Usage
- Medical Conditions: Nevirapine is an antiretroviral medication specifically indicated for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection. It is used in combination with other antiretroviral agents as part of Highly Active Antiretroviral Therapy (HAART). It is also used to prevent mother-to-child transmission of HIV during childbirth and breastfeeding.
- Pharmacological Classification: Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI).
- Mechanism of Action: Nevirapine binds directly to HIV-1 reverse transcriptase, an enzyme essential for viral replication. This binding inhibits the RNA-dependent and DNA-dependent DNA polymerase activities of the enzyme, blocking the conversion of viral RNA into DNA and thus preventing viral replication.
Alternate Names
- International Nonproprietary Name (INN): Nevirapine
- Brand Names: Viramune®, Viramune XR®
How It Works
- Pharmacodynamics: Nevirapine’s primary effect is inhibiting HIV-1 reverse transcriptase. It does not inhibit human DNA polymerases alpha, beta, gamma, or delta.
- Pharmacokinetics:
- Absorption: Nevirapine is readily absorbed orally, achieving peak plasma concentrations within 4 hours. Bioavailability is approximately 90%. Taking the medication with food does not significantly affect absorption.
- Metabolism: Primarily metabolized by the liver through the cytochrome P450 (CYP) system, specifically CYP3A4 and CYP2B6. It forms several hydroxylated metabolites.
- Elimination: Primarily eliminated via hepatic metabolism with subsequent renal excretion of metabolites. The elimination half-life is approximately 25-30 hours, allowing for once-daily dosing with the extended-release formulation.
- Mode of Action: Nevirapine acts allosterically, binding to a site near the active site of reverse transcriptase, inducing conformational changes that inhibit its activity. It does not require phosphorylation for activity, unlike nucleoside reverse transcriptase inhibitors (NRTIs).
- Receptor Binding/Enzyme Inhibition: Specifically inhibits HIV-1 reverse transcriptase. No known significant interactions with other receptors or enzymes.
- Elimination Pathways: Primarily hepatic metabolism via CYP3A4 and CYP2B6, followed by renal excretion of metabolites.
Dosage
Standard Dosage
Adults:
- Immediate-Release: 200 mg orally once daily for 14 days (lead-in period), then 200 mg twice daily.
- Extended-Release: 400 mg orally once daily (after the 14-day lead-in period with immediate-release formulation).
- Prevention of Mother-to-Child Transmission: A single 200 mg dose at the onset of labor. Infants receive a single dose of 2 mg/kg within 72 hours of birth.
Children:
- Immediate-Release: Dosing is based on body surface area (BSA). Refer to detailed pediatric dosing charts based on BSA and age for specific dosages, considering a lead-in period with a lower dose.
- Extended-Release: Not recommended for children under 6 years of age. Refer to detailed pediatric dosing charts based on BSA and age for specific dosages in older children.
Special Cases:
- Elderly Patients: No specific dose adjustments are typically required based on age alone. However, monitor for potential drug interactions and age-related changes in liver and kidney function.
- Patients with Renal Impairment: No dose adjustment necessary.
- Patients with Hepatic Dysfunction: Contraindicated in moderate to severe hepatic impairment (Child-Pugh B or C). Use with caution in mild hepatic impairment with close monitoring.
- Patients with Comorbid Conditions: Caution is advised in patients with a history of liver disease (including hepatitis B or C) or other conditions affecting liver function.
Clinical Use Cases
Nevirapine is specifically indicated for HIV-1 infection management and prevention of mother-to-child transmission. It is not indicated for intubation, surgical procedures, mechanical ventilation, or emergency situations like status epilepticus or cardiac arrest.
Dosage Adjustments
Dose modifications are primarily based on hepatic function and the occurrence of skin rash. No adjustments are required for renal impairment. Interrupt treatment in case of severe rash or moderate to severe hepatic dysfunction.
Side Effects
Common Side Effects:
Rash (including maculopapular, urticarial, or maculopapular eruptions), fever, headache, nausea, vomiting, diarrhea, abdominal pain, fatigue.
Rare but Serious Side Effects:
Hepatotoxicity (including hepatitis, liver failure), Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), severe skin reactions, hypersensitivity reactions.
Long-Term Effects:
Lipodystrophy (changes in body fat distribution), elevated liver enzymes, drug resistance.
Adverse Drug Reactions (ADR):
Hepatotoxicity, severe skin reactions, SJS/TEN, hypersensitivity reactions.
Contraindications
- Moderate to severe hepatic impairment (Child-Pugh B or C)
- Hypersensitivity to nevirapine
- Coadministration with strong CYP3A4 inducers that can significantly reduce nevirapine concentrations (e.g., rifampin, St. John’s wort).
- Post-exposure prophylaxis (PEP) for occupational or non-occupational HIV exposure.
Drug Interactions
Nevirapine interacts with numerous medications, including:
- CYP450 Inducers: Rifampin, St. John’s wort - decrease nevirapine levels.
- CYP450 Inhibitors: Ketoconazole, protease inhibitors - increase nevirapine levels.
- Other: Oral contraceptives (reduced effectiveness), Methadone (dose adjustment may be required). Consult a comprehensive drug interaction database for a full list of interactions.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: No official FDA category assigned. Not a first-line drug in pregnancy, but use is recommended when benefits outweigh the risk.
- Fetal Risks: Potential risk of hepatotoxicity in pregnant women, particularly those with higher CD4 counts. Monitor liver function tests closely. No evidence of increased teratogenicity.
- Breastfeeding: Nevirapine is present in breast milk. When the maternal viral load is undetectable, the benefits of breastfeeding often outweigh the risk of HIV transmission; otherwise, use formula or pasteurized donor milk. Infants of breastfeeding mothers taking nevirapine receive prophylactic nevirapine for a period after birth to reduce the risk of transmission.
Drug Profile Summary
- Mechanism of Action: NNRTI, inhibits HIV-1 reverse transcriptase.
- Side Effects: Rash, fever, headache, nausea, vomiting, hepatotoxicity (rare but serious), SJS/TEN (rare but serious).
- Contraindications: Moderate/severe hepatic impairment, hypersensitivity, concomitant use with strong CYP3A4 inducers.
- Drug Interactions: Numerous drug interactions, including CYP450 inducers and inhibitors.
- Pregnancy & Breastfeeding: Use with caution in pregnancy, monitor liver function. Present in breast milk; infant prophylaxis recommended in certain situations.
- Dosage: Adults: 200 mg daily x 14 days, then 200 mg twice daily (IR) or 400 mg once daily (XR). Pediatric dosing based on BSA.
- Monitoring Parameters: Liver function tests (LFTs), CD4 count, viral load, signs of rash or hypersensitivity.
Popular Combinations
Nevirapine is typically used in combination with two NRTIs, such as tenofovir disoproxil fumarate/emtricitabine or zidovudine/lamivudine.
Precautions
- General Precautions: Monitor LFTs, screen for hepatitis B and C coinfection, assess for rash regularly.
- Specific Populations: Pregnant women (monitor liver function, higher risk of hepatotoxicity), breastfeeding mothers (infant prophylaxis).
- Lifestyle Considerations: Alcohol consumption may exacerbate liver-related side effects.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Nevirapine?
A: Adults: 200 mg once daily for 14 days, followed by 200 mg twice daily (IR) or 400 mg once daily (XR). Pediatric dosing is based on BSA and age, with a lead-in period.
Q2: What are the most common side effects of Nevirapine?
A: Rash, fever, headache, nausea, vomiting, diarrhea, abdominal pain, and fatigue.
Q3: What are the serious side effects of Nevirapine?
A: Hepatotoxicity (including hepatitis, liver failure) and severe skin reactions, including Stevens-Johnson Syndrome and toxic epidermal necrolysis.
Q4: Can Nevirapine be used during pregnancy?
A: Not a first-line drug in pregnancy, but used when benefits outweigh risks. Monitor closely for hepatotoxicity, especially in women with CD4 counts >250 cells/mm³.
Q5: Is it safe to breastfeed while taking Nevirapine?
A: Nevirapine is present in breast milk. In settings where the maternal viral load is suppressed, breastfeeding is generally considered safe with infant NVP prophylaxis, but use formula or pasteurized donor milk if the viral load is detectable.
Q6: What are the contraindications for Nevirapine use?
A: Moderate to severe hepatic impairment, hypersensitivity to nevirapine, and concomitant use with strong CYP3A4 inducers.
Q7: Does Nevirapine interact with other medications?
A: Yes, nevirapine interacts with many medications. It is crucial to check for potential interactions before prescribing.
A: Primarily metabolized by the liver via the CYP450 system, specifically CYP3A4 and CYP2B6.
Q9: What should be monitored in patients taking Nevirapine?
A: Liver function tests (LFTs), CD4 count, viral load, and signs of rash or hypersensitivity reactions should be regularly monitored.
A: Yes, Viramune XR® allows for once-daily dosing after a 14-day lead-in period with the immediate-release formulation.
