Darunavir Ethanolate (3 brand names, 2 dosage forms, 1 route)
Available dosage forms: TABLET, TABLET, FOR SUSPENSION.
Routes of administration: ORAL.
Brand Names
- DARUNAVIR ETHANOLATE
- PREZCOBIX
- PREZCOBIX PED
Indications and Usage
PREZCOBIX and PREZCOBIX PED are indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) in treatment-naïve and treatment-experienced adults and pediatric patients 3 years of age and older weighing at least 15 kg with no darunavir resistance-associated substitutions (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V) [see Use in Specific Populations (8.4) and Clinical Studies (14)].
Contraindications
Darunavir and cobicistat are both inhibitors of the cytochrome P450 3A (CYP3A) isoform. PREZCOBIX should not be co-administered with medicinal products that are highly dependent on CYP3A for clearance and for which increased plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index). Darunavir and cobicistat are both substrates of the cytochrome P450 3A (CYP3A) isoform. Co-administration of PREZCOBIX or PREZCOBIX PED with CYP3A inducers may lead to lower exposures of darunavir and cobicistat and potential loss of efficacy of darunavir and possible resistance. Examples of drugs that are contraindicated for co-administration with PREZCOBIX or PREZCOBIX PED [see Drug Interactions (7.3) and Clinical Pharmacology (12.3)] are listed below. Alpha 1-adrenoreceptor antagonist: alfuzosin Anticonvulsants: carbamazepine, phenobarbital, phenytoin Anti-gout: colchicine, in patients with renal and/or hepatic impairment Antimycobacterial: rifampin Antipsychotics: lurasidone, pimozide Cardiac Disorders: dronedarone, ivabradine, ranolazine Ergot derivatives, e.g. dihydroergotamine, ergotamine, methylergonovine Herbal product: St. John’s wort (Hypericum perforatum) Hepatitis C direct acting antiviral: elbasvir/grazoprevir Lipid modifying agents: lomitapide, lovastatin, simvastatin Opioid Antagonist: naloxegol PDE-5 inhibitor: sildenafil when used for treatment of pulmonary arterial hypertension Sedatives/hypnotics: orally administered midazolam, triazolam
Adverse Reactions
The following adverse reactions are discussed in other sections of the labeling: Hepatotoxicity [see Warnings and Precautions (5.1)] Severe skin reactions [see Warnings and Precautions (5.2)] Effects on serum creatinine [see Warnings and Precautions (5.3)] New onset or worsening renal impairment when used with tenofovir DF [see Warnings and Precautions (5.4)] Immune Reconstitution Syndrome [see Warnings and Precautions (5.10)]
Mechanism of Action
PREZCOBIX and PREZCOBIX PED are fixed-dose combinations of an HIV-1 antiviral drug, darunavir and a CYP3A inhibitor, cobicistat [see Microbiology (12.4)].
Overdosage
Human experience of acute overdose with PREZCOBIX or PREZCOBIX PED is limited. No specific antidote is available for overdose with PREZCOBIX or PREZCOBIX PED. Treatment of overdose with PREZCOBIX or PREZCOBIX PED consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. Since both darunavir and cobicistat are highly protein bound, dialysis is unlikely to be beneficial in significant removal of the active substance.