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nevirapine (Viramune, NVP)

Tradename: Viramune. Indications: treatment of HIV infection Contraindications: 1) women with CD4 counts > 250/mm3 (unless benefits clearly outweigh risks) 2) single-dose nevirapine given to prevent mother-to-child HIV transmission adversely affects virologic response to nevirapine in both women who initiate therapy < 6 months postpartum & their infants [8] 3) may be continued in pregnanct women doing well [10] 4) moderate to severe liver disease [9] Dosage: 1) 200 mg PO QD (x 14 days), if no rash develops, 200 mg PO BID 2) may be administered with or without food Note: Must be used with a nucleoside analog antiviral agent. Pharmacokinetics: 1) readily absorbed (> 90%) after oral administration 2) penetrates the blood brain barrier into the CSF 3) peak serum concentration: 2-4 hours 4) plasma 1/2life is approximately 25-30 hours 5) extensively metabolized in liver: hydroxylated by cyt P450 to inactive metabolites 6) 80% of metabolites are excreted in the urine Monitor: -> liver function tests [6,9] a) every 2 weeks for 1st month b) monthly for months 2-4 (3 months) c) every 1-3 months thereafter Adverse effects: 1) common (> 10%) - headache, fever, rash*, nausea, diarrhea, abdominal pain, thrombocytopenia, fatigue 2) less common (1-10%) - ulcerative stomatitis, anemia, hepatitis#, peripheral neuropathy, paresthesia, myalgia 3) other - hypersensitivity [4] * rash (bullous)/ Stevens-Johnson syndrome - life threatening skin reactions have occurred, generally within 6 weeks; rash often accompanies or heralds hepatotoxcity [9] # mild to moderate increases in liver function tests are not uncommon Drug interactions: 1) rifampin* 2) rifabutin* 3) oral contraceptives* 4) protease inhibitors* 5) triazolam* 6) midazolam* 7) amoxicillin in combination may increase risk of skin rash including Stevens-Johnson syndrome 8) erythromycin SHOULD NOT BE USED in combination - increased risk of hepatotoxicity 9) tolbutamide SHOULD NOT BE USED in combination - increased risk of toxicity 10) nevirapine induces cyt P450 3A4 -> may diminish levels of drugs metabolized by cyt P450 3A4 * careful monitoring if 1-6 used in combination Laboratory: - nevirapine in serum/plasma Mechanism of action: 1) non-nucleoside reverse transcriptase inhibitor 2) induces cyt P450 3A4 3) binds to specific region of HIV reverse transcriptase 4) emergence of resistance is a problem

Interactions

drug interactions drug adverse effects (more general classes)

Related

cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

General

heterocyclic compound, 3 rings non-nucleoside reverse transcriptase inhibitor (NNRTI)

Properties

MISC-INFO: elimination route LIVER KIDNEY 1/2life 25-30 DAYS pregnancy-category C safety in lactation -

Database Correlations

PUBCHEM cid=4463

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, 17. American College of Physicians, Philadelphia 1998, 2015
  5. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  6. Prescriber's Letter 9(8):44 2002
  7. FDA public health advisory http://www.fda.gov/cder/drug/advisory/Nevirapine.htm
  8. Lockman S, Shapiro RL, Smeaton LM, Wester C, Thior I, Stevens L, Chand F, Makhema J, Moffat C, Asmelash A, Ndase P, Arimi P, van Widenfelt E, Mazhani L, Novitsky V, Lagakos S, Essex M. Response to Antiretroviral Therapy after a Single, Peripartum Dose of Nevirapine. N Engl J Med. 2007 Jan 11;356(2):135-147. PMID: 17215531
  9. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com
  10. Zuger A Use of Antiretroviral Drugs in Pregnancy. Physician's First Watch, April 22, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. 2014. AIDSinfo. Clinical Guidelines Portal. March 28, 2014. http://aidsinfo.nih.gov/Guidelines/HTML/3/perinatal-guidelines/0 (corresponding NGC guideline withdrawn March 2016)

Component-of

lamivudine/nevirapine/zidovudine