Usage
- This combination drug is prescribed for the treatment of HIV-1 infection in adults and children over 6 years old weighing at least 15kg. It is an antiretroviral therapy (ART) regimen.
- Pharmacological classification: Antiretroviral, specifically a combination of:
- Protease inhibitor (Atazanavir, boosted by Ritonavir)
- Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) (Lamivudine and Tenofovir disoproxil fumarate)
- Mechanism of Action: This combination targets multiple stages of the HIV-1 life cycle. Atazanavir, boosted by Ritonavir, inhibits the protease enzyme, preventing the cleavage of viral polyproteins necessary for the formation of mature infectious virions. Lamivudine and Tenofovir disoproxil fumarate, both NRTIs, interfere with viral reverse transcriptase, an enzyme that converts viral RNA to DNA, thus blocking viral replication. Ritonavir primarily boosts the levels of Atazanavir by inhibiting its metabolism, thereby increasing its effectiveness.
Alternate Names
- No widely used alternate names for the combination exist. It is often referred to by the abbreviations of its components: ATV/r + 3TC + TDF
- Brand Names: Numerous generic versions exist internationally. Brand names may vary regionally.
How It Works
- Pharmacodynamics: The combined effect results in suppression of HIV-1 replication, leading to a decreased viral load and increased CD4 cell counts.
- Pharmacokinetics:
- Atazanavir: Metabolized primarily by CYP3A4. Ritonavir inhibits CYP3A4, thus increasing Atazanavir concentrations. Absorption enhanced with food.
- Lamivudine: Well absorbed orally. Primarily renally excreted, with minimal metabolism.
- Ritonavir: Primarily metabolized by CYP3A4, also inhibits CYP3A4 and other CYP enzymes.
- Tenofovir disoproxil fumarate: Converted to the active metabolite Tenofovir. Primarily renally excreted.
- Mode of Action:
- Atazanavir: Binds to the active site of HIV-1 protease, preventing cleavage of viral polyproteins.
- Lamivudine and Tenofovir: Act as competitive substrates and chain terminators for HIV-1 reverse transcriptase.
- Elimination pathways: Atazanavir and Ritonavir are primarily hepatically metabolized and excreted in bile and feces. Lamivudine and Tenofovir are primarily renally excreted.
Dosage
Standard Dosage
Adults:
- Atazanavir 300mg + Ritonavir 100mg once daily with food, plus Lamivudine 300mg and Tenofovir disoproxil fumarate 300mg, both typically administered as a fixed-dose combination tablet, once daily, with or without food.
Children (6-18 years, ≥15 kg):
- Atazanavir dosing is weight-based. Lamivudine and Tenofovir disoproxil fumarate are also usually dosed based on weight or age.
Special Cases:
- Elderly Patients: No specific dosage adjustment is generally recommended unless renal impairment is present. Close monitoring of renal function is essential.
- Patients with Renal Impairment: Dose reductions or increased dosing intervals may be necessary for Tenofovir disoproxil fumarate and potentially lamivudine, based on creatinine clearance. Atazanavir/ritonavir dose is not typically affected, but caution is warranted due to the potential accumulation of ritonavir.
- Patients with Hepatic Dysfunction: Atazanavir/ritonavir should be used with caution in mild to moderate hepatic impairment, and is contraindicated in severe impairment. Lamivudine and Tenofovir disoproxil fumarate can generally be used without adjustment in mild to moderate hepatic impairment.
- Patients with Comorbid Conditions: Dose adjustments and careful monitoring may be necessary, especially in patients with diabetes, cardiovascular disease, or other conditions requiring concomitant medications.
Clinical Use Cases
The listed clinical settings (intubation, surgical procedures, mechanical ventilation, ICU, emergency situations) do not typically necessitate dosage adjustments for this specific drug combination. However, patient-specific factors, including renal and hepatic function, must always be considered and appropriate adjustments made if needed.
Dosage Adjustments
Dose modifications are necessary based on renal/hepatic dysfunction, interactions with other drugs, and certain concomitant medical conditions. Consult appropriate guidelines for detailed recommendations.
Side Effects
Common Side Effects
Nausea, vomiting, diarrhea, headache, abdominal pain, rash, fatigue, jaundice (usually benign, due to Atazanavir), increased bilirubin levels.
Rare but Serious Side Effects
Hepatotoxicity, nephrotoxicity (including Fanconi syndrome), lactic acidosis, severe skin reactions (Stevens-Johnson Syndrome), pancreatitis, cardiac conduction abnormalities (including QT prolongation), immune reconstitution inflammatory syndrome (IRIS).
Long-Term Effects
Dyslipidemia, insulin resistance, changes in body fat distribution, osteopenia/osteoporosis, renal impairment.
Adverse Drug Reactions (ADR)
Hypersensitivity reactions, drug-induced liver injury, acute renal failure, severe metabolic acidosis.
Contraindications
- Hypersensitivity to any component of the drug.
- Coadministration with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., astemizole, terfenadine, cisapride, pimozide, midazolam, triazolam, ergot derivatives, simvastatin, lovastatin).
- Moderate to severe hepatic impairment.
- Concomitant use of dofetilide.
Drug Interactions
Numerous drug interactions exist, notably with inducers or inhibitors of CYP3A4.
- Other antiretrovirals (e.g., efavirenz, nevirapine).
- H2-receptor antagonists, proton pump inhibitors (reduce Atazanavir absorption).
- Antiarrhythmics, some anticonvulsants, some immunosuppressants, some antifungals.
- Certain herbal supplements (e.g., St. John’s Wort).
Pregnancy and Breastfeeding
- Pregnancy: Atazanavir/ritonavir can be used during pregnancy, with dose adjustments sometimes necessary. Close monitoring is recommended.
- Breastfeeding: Breastfeeding is not recommended due to the potential for HIV transmission and the presence of the drugs in breast milk.
Drug Profile Summary
- Mechanism of Action: Multi-target antiretroviral therapy.
- Side Effects: Nausea, vomiting, diarrhea, rash, jaundice, hepatotoxicity, nephrotoxicity, metabolic abnormalities.
- Contraindications: Hypersensitivity, severe hepatic impairment, concomitant use of certain medications.
- Drug Interactions: Numerous, particularly with CYP3A4 modulators.
- Pregnancy & Breastfeeding: Can be used during pregnancy with monitoring; breastfeeding not recommended.
- Dosage: Adult: ATV/r 300/100mg + 3TC/TDF 300/300mg once daily with food. Pediatric: weight-based.
- Monitoring Parameters: HIV-1 RNA viral load, CD4 cell count, renal function (creatinine clearance, serum creatinine, urine protein), hepatic function (liver enzymes, bilirubin), lipid profile, blood glucose, bone mineral density.
Popular Combinations
This combination itself is a common and frequently used regimen for HIV-1 infection.
Precautions
- Assess renal and hepatic function before and during treatment.
- Monitor for adverse effects, especially hepatotoxicity, nephrotoxicity, and metabolic complications.
- Counsel patients on adherence and safe sex practices.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Atazanavir + Lamivudine + Ritonavir + Tenofovir disoproxil fumarate?
A: Adults: ATV/r 300/100mg once daily with food + 3TC/TDF 300/300mg once daily. Pediatric dosing is weight-based.
Q2: What are the most common side effects?
A: Nausea, vomiting, diarrhea, headache, rash, and jaundice (usually benign).
Q3: What are the serious side effects to watch out for?
A: Hepatotoxicity, nephrotoxicity, lactic acidosis, pancreatitis, severe skin reactions, and cardiac rhythm abnormalities.
Q4: What are the contraindications to this drug combination?
A: Hypersensitivity to any component, moderate-to-severe hepatic impairment, and concomitant use of certain medications.
Q5: What are the key drug interactions?
A: Many interactions exist, especially with drugs that affect CYP3A4 activity (inducers or inhibitors), H2 receptor antagonists, and proton pump inhibitors.
Q6: Can this combination be used in pregnant women?
A: Yes, but careful monitoring is necessary, and dose adjustments may be required.
Q7: Can this combination be used in breastfeeding women?
A: Breastfeeding is not recommended due to the risk of HIV transmission and drug exposure to the infant.
Q8: What monitoring parameters are important for patients taking this combination?
A: HIV viral load, CD4 count, renal and hepatic function, lipid profile, blood glucose, and bone mineral density.
Q9: What patient counseling points are crucial?
A: Adherence to the prescribed regimen, safe sex practices to prevent HIV transmission, reporting any side effects promptly, and awareness of potential drug interactions.
