Drug Guide
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate
Classification
Therapeutic: Antiretroviral for HIV infection
Pharmacological: Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
FDA Approved Indications
- Treatment of HIV-1 infection in combination with other antiretroviral agents
Mechanism of Action
Efavirenz is a non-nucleoside reverse transcriptase inhibitor that binds to reverse transcriptase, causing direct inhibition. Emtricitabine and Tenofovir Disoproxil Fumarate are nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) that incorporate into viral DNA, causing chain termination.
Dosage and Administration
Adult: Typically, one tablet (600 mg efavirenz, 200 mg emtricitabine, 300 mg tenofovir disoproxil fumarate) once daily on an empty stomach, preferably at bedtime.
Pediatric: Not approved for pediatric use.
Geriatric: No specific dosage adjustments, but caution in renal and hepatic impairment.
Renal Impairment: Use with caution; Tenofovir requires renal function monitoring.
Hepatic Impairment: Adjust dose and monitor liver function; contraindicated in severe hepatic impairment.
Pharmacokinetics
Absorption: Well absorbed orally, food may increase absorption of efavirenz.
Distribution: Wide distribution with high tissue penetration.
Metabolism: Efavirenz is extensively metabolized by CYP2B6 and CYP3A4. Emtricitabine and tenofovir are primarily excreted unchanged.
Excretion: Renally (emtricitabine, tenofovir); hepatic (efavirenz).
Half Life: Efavirenz: ~40-55 hours; Emtricitabine: ~10 hours; Tenofovir: ~17 hours.
Contraindications
- Hypersensitivity to efavirenz, emtricitabine, or tenofovir.
Precautions
- Neuropsychiatric symptoms (efavirenz), renal and hepatic impairment, concomitant use with other nephrotoxic drugs, osteoporosis.
Adverse Reactions - Common
- Rash (frequent)
- Dizziness (common)
- Fatigue (common)
- Nausea (common)
Adverse Reactions - Serious
- Severe rash or hypersensitivity reactions (rare)
- Lactic acidosis with hepatic steatosis (rare)
- Hepatotoxicity (rare)
- Neuropsychiatric symptoms (e.g., depression, hallucinations) (common)
Drug-Drug Interactions
- CYP3A4 inducers/inhibitors (e.g., rifampin, carbamazepine) affecting efavirenz levels.
- Other nephrotoxic or hepatotoxic agents.
Drug-Food Interactions
- High-fat meals may increase efavirenz absorption.
Drug-Herb Interactions
- St. John’s Wort reduces efavirenz levels.
Nursing Implications
Assessment: Monitor for neuropsychiatric symptoms, liver function, renal function, and adherence.
Diagnoses:
- Risk for ineffective tissue perfusion related to lactic acidosis or hepatotoxicity.
- Impaired cognition related to neuropsychiatric side effects.
Implementation: Administer on an empty stomach at bedtime. Educate patient on adherence and side effect management.
Evaluation: Assess viral load and CD4 count, monitor for adverse effects, and adherence.
Patient/Family Teaching
- Take medication exactly as prescribed.
- Report neuropsychiatric symptoms or rash.
- Use contraception to prevent pregnancy; efavirenz is teratogenic.
- Avoid alcohol and St. John’s Wort.
Special Considerations
Black Box Warnings:
- Severe psychiatric symptoms, including suicidal ideation.
- Lactic acidosis and severe hepatomegaly with steatosis.
Genetic Factors: CYP2B6 polymorphisms can affect efavirenz metabolism, influencing side effects.
Lab Test Interference: May interfere with certain liver function tests and serum glucose levels.
Overdose Management
Signs/Symptoms: CNS depression, dizziness, nausea.
Treatment: Supportive care; no specific antidote; monitor vital signs, provide symptomatic treatment.
Storage and Handling
Storage: Store at room temperature, 20°C to 25°C (68°F to 77°F).
Stability: Stable under recommended storage conditions until expiration date.