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. 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. Acenocoumarol is mainly metabolized by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Induction of CYP2C9 by ritonavir may lead to decreased acenocoumarol exposure. There is a case report of an HIV-infected patient on ART who was receiving the anticoagulant acenocoumarol for secondary prevention of recurrent venous thromboembolism. Whilst on either an efavirenz-based or an atazanavir/ritonavir-based regimen, the average acenocoumarol dose was increased to maintain INR in the target range. Eventually the patient was stabilised on a raltegravir regimen.

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 metabolism and clearance a clinically significant interaction is unlikely as aciclovir is eliminated renally via glomerular filtration and active renal secretion by OAT1. Atazanavir/ritonavir 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 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/ritonavir 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 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. However, 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.

Coadministration has not been studied. Agomelatine is metabolised predominantly by CYP1A2 which is induced by ritonavir. Coadministration with atazanavir/ritonavir could potentially decrease agomelatine exposure. Monitor clinical effect and increase dosage if needed.

Coadministration has not been studied. In vitro studies have demonstrated that CYP3A4 and the flavine-containing monooxygenase system are involved in 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/ritonavir is unlikely to significantly affect albendazole exposure when used for a short duration treatment but may reduce the clinical effect of albendazole when used for a long duration treatment.

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/ritonavir 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/ritonavir is unlikely to inhibit OAT and OCT renal transporters at clinically relevant concentrations.

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/ritonavir 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/ritonavir.

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. The American product label for almotriptan recommends using an initial almotriptan dose of 6.25 mg with a strong CYP3A4 inhibitor and not exceeding 12.5 mg within a 24 hour period. It also recommends to avoid use of almotriptan and a strong CYP3A4 inhibitor in patients with impaired renal or hepatic function.

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. In vitro data indicate that alosetron is metabolized by CYPs 2C9 (30%), 3A4 (18%) and 1A2 (10%); however, in vivo data suggest that CYP1A2 plays a more prominent role. In vitro data indicate that ritonavir induces CYP1A2, therefore coadministration with atazanavir/ritonavir could potentially decrease alosetron exposure.

Coadministration has not been studied. Alprazolam is mainly metabolized by CYP3A4. Interaction studies with ritonavir have shown inhibition of alprazolam metabolism following the introduction of ritonavir but no significant inhibitory effect at steady state. Based on these data, when combined with atazanavir/ritonavir, consider starting alprazolam at a lower dosage and increase if needed.

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/ritonavir is unlikely to inhibit OCTs at clinically relevant concentrations.

Coadministration has not been studied. 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 ritonavir induces CYP1A2. Atazanavir/ritonavir could potentially decrease theophylline concentrations. Monitor plasma concentrations and increase aminophylline dosage if needed.

Coadministration has not been studied and is not recommended. Amiodarone is metabolised by CYP3A4 and concentrations may be increased due to inhibition of CYP3A4 by atazanavir/ritonavir. 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/ritonavir is unlikely to inhibit OCTs at clinically relevant concentrations.

Coadministration has not been studied. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19 and atazanavir/ritonavir could potentially increase amitriptyline exposure although to a moderate extent. No a priori dosage adjustment is recommended. Note, both drugs have conditional risks of QT prolongation and/or TdP on the CredibleMeds.org website. Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, the risk of QT prolongation when combining these drugs is considered to be small given the limited PK drug-drug interaction.

Coadministration has not been studied. Amlodipine is metabolized by CYP3A4. Atazanavir/ritonavir is predicted to increase amlodipine exposure by ~2-fold based on drug-drug interactions studies with amlodipine and indinavir/ritonavir or paritaprevir/ritonavir. If coadministration is indicated, consider a dose reduction for amlodipine of 50%. Use with caution as both atazanavir and calcium channel blockers prolong the PR interval. 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 and ritonavir is a weak inducer of CYP2C8. The net effect is difficult to predict but atazanavir/ritonavir is unlikely to have a clinically relevant effect on amodiaquine exposure. No a priori dosage adjustment is recommended.

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/ritonavir is unlikely to inhibit OATs at clinically relevant concentrations.

Coadministration has not been studied. Amphetamine is metabolized by CYP2D6 and coadministration with atazanavir/ritonavir 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/ritonavir is unlikely to inhibit OAT and OCT renal transporters at clinically relevant concentrations.

Coadministration has not been studied. Anastrozole is mainly oxidized to hydroxyanastrozole by CYP3A4 (major) and glucuronidated by UGT1A4. The magnitude of the interaction is predicted to be of moderate intensity as ritonavir has an opposite effect on CYP3A4 (inhibition) and UGT1A4 (induction), which might result in a counterbalancing effect. No a priori dosage adjustment is recommended.

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/ritonavir 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. Concentrations of apixaban are expected to increase due to potent CYP3A4 and P-gp inhibition by atazanavir/ritonavir, 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. Apomorphine is metabolized by several pathways that include mainly glucuronidation and sulfation and to a lesser extent N-demethylation. Although atazanavir/ritonavir has the potential to induce glucuronidation, the clinical relevance of such an interaction is unknown considering the numerous pathways contributing to apomorphine metabolism. No a priori dosage adjustment is required. 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. Aprepitant is mainly metabolized by CYP3A4 and is a moderate inhibitor of CYP3A4. Atazanavir/ritonavir could potentially increase aprepitant concentrations. A decrease in aprepitant dose may be needed.

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/ritonavir is unlikely.

Coadministration has not been studied. Aripiprazole is metabolized by CYP3A4 and CYP2D6. Atazanavir and atazanavir/ritonavir 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. 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/ritonavir could potentially increase plasma levels of artemisinins. Close monitoring for artemisinin toxicity required.

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/ritonavir 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). As ritonavir induces CYP1A2 and UGT1A4, atazanavir/ritonavir could potentially decrease asenapine exposure. Monitor the clinical effect and increase dosage if needed. 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. 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.

Coadministration with atazanavir/ritonavir has not been studied. 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 with atazanavir/ritonavir as atenolol is mainly eliminated by the kidney, both by glomerular filtration and active secretion via the renal transporters OCT2 and MATE1. The impact on the PR interval has not been evaluated for the coadministration of atazanavir/ritonavir and atenolol however 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 with atrioventricular nodal blocking agents.

Coadministration of atazanavir/ritonavir and atorvastatin has not been studied but is expected to substantially increase atorvastatin due to inhibition of CYP3A4, OATP1B1 and BCRP by atazanavir/ritonavir. Coadministration of atazanavir/cobicistat and atorvastatin increased atorvastatin AUC and Cmax by 822% and 1785%. Coadministration is not recommended. If the use of atorvastatin/ritonavir 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.

A single dose study showed decreased atovaquone exposure with atazanavir/ritonavir, however, no significant effect on atovaquone AUC was observed with steady state administration of atovaquone and atazanavir/ritonavir. Coadministration of atovaquone (750 mg or 1500 mg, twice daily with food) with atazanavir/ritonavir (300/100 mg, once daily, plus 2 NRTIs) decreased atovaquone AUC for the 750 mg dose by 10% and AUC for the 1500 mg dose by 5%. Consider taking atovaquone/proguanil with a high fat meal to increase its bioavailability.

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/ritonavir.

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/ritonavir 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. Basiliximab 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. 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/ritonavir) 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/ritonavir, 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. 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/ritonavir. 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 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. 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 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. 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. Caution is needed when betamethasone is administered orally or intravenously at high doses or for a long duration as it may decrease atazanavir/ritonavir exposure.

Coadministration has not been studied. Betrixaban is largely eliminated unchanged through biliary secretion via P-gp. Coadministration with a P-gp inhibitor (such as atazanavir/ritonavir) 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 potentially decrease atazanavir/ritonavir 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.

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/cobicistat (300/150 mg once daily) or atazanavir alone (400 mg once daily) increased bictegravir AUC by 306% and 315%, respectively. A similar magnitude of increase could occur with atazanavir/ritonavir.

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. 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. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Coadministration with atazanavir/ritonavir 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/ritonavir 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. Bortezomib is mainly metabolized by CYPs 3A4 and 2C19 and to a lesser extent CYPs 1A2, 2D6 and 2C9. Atazanavir/ritonavir 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/ritonavir. 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 but may increase bosentan concentrations. When starting bosentan in patients already receiving atazanavir/ritonavir, use a bosentan dose of 62.5 mg once daily or every other day based on individual tolerability. When starting atazanavir/ritonavir in patients already on bosentan, discontinue bosentan at least 36 h prior to starting atazanavir/ritonavir and restart after at least 10 days at 62.5 mg once daily or every other day based on individual tolerability.

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. Bromazepam does not inhibit CYP3A4. Atazanavir/ritonavir 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/ritonavir. No a priori dosage adjustment is required.

Coadministration has not been studied and is not recommended. Concomitant use of atazanavir/ritonavir 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. Bupivacaine is predominantly metabolized by CYP3A4. CYP3A4 inhibitors such as atazanavir/ritonavir 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 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. If coadministered, monitor for sedation and cognitive effects and consider a dose reduction of buprenorphine. There are three case reports of clinical symptoms of opiate excess during coadministration which required dose reduction of buprenorphine.

Coadministration has not been studied. Bupropion is primarily metabolized by CYP2B6 and in vivo data indicate that ritonavir induces CYP2B6. Atazanavir/ritonavir could potentially decrease bupropion concentrations (due to CYP2B6 induction). Titrate bupropion dose based on response, but the recommended dose of bupropion should not be exceeded.

Coadministration has not been studied. Buspirone is metabolized by CYP3A4 but does not inhibit CYP3A4. Atazanavir/ritonavir 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. Caffeine is mainly metabolized by CYP1A2. In vivo data indicate that ritonavir induces CYP1A2 and therefore coadministration could potentially decrease caffeine concentrations. However, no a priori dose adjustment is required.

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/ritonavir should be administered 2 hours before or 1 hour after calcium supplements containing calcium carbonate.

Coadministration has not been studied. Canagliflozin is primarily metabolised by UGT1A9 and UGT2B4. Atazanavir inhibits primarily UGT1A1, but atazanavir/ritonavir could lead to reduced exposure to canagliflozin as a result of UGT enzyme induction by ritonavir as rifampicin (a nonselective inducer of several UGT enzymes, including UGT1A9, UGT2B4) decreased canagliflozin AUC by 51% which may result in reduced efficacy. If coadministration is deemed necessary, increasing canagliflozin to 300 mg once daily may be considered if patients are currently tolerating canagliflozin 100 mg once daily, have an eGFR ≥60 mL/min/1.73m2 or CrCl ≥60 mL/min, and require additional glycaemic control. Other glucose-lowering therapies should be considered for patients with an eGFR 45 mL/min/1.73m2 to <60 mL/min/1.73m2 or CrCl 45 mL/min to <60 mL/min taking canagliflozin 100 mg who are receiving concurrent therapy with a UGT enzyme inducer and who require additional glycaemic control.

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 may increase cannabidiol concentrations due to strong inhibition of CYP3A4 by atazanavir + ritonavir and decrease cannabidiol concentrations due to induction of CYP2C19 by ritonavir. The net effect of these interactions is unknown. Monitor effect and occurrence of side effects and adjust cannabidiol dosage accordingly.

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. In vivo data indicate that ritonavir is a weak inducer of CYP2C9 and a strong inhibitor of CYP3A4. The net clinical effect of this interaction is difficult to predict as atazanavir/ritonavir could potentially decrease THC exposure (induction of CYP2C9) or increase THC exposure (inhibition of CYP3A4).

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/ritonavir 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Capreomycin is predominantly excreted via the kidneys as unchanged drug. Atazanavir/ritonavir 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 but could potentially increase carbamazepine concentrations and reduce atazanavir concentrations. Use with caution. Monitor carbamazepine and atazanavir plasma concentrations and adjust dosages if needed. If patients beginning treatment with atazanavir/ritonavir have been titrated to a stable dose of carbamazepine, a dose reduction for carbamazepine may be necessary. 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. Enhanced levodopa effects including severe dyskinesia were described in a case report after initiation of an antiretroviral regimen containing indinavir to an individual who was previously stable on levodopa/carbidopa therapy. When reintroduced alone, indinavir monotherapy induced the abnormal movements, which resolved on discontinuation. Clinical monitoring for levodopa/carbidopa efficacy is warranted if co-administered with protease inhibitors, such as atazanavir/ritonavir.

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. 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. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. The net effect of atazanavir/ritonavir on carvedilol concentrations is difficult to predict but likely to be moderate in magnitude. 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 and ritonavir are inhibitors 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/ritonavir 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. Cefalexin is predominantly eliminated unchanged renally (by glomerular filtration and tubular secretion via OAT1 and MATE1. Atazanavir/ritonavir 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/ritonavir 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/ritonavir 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. Celecoxib is primarily metabolized by CYP2C9 and in vivo data indicate that ritonavir is a weak inducer of CYP2C9. A dose adjustment is unlikely to be required for celecoxib when coadministered with atazanavir/ritonavir.

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/ritonavir 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 and ritonavir. 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/ritonavir, the activity of chlordiazepoxide may be increased.

Coadministration has not been studied. Atazanavir/ritonavir 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/ritonavir 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. Chlorphenamine is predominantly metabolized in the liver via CYP2D6. Atazanavir/ritonavir could potentially increase chlorphenamine exposure although to a moderate extent as ritonavir is a weak inhibitor of CYP2D6. No a priori dosage adjustment is required.

Coadministration has not been studied. Chlorpromazine is metabolized mainly by CYP2D6, but also by CYP1A2. Atazanavir/ritonavir could potentially increase chlorpromazine although to a moderate extent. Furthermore, 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/ritonavir 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/ritonavir 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/ritonavir 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.

H2-receptor antagonists reduce the absorption of atazanavir, but the extent of the interaction can depend on dose and timing of administration. Famotidine decreased atazanavir AUC by ~20%. In the ABSENCE OF TENOFOVIR, the SmPC recommends no dose modification of atazanavir/ritonavir if the cimetidine dose does not exceed that comparable to famotidine 20 mg twice daily; at higher doses of cimetidine, atazanavir/ritonavir should be increased to 400/100 mg once daily. In the PRESENCE OF TENOFOVIR, the SmPC recommends atazanavir/ritonavir should be increased to 400/100 mg once daily. The US Prescribing Information states that in TREATMENT NAIVE patients, cimetidine should not exceed that comparable to famotidine 40 mg twice daily and atazanavir/ritonavir should be dosed at 300/100 mg once daily either with or at least 10 h after the H2RA. In TREATMENT EXPERIENCED patients, cimetidine should not exceed that comparable to famotidine 20 mg twice daily and atazanavir/ritonavir should be dosed at 300/100 mg once daily either with or at least 10 h after the H2RA. In TREATMENT EXPERIENCED patients WITH TENOFOVIR atazanavir/ritonavir should be increased to 400/100 mg once daily either with or at least 10 h after the H2RA. In TREATMENT EXPERIENCED pregnant patients atazanavir/ritonavir should be increased to 400/100 mg once daily either with or at least 10 h after the H2RA during the second and third trimester. Atazanavir is not recommended for pregnant women during the second and third trimester taking both tenofovir and an H2RA.

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/ritonavir 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. Cisplatin is eliminated renally via OCT2 and MATE1 and in vitro data indicate that ritonavir is a moderate inhibitor of MATE1. Ritonavir could potentially slow down cisplatin renal elimination and thus increase the risk of nephrotoxicity. Close monitoring of renal function is recommended.

Coadministration has not been studied. Citalopram is metabolized by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Atazanavir/ritonavir 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/ritonavir has not been studied. Clarithromycin is metabolized by CYP3A4 and concentrations may be increased due to inhibition of CYP3A4 by atazanavir/ritonavir. In addition, clarithromycin may increase atazanavir/ritonavir plasma concentrations. 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. Alternative antibiotics should be considered.

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. Clindamycin is metabolized by CYP3A4 and coadministration may increase clindamycin concentrations due to inhibition of CYP3A4 by atazanavir/ritonavir. 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. CYP3A4 inhibition by atazanavir + ritonavir may increase clobazam exposure and prolong the duration of its effect, whereas induction of CYP2C19 by ritonavir may decrease N-desmethylclobazam. The net effect of these interactions is unknown. Monitor for side effects and clinical effect. Clobazam is unlikely to significantly impact atazanavir + ritonavir.

Coadministration has not been studied. Clobetasol is a substrate of CYP3A4 and exposure may increase due to inhibition of CYP3A4 by atazanavir/ritonavir. 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. In vitro studies have suggested that transformation of clomifene to its active metabolite is likely to be mediated via CYP2D6. Atazanavir/ritonavir might increase clomifene exposure, although to a moderate extent, via CYP2D6 inhibition. No a priori dosage adjustment is recommended.

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. Coadministration could potentially increase clomipramine concentrations. 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 of clopidogrel and boosted regimens has been evaluated in clinical studies. Clopidogrel is a prodrug and is converted to its active metabolite via CYPs 3A4, 2B6, 2C19 and 1A2. 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 boosted regimens, 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/ritonavir 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/ritonavir 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/ritonavir 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. Cocaine is metabolized by several pathways, with metabolism to norcocaine by CYP3A4 being less than 10% of the overall metabolic clearance. Atazanavir/ritonavir 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. Codeine is a substrate of CYP2D6 (major) and CYP3A4. Ritonavir inhibits CYP2D6 at higher doses, but at the 100 mg dose ritonavir does not appear to markedly inhibit CYP2D6. While no a priori dose adjustment is required, monitoring the analgesic effect is recommended as the analgesic effect requires conversion of codeine to morphine via CYP2D6 and ritonavir could potentially reduce the analgesic efficacy.

Coadministration has not been studied and is expected to increase colchicine concentrations. Ritonavir (100 mg twice daily) significantly increased colchicine Cmax (2.7-fold) and AUC (3.5-fold) when given with a single dose of colchicine (0.6 mg). Atazanavir/ritonavir 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. When coadministered 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. When coadministered 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. When coadministered 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. 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/ritonavir 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 but based on metabolism and clearance, a clinically significant interaction is unlikely. Although several constituents of Piper cubeba were shown to inhibit CYP3A4 in vitro, any additional effect on exposure of atazanavir in the presence of ritonavir or cobicistat is unlikely.

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. Cyclophosphamide is metabolized by two pathways. Activation (major pathway) to 4-hydroxycyclophosphamide is catalyzed by CYPs 2B6 (major), 2C9 and 3A4. Inactivation (minor, 10%) to the neurotoxic chloroacetaldehyde metabolite is performed mainly by CYP3A4. The net effect on the activation pathway is difficult to predict as atazanavir/ritonavir inhibit CYP34 but in vivo data indicate that ritonavir induces CYP2B6. In theory, atazanavir/ritonavir 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/ritonavir. 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. 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 HIV negative subjects. Simultaneous administration did not significantly change dabigatran PK (possibly due to mixed induction and inhibition of P-gp by ritonavir as dabigatran is a substrate of P-gp). 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 used once daily to boost protease inhibitors such as atazanavir in patients with no renal impairment. 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/ritonavir. Note, dabigatran is not recommended in patients with severe renal impairment.

Coadministration has not been studied. Dacarbazine undergoes activation to MTIC primarily via CYP1A2 and to a lesser extent by CYP2E1, with CYP1A1 having a role in extrahepatic metabolism. In vitro data indicate that ritonavir induces CYP1A2. Atazanavir/ritonavir may increase the conversion to MTIC and thereby increase the efficacy and toxicity of dacarbazine. Monitor side effects.

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.

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, however, atazanavir/ritonavir may affect dapagliflozin due to UGT induction by ritonavir. A clinically relevant effect is not expected as coadministration of dapagliflozin with rifampicin (an inducer of several UGT enzymes) decreased dapagliflozin systemic exposure by 22% but had no clinically meaningful effect on 24-hour urinary glucose excretion. No dose adjustment is recommended.

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. 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/ritonavir), 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 and is not recommended. Appropriate doses of this combination with respect to safety, efficacy and pharmacokinetics of atazanavir have not been established.

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, atazanavir/ritonavir should not be used in combination with medicinal products containing cobicistat due to similar effects of cobicistat and ritonavir on CYP3A.

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. A clinical study reported that ritonavir had no effect on daunorubicin (liposomal) pharmacokinetics. An in vitro study has shown that daunorubicin was able to inhibit metabolism mediated by CYP3A4, but was unlikely to cause clinically significant drug interactions via this mechanism. 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/ritonavir 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. 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/ritonavir 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. Desipramine is metabolized by CYP2D6 and atazanavir/ritonavir could potentially increase desipramine 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; desipramine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

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 is predicted to increase etonogestrel (induction of CYP2C9 and inhibition of CYP3A4) and to moderately decrease ethinylestradiol (induction of glucuronidation by ritonavir). Contraceptive efficacy is likely to be maintained if atazanavir/ritonavir is used with a desogestrel COC which contains at least 30 µg 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/ritonavir.

Coadministration has not been studied. Dexmedetomidine undergoes extensive hepatic biotransformation through direct glucuronidation (mainly via UGT1A4, 2B10) and cytochrome P450 (mainly 2A6). Study data indicate that ritonavir decreases exposure of lamotrigine, a UGT1A4 probe substrate. Atazanavir/ritonavir could potentially decrease dexmedetomidine concentrations. No a priori dosage adjustment is recommended but monitor clinical effect. 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 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/ritonavir 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). As ritonavir induces glucuronidation, atazanavir/ritonavir could potentially decrease the analgesic effect although to a moderate extent as induction of glucuronidation may increase the formation of the active metabolite. Additionally, 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. No a priori dosage adjustment is recommended but 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/ritonavir 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. In vivo data indicate that ritonavir is a weak inducer of CYP2C9, however a dose adjustment is unlikely to be required for diclofenac.

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/ritonavir 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. The increased digoxin level may lessen over time as P-gp induction develops reason why digoxin levels should be monitored periodically. 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/ritonavir could potentially increase dihydrocodeine exposure (inhibition of CYP3A4 and CYP2D6) and increase the conversion to dihydrocodeine-6-glucuronide (induction of UGT2B7). 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 with atazanavir/ritonavir has not been studied. 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. No data are available for diltiazem and atazanavir/ritonavir. 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. Diphenhydramine is mainly metabolized by CYP2D6. Atazanavir/ritonavir could potentially increase diphenhydramine concentrations although to a moderate extent. No a priori dosage adjustment is recommended.

Coadministration has not been studied. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Ritonavir induces glucuronidation and atazanavir/ritonavir could potentially decrease dipyridamole exposure, thereby reducing the antiplatelet effect.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of disulfiram (62.5 mg or 250 mg once daily) with atazanavir (400 mg once daily) or ritonavir (100 mg twice daily) had no significant effect on atazanavir or ritonavir pharmacokinetics at either dose. Disulfiram is converted to an active metabolite by CYP3A4 and UGT. Coadministration of atazanavir alone with disulfiram 250 mg was associated with a lack of disulfiram‐associated inhibition of ALDH activity. However, no effect is expected with atazanavir/ritonavir due to ritonavir’s mixed effect on CYP3A4 (inhibition) and UGT (induction).

Coadministration has not been studied and is not recommended. Coadministration with ritonavir 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 boosted protease inhibitors or consider using an alternative taxane.

Coadministration has not been studied and is not recommended. Dofetilide is metabolized to a small degree by CYP3A4 and therefore atazanavir/ritonavir 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/ritonavir (300/100 mg once daily) and dolutegravir (30 mg once daily) increased dolutegravir Cmax and AUC by 34% and 62%, and increased Ctrough by 2.21-fold. Compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of atazanavir. 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.

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/ritonavir would be possible from a pharmacokinetic standpoint. Coadministration of atazanavir/ritonavir and dolutegravir increased dolutegravir AUC, Cmax and Ctrough by 62%, 34% and 121%, respectively. There was no effect on atazanavir or ritonavir. 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. No interaction is expected with lamivudine.

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/ritonavir would be possible from a pharmacokinetic standpoint. The European product label for Dovato advises that no dose adjustment is necessary with atazanavir/ritonavir. Coadministration of atazanavir/ritonavir and dolutegravir increased dolutegravir AUC, Cmax and Ctrough by 62%, 34% and 121%, respectively. There was no effect on atazanavir or ritonavir. No interaction is expected with lamivudine.

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/ritonavir would be possible from a pharmacokinetic standpoint. Coadministration of atazanavir/ritonavir (300/100 mg once daily) and dolutegravir (30 mg once daily) increased dolutegravir Cmax and AUC by 34% and 62%, and increased Ctrough by 2.21-fold. Compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of atazanavir. Coadministration of rilpivirine with atazanavir/ritonavir) 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/ritonavir. 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/ritonavir. Domperidone is mainly metabolized by CYP3A4. Atazanavir/ritonavir 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 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/ritonavir, or to be affected if co-administered with atazanavir/ritonavir.

Coadministration has not been studied. Coadministration with ritonavir increased doravirine AUC by 3.5-fold and Cmin by 2.9-fold. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Delstrigo (doravirine, lamivudine, tenofovir-DF) 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/ritonavir would be possible from a pharmacokinetic standpoint, but with close monitoring for tenofovir-associated adverse events. Coadministration with ritonavir increased doravirine AUC by 3.5-fold and Cmin by 2.9-fold, but no dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3- to 4-fold increase in exposure. In a combined analysis of several clinical studies with tenofovir-DF (300 mg) and atazanavir/ritonavir (300/100 mg), tenofovir AUC, Cmax and Cmin increased by 37%, 34% and 29%, respectively. Thus, patients should be closely monitored for tenofovir-associated adverse events, including renal disorders. Atazanavir/r should be dosed at 400/100 mg once daily in presence of tenofovir-DF and an H2-receptor antagonist due to the resulting decrease in atazanavir exposure.

Coadministration has not been studied. Doxazosin is metabolized mainly by CYP3A4 and coadministration may increase doxazosin exposure which can result in hypotension. For patients already taking atazanavir/ritonavir, start doxazosin at the lowest dose (i.e., 1 mg daily) and increase dose slowly based on tolerance until an effective dose is reached. For patients already taking doxazosin, monitor blood pressure and reduce doxazosin dose as needed if hypotension occurs on starting atazanavir/ritonavir.

Coadministration has not been studied. Doxepin is metabolized to nordoxepin (a metabolite with comparable pharmacological activity as the parent compound) mainly by CYP2C19. In addition, doxepin and nordoxepin are metabolized by CYP2D6. Atazanavir/ritonavir could potentially increase doxepin exposure although to a moderate extent. No a priori dose adjustment is recommended. Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, the risk of QT prolongation when combining these drugs is considered to be small given the limited PK drug-drug interaction.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Doxorubicin is mainly eliminated in the bile and does not undergo CYP-mediated metabolism. (Some product labels suggest doxorubicin is a substrate of CYP3A4, however, there are no strong data supporting the role of CYP3A4 in doxorubicin metabolism.) Doxorubicin is a substrate of P-glycoprotein, but coadministration with protease inhibitors did not modify significantly doxorubicin exposure. However caution is advised due to possible cardiac toxicities (ECG abnormalities and sometimes arrhythmias). Use with caution. ECG monitoring is recommended.

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

Coadministration has not been studied. Droloxifene is mainly glucuronidated (by several UGTs) and coadministration could potentially decrease droloxifene exposure due to induction of glucuronidation by ritonavir. Monitor droloxifene therapeutic effect.

Coadministration has not been studied. Dronabinol is mainly metabolized by CYP2C9 and to a lesser extent by CYP3A4. In vitro and in vivo data indicate that ritonavir is a weak inducer of CYP2C9 and a strong inhibitor of CYP3A4. The net clinical effect of this interaction is difficult to predict as atazanavir/ritonavir could potentially decrease dronabinol concentrations (induction of CYP2C9) or increase dronabinol concentrations (inhibition of CYP3A4). No a priori dosage adjustment is recommended.

Coadministration with a drospirenone-containing combined oral contraceptive (COC) has not been studied. Drospirenone is metabolised in part by CYP3A4. Coadministration is predicted to increase drospirenone exposure and to moderately decrease ethinylestradiol exposure (induction of glucuronidation by ritonavir). Clinical monitoring is recommended due to the potential risk for hyperkalaemia. However, contraceptive efficacy is likely to be maintained if atazanavir/ritonavir is used with a drospirenone COC which contains at least 30 µg ethinylestradiol.

Coadministration with drospirenone as hormone replacement therapy (HRT) has not been studied. CYP3A4 contributes to drospirenone metabolism. Coadministration is predicted to increase drospirenone exposure and clinical monitoring is recommended due to the potential risk for hyperkalaemia. 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 contrast, exposure of estrogens/estradiol administered as part of HRT may decrease. Monitor for signs of hormone deficiency. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary. 

Coadministration has not been studied. Dulaglutide is degraded by general protein catabolism pathways therefore no metabolic interaction is expected. Dulaglutide delays gastric emptying but interaction studies showed no clinically significant effect on the absorption of concomitantly orally administered drugs. However, caution is needed when coadministering atazanavir and GLP-1 agonists such as dulaglutide due to their potential to inhibit gastric secretion and thereby reduce the absorption of atazanavir. Consider monitoring virological response after initiating dulaglutide.

Coadministration has not been studied. Duloxetine is metabolized by CYP2D6 and CYP1A2. In vitro data indicate that ritonavir induces CYP1A2 but inhibits CYP2D6. The net clinical effect of this interaction is difficult to predict, but is expected to be of weak intensity. No a priori dosage adjustment is recommended.

Coadministration has not been studied. Dutasteride is mainly metabolized by CYP3A4. Atazanavir/ritonavir could potentially increase dutasteride concentrations. A reduction of dutasteride dosing frequency can be considered if side effects are noted.

Coadministration with dydrogesterone as hormone replacement therapy (HRT) has not been studied. Dydrogesterone is metabolized to dihydrodydrogesterone (possibly via CYP3A4). Coadministration is predicted to increase dydrogesterone exposure due to inhibition of CYP3A4. 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 is unknown. In contrast, exposure of estrogens/estradiol administered as part of HRT may decrease. Monitor for signs of hormone deficiency. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Studies using a cocktail of probe drugs showed Echinacea inhibited CYP1A2 and intestinal CYP3A activity, and induced hepatic CYP3A activity. However, coadministration of Echinacea and lopinavir/ritonavir showed no clinically significant effect of Echinacea on lopinavir or ritonavir concentrations (most likely due to the potent CYP3A inhibition by ritonavir). Based on these data, Echinacea is unlikely to alter atazanavir/ritonavir exposure.

Coadministration has not been studied. MDMA is metabolized mainly by CYP2D6. Atazanavir/ritonavir could potentially increase MDMA concentrations. Ensure the patient is aware of signs/symptoms of MDMA toxicity.

Coadministration has not been studied. Edoxaban is a substrate for P-gp and coadministration is expected to increase edoxaban concentrations due to P-gp inhibition. The European product label for edoxaban states to consider a dose reduction of edoxaban from 60 mg to 30 mg with strong P-gp inhibitors, however, the US product label recommends no dose modification.

Coadministration has not been studied. The European product label for atazanavir does not recommend coadministration, but if the combination is required suggests to consider increasing atazanavir/ritonavir to 400/200 mg once daily with close clinical monitoring. Based on historical comparison, atazanavir AUC, Cmax and Cmin were unchanged with coadministration of atazanavir/ritonavir (400/200 mg once daily) and efavirenz (600 mg once daily). The US Prescribing Information suggests atazanavir/ritonavir 400/100 mg for treatment naive patients, but advises not to coadminister to treatment experienced patients. Coadministration of atazanavir/ritonavir (400/100 mg once daily) and efavirenz (600 mg once daily) had no effect on atazanavir AUC, increased Cmax by 17% and decreased Cmin by 42%. Furthermore, a prolongation of the QT interval may occur with efavirenz treatment in carriers of CYP2B6*6/*6. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval. Efavirenz 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. Eflornithine is predominantly eliminated unchanged via the kidneys.

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

Coadministration has not been studied. Eltrombopag is metabolised by cleavage conjugation (UGTs 1A1 and 1A3) and oxidation (CYPs 1A2 and 2C8). Coadministration of eltrombopag (100 mg single dose) with lopinavir/ritonavir decreased eltrombopag AUC by 17%. Similarly, atazanavir/ritonavir could potentially decrease eltrombopag exposure. Caution should be used when coadministering these drugs and platelet count monitoring is recommended.

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and coadministration with other antiretroviral agents is not recommended in the Genvoya product labels. Atazanavir/ritonavir should not be used in combination with medicinal products containing cobicistat due to similar effects of cobicistat and ritonavir on CYP3A. Coadministration would be possible with unboosted atazanavir in clinical situations requiring treatment intensification. 

Stribild (elvitegravir, cobicistat, emtricitabine, 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 in the Stribild product labels. Atazanavir/ritonavir should not be used in combination with medicinal products containing cobicistat due to similar effects of cobicistat and ritonavir on CYP3A. Coadministration would be possible with unboosted atazanavir in clinical situations requiring treatment intensification. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Empagliflozin is metabolised by UGTs and is a substrate of P-gp, BCRP, OAT3 and OATP1B1/1B3. Although atazanavir/ritonavir inhibits P-gp and OATP, data with verapamil (a P-gp inhibitor) and rifampicin (an OATP1B1/1B3 inhibitor) suggest a clinically relevant effect on empagliflozin is unlikely.

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

Coadministration of atazanavir/ritonavir (300/100 mg once daily) and emtricitabine/tenofovir alafenamide (200/10 mg once daily) increased tenofovir AUC and Cmax by 162% and 112% (n=10). No significant effects were observed on atazanavir pharmacokinetics relative to historical controls. When administered with atazanavir/ritonavir, the recommended dose of Descovy is 200/10 mg once daily (where available).

Coadministration with emtricitabine/tenofovir-DF has not been studied. Coadministration of tenofovir-DF (300 mg once daily) and atazanavir/ritonavir (300/100 mg once daily) was studied in 12 subjects. Atazanavir AUC, Cmax and Cmin decreased by 25%, 28% and 26%, respectively. Tenofovir AUC, Cmax and Cmin increased by 37%, 34% and 29%, respectively. No dose adjustment is recommended. The increased exposure of tenofovir could potentiate tenofovir associated adverse events, including renal disorders. Renal function should be closely monitored. In HIV-1 infected patients with renal risk factors, the co-administration of tenofovir-DF with a boosted protease inhibitor should be carefully evaluated.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enalapril is hydrolysed to enalaprilat which is eliminated renally (possibly via OATs). Atazanavir/ritonavir is unlikely to inhibit the renal transporters OATs at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enflurane is predominantly metabolized by CYP2E1. There is no evidence that atazanavir/ritonavir inhibits or induces this metabolic enzyme.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Enoxaparin does not undergo cytochrome metabolism but is desulphated and depolymerised in the liver, and is predominantly excreted renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Entecavir is eliminated renally via glomerular filtration and active renal secretion by both organic anions and cations transporters. Atazanavir/ritonavir 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. Ephedrine is predominantly eliminated unchanged via the kidneys. Atazanavir/ritonavir is unlikely to inhibit OCTs at clinically relevant concentrations.

Coadministration has not been studied. Epirubicin is glucuronidated by UGT2B7. Atazanavir/ritonavir could potentially reduce epirubicin concentrations (induction of UGT2B7 by ritonavir) and thus decrease the efficacy. Epirubicin may lead to cardiotoxicity consisting of tachycardia and/or ECG abnormalities. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; epirubicin has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied and is contraindicated. Eplerenone is metabolized by CYP3A4 and coadministration is expected to substantially increase eplerenone exposure due to inhibition of CYP3A4 and thereby increase the risk of hyperkalaemia. Coadministration of ketoconazole, a strong CYP3A4 inhibitor, increased eplerenone AUC by 441%. There is a case report of a patient on fosamprenavir/ritonavir developing severe hyperkalaemia when eplerenone was initiated.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Epoprostenol is rapidly hydrolyzed in the blood.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eprosartan is largely excreted in bile and urine as unchanged drug.

Coadministration has not been studied and is contraindicated due to potential for serious and/or life threatening events such as acute ergot toxicity.

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

Coadministration has not been studied. Erlotinib is mainly metabolized by CYP3A4 and coadministration could potentially increase erlotinib concentrations. Ketoconazole (a strong CYP3A4 inhibitor) increased erlotinib AUC by 86%. As erlotinib is dosed at/near the maximum tolerated dose (MTD), any increase in erlotinib exposure may lead to toxicity. Coadministration of a potent CYP3A4 inhibitor should be avoided, but if this is not possible, use with caution and close monitoring for erlotinib mediated toxicity is necessary. The erlotinib dose should be reduced in 50 mg increments if toxicity is observed.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ertapenem is mainly eliminated through the kidneys by glomerular filtration with tubular secretion playing a minor role.

Coadministration has not been studied but may increase erythromycin concentrations due to inhibition of CYP3A4 by atazanavir/ritonavir. Use with caution and monitor for erythromycin-related adverse effects, especially cardiac adverse events as erythromycin is known to induce QT interval prolongation. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; erythromycin has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

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

Coadministration has not been studied. Eslicarbazepine is partly eliminated unchanged renally and partly glucuronidated by UGT2B4. Eslicarbazepine is a weak/moderate inducer of CYP3A4. Coadministration could potentially reduce atazanavir + ritonavir concentrations, leading to loss of therapeutic effect and possible development of resistance. Consider use of other anticonvulsants. If coadministration is necessary, closely monitor virological response and monitor atazanavir + ritonavir plasma concentrations (when possible). Note, PR interval monitoring may be warranted in patients with underlying block or those receiving known atrioventricular nodal blocking agents.

Coadministration of atazanavir with proton pump inhibitors is not recommended. No data are available with esomeprazole; lansoprazole decreased atazanavir AUC by 94%, omeprazole decreased atazanavir AUC by 75%. If coadministration is judged unavoidable, close clinical monitoring is recommended and doses of proton pump inhibitors comparable to omeprazole 20 mg should not be exceeded and must be taken approximately 12 hours prior to the atazanavir/ritonavir. The European SmPC recommends increasing the dose of atazanavir to 400 mg with 100 mg of ritonavir.

Coadministration has not been studied. Estazolam is metabolized to its major metabolite 4-hydroxyestazolam via CYP3A4. Atazanavir/ritonavir could potentially increase estazolam exposure. This could prolong sedation and a dosage reduction may be required.

Coadministration with estradiol as hormone replacement therapy (HRT) has not been studied. Estradiol is metabolized by CYP3A4, CYP1A2 and is glucuronidated. Coadministration could potentially decrease estradiol exposure due to induction of CYP1A2 and glucuronidation (rather than increase it due to inhibition of CYP3A4). Monitor for signs of estrogen deficiency.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Estramustine phosphate undergoes rapid dephosphorylation to yield estramustine which is then oxidized by 17B-hydroxysteroid dehydrogenases to estromustine. Estramustine and estromustine are subsequently metabolized to estradiol and estrone, respectively. Estradiol is then hydroxylated by CYP1A1, 1A2 and 3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethambutol is partly metabolized by alcohol dehydrogenase (20%) and partly eliminated unchanged in the faeces (20%) and in the urine (50%).

Coadministration of atazanavir/ritonavir (300/100 mg once daily) and ethinylestradiol (25 µg, with norgestimate) decreased ethinylestradiol AUC, Cmax and Cmin by 19%, 16% and 37%, respectively (induction of glucuronidation by ritonavir). The US Prescribing Information for atazanavir states that the oral contraceptive should contain should contain at least 35 µg of ethinylestradiol if coadministered with atazanavir/ritonavir. The European SmPC for atazanavir recommends that if an oral contraceptive is administered with atazanavir/ritonavir, that the oral contraceptive should contain at least 30 µg of ethinylestradiol. Coadministration with non-oral hormonal contraceptives, progestogens other than norethindrone or norgestimate, or less than 25 µg of ethinylestradiol, has not been studied. Note, use of ethinylestradiol as part of gender affirming treatment is not recommended due to thrombotic risks.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethionamide is extensively metabolized in the liver and animal studies suggest involvement of flavin-containing monooxygenases. Ethionamide does not affect metabolism mediated by CYP450 enzymes in vitro.

Coadministration has not been studied but may increase ethosuximide concentrations. Use with caution and perform therapeutic drug monitoring for ethosuximide.

Coadministration has not been studied. Etidocaine is metabolized by CYP3A4 and concentrations may increase due to inhibition of CYP3A4 by atazanavir/ritonavir. Use with caution.

Etonogestrel is metabolized by CYP3A4. Etonogestrel concentrations were measured in postpartum women (n=22) with an etonogestrel-containing progestogen-only implant receiving an atazanavir/ritonavir-based regimen. Median serum concentrations of etonogestrel were 604 pg/mL and were above the target minimum serum etonogestrel concentration for ovulation suppression (i.e., 90 pg/mL). Atazanavir and ritonavir pharmacokinetics were not significantly altered by etonogestrel. These data suggest that atazanavir/ritonavir is not expected to impair the contraceptive efficacy of etonogestrel when administered as an implant.

The use of a combined vaginal ring (CVR) releasing etonogestrel/ethinylestradiol (120/15 µg/day) in HIV positive women treated with an atazanavir/ritonavir containing regimen (300/100 mg once daily) increased etonogestrel exposure by 71% and decreased ethinylestradiol exposure by 38% compared to exposure of hormones in HIV positive women not yet on ART. All participants had endogenous progesterone values below the level of detection (0.5 ng/ml) by day 14 and remained undetectable through day 28. Thus, atazanavir/ritonavir is unlikely to influence the contraceptive effectiveness of the vaginal ring as etonogestrel exposure was higher than the control group. However, reduced ethinylestradiol may lead to more unscheduled bleeding. There was no clinically significant effect on the pharmacokinetics of atazanavir (Cmax, Cmin and AUC decreased by 24%, 30% and 23%) or ritonavir (Cmax, Cmin and AUC decreased by 41%, 33% and 37%).

Coadministration has not been studied. Etoposide is partly metabolized by CYP3A4 to reactive catechol metabolites. Conversion to reactive metabolites can also be mediated by prostaglandin synthase or myeloperoxidase. Furthermore, etoposide is partly glucuronidated by UGT1A1. Ketoconazole (a strong CYP3A4 inhibitor) increased etoposide exposure by 20%. The net effect of this interaction is difficult to predict as atazanavir/ritonavir could potentially increase (inhibition of CYP3A4) or decrease (induction of UGT1A1) etoposide exposure. Close monitoring of etoposide induced toxicity and efficacy is recommended. Adjust dose if clinically necessary or consider selection of an alternate non-CYP inhibiting antiretroviral regimen.

Coadministration of atazanavir/ritonavir (300/100 mg once daily) and etravirine decreased atazanavir AUC, Cmin and Cmax by 14%, 38% and 3%, respectively. Etravirine AUC, Cmin and Cmax increased by 30%, 26% and 30%. The decrease in atazanavir Cmin is unlikely to be clinically significant and no dose adjustment is required.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Eucalyptus is only a weak inhibitor of CYP3A4 and any additional effect on exposure of atazanavir in the presence of ritonavir is unlikely.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Evolocumab 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. Exemestane is metabolised by CYP3A4 but coadministration with ketoconazole (a potent CYP3A4 inhibitor) showed no clinically significant effects and no effect is expected due to inhibition of CYP3A4 by atazanavir/ritonavir. No a priori dose adjustment is required.

Coadministration has not been studied. Exenatide is primarily eliminated by glomerular filtration therefore no interaction is expected at the level of drug elimination. However, caution is needed when coadministering atazanavir and GLP-1 agonists such as exenatide due to their potential to inhibit gastric secretion and thereby reduce the absorption of atazanavir. Furthermore, exenatide has the potential to slow gastric emptying. Consider taking atazanavir/ritonavir 2-4 hours before the GLP-1 agonist.

Coadministration has not been studied. Ezetimibe is glucuronidated by UGTs 1A1 and 1A3 and to a lesser extent by UGTs 2B15 and 2B7. Ezetimibe is a substrate of OATP1B1. Atazanavir/ritonavir could potentially increase ezetimibe exposure. Start with the lowest possible dose. Close monitoring is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Famciclovir is converted to penciclovir by aldehyde oxidase. Penciclovir is secreted in the urine possibly by OAT1. Atazanavir/ritonavir is unlikely to inhibit OATs at clinically relevant concentrations.

H2-receptor antagonists reduce the absorption of atazanavir, but the extent of the interaction can depend on dose and timing of administration. Famotidine decreased atazanavir AUC by ~20%. In the ABSENCE OF TENOFOVIR, the SmPC recommends no dose modification of atazanavir/ritonavir if the famotidine dose does not exceed 20 mg twice daily; at higher doses of famotidine, atazanavir/ritonavir should be increased to 400/100 mg once daily. In the PRESENCE OF TENOFOVIR, the SmPC recommends atazanavir/ritonavir should be increased to 400/100 mg once daily. The US Prescribing Information states that in TREATMENT NAIVE patients, famotidine should not exceed 40 mg twice daily and atazanavir/ritonavir should be dosed at 300/100 mg once daily either with or at least 10 h after the H2RA. In TREATMENT EXPERIENCED patients, famotidine should not exceed 20 mg twice daily and atazanavir/ritonavir should be dosed at 300/100 mg once daily either with or at least 10 h after the H2RA. In TREATMENT EXPERIENCED patients WITH TENOFOVIR atazanavir/ritonavir should be increased to 400/100 mg once daily either with or at least 10 h after the H2RA. In TREATMENT EXPERIENCED pregnant patients atazanavir/ritonavir should be increased to 400/100 mg once daily either with or at least 10 h after the H2RA during the second and third trimester. Atazanavir is not recommended for pregnant women during the second and third trimester taking both tenofovir and an H2RA.

Coadministration has not been studied. Caution is warranted as atazanavir/ritonavir could increase concentrations of felodipine. Consider dose titration of felodipine. ECG monitoring is recommended.

Coadministration has not been studied. Data from an interaction study with fenofibrate (145 mg single dose) and lopinavir/ritonavir (400/100 mg twice daily) or ritonavir alone (100 mg twice daily) suggest that an interaction is unlikely to occur in patients taking ritonavir-boosted regimens. Fenofibrate AUC and Cmax decreased by 14% and 3% with lopinavir/ritonavir and by 11% and 1% with ritonavir alone.

Coadministration has not been studied. Fentanyl undergoes extensive CYP3A4 metabolism. Coadministration may increase fentanyl concentrations due to inhibition of CYP3A4, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. Monitor patients closely at frequent intervals and consider dosage reduction of fentanyl until stable drug effects are achieved. Discontinuation of a CYP3A4 inhibitor could decrease fentanyl concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to fentanyl. When discontinuing CYP3A4 inhibitors in fentanyl-treated patients, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur. Note, the use of fentanyl in a non-therapeutic setting (i.e., as a recreational drug) should be avoided with atazanavir/ritonavir as fentanyl exposure is expected to significantly increase and serious, life-threatening, or fatal respiratory depression may occur. Patients should be aware that recreational use could be potentially fatal.

Coadministration has not been studied. Fesoterodine is rapidly hydrolysed to its active metabolite which is subsequently metabolized by CYP2D6 and CYP3A4. Concentrations of the active metabolite of fesoterodine are likely to increase due to inhibition of CYP3A4. The maximum daily dose of fesoterodine should not exceed 4 mg when used concomitantly with potent CYP3A4 inhibitors such as atazanavir/ritonavir.

Coadministration has not been studied. Fexofenadine does not undergo CYP mediated metabolism but is a substrate of P-gp/OATP. Atazanavir/ritonavir could potentially increase fexofenadine exposure by inhibition of P-gp/OATP. However, due to the large therapeutic index of fexofenadine, no dosage adjustment is recommended.

Coadministration has not been studied. Finasteride is metabolised by CYP3A4 and coadministration may increase finasteride concentrations. However, any increase is unlikely to be of clinical significance due to finasteride’s wide margin of safety and no a priori dose alteration is recommended.

Coadministration has not been studied in humans but based on metabolism and clearance a clinically significant interaction is unlikely. Fish oils inhibited CYP3A-mediated metabolism of saquinavir in rat liver microsomes. Simultaneous coadministration with saquinavir in rats increased saquinavir exposure by ~3-fold. Separating the doses by 2 h overcame the interaction.

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

Coadministration has not been studied. Flibanserin is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C19. Coadministration of flibanserin with moderate or strong inhibitors of CYP3A4 (such as atazanavir/ritonavir) is contraindicated due to increased flibanserin concentrations which can cause severe hypotension and syncope.

Coadministration has not been studied. Flucloxacillin is mainly eliminated renally partly by glomerular filtration and partly by active secretion via OAT1. Atazanavir/ritonavir is unlikely to inhibit OATs at clinically relevant concentrations. Flucloxacillin is thought to be a weak inducer of CYP3A4 particularly at higher doses (>2-3 g daily). A modest reduction in atazanavir/ritonavir concentrations may be observed but this is unlikely to be clinically relevant unless flucloxacillin is prescribed at higher doses for a prolonged course (> 10-14 days).

Coadministration of atazanavir/ritonavir (300/100 mg once daily) and fluconazole (200 mg once daily) resulted in no clinically significant interaction. No dosage adjustments are needed for atazanavir/ritonavir and fluconazole. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; fluconazole has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. 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. Flucytosine is metabolised to 5-flurouracil which is further metabolised by dihydropyrimidine dehydrogenase.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fludarabine phosphate is rapidly metabolized to 2F-ara-A, the principal metabolite (non CYP mediated metabolism) which is then eliminated renally.

Coadministration has not been studied. Concomitant administration of atazanavir/ritonavir and corticosteroids is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects. Fludrocortisone is a substrate of CYP3A4 and its exposure may increase due to CYP3A4 inhibition by atazanavir/ritonavir. Use alternative treatments.

Coadministration has not been studied. Flunisolide undergoes CYP3A4-mediated metabolism and coadministration may increase flunisolide concentrations. Flunisolide has properties (low binding affinity to glucocorticoid receptors, low lipophilicity and short elimination half-life) associated with a lower propensity to cause a Cushing syndrome. If coadministered with atazanavir/ritonavir, it is recommended to use the lowest possible flunisolide dose with monitoring for corticosteroid side effects.

Coadministration has not been studied. Flunitrazepam is metabolized mainly via CYP3A4 and CYP2C19. Atazanavir/ritonavir could potentially increase flunitrazepam exposure which could result in increased sedation or respiratory sedation. A dosage reduction may be required.

Coadministration has not been studied but may increase fluocinolone concentrations. Careful monitoring of corticoid side effects is recommended. Note, the extent of percutaneous absorption is determined by many factors such as the degree of inflammation or alteration of the skin, the duration, frequency and surface of application and the use of occlusive dressings.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Fluorouracil is metabolised via the same mechanisms as endogenous uracil, including via dihydropyrimidine dehydrogenase. There is therefore little potential for interaction with atazanavir/ritonavir via modulation of, or competition for metabolic pathways. However, the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval; fluorouracil has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Fluoxetine is metabolized by CYPs 2D6 and 2C9 and to a lesser extent by CYPs 2C19 and 3A4 to form norfluoxetine. Atazanavir/ritonavir could potentially increase fluoxetine concentrations although to a moderate extent. No a priori dosage adjustment is recommended. Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, the risk of QT prolongation when combining these drugs is considered to be small given the limited PK drug-drug interaction.

Coadministration has not been studied. Fluphenazine is metabolised by CYP2D6. Atazanavir/ritonavir could potentially increase levels of fluphenazine via inhibition of CYP2D6 metabolism, increasing the likelihood of adverse events. Use with caution due to the risk of QT interval prolongation reported for both drugs. The European SmPC for fluphenazine contraindicates the concurrent use of other drugs that also prolong the QT interval.

Coadministration has not been studied. The metabolism of flurazepam is most likely CYP-mediated. Atazanavir/ritonavir could potentially increase flurazepam exposure which could result in increased sedation or respiratory sedation. A dosage reduction may be required.

Coadministration has not been studied. Concomitant use of atazanavir/ritonavir 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 inhaled or intranasally administered fluticasone propionate. 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.

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

Coadministration has not been studied. Fluvoxamine is metabolized mainly by CYP2D6 and to a lesser extent by CYP1A2. Atazanavir/ritonavir could potentially increase fluvoxamine concentrations although to a moderate extent. No a priori dosage adjustment is recommended. Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, the risk of QT prolongation when combining these drugs is considered to be small given the limited PK drug-drug interaction.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Folic acid is metabolized to dihydrofolic acid and tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide and folate reductases. Atazanavir/ritonavir does not interfere with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely when folic acid is administered in a multivitamin preparation. Folic acid is metabolized to dihydrofolic acid and tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide and folate reductases. Atazanavir/ritonavir does not interfere with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fondaparinux does not undergo cytochrome metabolism but is predominantly eliminated renally.

Coadministration has not been studied. Formestane undergoes reductive metabolism by hepatic hydroxysteroid dehydrogenase and glucuronidation. Coadministration with atazanavir/ritonavir could potentially decrease formestane exposure due to induction of glucuronidation by ritonavir. Monitor formestane therapeutic effect.

Coadministration has not been studied. Formoterol is eliminated primarily by direct glucuronidation, with O-demethylation (by CYPs 2D6, 2C19, 2C9, and 2A6) followed by further glucuronidation being another pathway. As multiple CYP450 and UGT enzymes catalyze the transformation the potential for a pharmacokinetic interaction is low. However, use with caution due to the risk of QT interval prolongation reported for both drugs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Foscarnet is cleared mainly by glomerular filtration.

Coadministration has not been studied. Fosinopril is hydrolysed by esterases in the GI mucosa and liver and is transported by MRP2. Atazanavir + ritonavir may increase fosinopril exposure due to inhibition of MRP2 by ritonavir. The clinical relevance of this interaction is unknown.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Furosemide is glucuronidated mainly in the kidney (UGT1A9) and to a lesser extent in the liver (UGT1A1). A large proportion of furosemide is also eliminated unchanged renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gabapentin is cleared mainly by glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ganciclovir is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporter OAT1. Atazanavir/ritonavir is unlikely to inhibit OATs at clinically relevant concentrations.

A case report describes treatment failure and a reduction of ~70% in atazanavir AUC in a patient consuming garlic cloves (six garlic cloves three times weekly) whilst taking atazanavir/ritonavir (300/100 mg once daily) and tenofovir/emtricitabine. This effect has been attributed to induction of intestinal CYP3A4 and/or P-gp by garlic. Patients should be advised against the use of garlic supplements.

Coadministration has not been studied. Gefitinib is metabolized by CYP3A4 and CYP2D6 and coadministration could potentially increase gefitinib concentrations. Itraconazole (a strong CYP3A4 inhibitor) increased gefitinib exposure by 80%. A similar effect is expected with atazanavir/ritonavir. If coadministration is necessary, close monitoring of gefitinib induced toxicity is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gemcitabine is metabolized in the liver by cytidine deaminase to an inactive metabolite. Atazanavir/ritonavir does not interfere with this metabolic pathway.

Coadministration has not been studied. Gemfibrozil is metabolised mainly by UGT2B7. As ritonavir induces glucuronidation, atazanavir/ritonavir could potentially decrease gemfibrozil exposure, although to a moderate extent. No a priori dosage adjustment is required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as gentamicin is eliminated unchanged predominantly via glomerular filtration.

Coadministration with a gestodene-containing combined oral contraceptive (COC) has not been studied. Gestodene is metabolized by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Coadministration is predicted to increase gestodene exposure and to moderately decrease ethinylestradiol (induction of glucuronidation by ritonavir). Contraceptive efficacy is likely to be maintained if atazanavir/ritonavir is used with a gestodene COC which contains at least 30 µg ethinylestradiol.

Coadministration has not been studied. A case was reported of a patient experiencing a near fatal reaction from a small dose of GHB while on saquinavir and ritonavir (400 mg twice daily). Atazanavir/ritonavir may increase gamma-hydroxybutyrate concentrations. Ensure the patient is aware of signs/symptoms of GHB toxicity.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Although gingerols moderately inhibit CYP3A4 in vitro, any additional effect on exposure of atazanavir in the presence of ritonavir is unlikely.

Coadministration has not been studied but may decrease atazanavir concentrations through induction of CYP3A4 by Ginkgo biloba. This is unlikely to be clinically significant when atazanavir is given with ritonavir.

Coadministration of glecaprevir/pibrentasvir with OATP1B inhibitors, such as atazanavir, is contraindicated due to increased risk of ALT elevations. Coadministration of atazanavir/ritonavir (300/100 mg once daily) and glecaprevir/pibrentasvir increased glecaprevir Cmax, AUC and Cmin by at least 4.06-fold, 6.53-fold and 14.3-fold, respectively. Pibrentasvir Cmax, AUC and Cmin increased by at least 29%, 64% and 129%, respectively (n=12).

Coadministration has not been studied. Glibenclamide is mainly metabolized by CYP3A4 and to a lesser extent by CYP2C9. Atazanavir/ritonavir could potentially increase glibenclamide concentrations. Monitor clinical effect and reduce glibenclamide dosage if needed.

Coadministration has not been studied. Gliclazide is metabolized mainly by CYP2C9 and to a lesser extent by CYP2C19. In vitro and in vivo data indicate that ritonavir is a weak inducer of CYP2C9. Atazanavir/ritonavir could potentially decrease gliclazide concentrations, although to a moderate extent. Monitor clinical effect and increase gliclazide dosage if needed.

Coadministration has not been studied. Glimepiride is mainly metabolized by CYP2C9. In vitro and in vivo data indicate that ritonavir is a weak inducer of CYP2C9. Atazanavir/ritonavir could potentially decrease glimepiride concentrations, although to a moderate extent. Monitor clinical effect and increase glimepiride dosage if needed.

Coadministration has not been studied. Glipizide is mainly metabolized by CYP2C9. In vitro and in vivo data indicate that ritonavir is a weak inducer of CYP2C9. Atazanavir/ritonavir could potentially decrease glipizide concentrations, although to a moderate extent. Monitor clinical effect and increase glipizide dosage if needed.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glyceryl trinitrate is metabolised by aldehyde dehydrogenase-2. Glyceryl trinitrate is not known to induce or inhibit CYP450 enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glycopyrronium bromide is mainly eliminated renally (active secretion via organic cation transporter) and is also partly hydroxylated via multiple CYPs. Inhibition or induction of its metabolism is unlikely to result in a significant change in exposure.