Coadministration with atazanavir alone has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Abatacept is a fusion protein consisting of the extracellular domain of human CTLA-4 linked to a modified Fc portion of human IgG1 and is likely to be eliminated via proteolytic catabolism throughout the body. Atazanavir is metabolized by CYP3A4.

Coadministration has been studied and is not recommended. Abemaciclib is metabolized by CYP3A4 and is a substrate of P-gp and BCRP. Clarithromycin (a strong CYP3A4 inhibitor) increased abemaciclib AUC by 3.4-fold and increased the AUC of abemaciclib with its three active metabolites by 2.2-fold. A similar effect is expected with atazanavir. Furthermore, atazanavir may cause QTc interval prolongation. No large QTc prolonging effect has been observed for abemaciclib, but the net effect on QT prolongation has not been reported and it is unknown whether there is a warning in place. Coadministration should be avoided if possible. If concurrent use is unavoidable, adjust the dose of abemaciclib to 50 mg twice daily with close monitoring for signs of toxicity.

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Abiraterone is metabolized by CYP3A4 and SULT2A1. A 15% increase in abiraterone exposure has been reported in presence of ketoconazole (a strong CYP3A4 inhibitor) and a similar effect is expected with atazanavir, but this is not considered to be clinically relevant. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; abiraterone has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website. Considering the modest pharmacokinetic interaction, the risk of a QT interval prolongation is low.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abrocitinib is metabolised predominantly by CYP2C19 and CYP2C9, and to a lesser extent by CYP3A4 and CYP2B6. Atazanavir inhibits CYP3A but a clinically significant effect on abrocitinib is not expected as CYP3A4 is a minor route of metabolism. Abrocitinib is not expected to have a clinically relevant effect on CYP3A4.

Coadministration has not been studied but should be avoided. Acalabrutinib is metabolized by CYP3A4. Itraconazole (a CYP3A4 inhibitor) increased acalabrutinib AUC and Cmax by 5.1- and 3.9-fold, respectively. A similar effect may occur with atazanavir. Increased acalabrutinib concentrations may result in increased toxicity, therefore, coadministration should be avoided.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acamprosate is eliminated unchanged in the urine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. After ingestion of acarbose, the majority of active unchanged drug remains in the lumen of the gastrointestinal tract to exert its pharmacological activity and is metabolised by intestinal enzymes and by the microbial flora.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acenocoumarol is mainly metabolized by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Atazanavir does not inhibit or induce these CYPs in the range of clinical concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acetazolamide is primarily excreted unchanged via the kidneys.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant drug-drug interaction is unlikely as aciclovir is eliminated renally via glomerular filtration and active renal secretion by OAT1. Atazanavir is unlikely to inhibit OATs at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acitretin undergoes isomerisation and glucuronidation.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aclidinium bromide is rapidly and extensively hydrolyzed (non-enzymatic and enzymatic transformation by esterases and butylrylcholineesterases) to its pharmacologically inactive metabolites with only a minor role for CYP metabolism.

Coadministration has not been studied. Activated charcoal absorbs substances in the stomach and intestines and may decrease absorption of orally administered medicines. If coadministration is required, administration of activated charcoal and atazanavir should be separated by 4 hours. [Note: this interaction is not specific for atazanavir, but for any oral medication taken with activated charcoal.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Adalimumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as adefovir is eliminated renally via glomerular filtration and active renal secretion by OAT1. Atazanavir is unlikely to inhibit OATs at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Adrenaline is rapidly inactivated, mostly in the liver by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO).

Coadministration has not been studied. Afatinib is mainly eliminated unchanged in the faeces and is a substrate of P-glycoprotein and BCRP. Administration of ritonavir (200 mg twice daily for 3 days) 1 hour before afatinib (20 mg single dose) increased afatinib AUC and Cmax by 48% and 39%. However, coadministration of ritonavir simultaneously or 6 hours after afatinib (40 mg) resulted in minimal increase in afatinib AUC and Cmax (19% and 4% for simultaneous administration; 11% and 5% for the staggered administration). The European product label for afatinib recommends to administer strong P-gp inhibitors (such as atazanavir) 6 hours apart from afatinib. The US product label includes a recommendation to decrease afatinib daily dose by 10 mg if not tolerated for patients who require a therapy with a P-gp inhibitor.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. African potato was shown to inhibit CYP3A4 and P-gp in vitro and to activate PXR suggesting that inhibition may occur initially followed by induction of CYP3A4 and P-gp when used for extended periods. Coadministration of African potato with lopinavir/ritonavir in healthy volunteers did not result in significant pharmacokinetic changes suggesting that boosting by ritonavir could offset the inducing effect of African potato. Consider administrating atazanavir with ritonavir or cobicistat.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely as agomelatine is metabolised predominantly via CYP1A2. Atazanavir does not inhibit or induce CYP1A2 at clinically relevant concentrations.

Coadministration has not been studied. In vitro studies have shown that CYP3A4 and the flavine-containing monooxygenase system are involved in the formation of the active metabolite albendazole sulfoxide. Short term (2 doses) coadministration with ritonavir (200 mg) did not impact albendazole pharmacokinetics whereas long-term coadministration (8 days) decreased albendazole exposure likely due to ritonavir inducing effect. Atazanavir has no inducing effect and therefore atazanavir alone is not expected to significantly impact albendazole when administered long-term.

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 has not been studied. Alcohol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase. The chronic use of alcohol may induce CYP2E1 and to a lesser extent CYP3A4. No a priori clinically relevant drug-drug interaction is anticipated.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alcuronium is predominantly eliminated unchanged via the kidneys. Atazanavir is unlikely to inhibit OAT and OCT renal transporters at clinically relevant concentrations.

Coadministration has not been studied. Alectinib is metabolised by CYP3A4 to an active metabolite (M4), which is also metabolised by CYP3A4. Alectinib does not inhibit CYP3A4 to a clinically relevant extent. Concentrations of alectinib and M4 may increase due to inhibition of CYP3A4 by atazanavir, although to a modest extent. Posaconazole (a strong CYP3A inhibitor) had only a minor effect on the combined exposure of alectinib and M4 (7% decrease in Cmax; 36% increase in AUC). Monitoring for alectinib toxicity should be considered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alemtuzumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Atazanavir is metabolized by CYP3A4. CYP-mediated drug interactions are not expected with alemtuzumab. Note, use of alemtuzumab (marketed as Lemtrada) for the treatment of relapsing remitting multiple sclerosis is contraindicated in patients with HIV infection as it causes prolonged reductions of CD4+ lymphocyte counts.

If taken at the same time, it is likely that food and beverages (including mineral water), calcium supplements, antacids, and some oral medicinal products will interfere with absorption of alendronate. Therefore, patients must wait at least 30 minutes after taking alendronate before taking any other oral medicinal product.

Coadministration has not been studied. Alfentanil undergoes extensive CYP3A4 metabolism. Atazanavir could potentially increase alfentanil exposure. Administer with caution due to the risk of prolonged or delayed respiratory depression. Adjust dose of alfentanil if needed.

Coadministration is contraindicated as alfuzosin concentrations may increase (due to inhibition of CYP3A4) which can result in hypotension. Furthermore, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; afluzosin has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

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.

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.

Coadministration has not been studied. Almotriptan is partly eliminated unchanged in the urine and partly metabolized mainly via monoamine oxidase-A and to a lesser extent by CYP450 (CYP3A4, CYP2D6) and flavin monooxygenase. Coadministration may increase almotriptan concentrations through inhibition of CYP3A4 however no dosage adjustment is required.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Aloe vera is only a weak inhibitor of CYPs in vitro and therefore is unlikely to cause clinically significant interactions. It does not inhibit P-gp and there is no evidence to suggest it impacts UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alogliptin is primarily excreted unchanged in the urine and undergoes negligible CYP-mediated metabolism. Alogliptin was shown to have no inhibitory or inducing effect on CYPs at concentrations achieved with the recommended dose of 25 mg alogliptin.

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. In vitro data indicate that alosetron is metabolized by CYP2C9 (30%), 3A4 (18%) and 1A2 (10%). However, in vivo data suggest that CYP1A2 plays a more prominent role. Atazanavir does not inhibit or induce CYP1A2 in the range of clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alpelisib is primarily metabolized by enzymatic hydrolysis to an inactive metabolite, with a minor contribution from CYP3A4. Atazanavir is a strong inhibitor of CYP3A4 and may increase alpelisib concentrations. However, no clinically significant effect is expected as CYP3A4 represents a minor pathway in alpelisib metabolism. A PBPK model predicted coadministration of ritonavir (100 mg twice daily) to increase alpelisib AUC by 1.16-fold. No dose adjustment of alpelisib is necessary and standard dosing can be continued.

Coadministration has not been studied. Alprazolam is mainly metabolized by CYP3A4. Coadministration of atazanavir may increase alprazolam concentrations and may result in enhanced sedation. A decrease in alprazolam dose may be needed.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following administration, ~80% of circulating alprostadil is rapidly metabolised in the lungs primarily by beta- and omega- oxidation and the resulting metabolites are mainly excreted in urine. Atazanavir is metabolized by CYP3A4. Alprostadil is unlikely to affect CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amantadine is mainly eliminated in the kidney by glomerular filtration and active secretion. A bicarbonate dependent organic cation transporter has been identified as amantadine major uptake transporter in the renal proximal tubule.

Coadministration has not been studied. Ambrisentan is mainly glucuronidated by UGT1A9, UGT2B7, UGT1A3 and is metabolized to a lesser extent by CYP3A4. Ambrisentan is also a substrate of P-gp and OATP1B1. Ambrisentan concentrations may increase due to inhibition of OATP1B1 by atazanavir. Start ambrisentan at 5 mg and closely monitor the patient for tolerability.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as amikacin is eliminated renally by glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amiloride is eliminated unchanged in the kidney. In vitro data indicate that amiloride is a substrate of OCT2. Atazanavir is unlikely to inhibit OCTs at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aminophylline is a complex of theophylline and ethylenediamine and is given for its theophylline activity. Theophylline is mainly metabolized by CYP1A2 and in vitro data indicate that atazanavir does not inhibit CYP1A2 at physiological concentrations.

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 clinically significant 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.

Coadministration has not been studied. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19. Atazanavir has no inhibitory effects on CYP2D6 and CYP2C19 and therefore no pharmacokinetic interaction is expected. 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. Amivantamab is a monoclonal IgG1 and is eliminated primarily via intracellular catabolism similarly to endogenous IgG. Atazanavir is metabolized by CYP3A4.

Coadministration has not been studied. Amlodipine is metabolized by CYP3A4. Caution is warranted as atazanavir could increase concentrations of the amlodipine. Use with caution as 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. Amodiaquine is metabolized mainly by CYP2C8 to N-desethylamodiaquine, an active metabolite but less potent than the parent compound. Atazanavir is a weak inhibitor of CYP2C8. Atazanavir could potentially increase amodiaquine exposure, although to a limited extent. No a priori dosage adjustment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amoxapine is mainly metabolised by CYP2D6. Atazanavir is metabolized by CYP3A4. Atazanavir does not inhibit or induce CYP2D6. Amoxapine is unlikely to affect CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as amoxicillin is mainly excreted in the urine by glomerular filtration and tubular secretion. In vitro data indicate that amoxicillin is a substrate of OAT3. Atazanavir is unlikely to inhibit OATs at clinically relevant concentrations.

Coadministration has not been studied. Amphetamine is metabolized by CYP2D6 and coadministration with atazanavir could potentially increase amphetamine exposure although to a moderate extent. However, as dosing of recreational drugs can be variable, caution is advised.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as amphotericin is not appreciably metabolized and is eliminated to a large extent in the bile.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ampicillin is mainly excreted in the urine by glomerular filtration and tubular secretion. Atazanavir is unlikely to inhibit OAT and OCT renal transporters at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anakinra is an IL-1 receptor antagonist which is predominantly cleared renally by glomerular filtration and subsequent tubular metabolism. Atazanavir is metabolized by CYP3A4. Patients requiring treatment with anakinra may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Anakinra, per se, has no inhibitory or inducing effects on cytochromes. 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.

Coadministration has not been studied. Anastrozole is mainly oxidized to hydroxyanastrozole by CYP3A4 (major) and glucuronidated via UGT1A4. Atazanavir could potentially increase anastrozole concentrations (via inhibition of CYP3A4). Monitor anastrozole related side effects.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as anidulafungin is not metabolised hepatically but undergoes chemical degradation at physiological temperature.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Thymoglobulins are cleared by the reticuloendothelial system.

Coadministration has not been studied but should be avoided. Apalutamide is primarily metabolized by CYP2C8 and CYP3A4. Apalutamide concentrations may increase as atazanavir is a weak inhibitor of CYP2C8 and inhibits CYP3A4. In addition, atazanavir is metabolized by CYP3A4 and apalutamide is a strong inducer of CYP3A4. Coadministration of apalutamide with midazolam (a CYP3A4 substrate) decreased midazolam AUC by 92%. A comparable decrease is expected in atazanavir exposure after coadministration with apalutamide, leading to loss of therapeutic effect and possible development of resistance. Furthermore, atazanavir has a conditional QT risk and androgen deprivation therapy may prolong the QT interval.

Coadministration has not been studied. Concentrations of apixaban are expected to increase due to potent CYP3A4 and P-gp inhibition by atazanavir, thereby increasing the bleeding risk. The product labels for apixaban do not recommend the concomitant use with strong dual CYP3A4 and P-gp inhibitors, although the US label gives the option to use apixaban at a reduced dose if needed. Note, patients already receiving apixaban at a dose of 2.5 mg twice daily should avoid coadministration with strong dual CYP3A4 and P-gp inhibitors. Of interest, there are case reports of no adverse outcomes in HIV infected patients treated with a reduced dose of apixaban (2.5 mg twice daily) while on ritonavir or cobicistat boosted regimens which supports the option of dose reduction given in the US label.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as apomorphine is metabolized by several pathways including glucuronidation, sulfation and to a lesser extent N-demethylation. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; apomorphine 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. Apremilast is metabolized by multiple pathways involving hydrolysis, glucuronidation and oxidation by CYP3A4. Coadministration of apremilast with ketoconazole (a strong CYP3A4 inhibitor) increased apremilast AUC by 36%. This effect is not considered to be clinically significant and does not warrant a dosage adjustment of apremilast. Similarly, atazanavir is unlikely to significantly alter apremilast exposure. Furthermore, apremilast has no inhibitory or inducing effects on CYPs or drug transporters. Note: severe diarrhoea, nausea and vomiting can occur within the first few weeks after initiating apremilast treatment. Patients should be instructed to contact their healthcare provider if they experience severe diarrhoea, nausea or vomiting as this could potentially alter the absorption of orally administered antiretroviral drugs.

Coadministration has not been studied. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYPs 1A2 and 2C19. Atazanavir is a strong inhibitor of CYP3A4 and could potentially increase aprepitant concentrations. The European product label for aprepitant advises caution with CYP3A4 inhibitors, whereas the American product label advises to avoid concomitant use of aprepitant and moderate to strong CYP3A4 inhibitors. If coadministration is necessary, reduced doses of aprepitant may be required to minimize side effects. Aprepitant shows an initial inhibitory effect on CYP3A4 followed by a weak inducing effect from day 8 which is clinically insignificant by two weeks. Any transient change in atazanavir exposure is unlikely to be clinically significant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Argatroban undergoes metabolism in the liver via hydroxylation and aromatization. In vitro studies indicate that CYP3A4 plays a role in argatroban metabolism, however, human drug-drug interactions studies suggest that metabolism via CYP3A4 is not a major elimination pathway in vivo. Erythromycin (a strong CYP3A4 inhibitor) had no effect on argatroban pharmacokinetics and pharmacodynamics and an interaction with atazanavir is unlikely.

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 SmPC 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. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Arsenic trioxide is hydrolysed to arsenious acid (the pharmacologically active metabolite) which is then methylated to less cytotoxic metabolites primarily in the liver (non-CYP mediated). Arsenious acid is also oxidated to arsenic acid, which may occur in numerous tissues via enzymatic or nonenzymatic processes. Atazanavir is metabolized by CYP3A4 and is unlikely to affect arsenic trioxide metabolism. Arsenic trioxide does not inhibit or induce CYP3A4. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval such as arsenic trioxide. Arsenic trioxide has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. If coadministration is necessary, assess the patient QTc interval before starting arsenic trioxide and continue QTc interval monitoring during use, particularly in at risk patients.

Coadministration has not been studied. Artemisinins undergo rapid metabolism via several CYP450 (CYPs 3A4, 2A6, 2B6) and the active metabolite (dihydroartemisinin, which has greater potency than the parent drug) is further metabolism via UGTs 1A9 and 2B7. Atazanavir could potentially increase plasma levels of artemisinins. Close monitoring for artemisinin toxicity required.

Coadministration has not been studied. Asciminib is metabolised by several pathways, including CYP3A4, UGT2B7 and UGT2B17. Atazanavir is metabolized by CYP3A and is a strong inhibitor of CYP3A4. Coadministration of asciminib (40 mg single dose) with clarithromycin (a strong CYP3A4 inhibitor) increased asciminib AUC and Cmax by 36% and 19%, although no clinically significant effect on asciminib concentrations was observed when coadministered with itraconazole, which is also a strong CYP3A4 inhibitor. Increased asciminib exposure is unlikely to be significant for patients on asciminib doses of 40-80 mg daily. However, for patients on the higher dose of 200 mg twice daily, closely monitor for adverse reactions if coadministered with atazanavir. In addition, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; QT prolongation has been reported in patients receiving asciminib.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ascorbic acid is oxidised to dehydroascorbic acid where some is metabolised to oxalic acid and the inactive ascorbate-2-sulphate. Large doses are rapidly excreted in the urine when in excess of the requirements of the body. Atazanavir does not interfere with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with vitamin C when given alone or in multivitamins. Ascorbic acid is oxidised to dehydroascorbic acid where some is metabolised to oxalic acid and the inactive ascorbate-2-sulphate. Large doses are rapidly excreted in the urine when in excess of the requirements of the body. Atazanavir does not interfere with this metabolic pathway.

Coadministration has not been studied. Asenapine is metabolized by glucuronidation (UGT1A4) and oxidative metabolism (mainly CYP1A2, with minor contributions from CYP3A4 and CYP2D6). Atazanavir could potentially increase asenapine exposure by inhibition of CYP3A4, although to a moderate extent as CYP3A4 does not play a major role in asenapine metabolism. 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; asenapine 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. Ashwagandha extracts had no effect on CYP enzymes in vitro.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Limited data suggest that asparaginase is likely to be eliminated by the reticulo-endothelial system.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to salicylic acid and then further metabolized mainly by glucuronidation (by several UGTs, major UGT1A6).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to salicylic acid and then further metabolized mainly by glucuronidation (by several UGT, major UGT1A6).

Coadministration is contraindicated as it may increase astemizole 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; astemizole has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website.

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. Note, PR interval monitoring may be warranted in patients with underlying block or those receiving known atrioventricular nodal blocking agents.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atezolizumab is eliminated through catabolism. Atazanavir is metabolized by CYP3A4.

Coadministration has not been studied. Atogepant is metabolized primarily by CYP3A4 and is a substrate of OATP. Concentrations of atogepant are expected to increase significantly due to strong inhibition of CYP3A4 and OATP by atazanavir. Atogepant AUC increased by 5.5-fold with itraconazole (a strong CYP3A4 inhibitor) and by 2.85-fold with single dose rifampicin (a strong OATP inhibitor). The European product label for atogepant recommends a dose reduction to 10 mg once daily with strong CYP3A4 and OATP inhibitors. For the treatment of episodic migraine, the American product label for atogepant recommends a dose reduction to 10 mg once daily with strong CYP3A4 inhibitors and recommends to avoid use with strong CYP3A4 inhibitors if treatment is for chronic migraine.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Atomoxetine is metabolized by CYP2D6 and atazanavir alone has no inhibitory effects on CYP2D6. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; atomoxetine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

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. Atovaquone is mainly eliminated unchanged in the faeces. Administration of a single dose of atovaquone/proguanil with lopinavir/ritonavir or atazanavir/ritonavir decreased atovaquone AUC by 70% or 40-50%, respectively. A possible mechanism was suggested to be induction of glucuronidation by ritonavir. Atazanavir has no inducing effect on UGTs and therefore is not expected to decrease atovaquone exposure.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although metabolism of atropine is not fully elucidated, up to 50% is excreted unchanged via the kidneys.

Coadministration has not been studied. Avanafil is primarily metabolized by CYP3A4 and coadministration with strong CYP3A4 inhibitors is contraindicated in the product labels for avanafil. Coadministration with ritonavir (600 mg twice daily) increased avanafil AUC by 13-fold. Similarly, a large increase in avanafil exposure is predicted in the presence of atazanavir.

Coadministration has not been studied and should be avoided. Avapritinib is predominantly mediated by CYP3A4 and to a minor extent by CYP2C9. Atazanavir is a strong inhibitor of CYP3A4 and could significantly increase avapritinib exposure. Based on drug interaction studies with other strong CYP3A4 inhibitors, avapritinib exposure is expected to increase by 600% after multiple doses.

Coadministration has not been studied. Avatrombopag is mainly metabolized by CYP2C9 and CYP3A4. Atazanavir is a strong inhibitor of CYP3A4 and is expected to increase concentrations of avatrombopag. Coadministration of avatrombopag and itraconazole (a strong CYP3A4 inhibitor) increased avatrombopag exposure by 37%. A similar effect may occur with atazanavir. No a priori dose adjustment is needed for avatrombopag but monitor platelet counts and adjust the avatrombopag dose as necessary as indicated in the avatrombopag product label.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avelumab is primarily metabolized through catabolic pathways and drug-drug interactions are not expected.

Coadministration has not been studied. Axitinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2, CYP2C19 and UGT1A1. Atazanavir is a strong inhibitor of CYP3A4 and is expected to increase concentrations of axitinib. Increased axitinib exposure may increase the risk of exposure-related toxicity. Coadministration of ketoconazole (a strong CYP3A4 inhibitor) with axitinib increased axitinib AUC by 2-fold. A similar effect is expected with atazanavir. Use with caution. If coadministration is unavoidable, a 50% dose reduction of axitinib is recommended and monitor for toxicity.

Coadministration has not been studied. Ayahuasca preparations contain N,N-dimethyltryptamine (DMT, a psychedelic substance along with monoamine oxidase inhibitors (MAOI) which attenuates the breakdown of DMT. MAOI are substrate of MRP2 which is inhibited by atazanavir thereby potentially increasing DMT toxicity by slowing its breakdown. Given the narrow therapeutic index of DMT, caution is advised. Harma alkaloids found in ayahuasca preparations may cause weak/moderate inhibition of CYP3A4 which is unlikely to alter exposure of atazanavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azacitidine undergoes spontaneous hydrolysis and deamination mediated by cytidine deaminase. Urinary excretion is the primary route of elimination of azacitidine and/or its metabolites. Following cellular uptake, azacitidine is sequentially phosphorylated via phosphokinases activities to azacitidine triphosphate which is able to incorporate into DNA and RNA. Atazanavir is metabolised by CYP3A4. Azacitidine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azathioprine is metabolized to 6-mercaptopurine which is further inactivated by xanthine oxidase and thiopurine methyltransferase.

Coadministration has not been studied. Azithromycin is mainly eliminated via biliary excretion and animal data suggest this may occur via P-glycoprotein and MRP2. Atazanavir could potentially increase azithromycin exposure (inhibition of P-gp and MRP2), but no a priori dosage adjustment is recommended for azithromycin. Azithromycin is not expected to have a clinically relevant effect on drugs metabolised by CYP enzymes. However, both azithromycin and atazanavir have risks of QT prolongation and/or TdP on the CredibleMeds.org website (known risk for azithromycin; conditional risk for atazanavir). Caution is advised. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Baclofen is primarily eliminated by glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Baricitinib is mainly eliminated renally through glomerular filtration and active secretion via OAT3, P-gp, BCRP and MATE2-K, with CYP3A4 metabolism representing less than 10% of its overall metabolism. Atazanavir is metabolized by CYP3A4 and is a strong inhibitor of CYP3A4. 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 has not been studied and is contraindicated. Barnidipine is metabolised by CYP3A4. Atazanavir is metabolized by CYP3A4. Barnidipine is unlikely to affect CYP3A4. However, atazanavir is a strong CYP3A4 inhibitor and is expected to increase barnidipine concentrations. Coadministration with strong CYP3A4 inhibitors is contraindicated in the European product label for barnidipine. In addition, both drugs can prolong the PR interval.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Basiliximab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body.

Coadministration with bazedoxifene alone or coformulated with conjugated estrogens as hormone replacement therapy (HRT) has not been studied. Bazedoxifene is glucuronidated by UGT1A1/8/10 and conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Coadministration is predicted to increase exposure of bazedoxifene and conjugated estrogens. The clinical significance of this increase in terms of overall risk of deep vein thrombosis, pulmonary embolism, stroke and myocardial infarction in postmenopausal women receiving substitution hormones in unknown. Bazedoxifene alone or with conjugated estrogens should be used at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for individual women. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary.

Coadministration 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 clinically significant interaction is unlikely. Belatacept is a protein that undergoes non-CYP mediated metabolism in the liver.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Belimumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Atazanavir is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bempedoic acid is glucuronidated by UGT2B7 and also converted to an active metabolite by aldo-keto reductase. No significant interaction is expected as atazanavir is an inhibitor of UGT1A1. Bempedoic acid does not inhibit or induce CYP3A4.

Coadministration has not been studied. Benazepril is rapidly hydrolyzed to its active metabolite benazeprilat. Benazeprilat is a substrate of UGTs (the specific UGTs have not been well described) and concentrations may increase due to inhibition of UGTs by atazanavir. In the absence of further data, close monitoring of cardiac parameters and for increased side effects is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bendamustine is metabolised by multiple routes including hydrolysis (main), glutathione conjugation and hepatic metabolism via CYP1A2. Atazanavir is metabolized by CYP3A4 and is unlikely to inhibit or induce CYP1A2 at clinically relevant concentrations. Bendamustine does not inhibit or induce CYP enzymes. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; bendamustine 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. 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benserazide is hydrolysed to trihydroxybenzylhydrazine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Available information on the metabolism of benzatropine is limited but no clinically significant interactions are expected. Atazanavir is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benznidazole undergoes non-CYP mediated metabolism and partly CYP mediated metabolism. Renal elimination of unchanged benznidazole appears to be minimal and there is little potential for an interaction via competition for renal elimination pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benzonatate is metabolized by plasma butyrylcholinesterase. Atazanavir is metabolized by CYP3A4 and is unlikely to affect benzonatate metabolism. Benzonatate is unlikely to inhibit or induce CYP3A4.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Beta-alanine is a non-essential amino acid and dietary supplements enter the same physiological processes as endogenous beta-alanine. Excess beta-alanine is excreted in the urine by the kidneys. Atazanavir is metabolized by CYP3A4. Beta-alanine is unlikely to affect CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betahistine is metabolized by monoamine oxidase. Betahistine does not induce or inhibit CYP450 enzymes.

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. Chronic or high doses of betamethasone may decrease atazanavir plasma concentrations due to CYP3A4 induction with the possible loss of therapeutic effect and development of resistance. However, this risk is expected to be lower when using lower doses of betamethasone. Furthermore, the risk of Cushing’s syndrome is less likely to occur when using betamethasone at a low dose or for a short treatment duration as compared to higher doses and long treatment duration.

Coadministration has not been studied but no clinically relevant drug interactions are expected with the topical use of betamethasone (for example, ointment, cream, lotion, emollient, foam).

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. 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. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; betrixaban has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. 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 has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bevacizumab is metabolized via proteolytic catabolism.

Coadministration has not been studied and should be avoided. Bexarotene is mainly metabolized by CYP3A4 and induces CYP3A4 (after repeated administration and especially at doses greater than 300 mg/m2/day). Coadministration could potentially increase bexarotene concentrations and thus increase the risk of side effects. Bexarotene could also potentially decrease atazanavir exposure and therefore coadministration should be avoided.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Half of a bezafibrate dose is eliminated unchanged in the urine.

Coadministration has not been studied. Bicalutamide is metabolized by CYP3A4 and UGT1A9. Atazanavir is metabolized by CYP3A4. Bicalutamide is a weak inhibitor of CYP3A4 but is unlikely to have a clinically significant effect on atazanavir. Inhibition of CYP3A4 by atazanavir may increase bicalutamide concentrations. No a priori dose reduction is required but use with caution and monitoring of side effects is recommended. Note, androgen deprivation treatment may prolong the QT interval. Caution should be taken when using with antiretroviral drugs that can potentially prolong the QT interval such as atazanavir.

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and should not be administered with other antiretroviral products. Furthermore, 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. Bilastine is mainly excreted unchanged and is a substrate of P-gp and OATP1A2. Atazanavir is metabolized by CYP3A4. Bilastine is unlikely to affect CYP3A4. However, atazanavir is a P-gp inhibitor and is expected to increase bilastine concentrations. No a priori dose modification is recommended but close monitoring for signs and symptoms of increased bilastine exposure is recommended. Coadministration of bilastine and P-gp inhibitors should be avoided in subjects with moderate or severe renal impairment. In addition, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; bilastine 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. Bimekizumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Atazanavir is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Binimetinib is primarily metabolised by UGT1A1 and the active metabolite M3 is metabolised by CYP1A2 and CYP2C19. Atazanavir is metabolized by CYP3A and inhibits UGT1A1. Binimetinib is unlikely to affect CYP3A4. Simulations to investigate the effect of atazanavir (400 mg) on the exposure of binimetinib (45 mg) predicted similar values for binimetinib Cmax in the presence or absence of atazanavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following absorption, vitamin B7 is stored in the liver, kidney and pancreas.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following absorption, vitamin B7 is stored in the liver, kidney and pancreas.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although limited human data suggest biperiden undergoes hydroxylation in the liver, there are no known or documented interactions with other drugs that have an effect on metabolism or transport.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following sublingual administration, birch tree pollen allergen is actively taken up through the oral mucosa by dendritic cells, in particular Langerhans cells. Allergen which is not absorbed is expected to be hydrolysed to amino acids and small polypeptides in the gastrointestinal tract and there is no evidence to suggest absorption into the vascular system to any significant extent. No interaction trials have been conducted in humans and no potential drug interactions have been identified from any source.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisacodyl is converted to an active metabolite by intestinal and bacterial enzymes. Absorption from the gastrointestinal tract is minimal and the small amount absorbed is excreted in the urine as the glucuronide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bismuth subsalicylate is largely hydrolysed in the stomach to form salicylic acid, which is rapidly absorbed, and insoluble bismuth salts, which are excreted unchanged in faeces. Atazanavir is metabolized by CYP3A4. Bismuth subsalicylate is unlikely to affect CYP3A4.

Coadministration has not been studied. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Coadministration with atazanavir could potentially increase bisoprolol concentrations, although to a moderate extent. Pharmacokinetic studies between atazanavir and drugs that prolong the PR interval including beta blockers (other than atenolol) have not been performed. An additive effect of atazanavir and these drugs cannot be excluded. Note, PR interval monitoring may be warranted in patients with underlying block or those with atrioventricular nodal blocking agents.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. No effect on atazanavir is expected as black cohosh had no significant effect on the pharmacokinetics of midazolam (a CYP3A4 substrate) or digoxin (a P-gp substrate).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bleomycin is inactivated by a cytosolic enzyme, bleomycin hydrolase. Furthermore, two third of the administered drug is excreted unchanged in urine probably by glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. An indirect effect of blinatumomab on CYPs may occur due to transient release of cytokines during the first days of therapy which can inhibit CYP450 metabolism, however, this is unlikely to be clinically relevant. The metabolic pathway of blinatumomab has not been characterised. Like other protein therapeutics, blinatumomab is expected to be degraded into small peptides and amino acids via catabolic pathways.

Coadministration has not been studied. Bortezomib is mainly metabolized by CYPs 3A4 and 2C19 and to a lesser extent CYPs 1A2, 2D6 and 2C9. Atazanavir could potentially increase bortezomib concentrations. Monitor for bortezomib related side effects. The US Prescribing Information suggests considering a dose reduction of bortezomib when given with strong CYP3A4 inhibitors, such as atazanavir. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; bortezomib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

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 but should be avoided. Bosutinib is metabolized by CYP3A4. Ketoconazole (a strong CYP3A4 inhibitor) increased bosutinib AUC by 8.6-fold. A similar effect may occur with atazanavir. Use an alternative antiretroviral drug with no inhibitory or inducing effects.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Branched chain amino acids (BCAAs) mainly undergo intracellular catabolism in skeletal muscle. Excess BCAAs and BCAA-derived metabolic products are excreted in the urine by the kidneys. Atazanavir is metabolized by CYP3A4. BCAAs are unlikely to affect CYP3A4.

Coadministration has not been studied but should be used with caution. Brentuximab vedotin is an antibody-drug conjugate comprising a monoclonal antibody and monomethyl auristatin E (MMAE), a potent chemotherapeutic agent. The monoclonal antibody undergoes elimination via intracellular catabolism and does not interact with atazanavir. However, MMAE is a substrate of CYP3A4 and P-gp, therefore atazanavir may increase concentrations of MMAE and the incidence of neutropenia. Coadministration of brentuximab vedotin and ketoconazole (a strong inhibitor of CYP3A4 and P-gp) increased MMAE AUC by 34%. Patients receiving atazanavir concomitantly with brentuximab vedotin should be closely monitored for adverse reactions of brentuximab vedotin. If neutropenia develops, refer to the dosing recommendations for neutropenia in the product label for brentuximab vedotin.

Coadministration has not been studied. Brexpiprazole is predominantly metabolised by CYP3A4 and CYP2D6. Atazanavir is metabolized by CYP3A4 and is a strong inhibitor of CYP3A4. Ketoconazole (a strong CYP3A4 inhibitor) increase brexpiprazole AUC by 97% and similar effect may occur with atazanavir. Product labels for brexpiprazole advise a dose reduction of 50% with strong CYP3A4 inhibitors. A dosing modification to a quarter of the recommended dose is required for known CYP2D6 poor metabolisers while taking strong inhibitors. Monitor for toxicity, such as confusion, restlessness and sedation.

Coadministration has not been studied. Brigatinib is metabolised by CYP2C8 and CYP3A4. Atazanavir is a strong inhibitor of CYP3A4 and is expected to increase brigatinib concentrations. Coadministration of brigatinib (90 mg single dose) and itraconazole, a strong CYP3A4 inhibitor (200 mg twice daily) increased brigatinib exposure by 101%. A similar effect is expected with atazanavir and coadministration is not recommended. If coadministration is necessary, reduce the dose of brigatinib by 50% and monitor for toxicity.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brimonidine is metabolized mainly by aldehyde oxidase.

Coadministration has not been studied. Brincidofovir is a prodrug converted to cidofovir which is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3. Atazanavir does not interfere with this pathway. However, brincidofovir is a substrate of OATP1B1 and concentrations may increase due to strong inhibition of OATP1B1 by atazanavir. If concomitant use with brincidofovir is necessary, increase the monitoring for adverse reactions associated with brincidofovir (i.e. elevations in transaminases and bilirubin, diarrhoea, or other gastro-intestinal adverse events) and postpone the dosing of atazanavir for at least 3 hours after brincidofovir administration.

Coadministration has not been studied. Brinzolamide is mainly metabolised by CYP3A4, and to a lesser extent by CYPs 2A6, 2C8 and 2C9. Atazanavir is metabolized by CYP3A4. Brinzolamide does not inhibit or induce CYP3A4. However, atazanavir is a strong CYP3A4 inhibitor and may increase brinzolamide concentrations. Caution is advised, and a dose reduction could be considered at higher doses. Monitor for increased side effects such as blurred vision or eye irritation and consider intraocular pressure checks during the first week of coadministration.

Coadministration has not been studied. Bromazepam undergoes oxidative biotransformation. Drug-drug interaction studies indicate that CYP3A4 plays a minor role in bromazepam metabolism, but other cytochromes such as CYP2D6 or CYP1A2 may play a role. Atazanavir could potentially increase bromazepam concentrations although to a moderate extent. Coadministration with itraconazole (a strong CYP3A4 inhibitor) increased bromazepam AUC by ~9%. A similar effect may occur with atazanavir. No a priori dosage adjustment is required.

Coadministration has not been studied. Bromocriptine is metabolised by CYP3A4. Atazanavir is metabolized by CYP3A4. Bromocriptine is unlikely to affect CYP3A4 at clinically relevant concentrations. However, atazanavir is a strong inhibitor of CYP3A4 and may increase bromocriptine concentrations. Erythromycin (a strong CYP3A4 inhibitor) increased bromocriptine AUC by 3.7-fold and a similar effect may occur with atazanavir. Use with caution. A decrease in bromocriptine dose may be needed.

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 dose reduction of the glucocorticoid should be considered with close monitoring of local and systemic effects or a switch to a glucocorticoid, which is not a substrate for CYP3A4 (e.g. beclometasone). 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 based on metabolism and clearance a clinically significant interaction is unlikely. Bumetanide is hepatically metabolized and approximately 50-80% of bumetanide is excreted in the urine by OAT1 and OAT3, mainly as unchanged drug (~50%). Atazanavir is metabolized by CYP3A4 and is unlikely to inhibit OATs at clinically relevant concentrations.

Coadministration has not been studied. Bupivacaine is predominantly metabolized by CYP3A4. CYP3A4 inhibitors such as atazanavir may increase levels of bupivacaine. A clinical study with bupivacaine and itraconazole, a CYP3A4 inhibitor, reported a 20-25% increase in steady state concentration of bupivacaine when administered with itraconazole, compared to placebo.

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupropion is primarily metabolized by CYP2B6. Atazanavir does not interact with this metabolic pathway.

Coadministration has not been studied. Buspirone is metabolized by CYP3A4 but does not inhibit CYP3A4. Atazanavir could potentially increase buspirone concentrations. A low dose of buspirone used cautiously is recommended and adjust dosage based on the clinical response.

Coadministration has not been studied. Busulfan is metabolised through conjugation with glutathione (spontaneous and GST-mediated) and then by hepatic oxidation (likely CYP3A4-mediated). Atazanavir is metabolized by CYP3A4. Busulfan is unlikely to affect CYP3A4. However, atazanavir is a strong inhibitor of CYP3A4 and may increase busulfan concentrations. Itraconazole (a strong CYP3A4 inhibitor) decreased busulfan clearance by approximately 20%. A similar effect may occur with atazanavir which may increase the risk and severity of myelosuppression. Patients should be monitored for signs of toxicity.

Coadministration has not been studied and should be used with caution. Cabazitaxel is metabolized by CYP3A4. Coadministration with ketoconazole (a strong CYP3A4 inhibitor) increased cabazitaxel exposure by 25% and a similar effect is expected with atazanavir. Thus, coadministration should be avoided but if coadministration is required, consider a dose reduction of cabazitaxel of up to 25% and monitor for cabazitaxel toxicity.

Coadministration has not been studied. Cabergoline is extensively metabolized by the liver, predominantly via hydrolysis (non-CYP mediated metabolism), and is a substrate of P-gp. Cabergoline exposure increased by 2.6- to 4-fold in the presence of the strong P-gp inhibitors itraconazole or clarithromycin. Similarly, coadministration with atazanavir is expected to increase cabergoline exposure. Consider a reduction in cabergoline dose if the patient presents with adverse drug effects. No effect on atazanavir is expected as cabergoline does not inhibit or induce drug metabolizing enzymes. 

Coadministration has not been studied but a clinically significant interaction is unlikely when cabergoline is administered as a single dose to suppress lactation. Cabergoline is extensively metabolized by the liver, predominantly via hydrolysis (non-CYP mediated metabolism), and is a substrate of P-gp. Cabergoline exposure was shown to increased 2.6- to 4-fold in the presence of the strong P-gp inhibitors itraconazole or clarithromycin. Although atazanavir inhibits P-gp, no dose adjustment of cabergoline is required when cabergoline is administered as a single dose to suppress lactation. No effect on ataznavir is expected as cabergoline does not inhibit or induce drug metabolizing enzymes.

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 not to be clinically relevant. Note, cabotegravir used as PrEP is not expected to be coadministered with antiretrovirals except in the case of breakthrough infection when an antiretroviral treatment should be initiated. Residual concentrations of cabotegravir may remain in the systemic circulation for prolonged periods (up to 12 months or longer) but are not expected to affect the exposure of antiretroviral drugs initiated after discontinuation of Apretude.

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.

Cabenuva (cabotegravir LA, rilpivirine LA) is indicated for use as a complete regimen for the treatment of HIV-1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with atazanavir would be possible from a pharmacokinetic standpoint. 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. Atazanavir may increase rilpivirine concentrations. However, no dose adjustment of rilpivirine is required. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with atazanavir. However, the product label for Cabenuva indicates that rilpivirine should be used with caution in combination with drugs with a risk of QT interval prolongation. Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for a prolonged period after discontinuation of intramuscular cabotegravir/rilpivirine but are not expected to affect exposure of antiretroviral drugs.

Coadministration has not been studied but should be used with caution. Cabozantinib is metabolized by CYP3A4. Ketoconazole (a strong CYP3A4 inhibitor) increased cabozantinib AUC by 38%. A similar effect may occur with atazanavir. Avoid concomitant use with strong inhibitors if possible. If a strong CYP3A4 inhibitor must be used, reduce the cabozantinib daily dose by 20 mg. Resume the dose that was used prior to initiating the CYP3A4 inhibitor 2-3 days after discontinuation of the strong inhibitor. Furthermore, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; cabozantinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caffeine is mainly metabolised by CYP1A2. Atazanavir is metabolized by CYP3A4 and does not affect CYP1A2. Caffeine is unlikely to affect CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caffeine is mainly metabolized by CYP1A2. In vitro data indicate that atazanavir does not inhibit CYP1A2 in the range of clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Calcitonin is primarily metabolized via proteolysis in the kidney. Atazanavir does not interfere with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Coadministration has not been studied. Calcium is eliminated through faeces, urine and sweat. Coadministration with calcium supplements containing calcium carbonate may decrease atazanavir concentrations as atazanavir solubility decreases as pH increases. Atazanavir should be administered 2 hours before or 1 hour after calcium supplements containing calcium carbonate.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Canagliflozin is primarily metabolised by UGT1A9 and UGT2B4. Atazanavir inhibits primarily UGT1A1 and atazanavir alone is unlikely to alter canagliflozin exposure. No dose adjustment is recommended

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Canakinumab is an IL-1 beta monoclonal antibody and is eliminated via intracellular catabolism. Atazanavir is metabolized by CYP3A4. Patients requiring treatment with anakinra may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Canakinumab, per se, has no inhibitory or inducing effects on cytochromes. 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Candesartan is mainly eliminated unchanged via urine and bile.

Coadministration has not been studied. Cannabidiol is mainly metabolized by CYP3A4 and CYP2C19. Coadministration is expected to significantly increase cannabidiol exposure (inhibition of CYP3A4 by atazanavir) which may result in a greater risk of adverse reactions. Consider a dose reduction of cannabidiol. Advise patients to be aware of adverse reactions to cannabidiol.

Coadministration has not been studied. Cannabis use appears to decrease atazanavir trough concentrations, with 50% of users in one study having trough concentrations below the therapeutic range. Tetrahydrocannabinol (THC, the psychoactive component of cannabis) is metabolized mainly by CYP2C9 and to a lesser extent by CYP3A4. Atazanavir could potentially modestly increase THC. Patients should be aware of the potential for increased side effects.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Atazanavir does not interfere with this metabolic pathway. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; capecitabine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Capmatinib is primarily metabolized by CYP3A4. Atazanavir is metabolized by CYP3A and is a strong inhibitor of CYP3A4. Coadministration of capmatinib (400 mg single dose) and itraconazole, a strong CYP3A4 inhibitor, (200 mg once daily), increased capmatinib exposure by 42% with no change in Cmax. A similar effect is expected with atazanavir. Given the modest increase in capmatinib exposure and its toxicity profile, no a priori dose adjustment of capmatinib is necessary, however, monitor as toxicity of capmatinib may be increased. If treatment-toxicities occur, a dose reduction should be considered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Capreomycin is predominantly excreted via the kidneys as unchanged drug. Atazanavir is unlikely to inhibit OAT and OCT renal transporters at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Captopril is largely excreted in the urine (40-50% as unchanged drug, the rest as disulfide and other metabolites).

Coadministration has not been assessed in pharmacokinetic studies 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. Limited data from a small number of patients showed TDM evaluations for carbamazepine and oxcarbazepine were within the therapeutic ranges but trough concentrations for atazanavir were ~65% lower when compared with HIV-infected patients not treated with antiepileptic drugs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carbidopa is partly metabolized and partly eliminated unchanged (30% of the total urinary excretion).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carbimazole is a pro-drug which undergoes rapid and virtually complete metabolism to the active metabolite, thiamazole (also known as methimazole). Despite this potential hepatic metabolism very few data exist on carbimazole drug interactions and a marked interaction is not expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carbocisteine is metabolized in the liver via acetylation, decarboxylation and sulfoxidation with up to 60% excreted unchanged in the urine. The likelihood of a clinically significant drug interaction is low and no studies have been performed. Atazanavir is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carboplatin is excreted primarily by renal glomerular filtration. In vitro studies have shown that carboplatin does not significantly inhibit cytochrome P450 metabolic enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carfilzomib is rapidly metabolized, mainly by peptidase cleavage and epoxide hydrolysis with CYP-mediated metabolism representing a minor pathway. Atazanavir is metabolized by CYP3A4 and is a strong inhibitor of CYP3A4. Carfilzomib is not expected to have a clinically relevant effect on drugs metabolised by CYPs and is unlikely to be affected by inhibitors and inducers of CYPs and P-gp.

Coadministration has not been studied and is not recommended. Metabolism of cariprazine and its major active metabolites is mediated mainly by CYP3A4 with a minor contribution from CYP2D6. Atazanavir is metabolized by CYP3A4. Cariprazine is unlikely to affect CYP3A4. However, atazanavir is a strong CYP3A4 inhibitor and is expected to increase cariprazine concentrations. Cariprazine and its metabolites have very long elimination half-lives and changes in dose may not be fully reflected in plasma for several weeks. The European product label for cariprazine contraindicates coadministration with strong CYP3A4 inhibitors, whereas the American product label advises dose modification if a strong CYP3A4 inhibitor is initiated while on a stable dose of cariprazine. Refer to the cariprazine product labels for more information.

Coadministration has not been studied. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. Atazanavir could potentially increase carvedilol although to a moderate extent. Pharmacokinetic studies between atazanavir and drugs that prolong the PR interval including beta blockers (other than atenolol) have not been performed. An additive effect of atazanavir and these drugs cannot be excluded. Note, PR interval monitoring may be warranted in patients with underlying block or those with atrioventricular nodal blocking agents.

Coadministration has not been studied. Caspofungin undergoes spontaneous chemical degradation and metabolism via a non CYP-mediated pathway. Caspofungin is a substrate of the hepatic transporter OATP1B1 and atazanavir is an inhibitor of OATP1B1. Coadministration with ciclosporin (OATP1B1 inhibitor) increased caspofungin exposure by 35% and resulted in a transient increase in liver ALT and AST of less than or equal to 3-fold the upper limit of normal. Similarly, atazanavir could potentially increase caspofungin exposure. No a priori dosage adjustment is recommended for caspofungin but monitoring of liver enzymes may be required as clinically indicated.

Cat’s claw is a strong inhibitor of CYP3A4 in vitro but has also been shown to induce CYP3A4 activity in vitro. Increased concentrations of atazanavir, saquinavir and ritonavir were reported in a patient receiving Cat’s claw. Coadministration should be avoided.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cedazuridine is eliminated renally and converted to its epimer (which is then renally excreted). Atazanavir is metabolised by CYP3A4. Cedazuridine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefalexin is predominantly eliminated unchanged renally (by glomerular filtration and tubular secretion via OAT1 and MATE1. Atazanavir is unlikely to inhibit OAT and OCT renal transporters at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefazolin is predominantly excreted unchanged in the urine, mainly by glomerular filtration with some renal tubular secretion. Atazanavir is unlikely to inhibit OAT and OCT renal transporters at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as cefixime is renally excreted predominantly by glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefotaxime is partially metabolized by non-specific esterases. Most of a dose of cefotaxime is excreted in the urine – about 60% as unchanged drug and a further 24% as desacetyl-cefotaxime, an active metabolite. In vitro studies indicate that OATs participate to the renal elimination of cefotaxime. Atazanavir is unlikely to inhibit OAT and OCT renal transporters at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as ceftazidime is excreted predominantly by renal glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceftriaxone is eliminated mainly as unchanged drug, approximately 60% of the dose being excreted in the urine predominantly by glomerular filtration and the remainder via the biliary and intestinal tracts.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefuroxime is not metabolised and is excreted predominantly by renal glomerular filtration, with no significant active renal tubular secretion. Atazanavir is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Celecoxib is primarily metabolized by CYP2C9 and in vitro data indicate that atazanavir is unlikely to induce or inhibit CYP2C9 in the range of clinical concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cemiplimab is primarily metabolised through catabolic pathways and drug-drug interactions are not expected. Atazanavir is metabolized by CYP3A4.

Coadministration has not been studied and is not recommended. Cenobamate is primarily glucuronidated by UGT2B7 and to a lesser extent by UGT2B4. CYP3A4 contributes to cenobamate metabolism but to a minor extent. Cenobamate is a dose-dependent inducer of CYP3A4 and was shown to reduce exposure of midazolam (a CYP3A4 substrate) by 72% at a dose of 200 mg daily and by 27% at a dose of 100 mg daily. Cenobamate is dose-titrated until the 200 mg maintenance dose is reached. Cenobamate at a daily dose of 200 mg or greater may significantly decrease atazanavir plasma concentrations due to CYP3A4 induction with the possible loss of therapeutic effect and development of resistance.

Coadministration has not been studied. Ceritinib is metabolized by CYP3A4. Atazanavir is a strong inhibitor of CYP3A4. Coadministration of ceritinib (450 mg single dose) with ketoconazole, a strong CYP3A/P-gp inhibitor (200 mg twice daily for 14 days) increased ceritinib AUC and Cmax by 2.9-fold and 1.2-fold. A similar effect is expected with atazanavir and therefore coadministration is not recommended. However, if coadministration is necessary, consider reducing ceritinib dose by 33% (dose rounded to the nearest multiple of the 150 mg dosage strength) and monitor 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; ceritinib 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. Certolizumab pegol is an antibody Fab’ fragment conjugated with polyethylene glycol (PEG). The Fab’ fragment is expected to be degraded to peptides and amino acids by proteolysis; the PEG moiety is mainly excreted in urine without further metabolism. Atazanavir is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cetirizine is only metabolised to a limited extent and is eliminated unchanged in the urine through both glomerular filtration and tubular secretion. Atazanavir is unlikely to inhibit OATs and OCTs at clinically relevant concentrations. The effect of cetirizine on ECG was studied in 10 HIV+ subjects receiving PIs (details not given) and no patient had significant ECG changes during cetirizine administration

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cetuximab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although little is known about chlorambucil metabolism in humans, in vitro studies have shown that chlorambucil does not inhibit cytochrome P450 metabolic enzymes.

Coadministration has not been studied. In vitro studies have shown that chloramphenicol can inhibit metabolism mediated by CYP3A4. Coadministration of chloramphenicol may potentially increase levels of atazanavir. The clinical significance of this interaction is unknown. Ocular use: Although chloramphenicol is systemically absorbed when used topically in the eye, the concentrations used are unlikely to cause a clinically significant interaction.

Coadministration has not been studied. Compounds that inhibit certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of benzodiazepines. When combined with atazanavir, the activity of chlordiazepoxide may be increased.

Coadministration with a chlormadinone-containing combined oral contraceptive (COC) has not been studied. Chlormadinone undergoes extensive hepatic metabolism by hydroxylation (likely CYP mediated). Coadministration is predicted to increase exposure of chlormadinone and ethinylestradiol. The US Prescribing information for atazanavir recommends that if atazanavir is administered without a pharmacoenhancer, the oral contraceptive should contain no more than 30 µg of ethinylestradiol.

Coadministration has not been studied. Atazanavir is metabolised by CYP3A4 and inhibits CYP3A4. Chloroquine undergoes CYP mediated metabolism by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney (50%). No effect on atazanavir is expected but chloroquine concentrations may increase due to inhibition of CYP3A4 (although to a moderate extent due to the multiple elimination pathways), thereby increasing the risk of QT prolongation as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (known risk for chloroquine; conditional risk for atazanavir). Due to the very long half-life, the risk of QT prolongation may persist even after discontinuation of chloroquine. ECG monitoring is advised. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolized in the liver via CYP2D6. Atazanavir alone does not inhibit CYP2D6.

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. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlortalidone is mainly excreted unchanged in the urine and faeces.

Coadministration has not been studied. Ciclesonide can be administered with atazanavir without dose adjustment, but with close monitoring. There is a risk of steroid side effects occurring, particularly if a high dose is used, or in case of prolonged administration, or if used with another medicine containing corticosteroids. These side effects are also more likely during periods of physiological stress. Ciclesonide is a pro-drug activated by esterases in the lungs to des-ciclesonide which then undergoes CYP3A4-mediated metabolism. Coadministration of the strong CYP3A4 inhibitor ketoconazole (400 mg daily for 7 days) with orally inhaled ciclesonide (320 µg once daily) did not alter ciclesonide but resulted in a 3.5-fold increase in the AUC and a 2-fold increase in the Cmax of des-ciclesonide. Ciclesonide is mainly absorbed by the lungs, has a high protein binding and a high clearance resulting in a lower potential to cause systemic effects compared to some other inhaled corticosteroids. Hence, any interaction with atazanavir would not require any dosage/therapy adjustments, particularly if ciclesonide is administered at lower or medium clinical doses, but close monitoring for Cushing’s syndrome signs is required when using a higher dose or with prolonged administration. 

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Cidofovir is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3. Atazanavir is unlikely to inhibit OATs at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cilazapril is mainly eliminated unchanged by the kidneys.

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. Atazanavir is not recommended for pregnant women during the second and third trimester taking both tenofovir and an H2RA.

Coadministration has not been studied. Cinacalcet is metabolized by multiple CYP enzymes, mainly CYP3A4, CYP2D6 and CYP1A2. Atazanavir is metabolized by CYP3A4. Cinacalcet does not inhibit or induce CYP3A4. However, concentrations of cinacalcet may increase due to inhibition of CYP3A4 by atazanavir. Use with caution and a dose adjustment of cinacalcet may be required. Monitoring of iPTH serum phosphorus and serum calcium is recommended when starting or discontinuing a strong CYP3A4 inhibitor. Note, decreases in serum calcium can prolong the QT interval. Caution should be taken when using with antiretroviral drugs that can potentially prolong the QT interval such as atazanavir.

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. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Cisatracurium undergoes mainly (80% of overall elimination) spontaneous degradation in plasma and tissues at physiological pH and temperature (Hofmann elimination)

Coadministration has not been studied but based on metabolism and clearance a clinically sigificaint interaction is unlikely. Cisplatin is eliminated renally via OCT2 and MATE1. Atazanavir alone has no inhibitory effects on these transporters.

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. 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. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration with atazanavir alone increased atazanavir and clarithromycin exposure and reduced exposure of the active metabolite, 14-OH clarithromycin, by 70%. The European SmPC 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 Prescribing Information 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. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clavulanic acid is extensively metabolized (likely by a non-CYP mediated pathway) and excreted in the urine by glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clemastine is extensively metabolised in the liver but the enzymes responsible are undefined. Atazanavir is metabolized by CYP3A4 and is unlikely to affect clemastine metabolism. Clemastine is unlikely to affect CYP3A4.

Coadministration has not been studied. Clindamycin is metabolized by CYP3A4 and coadministration may increase clindamycin concentrations due to inhibition of CYP3A4 by atazanavir. A decrease in clindamycin dose may be needed.

Coadministration has not been studied. Clobazam is metabolised by CYP3A4 (major) and CYP2B6 and CYP2C19 (minor) to the active metabolite N-desmethylclobazam, which is metabolised by CYP2C19. Ketoconazole (a strong CYP3A4 inhibitor) was shown to increase clobazam exposure by 54%. A similar effect is expected with atazanavir. Consider starting on the recommended dose, but with close monitoring for side effects associated with clobazam and decrease dose if necessary. Clobazam is unlikely to significantly impact atazanavir.

Coadministration has not been studied. Clobetasol is a substrate of CYP3A4 and exposure may increase due to inhibition of CYP3A4 by atazanavir. Topical clobetasol can be used with caution. Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycaemia, and glycosuria in some patients. If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. Note, 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 conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website. However, the risk of QT interval prolongation is considered to be low as no significant pharmacokinetic interaction is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofibrate is hydrolyzed to an active metabolite, clofibric acid. Excretion of clofibric acid glucuronide is possibly performed via OAT1.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies have suggested that transformation of clomifene to its active metabolite is likely to be mediated via CYP2D6. Atazanavir alone does not inhibit CYP2D6.

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. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration has not been studied but may increase clonazepam concentrations and a decrease in dose may be necessary. Use with caution and perform therapeutic drug monitoring for clonazepam.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately 70% of administered clonidine is excreted in the urine, mainly in form of the unchanged parent drug (40-60% of the dose).

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. Clorazepate is rapidly converted to nordiazepam which is then metabolized to oxazepam by CYP3A4. Atazanavir could potentially increase nordiazepam exposure which could prolong sedation. A dosage reduction may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cloxacillin is metabolised to a limited extent, and the unchanged drug and metabolites are excreted in the urine by glomerular filtration and renal tubular secretion. Atazanavir is unlikely to inhibit OAT and OCT renal transporters at clinically relevant concentrations.

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 should be avoided. Cobimetinib is metabolised by CYP3A4 and UGT2B7. Cobimetinib concentrations are expected to increase due to strong inhibition of CYP3A4 by atazanavir. Itraconazole (a strong CYP3A4 inhibitor) increased cobimetinib AUC by 6.7-fold. A similar effect is expected with atazanavir and therefore coadministration is not recommended. In addition, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; cobimetinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Cocaine is metabolized by several pathways, with metabolism to norcocaine by CYP3A4 being less than 10% of the overall metabolic clearance. Atazanavir could potentially increase concentrations of the parent compound. The clinical relevance is unknown as cocaine is metabolized by other non-CYP mediated pathways. Ensure the patient is aware of signs/symptoms of cocaine 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; cocaine 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. Codeine is a substrate of CYP2D6 (major) and CYP3A4. The analgesic effect requires conversion of codeine to morphine via CYP2D6. Atazanavir does not inhibit CYP2D6 and therefore no effect on analgesic efficacy is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The major route of elimination for coenzyme Q10 is by biliary and faecal excretion; only a small fraction is eliminated in the urine. Atazanavir is metabolised by CYP3A4. Coenzyme Q10 is unlikely to have a clinically significant effect on substrates of CYP3A4, UGTs and P-gp.

Coadministration has not been studied and is expected to increase colchicine concentrations. Dose reductions of colchicine may be required. Atazanavir is contraindicated with colchicine to patients with renal or hepatic impairment. A reduction in colchicine dosage or an interruption of colchicine treatment is recommended in patients with normal renal or hepatic function. The US Prescribing Information gives the following dose modifications. For treatment of gout flares, the recommended dosage is 0.6 mg (1 tablet) for 1 dose, followed by 0.3 mg (half tablet) 1 hour later. The dose is to be repeated no earlier than 3 days. For 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. For treatment of familial Mediterranean fever (FMF) do not exceed a maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day).

Coadministration has not been studied. Metabolism of vitamin D to active metabolites occurs in the liver and kidneys, and is thought to involve CYP3A4 and CYP24A1. In vitro studies have shown rifampicin (an enzyme inducer) increased metabolism of vitamin D and introduction of 6',7'-dihydroxybergamottin (a CYP3A4 inhibitor in grapefruit juice) reversed the effects of rifampicin on vitamin D clearance. Inhibition of CYP3A by atazanavir is not expected to reduce the effect of vitamin D, but the consequence of CYP3A inhibition on the clinical effect of vitamin D is not known. However, no effect of antiretroviral therapy on the response to vitamin D supplementation was found in a PK modelling study.

Coadministration has not been studied. No interaction is expected with vitamin D when given with calcium or in a multivitamin preparation. Metabolism of vitamin D to active metabolites occurs in the liver and kidneys, and is thought to involve CYP3A4 and CYP24A1. In vitro studies have shown rifampicin (an enzyme inducer) increased metabolism of vitamin D and introduction of 6',7'-dihydroxybergamottin (a CYP3A4 inhibitor in grapefruit juice) reversed the effects of rifampicin on vitamin D clearance. Inhibition of CYP3A by atazanavir is not expected to reduce the effect of vitamin D, but the consequence of CYP3A inhibition on the clinical effect of vitamin D is not known. However, no effect of antiretroviral therapy on the response to vitamin D supplementation was found in a PK modelling study

Coadministration has not been studied. Colesevelam is not absorbed from the gastrointestinal tract, is not metabolised and does not affect CYP enzymes. Atazanavir is metabolised by CYP3A4. However, given that colesevelam can reduce the gastrointestinal absorption of some drugs, colesevelam should be administered at least four hours before or after atazanavir to minimize the risk of reduced absorption.

Coadministration has not been studied. Colestyramine may delay or reduce the absorption of drugs. Administration of other drugs should be at least 1 hour before or 4-6 hours after colestyramine. [Note: this interaction is not specific for atazanavir, but for any medication taken with colestyramine.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Collagen hydrolysate is digested and absorbed as essential amino acids for use in essential physiological processes. Atazanavir is metabolized by CYP3A4. Collagen hydrolysate is unlikely to affect CYP3A4.

Coadministration with conjugated estrogens as hormone replacement therapy (HRT) has not been studied. Conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Coadministration is predicted to increase exposure of conjugated estrogens. The clinical significance of this increase in terms of overall risk of deep vein thrombosis, pulmonary embolism, stroke and myocardial infarction in postmenopausal women receiving substitution hormones in unknown. In addition, exposure of progestogens administered as part of HRT may also increase. The clinical relevance of this is unknown but increased progestogen concentrations may be associated with a higher incidence of side effects. The use of conjugated estrogens alone or in combination with a progestogen should be used at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for individual women. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary. Note, use of conjugated estrogens as part of gender affirming treatment should be avoided as they are associated with high thromboembolic risk.

Coadministration has not been studied. Copanlisib is metabolised by CYP3A (~90%) and CYP1A1 (~10%). Atazanavir is metabolized by CYP3A4. Copanlisib does not inhibit or induce CYP3A4. However, atazanavir is a strong inhibitor of CYP3A4 and may increase copanlisib concentrations. Coadministration of copanlisib (60 mg i.v. infusion) and a strong CYP3A4 inhibitor (itraconazole, 200 mg once daily for 10 days) increased copanlisib AUC by 53% with no effect on Cmax (3% increase). A similar effect can be expected with atazanavir. The American product label for copanlisib states that if coadministration with strong CYP3A inhibitors cannot be avoided, to reduce the copanlisib dose from 60 mg to 45 mg.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cortisone is rapidly converted in the liver to its active metabolite, hydrocortisone (cortisol); cortisone and hydrocortisone are metabolized by CYP3A4. Inhibition of CYP3A4 by atazanavir may increase cortisone and hydrocortisone concentrations. Careful monitoring of adverse effects is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cortisone is rapidly converted in the liver to its active metabolite, hydrocortisone (cortisol); cortisone and hydrocortisone are metabolized by CYP3A4. Although atazanavir inhibits CYP3A4, no clinically significant interaction is expected with topical cortisone.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Creatine monohydrate is not degraded during normal digestion and nearly 99% of orally ingested creatine monohydrate is either taken up by muscle or excreted in urine. Atazanavir is metabolized by CYP3A4. Creatine is unlikely to affect CYP3A4.

Coadministration has not been studied but should be avoided. Crizotinib is mainly metabolized by CYP3A4. Atazanavir is a strong inhibitor of CYP3A4 and is expected to increase crizotinib concentrations. Coadministration with ketoconazole (200 mg twice daily), a strong CYP3A inhibitor, increased crizotinib AUC and Cmax by 3.2-fold and 1.4-fold, respectively. A similar effect is expected with atazanavir and therefore coadministration is not recommended. In addition, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; crizotinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Several constituents of Piper cubeba were shown to inhibit CYP3A4 in vitro, and could potentially increase the exposure of atazanavir. No a priori dosage adjustment of atazanavir is needed.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with cyanocobalamin when given alone or in multivitamins. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine.

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 is metabolized by CYP3A4 and is unlikely to inhibit or induce CYP2D6.

Coadministration has not been studied. Cyclobenzaprine is primarily metabolized by CYP3A4 and CYP1A2 and to a lesser extent by CYP2D6. Atazanavir is metabolized by CYP3A4. Cyclobenzaprine is unlikely to affect CYP3A4. Atazanavir is a strong inhibitor of CYP3A4 and may increase cyclobenzaprine concentrations, although to a limited extent due to the multiple elimination pathways.

Coadministration has not been studied. Cyclophosphamide is metabolized by two pathways. Activation (major pathway) to 4-hydroxycyclophosphamide is metabolized by CYPs 2B6 (major), 2C9 and 3A4. Inactivation (minor, 10%) to the neurotoxic chloroacetaldehyde metabolite is performed mainly by CYP3A4. In theory, atazanavir could potentially reduce the risk of neurotoxicity by inhibiting the CYP3A4-mediated inactivation pathway and increase the amount of drug available for the activation pathway which may increase the efficacy and the toxicity of cyclophosphamide (i.e., myelosuppression, nausea, vomiting). Careful monitoring of cyclophosphamide related side effects is recommended. Adjust dose if clinically necessary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cycloserine is predominantly excreted renally via glomerular filtration.

Coadministration has not been studied. Cyproterone acetate is metabolized by CYP3A4 and concentrations may increase due to inhibition of CYP3A4 by atazanavir. A dose adjustment of cyproterone may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cytarabine is metabolized by cytidine deaminase.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cytisine is primarily excreted renally as unchanged drug. There are no reports of CYP or transporter involvement and significant pharmacokinetic interactions are unlikely. Atazanavir is metabolised by CYP3A4.

Coadministration has not been studied. Dabigatran is a substrate of P-gp. Coadministration of dabigatran (150 mg single dose) simultaneously with or 2 h before ritonavir alone (100 mg once daily administered at steady state) was studied in subjects without HIV. Simultaneous administration did not significantly change dabigatran pharmacokinetics (possibly due to mixed induction and inhibition of P-gp by ritonavir). Administration 2 hours before ritonavir decreased dabigatran AUC by 29% and Cmax by 27% (n=16). These results suggest that dabigatran can be administered simultaneously with ritonavir. These recommendations may also be applied to atazanavir given that atazanavir has been shown to have inhibitory and inducing effects on P-gp in vitro. Data with verapamil (a P-gp inhibitor) and dabigatran suggest caution is needed in patients with mild or moderate renal impairment as the dabigatran dose might need to be reduced in presence of a P-gp inhibitor such as atazanavir. Note, dabigatran is not recommended in patients with severe renal impairment.

Coadministration has not been studied but is not recommended. Dabrafenib is metabolized by CYP3A4 and CYP2C8 and the active metabolites are metabolized by CYP3A4. Atazanavir is metabolized by CYP3A4 and is a strong inhibitor of CYP3A4 and may increase dabrafenib concentrations. Coadministration of ketoconazole (another strong CYP3A4 inhibitor) and dabrafenib increased dabrafenib AUC and Cmax by 71% and 33%, respectively. The AUC of hydroxyl-dabrafenib and desmethyl-dabrafenib increased by 82% and 68%, respectively; Cmax of hydroxyl-dabrafenib and desmethyl-dabrafenib increased by 27% and 72%, respectively. In addition, dabrafenib is a strong inducer of CYP3A4 and may decrease atazanavir concentrations which may lead to loss of therapeutic effect and possible development of resistance. Furthermore, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; atazanavir 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. Dacarbazine undergoes activation to MTIC primarily via CYP1A2 and to a lesser extent by CYP2E1, with CYP1A1 having a role in extrahepatic metabolism. Atazanavir does not inhibit or induce these cytochromes at clinically relevant concentrations.

Coadministration with atazanavir alone has not been studied. Coadministration of atazanavir/ritonavir (300/100 mg once daily) and daclatasvir (20 mg once daily) increased daclatasvir AUC, Cmax and Cmin by 110%, 35% and 265%, respectively (results dose-normalised to 60 mg dose). The dose of daclatasvir should be reduced to 30 mg once daily when coadministered with atazanavir/ritonavir or atazanavir/cobicistat. However no dose reduction is required with unboosted atazanavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dacomitinib is metabolised by CYP2D6 (~26%) to O-desmethyl dacomitinib, an active metabolite with similar activity to dacomitinib, whilst CYP3A4 (~6%) contributes to the formation of other minor metabolites. Atazanavir is a strong inhibitor of CYP3A4 and may increase dacomitinib concentrations. However, this is unlikely to be clinically significant as CYP3A4 contributes to dacomitinib metabolism only to a small degree.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dactinomycin is minimally metabolized.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dalteparin is excreted largely unchanged by the kidneys.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapagliflozin is primarily metabolised by UGT1A9. Atazanavir inhibits primarily UGT1A1 and atazanavir alone is unlikely to alter dapagliflozin exposure. No dose adjustment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atazanavir is metabolized by CYP3A4. Dapivirine is metabolized mainly by CYP3A4 and to a lesser extent by glucuronidation. However, the risk of drug-drug interactions is low with the dapivirine vaginal ring due to its low systemic exposure. Furthermore, dapivirine concentrations in vaginal fluid exceed the in vitro HIV IC99 by 1000-fold.

Coadministration has not be studied. Metabolism of dapsone is mainly by N-acetylation with a component of N-hydroxylation, and is via multiple CYP P450 enzymes. Clinically significant interactions are unlikely, but cannot be excluded.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daptomycin is eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daratumumab, is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Atazanavir is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The mechanisms of darbepoetin alfa clearance and the site of degradation have not been fully determined but are likely to involve uptake and degradation via epoetin receptor expressing cells and degradation or metabolism via cells in the reticuloendothelial scavenging pathway or lymphatic system. Clinical results to date do not indicate any interaction of darbepoetin with other medicinal products.

Coadministration has not been studied but is contraindicated. Daridorexant is mainly metabolised by CYP3A4. Atazanavir is metabolized by CYP3A4. Daridorexant is a weak inhibitor of CYP3A4 but is unlikely to have a clinically significant effect on atazanavir. However, atazanavir is a strong CYP3A4 inhibitor and is expected to significantly increase daridorexant concentrations. Coadministration of daridorexant (25 mg) and the moderate CYP3A4 inhibitor diltiazem (240 mg once daily) increased daridorexant AUC and Cmax by 2.4- and 1.4-fold, respectively. No clinical study was conducted with a strong CYP3A4 inhibitor. Coadministration with strong CYP3A4 inhibitors is contraindicated in the European product label for daridorexant, whereas the American product label recommends to avoid coadministration.

Coadministration has not been studied. Darifenacin is metabolized by CYP3A4 and CYP2D6 and coadministration is likely to increase concentrations. A 5-fold increase in darifenacin exposure was seen with ketoconazole (a strong inhibitor of CYP3A4) and the magnitude of the interaction could be even more pronounced in poor metabolizer individuals. The European SmPC for darifenacin contraindicates its use with potent CYP3A4 inhibitors (such as atazanavir), but the US Prescribing Information recommends that the dose of darifenacin should not exceed 7.5mg when coadministered with potent CYP3A4 inhibitors.

Coadministration has not been studied. Darolutamide is primarily metabolised by CYP3A4, and to a lesser extent by UGT1A9 and UGT1A1, and is a substrate of P-gp. Atazanavir is metabolized by CYP3A4. Darolutamide is a weak inducer of CYP3A4 but is unlikely to have a clinically significant effect on atazanavir. Inhibition of CYP3A4 and P-gp by atazanavir may increase darolutamide concentrations. No a priori dose adjustment is required but monitor for adverse effects. Note, androgen deprivation treatment may prolong the QT interval. Caution should be taken when using with antiretroviral drugs that can potentially prolong the QT interval such as atazanavir.

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.

Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, 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 but should be avoided. Dasatinib is metabolized by CYP3A4 and coadministration may significantly increase exposure to dasatinib concentrations. Furthermore, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; dasatinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. If coadministration is unavoidable, close monitoring for toxicity and QT prolongation is required. The US product information for dasatinib recommends a dose reduction to 20 mg daily (for patients taking dasatinib 100 mg) and to 40 mg (for patients taking dasatinib 140 mg) in presence of strong inhibitors of CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. However, damage to the myocardium is one of the major risks of daunorubicin treatment and may include dose-independent supraventricular arrhythmias (sinus tachycardia, premature ventricular contractions, AV-block) and/or non-specific ECG abnormalities. Caution should be used when prescribing atazanavir in association with medicinal products which have the potential to increase the QT interval and/or in patients with pre-existing risk factors.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The primary route of decitabine metabolism is likely by cytidine deaminase. Decitabine is a prodrug and is activated intracellularly through sequential phosphorylation via phosphokinases activities to the active triphosphate. Atazanavir is metabolised by CYP3A4. Decitabine does not inhibit or induce CYP enzymes.

Coadministration has not been studied. Deferasirox is mainly glucuronidated by UGT1A1 and to a lesser extent by UGT1A3; CYP-mediated metabolism appears to be minor (~8%). Atazanavir is metabolized by CYP3A4. Deferasirox is a weak inducer of CYP3A4 and was shown to reduce midazolam exposure by 17%, although it is unlikely to significantly decrease atazanavir concentrations. However, atazanavir is a UGT1A1 inhibitor and may increase concentrations of deferasirox. If coadministration is necessary, closely monitor for deferasirox toxicity. A deferasirox dose reduction may be required to avoid serious renal or hepatic toxicity.

Coadministration has not been studied. Deflazacort is immediately metabolised by plasma esterases to the active metabolite (21-desdeflazacort) which is then metabolised mainly by CYP3A4 to several inactive metabolites which are excreted in the urine (~70%) and faeces (~30%). Atazanavir is metabolized by CYP3A4. Deflazacort and 21-desdeflazacort do not inhibit or induce CYP3A4. However, atazanavir is a strong inhibitor of CYP3A4 and may increase exposure of 21-desdeflazacort. Coadministration of deflazacort and clarithromycin (a strong CYP3A4 inhibitor), increased total exposure of 21-desdeflazacort by about 3-fold. The European product label for deflazacort recommends coadministration with CYP3A inhibitors should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects. The US product label suggests a dose reduction to one third of the normal recommended deflazacort dosage with moderate/strong CYP3A4 inhibitors.

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 throughout the full delamanid treatment period (for example, at least fortnightly for the first month and if the QTc interval remains within normal range to reduce this to monthly thereafter).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Denosumab is not eliminated via hepatic metabolism but follows the immunoglobulin clearance pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desflurane is almost exclusively eliminated unchanged by the lungs.

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 has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desloratadine is metabolized to the active metabolite 3-hydroxydesloratadine, which is subsequently glucuronidated. The enzyme(s) responsible for the formation of the active metabolite have not been identified, but no clinically relevant interactions have been observed with inhibitors of CYP enzymes. Atazanavir is metabolized by CYP3A4. Desloratadine does not inhibit CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desmopressin undergoes no significant hepatic metabolism and is not a substrate for CYP enzymes. Atazanavir is metabolized by CYP3A4. Desmopressin does not inhibit CYP enzymes and no metabolic drug interactions are expected.

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. The US Prescribing Information for atazanavir recommends that if atazanavir is administered without a pharmacoenhancer, the oral contraceptive should contain no more than 30 µg of ethinylestradiol.

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.

Coadministration has not been studied. Dexamethasone is metabolized by CYP3A4. Atazanavir may increase dexamethasone concentrations due to inhibition of CYP3A4. A dose reduction of the glucocorticoid may be necessary with monitoring for symptoms of hypercorticism. Dexamethasone is a dose-dependent inducer of CYP3A4 and is a moderate CYP3A4 inducer at doses above 16 mg. Chronic or high doses of dexamethasone may decrease atazanavir plasma concentrations due to CYP3A4 induction with the possible loss of therapeutic effect and development of resistance. Use with caution.

Coadministration has not been studied. Dexamethasone is metabolized by CYP3A4. Atazanavir may increase dexamethasone concentrations due to inhibition of CYP3A4. A dose reduction of the glucocorticoid may be necessary with monitoring for symptoms of hypercorticism. Dexamethasone is a weak CYP3A4 inducer at a low dose and is unlikely to have a clinically significant effect on atazanavir. Note, it is expected that the risk of Cushing’s syndrome is less likely to occur when using dexamethasone at a low dose and for a short treatment duration as compared to higher doses and long treatment duration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexketoprofen is mainly excreted as glucuronide conjugates; CYP2C8/9 plays a minor role in metabolism. Atazanavir is metabolized by CYP3A4. Dexketoprofen is unlikely to affect CYP3A4. Atazanavir is a weak CYP2C8 inhibitor but is unlikely to significantly increase dexketoprofen concentrations. In addition, no effect on dexketoprofen due to inhibition of UGTs by atazanavir is expected as It is likely that multiple UGTs are involved in the metabolism of dexketoprofen.

Coadministration has not been studied. Coadministration of atazanavir with proton pump inhibitors is not recommended. Lansoprazole decreased atazanavir (alone) AUC by 94%; omeprazole decreased atazanavir (+ ritonavir) AUC by 75%. A similar decrease is expected with dexlansoprazole. Coadministration is not recommended in treatment experienced patients. If coadministration is judged unavoidable in treatment-naive patients, 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant 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 has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextromethorphan is metabolized by CYP2D6. Atazanavir is metabolized by CYP3A4. Atazanavir does not inhibit or induce CYP2D6. Dextromethorphan does not inhibit or induce CYP3A4.

Coadministration has not been studied and is not recommended. Dextropropoxyphene has been withdrawn from most European and North American countries due to the risk of arrhythmias and fatalities. As it is metabolized mainly by CYP3A4, coadministration with atazanavir could markedly increase the exposure of dextropropoxyphene.

Coadministration has not been studied. Diamorphine is rapidly metabolized by sequential deacetylation to morphine which is then mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Atazanavir does not inhibit or induce UGT2B7. However, morphine and morphine-6-glucuronide are substrates of P-gp and coadministration may potentiate the effects of opiate in the CNS due to inhibition of P-gp at the blood-brain barrier. Monitor for signs of opiate toxicity.

Coadministration has not been studied. Diazepam is metabolized to nordiazepam (by CYPs 3A4 and 2C19) and to temazepam (mainly by CYP3A4). Atazanavir could potentially increase diazepam exposure by inhibition of CYP3A4. This could prolong sedation and a dosage reduction may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diclofenac is partly glucuronidated by UGT2B7 and partly oxidized by CYP2C9. There is no evidence that atazanavir inhibits or induces UGT2B7 or CYP2C9.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diethylcarbamazine is mainly excreted unchanged in the urine. Atazanavir is unlikely to inhibit OAT and OCT renal transporters at clinically relevant concentrations.

Coadministration has not been studied but may increase digoxin concentrations due to P-gp inhibition. Start with the lowest dose of digoxin, monitor serum digoxin concentrations and titrate the digoxin dose to obtain the desired clinical effects. Pharmacokinetic studies between atazanavir and other drugs that prolong the PR interval have not been performed. An additive effect of atazanavir and these drugs cannot be excluded; therefore, caution should be exercised when atazanavir is given concurrently with these drugs.

Coadministration has not been studied. Dihydrocodeine is converted to dihydromorphine (active metabolite) via CYP2D6, to dihydrocodeine-6-glucuronide via UGT2B7 (major pathway) and to nordihydrocodeine via CYP3A4. The analgesic effect appears to be primarily due to the parent compound. Atazanavir could potentially increase dihydrocodeine exposure by inhibition of CYP3A4. No a priori dose adjustment is required, but monitoring for analgesic effect and for signs of opiate toxicity may be required as clinically indicated.

Coadministration of dihydroergotamine and atazanavir is contraindicated due to potential for serious and/or life threatening events such as acute ergot toxicity.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diloxanide furoate is largely hydrolysed under the combined action of bacterial and gut esterases and consequently glucuronidated. No clinically-significant drug interactions are known, and significant interactions with antiretrovirals are unlikely.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Dimethyl fumarate is metabolized by esterases before entering the blood stream. Further metabolism occurs though the TCA cycle. Atazanavir is metabolised by CYP3A4. Dimethyl fumarate is unlikely to have a clinically significant effect on substrates of CYPs, UGTs and P-gp.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diphenhydramine is predominantly metabolized by CYP2D6. Atazanavir alone does not inhibit CYP2D6.

Coadministration has not been studied. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Atazanavir could potentially increase dipyridamole exposure due to inhibition of UGT1A1. No dosage adjustment is needed but monitor for increased side effects and toxicities of dipyridamole.

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 of disulfiram (62.5 mg or 250 mg once daily) with atazanavir (400 mg once daily) had no significant effect on atazanavir pharmacokinetics at either dose. Disulfiram is converted to an active metabolite by CYP3A4 and UGT, which may be inhibited by atazanavir. Coadministration with disulfiram 250 mg was associated with a lack of disulfiram‐associated inhibition of ALDH activity and is unlikely to be effective in deterring alcohol use. 

Coadministration has not been studied and is not recommended. Coadministration with atazanavir may increase concentrations of docetaxel and increase the risk of severe toxicities. There have been several case reports of severe haematological and cutaneous toxicity when coadministered with ritonavir, a potent CYP3A inhibitor. Ideally avoid coadministration with atazanavir or consider using an alternative taxane.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Docusate has been reported to undergo extensive first-pass metabolism and metabolism in the liver, but the metabolic pathway remains unclear. Atazanavir is metabolized by CYP3A4. Docusate is unlikely to inhibit or induce CYP3A4.

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.

Dolutegravir/lamivudine/tenofovir-DF is indicated for use as a complete regimen for the treatment of HIV-1 infection and coadministration with other antiretroviral agents is not recommended. Atazanavir alone should not be coadministered as tenofovir-DF may decrease atazanavir concentrations and the atazanavir product labels recommend boosted atazanavir with tenofovir-DF. Coadministration of tenofovir-DF (300 mg once daily) with atazanavir/ritonavir 300/100 mg once daily) decreased atazanavir AUC, Cmax and Cmin 22%, 16% and 23%, respectively.

Triumeq (dolutegravir, abacavir, lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with atazanavir would be possible from a pharmacokinetic standpoint. Coadministration of atazanavir alone and dolutegravir 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.

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with atazanavir would be possible from a pharmacokinetic standpoint. The European product label for Dovato advises that no dose adjustment is necessary with atazanavir. Coadministration of atazanavir alone and dolutegravir 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).

Juluca (dolutegravir/rilpivirine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with atazanavir would be possible from a pharmacokinetic standpoint. 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. 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. 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. However, the product labels for Juluca indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Atazanavir has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

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 (QT interval prolongation) which have been reported for both drugs. 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. Donepezil is metabolized by CYP3A4 and CYP2D6 (minor). A 30% increase in donepezil exposure has been reported in presence of ketoconazole, a strong CYP3A4 inhibitor. A similar effect is expected with atazanavir. No a priori dose modification is required but monitoring for increased side effects is recommended. Furthermore, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; donepezil 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. Dopamine is metabolised in the liver, kidneys, and plasma by monoamine oxidase (MAO) and catechol-O-methyltransferase to inactive compounds. About 25% of a dose of dopamine is metabolised to norepinephrine within the adrenergic nerve terminals. There is little potential for dopamine to affect the disposition of atazanavir, or to be affected if co-administered with atazanavir.