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Nevirapine
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DRUG INFO
Nevirapine
Drug Name:
Nevirapine
Indication: 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.
Drug Category: Anti-HIV Agents; Nonnucleoside Reverse Transcriptase Inhibitors; ATC:J05AG01
Brand Names/Synonyms: BIRG 0587; DRG-0116; HSDB 7164; NEV; NVP; Nevirapine; Nevirapine [Usan:Inn]; Viramune
Dosage Forms: Tablets, Oral suspension
Absorption: 90% (absolute bioavailability 93 ± 9%)
Interactions:
DrugBank: Interactions for Nevirapine
Interactions for Nevirapine:
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.
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Table 3 Established Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug
Interaction Studies
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Drug Name
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Effect on Concentration of Nevirapine or Concomitant Drug
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Clinical Comment
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Clarithromycin
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¯ Clarithromycin 14OH- clarithromycin
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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.
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Efavirenz
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¯ Efavirenz
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Appropriate doses for this combination are not established.
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Ethinyl estradiol and Norethindrone
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¯ Ethinyl estradiol ¯Norethindrone
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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.
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Fluconazole
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Nevirapine
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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.
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Indinavir
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¯ Indinavir
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Appropriate doses for this combination arenot established, but an increase in thedosage of indinavir may be
required.
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Ketoconazole
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¯ Ketoconazole
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Nevirapine and ketoconazole should not beadministered concomitantly becausedecreases in ketoconazole
plasmaconcentrations may reduce the efficacy of the drug.
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Lopinavir/Ritonavir
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¯ Lopinavir
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A dose increase of lopinavir/ritonavir to 533/133 mg twice daily with food isrecommended in combination with
nevirapine.
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Methadone
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¯ Methadonea
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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.
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Nelfinavir
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¯ Nelfinavir M8 Metabolite ¯NelfinavirCmin
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The appropriate dose for nelfinavir incombination with nevirapine, with respectto safety and efficacy, has
not been established.
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Rifabutin
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Rifabutin
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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.
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Rifampin
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¯ Nevirapine
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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.
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Saquinavir
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¯Saquinavir
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Appropriate doses for this combination arenot established, but an increase in thedosage of saquinavir may be
required.
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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 |
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Antiarrhythmics
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Amiodarone, disopyramide, lidocaine
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Anticonvulsants
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Carbamazepine, clonazepam, ethosuximide
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Antifungals
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Itraconazole
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Calcium channel blockers
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Diltiazem, nifedipine, verapamil
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Cancer chemotherapy
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Cyclophosphamide
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Ergot alkaloids
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Ergotamine
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Immunosuppressants
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Cyclosporin, tacrolimus, sirolimus
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Motility agents
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Cisapride
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Opiate agonists
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Fentanyl
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Examples of Drugs in Which Plasma Concentrations May Be Increased By Co-administration With
Nevirapine
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Antithrombotics
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Warfarin
Potential effect on anticoagulation. Monitoring of
anticoagulation levels is recommended.
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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.
Chemical IUPAC Name: 1-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido [3,2-b:2',3'-e][1,4] diazepin-6-one
Chemical Formula: C15H14N4O
Half Life: 45 hours
Drug Type: Approved Drug
# Accession No: APRD00705
CAS Registry Number: 129618-40-2
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Nevirapine News
(When available)
Aurobindo Pharma receives approval for Nevirapine Oral Suspension ... Jan 2, 2006
Myiris.com, This product is the first generic version of the approved product, Viramune Oral Suspension, 50 mg /5 ml, manufactured by Boehringer Ingelheim Pharmaceuticals. ...
Aurobindo Receives Tentative FDA Approval To Produce Oral Version ... Jan 5, 2006
Kaiser network.org, The approval is for 50-milligram/five milliliter oral solution of nevirapine, which is sold under the brand name Viramune by Boehringer Ingelheim (UNI/newKerala ...
ICAAC: Nevirapine’s manufacturer examines rates of liver ... Jan 9, 2006
Aidsmap, The high rates of liver side-effects seen in a major study of nevirapine (Viramune) may have been driven by unusual results from one study centre, according to ...
ICAAC: No added benefit from adding AZT to nevirapine to prevent ... Dec 18, 2005
Aidsmap, Adding a short course of AZT (zidovudine, Retrovir) to nevirapine (Viramune) therapy does not reduce the rate of mother-to-child transmission of HIV, according ...
ICAAC: Nevirapine still present in breastmilk two weeks after last ... Dec 19, 2005
Aidsmap, Nevirapine (Viramune) can persist in the breastmilk of HIV-positive women treated with the drug to prevent mother-to-child transmission of HIV for up to 14 ...
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