Nevirapine

Brand Names: Nevirapine

Drug Class: Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor

Overview

11 DESCRIPTION Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Nevirapine is structurally a member of the dipyridodiazepinone chemical class of compounds. The chemical name of nevirapine is 11-cyclopropyl-5, 11-dihydro-4-methyl-6H-dipyrido [3,2-b:2',3'-e][1,4] diazepin-6-one.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Nevirapine is an antiretroviral drug [see Microbiology ( 12.4 )]. 12.3 Pharmacokinetics Adults Absorption and Bioavailability The single-dose pharmacokinetics of nevirapine extended-release tablets was studied in 17 healthy volunteers. Nevirapine was absorbed with a median t max of approximately 24 hrs. The mean C max and AUC 0-∞ of nevirapine were 2060 ng per mL and 161,000 ng*hr/mL, respectively. The bioavailability of 400 mg of nevirapine extended-release tablets, relative to 400 mg of immediate-release nevirapine tablets, was approximately 75%.

Indications

  • 1 INDICATIONS & USAGE Nevirapine extended-release tablets are indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection in adults and pediatric patients 6 years of age or older with a body surface area (BSA) of 1.17 m 2 or greater [see Clinical Studies ( 14.1 , 14.2 )]. Limitations of Use: Based on serious and life-threatening hepatotoxicity observed in controlled and uncontrolled trials, nevirapine extended-release tablets are not recommended to be initiated, unless the benefit outweighs the risk, in: • adult females with...

Common Doses

  • 200 mg
  • 400 mg
  • 150 mg
  • 20 mL

Dosage

2 DOSAGE & ADMINISTRATION • The 14-day lead-in period with immediate-release nevirapine tablets (200 mg once daily) must be strictly followed; it has been demonstrated to reduce the frequency of rash. ( 2.5 , 5.2 ) • Must be swallowed whole and must not be chewed, crushed, or divided. ( 2.1 ) • Adult patients must initiate therapy with one 200 mg immediate-release nevirapine tablet once daily for the first 14 days, followed by one 400 mg tablet of nevirapine extended-release tablets once daily. ( 2.

Black Box Warning

WARNING: LIFE-THREATENING (INCLUDING FATAL) HEPATOTOXICITY and SKIN REACTIONS Severe, life-threatening, and in some cases fatal hepatotoxicity, particularly in the first 18 weeks, has been reported in patients treated with nevirapine. In some cases, patients presented with non-specific prodromal signs or symptoms of hepatitis and progressed to hepatic failure. These events are often associated with rash. Female sex and higher CD4+ cell counts at initiation of therapy place patients at increased risk; women with CD4+ cell counts greater than 250 cells/mm3, including pregnant women receiving...

Contraindications

  • 4 CONTRAINDICATIONS Nevirapine extended-release tablets are contraindicated: • in patients with moderate or severe (Child-Pugh Class B or C, respectively) hepatic impairment [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.7 )] . • for use as part of occupational and non-occupational post-exposure prophylaxis (PEP) regimens [see Warnings and Precautions ( 5.1 )]. • Patients with moderate or severe (Child-Pugh Class B or C, respectively) hepatic impairment. ( 4 , 5.1 , 8.

Side Effects

  • 6 ADVERSE REACTIONS • Adult patients: The most common adverse reaction is rash. During the lead-in period with immediate-release nevirapine tablets, the incidence of Grade 2 or higher drug-related rash in adults is 3%. After the lead-in period the incidence of Grade 2 or higher drug-related rash in subjects taking nevirapine extended-release tablets is 3%. The incidence of Grade 2 or higher drug-related clinical hepatitis after the lead-in phase was 2%. ( 6.1 ) • Pediatric patients: The incidence of Grade 2 or higher drug-related rash was 1%. ( 6.

Interactions

  • 7 DRUG INTERACTIONS Nevirapine is principally metabolized by the liver via the cytochrome P450 isoenzymes, 3A and 2B6. Nevirapine is known to be an inducer of these enzymes. As a result, drugs that are metabolized by these enzyme systems may have lower than expected plasma levels when co-administered with nevirapine. The results of drug interactions studies with immediate-release nevirapine tablets are expected to also apply to nevirapine extended-release tablets.