Darunavir with cobicistat

eMC SPC §4.2 (REZOLSTA 800 mg/150 mg film-coated tablets). Therapy should be initiated by a healthcare provider experienced in the management of HIV infection. INDICATION/POPULATION: the 800/150 mg once-daily regimen applies to adults and paediatric patients weighing at least 40 kg. ART-naive patients: recommended dose regimen is one 800 mg darunavir/150 mg cobicistat tablet once daily with food. ART-experienced patients: the same once-daily tablet may be used only in patients with prior antiretroviral exposure but WITHOUT darunavir resistance associated mutations (DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V, L89V) and who have plasma HIV-1 RNA < 100,000 copies/mL and CD4+ cell count >= 100 cells x 10^6/L. In all other ART-experienced patients, or if HIV-1 genotype testing is not available, use of this product is NOT appropriate and another antiretroviral regimen should be used. MISSED DOSE: if missed within 12 hours of the usual time, take the prescribed dose with food as soon as possible; if noticed later than 12 hours, skip the missed dose and resume the usual schedule. VOMITING: if the patient vomits within 4 hours of taking the dose, take another dose with food as soon as possible; if more than 4 hours after, no extra dose is needed until the next scheduled time. ELDERLY: limited information - use with caution above 65 years of age. HEPATIC IMPAIRMENT: no pharmacokinetic data for the combination; separate darunavir/ritonavir and cobicistat trials suggest no dose adjustment in mild (Child-Pugh A) or moderate (Child-Pugh B) impairment, but use with caution; must NOT be used in severe hepatic impairment (Child-Pugh C). PREGNANCY: treatment with darunavir/cobicistat 800/150 mg during pregnancy results in low darunavir exposure, so this combination should not be initiated during pregnancy and women who become pregnant on it should be switched to an alternative regimen (darunavir/ritonavir may be considered as an alternative). ADMINISTRATION AID: for patients unable to swallow the 800 mg/150 mg tablet whole it may be split into two pieces with a tablet-cutter, each piece consumed immediately after splitting. PAEDIATRIC (non-per-kg, fixed strengths - verify against a children's formulary): for paediatric patients aged 6 years and older weighing at least 25 kg to less than 40 kg the SPC states one 675 mg darunavir/150 mg cobicistat tablet once daily with food (ART-naive, and ART-experienced only under the same DRV-RAM / viral load / CD4 restrictions above); the 675/150 mg scored tablet may be split by hand into two pieces if it cannot be swallowed whole. Safety and efficacy in paediatric patients aged 3 to <6 years, or weighing <25 kg, have not been established (no data). Must NOT be used below 3 years of age because of toxicity and mortality observed in juvenile rats dosed with darunavir up to days 23 to 26 of age. NOTE ON US LABELLING: the openFDA label in this bundle is for darunavir given with RITONAVIR (not cobicistat) and therefore describes a different regimen; it was not used for the dose.