darunavir: clinical use

Prescribing considerations

• Use only with an appropriate pharmacokinetic enhancer and other active antiretrovirals.
• Review treatment history, resistance results and virological status when selecting the formulation and booster.
• Reconcile prescription, non-prescription, herbal and recreational substances because interactions may be serious and booster-specific.
• Use caution with sulphonamide allergy, pre-existing liver disease and in older people, for whom clinical experience is limited.

Contraindications and cautions

• Hypersensitivity to darunavir or the selected product’s excipients.
• Severe hepatic impairment.
• Strong CYP3A inducers, including rifampicin and St John’s wort; additional inducers are contraindicated with cobicistat boosting.
• Medicines highly dependent on CYP3A clearance where increased exposure could cause serious or life-threatening harm, as listed in the product-specific SmPC.

Monitoring

• Assess viral load regularly; investigate adherence, interactions and resistance if virological response is inadequate or lost.
• Check liver function before treatment and during therapy, with closer monitoring for hepatitis B or C, cirrhosis or raised baseline transaminases.
• Monitor weight, blood glucose and lipids as clinically appropriate.
• Interpret renal markers in the context of the booster and accompanying antiretrovirals; cobicistat can raise serum creatinine by inhibiting tubular secretion.

Clinical pharmacology

Darunavir inhibits HIV-1 protease dimerisation and catalytic activity, preventing cleavage of Gag-Pol polyproteins and formation of mature infectious virions. It is highly protein-bound and primarily metabolised through CYP3A; ritonavir or cobicistat increases exposure through CYP3A inhibition.

Formulation and product differences

• The selected product is a darunavir-only film-coated tablet; the booster and other antiretrovirals are supplied separately.
• The selected tablet is yellow, oval and marked “V” and “7”.
• Oral suspension and other tablet formulations exist for patients whose swallowing ability or treatment requirements differ; substitution requires specialist review.

Tablet

Route: Oral

Strengths: 400 mg, 600 mg, 800 mg