Usage
This fixed-dose combination medication is prescribed for the treatment of HIV-1 infection. It contains three antiretroviral drugs:
- Efavirenz: A non-nucleoside reverse transcriptase inhibitor (NNRTI).
- Lamivudine: A nucleoside reverse transcriptase inhibitor (NRTI).
- Zidovudine: Another nucleoside reverse transcriptase inhibitor (NRTI).
These drugs belong to the antiretroviral pharmacological class. They work together to inhibit HIV reverse transcriptase, an enzyme crucial for viral replication. By blocking this enzyme, the medication prevents the virus from multiplying and reduces the viral load in the body.
Alternate Names
This specific combination is often referred to as simply EFV/3TC/ZDV. It is marketed under various brand names, including Atripla (efavirenz, tenofovir disoproxil fumarate, and emtricitabine - note this is a similar but not identical combination). Brand names may vary regionally.
How It Works
Pharmacodynamics: Efavirenz, lamivudine, and zidovudine all target the HIV reverse transcriptase enzyme. Efavirenz binds directly to the enzyme at a site different from the NRTIs, inducing a conformational change that inhibits its activity. Lamivudine and zidovudine, being nucleoside analogues, are phosphorylated intracellularly to their active triphosphate forms. These active metabolites compete with natural nucleosides for incorporation into the viral DNA, causing chain termination and halting viral replication.
Pharmacokinetics:
- Absorption: All three drugs are absorbed orally. Efavirenz absorption is enhanced by food, while lamivudine and zidovudine absorption is less affected.
- Metabolism: Efavirenz is primarily metabolized by the CYP3A4 and CYP2B6 hepatic enzymes. Lamivudine undergoes minimal hepatic metabolism. Zidovudine is primarily metabolized in the liver to the inactive glucuronide conjugate.
- Elimination: Efavirenz is primarily excreted in the feces, with a small amount in urine. Lamivudine is primarily excreted unchanged in urine. Zidovudine is primarily excreted as glucuronide in urine.
Dosage
Standard Dosage
Adults: The standard adult dosage is one tablet containing 600 mg efavirenz, 300 mg lamivudine, and 300 mg zidovudine, taken orally once daily, preferably at bedtime.
Children: Pediatric dosing is weight-based and complex, and this fixed-dose combination may not be appropriate for all children. Consult specialized pediatric HIV treatment guidelines for appropriate dosing recommendations based on weight and age.
Special Cases:
- Elderly Patients: Dosage adjustments may be necessary based on renal function.
- Patients with Renal Impairment: Dosage adjustments are required based on creatinine clearance.
- Patients with Hepatic Dysfunction: Caution is advised, and dosage adjustments may be necessary for efavirenz.
- Patients with Comorbid Conditions: Dosage adjustments should be considered based on the specific comorbidity.
Clinical Use Cases
This combination is specifically indicated for chronic HIV-1 infection management and isn’t typically adjusted for specific clinical scenarios like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Dosage adjustments are generally based on individual patient characteristics (e.g., renal/hepatic function).
Dosage Adjustments
Dose modifications are necessary for patients with renal or hepatic impairment. Consult specific guidelines for detailed recommendations based on creatinine clearance and liver function tests. Genetic polymorphisms affecting drug metabolism, especially CYP2B6 for efavirenz, should be considered.
Side Effects
Common Side Effects:
- Rash
- Nausea
- Dizziness
- Headache
- Fatigue
- Diarrhea
- Insomnia
- Vivid dreams
Rare but Serious Side Effects:
- Severe skin reactions (Stevens-Johnson syndrome)
- Hepatotoxicity
- Lactic acidosis
- Pancreatitis
- Peripheral neuropathy
- Depression and suicidal ideation
Long-Term Effects:
- Dyslipidemia
- Insulin resistance
- Lipodystrophy
- Osteoporosis
Contraindications
- Hypersensitivity to any of the components.
- Coadministration with drugs that significantly prolong the QT interval.
- Severe hepatic impairment (for efavirenz).
Drug Interactions
- Efavirenz is a potent inducer of CYP3A4 and can decrease the concentrations of many drugs metabolized by this enzyme (e.g., some statins, hormonal contraceptives).
- Lamivudine and zidovudine have fewer significant drug interactions.
- Concomitant use of St. John’s Wort is contraindicated due to CYP3A4 induction.
- Alcohol and smoking may exacerbate side effects.
Pregnancy and Breastfeeding
Efavirenz is contraindicated in the first trimester of pregnancy due to the risk of neural tube defects. The combination may be used later in pregnancy if the benefits outweigh the risks. All three drugs are present in breast milk, and caution is advised during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Inhibition of HIV-1 reverse transcriptase.
- Side Effects: Rash, nausea, dizziness, headache, fatigue, and serious rare effects like hepatotoxicity and Stevens-Johnson syndrome.
- Contraindications: Hypersensitivity, coadministration with certain QT-prolonging drugs, severe hepatic impairment (efavirenz), first-trimester pregnancy (efavirenz).
- Drug Interactions: Numerous, primarily due to efavirenz’s CYP3A4 induction.
- Pregnancy & Breastfeeding: Efavirenz is contraindicated in the first trimester. Use with caution during breastfeeding.
- Dosage: Standard adult dose: 600/300/300 mg once daily. Pediatric and special population dosing requires adjustments.
- Monitoring Parameters: CD4 count, HIV viral load, liver function tests, renal function tests, complete blood count, and fasting lipid profile.
Popular Combinations
While this is already a combination product, in some cases, other antiretrovirals may be added depending on the patient’s specific needs and resistance patterns. Consult treatment guidelines for the most up-to-date recommendations.
Precautions
- General Precautions: Patients should be screened for pre-existing medical conditions, including hepatic and renal dysfunction, and any history of psychiatric illness.
- Specific Populations: Consult guidelines for specific recommendations regarding pregnant women, breastfeeding mothers, children, and the elderly.
- Lifestyle Considerations: Patients should be counseled on safe sex practices to prevent HIV transmission. Alcohol and smoking may worsen side effects. Driving and operating machinery may be impaired due to dizziness or other CNS effects.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Efavirenz + Lamivudine + Zidovudine?
A: The standard adult dose is 600 mg efavirenz, 300 mg lamivudine, and 300 mg zidovudine taken orally once daily, preferably at bedtime. Pediatric and special population dosing requires individual adjustments.
Q2: What are the most common side effects?
A: Common side effects include rash, nausea, dizziness, headache, fatigue, and sleep disturbances.
Q3: What are the serious side effects to watch out for?
A: Serious side effects include severe skin reactions (Stevens-Johnson syndrome), liver toxicity, lactic acidosis, pancreatitis, peripheral neuropathy, and psychiatric symptoms.
Q4: What are the contraindications to this medication?
A: Contraindications include hypersensitivity to any of the components, coadministration with certain QT-prolonging drugs, severe liver impairment, and use in the first trimester of pregnancy (for efavirenz).
Q5: What are the key drug interactions?
A: Efavirenz is a potent inducer of CYP3A4 and can interact with many medications, including statins, hormonal contraceptives, and antifungals.
Q6: Can this medication be used during pregnancy and breastfeeding?
A: Efavirenz is contraindicated in the first trimester of pregnancy. The combination can be used later in pregnancy if benefits outweigh risks. Caution is advised during breastfeeding.
Q7: What monitoring parameters are essential for patients on this medication?
A: Key monitoring parameters include CD4 count, HIV viral load, liver function tests, renal function tests, and complete blood count.
Q8: What should patients be advised about lifestyle modifications?
A: Patients should be counseled about safe sex practices, avoiding alcohol and smoking, and potential driving restrictions.
Q9: Are there any genetic factors that can influence the response to this drug?
A: Yes, genetic variations in CYP2B6 can affect efavirenz metabolism and increase the risk of certain side effects.
