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Active ingredient: Nevirapine - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Anti-HIV Agents
  • Nonnucleoside Reverse Transcriptase Inhibitors

Dosage Forms

  • Tablets
  • Oral suspension

Brands / Synonyms

NEV; Nevirapine [Usan:Inn]; NVP; Viramune; Viramune

Indications

For use in combination with other antiretroviral drugs in the ongoing treatment of HIV-1 infection.

Pharmacology

Nevirapine is a non-nucleoside reverse transcriptase inhibitor (nNRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). HIV-2 RT and eukaryotic DNA polymerases (such as human DNA polymerases alpha, beta, or sigma) are not inhibited by nevirapine. Nevirapine is, in general, only prescribed after the immune system has declined and infections have become evident. It is always taken with at least one other HIV medication such as Retrovir or Videx. The virus can develop resistance to nevirapine if the drug is taken alone, although even if used properly, nevirapine is effective for only a limited time.

Mechanism of Action

Nevirapine binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. The activity of nevirapine does not compete with template or nucleoside triphosphates.

Absorption

90% (absolute bioavailability 93 ± 9%)

Toxicity

Symptoms of overdose include edema, erythema nodosum, fatigue, fever, headache, insomnia, nausea, pulmonaryinfiltrates, rash, vertigo, vomiting, and weight decrease.

Biotrnasformation / Drug Metabolism

Hepatic. In vivo studies in humans and in vitro studies with human liver microsomes have shown that nevirapine is extensively biotransformed via cytochrome P450 3A4 metabolism to several hydroxylated metabolites.

Contraindications

VIRAMUNE (nevirapine) is contraindicated in patients with clinically significant hypersensitivity to any of the components contained in the tablet or the oral suspension.

Drug Interactions

Nevirapine is principally metabolized by the liver via the cytochrome P450 isoenzymes, 3A4 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 coadministered with nevirapine.

The specific pharmacokinetic changes that occur with co-administration of nevirapine and other drugs are listed in CLINICAL PHARMACOLOGY, Table 1. Clinical comments about possible dosage modifications based on these pharmacokinetic changes are listed in Table 3. The data inTables 1 and 3 are based on the results of drug interaction studies conducted in HIV-1 seropositive subjects unless otherwise indicated.

In addition to established drug interactions, there may be potential pharmacokinetic interactions between nevirapine and other drug classes that are metabolized by the cytochrome P450 system. These potential drug interactions are listed in Table 4. Although specific drug interaction studies in HIV-1 seropositive subjects have not been conducted for the classes of drugs listed in Table 4, additional clinical monitoring may be warranted when co-administering these drugs.

The in vitro interaction between nevirapine and the antithrombotic agent warfarin is complex. As a result, when giving these drugs concomitantly, plasma warfarin levels may change with the potential for increases in coagulation time. When warfarin is co-administered with nevirapine, anticoagulation levels should be monitored frequently.

Table 3 Established Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies
Drug Name
Effect on Concentration of Nevirapine or Concomitant Drug
Clinical Comment
Clarithromycin
¯ Clarithromycin ­14OH- clarithromycin
Clarithromycin exposure was significantly decreased by nevirapine; however, 14-OH metabolite concentrations were increased.Because clarithromycin active metabolite has reduced activity against Mycobacteriumavium-intracellulare complex, overallactivity against this pathogen may bealtered. Alternatives to clarithromycin,such as azithromycin, should be considered.
Efavirenz
¯ Efavirenz
Appropriate doses for this combination are not established.
Ethinyl estradiol and Norethindrone

¯ Ethinyl estradiol ¯Norethindrone

Oral contraceptives and other hormonalmethods of birth control should not be usedas the sole method of contraception inwomen taking nevirapine, since nevirapinemay lower the plasma levels of thesemedications. An alternative or additional method of contraception is recommended.
Fluconazole
­ Nevirapine
Because of the risk of increased exposure tonevirapine, caution should be used inconcomitant administration, and patients should be monitored closely for nevirapine-associated adverse events.
Indinavir
¯ Indinavir
Appropriate doses for this combination arenot established, but an increase in thedosage of indinavir may be required.
Ketoconazole
¯ Ketoconazole
Nevirapine and ketoconazole should not beadministered concomitantly becausedecreases in ketoconazole plasmaconcentrations may reduce the efficacy of the drug.
Lopinavir/Ritonavir
¯ Lopinavir
A dose increase of lopinavir/ritonavir to 533/133 mg twice daily with food isrecommended in combination with nevirapine.
Methadone
¯ Methadonea
Methadone levels may be decreased;increased dosages may be required toprevent symptoms of opiate withdrawal.Methadone maintained patients beginningnevirapine therapy should be monitored forevidence of withdrawal and methadone dose should be adjusted accordingly.
Nelfinavir

¯ Nelfinavir M8 Metabolite ¯NelfinavirCmin

 

The appropriate dose for nelfinavir incombination with nevirapine, with respectto safety and efficacy, has not been established.
Rifabutin
­Rifabutin
Rifabutin and its metabolite concentrationswere moderately increased. Due to highintersubject variability, however, somepatients may experience large increases inrifabutin exposure and may be at higher riskfor rifabutin toxicity. Therefore, caution should be used in concomitant administration.
Rifampin
¯ Nevirapine
Nevirapine and rifampin should not beadministered concomitantly becausedecreases in nevirapine plasmaconcentrations may reduce the efficacy ofthe drug. Physicians needing to treatpatients co-infected with tuberculosis andusing a nevirapine containing regimen mayuse rifabutin instead.
Saquinavir
¯Saquinavir
Appropriate doses for this combination arenot established, but an increase in thedosage of saquinavir may be required.

aBased on reports of narcotic withdrawal syndrome in patients treated with nevirapine and methadone concurrently, and evidence of decreased plasma concentrations of methadone.

Table 4        Potential Drug Interactions:Use With Caution, Dose Adjustment of Co-administered Drug May Be Needed due to Possible Decrease in Clinical Effect
Examples of Drugs in Which Plasma Concentrations May Be Decreased By Co-administration With Nevirapine
Drug Class Examples of Drugs
Antiarrhythmics
Amiodarone, disopyramide, lidocaine
Anticonvulsants
Carbamazepine, clonazepam, ethosuximide
Antifungals
Itraconazole
Calcium channel blockers
Diltiazem, nifedipine, verapamil
Cancer chemotherapy
Cyclophosphamide
Ergot alkaloids
Ergotamine
Immunosuppressants
Cyclosporin, tacrolimus, sirolimus
Motility agents
Cisapride
Opiate agonists
Fentanyl
Examples of Drugs in Which Plasma Concentrations May Be Increased By Co-administration With Nevirapine
Antithrombotics
Warfarin
Potential effect on anticoagulation. Monitoring of
anticoagulation levels is recommended.

Fat redistribution: Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.

 

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