Coadministration with atazanavir alone has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of abacavir (600 mg once daily) and atazanavir/ritonavir (300/100 mg once daily) had no effect on atazanavir or ritonavir pharmacokinetics, but decreased abacavir AUC (17%) and Cmax (20%). These changes are unlikely to be clinically significant.

Coadministration has not been studied. Albuvirtide is a peptide which is eliminated by catabolism to its constituent amino acids. Based on data from studies with lopinavir/ritonavir, concentrations of atazanavir may decrease but this is not expected to be clinically relevant. Coadministration of albuvirtide (320 mg once weekly intravenous) and oral lopinavir/ritonavir (400/100 mg twice daily) was evaluated in HIV-infected individuals. Albuvirtide exposure was not significantly affected by lopinavir/ritonavir. However, both lopinavir and ritonavir concentrations were lower in presence of albuvirtide compared with lopinavir/ritonavir alone (lopinavir AUC, Cmax and Ctrough decreased by 37%, 33% and 35%, respectively; ritonavir AUC, Cmax and Ctrough decreased by 38%, 39% and 28%, respectively). The mean lopinavir Ctrough in presence of albuvirtide (7.1 µg/ml) remained higher than the minimal lopinavir Ctrough previously associated with efficacy. Furthermore, a randomized, phase 3 study (TALENT study) showed that albuvirtide + lopinavir/ritonavir was non-inferior to the standard second-line regimen lopinavir/ritonavir + zidovudine/tenofovir disoproxil fumarate + lamivudine in HIV infected Chinese individuals suggesting that this interaction has no clinical consequences. In vitro human microsomal studies indicate that albuvirtide has no inducing properties on P450 enzymes. In addition, albuvirtide binds to <1% of serum albumin in the range of clinical concentrations, thus the observed decrease in lopinavir and ritonavir concentrations is unlikely to result from protein binding displacement. However, binding of the albuvirtide-albumin complex to the HIV protease inhibitor cannot be excluded.

Coadministration with alfuzosin is contraindicated as it may increase alfuzosin concentrations due to potent CYP3A4 inhibition by atazanavir. This may result in severe hypotension.

Coadministration has not been studied and is not recommended. Aliskiren is minimally metabolized by CYP450, however, P-gp is a major determinant of aliskiren bioavailability. A 5-6 fold increase in exposure was observed with itraconazole 100 mg twice daily (a CYP3A4 and P-gp inhibitor) and a similar interaction is possible with atazanavir. The product labels for aliskiren recommend avoiding concomitant use with CYP3A4 and P-gp inhibitors.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase. Atazanavir is unlikely to affect these enzymes and is metabolized by CYP3A4.

Coadministration has not been studied and is not recommended. Amiodarone is metabolized by CYP2C8 and CYP3A4 and atazanavir could potentially increase amiodarone concentrations by inhibition of CYP3A4. Elevated plasma concentrations are associated with serious and/or life-threatening events including cardiac arrhythmias. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; amiodarone has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Amisulpride is weakly metabolized and is primarily eliminated renally (possibly via OCT). Atazanavir is unlikely to inhibit OCTs at clinically relevant concentrations. Note, both drugs have conditional risks of QT prolongation and/or TdP on the CredibleMeds.org website. Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, in the absence of PK drug-drug interactions, there is no anticipated increased risk of QT prolongation when combining these drugs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19. Atazanavir has no inhibitory effects on CYP2D6 and CYP2C19. Note, both drugs have conditional risks of QT prolongation and/or TdP on the CredibleMeds.org website. Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, in the absence of PK drug-drug interactions, there is no anticipated increased risk of QT prolongation when combining these drugs.

Coadministration has not been studied. Amlodipine is metabolized by CYP3A4. Use with caution as atazanavir could increase concentrations of the amlodipine. If coadministration is indicated, consider a dose reduction for amlodipine of 50%. Use with caution as both atazanavir and calcium channel blockers prolong the PR interval. Close monitoring is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Amphotericin is not appreciably metabolized and is eliminated to a large extent in the bile. Note, both drugs have conditional risks of QT prolongation and/or TdP on the CredibleMeds.org website. Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, in the absence of PK drug-drug interactions, there is no anticipated increased risk of QT prolongation when combining these drugs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atazanavir is metabolized by CYP3A4. Anakinra, per se, has no inhibitory or inducing effects on cytochromes. Patients infected with COVID-19 may experience an elevation of IL-1 which has been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Anakinra will normalize cytochrome activity (via inhibition of IL-1) but no significant effect on atazanavir is expected and no a priori dose adjustment is required. Atazanavir is an inhibitor of CYP3A4 and UGT1A1 and is a strong inhibitor of OATP1B1 but no effect on anakinra is expected as it is eliminated by glomerular filtration and subsequent tubular metabolism.

Coadministration with antacids may reduce atazanavir plasma concentrations as atazanavir solubility decreases as pH increases. Atazanavir should be administered 2 hours before or 1 hour after antacids.

Coadministration has not been studied and is not recommended. Apixaban is a substrate of P-gp and is metabolized by CYP3A4 and to a lesser extent CYP1A2, CYP2C8, CYP2C9 and CYP2C19. Concentrations of apixaban are expected to increase due to potent CYP3A4 and P-gp inhibition by atazanavir. Increased concentrations of apixaban increase the bleeding risk and the combination should be avoided if possible. There is emerging evidence that inflammatory changes also have an inhibitory effect on CYP3A4 and P-gp; the magnitude of this additional effect is expected to be less pronounced in COVID-19 patients with low levels of inflammation.

Coadministration has not been studied. Aripiprazole is metabolized by CYP3A4 and CYP2D6. Atazanavir could potentially increase aripiprazole concentrations. Monitor adverse effects and decrease aripiprazole dosage if needed. The European product label advises reducing the aripiprazole dose to approximately one-half of its prescribed dose when given with potent inhibitors of CYP3A4, such as HIV protease inhibitors. In addition, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; aripiprazole has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atazanavir is metabolized by CYP3A4 and is an inhibitor of CYP3A4 and UGT1A1 and is a strong inhibitor of OATP1B1. Aspirin (acetylsalicylic acid) is rapidly metabolised to salicylic acid, which is further glucuronidated by several UGTs (major UGT1A6). Salicylic acid and its metabolites are predominantly excreted via the kidneys. Aspirin and salicylic acid are extensively bound to plasma proteins, primarily albumin. Interactions with aspirin and substrates, inducers, or inhibitors of CYP enzymes are unlikely.

The recommended dose of atazanavir/ritonavir is 300/100 mg once daily. Coadministration with additional atazanavir is not recommended except in certain clinical situations (refer to atazanavir product labels for details).

The recommended adult dose of atazanavir/cobicistat is 300/150 mg once daily. Coadministration with additional atazanavir is not recommended.

No clinically significant pharmacokinetic interaction was observed when atazanavir alone (400 mg once daily) was coadministered with atenolol (50 mg once daily). No dose adjustment of atenolol is required when used in combination with atazanavir alone as atenolol is mainly eliminated unchanged in the kidney, both by glomerular filtration and active secretion via the renal transporters OCT2 and MATE1. No additive effect on the PR interval was noted for the coadministration of atazanavir and atenolol. However, PR interval monitoring may be warranted in patients with underlying block or those receiving known atrioventricular nodal blocking agents.

Coadministration of unboosted atazanavir and atorvastatin has not been studied but is expected to substantially increase atorvastatin due to inhibition of CYP3A4, OATP1B1 and BCRP by atazanavir. Coadministration of atazanavir/cobicistat and atorvastatin increased atorvastatin AUC and Cmax by 822% and 1785%. Coadministration is not recommended. If the use of atorvastatin is considered necessary, the lowest possible dose of atorvastatin should be used and the daily dose should not exceed 10 mg with careful safety monitoring.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atazanavir is metabolised by CYP3A4 and inhibits this enzyme. Baricitinib is not expected to have a clinically relevant effect on drugs metabolised by CYP enzymes. No effect on baricitinib is expected as it is mainly eliminated renally and CYP3A4 contributes to less than 10% of its overall metabolism. Coadministration with ketoconazole (a strong CYP3A4 inhibitor) had no significant impact on baricitinib exposure.

Coadministration atazanavir has not been studied. In vitro data indicate that beclometasone is a pro-drug which is hydrolysed via esterase enzymes to the highly active metabolite beclometasone-17-monopropionate. This active metabolite is subsequently converted to inactive metabolites via CYP3A4/5. Coadministration of ritonavir (100 mg twice daily) and inhaled beclomethasone dipropionate (160 mg twice daily) increased the AUC and Cmax of beclomethasone-17-monoproprionate by 108% and 67%, respectively. However, coadministration of a boosted PI (darunavir/ritonavir, 600/100 mg twice daily) decreased the AUC and Cmax of the active metabolite by 11% and 19%, respectively. Although statistically significant, the 2-fold increase in AUC of the active metabolite seen with ritonavir is unlikely to be of clinical significance as no significant effect on adrenal function was seen with either ritonavir or darunavir/ritonavir. Use the lowest possible corticosteroid dose with caution and monitor for corticosteroid side effects.

Coadministration has not been studied. Bedaquiline is metabolised by CYP3A4 and moderate or strong CYP3A4 inhibitors (such as atazanavir) may increase bedaquiline exposure which could potentially increase the risk of adverse reactions. Bedaquiline has a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval. When bedaquiline is coadministered with other medicinal products that prolong the QTc interval, such as atazanavir, an additive or synergistic effect on QT prolongation cannot be excluded. The combination of bedaquiline and moderate or strong CYP3A4 inhibitors used systemically for more than 14 consecutive days should be avoided. If coadministration is necessary, clinical monitoring including frequent electrocardiogram assessment and monitoring of transaminases is recommended. There are no clinical data on the safety and efficacy of bedaquiline when co-administered with antiretroviral agents.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bendroflumethiazide is mainly eliminated by hepatic metabolism (70%), although the exact pathway is not known. It is unlikely that CYP enzymes are involved in this process and no transporter interactions have been described. There is no evidence that bendroflumethiazide inhibits or induces CYP450 enzymes. Note, both drugs have conditional risks of QT prolongation and/or TdP on the CredibleMeds.org website. Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, in the absence of PK drug-drug interactions, there is no anticipated increased risk of QT prolongation when combining these drugs.

Coadministration has not been studied and is contraindicated in the European product label for atazanavir. Coadministration may increase bepridil concentrations and has the potential to produce serious and/or life-threatening adverse events. In addition, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; bepridil has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Betamethasone is metabolized by CYP3A4 and coadministration may therefore lead to elevated corticosteroid levels, Cushing’s syndrome and adrenal axis suppression. A case of Cushing’s syndrome and adrenal suppression in a patient on atazanavir/ritonavir and dexamethasone 0.1% eye drops and betamethasone 0.1% eye ointment has been reported. Betamethasone is a moderate inducer of CYP3A4. Caution is needed when betamethasone is administered orally or intravenously at high doses or for a long duration as it may decrease atazanavir exposure.

Coadministration has not been studied. Betrixaban is largely eliminated unchanged through biliary secretion via P-gp. Coadministration with a P-gp inhibitor (such as atazanavir) is expected to increase betrixaban exposure. There is emerging evidence that inflammatory changes also have an inhibitory effect on P-gp; the magnitude of this additional effect is expected to be less pronounced in COVID-19 patients with low levels of inflammation. The US product label for betrixaban recommends for patients receiving or starting a strong P-gp inhibitor to reduce betrixaban dose and use an initial dose of 80 mg followed by 40 mg once daily. Furthermore, patients should be monitored closely and any signs or symptoms of blood loss should be evaluated promptly. Betrixaban has demonstrated an exposure dependent increase in QT interval therefore caution is required when coadministering with another drug that may prolong the QTc interval. Of note, coadministration of betrixaban might need to be reconsidered in patients with concomitant renal impairment (creatinine clearance <60 ml/ml) as renal impairment per se does increase betrixaban exposure.

Coadministration of bictegravir with medicinal products that potently inhibit both CYP3A and UGT1A1, such as atazanavir, may significantly increase plasma concentrations of bictegravir, therefore coadministration is not recommended. Coadministration of bictegravir (75 mg) and atazanavir alone (400 mg once daily) increased bictegravir AUC by 315%.

Coadministration has not been studied and is not recommended. Coadministration may increase bosentan concentrations but decrease atazanavir concentrations. If coadministration is required, consider atazanavir with ritonavir or cobicistat.

Coadministration has not been studied. Atazanavir is metabolized by CYP3A. Atazanavir is an inhibitor of CYP3A4 and UGT1A1 and is a strong inhibitor of OATP1B1. Budesonide does not induce or inhibit CYPs but is metabolized by CYP3A4. Concentrations of budesonide may increase due to CYP3A4 inhibition by atazanavir. This is unlikely to be clinically relevant due to the short duration of inhaled budesonide used in COVID-19 treatment (2 weeks). However, prescribers should be aware of and to look out for signs of systemic corticosteroid side effects.

Coadministration has not been studied and is not recommended. Concomitant use of atazanavir and glucocorticoids metabolised by CYP3A4 is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression. Systemic corticosteroid effects have been reported in patients receiving ritonavir and fluticasone; this could also occur with other corticosteroids metabolised via the P450 3A pathway e.g. budesonide. A switch to a glucocorticoid which is not a substrate for CYP3A4 (e.g. beclometasone) should be considered. Moreover, in case of withdrawal of glucocorticoids progressive dose reduction may have to be performed over a longer period. There is a case report of a patient stable on atazanavir/ritonavir, nevirapine and lamivudine who developed oedema, weight gain, uncontrolled hypertension, Cushingoid facies, hypokalaemia, and metabolic alkalosis shortly after initiation of budesonide, with resolution of all symptoms soon after it was stopped.

Coadministration has not been studied, but is expected to increase buprenorphine plasma concentrations. Coadministration of atazanavir/ritonavir (300/100 mg once daily) and buprenorphine (stable maintenance dose, once daily) increased buprenorphine AUC, Cmax and Cmin by 67%, 37% and 69%, respectively; norbuprenorphine increased by ~2-fold. Similarly, unboosted atazanavir is expected to increase buprenorphine exposure. Coadministration warrants clinical monitoring for sedation and cognitive effects. A dose reduction of buprenorphine may be considered. In addition, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; buprenorphine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been formally studied but based on current knowledge of the effect of vaccines on drug disposition a clinically significant interaction is considered unlikely.

Coadministration has not been studied. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Coadministration with the strong UGT1A1 inhibitor atazanavir was predicted to increase cabotegravir (30 mg once daily) exposure by 11% which is considered not to be clinically relevant. Cabotegravir is not expected to alter concentrations of other antiretroviral products. No dosage adjustment is necessary.

Coadministration has not been studied. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Coadministration with the strong UGT1A1 inhibitor atazanavir was predicted to increase oral cabotegravir (30 mg once daily) exposure by 11% which is considered to be not clinically relevant. Similarly, no significant effect is expected when cabotegravir is administered intramuscularly. Rilpivirine is metabolized primarily by CYP3A and atazanavir may increase rilpivirine concentrations. However, no dose adjustment of rilpivirine is required as the expected increase in rilpivirine concentrations is not considered clinically relevant. Cabotegravir and rilpivirine are not expected to affect concentrations of atazanavir. Note, both atazanavir and rilpivirine have risks of QT prolongation and/or TdP on the CredibleMeds.org website (conditional risk for atazanavir; possible risk for rilpivirine). Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, there is no anticipated increased risk of QT prolongation when combining these drugs. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but equivalent rilpivirine concentrations are unlikely to occur during coadministration with atazanavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atazanavir is metabolized by CYP3A4. Canakinumab, per se, has no inhibitory or inducing effects on cytochromes. Patients infected with COVID-19 may experience an elevation of IL-1 which has been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Canakinumab will normalize cytochrome activity (via inhibition of IL-1) but no significant effect on atazanavir is expected and no a priori dose adjustment is required. Atazanavir is an inhibitor of CYP3A4 and UGT1A1 and is a strong inhibitor of OATP1B1 but no effect on canakinumab is expected as it is eliminated via intracellular catabolism.

Coadministration has not been studied and is not recommended. Coadministration could potentially increase carbamazepine concentrations and significantly reduce atazanavir concentrations, leading to loss of therapeutic effect and possible development of resistance. If coadministration is unavoidable, monitor carbamazepine serum concentrations and adjust dose as necessary. Closely monitor virological response and consider use of atazanavir/ritonavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atazanavir is metabolized by CYP3A4 and is an inhibitor of CYP3A4 and UGT1A1 and is a strong inhibitor of OATP1B1. Bamlanivimab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Bamlanivimab is not metabolized by CYP enzymes. Interactions with concomitant medications that are substrates, inducers, or inhibitors of CYP enzymes are unlikely.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Chlorpromazine is metabolized mainly by CYP2D6, but also by CYP1A2. Atazanavir alone does not inhibit CYP2D6 or CYP1A2. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; chlorpromazine has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration may increase plasma concentrations of ciclosporin due to inhibition of CYP3A4 and could increase or prolong its therapeutic and adverse events. More frequent therapeutic concentration monitoring is recommended until plasma levels have been stabilised.

Coadministration has not been studied as is not recommended. H2-receptor antagonists reduce the absorption of atazanavir, but the extent of the interaction can depend on dose and timing of administration. It is recommended to give atazanavir with a ritonavir or cobicistat if coadministration with an H2RA is required. For patients unable to tolerate ritonavir (who are not pregnant), atazanavir 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. Note, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; cimetidine has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Ciprofloxacin is primarily eliminated unchanged through the kidneys (by glomerular filtration and tubular secretion via OAT3. Ciprofloxacin is also metabolized and partially cleared through the bile and intestine. Atazanavir is unlikely to inhibit OATs at clinically relevant concentrations. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; ciprofloxacin has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration is contraindicated as it may increase cisapride concentrations which may increase potential serious and/or life-threatening adverse reactions such as cardiac arrhythmias. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; cisapride has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Citalopram is metabolized by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Atazanavir could potentially increase citalopram concentrations although to a moderate extent and no a priori dosage adjustment is recommended. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; citalopram has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration with atazanavir alone increased atazanavir and clarithromycin exposure and reduced exposure of the active metabolite, 14-OH clarithromycin, by 70%. The European product label for atazanavir states "No recommendation regarding dose reduction [of clarithromycin] can be made" and "a dose reduction of clarithromycin may result in subtherapeutic concentrations of 14-OH clarithromycin", but the US product label suggests a 50% reduction in clarithromycin dose should be considered. In addition, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; clarithromycin has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; clofazimine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Clomipramine is metabolized by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. In addition, clomipramine and desmethylclomipramine are metabolized by CYP2D6. Atazanavir could potentially increase clomipramine concentration. Monitor adverse effects. Note, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; clomipramine has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but is not recommended. Clopidogrel is a prodrug and is converted to its active metabolite via CYPs 3A4, 2B6, 2C19 and 1A2. Atazanavir inhibits CYP3A4, and other CYP3A4 inhibitors (ritonavir and cobicistat) have been shown to decrease clopidogrel exposure. In HIV-positive subjects, the presence of a pharmacoenhancer (ritonavir n=8; cobicistat n=1) decreased the AUC and Cmax of clopidogrel’s active metabolite both by 69% when compared to values obtained in HIV-negative subjects (n=12). In HIV-negative subjects (n=12), coadministration of clopidogrel and ritonavir (100 mg twice daily) decreased the AUC and Cmax of clopidogrel’s active metabolite by 51% and 48%. Importantly, the decrease in clopidogrel’s active metabolite lead to insufficient inhibition of platelet aggregation in 44% of the patients treated with clopidogrel and ritonavir or cobicistat. Consistently, the study in HIV-negative subjects showed that the average inhibition of platelet aggregation was decreased from 51% (clopidogrel alone) to 31% (clopidogrel + ritonavir). Of interest, the study with HIV-infected patients showed a comparable decrease in prasugrel’s active metabolite AUC (52% decrease), however this decrease did not impair prasugrel’s antiplatelet effect. The differential impact on clopidogrel and prasugrel pharmacodynamics effect is in line with clinical observations. Early thrombosis of a coronary stent was reported in a patient treated with darunavir/ritonavir concomitantly with clopidogrel while subsequent replacement of clopidogrel by prasugrel did not lead to novel stent thrombosis episodes. Taken together these data suggest that given the risk of diminished clopidogrel response, prasugrel should be preferred in presence of atazanavir, unless the patient has a clinical condition which contraindicates its use in which case an alternative antiplatelet agent should be considered.

Coadministration has not been studied. Clozapine is metabolized by CYPs 1A2, 2C19, 3A4, and to a lesser extent by CYPs 2C9 and 2D6. Atazanavir could potentially increase clozapine exposure. Monitor patient closely for toxicity. In addition, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; clozapine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of cyclizine has not been fully described but may involve CYP2D6. Atazanavir alone does not affect CYP2D6 and is metabolized by CYP3A4.

Coadministration has not been studied and is not recommended. Dabigatran is a substrate of P-gp and atazanavir is an inhibitor of P-gp. Pharmacokinetic interactions were observed with simultaneous or separated administration with other P-gp inhibitors - ritonavir had no effect or decreased dabigatran AUC (due to the mixed induction and inhibition of intestinal P-gp by ritonavir), but cobicistat increased dabigatran AUC by 110-127% (due to inhibition of intestinal P-gp). Similarly to atazanavir/cobicistat, unboosted atazanavir has no inducing effects and therefore is expected to increase dabigatran exposure and result in a more pronounced anticoagulant response; therefore, coadministration is not recommended. There is emerging evidence that inflammatory changes also have an inhibitory effect on P-gp; the magnitude of this additional effect is expected to be less pronounced in COVID-19 patients with low levels of inflammation.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atazanavir is metabolized by CYP3A4 and is an inhibitor of CYP3A4 and UGT1A1 and is a strong inhibitor of OATP1B1. Dalteparin is excreted largely unchanged by the kidneys and does not induce or inhibit CYPs or P-gp.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapsone is mainly metabolized by N-acetylation with a component of N-hydroxylation, and is via multiple CYP P450 enzymes.

Note: this interaction was studied using a darunavir/ritonavir dose lower than that licensed. Coadministration of atazanavir (300 mg once daily) and darunavir/ritonavir (400/100 mg twice daily) had no significant effect on darunavir or atazanavir exposure. Darunavir Cmax, AUC and Cmin increased by 2%, 3% and 1%, respectively. Atazanavir Cmax decreased by 11%; AUC and Cmin increased by 8% and 52%, respectively (relative to atazanavir/ritonavir 300/100 mg once daily alone). No dosage adjustments are recommended when darunavir/ritonavir is coadministered with atazanavir.

Coadministration has not been studied and is not recommended. Appropriate doses of this combination with respect to safety, efficacy and pharmacokinetics have not been established.

Coadministration has not been studied and is not recommended. Appropriate doses of this combination with respect to safety, efficacy and pharmacokinetics of atazanavir have not been established.

Coadministration has not been studied. Delamanid is primarily metabolised by albumin to DM-6705; metabolism of DM-6705 to other metabolites is thought to involve pathways mediated by CYP enzymes, including CYP3A4. Co-administration of delamanid with a strong inhibitor of CYP3A4 (lopinavir/ritonavir) increased DM-6705 exposure by 25-30%. QTc prolongation has been reported with delamanid (and is very closely correlated with the metabolite DM-6705), therefore, caution is advised with atazanavir due to potent CYP3A4 inhibition and due to the risk of QT prolongation associated with both drugs. If coadministration is considered necessary, frequent ECG monitoring is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Desipramine is metabolized by CYP2D6. Unboosted atazanavir has no inhibitory effects on CYP2D6. Note, both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (conditional risk for atazanavir; possible risk for desipramine). Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, in the absence of PK drug-drug interactions, there is no anticipated increased risk of QT prolongation when combining these drugs.

Coadministration with a desogestrel-containing combined oral contraceptive (COC) has not been studied. Desogestrel is a prodrug that requires activation to etonogestrel. Activation to etonogestrel is by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Coadministration with atazanavir is predicted to increase the conversion to the active metabolite etonogestrel due to inhibition of CYP3A4 and to increase ethinylestradiol. However, no action is needed due to the short treatment duration of the COVID-19 therapy.

Coadministration with a desogestrel-containing progestogen-only pill (POP) has not been studied. Desogestrel is a prodrug that requires activation to etonogestrel. Activation to etonogestrel is by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Coadministration is predicted to increase etonogestrel and, based on studies with norethisterone used as a POP, the contraceptive efficacy of a desogestrel POP is unlikely to be compromised by atazanavir. No action is needed due to the short treatment duration of the COVID-19 therapy.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atazanavir is metabolized by CYP3A4. Atazanavir is an inhibitor of CYP3A4 and UGT1A1 and is a strong inhibitor of OATP1B1. Product labels for dexamethasone do not recommend coadministration of strong CYP3A4 inhibitors with dexamethasone but based on the low dose of dexamethasone used in COVID-19 treatment this is unlikely to be clinically significant. Dexamethasone is a moderate CYP3A4 inducer but is unlikely to have a clinically significant effect on atazanavir.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Dexmedetomidine undergoes extensive hepatic metabolism biotransformation through direct glucuronidation (mainly via UGT1A4, 2B10) and cytochrome P450 (mainly CYP2A6). There is no evidence that atazanavir inhibits or induces these metabolic enzymes. Note, both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (conditional risk for atazanavir; possible risk for dexmedetomidine). Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, in the absence of PK drug-drug interactions, there is no anticipated increased risk of QT prolongation when combining these drugs.

Coadministration of diltiazem and atazanavir alone resulted in a 2- to 3-fold increase in diltiazem and desacetyl-diltiazem exposure and no change in the pharmacokinetics of atazanavir (data from HIV- subjects). There was an increase in the maximum PR interval compared to atazanavir alone. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; diltiazem has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website. An initial dose reduction of diltiazem by 50% is recommended, with subsequent titration as needed and ECG monitoring.

Coadministration has not been studied and is not recommended. Disopyramide is metabolized by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine. Coadministration may increase disopyramide exposure and thereby the risk of cardiac arrhythmias. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; disopyramide has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied and is not recommended. Dofetilide is metabolized to a small degree by CYP3A4 and therefore atazanavir could potentially increase dofetilide exposure and thereby increase the risk of cardiac arrhythmias. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; dofetilide has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Dolasetron is converted by carbonyl reductase to its active metabolite, hydrodolasetron, which is mainly glucuronidated (60%) and metabolized by CYP2D6 (10-20%) and CYP3A4 (<1%). Coadministration could potentially increase dolasetron concentrations although this is unlikely to be clinically meaningful since CYP-mediated metabolism is minor and dolasetron has a wide therapeutic margin. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; dolasetron has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration of atazanavir (400 mg once daily) and dolutegravir (30 mg once daily) increased dolutegravir Cmax and AUC by 50% and 91%, with Ctrough increasing by 2.8-fold. Compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of atazanavir. No dosage adjustment is necessary. The European SmPC for dolutegravir advises that dolutegravir should not be dosed higher than 50 mg twice daily in combination with atazanavir due to lack of data.

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied but based on metabolism a clinically significant interaction is unlikely. Coadministration of atazanavir alone (400 mg once daily) and dolutegravir (30 mg once daily) increased dolutegravir AUC, Cmax and Ctrough by 91%, 50% and 180%, respectively. No significant effect on lamivudine and zidovudine concentrations was observed when atazanavir (400 mg once daily) was coadministered with lamivudine/zidovudine (150/300 mg twice daily). The European product label for Dovato (dolutegravir/lamivudine) advises that no dose adjustment is necessary with atazanavir. 

Coadministration with dolutegravir/rilpivirine has not been studied. Coadministration of atazanavir alone (400 mg once daily) and dolutegravir (30 mg once daily) increased dolutegravir Cmax and AUC by 50% and 91%, with Ctrough increasing by 2.8-fold. Coadministration of atazanavir/ritonavir (300/100 mg once daily) and dolutegravir (30 mg once daily) increased dolutegravir Cmax and AUC by 34% and 62%, and increased Ctrough by 2.21-fold. Compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of atazanavir. Coadministration of rilpivirine and atazanavir has not been studied but may increase rilpivirine concentrations. Rilpivirine is not expected to affect concentrations of atazanavir. Note, both atazanavir and rilpivirine have risks of QT prolongation and/or TdP on the CredibleMeds.org website (conditional risk for atazanavir; possible risk for rilpivirine). Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, there is no anticipated increased risk of QT prolongation when combining these drugs. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but equivalent rilpivirine concentrations are unlikely to occur during coadministration with atazanavir.

Coadministration with dolutegravir/abacavir/lamivudine has not been studied. Coadministration of atazanavir alone (400 mg once daily) and dolutegravir (30 g once daily) increased dolutegravir AUC, Cmax and Ctrough by 91%, 50% and 180%, respectively. No significant effect on lamivudine and zidovudine concentrations was observed when atazanavir (400 mg once daily) was coadministered with lamivudine/zidovudine (150/300 mg twice daily). No interaction is expected with abacavir.

Coadministration has not been studied and is contraindicated with potent CYP3A4 inhibitors, such as atazanavir. Domperidone is mainly metabolized by CYP3A4. Atazanavir could potentially increase domperidone exposure and increase the risk of cardiac adverse effects. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; domperidone has a known  risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Doravirine is metabolized by CYP3A4 and coadministration may increase doravirine concentrations due to inhibition of CYP3A4 by atazanavir. Coadministration with ritonavir (a strong inhibitor of CYP3A4) increased doravirine exposure by ~3.5-fold. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration with Delstrigo (doravirine, lamivudine, tenofovir-DF) has not been studied and is not recommended as tenofovir-DF may decrease atazanavir concentrations. Coadministration of tenofovir-DF (300 mg once daily; a component of Delstrigo) and atazanavir (400 mg) decreased atazanavir AUC, Cmax and Cmin by 25%, 21% and 40%, respectively, but increased tenofovir AUC, Cmax and Cmin by 24%, 14% and 22%, respectively. Doravirine concentrations may increase due to inhibition of CYP3A4 by atazanavir as coadministration with ritonavir (a strong inhibitor of CYP3A4) increased doravirine exposure by ~3.5-fold. However, phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure. No effect on lamivudine is expected.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Doxepin is metabolized to nordoxepin (a metabolite with comparable pharmacological activity as the parent compound) mainly by CYP2C19. In addition, doxepin and nordoxepin are metabolized by CYP2D6. Atazanavir alone does not inhibit CYP2C19 or CYP2D6. Note, both drugs have conditional risks of QT prolongation and/or TdP on the CredibleMeds.org website. Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, in the absence of PK drug-drug interactions, there is no anticipated increased risk of QT prolongation when combining these drugs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No significant metabolism of doxycycline occurs – it is cleared intact by renal and biliary mechanisms. No pharmacokinetic interaction was observed with doxycycline and protease inhibitors (lopinavir/ritonavir, atazanavir/ritonavir, atazanavir alone) but a specific drug effect could not be determined due to small groups and the lack of statistical power.

Coadministration with a drospirenone-containing combined oral contraceptive (COC) has not been studied. Drospirenone is metabolised in part by CYP3A4. Coadministration is predicted to increase drospirenone and ethinylestradiol exposures. However, no action is needed due to the short treatment duration of the COVID-19 therapy.

Coadministration has not been studied. Edoxaban is a substrate for P-gp and coadministration is expected to increase edoxaban concentrations due to P-gp inhibition. There is emerging evidence that inflammatory changes also have an inhibitory effect on P-gp; the magnitude of this additional effect is expected to be less pronounced in COVID-19 patients with low levels of inflammation. The European product label for edoxaban states to consider a dose reduction of edoxaban from 60 mg to 30 mg with strong P-gp inhibitors, however, the US product label recommends no dose modification.

Coadministration with atazanavir alone is not recommended as efavirenz decreases atazanavir exposure. Coadministration of atazanavir (400 mg once daily) and efavirenz (600 mg once daily) decreased atazanavir AUC, Cmax and Cmin by 74%, 59% and 93%, respectively. In addition, both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (conditional risk for atazanavir; possible risk for efavirenz). 

Coadministration of elbasvir/grazoprevir with OATP1B inhibitors, such as atazanavir is contraindicated. Coadministration with atazanavir/ritonavir increased grazoprevir AUC, Cmax and Cmin by 10.58-fold, 6.24-fold and 11.64-fold. The risk of ALT elevations may be increased due to the significant increase in grazoprevir plasma concentrations caused by OATP1B1/3 inhibition.

Coadministration Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) has not been studied but is expected to increase atazanavir concentrations due to inhibition of CYP3A4 by cobicistat. Tenofovir exposure may increase due inhibition of P-gp by atazanavir. However, tenofovir alafenamide is present in Genvoya at 10 mg which is the recommended dose when given with P-gp inhibitors such as atazanavir. No effect on elvitegravir or emtricitabine is expected.

Coadministration has not been studied. Atazanavir concentrations may increase due to inhibition of CYP3A4 by cobicistat. Tenofovir exposure may increase due to inhibition of P-gp by atazanavir. If coadministration is necessary, patients should be closely monitored for tenofovir-associated adverse events, including renal disorders. No effect on elvitegravir or emtricitabine is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Based on the results of in vitro experiments and the known elimination pathways of emtricitabine, the potential for CYP450 mediated interactions involving emtricitabine with other medicinal products is low.

Coadministration with atazanavir alone has not been studied. Coadministration of atazanavir/ritonavir (300/100 mg once daily) and emtricitabine/tenofovir alafenamide (200/10 mg once daily) increased tenofovir AUC and Cmax by 162% and 112% (n=10). Coadministration of atazanavir/ritonavir (300/100 mg once daily) and tenofovir alafenamide alone (10 mg) increased tenofovir AUC and Cmax by 91% and 77%. Coadministration of atazanavir/cobicistat (300/150 mg once daily) and tenofovir alafenamide increased tenofovir alafenamide AUC and Cmax by 75% and 80%. No significant effects were observed on atazanavir pharmacokinetics. When given with P-gp inhibitors such as atazanavir, the recommended dose of tenofovir alafenamide is 10 mg once daily (where available).

Coadministration has not been studied and is not recommended. The US product label for emtricitabine/tenofovir-DF states that atazanavir should not be given alone with emtricitabine/tenofovir-DF, but should be administered at a dose of 300 mg once daily with ritonavir 100 mg once daily. Coadministration of tenofovir-DF (300 mg once daily) and atazanavir alone (400 mg once daily) decreased atazanavir AUC, Cmax and Cmin by 25%, 21% and 40%, respectively (n=34); tenofovir AUC, Cmax and Cmin increased by 24%, 14% and 22%, respectively (n=33).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atazanavir is metabolized by CYP3A4 and is an inhibitor of CYP3A4 and UGT1A1 and is a strong inhibitor of OATP1B1. Enoxaparin does not undergo cytochrome metabolism but is desulphated and depolymerised in the liver and is excreted predominantly renally. Enoxaparin does not induce or inhibit CYPs or P-gp.

Coadministration has not been studied and is not recommended. Erythromycin concentrations may increase due to inhibition of CYP3A4 by atazanavir. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; erythromycin has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Escitalopram is metabolized by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Atazanavir could potentially increase escitalopram concentrations although to a moderate extent. No a priori dosage adjustment is recommended but monitor adverse effects. In addition, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; escitalopram has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Eslicarbazepine is partly eliminated unchanged renally and partly glucuronidated by UGT2B4. Eslicarbazepine is a weak/moderate inducer of CYP3A4. Coadministration could potentially reduce atazanavir concentrations, leading to loss of therapeutic effect and possible development of resistance. Consider boosting with ritonavir or use of other anticonvulsants. Eslicarbazepine has the potential to prolong the PR interval. An additive effect of atazanavir cannot be excluded therefore caution is needed. PR interval monitoring may be warranted in patients with underlying block or those receiving known atrioventricular nodal blocking agents.

Coadministration of atazanavir with proton pump inhibitors is not recommended. No data are available with esomeprazole; lansoprazole decreased atazanavir AUC by 94%, omeprazole decreased atazanavir AUC by 75%. If coadministration is judged unavoidable, close clinical monitoring is recommended and doses of proton pump inhibitors comparable to omeprazole 20 mg should not be exceeded and must be taken approximately 12 hours prior to the atazanavir. The European product label recommends increasing the dose of atazanavir to 400 mg with 100 mg of ritonavir. Note, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; esomeprazole has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration of atazanavir (400 mg once daily) and ethinylestradiol/norethindrone increased ethinylestradiol Cmax, AUC and Cmin by 15%, 48% and 91%, respectively. However, no action is needed due to the short treatment duration of the COVID-19 therapy.

Coadministration with atazanavir alone is not recommended. Coadministration of atazanavir alone (400 mg once daily) and etravirine decreased atazanavir Cmax, AUC and Cmin by 3%, 17% and 47%, respectively. Etravirine Cmax, AUC and Cmin increased by 47%, 50% and 58%, respectively, but this is not considered clinically relevant. Atazanavir should only be used with etravirine in the presence of low dose ritonavir.

Coadministration of these drugs has not been studied but should be avoided. Everolimus is metabolized by CYP3A4. Coadministration with ketoconazole, a potent inhibitor of CYP3A4, increased everolimus exposure by 15-fold. Similarly, a large increase in everolimus exposure is predicted in presence of atazanavir. Coadministration is not recommended as there are currently not sufficient data to allow dosing recommendations with potent CYP3A4 inhibitors.

H2-receptor antagonists reduce the absorption of atazanavir, but the extent of the interaction can depend on dose and timing of administration. When given simultaneously with atazanavir (400 mg once daily), atazanavir Cmax, AUC and Cmin decreased by 47%, 41% and 42% respectively. When atazanavir (400 mg once daily) was given 10 h after and 2 h before famotidine, atazanavir Cmax increased by 8% and AUC and Cmin decreased by 5% and 21% respectively. If coadministration with an H2-receptor antagonist is required, it is recommended to give atazanavir with ritonavir or cobicistat. For patients unable to tolerate ritonavir, atazanavir 400 mg once daily with food should be administered at least 2 hours before and at least 10 hours after a dose of the H2-receptor antagonist. No single dose of famotidine should exceed 20 mg, and the total daily dose should not exceed 40 mg. Note, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; famotidine has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Favipiravir is mainly metabolised by aldehyde oxidase and undergoes no CYP-mediated metabolism. Atazanavir is metabolised by CYP3A4 and is an inhibitor of CYP3A4 and UGT1A1. Favipiravir does not affect CYP3A4 and is not metabolised by CYPs or UGTs.

Coadministration has not been studied. Felodipine is metabolized by CYP3A4. Use with caution as atazanavir could increase concentrations of the felodipine and both atazanavir and calcium channel blockers prolong the PR interval. Dose titration of the calcium channel blocker should be considered. ECG monitoring is recommended.

Coadministration has not been studied but is not recommended. Flecainide and atazanavir should not be coadministered as it is likely to increase flecainide concentrations and has the potential to produce serious and/or life threatening reactions such as cardiac arrhythmias. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; flecainide has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration with atazanavir alone has not been studied. Coadministration of atazanavir/ritonavir (300/100 mg once daily) and fluconazole (200 mg once daily) resulted in no clinically significant interaction. No dosage adjustments are needed for atazanavir and fluconazole. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; fluconazole has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Fluoxetine is metabolized by CYPs 2D6 and 2C9 and to a lesser extent by CYPs 2C19 and 3A4 to form norfluoxetine. Atazanavir alone is unlikely to have a significant effect on fluoxetine concentrations. Note, both drugs have conditional risks of QT prolongation and/or TdP on the CredibleMeds.org website. Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, in the absence of PK drug-drug interactions, there is no anticipated increased risk of QT prolongation when combining these drugs.

Coadministration has not been studied. Concomitant use of atazanavir and glucocorticoids metabolised by CYP3A4 is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression. Alternative inhaled or nasal corticosteroids may be considered, particularly for long term use. Systemic corticosteroid effects have been reported in patients receiving strong inhibitors of CYP3A4 and inhaled or intranasally administered fluticasone propionate. A switch to a glucocorticoid which is not a substrate for CYP3A4 (e.g. beclomethasone) should be considered. Moreover, in case of withdrawal of glucocorticoids, progressive dose reduction may have to be performed over a longer period

Coadministration has not been studied. Fluvastatin is partially metabolised by CYP2C9 and is a substrate of OATP1B1 and there is a potential for a moderate increase in fluvastatin exposure when coadministered with atazanavir. Start fluvastatin at the lowest recommended dose and titrate as clinically indicated.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Fluvoxamine is extensively metabolized, mainly by CYP2D6 and to a lesser extent by CYP1A2. Atazanavir alone does not interact with CYP2D6. Atazanavir is metabolized by CYP3A4 and fluvoxamine is a moderate inhibitor of CYP3A4. However, coadministration of fluconazole (a moderate CYP3A4 inhibitor) and atazanavir had no effect on the pharmacokinetics of atazanavir. Similarly, no significant effect is expected with fluvoxamine. Note, both drugs have conditional risks of QT prolongation and/or TdP on the CredibleMeds.org website. Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, in the absence of PK drug-drug interactions, there is no anticipated increased risk of QT prolongation when combining these drugs.

Coadministration has not been studied. Formoterol is eliminated primarily by direct glucuronidation, with O-demethylation (by CYPs 2D6, 2C19, 2C9, and 2A6) followed by further glucuronidation being another pathway. As multiple CYP450 and UGT enzymes catalyze the transformation the potential for a pharmacokinetic interaction is low. However, formoterol may induce prolongation of the QT interval and the product label for formoterol advises caution in patients treated with drugs affecting the QT interval. Atazanavir has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Furosemide is glucuronidated mainly in the kidney (UGT1A9) and to a lesser extent in the liver (UGT1A1). A large proportion of furosemide is also eliminated unchanged renally. Note, both drugs have conditional risks of QT prolongation and/or TdP on the CredibleMeds.org website. Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, in the absence of PK drug-drug interactions, there is no anticipated increased risk of QT prolongation when combining these drugs.

Coadministration with a gestodene-containing combined oral contraceptive (COC) has not been studied. Gestodene is metabolized by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Coadministration is predicted to increase gestodene and ethinylestradiol exposure. However, no action is needed due to the short treatment duration of the COVID-19 therapy.

Coadministration has not been studied and is contraindicated. Coadministration of glecaprevir/pibrentasvir with OATP1B inhibitors, such as atazanavir, is contraindicated due to increased risk of ALT elevations. Coadministration of atazanavir/ritonavir (300/100 mg once daily) and glecaprevir/pibrentasvir increased glecaprevir Cmax, AUC and Cmin by at least 4.06-fold, 6.53-fold and 14.3-fold, respectively. Pibrentasvir Cmax, AUC and Cmin increased by at least 29%, 64% and 129%, respectively (n=12).

Coadministration has not been studied. In vitro studies have shown that granisetron is metabolized by CYP3A4. The clinical relevance of drug interactions involving strong CYP3A4 inhibitors is unknown. The strong CYP3A4 inducer phenobarbital increased granisetron’s clearance by 25% in a human pharmacokinetic study but the clinical significance of this change is not known. In addition, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; granisetron has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied and is not recommended. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGT2B7 > 1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYPs 3A4, 2D6). Atazanavir could potentially increase haloperidol exposure although to a moderate extent. Monitor side effects. In addition, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; haloperidol has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Hydrochlorothiazide is not metabolised and is cleared by the kidneys via OAT1. Atazanavir is unlikely to inhibit the renal transporters OATs at clinically relevant concentrations. Note, both drugs have conditional risks of QT prolongation and/or TdP on the CredibleMeds.org website. Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, in the absence of PK drug-drug interactions, there is no anticipated increased risk of QT prolongation when combining these drugs.

Coadministration has not been studied. Hydrocodone is metabolised by CYP2D6 to hydromorphone and by CYP3A4 to norhydrocodone, both of which have analgesic effects. Inhibition of CYP3A4 by atazanavir may increase hydromorphone concentrations but decrease concentrations of norhydrocodone. The clinical significance of this is unclear. Monitor the analgesic effect and for signs of opiate toxicity. In addition, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; hydrocodone has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atazanavir is metabolized by CYP3A4. Atazanavir is an inhibitor of CYP3A4 and UGT1A1 and is a strong inhibitor of OATP1B1. Product labels for hydrocortisone do not recommend coadministration of strong CYP3A4 inhibitors with hydrocortisone but based on the low dose of hydrocortisone used in COVID-19 treatment this is unlikely to be clinically significant. Hydrocortisone neither induces nor inhibits CYPs.

Coadministration has not been studied. Hydroxyzine is partly metabolized by alcohol dehydrogenase and partly by CYP3A4. Coadministration could potentially increase hydroxyzine exposure due to inhibition of CYP3A4. Note, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; hydroxyzine has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No drug interaction studies have been conducted with ibalizumab: based on ibalizumab’s mechanism of action and target-mediated drug disposition, drug-drug interactions are not expected. Inhibition of metabolism by atazanavir is unlikely to affect ibalizumab, a monoclonal antibody binding to the CD4 receptor, which is likely to be eliminated via intracellular catabolism similarly to other monoclonal antibodies.

Coadministration has not been studied. Iloperidone is metabolised by CYP3A4 and CYP2D6 and coadministration may increase iloperidone concentrations. The US product label for iloperidone suggests a dose reduction of ~50% when coadministered with strong inhibitors of CYP3A4 but recommends avoiding the use of iloperidone in combination with other drugs known to prolong the QT interval. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; iloperidone has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Imipramine is metabolized by CYPs 3A4, 2C19 and 1A2 to desipramine. Imipramine and desipramine are both metabolized by CYP2D6. Atazanavir could potentially increase imipramine concentrations. Monitor side effects and consider dose reduction if needed. In addition, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; imipramine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Indapamide is extensively metabolized by CYP450. Atazanavir could potentially increase indapamide concentrations. Monitor the clinical effect and reduce the dosage of indapamide if needed. Note, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; indapamide has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but is not recommended. Isavuconazole is metabolised by CYP3A4/5 and UGTs. Coadministration with lopinavir/ritonavir or ketoconazole was shown to increase isavuconazole exposure by 2-fold and 5-fold, respectively. The difference in the magnitude of the drug-drug interaction may be explained by the inducing effect of ritonavir on UGTs. The magnitude of the interaction with atazanavir is expected to be more pronounced than with lopinavir/ritonavir given that unboosted atazanavir has no inducing effect and inhibits both CYP3A4 and UGT1A1. The product label for isavuconazole contraindicates coadministration with ketoconazole; similarly, coadministration with unboosted atazanavir should be avoided. 

Coadministration has not been studied. Based on data with ketoconazole, no effect of itraconazole on atazanavir is expected. However, atazanavir may increase itraconazole concentrations due to inhibition of CYP3A4. When coadministration is required caution is warranted and clinical monitoring is recommended. The daily dose of itraconazole should not exceed 200 mg. Note, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; itraconazole has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration is contraindicated with strong inhibitors of CYP3A4. Coadministration is likely to increase ivabradine concentrations which may be associated with the risk of excessive bradycardia. Note, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; ivabradine has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration of ketoconazole (200 mg once daily) with atazanavir (400 mg once daily) had no significant effect on atazanavir (Cmax decreased by 1%; AUC and Cmin increased by 10% and 3%). However, atazanavir could potentially increase ketoconazole concentrations due to inhibition of CYP3A4. Caution is advised and high doses of ketoconazole (>200 mg/day) are not recommended. Note, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; ketoconazole has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Lacidipine is metabolized by CYP3A4. Atazanavir is predicted to increase lacidipine exposure. Use with caution and consider dose titration of lacidipine. In addition, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; lacidipine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration with lamivudine alone has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. No significant effect on lamivudine and zidovudine concentrations was observed when atazanavir (400 mg once daily) was coadministered with lamivudine/zidovudine (150/300 mg twice daily).

Coadministration of lamotrigine (100 mg single dose) and with atazanavir alone (400 mg once daily) had no significant effect on lamotrigine AUC or Cmax. No dose adjustment of lamotrigine is required when coadministered with unboosted atazanavir.

Coadministration of atazanavir with proton pump inhibitors is not recommended. Lansoprazole decreased atazanavir (alone) AUC by 94%, omeprazole decreased atazanavir (+ ritonavir) AUC by 75%. If coadministration is judged unavoidable, close clinical monitoring is recommended and doses of proton pump inhibitors comparable to omeprazole 20 mg should not be exceeded and must be taken approximately 12 hours prior to the atazanavir. Note, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; lansoprazole has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied, but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Levofloxacin is eliminated renally mainly by glomerular filtration and active secretion (possibly OCT2). However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; levofloxacin has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Levomepromazine is metabolized mainly by CYP2D6. Atazanavir alone does not inhibit CYP2D6. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; levomepromazine has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration of atazanavir with a levonorgestrel-containing combined oral contraceptive (COC) has not been studied. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Coadministration is predicted to increase levonorgestrel and ethinylestradiol exposure. However, no action is needed due to the short treatment duration of the COVID-19 therapy.

Coadministration has not been studied but there is little potential for interaction given the local mechanism of action of levonorgestrel intra-uterine device.

Coadministration has not been studied. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Coadministration is predicted to increase levonorgestrel and therefore, based on studies with norethisterone used as a progestogen only pill, the contraceptive efficacy of levonorgestrel POP is unlikely to be compromised by atazanavir. No action is needed due to the short treatment duration of the COVID-19 therapy.

Coadministration with a levonorgestrel progestogen-only implant has not been studied. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent; coadministration is predicted to increase levonorgestrel concentrations. Based on studies with norethisterone used as a progestogen only pill, the contraceptive efficacy of levonorgestrel progestogen-only implant is unlikely to be compromised by atazanavir. No action is needed due to the short treatment duration of the COVID-19 therapy.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Levothyroxine is metabolized by deiodination (by enzymes of deiodinase family) and glucuronidation. Although atazanavir is an inhibitor of UGT1A1, a clinically significant interaction is unlikely given the short duration of atazanavir treatment for COVID-19 therapy.

Coadministration has not been studied but may increase lidocaine concentrations. CYP1A2 is the predominant enzyme involved in lidocaine metabolism in the range of therapeutic concentrations with a minor contribution from CYP3A4. Caution is warranted and therapeutic concentration monitoring is recommended when available.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Lithium is mainly eliminated unchanged through the kidneys. Lithium is freely filtered at a rate that is dependent upon the glomerular filtration rate. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; lithium has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Atazanavir could potentially increase loperamide exposure (inhibition CYP3A4 and CYP2C8), but this is unlikely to result in opioid CNS effects as demonstrated by the lack of central effects when coadministering ritonavir (600 mg) and loperamide (16 mg). Note: The US Food and Drug Administration has issued a safety alert over the use of high doses of loperamide from abuse and misuse with case reports of cardiac events including QT interval prolongation. Cardiac events are unlikely to occur when loperamide is dosed as an antidiarrheal even if coadministered with atazanavir. However, caution is advised when loperamide is used at high doses for reducing stoma output, particularly as patients may be at increased risk of cardiac events due to electrolytes disturbances. Note, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; loperamide has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied is contraindicated due to the potential for serious reactions such as myopathy including rhabdomyolysis. Lovastatin is metabolised by CYP3A4 and coadministration may increase concentrations.

Oral magnesium salts have the properties of antacids. Coadministration with antacids may reduce atazanavir plasma concentrations as atazanavir solubility decreases as pH increases. Atazanavir should be administered 2 hours before or 1 hour after antacids.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Maprotiline is mainly metabolized by CYP2D6. Atazanavir alone does not inhibit CYP2D6. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; maprotiline has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration of maraviroc (300 mg twice daily) with atazanavir alone (400 mg once daily) increased maraviroc AUC (3.6-fold) and Cmax (2.1-fold). Decrease maraviroc to 150 mg twice daily when coadministered. The European SmPC for maraviroc recommends when coadministering potent CYP3A inhibitors and maraviroc to patients with impaired renal function (creatinine clearance less than 80 ml/min), maraviroc should be reduced to 150 mg once daily. The US Prescribing Information recommends 150 mg twice daily for patients with creatinine clearance of 30-80 ml/min and contraindicates coadministration in patients with creatinine clearance less than 30 ml/min or on haemodialysis.

Coadministration has not been studied but studies with PIs and NNRTIs seem to indicate that there is no significant pharmacokinetic interaction with depo-medroxyprogesterone.

Coadministration with medroxyprogesterone as hormone replacement therapy (HRT) has not been studied. Medroxyprogesterone is metabolized by CYP3A4. Coadministration is predicted to increase medroxyprogesterone exposure. However, no action is needed due to the short treatment duration of the COVID-19 therapy.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Melatonin is metabolized by CYP1A2 and CYP1A1. Atazanavir is unlikely to inhibit or induce CYP1A2 at clinically relevant concentrations.

Coadministration of atazanavir (400 mg once daily) and methadone (stable maintenance dose) had no significant effect on methadone concentrations. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; methadone has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atazanavir is metabolized by CYP3A4. Atazanavir is an inhibitor of CYP3A4 and UGT1A1 and is a strong inhibitor of OATP1B1. Methylprednisolone neither induces nor inhibits CYPs, but is metabolized by CYP3A4. Product labels for methylprednisolone do not recommend coadministration of strong CYP3A4 inhibitors with methylprednisolone but based on the low dose of methylprednisolone used in COVID-19 treatment this is unlikely to be clinically significant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with the topical use of methylprednisolone. Methylprednisolone is metabolized by CYP3A4, but neither induces nor inhibits CYPs. Inhibition of CYP3A4 by atazanavir is unlikely to have significant effect on topical methylprednisolone.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Metoclopramide is partially metabolized by CYP450 system (mainly CYP2D6). Atazanavir alone does not inhibit CYP2D6. Note, both drugs have conditional risks of QT prolongation and/or TdP on the CredibleMeds.org website. Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, in the absence of PK drug-drug interactions, there is no anticipated increased risk of QT prolongation when combining these drugs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Metolazone is largely excreted unchanged in the urine. Note, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; metolazone has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Metronidazole is eliminated via glomerular filtration. Note, both drugs have conditional risks of QT prolongation and/or TdP on the CredibleMeds.org website). Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, the risk of QT prolongation when combining these drugs is low.

Coadministration has not been studied. Mianserin is metabolized by CYPs 2D6 and 1A2, and to a lesser extent by CYP3A4. Atazanavir could potentially increase mianserin concentrations although to a limited extent. No a priori dosage adjustment is recommended. Note, both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (conditional risk for atazanavir; possible risk for mianserin). Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, given the modest PK drug-drug interaction, there is no anticipated increased risk of QT prolongation when combining these drugs.

Coadministration of ORAL midazolam and atazanavir/ritonavir is contraindicated due to potential for serious and/or life threatening events such as prolonged or increased sedation or respiratory depression. Coadministration of PARENTERAL midazolam should be done with caution and 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.

Coadministration of PARENTERAL midazolam should be done with caution and 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. Coadministration of ORAL midazolam and atazanavir is contraindicated due to potential for serious and/or life threatening events such as prolonged or increased sedation or respiratory depression.

Coadministration has not been studied. Mirtazapine is metabolised to 8-hydroxymirtazapine by CYP2D6 and CYP1A2, and to N-desmethylmirtazapine mainly by CYP3A4. Atazanavir could potentially increase mirtazapine concentration. Monitor side effects and consider dose reduction if needed. In addition, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; mirtazapine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied and is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects. Systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression have been reported in patients receiving a strong CYP3A4 inhibitor and inhaled administered fluticasone; this could also occur with other corticosteroids metabolized by CYP3A4, e.g. mometasone.