Drug Guide
Dolutegravir; Lamivudine; Tenofovir Disoproxil Fumarate
Classification
Therapeutic: Antiretroviral Agent, HIV-1 Infection
Pharmacological: Integrase Strand Transfer Inhibitor (Dolutegravir), Nucleoside Reverse Transcriptase Inhibitors (Lamivudine, Tenofovir Disoproxil Fumarate)
FDA Approved Indications
- Treatment of HIV-1 infection in adults and adolescents ≥12 years with no antiretroviral treatment history or to replace the current antiretroviral regimen in certain circumstances.
Mechanism of Action
Dolutegravir inhibits HIV integrase, preventing viral DNA from integrating into the host genome. Lamivudine and Tenofovir Disoproxil Fumarate are nucleoside reverse transcriptase inhibitors that inhibit HIV reverse transcriptase, blocking viral replication.
Dosage and Administration
Adult: Once daily orally, with or without food. Dosage may vary based on clinical judgment.
Pediatric: Not approved for children under 12 years or weighing less than 40 kg.
Geriatric: No specific dose adjustment recommended, but caution in elderly due to comorbidities and concomitant medications.
Renal Impairment: Adjustments may be necessary, especially for Tenofovir, based on renal function.
Hepatic Impairment: Use with caution; no specific dose adjustment recommended.
Pharmacokinetics
Absorption: Well absorbed orally.
Distribution: Widely distributed in body tissues; plasma protein binding data vary.
Metabolism: Metabolized minimally, primarily via hepatic processes for Dolutegravir.
Excretion: Excreted mainly via urine (Lamivudine, Tenofovir) and feces.
Half Life: Dolutegravir: approximately 14 hours; Lamivudine: approximately 5-7 hours; Tenofovir: approximately 17 hours.
Contraindications
- Hypersensitivity to any components.
- Coadministration with dofetilide due to risk of arrhythmias.
Precautions
- Hepatitis B virus (HBV) coinfection: Lamivudine and Tenofovir have activity against HBV; assess liver function.
- Renal impairment: monitor renal function due to Tenofovir nephrotoxicity.
- Pregnancy/lactation: consult current guidelines; benefits vs. risks.
Adverse Reactions - Common
- Nausea (Common)
- Headache (Common)
- Insomnia (Common)
- Fatigue (Common)
Adverse Reactions - Serious
- Lactic acidosis with severe hepatomegaly and steatosis (Rare but serious)
- Hepatotoxicity (Rare)
- Decreases in renal function or Fanconi syndrome with Tenofovir (Rare)
Drug-Drug Interactions
- Metformin (may increase risk of lactic acidosis)
- Dofetilide (contraindicated)
- Other drugs affecting renal function
Drug-Food Interactions
- None significant
Drug-Herb Interactions
- St. John’s Wort (reduces efficacy)
Nursing Implications
Assessment: Monitor renal function, hepatic function, and for signs of lactic acidosis.
Diagnoses:
- Risk for infection due to immunosuppression
- Risk for renal impairment
Implementation: Advise compliance, monitor therapy effects, manage adverse effects.
Evaluation: Adequate viral suppression, no adverse drug reactions.
Patient/Family Teaching
- Take medication exactly as prescribed.
- Report symptoms of hypersensitivity, liver problems, or renal issues.
- Use safe sex practices to prevent HIV transmission.
- Attend regular follow-up appointments.
Special Considerations
Black Box Warnings:
- Lactic acidosis and severe hepatomegaly with steatosis associated with nucleoside analogs.
- Risk of HIV drug resistance if adherence is poor.
Genetic Factors: Pharmacogenetics may influence efficacy and toxicity.
Lab Test Interference: Can affect serum creatinine and other renal function tests.
Overdose Management
Signs/Symptoms: Nausea, vomiting, diarrhea, dizziness, hepatotoxicity.
Treatment: Supportive care, monitor renal function, no specific antidote.
Storage and Handling
Storage: Store at room temperature, 20-25°C (68-77°F).
Stability: Stable under recommended storage conditions, check manufacturer specifics.