Interactions : אינטראקציות

7. DRUG INTERACTIONS
7.1. Potential for Atazanavir Teva to Affect Other Drugs
Atazanavir is an inhibitor of CYP3A and UGT1A1. Coadministration of Atazanavir Teva and drugs primarily metabolized by CYP3A or UGT1A1 may result in increased plasma concentrations of the other drug that could increase or prolong its therapeutic and adverse effects.
Atazanavir is a weak inhibitor of CYP2C8. Use of Atazanavir Teva without ritonavir is not recommended 
when coadministered with drugs highly dependent on CYP2C8 with narrow therapeutic indices (eg, paclitaxel, repaglinide). When Atazanavir Teva with ritonavir is coadministered with substrates of CYP2C8, clinically significant interactions are not expected [see Clinical Pharmacology, Table 21 (11.3)].
The magnitude of CYP3A-mediated drug interactions on coadministered drug may change when Atazanavir Teva is coadministered with ritonavir. See the complete prescribing information for ritonavir for information on drug interactions with ritonavir.


7.2. Potential for Other Drugs to Affect Atazanavir Teva
Atazanavir is a CYP3A4 substrate; therefore, drugs that induce CYP3A4 may decrease atazanavir plasma concentrations and reduce Atazanavir Teva's therapeutic effect.
Atazanavir solubility decreases as pH increases. Reduced plasma concentrations of atazanavir are expected if proton-pump inhibitors, antacids, buffered medications, or H2-receptor antagonists are administered with Atazanavir Teva [see Dosage and Administration (2.3, 2.4, 2.5 and 2.6)] .


7.3. Established and Other Potentially Significant Drug Interactions
Table 16 provides dosing recommendations in adults as a result of drug interactions with Atazanavir Teva.
These recommendations are based on either drug interaction studies or predicted interactions due to the expected magnitude of interaction and potential for serious events or loss of efficacy.

Table 16: Established and Other Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studiesa or Predicted Interactions (Information in the table applies to Atazanavir Teva with or without ritonavir, unless otherwise indicated)

Effect on
Concentration of
Concomitant Drug             Atazanavir or
Class:                       Concomitant
Specific Drugs                   Drug                               Clinical Comment HIV Antiviral Agents
Nucleoside Reverse        ↓atazanavir            It is recommended that Atazanavir Teva be given (with Transcriptase Inhibitors ↓ didanosine            food) 2 h before or 1 h after didanosine buffered (NRTIs):                                         formulations. Simultaneous administration of didanosine EC didanosine buffered                              and Atazanavir Teva with food results in a decrease in formulations enteric-                            didanosine. Thus, Atazanavir Teva and didanosine EC coated (EC) capsules                             should be administered at different times.
Nucleotide Reverse        ↓atazanavir            When coadministered with tenofovir DF in adults, it is Transcriptase Inhibitors: ↑tenofovir             recommended that Atazanavir Teva 300 mg be given with tenofovir disoproxil                             ritonavir 100 mg and tenofovir DF 300 mg (all as a single fumarate (DF)                                    daily dose with food)The mechanism of this interaction is 
unknown. Higher tenofovir concentrations could potentiate tenofovir -associated adverse reactions, including renal disorders. Patients receiving Atazanavir Teva and tenofovir
DF should be monitored for tenofovir-associated adverse reactions. For pregnant women taking AtazanavirTeva with ritonavir and tenofovir DF, see Dosage and Administration
(2.6).
Non-nucleoside Reverse ↓atazanavir               In HIV-treatment-naive adult patients:If Atazanavir Teva Transcriptase Inhibitors                         is combined with efavirenz, Atazanavir Teva 400 mg (two (NNRTIs): efavirenz                              200-mg capsules) should be administered with ritonavir 100 mg simultaneously once daily with food, and efavirenz 600 mg should be administered once daily on an empty stomach,
preferably at bedtime.

In HIV treatment-experienced adult patients:
Coadministration of Atazanavir Teva with efavirenz is not recommended.
nevirapine                  ↓atazanavir          Coadministration of Atazanavir Teva with nevirapine is ↑ nevirapine         contraindicateddue to the potential loss of virologic response and development of resistance, as well as potential risk for nevirapine-associated adverse reactions [see
Contraindications (4)].
Protease Inhibitors:        ↑saquinavir          Appropriate dosing recommendations for this combination, saquinavir (soft gelatin                         with or without ritonavir, with respect to efficacy and safety capsules)                                        have not been established. In a clinical study, saquinavir 1200 mg coadministered with atazanavir 400 mg and tenofovir DF 300 mg (all given once daily) plus nucleoside analogue reverse transcriptase inhibitors did not provide adequate efficacy [see Clinical Studies (13.2)].
indinavir                                        Coadministration of Atazanavir Teva with indinavir is contraindicated. Both Atazanavir Teva and indinavir are associated with indirect (unconjugated) hyperbilirubinemia
[see Contraindications (4)].
Ritonavir                   ↑ atazanavir         If Atazanavir Teva is coadministered with ritonavir, it is recommended that Atazanavir Teva 300 mg once daily be given with ritonavir 100 mg once daily with food in adults.
See the complete prescribing information for ritonavir for information on drug interactions with ritonavir.
Others                      ↑other protease      Coadministration with other protease inhibitors is not inhibitor            recommended.

Hepatitis C Antiviral Agents
Effect on
Concentration of
Concomitant Drug              Atazanavir or
Class:                        Concomitant
Specific Drugs                    Drug                                Clinical Comment  elbasvir/grazoprevir        ↑grazoprevir         Coadministration of Atazanavir Teva with grazoprevir is contraindicated due to the potential increased risk of ALT elevations [see Contraindications (4)].
glecaprevir/pibrentasvir ↑glecaprevir            Coadministration of Atazanavir Teva with ↑ pibrentasvir          glecaprevir/pibrentasvir is contraindicated due to the potential for increased the risk of ALT elevations [see
Contraindications (4)].
voxilaprevir/sofosbuvir/ ↑voxilaprevir           Coadministration with Atazanavir Teva is not recommended velpatasvir

Other Agents
Effect on
Concomitant Drug           Concentration of
Class:                      Atazanavir or
Specific Drugs            Concomitant Drug                         Clinical Comment Alpha 1-Adrenoreceptor ↑alfuzosin            Coadministration of Atazanavir Teva with alfuzosin is Antagonist: alfuzosin                        contraindicated due to risk for hypotension [see Contraindications (4)].
Antacids and buffered    ↓ atazanavir        Atazanavir should be administered 2 hours before or 1 medications                                  hour after anatacids and buffered medications.
Antiarrhythmics:                             Concomitant use of Atazanavir Teva with ritonavir and amiodarone, quinidine                        either quinidine or amiodarone is contraindicated due to the potential for serious or life-threatening reactions such as cardiac arrhythmias [see Contraindications (4)].
↑amiodarone,
bepridil, lidocaine
(systemic),         Coadministration with Atazanavir Teva without ritonavir quinidine           has the potential to produce serious and/or life-threatening amiodarone, bepridil,                        adverse events but has not been studied. Caution is lidocaine (systemic),                        warranted and therapeutic concentration monitoring of quinidine                                    these drugs is recommended if they are used concomitantly with Atazanavir without ritonavir.
Anticoagulants: warfarin ↑warfarin           Coadministration with Atazanavir Teva has the potential to produce serious and/or life-threatening bleeding and has not been studied. It is recommended that International
Normalized Ratio (INR) be monitored.
Direct-Acting Oral       ↑ betrixaban        Concomitant use of Atazanavir Teva with ritonavir, a Anticoagulants:           ↑dabigatran        strong CYP3A4/P-gp inhibitor, may result in increased betrixaban,               ↑edoxaban          risk of bleeding. Refer to the respective DOAC prescribing dabigatran, edoxaban                         information regarding dosing instructions for coadministration with P-gp inhibitors.
 rivaroxaban                 Atazanavir with        Coadministration of Atazanavir Teva with ritonavir, a ritonavir              strong CYP3A4/P-gp inhibitor, and rivaroxaban is not ↑ rivaroxaban          recommended, as it may increase risk of bleeding.

Coadministration of Atazanavir Teva, a CYP3A4 inhibitor,
and rivaroxaban may result in increased increase. Close
Atazanavir             monitoring is recommended when Atazanavir Teva is ↑ rivaroxaban          coadministered with rivaroxaban.
Effect on
Concomitant Drug             Concentration of
Class:                        Atazanavir or
Specific Drugs              Concomitant Drug                          Clinical Comment 
Atazanavir with        Concomitant use of Atazanavir Teva with ritonavir, a apixaban                    ritonavir              strong CYP3A4/P-gp inhibitor, may result in increased risk ↑ apixaban             of bleeding. Refer to apixaban dosing instructions for coadministration with strong CYP3A4 and P-gp inhibitors in the apixaban prescribing information.
Concomitant use of Atazanavir, a CYP3A4 inhibitor, and
Atazanavir apixaban may result in increased risk of bleeding. Close
↑ apixaban monitoring is recommended when apixaban is coadministered with Atazanavir Teva.
Antidepressants: tricyclic ↑tricyclic              Coadministration with Atazanavir Teva has the potential to antidepressants            antidepressants         produce serious and/or life-threatening adverse events and has not been studied. Concentration monitoring of these drugs is recommended if they are used concomitantly with
Atazanavir Teva.
trazodone                   ↑trazodone             Nausea, dizziness, hypotension, and syncope have been observed following coadministration of trazodone with ritonavir. If trazodone is used with a CYP3A4 inhibitor such as Atazanavir Teva, the combination should be used with caution and a lower dose of trazodone should be considered.
Antiepileptics:             ↓Atazanavir            Coadministered with Atazanavir Teva (without or whitout carbamazepine               ↑carbamazepine         ritonavir) with carbamazepine is contraindicated due to the risk for loss of virologic response and development of resistance [see Contraindications (4)].
phenytoin, phenobarbital ↓atazanavir               Coadministration Atazanavir Teva (without or whitout ↓phenytoin                ritonavir) with phenytoin or phenobarbital is ↓phenobarbital            contraindicated due to the risk for loss of virologic response and development of resistance [see
Contraindications (4)].
Lamotrigine                 ↓lamotrigine            Coadministration of lamotrigine and Atazanavir Teva with ritonavir may require dosage adjustment of lamotrigine.

No dose adjustment of lamotrigine is required when coadministered with Atazanavir Teva without ritonavir.
Antifungals:                Atazanavir with        Coadministration of ketoconazole has only been studied ketoconazole,               ritonavir:             with Atazanavir Teva without ritonavir (negligible increase itraconazole                ↑ketoconazole          in atazanavir AUC and Cmax). Due to the effect of ↑itraconazole          ritonavir on ketoconazole, high doses of ketoconazole and itraconazole (>200 mg/day) should be used cautiously when administering Atazanavir Teva with ritonavir.
Voriconazole                Atazanavir Teva        The use of voriconazole in patients receiving Atazanavir with ritonavir in      Teva/ritonavir is not recommended unless an assessment 
Effect on
Concomitant Drug              Concentration of
Class:                         Atazanavir or
Specific Drugs               Concomitant Drug                        Clinical Comment subjects with a    of the benefit/risk to the patient justifies the use of functional CYP2C19 voriconazole. Patients should be carefully monitored for allele:            voriconazole- associated adverse reactions and loss of ↓voriconazole      either voriconazole or atazanavir efficacy during the ↓atazanavir        coadministration of voriconazole and Atazanavir Teva /ritonavir. Coadministration of voriconazole with
Atazanavir Teva (without ritonavir) may affect atazanavir concentrations; however, no data are available.
Atazanavir Teva with ritonavir in subjects without a functional CYP2C19 allele:
↑ voriconazole
↓atazanavir
Antigout: colchicine        ↑colchicine        The coadministration of Atazanavir Teva with colchicine in patients with renal or hepatic impairment is not recommended.

Recommended adult dosage of colchicine when administered with Atazanavir Teva:
Treatment of gout flares:
0.6 mg (1 tablet) for 1 dose, followed by 0.3 mg (half tablet) 1 hour later. Not to be repeated before 3 days.
Prophylaxis of gout flares:
If the original regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day.
If the original regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once every other day.
Treatment of familial Mediterranean fever (FMF):
Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day).
Antimycobacterials:         ↓atazanavir            Coadministration of Atazanavir Teva with rifampin is rifampin                                           contraindicated due to risk for loss of virologic response and development of resistance [see Contraindications (4)].
rifabutin                   ↑ rifabutin            A rifabutin dose reduction of up to 75% (eg, 150 mg every other day or 3 times per week) is recommended. Increased monitoring for rifabutin-associated adverse reactions including neutropenia is warranted.
Antineoplastics:            ↑irinotecan            Coadministration of Atazanavir Teva with irinotecan is irinotecan                                         contraindicated. Atazanavir inhibits UGT1A1 and may interfere with the metabolism of irinotecan, resulting in increased irinotecan toxicities [see Contraindications (4)].
apalutamide                 ↓atazanavir            Coadministration of Atazanavir Teva (with or without ritonavir) and apalutamide is contraindicated due to the

Effect on
Concomitant Drug             Concentration of
Class:                        Atazanavir or
Specific Drugs              Concomitant Drug                            Clinical Comment potential for subsequent loss of virologic response and possible resistance to the class of protease inhibitors [see
Contraindications (4)].
 ivosidenib                  ↓atazanavir            Coadministration of ivosidenib with Atazanavir Teva (with ↑ ivosidenib           or without ritonavir) is contraindicated due to the potential for loss of virologic response and risk of serious adverse events such as QT interval prolongation.

Coadministration of encorafenib with Atazanavir Teva encorafenib                 ↓atazanavir            (with or without ritonavir) is contraindicated due to the ↑encorafenib           potential for the loss of virologic response and risk of serious adverse events such as QT interval prolongation.
Antiplatelets
Coadministration with ticagrelor is not recommended due ticagrelor                  ↑ ticagrelor           to potential increase in the risk of dyspnea, bleeding and other adverse events associated with ticagrelor.

Coadministration of Atazanavir Teva (with or without clopidogrel                 ↓ clopidogrel active ritonavir) and clopidogrel is not recommended. This is due metabolite           to the potential reduction of the antiplatelet activity of clopidogrel.
Antipsychotics:              ↑pimozide           Coadministration of Atazanavir Teva with pimozide is pimozide                                         contraindicated. This is due to the potential for serious and/or life-threatening reactions such as cardiac arrhythmias [see Contraindications (4)] lurasidone                  Atazanavir Teva      Atazanavir Teva withritonavir with ritonavir       Coadministration of lurasidone with Atazanavir Teva with ↑ lurasidone         ritonavir is contraindicated.
This is due to the potential for serious and/or life- threatening reactions [see Contraindications (4)].

Atazanavir Teva without ritonavir
Atazanavir Teva        If coadministration is necessary, reduce the lurasidone ↑ lurasidone           dose. Refer to the lurasidone prescribing information for concomitant use with moderate CYP3A4 inhibitors.

Initiation of Atazanavir Teva with ritonavir in patients taking quetiapine: Consider alternative antiretroviral therapy to avoid increases in quetiapine exposures. If
↑ quetiapine           coadministration is necessary, reduce the quetiapine dose quetiapine                                         to 1/6 of the current dose and monitor for quetiapine- associated adverse reactions. Refer to the quetiapine prescribing information for recommendations on adverse reaction monitoring.


Effect on
Concomitant Drug             Concentration of
Class:                        Atazanavir or
Specific Drugs              Concomitant Drug                            Clinical Comment Initiation of quetiapine in patients taking Atazanavir
Teva with ritonavir: Refer to the quetiapine prescribing information for initial dosing and titration of quetiapine.

Benzodiazepines:            ↑ midazolam         Coadministration of Atazanavir Teva with either orally Midazolam (oral)            ↑ triazolam         administered midazolam or triazolam is contraindicated.
triazolam                                       Triazolam and orally administered midazolam are extensively metabolized by CYP3A4, and coadministration with Atazanavir Teva can lead to the potential for serious and/or life-threatening events such as prolonged or increased sedation or respiratory depression [see
Contraindications (4)].
parenterally administered ↑midazolam            . Coadministration parenteral with midazolam should be midazolam b                                     done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered.
Calcium channel             ↑ diltiazem and     Caution is warranted. A dose reduction of diltiazem by blockers:                   desacetyl-diltiazem 50% should be considered. ECG monitoring is diltiazem                                       recommended. Coadministration of diltiazem and atazanavir with ritonavir has not been studied.
felodipine, nifedipine,     ↑calcium channel Caution is warranted. Dose titration of the calcium channel nicardipine, and            blocker             blocker should be considered. ECG monitoring is verapamil                                       recommended.
Corticosteroids:            ↓ atazanavir        Coadministration with dexamethasone or other dexamethasone and other ↑ corticosteroids       corticosteroids that induce CYP3A may result in loss of corticosteroids (all routes                     therapeutic effect of REYATAZ and development of of administration)                              resistance to atazanavir and/or ritonavir. Alternative corticosteroids should be considered. Coadministration with corticosteroids (all routes of administration) that are metabolized by CYP3A, particularly for long-term use,
may increase the risk for development of systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression. Consider the potential benefit of treatment versus the risk of systemic corticosteroid effects.
For coadministration of cutaneously administered corticosteroids sensitive to CYP3A inhibition, refer to the prescribing information of the corticosteroid for additional information



Effect on
Concomitant Drug             Concentration of
Class:                         Atazanavir or
Specific Drugs              Concomitant Drug                       Clinical Comment Endothelin receptor         Atazanavir        Coadministration of bosentan antagonists:                ↓atazanavir       and Atazanavir Teva without ritonavir is not Bosentan                                      recommended.
Atazanavir with ritonavir            For adult patients who have been receiving Atazanavir ↑bosentan            Teva with ritonavir for at least 10 days, start bosentan at 62.5 mg once daily or every other day based on individual tolerability.

For adult patients who have been receiving bosentan,
discontinue bosentan at least 36 hours before starting
Atazanavir Teva with ritonavir. At least 10 days after starting Atazanavir Teva with ritonavir, resume bosentan at 62.5 mg once daily or every other day based on individual tolerability.
Ergot derivatives:                                 Coadministration of Atazanavir Teva with ergot dihydroergotamine,      ↑ergot derivatives         derivatives is contraindicated. This is due to the potential ergotamine, ergonovine,                            for serious and/or life-threatening events such as acute methylergonovine                                   ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues [see
Contraindications (4)].
GI Motility Agents:                                Coadministration of Atazanavir Teva with cisapride is cisapride                   ↑cisapride             contraindicated. This is due to the potential for serious and/or life-threatening reactions such as cardiac arrhythmias [see Contraindications (4)].
Gonadotropin-releasing                             Coadministration of elagolix and REYATAZ with or hormone Receptor       ↓atazanavir                 without ritonavir is not (GnRH)                 ↑ elagolix                  recommended due to the potential of loss of virologic Antagonists:                                       response and the potential risk of adverse events such as elagolix                                           bone loss and hepatic transaminase elevations associated with elagolix.
In the event coadministration is necessary, limit concomitant use of elagolix 200mg twice daily with
REYATAZ with or without ritonavir for up to 1 month or limit concomitant use of elagolix 150 mg once daily with
REYATAZ (with or without ritonavir) for up to 6 months and monitor virologic response.
Herbal Products:                                   Coadministration of products containing St. John’s wort St. John’s wort       ↓atazanavir                  with Atazanavir Teva is contraindicated. This may result in (Hypericum perforatum                              loss of therapeutic effect of Atazanavir Teva and the development of resistance [see Contraindications (4)].
Kinase inhibitors:          ↑ R406 (active         When coadministering fostamatinib with REYATAZ (with fostamatinib                metabolite of          or without ritonavir), monitor for toxicities of R406 fostamatinib)          exposure resulting in dose-related adverse events such as hepatotoxicity and neutropenia. Fostamatinib dose reduction may be required.
Effect on
Concomitant Drug             Concentration of
Class:                        Atazanavir or
Specific Drugs              Concomitant Drug                            Clinical Comment Lipid-modifying agents                             Coadministration of Atazanavir Teva with lovastatin or HMG-CoA reductase       ↑Lovastatin                simvastatin is contraindicated. This is due to the potential inhibitors: lovastatin,                            for serious reactions such as myopathy, including simvastatin             ↑simvastatin               rhabdomyolysis [see Contraindications (4)].
↑ atorvastatin             Titrate atorvastatin dose carefully and use the lowest atorvastatin,           ↑ rosuvastatin             necessary dose.
rosuvastatin                                       Rosuvastatin dose should not exceed 10 mg/day. The risk of myopathy, including rhabdomyolysis, may be increased when HIV protease inhibitors, including Atazanavir Teva,
are used in combination with these drugs.
Other Lipid Modifying       ↑lomitapide            Coadministration of Atazanavir Teva with lomitapide is Agents: lomitapide                                 contraindicated. This is due to the potential for risk of markedly increased transaminase levels and hepatotoxicity associated with increased plasma concentrations of lomitapide. The mechanism of interaction is CYP3A4 inhibition by atazanavir and/or ritonavir [see
Contraindications (4)].
H2-Receptor antagonists ↓atazanavir                Coadministration may result in loss of virologic response and development of resistance.

In HIV treatment-naive adult patients:
Atazanavir Teva 300 mg with ritonavir 100 mg once daily with food should be administered simultaneously with,
and/or at least 10 hours after, a dose of the H2-receptor antagonist (H2RA). An H2RA dose comparable to famotidine 20 mg once daily up to a dose comparable to famotidine 40 mg twice daily can be used with Atazanavir
Teva 300 mg with ritonavir 100 mg in treatment-naive patients.
OR
For patients unable to tolerate ritonavir, Atazanavir Teva
400 mg once daily with food should be administered at least 2 hours before and at least 10 hours after a dose of the
H2RA. No single dose of the H2RA should exceed a dose comparable to famotidine 20 mg, and the total daily dose should not exceed a dose comparable to famotidine 40 mg.
The use of Atazanavir Teva without ritonavir in pregnant women is not recommended.

In treatment-experienced adult patients:
Whenever an H2RA is given to a patient receiving
Atazanavir Teva with ritonavir, the H2RA dose should not exceed a dose comparable to famotidine 20 mg twice daily,
and the Atazanavir Teva and ritonavir doses should be administered simultaneously with, and/or at least 10 hours after, the dose of the H2RA.
Effect on
Concomitant Drug             Concentration of
Class:                        Atazanavir or
Specific Drugs              Concomitant Drug                            Clinical Comment • Atazanavir Teva 300 mg with ritonavir 100 mg once daily (all as a single dose with food) if taken with an
H2RA.
• Atazanavir Teva 400 mg with ritonavir 100 mg once daily (all as a single dose with food) if taken with both tenofovir DF and an H2RA.

• Atazanavir Teva 400 mg with ritonavir 100 mg once daily (all as a single dose with food) if taken with both tenofovir DF and an H2RA.
• Atazanavir Teva 400 mg with ritonavir 100 mg once daily (all as a single dose with food) if taken with either tenofovir DF or an H2RA for pregnant patient during the second and third trimester. Atazanavir Teva is not recommended for pregnant patients during the second and third trimester taking Atazanavir Teva with both tenofovir DF and an H2RA.
Hormonal                 ↓ethinyl estradiol  Use caution if considering coadministration of oral contraceptives: ethinyl ↑norgestimatec       contraceptives with Atazanavir Teva or Atazanavir Teva estradiol and                                with ritonavir.
norgestimate or                              If Atazanavir with ritonavir is coadministered with an oral norethindrone                                contraceptive , it is recommended that the oral contraceptive contain at least 35 mcg of ethinyl estradiol.
If Atazanavir Teva is administered without ritonavir, the oral contraceptive should contain no more than 30 mcg of ethinyl estradiol.
↑ ethinyl estradiol Potential safety risks include substantial increases in ↑norethindroned     progesterone exposure. The long-term effects of increases in concentration of the progestational agent are unknown and could increase the risk of insulin resistance,
dyslipidemia, and acne.
Coadministration of atazanavir or atazanavir with ritonavir and other hormonal contraceptives (eg, contraceptive patch, contraceptive vaginal ring, or injectable contraceptives) or oral contraceptives containing progestogens other than norethindrone or norgestimate, or less than 25 mcg of ethinyl estradiol, has not been studied;
therefore, alternative methods of contraception are recommended.
Immunosuppressants:      ↑                   Therapeutic concentration monitoring is recommended for cyclosporine, sirolimus, immunosuppressants these immunosuppressants when coadministered with tacrolimus                                   Atazanavir Teva.
Inhaled beta agonist:    ↑ salmeterol        Coadministration of salmeterol with Atazanavir Teva is Salmeterol                                   not recommended.
Concomitant use of salmeterol and Atazanavir Teva may result in increased risk of cardiovascular adverse reactions
Effect on
Concomitant Drug             Concentration of
Class:                        Atazanavir or
Specific Drugs              Concomitant Drug                            Clinical Comment associated with salmeterol, including QT prolongation,
palpitations, and sinus tachycardia.
Inhaled nasal steroid:      Atazanavir             Concomitant use of fluticasone propionate and Atazanavir fluticasone                 ↑ fluticasone          Teva without ritonavir shold be used withuse with caution.
Consider alternatives to fluticasone propionate, particularly for long term use.

With concomitant use of fluticasone propionate and
Atazanavir with        Atazanavir Teva with ritonavir systemic corticosteroid ritonavir              effects, including Cushing's syndrome and adrenal ↑fluticasone           suppression, have been reported during postmarketing use in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate. Coadministration of fluticasone propionate and Atazanavir Teva with ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects [see Warnings and Precautions (5.1)].
Macrolide antibiotics:      ↑ clarithromycin       Increased concentrations of clarithromycin may cause QTc clarithromycin              ↓ 14-OH                prolongations; therefore, a dose reduction of clarithromycin         clarithromycin by 50% should be considered when it is ↑atazanavir            coadministered with Atazanavir Teva. In addition, concentrations of the active metabolite 14-OH clarithromycin are significantly reduced; consider alternative therapy for indications other than infections due to Mycobacterium avium complex. Coadministration of
Atazanavir /ritonavir with clarithromycin has not been studied.
Opioids: Buprenorphine Atazanavit Teva or
Coadministration of Atazanavir Teva plus ritonavir with
Atazanavir with buprenorphine warrants clinical monitoring for sedation ritonavir and cognitive effects. A dose reduction of buprenorphine
↑ buprenorphine may be considered. Coadministration of buprenorphine
↑norbuprenorphine and Atazanavir Teva with ritonavir is not expected to decrease atazanavir plasma concentrations. The coadministration of Atazanavir Teva and buprenorphine
Atazanavit without ritonavir is not recommended.
↓ atazanavir
PDE5 inhibitors:            ↑ sildenafil           Coadministration with atazanavir has not been studied but sildenafil, tadalafil,      ↑ tadalafil            may result in an increase in PDE5 inhibitor-associated vardenafil                  ↑ vardenafil           adverse reactions, including hypotension, syncope, visual disturbances, and priapism.

Use of PDE5 inhibitors for pulmonary arterial hypertension (PAH): contraindicated of Atazanavir Teva with REVATIO®
(sildenafil) for the treatment of pulmonary hypertension
(PAH) is contraindicated [see Contraindications (4)].

Effect on
Concomitant Drug             Concentration of
Class:                        Atazanavir or
Specific Drugs              Concomitant Drug                             Clinical Comment The following dose adjustments are recommended for the use of ADCIRCA® (tadalafil) with Atazanavir
Teva:
Coadministration of ADCIRCA® in patients on
Atazanavir (with or without ritonavir):
• For patients receiving Atazanavir Teva (with or without ritonavir) for at least one week, start
ADCIRCA® * at 20 mg once daily. Increase to
40 mg once daily based on individual tolerability.
Coadministration of Atazanavir Teva (with or without ritonavir) in patients on ADCIRCA®:

•    Avoid the use of ADCIRCA® when starting
Atazanavir Teva (with or without ritonavir). Stop
ADCIRCA® at least 24 hours before starting
Atazanavir Teva (with or without ritonavir). At least one week after starting Atazanavir Teva (with or without ritonavir), resume ADCIRCA® at 20 mg once daily. Increase to 40 mg once daily based on individual tolerability.

Use of PDE5 inhibitors for erectile dysfunction:
Use VIAGRA® (sildenafil) with caution at reduced doses of 25 mg every 48 hours with increased monitoring for adverse events.
Use CIALIS® (tadalafil) with caution at reduced doses of 10 mg every     72 hours with increased monitoring for adverse events.
Atazanavir Teva /ritonavir: Use vardenafil with caution at reduced doses of no more than 2.5 mg every 72 hours with increased monitoring for adverse reactions.

Atazanavir Teva: Use vardenafil with caution at reduced doses of no more than 2.5 mg every 24 hours with increased monitoring for adverse reactions.
Proton-pump inhibitors: ↓ atazanavir               Coadministration Atazanavir Teva with or without omeprazole                                         ritonavir and omeprazole may result in loss of virologic response and development of resistance.

In HIV- treatment-naive adult patients:
The proton-pump inhibitor (PPI) dose should not exceed a dose comparable to omeprazole 20 mg and must be taken approximately 12 hours prior to the Atazanavir Teva 300 mg with ritonavir 100 mg dose.

Effect on
Concomitant Drug             Concentration of
Class:                        Atazanavir or
Specific Drugs              Concomitant Drug                        Clinical Comment In HIV-treatment-experienced adult patients:
Coadministration Atazanavir Teva PPIs is not recommended.
a
For magnitude of interactions see Clinical Pharmacology, Tables 20 and 21 (11.3).
b
See Contraindications (4), Table 6 for orally administered midazolam.
c
In combination with atazanavir 300 mg with ritonavir 100 mg once daily.
d
In combination with atazanavir 400 mg once daily

7.4. Drugs with No Observed Interactions with Atazanavir Teva
No clinically significant drug interactions were observed when Atazanavir Teva was coadministered with methadone, fluconazole, acetaminophen, atenolol, or the nucleoside reverse transcriptase inhibitors lamivudine or zidovudine [see Clinical Pharmacology, Tables 20 and 21 (11.3)].