Atazanavir

Mechanism :

Atazanavir (ATV) is an azapeptide HIV-1 protease inhibitor (PI). The compound selectively inhibits the virus-specific processing of viral Gag and Gag-Pol polyproteins in HIV-1 infected cells, thus preventing formation of mature virions.

Indication :

HIV-1 infection

Contraindications :

Atazanavir is contraindicated in patients with known hypersensitivity to any of its ingredients, including atazanavir.

Dosing :

Infants ≥3 months, Children, and Adolescents: Oral

5 to <15 kg: Atazanavir 200 mg plus ritonavir 80 mg once daily.

15 to <35 kg: Atazanavir 250 mg plus ritonavir 80 mg once daily.

≥35 kg: Atazanavir 300 mg plus ritonavir 100 mg once daily.

Adolescents ≥18 years:

Oral: Atazanavir 300 mg once daily plus ritonavir 100 mg or cobicistat 150 mg once daily.

Adverse Effect :

Edema, fever, cough, second-degree AV block, pancreatitis, nausea, hepatic function abnormalities, hyperglycemia, diabetes mellitus, hypercholesterolemia, arthralgia, pruritus, alopecia, maculopapular rash.

Interaction :

Cisapride, Dihydroergotamine, Ergotamine, Ergonovine, Methylergonovine, Midazolam, Pimozide, Triazolam: Atazanavir may inhibit the metabolism of the following drugs and cause serious or life-threatening adverse effects. Concurrent therapy of atazanavir with these drugs are contraindicated.
Rifabutin: Atazanavir significantly increases the AUC of rifabutin by 200%.
Irinotecan: It may increase the serum concentrations or serious toxicities of irinotecan (concurrent use is not recommended).
Amiodarone, Bepridil, Lidocaine, Quinidine, Tricyclic Antidepressants, Warfarin: Monitor INR.
Diltiazem: Consider a 50% dosage reduction in diltiazem, monitor EKG
Nifedipine, Felodipine, Nicardipine, Verapamil, Sildenafil and other Phophodiesterase-5 Enzyme Inhibitors: Decrease dose of sildenafil.
Cholesterol lowering agents: Concurrent use of lovastatin or simvastatin is not recommended, use atorvastatin with care.
Cyclosporine, Sirolimus, Tacrolimus: Monitor immunosuppressant serum concentrations.
Clarithromycin: Consider a 50% dosage reduction in clarithromycin; consider alternative antibiotic for non-MAC infections.
Ethinyl Estradiol and Norethindrone oral Contraceptive Agents or Contraceptive Patch.
Atazanavir: Increases serum concentrations of saquinavir.
Ritonavir: Significantly increases fluticasone levels in the serum and may result in systemic corticosteroid effects, when ritonavir and atazanavir are used together they have the same effect on fluticasone. Moreover, caution is advised while using atazanavir without ritonavir since it may increase fluticasone levels as well.
Proton Pump Inhibitors: Concurrent use with proton pump inhibitors is not recommended since it decreases the gastrointestinal pH and thus decreases the solubility and subsequently decrease the plasma concentrations of atazanavir in the plasma.
St John's warts: The herbal medicine St John's warts may significantly decrease concentrations of atazanavir and is not recommended for concurrent use.

Renal Dose :

Dose in Renal Impairment GFR (mL/min)

20-50	Dose as in normal renal function
10-20	Dose as in normal renal function
<10	Dose as in normal renal function

Dose in Patients undergoing Renal Replacement Therapies

CAPD	Unlikely to be dialysed. Dose as in normal renal function
HD	Unlikely to be dialysed. Dose as in normal renal function
HDF/High flux	Unlikely to be dialysed. Dose as in normal renal function
CAV/VVHD	Unknown dialysability. Dose as in normal renal function

Hepatic Dose :

Mild to moderate hepatic impairment: Use reduced dose of atazanavir (300mg PO OD) without ritonavir.
Severe hepatic impairment: Use is contraindicated.