cobicistat + darunavir ethanolate: prescribing and clinical use
Focused clinical detail for use alongside current product information, local policy and patient-specific assessment.
cobicistat + darunavir ethanolate: clinical details
Prescribing considerations
- Management by an HIV-experienced clinician.
- Review genotype, darunavir resistance-associated mutations, previous antiretroviral exposure, virological status and CD4 count when assessing suitability.
- Complete a comprehensive interaction review, including corticosteroids, recreational substances, herbal products and non-prescription products.
- Do not initiate during pregnancy; arrange prompt specialist review if pregnancy occurs.
- Use caution in older adults and in mild or moderate hepatic impairment.
Contraindications and cautions
- Hypersensitivity to darunavir, cobicistat or an excipient.
- Severe hepatic impairment.
- Strong CYP3A inducers, including rifampicin, carbamazepine, phenobarbital, phenytoin and St John’s wort.
- Products for which CYP3A inhibition could cause serious toxicity, including selected antiarrhythmics, antipsychotics, sedatives and statins.
Monitoring
- HIV viral load and clinical response; perform resistance testing if response is absent or lost.
- Liver function, with closer monitoring for chronic hepatitis, cirrhosis or elevated baseline transaminases.
- Renal function and interacting renal medicines; cobicistat can modestly raise creatinine by inhibiting tubular creatinine secretion.
- Blood lipids, glucose and weight as clinically appropriate.
- Adverse effects and response of interacting medicines.
Clinical pharmacology
Darunavir inhibits HIV-1 protease-mediated polyprotein cleavage. Cobicistat is a mechanism-based CYP3A inhibitor that enhances darunavir exposure and inhibits P-glycoprotein and several other transporters; it has no intrinsic anti-HIV activity.
Formulation and product differences
- The selected product is a fixed-combination film-coated tablet.
- It should normally be swallowed whole; when necessary, it may be split with a tablet cutter and both pieces consumed immediately.
- It must be taken with food because darunavir exposure is substantially higher under fed conditions.
cobicistat + darunavir ethanolate preparations and strengths
Tablet
Route: Oral
Strengths: 800 mg + 150 mg
cobicistat + darunavir ethanolate interactions
Clinically important interactions are common. The HIV team should check all products before they are started, stopped or changed.
Rifampicin, carbamazepine, phenytoin, phenobarbital or St John’s wort
These can markedly reduce treatment exposure and cause loss of HIV control; co-administration is contraindicated.
Simvastatin or lovastatin
Concentrations and muscle-toxicity risk may rise substantially; co-administration is contraindicated.
Fluticasone, budesonide and other CYP3A-metabolised corticosteroids
Systemic steroid exposure may increase, causing adrenal suppression or Cushing’s syndrome; alternatives and monitoring may be needed.
Sources
These sources were used to prepare and review this medicine page.
Prepared and reviewed by the iatroX editorial team.