Makindo Medical Notes

💊 About

Atazanavir is a once-daily protease inhibitor (PI) used in combination antiretroviral therapy (ART) for HIV-1 infection. It is often “boosted” with ritonavir or cobicistat to increase plasma concentrations via CYP3A4 inhibition. Always 🔗 check the BNF entry for current dosing, cautions, and interactions.

🧠 Mode of Action

• Atazanavir inhibits the HIV-1 protease enzyme, preventing cleavage of viral gag-pol polyproteins.
• This blocks the maturation of infectious virions, producing non-infectious viral particles.
• Boosting with ritonavir or cobicistat reduces hepatic metabolism and maintains therapeutic levels.

📋 Indications & Dose

• HIV-1 infection: 300 mg once daily with food, plus ritonavir 100 mg once daily to inhibit CYP3A4 metabolism.
• Alternatively, a fixed-dose combination with cobicistat may be used.
• Should be taken with food to enhance absorption and minimise GI upset.

⚠️ Interactions

• Extensive metabolism by CYP3A4 — strong inducers (e.g. rifampicin) greatly reduce efficacy.
• Proton-pump inhibitors and antacids decrease absorption due to higher gastric pH — avoid or separate dosing.
• May increase levels of other CYP3A4 substrates (e.g. statins, benzodiazepines).
• Always confirm specific interactions in the BNF.

🚧 Cautions

• Monitor for PR interval prolongation — use with caution in patients with conduction abnormalities.
• May cause hyperbilirubinaemia and visible jaundice (usually benign and reversible).
• Use caution in moderate hepatic impairment.
• Monitor lipids and glucose during long-term therapy.

⛔ Contraindications

• Co-administration with potent CYP3A4 inducers (e.g. rifampicin, St John’s wort).
• Severe hepatic impairment.
• Known hypersensitivity to atazanavir or any component of the formulation.

💥 Side Effects

• ⚡ Hyperbilirubinaemia → yellow sclerae/jaundice (cosmetic, not hepatotoxic).
• 💇‍♀️ Alopecia, anaemia, angioedema, rash.
• 😣 GI disturbance, nausea, abdominal discomfort.
• 📈 Metabolic effects: insulin resistance, hyperlipidaemia, fat redistribution.
• Rare: nephrolithiasis, cardiac conduction disturbances.

📚 References

• BNF: Atazanavir
• British HIV Association (BHIVA) Guidelines, 2023.
• European AIDS Clinical Society (EACS) Guidelines, 2023.