Darunavir

Brand Names: Darunavir

Drug Class: Protease Inhibitor

Overview

11 DESCRIPTION Darunavir is an inhibitor of the human immunodeficiency virus (HIV-1) protease. Darunavir tablets contain the active ingredient darunavir which has the following chemical name: [(1S,2R)-3-[[(4-aminophenyl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Darunavir is an HIV-1 antiviral drug [see Microbiology ( 12.4 )] . 12.2 Pharmacodynamics Cardiac Electrophysiology In a thorough QT/QTc study in 40 healthy subjects, darunavir/ritonavir doses of 1.33 times the maximum recommended dose did not affect the QT/QTc interval. 12.3 Pharmacokinetics Pharmacokinetics in Adults General Darunavir is primarily metabolized by CYP3A. Ritonavir inhibits CYP3A, thereby increasing the plasma concentrations of darunavir. When a single dose of darunavir 600 mg was given orally in combination with 100 mg ritonavir twice daily, there was an approximate 14-fold increase in the systemic exposure of darunavir.

Indications

  • 1 INDICATIONS AND USAGE Darunavir, co-administered with ritonavir (darunavir/ritonavir), in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV-1) infection in adult and pediatric patients 3 years of age and older [see Use in Specific Populations ( 8.4 ) and Clinical Studies ( 14 )]. Darunavir is a human immunodeficiency virus (HIV-1) protease inhibitor indicated for the treatment of HIV-1 infection in adult and pediatric patients 3 years of age and older.

Common Doses

  • 800 mg
  • 100 mg
  • 600 mg
  • 8 mL

Dosage

2 DOSAGE AND ADMINISTRATION Testing: In treatment-experienced patients, treatment history genotypic and/or phenotypic testing is recommended prior to initiation of therapy with darunavir/ritonavir to assess drug susceptibility of the HIV-1 virus ( 2.1 , 12.4 ) Monitor serum liver chemistry tests before and during therapy with darunavir/ritonavir. ( 2.1 , 2.2 , 5.2 ) Treatment-naïve adult patients and treatment-experienced adult patients with no darunavir resistance associated substitutions: 800 mg (one 800 mg tablet) taken with ritonavir 100 mg once daily and with food. ( 2.

Contraindications

  • 4 CONTRAINDICATIONS Co-administration of darunavir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index). Examples of these drugs and other contraindicated drugs (which may lead to reduced efficacy of darunavir) are listed below [see Drug Interactions ( 7.3 )] . Due to the need for co-administration of darunavir with ritonavir, please refer to ritonavir prescribing information for a description of ritonavir contraindications.

Side Effects

  • 6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of labeling: Hepatotoxicity [see Warnings and Precautions ( 5.2 )] Severe Skin Reactions [see Warnings and Precautions ( 5.3 )] Diabetes Mellitus/Hyperglycemia [see Warnings and Precautions ( 5.6 )] Fat Redistribution [see Warnings and Precautions ( 5.7 )] Immune Reconstitution Syndrome [see Warnings and Precautions ( 5.8 )] Hemophilia [see Warnings and Precautions ( 5.

Interactions

  • 7 DRUG INTERACTIONS Co-administration of darunavir/ritonavir with other drugs can alter the concentrations of other drugs and other drugs may alter the concentrations of darunavir. The potential drug-drug interactions must be considered prior to and during therapy. ( 4 , 5.5 , 7 , 12.3 ) 7.1 Potential for Darunavir/ritonavir to Affect Other Drugs Darunavir co-administered with ritonavir is an inhibitor of CYP3A, CYP2D6 and P-gp.