Trade Names:Viramune- Tablets 200 mg- Solution, oral 50 mg/mL (as hemihydrate)
NNRTI of HIV-1. Binds directly to reverse transcriptase and blocks the RNA-dependent and DNA-dependent DNA polymerase activities.
Nevirapine oral absorption is more than 90%, bioavailability is 93% (tablets) and 91% (oral solution), T max is 4 h, and C max is approximately 2 mcg/mL.
Nevirapine crosses the placenta and is found in breast milk. Protein binding is approximately 60% and is highly lipophilic and widely distributed. Nevirapine Vd is 1.21 L/kg (IV), and CSF approximates 45% of concentration in plasma.
Extensively metabolized by CYP isozymes. In vitro studies indicated that metabolism is primarily by CYP2B6 and CYP3A4.
Nevirapine is eliminated in urine (81.3%) and feces (10.1%). Less than 3% of the parent compound is excreted in urine. Autoinduction results in a decrease of the half-life from 45 h (single dose) to approximately 25 to 30 h (multiple doses).
No change in pharmacokinetics in patients with mild, moderate, or severe renal impairment.Elderly
Pharmacokinetics do not appear to change within the range of 18 to 68 yr of age.Gender
Cl is 13.8% lower in women than men.Race
Pharmacokinetics have not been fully evaluated; however, no difference in steady-state trough levels were found based on ethnicity.
In combination with other antiretroviral agents for treatment of HIV-1 infection.
Moderate or severe (Child-Pugh class B or C) hepatic impairment.
PO 200 mg daily for 14 days. Total daily dose not to exceed 400 mg.Maintenance therapy
PO 200 mg twice daily in combination with other antiretroviral agents.Children 15 days of age and older
PO 150 mg/m 2 once daily for 14 days followed by 150 mg/m 2 twice daily thereafter (max, 400 mg daily).DialysisAdults and Children 15 days of age and older
PO An additional 200 mg following each dialysis.
Store tablets and oral suspension at 59° to 86°F.
Plasma levels may be decreased by nevirapine.Clarithromycin
Clarithromycin concentrations may be reduced, while concentrations of the active metabolite of clarithromycin may be increased.Contraceptives, hormonal
Lower hormone levels and potential contraceptive failure.Efavirenz, methadone
Concentrations of these agents may be decreased by nevirapine.Fluconazole
Nevirapine concentrations may be increased.HMG-CoA reductase inhibitors (eg, atorvastatin, simvastatin)
Risk of severe myopathy or rhabdomyolysis may be increased.Ketoconazole
Coadministration resulted in significant reduction in ketoconazole plasma concentrations. Do not coadminister ketoconazole and nevirapine.Protease inhibitors (eg, indinavir)
Lower protease inhibitor plasma levels.Rifabutin
Rifabutin concentrations may be increased.Rifampin, rifabutin, rosiglitazone
Lower nevirapine plasma levels.St. John's wort
May reduce nevirapine concentrations, resulting in loss of virologic response and possible resistance to nevirapine and the class of NNRTIs.Warfarin
Plasma concentrations of warfarin may be altered, resulting in potential increases in coagulation time.
None well documented.
Fatigue (5%); headache (4%); malaise, paresthesia, somnolence (postmarketing).
Rash (7% [21% in children]); Stevens-Johnson syndrome; toxic epidermal necrolysis (TEN); angioedema, blistering, bullous eruptions, facial edema, urticaria (postmarketing).
Nausea (9%); abdominal pain, diarrhea (2%); oral lesions, ulcerative stomatitis, vomiting (postmarketing).
Symptomatic hepatic events (4%); cholestatic hepatitis, hepatic failure, hepatic necrosis, hepatitis including fatal fulminant hepatitis, jaundice (postmarketing).
Neutropenia (9% in children); anemia (7% in children); anemia, eosinophilia, granulocytopenia, lymphadenopathy, neutropenia (postmarketing).
Hypersensitivity, including anaphylaxis, severe rash, or rash accompanied by blisters; conjunctivitis; facial edema; fatigue; fever; general malaise; muscle or joint aches; oral lesions (postmarketing).
Elevated ALT (14%); elevated AST (8%).
Redistribution and accumulation of body fat (postmarketing).
Arthralgia, rhabdomyolysis associated with skin and/or liver reaction (postmarketing).
Impaired renal function (postmarketing).
Severe, life-threatening skin reactions (sometimes fatal) occurred during therapy. Cases include Stevens-Johnson syndrome, TEN, and hypersensitivity reactions.Dosing
A 14-day initiation period (200 mg/day) must be strictly followed.Hepatotoxicity
Severe, life-threatening, and in some cases, fatal hepatotoxicity has been reported, especially in the first 18 wk. These events are often associated with a rash. The risk of reactions is increased in women and in patients with higher CD4 counts at the start of therapy. Women with CD4 counts higher than 250 cells/mm 3 receiving nevirapine with other antiretroviral agents are at the greatest risk. If clinical hepatitis or transaminase elevations combined with rash or other systemic symptoms occur, permanently discontinue therapy.Patient monitoring
Closely monitor for first 18 wk to detect signs and symptoms of skin/hepatic reactions.
Check transaminases immediately if a patient experiences signs or symptoms suggestive of hepatitis and/or hypersensitivity reactions. Check transaminases immediately for all patients who develop a rash in the first 18 wk of treatment. Monitor patients intensively during the first 18 wk of therapy to detect potentially life-threatening hepatotoxicity or skin reactions. Extra vigilance is warranted during the first 6 wk of therapy, which is the period of greatest risk.
Category B .
Excreted in breast milk. Ensure that HIV-infected mothers do not breast-feed their infants.
For use in children 15 days of age and older.
Select dose with caution, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.
In patients receiving chronic hemodialysis, additional dosing is needed following each dialysis treatment.
Do not administer to patients with moderate or severe hepatic impairment.
Do not restart treatment following severe hepatic, skin, or hypersensitivity reactions. Hepatic injury can progress after discontinuation of treatment.
Redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance, may occur.
Consider the possibility of hepatotoxicity for the appearance of signs or symptoms of hepatitis, including fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness, or hepatomegaly.
Has been reported.
Restart patients who interrupt maintenance dosing for more than 7 days on the recommended dosing (1 daily for 14 days followed by 1 twice daily).
When used as monotherapy, resistant virus emerges rapidly and uniformly.
Discontinue drug if skin rash accompanied by constitutional symptoms (eg, blistering, conjunctivitis, fever, general malaise, muscle or joint aches, oral lesions, swelling) occurs. If rash is mild to moderate in severity and not accompanied by constitutional symptoms, the drug can be continued with close monitoring. If rash develops during first 14 days of therapy, do not increase dosage beyond 200 mg daily until rash resolves.
Edema, erythema nodosum, fatigue, fever, headache, insomnia, nausea, pulmonary infiltrates, rash, vertigo, vomiting, weight decrease.
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