nevirapine (Rx)

Brand and Other Names:NVP, Viramune, more...Viramune XR
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

oral suspension

  • 10mg/mL

tablet, immediate-release

  • 200mg

tablet, extended-release

  • 100mg
  • 400mg

HIV Infection

Indicated for treatment of HIV-1 infection in combination with other antiretrovirals; also used for prevention of maternal-fetal HIV transmission in women with no prior antiretroviral treatment

200 mg PO qDay x 14 days, THEN

If no rash, increase to 200 mg q12hr; if rash occurs wait until it is resolved before increasing

Prevention of maternal-fetal HIV transmission: 200 mg PO as a single dose at onset of labor, in combination with IV zidovudine

Extended-release tablets

  • Initial therapy: When initiating therapy, give immediate-release tablet 200 mg PO qDay for 14 days, then extended-release tablet 400 mg PO qDay thereafter
  • Switch from immediate-release: If already taking immediate-release regimen, may switch to extended-release 400 mg PO qDay without 14-day lead-in period of immediate-release nevirapine

Dosing Considerations

Based on serious and life-threatening hepatotoxicity observed in controlled and uncontrolled trials, nevirapine should not be initiated in adult females with CD4+ cell counts >250 cells/mm³ or in adult males with CD4+ cell counts >400 cells/mm³ unless the benefit outweighs the risk

The 14-day lead-in period with immediate-release dosing must be strictly followed; it has been demonstrated to reduce the frequency of rash

If nevirapine extended-release interrupted >7 days, restart with lead-in dosing with immediate-release nevirapine

If mild-to-moderate rash (without constitutional symptoms) occurs during 14-day lead-in period, do not increase immediate-release dose or initiate extended-release regimen until the rash has resolved; duration of the lead-in dosing should not exceed 28 days, at which point an alternative regimen should be chosen; discontinue also if severe rash develops or rash with elevated hepatic transaminases or with constitutional symptoms occur

Dosage Forms & Strengths

oral suspension

  • 10mg/mL

tablet, immediate-release

  • 200mg

tablet, extended-release

  • 100mg
  • 400mg

HIV Infection

Indicated for treatment of HIV-1 infection in combination with other antiretrovirals

Immediate-release

  • <15 days: Safety and efficacy not established
  • ≥15 days to 16 years: 150 mg/m² PO qDay for 2 wk; if no rash, then increase to 150 mg/m² q12hr; not to exceed 200 mg/dose  
  • >16 years: As adults; 200 mg PO qDay for 2 wk; if no rash or untoward effect occurs, then increase to 200 mg PO q12h

Extended-release

  • <6 years: Safety and efficacy not established
  • 6-18 years
    • Switch from immediate-release tabs: If already taking immediate-release, may switch to extended- release without 14-day lead-in period of immediate-release nevirapine
    • Initial therapy: Initiate with immediate-release 150 mg/m² PO qDay for 14 days (not to exceed 200 mg/day), THEN  
    • Extended-release dose based on BSA as follows:
    • 0.58-0.83 m²: 200 mg PO qDay
    • 0.84-1.16 m²: 300 mg PO qDay
    • ≥1.17 m²: 400 mg PO qDay

Alternate dosing based on HIV treatment guidelines (March, 2016)

  • Immediate-release and suspension formulations
  • <1 month (investigational dose)
    • 34-37 weeks gestational age: 4 mg/kg/dose PO BID for 1 week, then increase to 6 mg/kg/dose BID thereafter
    • ≥37 weeks gestational age: 6 mg/kg/dose PO BID
  • ≥1 month
    • ≥1 month to <8 years: 200 mg/m² PO BID
    • ≥8 years: 120-150 mg/m² PO BID
    • Not to exceed 200 mg BID

Prevention of Maternal-Fetal HIV Transmission in Neonates

Additional prophylaxis with nevirapine is needed for HIV-exposed infants of women who did not receive antepartum ART (NIH perinatal guidelines July 2012)

Birth weight 1.5-2 kg: 8 mg/dose PO

Birth weight >2 kg: 12 mg/dose PO

Administer 3 doses in the first week of life; 1st dose 48 hr after birth, give 2nd dose 48 hr after 1st dose, and 3rd dose 96 hr after 2nd dose

Recommended in combination with 6 weeks of zidovudine

Dosing Considerations

The 14-day lead-in period with immediate-release dosing must be strictly followed; it has been demonstrated to reduce the frequency of rash

If nevirapine extended-release interrupted >7 days, restart with lead-in dosing with immediate-release nevirapine

If mild-to-moderate rash (without constitutional symptoms) occurs during 14-day lead-in period, do not increase immediate-release dose or initiate extended-release regimen until the rash has resolved; duration of the lead-in dosing should not exceed 28 days, at which point an alternative regimen should be chosen

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Interactions

Interaction Checker

and nevirapine

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    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Diarrhea (15-20%)

            Rash (15-20%)

            Headache (11%)

            Neutropenia (10-11%)

            Fever (8-11%)

            1-10%

            Ulcerative stomatitis (4%)

            Increased LFTs (2-4%)

            Abdominal pain (2%)

            Paresthesia (2%)

            Nausea

            Anemia

            Peripheral neuropathy

            Myalgia

            Frequency Not Defined

            Potentially fatal hepatotoxicity (fulminant hepatitis, cholestatic hepatitis, hepatic failure, hepatic necrosis)

            Stevens-Johnson syndrome

            Toxic epidermal necrolysis

            Rhabdomyolysis

            Postmarketing Reports

            Body as a whole: Fever, somnolence, drug withdrawal, redistribution/accumulation of body fat

            Gastrointestinal: Vomiting

            Liver and biliary: Jaundice, fulminant and cholestatic hepatitis, hepatic necrosis, hepatic failure

            Hematology: Anemia, eosinophilia, neutropenia Investigations: decreased serum phosphorus

            Investigations: Decreased serum phosphorus

            Musculoskeletal: Arthralgia, rhabdomyolysis associated with skin and/or liver reactions

            Neurologic: Paraesthesia

            Skin and appendages: Allergic reactions including anaphylaxis, angioedema, bullous eruptions, ulcerative stomatitis and urticaria have all been reported; hypersensitivity syndrome and hypersensitivity reactions with rash associated with constitutional findings (eg, fever, blistering, oral lesions, conjunctivitis, facial edema, muscle or joint aches, general malaise, fatigue, or significant hepatic abnormalities, drug reaction with eosinophilia and systemic symptoms [DRESS])

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            Warnings

            Black Box Warnings

            Monitoring during the first 18 wk of therapy essential; extra vigilance warranted during first 6 wk of therapy (period of greatest risk)

            Fatal and nonfatal hepatotoxicity

            • Discontinue immediately with signs or symptoms of hepatitis or increased transaminase levels combined with rash or other systemic symptoms

            Fatal and nonfatal skin reactions

            • Discontinue immediately if severe skin or hypersensitivity reactions occur or if any rash with systemic symptoms occurs

            Contraindications

            Hypersensitivity

            Moderate or severe hepatic impairment (Child-Pugh class B or C)

            Coadministration with drugs (eg, CYP inducers) where significant decreases in nevirapine plasma concentrations may occur, which may result in loss of virologic response and possible resistance and cross-resistance to other NNRTIs

            Use as part of postexposure prophylaxis (PEP) regimens

            Cautions

            Do not restart therapy following severe skin rash, skin rash combined with increased transaminases or other symptoms, or hypersensitivity reaction

            Risk of severe, life threatening skin reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity

            Discontinue if severe rash or any rash accompanied by constitutional findings occurs

            Risk of immune reconstitution syndrome if used in combination with other antiretroviral drugs

            Redistribution/accumulation of body fat may occur (cushingoid appearance)

            Limited human data are insufficient to determine risk of infertility in humans; based on results from animal fertility studies conducted in rats, therapy may reduce fertility in females of reproductive potential; not known if these effects on fertility are reversible

            Risk of hepatotoxicity

            • Rhabdomyolysis reported in some patients experiencing skin and/or liver reactions associated with therapy; hepatitis/hepatic failure may be associated with signs of hypersensitivity which can include severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, eosinophilia, granulocytopenia, lymphadenopathy, or renal dysfunction; patients with signs or symptoms of hepatitis must be advised to discontinue therapy and immediately seek medical evaluation, which should include liver enzyme tests
            • The first 18 weeks of therapy are a critical period during which intensive clinical and laboratory monitoring of patients is required to detect potentially life-threatening hepatic events; some experts recommend clinical and laboratory monitoring more often than once per month, and in particular, include monitoring of liver enzyme tests at baseline, prior to dose escalation and at two weeks post-dose escalation; after initial 18-week period, frequent clinical and laboratory monitoring should continue throughout treatment
            • Hepatic injury may progress despite treatment discontinuation
            • Female gender and higher CD4 are higher risk factors
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            Pregnancy & Lactation

            Pregnancy

            There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to nevirapine during pregnancy; healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263

            Available data from the APR show no difference in risk of overall major birth defects for nevirapine compared with background rate for major birth defects of 2.7% in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP); rate of miscarriage is not reported in the APR

            Severe hepatic events, including fatalities, reported in pregnant women receiving chronic therapy as part of combination treatment of HIV-1 infection; regardless of pregnancy status, women with CD4+ cell counts greater than 250 cells/mm3 should not initiate therapy unless benefit outweighs risk; it is unclear if pregnancy augments risk observed in non-pregnant women

            Lactation

            The Centers for Disease Control and Prevention recommend that HIV-1 infected mothers in the United States not breastfeed infants to avoid risking postnatal transmission of HIV-1 infection; published data report that nevirapine is present in human milk; there are limited data on effects of nevirapine on breastfed infant; there is no information on effects of nevirapine on milk production; because of potential for (1) HIV-1 transmission (in HIV-negative infants), (2) developing viral resistance (in HIV-positive infants), and (3) serious adverse reactions in nursing infants, mothers should not breastfeed if they are receiving therapy; published literature indicates that rash and hyperbilirubinemia have been seen in infants exposed to nevirapine through breastmilk

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI); activity against HIV-1 by binding to reverse transcriptase, and thereby blocking RNA- and DNA-dependent DNA polymerase actions including HIV-1 replication

            Does not require intracellular phosphorylation for activity

            Absorption

            Bioavailability: >90%

            Peak Plasma: 2-4 hr

            Distribution

            Distributed widely; crosses placenta; enters breast milk; CSF penetration approximates 50% of plasma

            Protein Bound: 50-60%

            Vd: 1.2-1.4 L/kg

            Metabolism

            Extensively hepatic via CYP3A4 (hydroxylation to inactive compounds)

            May undergo enterohepatic recycling

            Elimination

            Half-life: Decreases over 2-4 wk with chronic dosing due to autoinduction (ie, half-life initially 45 hr and decreases to 23 hr)

            Excretion: Urine (~81% as metabolites, <3% as unchanged drug); feces (10%)

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            Administration

            Oral Administration

            Shake suspension gently and administer entire measured dose

            5 mL or less: Use oral syringe

            Extended-release tablets should be swallowed whole; do not chew, crush, or split

            May take with or without food

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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
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            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
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