Usage
This combination of drugs is prescribed for the treatment of HIV-1 infection. It’s classified as an antiretroviral agent, specifically a nucleoside reverse transcriptase inhibitor (NRTI) (zidovudine and lamivudine) combined with a non-nucleoside reverse transcriptase inhibitor (NNRTI) (nevirapine). These drugs work together to inhibit the reverse transcriptase enzyme, essential for HIV replication, preventing the virus from multiplying and spreading within the body.
Alternate Names
This combination doesn’t have a specific generic name as it’s a combination of three different drugs. However, each of the drugs is known by their generic and various brand names. Zidovudine is also known as AZT or ZDV. Brand names include Retrovir. Lamivudine is also known as 3TC. Epivir is one brand name for lamivudine. Nevirapine is also known as NVP. Viramune is one brand name for nevirapine. Several brand names may exist for the individual components as well as for the combination.
How It Works
Pharmacodynamics: Lamivudine and zidovudine are nucleoside analog reverse-transcriptase inhibitors (NRTIs) that, after intracellular phosphorylation to their active triphosphate form, inhibit HIV reverse transcriptase by competing with the natural substrate, deoxycytidine triphosphate. Incorporation of the lamivudine and zidovudine triphosphates into the viral DNA chain causes chain termination. Nevirapine is a non-nucleoside reverse-transcriptase inhibitor (NNRTI) that binds directly to reverse transcriptase and blocks RNA- and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme’s catalytic site. The combination acts synergistically to suppress HIV replication.
Pharmacokinetics:
- Absorption: All three drugs are absorbed orally.
- Metabolism: Lamivudine is minimally metabolized. Zidovudine is primarily metabolized in the liver to the inactive glucuronide form. Nevirapine is extensively metabolized in the liver by cytochrome P450 (CYP) enzymes, specifically CYP3A4 and CYP2B6.
- Elimination: Lamivudine is primarily excreted renally. Zidovudine metabolites are also eliminated renally. Nevirapine metabolites are excreted in urine and feces.
Dosage
Standard Dosage
Adults:
- Lamivudine: 300 mg orally once daily or 150 mg twice daily.
- Nevirapine: 200 mg daily for 14 days, then 200 mg twice daily.
- Zidovudine: 300 mg orally twice daily or 200 mg three times a day, or 600 mg daily as extended release tablets. It can also be administered intravenously as 1 mg/kg every 4 hours (six times daily).
Children:
Dosing in children is weight-based and should be determined by a doctor, as it varies based on age, weight, and clinical presentation.
Special Cases:
- Elderly Patients: Dosage adjustments may be needed based on renal function.
- Patients with Renal Impairment: Dose reduction may be needed for lamivudine and zidovudine based on creatinine clearance.
- Patients with Hepatic Dysfunction: Caution is advised with nevirapine in patients with hepatic impairment. Dose adjustments may be necessary.
- Patients with Comorbid Conditions: Dosage adjustments should be considered case by case, based on individual patient characteristics.
Clinical Use Cases
The combination is specifically for HIV-1 infection. The dosage does not change specifically for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. The standard dosage considerations and adjustments apply.
Dosage Adjustments
Dosage adjustments are based on renal and hepatic function, potential drug interactions, and comorbid conditions.
Side Effects
Common Side Effects
- Nausea, vomiting, diarrhea, abdominal pain
- Headache, fatigue, fever
- Rash (especially with nevirapine)
- Anemia, neutropenia (zidovudine)
Rare but Serious Side Effects
- Hepatic failure (nevirapine)
- Lactic acidosis (NRTIs)
- Stevens-Johnson syndrome (nevirapine)
- Pancreatitis (zidovudine)
Long-Term Effects
- Peripheral neuropathy
- Lipodystrophy
- Renal dysfunction
- Cardiovascular disease
Adverse Drug Reactions (ADR)
- Severe skin reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)
- Hepatotoxicity (especially with nevirapine)
- Myopathy
- Bone marrow suppression
Contraindications
- Hypersensitivity to any of the drugs
- Severe hepatic impairment (especially nevirapine)
- Pre-existing bone marrow suppression
Drug Interactions
- Other antiretrovirals
- Rifampicin, rifabutin
- St. John’s wort
- Methadone
- Certain anticonvulsants
Pregnancy and Breastfeeding
- All three drugs can be used during pregnancy and breastfeeding, with careful consideration of risks and benefits. They are often part of regimens for the prevention of mother-to-child transmission of HIV. Close monitoring is essential.
Drug Profile Summary
- Mechanism of Action: Inhibits HIV reverse transcriptase, preventing viral replication.
- Side Effects: Nausea, vomiting, rash, headache, fatigue, hepatotoxicity, lactic acidosis, bone marrow suppression, anemia.
- Contraindications: Hypersensitivity, severe hepatic impairment, pre-existing bone marrow suppression.
- Drug Interactions: Rifampicin, rifabutin, St. John’s wort, methadone.
- Pregnancy & Breastfeeding: Can be used with caution and monitoring.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: CD4 cell count, HIV viral load, liver function tests, complete blood count, renal function.
Popular Combinations
This combination itself is a popular combination for treating HIV. Other combinations may be considered based on patient-specific factors and resistance testing.
Precautions
- Monitor for hepatotoxicity, especially with nevirapine.
- Monitor for bone marrow suppression, especially with zidovudine.
- Monitor renal function.
- Assess for rash and skin reactions, especially with nevirapine.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Lamivudine + Nevirapine + Zidovudine?
A: Adults: Lamivudine 300 mg daily, Nevirapine 200 mg daily for 14 days then 200 mg twice daily, Zidovudine 300mg twice daily. Pediatric and special population dosages require weight-based calculations and individual adjustments by a physician.
Q2: What are the most common side effects?
A: Common side effects include nausea, vomiting, diarrhea, headache, fatigue, and rash.
Q3: What are the serious side effects of this combination?
A: Severe hepatic reactions, lactic acidosis, Stevens-Johnson Syndrome, pancreatitis, anemia and neutropenia are the serious side effects.
Q4: Can this combination be used during pregnancy?
A: Yes, this combination can be used in pregnant and breastfeeding women for the prevention of mother-to-child HIV transmission but under close monitoring.
Q5: Are there any specific monitoring parameters for this combination?
A: Yes, regular monitoring of CD4 count, HIV viral load, liver function tests (LFTs), complete blood count (CBC), and renal function tests is crucial.
Q6: What are the major contraindications for this combination?
A: Known hypersensitivity to any of the component drugs, severe hepatic impairment and pre-existing bone marrow suppression are contraindications.
Q7: What if a patient misses a dose?
A: The missed dose should be taken as soon as possible. Do not double the next dose.
Q8: What are the potential drug interactions for this combination?
A: The combination should not be prescribed with drugs such as Rifampicin, Rifabutin, St. John’s wort, and Methadone. It can also interact with certain anticonvulsants.
Q9: What is the mechanism of action of this combination?
A: The combination inhibits the HIV reverse transcriptase enzyme, essential for HIV replication. This prevents the virus from multiplying and lowers the viral load.
