No

Antiretroviral Agent, Reverse Transcriptase Inhibitor (Non-Nucleoside)

In combination therapy with other antiretroviral agents for the treatment of HIV-1 in adults

C

Clinical effects on the fetus: Administer nevirapine during pregnancy only if benefits to the mother outweigh the risk to the fetus

Breast-feeding/lactation: Avoid use during lactation, if possible

Previous hypersensitivity to nevirapine or its components; concurrent use with oral contraceptives and protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir)

Consider alteration of antiretroviral therapies if disease progression occurs while patients are receiving nevirapine. Resistant HIV virus emerges rapidly and uniformly when nevirapine is administered as monotherapy. Therefore, always administer in combination with at least 1 additional antiretroviral agent. Severe life-threatening skin reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, hypersensitivity reactions with rash and organ dysfunction) have occurred, usually within 6 weeks. If a severe skin or hypersensitivity reaction (severe rash, rash with fever, blisters, oral lesions, conjunctivitis, facial edema, muscle or joint aches, general malaise and/or hepatic abnormalities) occurs, discontinue nevirapine as soon as possible; mild to moderate alterations in LFTs are not uncommon, however, severe hepatotoxic reactions may occur rarely, and if abnormalities reoccur after temporarily discontinuing therapy, treatment should be permanently halted. Safety and efficacy have not been established in children.

>10%:

Central nervous system: Headache (11%), fever (8% to 11%)

Dermatologic: Rash (15% to 20%)

Gastrointestinal: Diarrhea (15% to 20%)

Hematologic: Neutropenia (10% to 11%)

1% to 10%:

Gastrointestinal: Ulcerative stomatitis (4%), nausea, abdominal pain (2%)

Hematologic: Anemia

Hepatic: Hepatitis, increased LFTs (2% to 4%)

Neuromuscular & skeletal: Peripheral neuropathy, paresthesia (2%), myalgia

<1%: Thrombocytopenia, Stevens-Johnson syndrome, hepatotoxicity, hepatic necrosis

No toxicities have been reported with acute ingestions of large sums of tablets

CYP3A3/4 enzyme substrate; CYP3A3/4 enzyme inducer; CYP3A3/4 enzyme inhibitor

Increased effect/toxicity with cimetidine, macrolides, ketoconazole

Methadone's plasma concentrations may decrease. Monitor for narcotic withdrawal and adjust methadone dose as needed.

Store at room temperature

As a non-nucleoside reverse transcriptase inhibitor, nevirapine has activity against HIV-1 by binding to reverse transcriptase. It consequently blocks the RNA-dependent and DNA-dependent DNA polymerase activities including HIV-1 replication. It does not require intracellular phosphorylation for antiviral activity.

Absorption: Oral: >90%

Distribution: V_d: 1.2-1.4 L/kg; widely distributed; distributes well into breast milk and crosses the placenta; CSF penetration approximates 50% of that found in the plasma

Protein binding, plasma: 50% to 60%

Metabolism: Extensively metabolized via cytochrome P-450 system (hydroxylation to inactive compounds); may undergo enterohepatic recycling

Half-life: Decreases over 2- to 4-week time with chronic dosing due to autoinduction (ie, half-life = 45 hours initially and decreases to 23 hours)

Time to peak serum concentration: 2-4 hours

Elimination: Renal elimination of metabolites; <3% of parent compound excreted in urine

Adults: Oral:

Maintenance: 200 mg twice daily (in combination with an additional antiretroviral agent)

Liver function tests periodically throughout therapy; observe for CNS side effects

None reported

Neutropenia is common; avoid clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

If rash develops stop medicine and contact prescriber. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

May be given with food, antacids, or didanosine; if a therapy is interrupted for >7 days, the dose should be decreased to the initial regimen and increased after 14 days

Suspension, oral: 50 mg/5 mL (240 mL)

Tablet: 200 mg

D'Aquila RT, Hughes MD, Johnson VA, et al, "Nevirapine, Zidovudine, and Didanosine Compared With Zidovudine and Didanosine in Patients With HIV-1 Infection. A Randomized, Double-Blind, Placebo-Controlled Trial. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group Protocol 241 Investigators," Ann Intern Med, 1996, 124(12):1019-30.

Hammer SM, Kessler HA, and Saag MS, "Issues in Combination Antiretroviral Therapy: A Review," J Acquir Immune Defic Syndr, 1994, 7(Suppl 2):S24-35.

Havlir DV and Lange JM, "New Antiretrovirals and New Combinations," AIDS, 1998, 12(Suppl A):S165-74.

Hilts AE and Fish DN, "Dosage Adjustment of Antiretroviral Agents in Patients With Organ Dysfunction," Am J Health Syst Pharm, 1998, 55:2528-33.

Mueller BU, Sei S, Anderson B, et al, "Comparison of Virus Burden in Blood and Sequential Lymph Node Biopsy Specimens From Children Infected With Human Immunodeficiency Virus," J Pediatr, 1996, 129(3):410-8.

Weverling GJ, Lange JM, Jurriaans S, et al, "Alternative Multidrug Regimen Provides Improved Suppression of HIV-1 Replication Over Triple Therapy," AIDS, 1998, 12(11):F117-22.

Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, "Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection," March 1, 1999, http://www.hivatis.org.