Usage
- Medical Conditions: This fixed-dose combination (FDC) tablet is prescribed for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adults and pediatric patients weighing at least 25 kg with creatinine clearance greater than or equal to 30 mL per minute. It is indicated as a complete regimen for those who are treatment-naïve or treatment-experienced but INSTI-naïve. It can also replace the current antiretroviral regimen in virologically suppressed adults (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure and no known resistance to the components of this FDC.
- Pharmacological Classification: Antiretroviral; Integrase Strand Transfer Inhibitor (INSTI) + Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs).
- Mechanism of Action:
- Dolutegravir: Inhibits HIV integrase, preventing integration of viral DNA into the host cell’s genome, thereby blocking HIV replication.
- Emtricitabine & Tenofovir Alafenamide: NRTIs that interfere with HIV reverse transcriptase, an enzyme crucial for viral replication by acting as competitive substrates and chain terminators. Tenofovir alafenamide is a prodrug of tenofovir.
Alternate Names
- No official alternate names exist for this specific FDC.
- Brand Names: Several brand names exist including Spegra, Kocitaf.
How It Works
- Pharmacodynamics: The combination effectively suppresses HIV replication leading to increased CD4 T-cell counts and improved immune function. This reduces the risk of opportunistic infections and disease progression.
- Pharmacokinetics:
- Absorption: All three components are orally absorbed. Tenofovir alafenamide achieves higher intracellular tenofovir concentrations with lower plasma concentrations compared to tenofovir disoproxil fumarate.
- Metabolism: Dolutegravir is primarily metabolized via UGT1A1 with minor CYP3A contribution. Emtricitabine and tenofovir alafenamide are minimally metabolized.
- Elimination: Dolutegravir is eliminated primarily in feces. Emtricitabine and tenofovir are primarily eliminated renally.
- Mode of Action (Cellular/Molecular): Dolutegravir binds to the integrase active site and prevents the strand transfer step of HIV integration. Emtricitabine and tenofovir alafenamide, after intracellular phosphorylation to their active forms, compete with natural substrates and cause chain termination during reverse transcription of viral RNA.
- Receptor Binding/Enzyme Inhibition: Dolutegravir inhibits HIV integrase. Emtricitabine and tenofovir alafenamide inhibit HIV reverse transcriptase.
Dosage
Standard Dosage
Adults: One tablet containing dolutegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg, taken orally once daily with or without food. Weight must be at least 25 kg.
Special Cases:
- Elderly Patients: No dosage adjustment is specifically recommended, but consider age-related organ function decline. Close monitoring of renal function is essential.
- Patients with Renal Impairment: Not recommended for patients with creatinine clearance (CrCl) less than 30 mL/min.
- Patients with Hepatic Dysfunction: Not recommended for patients with severe hepatic impairment.
- Patients with Comorbid Conditions: Dosage adjustments might be necessary based on specific comorbid conditions. Consult specialized guidelines for co-infections like hepatitis B or C.
Clinical Use Cases This medication is specifically designed for chronic HIV treatment, not acute clinical scenarios. The dosage recommendations do not change for use in situations such as intubation, surgical procedures, mechanical ventilation, or emergency situations.
Dosage Adjustments
- Refer to sections on renal and hepatic impairment. Dose adjustments may be required when co-administered with certain medications; refer to drug interaction section.
Side Effects
Common Side Effects:
Headache, nausea, diarrhea, insomnia, fatigue, rash, and dizziness.
Rare but Serious Side Effects:
Hypersensitivity reactions (rash, fever, organ dysfunction), hepatotoxicity, new onset or worsening renal impairment, immune reconstitution inflammatory syndrome (IRIS).
Long-Term Effects:
Changes in bone mineral density, metabolic abnormalities.
Contraindications
- Hypersensitivity to any component of the FDC.
- Coadministration with dofetilide.
- Severe hepatic impairment (Child-Pugh Class C).
- CrCl less than 30 mL/min.
Drug Interactions
- Drug Interactions: Drugs that induce UGT1A1 or CYP3A (e.g., rifampin, some anticonvulsants) may reduce dolutegravir concentrations. Coadministration requires dosage adjustment of dolutegravir. Refer to specific drug interaction resources for further information.
- Antacids containing polyvalent cations (aluminum, magnesium, calcium) can decrease absorption and should be separated by at least 2 hours.
Pregnancy and Breastfeeding
- Pregnancy: Dolutegravir may be used during pregnancy. While an association with neural tube defects has been suggested in some studies, it is not definitively established. Close monitoring and informed decision-making are necessary. Discuss with the patient the benefits and risks of dolutegravir versus alternative regimens.
- Breastfeeding: HIV transmission through breastfeeding is a significant risk. Mothers living with HIV should be advised not to breastfeed regardless of antiretroviral therapy.
Drug Profile Summary
- Mechanism of Action: Integrase inhibition (dolutegravir), NRTI (emtricitabine and tenofovir alafenamide).
- Side Effects: See above.
- Contraindications: See above.
- Drug Interactions: See above.
- Pregnancy & Breastfeeding: See above.
- Dosage: See above.
- Monitoring Parameters: HIV-1 RNA viral load, CD4 T-cell count, renal function (serum creatinine, estimated CrCl), liver function tests, and bone mineral density.
Popular Combinations
- This FDC is itself a popular combination and represents a complete HIV regimen. No additional antiretrovirals are typically added.
Precautions
- General Precautions: Evaluate for pre-existing medical conditions, drug allergies, and potential drug interactions. Monitor renal and hepatic function.
- Specific Populations: See information above regarding pregnancy, breastfeeding, children, and elderly patients.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dolutegravir + Emtricitabine + Tenofovir Alafenamide?
A: One tablet daily for adults and children weighing at least 25 kg with CrCl ≥30 mL/min.
Q2: Can this FDC be used in pregnancy?
A: Yes, but careful consideration of potential risks and benefits is essential. Consult current guidelines regarding neural tube defect risk.
Q3: Can this FDC be used during breastfeeding?
A: No. Breastfeeding is not recommended for HIV-positive mothers.
Q4: What are the common side effects?
A: Headache, nausea, diarrhea, insomnia, and fatigue.
Q5: What monitoring is required?
A: Monitor HIV-1 RNA, CD4 count, renal function, liver function, and bone mineral density.
Q6: Are there any significant drug interactions?
A: Yes. Interactions with drugs that induce UGT1A1 or CYP3A may necessitate dolutegravir dosage adjustments.
Q7: Can it be used in patients with renal impairment?
A: Not recommended for patients with CrCl < 30 mL/min.
Q8: What should be done if a patient develops a rash?
A: Evaluate for hypersensitivity reaction immediately. Discontinue the drug if hypersensitivity is suspected.
Q9: Can it be used with antacids?
A: Administer antacids containing polyvalent cations at least 2 hours apart from this FDC.
Q10: What is the role of therapeutic drug monitoring (TDM)?
A: TDM is not routinely recommended, but can be considered in cases of suspected toxicity or suboptimal drug levels.
