Reyataz

Generic Name: 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

Introduction

Antiretroviral; HIV protease inhibitor (PI).¹

Uses for Reyataz

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}

For initial treatment in HIV-infected adults and adolescents, some experts state that ritonavir-boosted atazanavir is a preferred PI for use in PI-based regimens in conjunction with 2 NRTIs.²⁰⁰

For initial treatment in HIV-infected children, some experts state that 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 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.¹⁸ Used in conjunction with other antiretrovirals.¹⁸

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.¹⁷ Used in conjunction with other antiretrovirals.¹⁷

Reyataz Dosage and Administration

Administration

Oral Administration

Administer orally once daily with food.^{1 200}

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.^{1 200 201}

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

Must be given in conjunction with other antiretrovirals.^{1 200} If used with efavirenz, ritonavir, or tenofovir, dosage adjustment may be necessary.^{1 200} If used with didanosine, administer at separate times.^{1 200} (See Specific Drugs under Interactions.)

Pediatric Patients

Treatment of HIV Infection

Antiretroviral-naive Children

Oral

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

Body Weight	Atazanavir Dosage	Ritonavir Dosage
15 to <25 kg	150 mg once daily	80 mg once daily
25 to <32 kg	200 mg once daily	100 mg once daily
32 to <39 kg	250 mg once daily	100 mg once daily
≥39 kg	300 mg once daily	100 mg once daily

Adolescents ≥13 years of age who weigh ≥39 kg and are unable to tolerate ritonavir: Recommended dosage of atazanavir (without low-dose ritonavir) is 400 mg once daily.¹

Antiretroviral-experienced Children

Oral

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

Body Weight	Atazanavir Dosage	Ritonavir Dosage
25 to <32 kg	200 mg once daily	100 mg once daily
32 to <39 kg	250 mg once daily	100 mg once daily
≥39 kg	300 mg once daily	100 mg once daily

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.)

Dosage recommendations not established for use with efavirenz in antiretroviral-experienced adults.¹

Postexposure Prophylaxis of HIV†

Occupational Exposure†

Oral

400 mg once daily.¹⁸ If tenofovir included in the regimen, use 300 mg of atazanavir once daily boosted with low-dose ritonavir (100 mg once daily).¹⁸

Initiate postexposure prophylaxis as soon as possible following exposure (within hours rather than days) and continue for 4 weeks, if tolerated.¹⁸

Nonoccupational Exposure†

Oral

400 mg once daily.¹⁷ If tenofovir included in the regimen, use 300 mg of atazanavir once daily boosted with low-dose ritonavir.¹⁷

Initiate postexposure prophylaxis as soon as possible following exposure (preferably ≤72 hours after exposure) and continue for 28 days.¹⁷

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection

Oral

300 mg once daily boosted with low-dose ritonavir (100 mg once daily).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 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.^{1 200}

Antiretroviral-naive patients with end-stage renal disease undergoing hemodialysis: 300 mg once daily boosted with low-dose ritonavir (100 mg once daily).^{1 200}

Antiretroviral-experienced patients with end-stage renal disease undergoing hemodialysis: Atazanavir (with or without low-dose ritonavir) not recommended.^{1 200}

Geriatric Patients

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

Pregnant and Postpartum Women

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

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 Reyataz

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 or possible loss of virologic response (e.g., alfuzosin, cisapride, ergot alkaloids, indinavir, irinotecan, lovastatin, oral midazolam, pimozide, rifampin, sildenafil used for treatment of pulmonary arterial hypertension [PAH], simvastatin, 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 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, new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with PIs; diabetic ketoacidosis has occurred.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

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

Spontaneous bleeding noted with PIs; causal relationship not established.¹

Caution in patients with a history of hemophilia type A or B.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 PIs.¹ Resistance to atazanavir may not preclude subsequent use of other 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.^{1 202} Use in pregnant women only if clearly needed and when HIV-1 is susceptible to atazanavir.¹ Some experts state that ritonavir-boosted atazanavir is an alternative PI (not preferred PI) for use in pregnant women.²⁰² Dosage adjustments may be necessary.¹ (See Pregnant and Postpartum Women under Dosage.)

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

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.^{1 200}

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 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

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

Interactions for Reyataz

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 200	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 (e.g., warfarin)	Potential for increased warfarin plasma concentrations and serious and/or life-threatening bleeding episodes1	Monitor INR1
Anticonvulsants (carbamazepine, phenobarbital, phenytoin)	Possible decreased atazanavir concentrations200	Monitor anticonvulsant concentrations and virologic response; consider use of an alternative anticonvulsant, monitoring atazanavir concentrations, and use of ritonavir-boosted atazanavir200
Antidepressants, tricyclics	Possible increased concentrations of tricyclic antidepressants and potential for serious and/or life-threatening effects1	Monitor tricyclic antidepressant concentrations1
Antifungals, azoles	Fluconazole: No clinically important pharmacokinetic interactions with ritonavir-boosted atazanavir1 Itraconazole: Possible pharmacokinetic interaction with ritonavir-boosted atazanavir;1 200 increased itraconazole and atazanavir concentrations200 Ketoconazole: No clinically important increases in atazanavir concentrations if atazanavir used without 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 concentrations if atazanavir used without ritonavir; decreased antifungal concentrations with ritonavir-boosted atazanavir1	Itraconazole: 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 atazanavir used without ritonavir;200 concomitant use of ritonavir-boosted atazanavir and voriconazole not recommended unless potential benefits outweigh risk1 200 and voriconazole concentration monitoring considered200
Antimycobacterials (rifabutin, rifampin, rifapentine)	Rifabutin: Increased rifabutin concentrations and AUC1 200 Rifampin: Substantially decreased atazanavir concentrations; possible loss of virologic response and development of resistance1	Rifabutin: If used with atazanavir (with or without low-dose ritonavir), reduce rifabutin dosage (use 150 mg every other day or 3 times weekly);1 200 monitor for rifabutin-associated adverse effects (e.g., neutropenia)1 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
Benzodiazepines	Midazolam or triazolam: Possible increased plasma 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 200 Parenteral midazolam: 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 plasma concentrations and AUC of atenolol; no effect on PR interval observed1	Use concomitantly with caution;1 atenolol dosage adjustment not needed1
Bosentan	Possible increased bosentan concentrations and decreased atazanavir concentrations1 200	Do not use atazanavir without low-dose ritonavir in patients receiving bosentan1 200 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 200 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 200
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;1 200 monitor for sedation and adverse cognitive effects and consider reduced buprenorphine dosage1 200
Calcium-channel blocking agents (diltiazem, felodipine, nicardipine, nifedipine, verapamil)	Diltiazem: Increased diltiazem concentrations and AUC if used with atazanavir (without low-dose ritonavir);1 200 concomitant use with ritonavir-boosted atazanavir not evaluated1 Felodipine, nicardipine, nifedipine, verapamil: Possible increased concentrations and AUC of calcium-channel blocking agent1 Possible additive effect on PR interval1	Diltiazem: Use concomitantly with caution; ECG monitoring recommended; consider reducing diltiazem dosage by 50%1 200 Felodipine, nicardipine, nifedipine, verapamil: Use concomitantly with caution; ECG monitoring recommended; consider dosage titration of the calcium-channel blocker1 200
Cisapride	Possible increased cisapride plasma concentrations;1 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: Avoid concomitant use of colchicine and atazanavir (with or without low-dose ritonavir)1 Colchicine for treatment of gout flares: In those receiving atazanavir (with or without 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 200 Colchicine for prophylaxis of gout flares: In those receiving atazanavir (with or without 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 200 Colchicine for treatment of familial Mediterranean fever (FMF): In those receiving atazanavir (with or without ritonavir), use maximum colchicine dosage of 0.6 mg daily (may be given as 0.3 mg twice daily)1 200
Corticosteroids	Fluticasone nasal spray/oral inhalation: Increased fluticasone concentrations with atazanavir (with or without low-dose ritonavir) resulting in decreased cortisol concentrations1 Dexamethasone: Potential decreased atazanavir concentrations200	Fluticasone nasal spray/oral inhalation: Consider alternative to fluticasone in patients receiving atazanavir without 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 Dexamethasone: Use caution; consider alternative corticosteroids if long-term systemic therapy anticipated200
Co-trimoxazole	Pharmacokinetic interactions unlikely1
Dapsone	Pharmacokinetic interactions unlikely1
Darunavir		Usual dosage of ritonavir-boosted darunavir can be used concomitantly with atazanavir 300 mg once daily200 204
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	Decreased atazanavir concentrations and AUC;1 200 no change in efavirenz concentrations200 No in vitro evidence of antagonistic antiretroviral effects1	Do not use atazanavir without low-dose ritonavir in patients receiving efavirenz1 In antiretroviral-naive adults, a regimen of atazanavir 400 mg, ritonavir 100 mg, and efavirenz 600 mg given once daily with food is recommended1 200 Concomitant use of atazanavir and efavirenz in antiretroviral-experienced adults not recommended1 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 plasma 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 200 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 plasma 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 200 Atazanavir (without low-dose ritonavir): Use an oral contraceptive containing no more than 30 mcg of ethinyl estradiol1 200
Etravirine	Atazanavir or ritonavir-boosted atazanavir: Increased etravirine concentrations and decreased atazanavir concentrations200 214	Concomitant use with atazanavir (with or without low-dose ritonavir) not recommended200 214
Fosamprenavir	Ritonavir-boosted fosamprenavir: Decreased atazanavir concentrations; no change in amprenavir concentrations205 Fosamprenavir (without low-dose ritonavir): No data205 In vitro evidence of synergistic antiretroviral effects205	Appropriate dosages for concomitant use with fosamprenavir (with or without low-dose ritonavir) with respect to safety and efficacy not established200 205
Histamine H2-receptor antagonists	Famotidine: Decreased atazanavir concentrations with possible loss of therapeutic effect and development of resistance when atazanavir (without 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, simvastatin, rosuvastatin: Possible decreased clearance and increased plasma concentrations of HMG-CoA reductase inhibitor with potential for increased risk of myopathy (including rhabdomyolysis)1 200 Fluvastatin or pravastatin: Interaction not expected1 Pitavastatin: Possible increased pitavastatin concentrations200	Lovastatin or simvastatin: Concomitant use contraindicated1 Atorvastatin or rosuvastatin: Use lowest possible initial dose of HMG-CoA reductase inhibitor with careful monitoring or consider using fluvastatin or pravastatin1 200 Pitavastatin: Dosage adjustments not needed if used with atazanavir (without ritonavir);200 some experts do not recommend concomitant use with ritonavir-boosted atazanavir200
Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)	Potential for increased plasma concentrations of cyclosporine, sirolimus, or tacrolimus1	Monitor plasma concentrations of the immunosuppressive agent1
Indinavir	Potential for additive hyperbilirubinemia1 200 No in vitro evidence of antagonistic antiretroviral effects1	Concomitant use contraindicated1
Irinotecan	Possible interference with metabolism of irinotecan; increased risk of irinotecan toxicity1	Concomitant use contraindicated1 200
Lamivudine	No in vitro evidence of antagonistic antiretroviral effects1
Lopinavir	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 and lopinavir 400 mg/ritonavir 100 mg twice daily200
Macrolides (azithromycin, clarithromycin, erythromycin)	Azithromycin: Pharmacokinetic interactions unlikely1 Clarithromycin: Increased plasma concentrations and AUC of atazanavir;1 increased clarithromycin plasma concentrations and decreased 14-hydroxyclarithromycin plasma concentrations;1 increased clarithromycin concentrations may cause QTc prolongation1 Erythromycin: Pharmacokinetic interactions unlikely1	Clarithromycin: Consider reducing clarithromycin dosage by 50%;1 200 consider alternative to clarithromycin1 200 for indications other than Mycobacterium avium complex (MAC)1
Maraviroc	Atazanavir or ritonavir-boosted atazanavir: Increased maraviroc concentrations