits lopinavir metabolism, resulting in a prolonged lopinavir half-life (~5-6 hours) allowing twice-daily dosing. |
| Protein binding | Lopinavir: 98-99% bound to alpha-1-acid glycoprotein and albumin; Ritonavir: 98-99% bound primarily to alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | Lopinavir: 0.8-1.0 L/kg (high tissue penetration); Ritonavir: 0.4-0.6 L/kg. Large Vd indicates extensive extravascular distribution. |
| Bioavailability | Oral: Lopinavir alone has low bioavailability (~25%); coformulation with ritonavir (as a pharmacokinetic booster) increases lopinavir bioavailability to approximately 70-80%. |
| Onset of Action | Oral: Maximum viral load reduction occurs within 2-4 weeks of continuous therapy; no immediate clinical effect. |
| Duration of Action | Therapeutic drug concentrations maintained over 12 hours with twice-daily dosing; trough concentrations should remain above 1 μg/mL for optimal virologic suppression. |
Lopinavir 400 mg / Ritonavir 100 mg (two tablets or 5 mL oral solution) orally twice daily with food. Alternatively, once-daily dosing (800/200 mg) may be used in treatment-naïve patients with <3 lopinavir resistance mutations.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment (including hemodialysis) as lopinavir/ritonavir is hepatically metabolized and <3% excreted renally. However, the oral solution contains 42.4% ethanol and 15.3% propylene glycol; avoid in patients with end-stage renal disease due to accumulation of propylene glycol. |
| Liver impairment | Child-Pugh A: No dose adjustment. Child-Pugh B: Reduce dose to lopinavir 300 mg / ritonavir 75 mg twice daily (not available as fixed-dose; consider alternative if unable to achieve adjusted dose). Child-Pugh C: Contraindicated due to risk of toxicity. |
| Pediatric use | Based on body weight or BSA. For children ≥14 days old: 300 mg/m² lopinavir / 75 mg/m² ritonavir orally twice daily (oral solution preferred for doses <400/100 mg). Capsules: if weight ≥40 kg or BSA ≥1.4 m², use adult dose. Oral solution: lopinavir 10–16 mg/kg (max 400 mg) plus ritonavir 2.5–4 mg/kg (max 100 mg) twice daily, based on weight bands (e.g., 7–10 kg: 1.25 mL twice daily). |
| Geriatric use |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
A strong inhibitor of CYP3A4 affecting many drugs Can cause GI intolerance hepatotoxicity and pancreatitis.
| Breastfeeding | Lopinavir/ritonavir is excreted into human milk in low concentrations. Milk-to-plasma ratio is approximately 0.2 for lopinavir. Limited data suggest minimal risk to breastfed infant; however, current guidelines in high-income countries recommend avoidance of breastfeeding in HIV-positive women to prevent transmission. In other contexts, consider infant exposure and alternative antiretroviral options. |
| Teratogenic Risk | Lopinavir/ritonavir is classified as FDA Pregnancy Category C. First trimester: limited human data, but no increased risk of major malformations observed in cohort studies; theoretical risk due to CYP3A4 inhibition. Second and third trimesters: no evidence of fetal toxicity; pharmacokinetic changes may reduce drug exposure. Overall risk is low, but use only if benefit outweighs risk. |
■ FDA Black Box Warning
None
| Common Effects | Nausea |
| Serious Effects |
["Hypersensitivity to any component","Concomitant use with drugs highly dependent on CYP3A4 clearance (e.g., alfuzosin, amiodarone, astemizole, colchicine, dronedarone, ergot derivatives, lovastatin, midazolam, pimozide, rifampin, sildenafil for PAH, simvastatin, St. John's wort, tadalafil for PAH, triazolam)","Severe hepatic impairment (Child-Pugh Class C)"]
| Precautions | ["Hepatotoxicity: cases of hepatic injury, including fatalities, reported; monitor liver enzymes.","Pancreatitis: use with caution in patients with history of pancreatitis.","Cardiac conduction abnormalities: PR interval prolongation, risk of atrioventricular block.","Lipid disorders: elevations in triglycerides and cholesterol.","Drug interactions: many due to CYP3A4 inhibition; avoid coadministration with drugs highly dependent on CYP3A4.","Hemophilia: increased bleeding in patients with hemophilia A or B.","Immune reconstitution syndrome."] |
Loading safety data…
| No specific dose adjustment is recommended but caution is advised due to age-related decreases in hepatic function, potential for decreased renal function (though not affecting lopinavir clearance), and increased risk of comorbidities (e.g., cardiac conduction abnormalities). Monitor for side effects and drug interactions. No routine dose reduction; start at standard dose and titrate based on tolerability. |
| Fetal Monitoring | Maternal monitoring: complete blood count, liver function tests, renal function, lipid profile, glucose tolerance test (due to risk of hyperglycemia), and adherence assessment. Fetal monitoring: routine prenatal ultrasound; consider growth scans if prolonged use. Neonatal monitoring: observe for potential hypoglycemia, hyperbilirubinemia, and hepatic effects. |
| Fertility Effects | Lopinavir/ritonavir does not significantly impair fertility in males or females based on animal and limited human data. In women, no known impact on ovulation or implantation. In men, no significant effect on sperm parameters. However, HIV infection itself may reduce fertility, and treatment may improve overall reproductive health. |