nevirapine
Viramune

Available forms
Available by prescription only
Oral suspension: 50 mg/5 ml
Tablets: 200 mg

Indications and dosages
 Treatment of patients with HIV-1 infection (with other antiretrovirals). Adults and adolescents: 200 mg P.O. daily for first 14 days, followed by 200 mg P.O. q 12 hours.
Children ages 2 months to 8 years: 4 mg/kg P.O. once daily for first 14 days, followed by 7 mg/kg P.O. q 12 hours thereafter. Maximum, 400 mg daily.
Children age 8 and older: 4 mg/kg P.O. once daily for first 14 days, followed by 4 mg/kg P.O. q 12 hours thereafter. Maximum, 400 mg daily. Or, children may receive 120 mg/m² P.O. daily for first 14 days, followed by 120 to 200 mg/m² q 12 hours.
Neonates ◇: 5 mg/kg P.O. daily for first 14 days followed by 120 mg/m² q 12 hours for next 14 days; then 200 mg/m² q 12 hours.

Pharmacodynamics
Antiviral action: Nevirapine binds directly to reverse transcriptase and blocks RNA-dependent and DNA-dependent DNA polymerase activities by disrupting the catalytic site of the enzyme.

Pharmacokinetics
Absorption: Readily absorbed.
Distribution: Widely distributed, crosses the placental barrier, and appears in breast milk. It’s about 60% bound to plasma proteins.
Metabolism: Extensively metabolized in the liver.
Excretion: Metabolites are primarily excreted in urine; a small amount of drug is excreted in feces.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use cautiously in patients with impaired renal or hepatic function because the pharmacokinetics of nevirapine haven’t been evaluated in these patients.

Interactions
Drug-drug. Drugs extensively metabolized by P-450 CYP3A: Nevirapine may lower plasma levels of these drugs. Dosage adjustment of these drugs may be required.
Hormonal contraceptives, protease inhibitors: Decreases plasma levels of these drugs. Use cautiously.
Ketoconazole: Decreases ketoconazole levels. Avoid using together.
Drug-herb. St. John’s wort: Decreases nevirapine levels. Discourage use together.

Adverse reactions
CNS: headache, peripheral neuropathy, paresthesia, fever.
GI: nausea, diarrhea, abdominal pain, ulcerative stomatitis.
Hematologic: neutropenia, eosinophilia.
Hepatic: hepatitis, hepatotoxicity.
Musculoskeletal: myalgia.
Skin: rash, Stevens-Johnson syndrome, facial edema, epidermic necrolysis.

Effects on lab test results
• May increase ALT, AST, GGT, and bilirubin levels.
• May increase eosinophil count. May decrease hemoglobin and neutrophil count.

Overdose and treatment
No information available.

Special considerations
• Nevirapine is usually used in three-drug regimens.
• Resistant virus emerges rapidly when drug is given alone. Always administer with at least one other antiretroviral.
• Using a 200-mg lead-in dose may decrease rash.
• Discontinue drug if patient develops a severe rash or a rash accompanied by fever, blistering, oral lesions, conjunctivitis, swelling, muscle or joint aches, or general malaise. If rash occurs during the initial 14 days, don’t increase dosage until it has resolved. Most rashes occur during the first 6 weeks of therapy.
• Severe, life-threatening cases of hepatotoxicity, including hepatitis, hepatic necrosis, and hepatic failure, have been reported.
• Stop drug temporarily in patients with moderate or severe liver function test abnormalities (excluding GGT) until values have returned to baseline. May restart drug at half the previous dose level. If moderate or severe liver function test abnormalities recur, discontinue drug therapy. Monitor liver function test results closely.
• If therapy is interrupted for longer than 7 days, restart it as though giving drug for the first time.
• If disease progresses during therapy, consider alternative antiretroviral therapy.
Breast-feeding patients
• Drug appears in breast milk. HIV-infected women shouldn’t breast-feed.
Pediatric patients
• Safety and efficacy in children haven’t been established.

Patient education
• Inform patient that drug doesn’t cure HIV infection and that illnesses linked to advanced HIV-1 infection may still occur. Also, tell patient that drug doesn’t reduce risk of transmission of HIV-1 to others through sexual contact or blood contamination.
• Instruct patient to report rash immediately. Therapy may need to be stopped temporarily.
• Advise patient that drug may be taken with or without food.
• Stress the importance of taking drug exactly as prescribed. Tell patient to take a missed dose as soon as possible but not to double the next dose if he skips one.
• Tell patient not to take other drugs without medical approval.
• Advise women of childbearing age to avoid hormonal contraceptives and other hormonal methods of birth control during therapy.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use