darunavir ethanolate: clinical use

Prescribing considerations

• Initiate and supervise through clinicians experienced in HIV management.
• Use within combination antiretroviral therapy with pharmacokinetic enhancement.
• Review treatment history, resistance-associated mutations and virological history.
• Interaction profiles differ between ritonavir and cobicistat.
• Use caution with sulphonamide allergy, pre-existing liver disease and older age.
• Darunavir with cobicistat is unsuitable during pregnancy.

Contraindications and cautions

• Hypersensitivity to darunavir or formulation excipients.
• Severe hepatic impairment.
• Rifampicin, St John's wort and lopinavir/ritonavir.
• Strong CYP3A inducers with cobicistat-enhanced darunavir.
• CYP3A-dependent medicines whose increased exposure can cause serious or life-threatening toxicity; consult the product-specific list.

Monitoring

• HIV viral load and clinical response; resistance testing if response is lost.
• Liver tests before and during treatment.
• Glucose and lipid changes.
• Rash and systemic hypersensitivity features.
• Renal function and creatinine-based estimates when cobicistat is used.
• Interactions whenever medicines, supplements or recreational substances change.

Clinical pharmacology

Darunavir inhibits HIV-1 protease dimerisation and catalytic activity, preventing cleavage of Gag-Pol polyproteins and production of mature infectious virions. It is extensively protein-bound and predominantly metabolised through CYP3A; ritonavir or cobicistat increases exposure by inhibiting clearance.

Formulation and product differences

• Film-coated tablets are intended for people able to swallow tablets.
• Oral suspension can be used when tablets cannot be swallowed and supports weight-based paediatric prescribing.
• Shake suspension vigorously and measure it using its dedicated oral pipette.
• The suspension contains sodium methyl parahydroxybenzoate, which may cause delayed allergic reactions.
• Do not change between tablet and suspension without specialist review.

Oral suspension

Route: Oral

Strengths: 100 mg/mL

Tablet

Route: Oral

Strengths: 800 mg