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Pharmacologic class: HIV-1 protease azapeptide inhibitor
Therapeutic class: Antiretroviral
Pregnancy risk category B
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
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
• 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
• 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
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).
• Perform liver function tests before starting therapy.
• Administer drug with food.
☞ Be aware that drug isn't recommended for treatment-experienced patients with prior virologic failure.
☞ Don't administer to patient with severe hepatic impairment or treatment-experienced patient who is receiving dialysis for end-stage renal disease.
CNS: headache, insomnia, dizziness, peripheral neurologic symptoms, depression
CV: cardiac conduction abnormalities
EENT: scleral icterus
GI: nausea, vomiting, diarrhea, abdominal pain
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
Skin: rash, erythema multiforme, toxic skin eruptions, Stevens-Johnson syndrome
Other: fever, body fat redistribution or accumulation, immune reconstitution syndrome
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 Cmax, 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 Cmin, 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
☞ Monitor patient closely and discontinue drug if severe rash occurs (possible sign of Stevens-Johnson syndrome).
☞ 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.
☞ 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.
• 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.
☞ 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.
Pharmacologic: protease inhibitors
Time/action profile (blood levels)
|PO||rapid||2.5 hr||24 hr|
Adverse Reactions/Side EffectsWhen used in combination with other antiretrovirals
Central nervous system
- ↑ PR interval
- heart block
- hepatotoxicity (life-threatening)
- nausea (most frequent)
- abdominal pain
- ↑ bilirubin
- ↑ liver enzymes
- dress syndrome (life-threatening)
- erythema multiforme (life-threatening)
- stevens-johnson syndrome (life-threatening)
- fat redistribution
- angioedema (life-threatening)
- immune reconstitution syndrome
Drug-Drug interactionAtazanavir is an inhibitor of CYP3A and UGT1A1 enzyme systems. It is also a substrate of CYP3A.↑ blood levels and risk of toxicity from ergot derivatives (ergotamine, ergonovine, dihydroergotamine, methylergonovine ), midazolam (PO), pimozide, triazolam, lovastatin, simvastatin, sildenafil (Revatio), alfuzosin, and irinotecan ; concurrent use is contraindicated.Concurrent use with indinavir may ↑ risk of hyperbilirubinemia; concurrent use is contraindicated.Levels are significantly ↓ by rifampin ; may promote viral resistance; concurrent use is contraindicated.Combination therapy with tenofovir may lead to ↓ virologic response and possible resistance (100 mg ritonavir should be added to boost blood levels and dose of atazanavir ↓ to 300 mg/day).Levels are significantly ↓ by omeprazole ; do not exceed omeprazole dose of 20 mg/day when used with atazanavir and ritonavir in treatment-naive patients (should be taken at least 12 hr before atazanavir and ritonavir); should not be used in treatment-experienced patients.Concurrent use with didanosine buffered tablets will ↓ absorption and levels; give atazanavir with food 2 hr before or 1 hr after didanosine.Efavirenz ↓ levels and may promote viral resistance; 600 mg efavirenz should be given with atazanavir 400 mg/day and ritonavir 100 mg/day to counteract this effect in treatment-naive patients (should not be used with atazanavir in treatment-experienced patients).↑ saquinavir levels.Levels are ↑ by ritonavir ; ↓ atazanavir dose to 300 mg/day.Nevirapine may ↓ levels and atazanavir may ↑ nevirapine levels; avoid concurrent use.Antacids or buffered medications will ↓ absorption; atazanavir should be given 2 hr before or 1 hr after.↑ levels of lidocaine, amiodarone, or quinidine ; blood level monitoring is recommended.↑ risk of bleeding with warfarin.↑ of tricyclic antidepressants ; blood level monitoring is recommended.↑ levels of rifabutin ; ↓ rifabutin dose by 75% (150 mg every other day or 3 times weekly).↑ levels of diltiazem and its active metabolite; ↓ diltiazem dose by 50% and ECG monitoring recommended. Similar precautions may be needed with felodipine, nifedipine, nicardipine, and verapamil.↑ levels of fluticasone ; consider alternative therapy; should not be used when atazanavir used with ritonavir.↓ levels of voriconazole when atazanavir is used with ritonavir; avoid concurrent use. Voriconazole may also ↑ levels of atazanavir (when used without ritonavir).↑ levels of ketoconazole or itraconazole when atazanavir is used with ritonavir.↑ levels of trazodone ; ↓ dose of trazodone.↑ levels of sildenafil, vardenafil, and tadalafil ; ↓ sildenafil dose to 25 mg every 48 hr; ↓ vardenafil dose to 2.5 mg every 72 hr (when atazanavir used with ritonavir) or 2.5 mg every 24 hr (when atazanavir used alone); ↓ tadalafil dose to 10 mg every 72 hr. Exercise caution and monitor for hypertension, visual changes, and priapism.↑ levels and risk of myopathy from atorvastatin or rosuvastatin ; use lowest possible dose of statin; do not exceed rosuvastatin dose of 10 mg/day.Levels may be ↓ by histamine H2 antagonists, promoting viral resistance; separate doses by at least 10 hr.↑ levels of cyclosporine, sirolimus, and tacrolimus ; monitor immunosuppressant blood levels.↑ levels of clarithromycin ; ↓ clarithromycin dose by 50% or consider alternative therapy.May ↓ levels of some estrogens found in hormonal contraceptives ; use alternative nonhormonal method of contraception.May ↑ levels of buprenorphine ; consider ↓ dose of buprenorphine.Concurrent use of other drugs known to ↑ PR interval may ↑ risk of heart block.May ↑ risk of adverse effects with salmeterol ; concurrent use not recommended.May ↑ bosentan levels; initiate bosentan at 62.5 mg once daily or every other day; if patient already receiving bosentan, discontinue bosentan at least 36 hr before initiation of atazanavir and then restart bosentan at least 10 days later at 62.5 mg once daily or every other day; do not use with atazanavir alone (should be used with atazanavir and ritonavir).May ↑ tadalafil (Adcirca) levels; initiate tadalafil (Adcirca) at 20 mg once daily; if patient already receiving tadalfil (Adcirca), discontinue tadalafil (Adcirca) at least 24 hr before initiation of atazanavir and then restart tadalafil (Adcirca) at least 7 days later at 20 mg once daily.May ↑ colchicine levels; ↓ dose of colchicine; do not administer colchicine if patients have renal or hepatic impairment.Concurrent use with telaprevir results in ↓ telaprevir levels and ↑ atazanavir levels.Concurrent use of boceprevir with atazanavir and ritonavir results in ↓ atazanavir and ritonavir levels; concurrent use not recommended.Carbamazepine, phenytoin, and phenobarbiral may ↓ levels; do not give concurrently with atazanvir without using ritonavirConcurrent use of lamotrigine with atazanavir and ritonavir results in ↓ lamotrigine levels; concurrent use not recommended.Concurrent use of voriconazole with atazanavir and ritonavir may result in either ↓ or ↑ voriconazole levels; concurrent use not recommended.St. John’s wort significantly ↓ blood levels; concurrent use is contraindicated.
Renal ImpairmentOral (Adults) Therapy-Naive and HD—300 mg once daily with ritonavir 100 mg once daily; Therapy-Experienced and HD—contraindicated.
Hepatic ImpairmentOral (Adults) Moderate hepatic impairment—300 mg once daily (do not use with ritonavir).
- Assess for change in severity of HIV symptoms and for symptoms of opportunistic infections throughout therapy.
- Assess for rash which can occur within initial 8 wk of therapy. Usually resolves within 2 weeks without altering therapy. Discontinue therapy if rash becomes severe.
- Lab Test Considerations: Monitor viral load and CD4 cell count regularly during therapy.
- May cause ↑ serum amylase, lipase and hyperglycemia.
- May ↑ liver enzymes.
- May ↑ creatine kinase.
- May cause ↓ hemoglobin, neutrophils, and platelets.
- May cause ↑ in unconjugated bilirubin; reversible on discontinuation.
Potential Nursing DiagnosesRisk for infection (Indications)
Noncompliance (Patient/Family Teaching)
- Oral: Administer daily with food to enhance absorption. Capsules should be swallowed whole; do not open.
- Emphasize the importance of taking atazanavir with food as directed. Advise patient to read the Patient Information before taking and with each Rx refill; may be updated. Atazanavir must always be used in combination with other antiretroviral drugs. Do not take more than prescribed amount and do not stop taking without consulting health care professional. Take missed doses as soon as remembered, then return to regular dose schedule. If within 6 hr of next dose, omit dose and take next dose at regular time. Do not double doses.
- Instruct patient that atazanavir should not be shared with others.
- Inform patient that atazanavir does not cure HIV or prevent associated or opportunistic infections. Atazanavir does not reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and to avoid sharing needles or donating blood to prevent spreading the HIV virus to others. Advise patient that atazanavir may cause lipodystrophy (redistribution or accumulation of body fat) and the long-term effects of atazanavir are unknown at this time.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort; interactions may be fatal.
- May cause dizziness. Caution patient to notify health care professional if this occurs and to avoid driving and other activities requiring alertness until response to medication is known.
- Notify health care professional immediately if yellowing of eyes, change in heart rhythm, or high blood sugar occur.
- Instruct patient to notify health care professional immediately if signs and symptoms of hepatitis (flu-like symptoms, tiredness, nausea, lack of appetite, yellow skin or eyes, dark urine, pale stools, pain or sensitivity to touch on right side below ribs), skin reactions with symptoms (flu-like symptoms, fever, muscle aches, conjunctivitis, blisters, mouth sores, swelling of face, tiredness), gallbladder disorder (right or middle upper stomach pain, fever, nausea, vomiting, or yellowing of skin and whites of eyes), kidney stones (side pain, blood in urine, pain upon urination), or signs of immune reconstitution syndrome (signs and symptoms of an infection) occur.
- Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance. The cause and long-term effects are not known.
- Instruct females using hormonal contraceptives to use an alternative nonhormonal method of contraception. Advise patient to notify health care professional if pregnancy is planned or suspected or if breast feeding. If pregnant patient is exposed to atazanavir, register patient in Antiretroviral Pregnancy Registry by calling 1-800-258-4263.
- Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.
- Delayed progression of HIV and decreased opportunistic infections in patients with HIV.
- Decrease in viral load and increase in CD4 cell counts.