lopinavir + ritonavir: clinical use

Prescribing considerations

• Prescribing should be supervised by clinicians experienced in HIV treatment and used as part of combination antiretroviral therapy.
• Review complete medication, supplement and recreational-drug history because CYP3A and transporter interactions are extensive.
• Use resistance testing and treatment history when considering use after previous protease-inhibitor exposure.
• Consider pancreatitis risk, significant hypertriglyceridaemia, haemophilia, diabetes, chronic viral hepatitis and cardiac conduction disease.
• For the oral solution, account for alcohol and propylene glycol from all sources and minimise calculation, transcription and measurement errors, particularly in infants.

Contraindications and cautions

• Hypersensitivity to lopinavir, ritonavir or product excipients.
• Severe hepatic insufficiency.
• Co-administration with medicines whose CYP3A-mediated accumulation can cause serious or life-threatening toxicity, including specified antiarrhythmics, sedatives, antipsychotics, statins and ergot derivatives.
• St John's wort because it may reduce antiviral exposure.
• The oral solution is additionally contraindicated in children younger than 14 days, pregnancy, hepatic or renal failure, and with disulfiram or metronidazole because of propylene glycol toxicity risk.

Monitoring

• HIV viral load, clinical response and adherence; CD4 count where clinically appropriate.
• Baseline and ongoing liver function, with closer observation in pre-existing liver disease or viral hepatitis.
• Blood lipids and glucose.
• Clinical assessment and pancreatic enzymes if pancreatitis is suspected.
• ECG where conduction disease or interacting medicines create PR- or QT-related risk.
• For oral-solution use in vulnerable infants, monitor for metabolic, renal, neurological, respiratory and cardiac toxicity.

Clinical pharmacology

Lopinavir inhibits HIV-1 and HIV-2 protease. Ritonavir inhibits CYP3A-mediated lopinavir metabolism, producing pharmacokinetic boosting; lopinavir provides the principal antiviral activity.

Formulation and product differences

• Tablets must be swallowed whole and may be taken with or without food.
• The oral solution must be taken with food, requires calibrated-syringe measurement and contains substantial alcohol and propylene glycol.
• The oral solution is normally refrigerated; once stored outside the refrigerator at no more than 25°C, unused solution should be discarded after 42 days.

Oral solution

Route: Oral

Strengths: 80 mg + 20 mg