Action

Selectively inhibits the virus-specific processing of viral Gag and Gag-Pol polyproteins in human immunodeficiency virus (HIV)-1 infected cells, preventing formation of mature virions

Availability

Capsules: 100 mg, 150 mg, 200 mg, 300 mg

Indications and dosages

➣ Treatment-naïve patients with HIV-1 infection in combination with ritonavir

Adults: 300 mg with ritonavir 100 mg P.O. daily. When administered with tenofovir, H2-receptor antagonists, or proton pump inhibitors, give 300 mg with ritonavir 100 mg P.O. daily. When administered with efavirenz, give 400 mg with ritonavir 100 mg P.O. daily. Give 400 mg P.O. daily if patient is unable to tolerate ritonavir.

Adults and children at least age 13 weighing at least 40 kg ( 88 lb) who are unable to tolerate ritonavir: 400 mg (without ritonavir) P.O. daily (For patients at least age 13 and at least 40 kg receiving concomitant tenofovir, H₂-receptor antagonists, or proton pump inhibitors, atazanavir should not be administered without ritonavir.)

➣ Treatment-experienced patients with HIV-1 infection in combination with other antiretrovirals

Adults: 300 mg with ritonavir 100 mg P.O. daily. When administered with an H₂-receptor antagonist, give 300 mg with ritonavir 100 mg P.O. daily. When administered with tenofovir and an H₂-receptor antagonist, give 400 mg with ritonavir 100 mg P.O. daily.

➣ HIV-1 infection

Children ages 6 to younger than 18 weighing at least 40 kg (88 lb): 300 mg with ritonavir 100 mg P.O. daily

Children ages 6 to younger than 18 weighing at least 20 kg (44 lb) to less than 40 kg: 200 mg with ritonavir 100 mg P.O. daily

Children ages 6 to younger than 18 weighing at least 15 kg (33 lb) to less than 20 kg: 150 mg with ritonavir 100 mg P.O. daily

Dosage adjustment

• Hepatic impairment

• Administration with sildenafil citrate, tadalafil, or vardenafil

• Treatment-experienced pregnant women during second or third trimester, when administered with either an H₂-receptor antagonist or tenofovir

Contraindications

• Hypersensitivity to drug or its components

• Administration with alfuzosin, triazolam, oral midazolam, ergot derivatives, rifampin, irinotecan, lovastatin, simvastatin, indinavir, cisapride, pimozide, sildenafil (Revatio), or St. John's wort

Precautions

Use cautiously in:

• hepatic impairment (use not recommended)

• renal impairment (drug shouldn't be administered to HIV treatment-experienced patients with end-stage renal disease managed with hemodialysis)

• conduction abnormalities and coadministration of drugs that may prolong PR interval, especially those metabolized by CYP3A (such as verapamil)

• concomitant use of antiarrhythmics (such as amiodarone, bepridil, systemic lidocaine, quinidine); antidepressants (such as trazodone, tricyclic antidepressants); high doses of ketoconazole and itraconazole (above 200 mg/day); calcium channel blockers; hormonal contraceptives

• concomitant use of endothelin-receptor antagonist (such as bosentan) without ritonavir (use not recommended)

• concomitant use of inhaled nasal steroid (such as fluticasone propionate) and atazanavir without ritonavir

• concomitant use of inhaled nasal steroid (such as fluticasone propionate) and atazanavir with ritonavir (use not recommended unless potential benefit to patient outweighs risk of systemic corticosteroid adverse effects)

• concomitant use of proton pump inhibitors (such as omeprazole) (shouldn't be used in treatment-experienced patients receiving atazanavir)

• concomitant use of opioid (such as buprenorphine) and atazanavir without ritonavir (shouldn't be coadministered)

• administration of drugs highly dependent on CYP2C8 with narrow indices (such as paclitaxel, repaglinide) when atazanavir is administered without ritonavir

• concomitant use of antifungal (such as voriconazole) (shouldn't be administered with atazanavir/ritonavir unless benefit/risk assessment justifies use of voriconazole)

• concomitant use of antigout agent (such as colchicine) (shouldn't be administered with atazanavir to patients with hepatic or renal impairment)

• concomitant use of atazanavir with efavirenz in treatment-experienced patients (don't coadminister)

• concomitant use of inhaled beta agonist (such as salmeterol) (use not recommended)

• pregnant (avoid use without ritonavir) or breastfeeding patients

• patients less than 40 kg (88 lb) receiving concomitant tenofovir, H₂-receptor antagonists, or protonpump inhibitors (not recommended)

• children younger than age 13 (avoid use without ritonavir)

• children ages 3 months to 6 years (safety and efficacy not established)

• children younger than age 3 months (avoid use).

Administration

• Perform liver function tests before starting therapy.

• Administer drug with food.

See Be aware that drug isn't recommended for treatment-experienced patients with prior virologic failure.

See Don't administer to patient with severe hepatic impairment or treatment-experienced patient who is receiving dialysis for end-stage renal disease.

Adverse reactions

CNS: headache, insomnia, dizziness, peripheral neurologic symptoms, depression

CV: cardiac conduction abnormalities

EENT: scleral icterus

GI: nausea, vomiting, diarrhea, abdominal pain

GU: nephrolithiasis

Hematologic: neutropenia, thrombocytopenia, leukopenia, increased bleeding (in patients with hemophilia A and B)

Hepatic: jaundice, hepatotoxicity

Metabolic: hyperbilirubinemia, hyperglycemia, possible exacerbation of or new-onset diabetes mellitus

Musculoskeletal: myalgia

Respiratory: cough

Skin: rash, erythema multiforme, toxic skin eruptions, Stevens-Johnson syndrome

Other: fever, body fat redistribution or accumulation, immune reconstitution syndrome

Interactions

Drug-drug. Antacids, buffered drugs, H₂-receptor antagonists, proton pump inhibitors: decreased atazanavir plasma concentration

Antiarrhythmics (such as amiodarone, bepridil, systemic lidocaine, quinidine), tricyclic antidepressants): increased risk of serious or life-threatening adverse reactions

Atorvastatin, rosuvastatin: increased risk of myopathy including rhabdomyolysis

Bosentan: decreased atazanavir level, increased bosentan level

Buprenorphine: increased buprenorphine and its active metabolite norbuprenorphine plasma concentrations, decreased atazanavir level

Calcium channel blockers (such as diltiazem, felodipine, nifedipine, nicardipine, verapamil): increased calcium channel blocker effect

Clarithromycin: increased atazanavir and clarithromycin levels resulting in prolonged QTc interval; significantly reduced active clarithromycin metabolite level

Colchicine: increased colchicine effect

Cyclosporine, sirolimus, tacrolimus: increased immunosuppressant levels

Didanosine (buffered tablets): marked decrease in atazanavir exposure

Drugs primarily metabolized by CYP3A, UGT1A1, other drugs (such as alfuzosin, cisapride, ergot derivatives, indinavir, irinotecan, lovastatin, oral midazolam, pimozide, rifampin, sildenafil [Revatio], simvastatin, triazolam): increased plasma concentration of these drugs resulting in serious or life-threatening adverse reactions

Drugs that prolong PR interval (beta blockers other than atenolol, digoxin, verapamil): expected additive effect of atazanavir

Efavirenz: decreased atazanavir exposure

Ethinyl estradiol with norgestimate: decreased ethinyl estradiol level, increased norgestimate level

Ethinyl estradiol with norethindrone: increased ethinyl estradiol and norethindrone levels

Fluticasone: increased fluticasone plasma concentration

Fluticasone and atazanavir/ritonavir: increased fluticasone plasma concentration resulting in significantly reduced cortisol levels

H₂-receptor antagonists: decreased atazanavir plasma concentration resulting in loss of therapeutic effect and development of resistance

Itraconazole, ketoconazole: increased atazanavir area under the curve (AUC) and C_max, increased itraconazole and ketoconazole effects

Midazolam (parenteral): increased midazolam plasma concentrations, risk of respiratory depression and prolonged sedation

Nevirapine: markedly decreased atazanavir effect; increased nevirapine effect with risk of nevirapine-associated toxicity

Other protease inhibitors: expected increased effect of these drugs

Rifabutin: increased risk of rifabutin-associated adverse reactions

Ritonavir: increased atazanavir effect

Salmeterol: increased risk of cardiovascular adverse reactions including prolonged QT interval, palpitations, and sinus tachycardia

Sildenafil, tadalafil, vardenafil: possible increased phosphodiesterase inhibitor-associated adverse reactions (hypotension, syncope, visual disturbances, priapism)

Tenofovir: decreased atazanavir AUC and C_min, increased tenofovir level

Trazodone: increased trazodone plasma level

Warfarin: increased risk of serious or life-threatening bleeding

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, amylase, blood glucose, creatine kinase, high-density lipoproteins, lipase, low-density lipoproteins, total bilirubin, total cholesterol, triglycerides: increased levels

Hemoglobin, neutrophils, platelets: decreased levels

Drug-food. Any food: enhanced bioavailability and reduced pharmacokinetic variability

Drug-herbs. St. John's wort: decreased atazanavir plasma concentrations

Patient monitoring

See Monitor patient closely and discontinue drug if severe rash occurs (possible sign of Stevens-Johnson syndrome).

See Be aware that immune reconstitution syndrome may occur in patients receiving combination antiretroviral therapy. During initial phase of therapy, patient whose immune system responds may develop inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium complex, cytomegalovirus, Pneumocystis jiroveci pneumonia, tuberculosis), which may necessitate further evaluation and treatment.

See Temporarily interrupt or discontinue drug if signs or symptoms of nephrolithiasis occur.

• Monitor blood glucose level during therapy; watch for signs or symptoms of new-onset or exacerbation of diabetes mellitus and redistribution or accumulation of body fat.

• Monitor CBC with differential and liver and kidney function tests closely.

Patient teaching

• Instruct patient to take drug by mouth with food, to swallow capsules whole, and not to crush or chew them.

• Instruct patient to take drug 2 hours before or 1 hour after taking antacids or a buffered form of drugs.

See Instruct patient to immediately report severe rash, changes in pulse or heart beat, signs or symptoms of kidney stones (pain in the side, blood in urine, or pain when urinating), yellowing of eyes, or signs and symptoms of immune reconstitution syndrome (such as new signs or symptoms of a previously subclinical infection, worsening or progression of a known infection despite treatment, a new infection or illness, or failure of antiretroviral therapy).

• Inform patient that drug may cause increase in blood glucose level and redistribution or accumulation of body fat.

• Advise patient to consult prescriber before using other prescription or over-the-counter drugs or herbs.

• Advise male patient taking sildenafil, tadalafil, or vardenafil to promptly report hypotension, visual changes, or prolonged penile erection to prescriber.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.