Medication Guide App

Atazanavir Sulfate

Class: HIV Protease Inhibitors
VA Class: AM800
Chemical Name: (3S,8S,9S,12S) - 3,12 - Bis(1,1 - dimethylethyl) - 8 - hydroxy - 4,11 - dioxo - 9 - (phenylmethyl) - 6 - {[4 - (2 - pyridinyl)phenyl]methyl{ - 2,5,6,10,13 - pentaazatetradecanedioic acid dimethyl ester, sulfate (1:1)
Molecular Formula: C38H52N6O7•H2SO4
CAS Number: 22997597-7
Brands: Reyataz

Introduction

Antiretroviral; HIV protease inhibitor (PI).1

Uses for Atazanavir Sulfate

Treatment of HIV Infection

Treatment of HIV-1 infection in conjunction with other antiretrovirals.1 2 3 4 7 14 200 201

Usually used in conjunction with low-dose ritonavir (ritonavir-boosted atazanavir) in PI-based regimens that include a PI and 2 nucleoside reverse transcriptase inhibitors (NRTIs).1 200 201

Slideshow: Flashback: FDA Drug Approvals 2013

For initial treatment in antiretroviral-naive adults and adolescents, ritonavir-boosted atazanavir in conjunction with tenofovir and either emtricitabine or lamivudine is a preferred PI-based regimen and ritonavir-boosted atazanavir in conjunction with abacavir and either lamivudine or emtricitabine is an alternative PI-based regimen.200

For initial treatment in antiretroviral-naive children, ritonavir-boosted atazanavir in conjunction with 2 NRTIs is a preferred PI-based regimen in those ≥6 years of age.201

Atazanavir (without low-dose ritonavir) can be used in adults and adolescents ≥13 years of age weighing ≥40 kg who cannot tolerate ritonavir,1 200 201 but should not be used in antiretroviral-experienced (previously-treated) patients with prior virologic failure.1

Postexposure Prophylaxis of HIV

Postexposure prophylaxis of HIV infection in health-care workers and others exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with a risk for transmission of the virus.199 Used in conjunction with other antiretrovirals.199

Postexposure prophylaxis of HIV infection in individuals who have had nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.198 Used in conjunction with other antiretrovirals.198

Atazanavir Sulfate Dosage and Administration

Administration

Oral Administration

Administer orally once daily with food.1

Swallow capsules whole; do not open.1

Usually administered with low-dose ritonavir (ritonavir-boosted atazanavir);1 200 201 may be used without low-dose ritonavir in adults and adolescents ≥13 years of age unable to tolerate ritonavir.1

If used with low-dose ritonavir, take both drugs at same time.1

If used with a histamine H2-receptor antagonist in antiretroviral-naive or antiretroviral-experienced adults, administer ritonavir-boosted atazanavir simultaneously with, and/or at least 10 hours after, the histamine H2-receptor antagonist.1 (See Specific Drugs under Interactions.)

If used with a histamine H2-receptor antagonist in antiretroviral-naive adults unable to tolerate ritonavir, administer atazanavir at least 2 hours before and 10 hours after the histamine H2-receptor antagonist.1 (See Specific Drugs under Interactions.)

If used with a proton-pump inhibitor in antiretroviral-naive adults, administer proton-pump inhibitor approximately 12 hours before ritonavir-boosted atazanavir.1 (See Specific Drugs under Interactions.)

Dosage

Available as atazanavir sulfate;1 dosage expressed in terms of atazanavir.1

Pediatric Patients

Treatment of HIV Infection
Oral

Children 6 years to <18 years of age: Dosage is based on body weight.1 (See Table 1.) Do not exceed adult dosage.1

Dosage of Ritonavir-boosted Atazanavir for Pediatric Patients 6 Years to <18 Years of Age1

Body Weight

Atazanavir Dosage

Ritonavir Dosage

15 to <20 kg

150 mg once daily

100 mg once daily

20 to <40 kg

200 mg once daily

100 mg once daily

≥40 kg

300 mg once daily

100 mg once daily

Adolescents ≥13 years of age who weigh ≥40 kg and are unable to tolerate ritonavir: Recommended dosage of atazanavir (without low-dose ritonavir) is 400 mg once daily.1

Do not use atazanavir (without low-dose ritonavir) in patients ≥13 years of age weighing ≥40 kg who are receiving concomitant therapy with tenofovir, a histamine H2-receptor antagonist, or a proton-pump inhibitor.1

Adults

Treatment of HIV Infection
Antiretroviral-naive Adults
Oral

300 mg once daily boosted with low-dose ritonavir (100 mg once daily).1 For adults unable to tolerate ritonavir, recommended dosage of atazanavir (without low-dose ritonavir) is 400 mg once daily.1

If tenofovir is included in the regimen, use 300 mg of atazanavir once daily boosted with low-dose ritonavir (100 mg once daily).1

If efavirenz is included in the regimen, use 400 mg of atazanavir once daily boosted with low-dose ritonavir (100 mg once daily).1

If a histamine H2-receptor antagonist or proton-pump inhibitor is given concomitantly, use 300 mg of atazanavir once daily boosted with low-dose ritonavir (100 mg once daily).1 (See Specific Drugs under Interactions.)

If a histamine H2-receptor antagonist is given concomitantly and patient cannot tolerate ritonavir, use 400 mg of atazanavir once daily.1 (See Specific Drugs under Interactions.)

Antiretroviral-experienced Adults
Oral

300 mg once daily boosted with low-dose ritonavir (100 mg once daily).1

If a histamine H2-receptor antagonist is given concomitantly, use 300 mg of atazanavir once daily boosted with low-dose ritonavir (100 mg once daily).1 (See Specific Drugs under Interactions.)

If tenofovir is included in the regimen and a histamine H2-receptor antagonist is given concomitantly, use 400 mg of atazanavir once daily boosted with low-dose ritonavir (100 mg once daily).1 (See Specific Drugs under Interactions.)

Postexposure Prophylaxis of HIV
Occupational Exposure
Oral

400 mg once daily.199 If tenofovir included in the regimen, use 300 mg of atazanavir once daily boosted with low-dose ritonavir (100 mg once daily).199

Initiate postexposure prophylaxis as soon as possible following exposure (within hours rather than days) and continue for 4 weeks, if tolerated.199

Nonoccupational Exposure
Oral

400 mg once daily.198 If tenofovir included in the regimen, use 300 mg of atazanavir once daily boosted with low-dose ritonavir.198

Initiate postexposure prophylaxis as soon as possible following exposure (preferably ≤72 hours after exposure) and continue for 28 days.198

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection
Oral

Do not exceed adult dosage.1

Children ≥6 years of age: Maximum 300 mg once daily boosted with low-dose ritonavir (100 mg once daily).1

Antiretroviral-naive adolescents ≥13 years of age weighing ≥40 kg: Maximum 400 mg once daily (without low-dose ritonavir).1

Special Populations

Hepatic Impairment

Oral

Patients with moderate hepatic impairment (Child-Pugh class B) without prior virologic failure: Consider reduced dosage of 300 mg once daily (without low-dose ritonavir).1 200 Do not use in those with severe hepatic impairment (Child-Pugh class C).1

Ritonavir-boosted atazanavir not recommended in patients with hepatic impairment.1

Renal Impairment

Oral

Patients with renal impairment, including those with severe renal impairment not undergoing hemodialysis: Dosage adjustments not needed.1

Antiretroviral-naive patients with end-stage renal disease undergoing hemodialysis: 300 mg once daily boosted with low-dose ritonavir (100 mg once daily).1

Antiretroviral-experienced patients with end-stage renal disease undergoing hemodialysis: Atazanavir (with or without low-dose ritonavir) not recommended.1

Geriatric Patients

Dosage adjustments based solely on age not required in patients ≥65 years of age.1

Pregnant and Postpartum Women

Do not use atazanavir without low-dose ritonavir.1 Monitor closely for adverse effects, especially during first 2 months after delivery.1 (See Pregnancy under Cautions.)

Manufacturer states dosage adjustments not usually necessary during pregnancy or the postpartum period unless used concomitantly with certain drugs.1 Experts recommend using increased dosage of 400 mg once daily with low-dose ritonavir (100 mg once daily) during second and third trimesters.202

Antiretroviral-experienced pregnant women in second or third trimester also receiving either a histamine H2-receptor antagonist or tenofovir: Increase atazanavir dosage to 400 mg once daily boosted with ritonavir (100 mg once daily).1 Dosage recommendations not available for antiretroviral-experienced pregnant women receiving both a histamine H2-receptor antagonist and tenofovir.1

Cautions for Atazanavir Sulfate

Contraindications

  • History of clinically important hypersensitivity reaction (e.g., Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions) to atazanavir or any ingredient in the formulation.1

  • Concomitant use with drugs highly dependent on CYP3A or uridine diphosphate-glucuronosyltransferase (UGT) 1A1 for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., alfuzosin, cisapride, ergot alkaloids, indinavir, irinotecan, lovastatin, oral midazolam, pimozide, sildenafil used for treatment of pulmonary arterial hypertension [PAH], simvastatin, triazolam) or with drugs that may decrease atazanavir concentrations resulting in possible loss of virologic response (e.g., rifampin, St. John’s wort [Hypericum perforatum], triazolam).1 (See Specific Drugs under Interactions.)

Warnings/Precautions

Interactions

Concomitant use with certain drugs is contraindicated or requires particular caution.1 (See Specific Drugs under Interactions.)

When ritonavir-boosted atazanavir is used, the usual cautions, precautions, and contraindications associated with ritonavir should be considered.1

Cardiovascular Effects

Abnormalities in AV conduction (including prolongation of PR interval) reported.1 Cardiac conduction abnormalities generally are asymptomatic and limited to first-degree AV block.1

Use with caution in patients with preexisting cardiac conduction abnormalities (e.g., marked first-degree AV block; second- or third-degree AV block) because of lack of clinical experience.1

Caution advised if used with other drugs that prolong PR interval (e.g., some β-adrenergic blocking agents, some calcium-channel blocking agents, digoxin, fixed combination of lopinavir and ritonavir [lopinavir/ritonavir]).1 207 (See Specific Drugs under Interactions.)

Sensitivity Reactions

Dermatologic Reactions

Rash (generally mild to moderate maculopapular eruptions) reported frequently.1 Median time to onset is 7.3 weeks; median duration is 1.4 weeks.1 Stevens-Johnson syndrome, erythema multiforme, and toxic skin eruptions, including drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, reported.1

Discontinue atazanavir in patients who develop severe rash.1

Hyperbilirubinemia

Reversible, asymptomatic elevations in indirect (unconjugated) bilirubin occur in most patients since atazanavir is a competitive inhibitor of UGT 1A1 (an enzyme that catalyzes the glucuronidation of bilirubin).1

Total bilirubin concentrations ≥2.6 times ULN reported in 35–49% of patients; long-term safety data not available for patients with persistent elevations in total bilirubin >5 times ULN.1

If increases in serum AST and/or ALT occur with hyperbilirubinemia, evaluate for etiologies other than hyperbilirubinemia.1

If jaundice or scleral icterus resulting from elevated bilirubin causes cosmetic concerns, alternative antiretroviral therapy can be considered; reduction of atazanavir dosage not recommended since efficacy data not available.1

Hyperbilirubinemia reported in pregnant women receiving atazanavir.1 Neonates exposed in utero also at risk; monitor for severe hyperbilirubinemia during first few days of life.1

Nephrolithiasis

Nephrolithiasis reported in postmarketing surveillance.1 If nephrolithiasis occurs, temporarily interrupt or discontinue atazanavir.1

Hyperglycemic and Diabetogenic Effects

Hyperglycemia (potentially persistent), new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with HIV PIs; diabetic ketoacidosis has occurred.1

Initiate or adjust antidiabetic therapy (e.g., insulin, oral hypoglycemic agents) as needed.1

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jiroveci [formerly P. carinii]); this may necessitate further evaluation and treatment.1

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) reported in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.1

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, facial wasting, breast enlargement, and general cushingoid appearance.1

Hemophilia A and B

Increased bleeding, including spontaneous hematomas and hemarthrosis, reported with HIV PIs; causal relationship not established.1

Increased hemostatic (e.g., antihemophilic factor) therapy may be needed.1

HIV Resistance

Possibility of HIV-1 resistant to atazanavir.1 9 11

Varying degrees of cross-resistance occur among the various HIV PIs.1 Resistance to atazanavir may not preclude subsequent use of other HIV PIs.1

Specific Populations

Pregnancy

Category B.1

Antiretroviral Pregnancy Registry at 800-258-4263 or .1 202

In pregnant or postpartum women, administer only as ritonavir-boosted atazanavir.1

Manufacturer states use in pregnant women only if clearly needed and when HIV-1 is susceptible to atazanavir.1

Experts state that ritonavir-boosted atazanavir is a preferred PI for use in pregnant women.202 Dosage adjustments may be necessary.1 (See Pregnant and Postpartum Women under Dosage.)

Available data suggest atazanavir does not elevate risk of major birth defects.1 202

Lactic acidosis, sometimes fatal, and symptomatic hyperlactatemia reported in pregnant women receiving atazanavir in conjunction with NRTIs.1

Hyperbilirubinemia reported in pregnant women receiving ritonavir-boosted atazanavir.1 Bilirubin concentrations ≥4 mg/dL reported within 24 hours of birth in some neonates born to women who received the drug during pregnancy.1 Monitor neonates exposed to atazanavir in utero for development of severe hyperbilirubinemia during first few days of life.1

Monitor postpartum women closely for adverse effects during first 2 months after delivery; atazanavir concentrations and AUC may be increased during postpartum period.1 (See Special Populations under Pharmacokinetics: Absorption.)

Lactation

Distributed into milk in low concentrations.202 (See Distribution under Pharmacokinetics.)

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.1

Pediatric Use

Should not be used in neonates and infants <3 months of age because of risk of kernicterus.1 Closely monitor any infant exposed to the drug in utero.1 (See Pregnancy under Warnings/Precautions.)

Safety, efficacy, and pharmacokinetic profile not established in children 3 months to <6 years of age.1

Adverse effects in children 6–18 years of age generally similar to those reported in adults.1

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.1

Use with caution and monitor because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Hepatic Impairment

Principally metabolized and eliminated by the liver; increased plasma atazanavir concentrations expected in patients with moderate to severe hepatic impairment.1

Use with caution in those with mild to moderate hepatic impairment.1 Consider dosage adjustments in those with moderate hepatic impairment (Child-Pugh class B).1 (See Hepatic Impairment under Dosage and Administration.)

Do not use in those with severe hepatic impairment (Child-Pugh class C).1

Those with HBV or HCV infection and those with marked increases in AST or ALT prior to atazanavir therapy may be at increased risk for further elevations in hepatic enzymes or for hepatic decompensation.1 Perform liver function testing prior to and periodically during atazanavir therapy in such individuals.1

Ritonavir-boosted atazanavir not recommended in those with hepatic impairment.1

Renal Impairment

Plasma concentrations in individuals with severe renal impairment not undergoing dialysis generally are similar to those in individuals with normal renal function.1 Dosage adjustment not needed.1

Atazanavir boosted with low-dose ritonavir can be used in antiretroviral-naive patients with end-stage renal disease who are undergoing hemodialysis.1

Do not use atazanavir (with or without low-dose ritonavir) in antiretroviral-experienced patients with end-stage renal disease undergoing hemodialysis.1 200

Common Adverse Effects

Adults: Headache, nausea, jaundice/scleral icterus, abdominal pain, rash, vomiting, diarrhea, insomnia, peripheral neurologic symptoms, dizziness, myalgia, depression, fever.1

Pediatric patients 6 years to <18 years of age: Elevated total bilirubin, cough, fever, jaundice/scleral icterus, rash, vomiting, diarrhea, neutropenia, headache, peripheral edema, extremity pain, nasal congestion, oropharyngeal pain, wheezing, rhinorrhea, hypoglycemia.1

Interactions for Atazanavir Sulfate

Atazanavir metabolized by CYP3A.1

Atazanavir inhibits CYP3A, CYP2C8, and UGT1A1.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inducers of CYP3A4 or substrates of CYP3A with possible alteration in metabolism and concentrations of atazanavir and/or the other drug.1

Pharmacokinetic interactions possible with drugs that are CYP3A or 2C8 substrates.1

Drugs Metabolized by Uridine Diphosphate-glucuronosyltransferase 1A1

Pharmacokinetic interactions possible with drugs that are UGT 1A1 substrates.1

Specific Drugs

Drug

Interaction

Comments

Abacavir

No in vitro evidence of antagonistic antiretroviral effects1

Acetaminophen

Pharmacokinetic interaction unlikely1

Alfuzosin

Possible increased alfuzosin concentrations; may result in hypotension1

Concomitant use contraindicated1

Antacids

Possible decreased atazanavir concentrations1

Take atazanavir at least 2 hours before or 1 hour after antacids1 200

Antiarrhythmic agents (amiodarone, systemic lidocaine, quinidine)

Possible increased antiarrhythmic agent concentrations; potential for serious and/or life-threatening effects1

Use concomitantly with caution; monitor serum concentrations of antiarrhythmic agent1

Anticoagulants, oral

Potential for increased warfarin concentrations and serious and/or life-threatening bleeding episodes1

Monitor INR,1 especially when initiating or discontinuing atazanavir;200 adjust warfarin dosage accordingly200

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Carbamazepine: Possible decreased atazanavir concentrations if used with atazanavir (without low-dose ritonavir);200 possible decreased atazanavir concentrations and increased carbamazepine concentrations if used with ritonavir-boosted atazanavir200

Phenobarbital: Possible decreased atazanavir concentrations200

Phenytoin: Possible decreased atazanavir concentrations if used with atazanavir (without low-dose ritonavir);200 possible decreased atazanavir and phenytoin concentrations if used with ritonavir-boosted atazanavir200

Carbamazepine, phenobarbital, phenytoin: Consider use of ritonavir-boosted atazanavir or use an alternative anticonvulsant;200 If used with atazanavir (with or without low-dose ritonavir), monitor serum concentrations of both drugs and virologic response200

Antifungals, azoles (fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole)

Fluconazole: No clinically important pharmacokinetic interactions with ritonavir-boosted atazanavir1

Itraconazole: Possible increased atazanavir and itraconazole concentrations if used with atazanavir or ritonavir-boosted atazanavir 1 200

Ketoconazole: No clinically important increases in atazanavir concentrations if used with atazanavir (without low-dose ritonavir);1 possible increased ketoconazole concentrations with ritonavir-boosted atazanavir1

Posaconazole: Increased atazanavir concentrations if used with atazanavir (with or without low-dose ritonavir)32 200

Voriconazole: Possible increased atazanavir and voriconazole concentrations if used with atazanavir (without low-dose ritonavir); possible decreased voriconazole concentrations and AUC if used with ritonavir-boosted atazanavir1 200

Fluconazole: Dosage adjustments not needed if used with ritonavir-boosted atazanavir200

Itraconazole: In patients receiving atazanavir (with or without low-dose ritonavir), consider monitoring itraconazole concentrations to guide dosage adjustments;200 caution if itraconazole dosage >200 mg daily is used with ritonavir-boosted atazanavir;1 monitor itraconazole concentrations in those receiving >200 mg daily200

Ketoconazole: Caution if ketoconazole dosage >200 mg daily is used with ritonavir-boosted atazanavir1

Posaconazole: If used with atazanavir (with or without low-dose ritonavir), monitor for atazanavir-associated adverse effects32 200

Voriconazole: Monitor for toxicities if used with atazanavir (without low-dose ritonavir);200 do not use with ritonavir-boosted atazanavir unless potential benefits outweigh risk;1 200 if used with ritonavir-boosted atazanavir, consider monitoring voriconazole concentration and adjusting voriconazole dosage accordingly200

Antimycobacterials (rifabutin, rifampin, rifapentine)

Rifabutin: Increased concentrations and AUC of rifabutin and its metabolite1 200

Rifampin: Substantially decreased atazanavir concentrations; possible loss of virologic response and development of resistance1

Rifapentine: Possible decreased atazanavir concentrations200

Rifabutin: If used with atazanavir (with or without low-dose ritonavir), reduce rifabutin dosage to 150 mg every other day or 3 times weekly;1 if used with ritonavir-boosted atazanavir, some experts suggest rifabutin 150 mg once daily or 300 mg 3 times weekly;200 monitor for rifabutin-associated adverse effects (e.g., neutropenia);1 monitor for antimycobacterial response and consider therapeutic drug monitoring200

Rifampin: Concomitant use contraindicated1

Rifapentine: Concomitant use not recommended200

Atovaquone and Proguanil

Ritonavir-boosted atazanavir: Decreased atovaquone and proguanil concentrations200

Consider alternative for malaria prophylaxis, if possible200

Avanafil

Possible increased avanafil concentrations and AUC188

Do not use concomitantly188

Benzodiazepines

Midazolam or triazolam: Possible increased concentrations of midazolam or triazolam; potential for serious and/or life-threatening effects (e.g., prolonged or increased sedation or respiratory depression)1

Alprazolam or diazepam: Possible increased benzodiazepine concentrations200

Lorazepam, oxazepam, temazepam: No data, but may have less potential for pharmacokinetic interaction with PIs compared with other benzodiazepines200

Oral midazolam or triazolam: Concomitant use contraindicated1

Parenteral midazolam: Use with caution in monitored setting where respiratory depression and/or prolonged sedation can be managed; consider reduced midazolam dosage, particularly if multiple doses are administered;1 some experts state a single parenteral midazolam dose can be used with caution in a monitored situation for procedural sedation200

Alprazolam or diazepam: Consider alternative benzodiazepine with less potential for interaction (e.g., lorazepam, oxazepam, temazepam)200

β-Adrenergic blocking agents (atenolol)

Increased concentrations and AUC of atenolol; no effect on PR interval observed1

Use concomitantly with caution;1 atenolol dosage adjustment not needed1

Boceprevir

Ritonavir-boosted atazanavir: Decreased concentrations and AUC of boceprevir, atazanavir, and ritonavir;17 18 185 200 possible reduced efficacy of HCV and HIV treatment regimens17 18

Ritonavir-boosted atazanavir: Concomitant use not recommended12 18 185 200

If boceprevir was initiated for treatment of chronic HCV in a patient coinfected with HIV receiving a suppressive antiretroviral regimen containing ritonavir-boosted atazanavir, inform patient of possible drug interactions and closely monitor for HCV treatment response and potential HCV and HIV virologic rebound12 17 18 200

Bosentan

Possible increased bosentan concentrations and decreased atazanavir concentrations1

Do not use atazanavir without low-dose ritonavir in patients receiving bosentan1

In patients already receiving ritonavir-boosted atazanavir for ≥10 days, initiate bosentan using dosage of 62.5 mg once daily or every other day based on individual tolerability1

In patients already receiving bosentan, discontinue bosentan for at least 36 hours prior to initiating ritonavir-boosted atazanavir; after ≥10 days of ritonavir-boosted atazanavir, resume bosentan using dosage of 62.5 mg once daily or every other day based on individual tolerability1

Buprenorphine

Atazanavir or ritonavir-boosted atazanavir: Increased buprenorphine and norbuprenorphine concentrations;1 possible decreased atazanavir concentrations when used without low-dose ritonavir1

Do not use atazanavir without low-dose ritonavir in patients receiving buprenorphine;1 monitor for sedation and adverse cognitive effects and consider reduced buprenorphine dosage1

Calcium-channel blocking agents (diltiazem, felodipine, nicardipine, nifedipine, verapamil)

Diltiazem: Increased diltiazem concentrations and AUC1 200

Felodipine, nicardipine, nifedipine, verapamil: Possible increased concentrations of calcium-channel blocking agent1

Possible additive effect on PR interval1

Diltiazem: Use concomitantly with caution; consider reducing diltiazem dosage by 50%; ECG monitoring recommended1

Felodipine, nicardipine, nifedipine, verapamil: Use concomitantly with caution; consider dosage titration of the calcium-channel blocker; ECG monitoring recommended1

Cisapride

Possible increased cisapride concentrations and potential for serious and/or life-threatening effects (e.g., cardiac arrhythmias)1

Concomitant use contraindicated1

Colchicine

Increased colchicine concentrations1

Patients with renal or hepatic impairment: Concomitant use of colchicine and atazanavir (with or without low-dose ritonavir) not recommended1

Colchicine for treatment of gout flares: In those receiving atazanavir (with or without low-dose ritonavir), use initial colchicine dose of 0.6 mg followed by 0.3 mg 1 hour later and repeat dose no earlier than 3 days later1

Colchicine for prophylaxis of gout flares: In those receiving atazanavir (with or without low-dose ritonavir), decrease colchicine dosage to 0.3 mg once daily in those originally receiving 0.6 mg twice daily or decrease dosage to 0.3 mg once every other day in those originally receiving 0.6 mg once daily1

Colchicine for treatment of familial Mediterranean fever (FMF): In those receiving atazanavir (with or without low-dose ritonavir), use maximum colchicine dosage of 0.6 mg daily (may be given as 0.3 mg twice daily)1

Corticosteroids (dexamethasone, fluticasone)

Fluticasone nasal spray/oral inhalation: Increased fluticasone concentrations with atazanavir (with or without low-dose ritonavir) resulting in decreased cortisol concentrations1

Dexamethasone: Possible decreased atazanavir concentrations200

Fluticasone nasal spray/oral inhalation: Consider alternative to fluticasone in patients receiving atazanavir without low-dose ritonavir, especially when long-term corticosteroid therapy is anticipated; concomitant use with ritonavir-boosted atazanavir not recommended unless potential benefits outweigh risk of systemic corticosteroid adverse effects1

Systemic dexamethasone: Use concomitantly with caution; consider alternative corticosteroid for long-term use200

Co-trimoxazole

Pharmacokinetic interactions unlikely1

Dapsone

Pharmacokinetic interactions unlikely1

Darunavir

Depending on regimen used, no clinically important change in atazanavir or darunavir concentrations or AUC1

No in vitro evidence of antagonistic antiretroviral effects204

Ritonavir-boosted atazanavir: Concomitant use not recommended204

If used concomitant, some experts recommend darunavir 600 mg twice daily, ritonavir 100 mg twice daily, and atazanavir 300 mg once daily200

Delavirdine

No in vitro evidence of antagonistic antiretroviral effects1

Didanosine

Buffered didanosine: Decreased atazanavir concentrations and AUC;1 decreased didanosine concentrations and AUC1

Didanosine delayed-release capsules: Decreased didanosine concentrations and AUC if given with atazanavir and food;1 200 no change in atazanavir concentrations200

No in vitro evidence of antagonistic antiretroviral effects1

Administer atazanavir (with food) 2 hours before or 1 hour after buffered or delayed-release didanosine preparations (without food)1 200

Digoxin

Potential additive effect on PR interval1

Use concomitantly with caution1

Efavirenz

Atazanavir (without low-dose ritonavir): Substantially decreased atazanavir concentrations and AUC;1 213 200 no clinically important change in efavirenz concentrations200

Ritonavir-boosted atazanavir: Possible increased atazanavir concentrations and AUC depending on specific regimen1 213

No in vitro evidence of antagonistic antiretroviral effects1

Ritonavir-boosted atazanavir in antiretroviral-naive adults: Use atazanavir 400 mg and ritonavir 100 mg once daily (with food) and efavirenz 600 mg once daily (without food, preferably at bedtime)1 200 213

Ritonavir-boosted atazanavir in antiretroviral-experienced adults: Concomitant use not recommended1 200

Atazanavir (without low-dose ritonavir): Do not use with efavirenz1 200

Emtricitabine

No in vitro evidence of antagonistic antiretroviral effects1

Enfuvirtide

No in vitro evidence of antagonistic antiretroviral effects1

Ergot alkaloids (dihydroergotamine, ergonovine, ergotamine, methylergonovine)

Possible increased concentrations of ergot alkaloids and potential for serious and/or life-threatening effects such as ergot toxicity (peripheral vasospasm, ischemia of the extremities and other tissues)1

Concomitant use contraindicated1

If treatment of uterine atony and excessive postpartum bleeding is indicated in a woman receiving atazanavir, use methylergonovine maleate (Methergine) only if alternative treatments cannot be used and if potential benefits outweigh risks; use methylergonovine at lowest dosage and shortest duration possible202

Estrogens/Progestins

Oral hormonal contraceptives containing ethinyl estradiol and norgestimate or norethindrone: Possible increase or decrease in concentrations of ethinyl estradiol and increase in progestin concentrations1 200

Ritonavir-boosted atazanavir: Use an oral contraceptive containing at least 35 mcg of ethinyl estradiol1

Atazanavir (without low-dose ritonavir): Use an oral contraceptive containing no more than 30 mcg of ethinyl estradiol1

Etravirine

Atazanavir or ritonavir-boosted atazanavir: Increased etravirine concentrations, decreased atazanavir concentrations; possible decreased antiretroviral efficacy200 214

No in vitro evidence of antagonistic antiretroviral effects214

Atazanavir (with or without low-dose ritonavir): Do not use concomitantly200 214

Fosamprenavir

Ritonavir-boosted fosamprenavir: Decreased atazanavir concentrations and AUC; no change in concentrations and AUC of amprenavir (active metabolite of fosamprenavir)205

Fosamprenavir (without low-dose ritonavir): No data205

In vitro evidence of synergistic antiretroviral effects205

Fosamprenavir (with or without low-dose ritonavir): Appropriate dosages for concomitant use with respect to safety and efficacy not established205

Histamine H2-receptor antagonists

Famotidine: Decreased atazanavir concentrations with possible loss of therapeutic effect and development of resistance when atazanavir (without low-dose ritonavir) is administered at the same time as the histamine H2-receptor antagonist 1

Antiretroviral-naive and antiretroviral-experienced patients: Administer atazanavir 300 mg and ritonavir 100 mg once daily with food simultaneously with, and/or at least 10 hours after, the histamine H2-receptor antagonist1

Antiretroviral-naive patients unable to tolerate ritonavir: Administer atazanavir 400 mg once daily at least 2 hours before and 10 hours after the histamine H2-receptor antagonist1

Antiretroviral-naive patients: Dosage of histamine H2-receptor antagonist should not exceed famotidine 40 mg twice daily (or equivalent)1

Antiretroviral-experienced patients: Dosage of histamine H2-receptor antagonist should not exceed famotidine 20 mg twice daily (or equivalent)1

If used concomitantly with tenofovir and a histamine H2-receptor antagonist in antiretroviral-experienced patients, a regimen of atazanavir 400 mg, tenofovir disoproxil fumarate 300 mg, and ritonavir 100 mg once daily with food is recommended1 200

Antiretroviral-experienced pregnant women in second and third trimester: Increase dosage of atazanavir to 400 mg once daily with ritonavir 100 mg once daily1

Dosage recommendations not available for antiretroviral-experienced pregnant women receiving atazanavir and both tenofovir and a histamine H2-receptor antagonist 1

HMG-CoA reductase inhibitors

Atorvastatin, lovastatin, pitavastatin, rosuvastatin, simvastatin: Possible increased concentrations and AUC of the antilipemic agents with atazanavir (with or without low-dose ritonavir); increased risk of statin-associated adverse effects, including myopathy and rhabdomyolysis1 186 200

Atorvastatin: Carefully titrate atorvastatin dosage and use lowest necessary dosage1 200

Lovastatin: Concomitant use contraindicated1 186

Pitavastatin: Dosage adjustments not necessary186 200

Rosuvastatin: Do not exceed rosuvastatin dosage of 10 mg once daily;1 186 200 carefully titrate rosuvastatin dosage and use lowest necessary dosage1 200

Simvastatin: Concomitant use contraindicated1 186 200

Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)

Potential for increased concentrations of cyclosporine, sirolimus, or tacrolimus1

Monitor plasma concentrations of the immunosuppressive agent1

Indinavir

Potential for additive hyperbilirubinemia1

Concomitant use contraindicated1

Irinotecan

Possible interference with metabolism of irinotecan; increased risk of irinotecan toxicity1

Concomitant use contraindicated1

Lamivudine

No in vitro evidence of antagonistic antiretroviral effects1

Lopinavir/ritonavir

Prolonged PR interval reported with both atazanavir and lopinavir207

In vitro evidence of additive to synergistic antiretroviral effects;207 no in vitro evidence of antagonism1

Use concomitantly with caution and clinical monitoring207

Some experts recommend a dosage of atazanavir 300 mg once daily with lopinavir 400 mg/ritonavir 100 mg twice daily200

Macrolides (azithromycin, clarithromycin, erythromycin)

Azithromycin: Pharmacokinetic interactions unlikely1

Clarithromycin: Increased concentrations and AUC of atazanavir;1 increased clarithromycin concentrations and decreased 14-hydroxyclarithromycin concentrations;1 increased clarithromycin concentrations may cause QTc prolongation1

Erythromycin: Pharmacokinetic interactions unlikely1

Clarithromycin: Consider reducing clarithromycin dosage by 50%;1 consider alternative to clarithromycin1 for indications other than Mycobacterium avium complex (MAC)1

Maraviroc

Atazanavir (with or without low-dose ritonavir): Increased maraviroc concentrations and AUC224

No in vitro evidence of antagonistic antiretroviral effects224

Atazanavir (with or without low-dose ritonavir): Recommended maraviroc dosage is 150 mg twice daily200

Methadone

Atazanavir: Pharmacokinetic interactions unlikely1

Ritonavir-boosted atazanavir: Decreased R-methadone (active isomer) concentrations200

Ritonavir-boosted atazanavir: Dosage adjustment of methadone not needed; closely monitor for signs of opiate withdrawal and adjust methadone dosage if needed200

Nelfinavir

No in vitro evidence of antagonistic antiretroviral effects1

Nevirapine

Ritonavir-boosted atazanavir: Decreased atazanavir concentrations and AUC; increased nevirapine concentrations and AUC1 200 215

In vitro evidence of additive to synergistic antiretroviral effects;215 no in vitro evidence of antagonistic antiretroviral effects1

Atazanavir (with or without low-dose ritonavir): Do not use concomitantly1 200 215

Paclitaxel

Atazanavir (without low-dose ritonavir): Possible increased paclitaxel concentrations1

Ritonavir-boosted atazanavir: Clinically important interaction not expected1

Atazanavir (without low-dose ritonavir): Use concomitantly with caution1

Pimozide

Atazanavir (with or without low-dose ritonavir): Potential for serious and/or life-threatening effects (e.g., cardiac arrhythmias)1

Concomitant use contraindicated1

Proton-pump inhibitors

Omeprazole: Substantially decreased atazanavir concentrations1

Possible loss of virologic response and development of atazanavir resistance1

Antiretroviral-naive patients: Administer atazanavir 300 mg and ritonavir 100 mg once daily with food; administer the proton-pump inhibitor approximately 12 hours before ritonavir-boosted atazanavir;1 dosage of proton-pump inhibitor should not exceed omeprazole 20 mg daily (or equivalent)1

Antiretroviral-experienced patients: Do not use proton-pump inhibitors concomitantly with atazanavir1

Raltegravir

Atazanavir or ritonavir-boosted atazanavir: Increased raltegravir concentrations and AUC225

In vitro evidence of additive to synergistic antiretroviral effects225

Atazanavir (with or without low-dose ritonavir): Dosage adjustments not needed200 225

Repaglinide

Atazanavir (without low-dose ritonavir): Possible increased repaglinide concentrations1

Ritonavir-boosted atazanavir: Clinically important interaction not expected1

Atazanavir (without low-dose ritonavir): Use concomitantly with caution1

Rilpivirine

Atazanavir or ritonavir-boosted atazanavir: Possible increased rilpivirine concentrations; not expected to affect atazanavir concentrations226

No in vitro evidence of antagonistic antiretroviral effects226

Atazanavir (with or without low-dose ritonavir): Dosage adjustments not needed200

Ritonavir

Increased atazanavir concentrations and AUC ;1 concomitant low-dose ritonavir used to therapeutic advantage (ritonavir-boosted atazanavir)1 13 200

Possibility of additional pharmacokinetic interactions if ritonavir-boosted atazanavir used with other HIV PIs1

Prolonged PR interval reported with both atazanavir and ritonavir209

No in vitro evidence of antagonistic antiretroviral effects1

Recommended dosage is atazanavir 300 mg once daily and ritonavir 100 mg once daily with food;1 safety and efficacy of concomitant use of ritonavir dosages >100 mg once daily not established1

Use concomitantly with caution and clinical monitoring209

Concomitant use of ritonavir-boosted atazanavir with other HIV PIs not recommended1

St. John’s wort (Hypericum perforatum)

Possible decreased atazanavir concentrations; possible loss of virologic response and increased risk of atazanavir resistance1

Concomitant use contraindicated1

Salmeterol

Atazanavir (with or without low-dose ritonavir): Possible increased salmeterol concentrations and increased risk of QT interval prolongation, palpitations, and sinus tachycardia1

Concomitant use not recommended1

Saquinavir

Ritonavir-boosted saquinavir: Increased saquinavir concentrations and AUC; no change in atazanavir concentrations210

Prolonged PR interval reported with both drugs; potential additive effects on PR interval210

In vitro evidence of synergistic antiretroviral effects;210 no in vitro evidence of antagonism1

Appropriate dosage for concomitant use with respect to safety and efficacy not established1 200

Ritonavir-boosted saquinavir: Use concomitantly with caution and clinical monitoring210

Sildenafil

Possible increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (hypotension, syncope, visual disturbances, priapism)1

Sildenafil (Revatio) for treatment of pulmonary arterial hypertension (PAH): Concomitant use with atazanavir (with or without low-dose ritonavir) contraindicated;1 safe and effective dosages for concomitant use not established1

Sildenafil for treatment of erectile dysfunction: Use with caution and with reduced sildenafil dosage (do not exceed 25 mg every 48 hours);1 closely monitor for sildenafil-associated adverse effects1

Stavudine

No in vitro evidence of antagonistic antiretroviral effects1

Tadalafil

Possible increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (hypotension, syncope, visual disturbances, priapism)1

Tadalafil (Adcirca) for treatment of PAH in patients who have been receiving atazanavir (with or without low-dose ritonavir) for ≥1 week: Use initial tadalafil dosage of 20 mg once daily; if tolerated, increase dosage to 40 mg once daily1

Atazanavir (with or without low-dose ritonavir) in patients receiving tadalafil (Adcirca) for PAH: Discontinue tadalafil for at least 24 hours prior to initiating atazanavir; after ≥1 week of the antiretroviral agent, may resume tadalafil at a dosage of 20 mg once daily and, if tolerated, may increase dosage to 40 mg once daily1

Tadalafil for treatment of erectile dysfunction: Do not exceed tadalafil dosage of 10 mg once every 72 hours; use with caution and closely monitor for adverse effects1

Tadalafil for treatment of benign prostatic hyperplasia: Do not exceed tadalafil dosage of 2.5 mg once daily200

Telaprevir

Ritonavir-boosted atazanavir: Decreased telaprevir concentrations and AUC; increased atazanavir trough concentrations and AUC184 200

Ritonavir-boosted atazanavir: Dosage adjustments not needed200

Tenofovir

Atazanavir or ritonavir-boosted atazanavir: Decreased atazanavir concentrations and AUC; increased tenofovir concentrations and AUC and possible increased risk of tenofovir-associated adverse effects, including renal disorders1 200 221

No in vitro evidence of antagonistic antiretroviral effects1

Atazanavir (without low-dose ritonavir): Do not use concomitantly1 200 221

Ritonavir-boosted atazanavir: Use atazanavir 300 mg, ritonavir 100 mg, and tenofovir disoproxil fumarate 300 mg once daily with food;1 200 221 monitor for tenofovir toxicity;1 200 221 discontinue tenofovir if tenofovir-associated adverse effects occur221

Ritonavir-boosted atazanavir: If used concomitantly with tenofovir and a histamine H2-receptor antagonist in antiretroviral-experienced adults, use atazanavir 400 mg, ritonavir 100 mg, and tenofovir disoproxil fumarate 300 mg once daily with food1 200

Antiretroviral-experienced pregnant women in second or third trimester receiving ritonavir-boosted atazanavir and either a histamine H2-receptor antagonist or tenofovir: Use atazanavir 400 mg and ritonavir 100 mg once daily with food1

Dosage recommendations not available for antiretroviral-experienced pregnant women receiving ritonavir-boosted atazanavir and both tenofovir and a histamine H2-receptor antagonist1

Tipranavir

Ritonavir-boosted atazanavir: Decreased atazanavir concentrations and AUC; increased tipranavir concentrations and AUC211

In vitro evidence of additive to antagonistic antiretroviral effects211

Concomitant use not recommended211

Trazodone

Atazanavir (with or without low-dose ritonavir): Possible increased trazodone concentrations; adverse effects (nausea, dizziness, hypotension, syncope) reported when trazodone and ritonavir used concomitantly1

Use concomitantly with caution; consider using decreased trazodone dosage1

Tricyclic antidepressants (amitriptyline, desipramine, imipramine, nortriptyline)

Possible increased concentrations of tricyclic antidepressants and potential for serious and/or life-threatening effects1 200

Monitor tricyclic antidepressant concentrations;1 use lowest possible antidepressant dosage; titrate antidepressant dosage based on plasma antidepressant concentrations and/or clinical assessment200

Vardenafil

Possible increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (hypotension, syncope, visual disturbances, priapism)1 200

If ritonavir-boosted atazanavir is used in patients receiving vardenafil for treatment of erectile dysfunction, use with caution; do not exceed vardenafil dosage of 2.5 mg once every 72 hours and closely monitor for adverse effects (e.g., hypotension, syncope, visual changes, prolonged erection)1

If atazanavir (without low-dose ritonavir) is used in patients receiving vardenafil for treatment of erectile dysfunction, use with caution; do not exceed vardenafil dosage of 2.5 mg once every 24 hours and closely monitor for adverse effects (e.g., hypotension, syncope, visual changes, prolonged erection)1

Zidovudine

No change in zidovudine AUC; possible decreased trough zidovudine concentrations200

No in vitro evidence of antagonistic antiretroviral effects1

Clinical importance unknown200

Atazanavir Sulfate Pharmacokinetics

Absorption

Bioavailability

Atazanavir: Rapidly absorbed following oral administration;1 peak plasma concentrations attained approximately 2–2.5 hours after a dose.1

Ritonavir-boosted atazanavir: Peak plasma concentrations attained approximately 2.7–3 hours after a dose.1

Food

Food increases bioavailability and reduces pharmacokinetic variability.1

Administration of atazanavir with a light meal (357 kcal, 8.2 g fat, 10.6 g protein) increases AUC by 70% and peak plasma concentration by 57% compared with fasting.1 A high-fat meal (721 kcal, 37.3 g fat, 29.4 g protein) increases AUC by 35% with no increase in peak plasma concentration.1

Administration of ritonavir-boosted atazanavir with a light meal (336 kcal, 5.1 g fat, 9.3 g protein) increases AUC by 33% and peak plasma concentration by 40% compared with fasting.1 A high-fat meal (951 kcal, 54.7 g fat, 35.9 g protein) does not affect AUC compared with fasting.1

Plasma Concentrations

Nonlinear pharmacokinetics with greater than dose-proportional increases in plasma concentrations and AUC.1

Steady-state concentrations attained between days 4–8 with an accumulation of approximately 2.3-fold.1

Special Populations

Hepatic Impairment: Following a single 400-mg dose of atazanavir, AUC increased 42% in adults with moderate to severe hepatic impairment (Child-Pugh class B and C) compared with healthy adults.1

Renal Impairment: Plasma concentrations in adults with severe renal impairment not undergoing dialysis generally are similar to those in adults with normal renal function.1 When administered before or after dialysis, plasma concentrations are lower than those in adults with normal renal function (mechanism of this change unknown).1

Postpartum women: Atazanavir steady-state peak plasma concentrations and AUC are approximately 28–43% higher during postpartum period (4–12 weeks) compared with historical data in HIV-infected, nonpregnant patients.1

Distribution

Extent

Low concentrations attained in CSF and semen after oral administration.1

Distributed into cord blood in low concentrations.1 202 When ritonavir-boosted atazanavir used in pregnant women, atazanavir concentrations in cord blood approximately 12–19% of maternal plasma concentrations at delivery.1

Distributed into milk in low concentrations.202

Plasma Protein Binding

86% bound to serum proteins; binding independent of concentration.1

Binds to both α-1-acid glycoprotein (89%) and albumin (86%).1

Elimination

Metabolism

Extensively metabolized and eliminated in liver.1 CYP3A involved in metabolism of the drug.1

Elimination Route

Approximately 79% of a dose eliminated in feces and 13% eliminated in urine as metabolites and unchanged drug.1

Not removed by hemodialysis.1

Half-life

Atazanavir: 6.5–7.9 hours.1

Ritonavir-boosted atazanavir: 8.6–18.1 hours.1

Special Populations

No clinically important differences in pharmacokinetics in those >65 years of age compared with younger adults.1

Atazanavir: Half-life is 12.1 hours in those with moderate to severe hepatic impairment.1

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).1

Actions and Spectrum

  • Pharmacologically related to other HIV PIs (e.g., darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir); differs structurally from these drugs and also differs pharmacologically and structurally from other currently available antiretrovirals.1

  • Active against HIV-1;1 some activity against HIV-2.1 40

  • Inhibits replication of HIV-1 by interfering with HIV protease.1

  • HIV-1 with reduced susceptibility to atazanavir have been selected in vitro and have emerged during therapy with the drug.1 11

  • Varying degrees of cross-resistance occur among HIV PIs.1

Advice to Patients

  • Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician.1 200 Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.1

  • Importance of using in conjunction with other antiretrovirals—not for monotherapy.1 200

  • Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.1 Sustained decreases in plasma HIV RNA have been associated with reduced risk of progression to AIDS and death.1

  • Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others.200 Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles.1

  • Importance of reading patient information provided by the manufacturer.1

  • Importance of taking with food to enhance absorption.1

  • If a dose is missed, it should be taken as soon as it is remembered and the next dose taken at the regularly scheduled time; if a dose is skipped, the next dose should not be doubled.1

  • Advise patients that ECG changes (PR prolongation) have occurred; importance of consulting clinician if dizziness or lightheadedness occurs.1

  • Possibility of asymptomatic increases in indirect bilirubin that may be accompanied by yellowing of the skin or whites of the eyes;1 alternative antiretroviral therapy can be considered if these cosmetic changes are a concern.1

  • Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.1

  • Advise patients that mild rash and severe skin reactions, including Stevens-Johnson syndrome, erythema multiforme, and toxic skin eruptions, have occurred.1 Importance of immediately discontinuing atazanavir and contacting clinician if manifestations of severe skin reactions or hypersensitivity occur (e.g., severe rash or rash accompanied by shortness of breath, fever, general malaise, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema).1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements (e.g., St. John’s wort), and any concomitant illnesses.1

  • Advise patients receiving a selective PDE5 inhibitor (e.g., sildenafil, tadalafil, vardenafil) that they may be at increased risk of PDE5 inhibitor-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged penile erection) and that any symptoms should be promptly reported to clinician.1 Should not be used in patients receiving avanafil for treatment of erectile dysfunction188 or sildenafil for treatment of PAH.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Advise HIV-infected women not to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Atazanavir Sulfate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

100 mg (of atazanavir)

Reyataz

Bristol-Myers Squibb

150 mg (of atazanavir)

Reyataz

Bristol-Myers Squibb

200 mg (of atazanavir)

Reyataz

Bristol-Myers Squibb

300 mg (of atazanavir)

Reyataz

Bristol-Myers Squibb

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Reyataz 150MG Capsules (B-M SQUIBB U.S. (PRIMARY CARE)): 30/$557.97 or 90/$1,616.92

Reyataz 200MG Capsules (B-M SQUIBB U.S. (PRIMARY CARE)): 60/$1,064.94 or 180/$3,105.92

Reyataz 300MG Capsules (B-M SQUIBB U.S. (PRIMARY CARE)): 30/$1,067.99 or 90/$3,155.91

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 2, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Bristol-Myers Squibb. Reyataz (atazanavir sulfate) capsules prescribing information. Princeton, NJ; 2012 Mar.

2. Sanne I, Piliero P, Squires K et al. Results of a phase 2 clinical trial at 48 weeks (A1424-007); a dose-ranging, safety, and efficacy comparative trial of atazanavir at three doses in combination with didanosine and stavudine in antiretroviral-naive subjects. J Acquir Immune Defic Syndr. 2003; 32:18-29. [IDIS 492665] [PubMed 12514410]

3. Haas DW, Zala C, Schrader S et al. Therapy with atazanavir plus saquinavir in patients failing highly active antiretroviral therapy: a randomized comparative pilot trial. AIDS. 2003; 17:1339-49. [PubMed 12799555]

4. Piliero PJ. Atazanavir: a novel HIV-1 protease inhibitor. Expert Opin Investig Drugs. 2002; 11:1295-1301 [PubMed 12225250]

7. Squires K, Lazzarin A, Gatell JM et al. Comparison of once-daily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV. J Acquir Immune Defic Syndr. 2004; 36:1011-9. [PubMed 15247553]

8. Wood R, Phanuphak P, Cahn P et al. Long-term efficacy and safety of atazanavir with stavudine and lamivudine in patients previously treated with nelfinavir or atazanavir. J Acquir Immune Defic Syndr. 2004; 36:684-92. [PubMed 15167287]

9. Murphy RL. Reviving protease inhibitors: new data and more options. J Acquir Immune Defic Syndr. 2003; 33(suppl 1):S43-52. [IDIS 511780] [PubMed 12946064]

11. Colonno RJ, Thiry A, Limoli K et al. Activities of atazanavir 9BMS-232632) against a large panel of human immunodeficiency virus type 1 clinical isolates resistant to one or more approved protease inhibitors. Antimicrob Agents Chemother. 2003; 47:1324-3. [PubMed 12654666]

12. Reddy SS. Dear healthcare professional letter. Results of pharmacokinetic study in healthy volunteers given Victrelis (boceprevir) and ritonavir-boosted HIV protease inhibitors may indicate clinically significant drug interactions for patients coinfected with chronic hepatitis C and HIV. West Point, PA: Merck; 2012 Feb 6.

13. Hodder S. Dear healthcare provider letter: important new pharmacokinetic data for Reyataz (atazanavir sulfate) in combination with Viread (tenofovir disoproxil fumarate). Princeton, NJ: Bristol-Myers Squibb; 2003 Aug 8.

14. Goldsmith DR, Perry CM. Atazanavir. Drugs. 2003; 63:1679-93. [PubMed 12904086]

17. Food and Drug Administration. FDA drug safety communication: Important drug interactions between Victrelis (boceprevir) and ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitor drugs. 2012 Feb 8. From FDA website. Accessed 2012 Apr 23.

18. Food and Drug Administration. FDA drug safety communication: Updated information on drug interactions between Victrelis (boceprevir) and certain boosted HIV protease inhibitor drugs. 2012 Apr 26. From FDA website. Accessed 2012 Jul 9.

28. Molina JM, Andrade-Villanueva J, Echevarria J et al. Once-daily atazanavir/ritonavir versus twice daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1 infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet. 2008; 372:646-55. [PubMed 18722869]

29. Molina JM, Andrade-Villanueva J, Echevarria J et al. Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE study. J Acquir Immune Defic Syndr. 2010; 53:323-32. [PubMed 20032785]

30. Johnson M, Grinsztejn B, Rodriguez C et al. Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures. AIDS. 2005; 19:685-94. [PubMed 15821394]

31. Johnson M, Grinsztejn B, Rodriguez C et al. 96-week comparison of once-daily atazanavir/ritonavir and twice-daily lopinavir/ritonavir in patients with multiple virologic failures. AIDS. 2006; 20:711-8. [PubMed 16514301]

32. Schering Corp. Noxafil (posaconazole) oral solution prescribing information. Whitehouse Station, NJ; 2012 Jun.

35. Murphy RL, Sanne I, Cahn P et al. Dose-ranging, randomized, clinical trial of atazanavir with lamivudine and stavudine in antiretroviral-naive subjects: 48-week results. AIDS. 2003; 17:2603-14. [PubMed 14685054]

40. Desbois D, Roquebert B, Peytavin G et al. In vitro phenotypic susceptibility of human immunodeficiency virus type 2 clinical isolates to protease inhibitors. Antimicrob Agents Chemother. 2008; 52:1545-8. [PubMed 18227188]

184. Vertex Pharmaceuticals. Incivek (telaprevir) tablets prescribing information. Cambridge, MA; 2012 Jun.

185. Merck & Co. Victrelis (boceprevir) capsules prescribing information. Whitehouse Station, NJ; 2012 Apr.

186. Food and Drug Administration. FDA drug safety communication: Interactions between certain HIV or hepatitis C drugs and cholesterol-lowering statin drugs can increase the risk of muscle injury. 2012 Mar 1. From FDA website. Accessed 2012 Apr 23.

188. Vivus. Stendra (avanafil) tablets prescribing information. Mountain View, CA; 2012 Apr.

198. Center for Disease Control and Prevention. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: Recommendations from the U.S. Department of Health and Human Services. MMWR Morb Mortal Wkly Rep. 2005; 54(No. RR-2):1-19. [PubMed 15647722]

199. Center for Disease Control and Prevention. Updated U.S. public health service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Morb Mortal Wkly Rep. 2005; 54(No. RR-9):1-17. [PubMed 15647722]

200. Panel on Antiretroviral Guidelines for Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (April 18, 2012). Updates may be available at HHS AIDS Information (AIDSinfo) website.

201. Panel on Antiretroviral Therapy and Medical Management of HIV-infected Children, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in pediatric HIV infection (August 11, 2011). Updates may be available at HHS AIDS Information (AIDSinfo) website.

202. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, US Department of Health and Human Services (HHS). Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States (July 31, 2012). Updates may be available at HHS AIDS Information (AIDSinfo) website.

204. Janssen. Prezista (darunavir) oral suspension and tablets prescribing information. Titusville, NJ; 2012 Jun.

205. ViiV Healthcare. Lexiva (fosamprenavir calcium) tablets and oral suspension prescribing information. Research Triangle Park, NC; 2012 Feb.

207. Abbott Laboratories. Kaletra (lopinavir/ritonavir) tablets and oral solution prescribing information. North Chicago, IL; 2012 Feb.

209. Abbott Laboratories. Norvir (ritonavir) tablets and oral solution prescribing information. North Chicago, IL; 2012 Feb.

210. Genentech USA. Invirase (saquinavir mesylate) capsules and tablets prescribing information. South San Francisco, CA; 2012 Feb.

211. Boehringer Ingelheim. Aptivus (tipranavir) capsules and oral solution prescribing information. Ridgefield, CT; 2012 Apr.

213. Bristol-Myers Squibb. Sustiva (efavirenz) capsules and tablets prescribing information. Princeton, NJ; 2012 Jun.

214. Janssen. Intelence (etravirine) tablets prescribing information. Raritan, NJ; 2012 Mar.

215. Boehringer Ingelheim. Viramune (nevirapine) tablets and oral suspension prescribing information. Ridgefield, CT; 2011 Nov.

221. Gilead Sciences. Viread (tenofovir disoproxil fumarate) tablets prescribing information. Foster City, CA; 2012 Jan.

224. ViiV Healthcare. Selzentry (maraviroc) tablets prescribing information. Research Triangle Park, NC; 2011 Nov.

225. Merck Sharp & Dohme. Isentress (raltegravir) film-coated tablets and chewable tablets prescribing information. Whitehouse Station, NJ; 2012 Apr.

226. Tibotec Therapeutics. Edurant (rilpivirine) tablets prescribing information. Raritan, NJ; 2011 May.

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