No data with indinavir/ritonavir. Coadministration with indinavir alone to HIV+ subjects showed that abacavir had no significant effect on indinavir concentrations.

Coadministration has been studied but is contraindicated. Abemaciclib is metabolized by CYP3A4 and is a substrate of P-gp and BCRP. Ketoconazole (a strong CYP3A4 and P-gp inhibitor) has been predicted to increase abemaciclib AUC by 1470% and to increase the AUC of abemaciclib’s active metabolites (sum of 3 metabolites) by 615%. A similar effect is expected with indinavir and therefore coadministration should be avoided.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abiraterone is metabolized by CYP3A4 and SULT2A1. A 15% increase in abiraterone exposure has been reported in presence of ketoconazole (a strong CYP3A4 inhibitor) and a similar effect is expected with indinavir/ritonavir, but this is not considered to be clinically relevant.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acetazolamide is primarily excreted unchanged via the kidneys, there is therefore little potential for interaction with indinavir via modulation of, or competition for metabolic pathways.

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.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Adrenaline is rapidly inactivated, mostly in the liver by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). There is therefore little potential for interaction with indinavir via modulation of, or competition for metabolic or elimination pathways.

Coadministration has not been studied but based on the metabolic data there is little potential for pharmacokinetic interactions. 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. Similarly, no significant effect is expected on the pharmacokinetics of indinavir.

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. Indinavir/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 indinavir and 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.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs there is little potential for interaction. Alcuronium is predominantly eliminated unchanged via the kidneys.

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 is contraindicated as it could increase alfuzosin concentrations which can result in hypotension.

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

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

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

Coadministration is contraindicated as it may increase alprazolam concentrations, which could result in serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression.

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 indinavir. Start ambrisentan at 5 mg and closely monitor the patient for tolerability.

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. Indinavir/ritonavir could potentially decrease theophylline concentrations. Monitor plasma concentrations and increase aminophylline dosage if needed. Coadministration of indinavir alone and theophylline showed no clinically significant interactions.

Coadministration is contraindicated as it may increase amiodarone concentrations, which could result in serious and/or life-threatening reactions such as cardiac arrhythmias.

Coadministration has not been studied. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19. Indinavir and indinavir/ritonavir could potentially increase amitriptyline exposure, although to a moderate extent. No a priori dosage adjustment is recommended.

Coadministration of indinavir/ritonavir (800/100 mg twice daily) and amlodipine (5 mg once daily) increased amlodipine AUC and Cmax by ~80%. There was no effect on the pharmacokinetics of indinavir or ritonavir. If coadministration is indicated, consider a dose reduction for amlodipine of 50%. Close 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. Ritonavir dosed as a pharmacokinetic booster is a weak inhibitor of CYP2C8. Indinavir/ritonavir could potentially increase amodiaquine exposure, although to a moderate extent. No a priori dosage adjustment is recommended.

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

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Ampicillin is predominantly eliminated unchanged via renal pathways.

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. Thymoglobulins are cleared by the reticuloendothelial system.

Coadministration has not been studied and is not recommended. Concentrations of apixaban are expected to increase due to potent CYP3A4 and P-gp inhibition by ritonavir. Increased concentrations of apixaban increase the bleeding risk and the combination should be avoided if possible.

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 protease inhibitors have 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apremilast is metabolized by multiple pathways involving hydrolysis, glucuronidation and oxidation by CYP3A4. Coadministration of apremilast with ketoconazole (a strong CYP3A4 inhibitor) increased apremilast AUC by 36%. This effect is not considered to be clinically significant and warrant a dosage adjustment of apremilast. Similarly, indinavir/ritonavir is unlikely to significantly alter apremilast exposure. Furthermore, apremilast has no inhibitory or inducing effects on CYPs or drug transporters. Note: severe diarrhoea, nausea and vomiting can occur within the first few weeks after initiating apremilast treatment. Patients should be instructed to contact their healthcare provider if they experience severe diarrhoea, nausea or vomiting as this could potentially alter the absorption of orally administered antiretroviral drugs.

Coadministration has not been studied 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 indinavir is unlikely.

Coadministration has not been studied. Aripiprazole is metabolized by CYP3A4 and CYP2D6. Indinavir and indinavir/ritonavir could potentially increase aripiprazole concentrations. Monitor adverse effects and decrease aripiprazole dosage if needed. The European SPC 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.

Coadministration with indinavir/ritonavir has not been studied. Coadministration of high doses of ascorbic acid (1000 mg daily) and indinavir alone (800 mg every 8 hours) decreased steady state indinavir Cmax and AUC by 20%, 14% and 32%, respectively (n=7). The mechanism of this interaction and clinical significance are unknown.

Coadministration with indinavir/ritonavir has not been studied. Coadministration of high doses of ascorbic acid (1000 mg daily) and indinavir alone (800 mg every 8 hours) significantly reduced steady state indinavir Cmax and AUC by 20% and 14%, respectively (n=7). The mechanism of this interaction and clinical significance are unknown.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Ashwagandha extracts had no effect on CYP enzymes in vitro.

This interaction has not been studied. Based on the metabolic profiles of both drugs, there is little potential for pharmacokinetic interaction. Limited data suggest that asparaginase is likely to be eliminated by the reticuloendothelial 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 UGT, major UGT1A6).

Coadministration is contraindicated as it may increase astemizole concentrations, which could result in serious and/or life-threatening reactions.

Coadministration has not been studied and is not recommended as both atazanavir and indinavir are associated with indirect (unconjugated) hyperbilirubinemia.

Coadministration has not been studied and is not recommended as both atazanavir and indinavir are associated with indirect (unconjugated) hyperbilirubinemia.

Coadministration has not been studied and is not recommended as both atazanavir and indinavir are associated with indirect (unconjugated) hyperbilirubinemia.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as atenolol is mainly eliminated unchanged by the kidney, both by glomerular filtration and active secretion via the renal transporters OCT2 and MATE1.

Coadministration has not been studied. Atomoxetine is metabolized by CYP2D6. Atomoxetine exposure could potentially increase, although to a limited extent, as ritonavir is a weak inhibitor of CYP2D6 when used as a pharmacokinetic booster. No a priori dosage adjustment is recommended.

Coadministration is likely to increase atorvastatin concentrations. Caution should be exercised if coadministering indinavir and atorvastatin as the risk of myopathy including rhabdomyolysis may be increased. Titrate the atorvastatin dose carefully and use the lowest necessary dose with careful monitoring.

No data with indinavir/ritonavir. Ritonavir may decrease atovaquone concentrations. Coadministration of indinavir alone to HIV- subjects increased atovaquone AUC (13%) and Cmax (16%). Indinavir exposure was decreased by 5-7%. No dosage adjustments are necessary for indinavir or atovaquone when given without ritonavir, but careful monitoring of therapeutic and adverse effects is recommended.

This interaction has not been studied. Based on the metabolism/elimination profiles of both drugs, there is little potential for interaction when atropine is used either systemically or as eye drops. Although metabolism of atropine is not fully elucidated, up to 50% is excreted unchanged via the kidneys. There is therefore little potential for clinically significant interactions with lopinavir via modulation of, or competition for metabolic pathways.

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 indinavir.

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

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

Coadministration has not been studied. Azilsartan is metabolized mainly by CYP2C9. In vitro and in vivo data indicate that ritonavir is a modest inducer of CYP2C9. Indinavir/ritonavir could potentially decrease azilsartan concentrations, however, the clinical relevance of this is unknown. No a priori dose adjustment is required.

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

Coadministration with bazedoxifene alone or coformulated with conjugated estrogens as hormone replacement therapy (HRT) has not been studied. Bazedoxifene is glucuronidated by UGT1A1/8/10 and conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Coadministration could potentially decrease exposure of bazedoxifene and conjugated estrogens due to induction of CYP1A2 and glucuronidation. Monitor for signs of estrogen deficiency.

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 diproprionate (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. No significant effect on adrenal function was seen with either ritonavir or darunavir/ritonavir. Although statistically significant, the 2-fold increase in AUC of the active metabolite seen with ritonavir is unlikely to be of clinical significance. Use the lowest possible corticosteroid dose with caution and monitor for corticosteroid side effects.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Belatacept is a protein that undergoes non-CYP mediated metabolism in the liver.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benazepril is rapidly hydrolyzed to its active metabolite benazeprilat which is eliminated predominantly renally.

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. 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.

Coadminsitration is contraindicated with indinavir/ritonavir in the European SPC, but caution is advised with indinavir in the US Prescribing Information. If administered with indinavir, therapeutic concentration monitoring is recommended for antiarrhythmics.

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 indinavir or indinavir/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 indinavir) 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. 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 pharmacokinetic interaction is unlikely as bevacizumab is metabolized via proteolytic catabolism.

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) 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 indinavir or indinavir/ritonavir would be possible from a pharmacokinetic standpoint. The recommended dose of 10 mg tenofovir alafenamide with P-gp inhibitors is not possible with Biktarvy which is only available as a fixed dose combination containing 25 mg tenofovir alafenamide, but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile.

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. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the kidney. Indinavir and indinavir/ritonavir could potentially increase bisoprolol 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. No effect on indinavir 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. An indirect effect of blinatumomab on CYPs may occur due to transient release of cytokines during the first days of therapy which can inhibit CYP450 metabolism, however, this is unlikely to be clinically relevant. The metabolic pathway of blinatumomab has not been characterised. Like other protein therapeutics, blinatumomab is expected to be degraded into small peptides and amino acids via catabolic pathways.

Coadministration may increase bosentan concentrations and decrease indinavir concentrations. When starting bosentan in patients on indinavir, or starting indinavir in patients on bosentan, start at or adjust bosentan to 62.5 mg once daily or every other day based upon individual tolerability. A case has been reported with unboosted indinavir of a possible reduction in indinavir concentrations. Indinavir trough concentrations were sub-therapeutic (<0.05 mg/L) when bosentan was added to a regimen of abacavir, tenofovir and indinavir (800 mg three times daily). Increasing indinavir to 1000 mg three times daily failed to result in therapeutic concentrations. Despite sub-therapeutic plasma indinavir trough concentrations after 11 months viral load remained undetectable and CD4 count had increased.

Coadministration has not been studied but should be avoided. Bosutinib is metabolized by CYP3A4. Ketoconazole (a strong CYP3A4 inhibitor) increased bosutinib AUC by 8.6-fold. A similar effect may occur with indinavir/ritonavir. Use an alternative antiretroviral drug with no inhibitory or inducing effects.

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

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

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

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. Indinavir and indinavir/ritonavir could potentially increase bromazepam concentrations although to a moderate extent. No a priori dosage adjustment is required.

Coadministration is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects. Coadministration has not been studied but may increase budesonide concentrations. A dose reduction of the glucocorticoid may be necessary with monitoring for symptoms of hypercorticism or a switch to a glucocorticoid, which is not a substrate for CYP3A4 (e.g. beclometasone).

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

Coadministration has not been studied. Buspirone is metabolized by CYP3A4 but does not inhibit CYP3A4. Indinavir and indinavir/ritonavir could potentially increase buspirone concentrations. A low dose of buspirone and careful monitoring of therapeutic and adverse effects is recommended. Adjust dosage based on the clinical response.

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Induction of UGTs by ritonavir used to boost indinavir is unlikely to cause a clinically relevant decrease in cabotegravir exposure based on drug-drug interaction studies with rifabutin, another moderate inducer. Note, cabotegravir used as PrEP is not expected to be coadministered with antiretrovirals except in the case of breakthrough infection when an antiretroviral treatment should be initiated. Residual concentrations of cabotegravir may remain in the systemic circulation for prolonged periods (up to 12 months or longer) but are not expected to affect the exposure of antiretroviral drugs initiated after discontinuation of Apretude.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Induction of UGTs by ritonavir used to boost indinavir is unlikely to cause a clinically relevant decrease in cabotegravir exposure based on drug-drug interaction studies with rifabutin, another moderate inducer. Cabotegravir is not expected to alter concentrations of other antiretroviral products. 

Cabenuva (cabotegravir LA, rilpivirine LA) is indicated for use as a complete regimen for the treatment of HIV-1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with indinavir would be possible from a pharmacokinetic standpoint. Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for a prolonged period after discontinuation of intramuscular cabotegravir/rilpivirine but are not expected to affect exposure of antiretroviral drugs.

Coadministration has not been studied but should be used with caution. Cabozantinib is metabolized by CYP3A4. Ketoconazole (a strong CYP3A4 inhibitor) increased cabozantinib AUC by 38%. A similar effect may occur with indinavir/ritonavir. Avoid concomitant use with strong inhibitors if possible. If a strong CYP3A4 inhibitor must be used, reduce the cabozantinib daily dose by 20 mg. Resume the dose that was used prior to initiating the CYP3A4 inhibitor 2-3 days after discontinuation of the strong inhibitor

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

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

Coadministration has not been studied. Canagliflozin is primarily metabolised by UGT1A9 and UGT2B4. Unboosted indinavir is unlikely to alter canagliflozin exposure. Indinavir/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. Cannabidiol is mainly metabolized by CYP3A4 and CYP2C19. Coadministration may increase cannabidiol concentrations due to strong inhibition of CYP3A4 by indinavir + 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 with indinavir/ritonavir has not been studied. 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 modest inducer of CYP2C9. Indinavir/ritonavir could potentially decrease THC exposure although to a moderate extent. Coadministration of indinavir alone (800 mg three times daily) and cannabis cigarettes decreased indinavir AUC, Cmax and Cmin by 24%, 21% and 22%, respectively. Although the decreases were statistically significant there was a large interindividual variability. It is unknown if these pharmacokinetic changes will confer long-term clinical significance.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Capreomycin is predominantly excreted via the kidneys as unchanged drug.

Use with caution. Coadministration may reduce indinavir concentrations and increase carbamezepine concentrations. Careful monitoring of therapeutic and adverse effects is recommended.

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 and therefore there is little potential for a pharmacokinetic interaction.

Coadministration has not been studied. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and additionally metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. Indinavir/ritonavir could potentially increase carvedilol concentrations via CYP2D6 inhibition or decrease carvedilol concentrations via induction of glucuronidation. The net effect on carvedilol concentrations is difficult to predict but likely to be moderate in magnitude. No a priori dosage adjustment is required.

Coadministration has not been studied. Cat’s claw is a strong inhibitor of CYP3A4 in vitro and increased concentrations of atazanavir, saquinavir and ritonavir were reported in a patient receiving Cat’s claw. Similar increases would be expected for other CYP3A4 substrates, such as indinavir. Coadministration should be avoided.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Cefalexin is predominantly eliminated unchanged via the kidneys.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Cefazolin is predominantly eliminated unchanged via the kidneys.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Approximately 50% of the absorbed dose is excreted unchanged in the urine; there is no evidence of metabolism of cefixime in vivo. In vitro studies have shown that cefixime does not inhibit/induce major cytochrome P450 metabolic enzymes, and would not be expected to cause clinically significant interactions with other drugs, which are metabolized by CYP450 enzymes.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Cefotaxime is predominantly eliminated unchanged via the kidneys.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Ceftazidime is predominantly eliminated unchanged via renal glomerular filtration.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Ceftriaxone is eliminated mainly as unchanged drug; approximately 60% of the dose being excreted in the urine, almost exclusively 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. 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. In vitro studies have shown that chloramphenicol can inhibit metabolism mediated by CYP3A4. Coadministration of chloramphenicol may potentially increase levels of indinavir via this mechanism, increasing the risk of adverse events. 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 with a chlormadinone-containing combined oral contraceptive (COC) has not been studied. Chlormadinone undergoes extensive hepatic metabolism by hydroxylation (likely CYP mediated). Coadministration is predicted to increase exposure of chlormadinone. When used in a combined pill, the estrogen component is reduced. Given the lack of clinical data on the contraceptive efficacy, caution is recommended and additional contraceptives measures should be used.

Coadministration has not been studied. Chloroquine is metabolised by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney (50%). Indinavir and indinavir/ritonavir could potentially increase chloroquine exposure by inhibition of CYPs 3A4 and 2D6 (indinavir) and CYPs 2C8, 3A4 and 2D6 (indinavir/ritonavir), although to a moderate extent due to the multiple elimination pathways. No dosage adjustment is recommended for chloroquine but monitor toxicity.

Coadministration has not been studied. Chlorphenamine is predominantly metabolized in the liver via CYP2D6. Indinavir and indinavir/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. Indinavir and indinavir/ritonavir could potentially increase chlorpromazine exposure although to a moderate extent. No a priori dosage adjustment is recommended but monitor side effects.

Coadministration has not been studied. Ciclesonide can be administered with indinavir 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 indinavir 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. 

Ciclosporin levels were markedly increased in patients on PIs, including indinavir. Case reports of transplants subject receiving ciclosporin and indinavir suggest that indinavir concentrations may be decreased and ciclosporin doses had to be decreased by more than 75% to maintain the AUC within the target range. Ciclosporin dose adjustments should be made according to measured ciclosporin trough blood levels.

No data with indinavir/ritonavir. Coadministration of indinavir alone (400 mg single dose) and cimetidine (600 mg twice daily) had no clinically significant effect on indinavir exposure.

Coadministration is contraindicated as it may increase cisapride concentrations, which could result in serious and/or life-threatening reactions such as cardiac arrhythmias.

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%). Indinavir/ritonavir could potentially increase citalopram concentrations, although to a moderate extent. No a priori dosage adjustment is recommended.

No data with indinavir/ritonavir. Coadministration with indinavir alone increased clarithromycin Cmax (19%), AUC (47%) and Cmin (97%). Indinavir Cmax, AUC and Cmin increased by 8%, 19% and 57%, respectively. The effects are not considered clinically significant and no dose adjustment is required.

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 indinavir/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 indinavir/ritonavir.

Coadministration has not been studied. Clobetasol is a substrate of CYP3A4 and exposure may increase due to inhibition of CYP3A4 by 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, hyperglycemia, and glucosuria 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. In vitro studies have suggested that transformation of clomifene to its active metabolite is likely to be mediated via CYP2D6. Indinavir/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.

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.

Indinavir/ritonavir should not be administered with clorazepate.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. 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.

Indinavir/ritonavir should not be administered with clozapine.

Coadministration has not been studied. Codeine is a substrate of CYP2D6 (major) and CYP3A4. Indinavir inhibits CYP2D6 and 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, the analgesic effect requires conversion of codeine to morphine via CYP2D6 and indinavir or indinavir/ritonavir could potentially reduce the analgesic efficacy.

Coadministration 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). Patients with renal or hepatic impairment should not be coadministered colchicine. 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. 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 indinavir is not expected to reduce the effect of vitamin D, but the consequence of CYP3A inhibition on the clinical effect of vitamin D is not known. However, no effect of antiretroviral therapy on the response to vitamin D supplementation was found in a PK modelling study.

Coadministration has not been studied. No interaction is expected with vitamin D when given with calcium or in a multivitamin preparation. Metabolism of vitamin D to active metabolites occurs in the liver and kidneys, and is thought to involve CYP3A4 and CYP24A1. In vitro studies have shown rifampicin (an enzyme inducer) increased metabolism of vitamin D and introduction of 6',7'-dihydroxybergamottin (a CYP3A4 inhibitor in grapefruit juice) reversed the effects of rifampicin on vitamin D clearance. Inhibition of CYP3A by indinavir 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. Colestyramine may delay or reduce the absorption of drugs. Administration of other drugs should be at least 1 hour before or 4-6 hours after colestyramine. [Note: this interaction is not specific for indinavir, but for any medication taken with colestyramine.]

Coadministration with conjugated estrogens as hormone replacement therapy (HRT) has not been studied. Conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Coadministration could potentially decrease exposure of conjugated estrogens due to induction of CYP1A2 and glucuronidation (rather than increase it due to inhibition of CYP3A4). Monitor for signs of estrogen deficiency. In contrast, exposure of progestogens administered as part of HRT may increase. The clinical relevance of this is unknown but increased progestogen concentrations may be associated with a higher incidence of side effects. Note, use of conjugated estrogens as part of gender affirming treatment should be avoided as they are associated with high thromboembolic risk.

Coadministration has not been studied 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 indinavir in the presence of ritonavir is unlikely.

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

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

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. 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 indinavir. A dose adjustment of cyproterone may be required.

Coadministration with indinavir 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 when used once daily as a pharmacokinetic enhancer in patients with no renal impairment, though no data are available when ritonavir is used twice daily as a pharmacokinetic enhancer. 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 indinavir/ritonavir. Note, dabigatran is not recommended in patients with severe renal impairment.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapagliflozin is primarily metabolised by UGT1A9. Unboosted indinavir is unlikely to alter dapagliflozin exposure. Indinavir/ritonavir may affect dapagliflozin due to UGT induction by ritonavir but 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 been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Indinavir is metabolized by CYP3A4. Dapivirine is metabolized mainly by CYP3A4 and to a lesser extent by glucuronidation. However, the risk of drug-drug interactions is low with the dapivirine vaginal ring due to its low systemic exposure. Furthermore, dapivirine concentrations in vaginal fluid exceed the in vitro HIV IC99 by 1000-fold.

Coadministration has not 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 Summary of Product Characteristics for darifenacin contraindicates its use with potent CYP3A4 inhibitors (such as ritonavir), but the US Prescribing Information recommends that the dose of darifenacin should not exceed 7.5mg when coadministered with potent CYP3A4 inhibitors.

Note: this interaction was studied using a darunavir/ritonavir dose lower than that licensed. Coadministration of indinavir (800 mg twice daily) and darunavir/ritonavir (400/100 mg twice daily) increased darunavir Cmax (11%), AUC (24%) and Cmin (44%), and also increased indinavir Cmax (8%), AUC (23%) and Cmin (125%), relative to indinavir/ritonavir 800/100 mg twice daily alone. Dose adjustment of indinavir from 800 to 600 mg twice daily may be warranted in cases of intolerance.

Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, appropriate doses of this combination with respect to safety, efficacy and pharmacokinetics of indinavir have not been established.

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

Coadministration has not been studied but should be avoided. Dasatinib is metabolized by CYP3A4 and indinavir may significantly increase dasatinib concentrations when boosted with ritonavir. If coadministration is unavoidable, close monitoring for toxicity is required and dasatinib dose reduction to 20-40 mg daily should be considered.

A clinical study reported that indinavir had no effect on daunorubicin pharmacokinetics (liposomal). 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.

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). A similar increase would be expected with indinavir/ritonavir and caution is advised. If coadministration is considered necessary, frequent monitoring of ECGs 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. Desipramine is metabolized by CYP2D6. Indinavir and indinavir/ritonavir could potentially increase desipramine concentrations although to a moderate extent. No a priori dosage adjustment is recommended.

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 possible CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Coadministration is predicted to increase etonogestrel due to induction of CYP2C9 and inhibition of CYP3A4. When used in a combined pill, the estrogen component is reduced. Given the lack of clinical data on the contraceptive efficacy, caution is recommended and additional contraceptives measures should be used.

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 indinavir.

Coadministration with dexlansoprazole has not been studied. Coadministration of indinavir and omeprazole decreased indinavir AUC (47%) and Cmin (55%). The addition of ritonavir (200 mg single dose) reversed the effects of omeprazole. Similarly, dexlansoprazole is predicted to decrease the exposure of indinavir alone whereas no significant interaction is predicted for indinavir/ritonavir.

Indinavir/ritonavir should not be administered with diazepam.

This interaction has not been studied. Based on limited data concerning the metabolism/elimination and toxicity profile of diethylcarbamazine, there is little potential for interaction with indinavir.

The interaction with indinavir/ritonavir has not been studied. Coadministration of digoxin (0.4 mg single dose) and ritonavir (200 mg twice daily) increased digoxin AUC by 22%. Careful monitoring of digoxin levels is recommended when coadministered with indinavir/ritonavir.

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. Indinavir/ritonavir could potentially increase dihydrocodeine exposure (inhibition of CYP3A4 and CYP2D6) and increase the conversion to dihydrocodeine-6-glucuronide (induction of UGT2B7). The net clinical effect of this interaction is difficult to predict. 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 is contraindicated as it may increase dihydroergotamine concentrations, which could result in serious and/or life-threatening reactions such as acute ergot toxicity.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Diloxanide furoate is largely hydrolysed under the combined action of bacterial and gut esterases and consequently glucuronidated. No clinically-significant drug interactions are known, and significant interactions with antiretrovirals are unlikely.

Coadministration of indinavir/ritonavir (800/100 mg twice daily) and diltiazem (120 mg once daily) increased diltiazem AUC by 43%, desacetyldiltiazem AUC by 102% and desmethyldiltiazem AUC by 27%. There was no effect on the pharmacokinetics of indinavir or ritonavir. If coadministration is indicated, diltiazem should be initiated at low doses with careful titration to response and side effects.

Coadministration has not been studied. Diphenhydramine is mainly metabolized by CYP2D6. Indinavir/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. Coadministration could potentially decrease dipyridamole exposure due to induction of glucuronidation, thereby reducing the antiplatelet effect.

Coadministration has not been studied but may increase disopyramide exposure and thereby the risk of cardiac arrhythmias. Coadministration is not recommended. Disopyramide is metabolized by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine.

Coadministration has not been studied and is not recommended. Dofetilide is metabolized to a small degree by CYP3A4 and therefore indinavir could potentially increase dofetilide exposure and thereby increase the risk of cardiac arrhythmias.

Coadministration has not been studied. Based on studies with other boosted PIs, indinavir/ritonavir is not expected to significantly affect dolutegravir pharmacokinetics. No dosage adjustment is necessary.

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 indinavir or indinavir/ritonavir would be possible from a pharmacokinetic standpoint. No interaction is expected with dolutegravir. Coadministration of indinavir alone with lamivudine or abacavir showed no clinically significant interactions.

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 indinavir or indinavir/ritonavir would be possible from a pharmacokinetic standpoint. Based on studies with other boosted PIs, indinavir/ritonavir is not expected to significantly affect dolutegravir pharmacokinetics. Coadministration of indinavir alone with lamivudine/zidovudine showed no clinically significant interactions.

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 indinavir or indinavir/ritonavir would be possible from a pharmacokinetic standpoint. Based on studies with other boosted PIs, indinavir/ritonavir is not expected to significantly affect dolutegravir pharmacokinetics. Coadministration with indinavir (alone or with ritonavir) may increase rilpivirine concentrations, however, no dose adjustment is required. Rilpivirine is not expected to affect concentrations of indinavir.

Coadministration has not been studied. Donepezil is metabolized by CYP3A4 and CYP2D6 (minor). A 30% increase in donepezil exposure has been reported in presence of ketoconazole, a strong CYP3A4 inhibitor. A similar effect is expected with indinavir/ritonavir. No a priori dose modification is required but monitoring for increased side effects is recommended.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs there is little potential for interaction. 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 disposition of antiretrovirals, or to be affected if co-administered with antiretrovirals.

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 indinavir or indinavir/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. 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. Coadministration of tenofovir-DF (300 mg once daily) and indinavir (800 mg three times daily for 7 days) resulted in no change in AUC or Cmin of tenofovir and a 14% increase in Cmax. There was no change in indinavir AUC or Cmin, and a 11% decrease in Cmax. A higher risk of renal impairment has been reported in patients receiving tenofovir-DF in combination with a ritonavir boosted protease inhibitor. Close monitoring of renal function is required in these patients. 

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 indinavir, 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 indinavir.

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. Indinavir/ritonavir could potentially increase doxepin exposure although to a moderate extent. No a priori dose adjustment is required.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. No significant metabolism of doxycycline occurs, it is cleared intact by renal and biliary mechanisms.

Coadministration has not been studied. Dronabinol is mainly metabolized by CYP2C9 and to a lesser extent 3A4. In vitro and in vivo data indicate that ritonavir is a modest inducer of CYP2C9. Indinavir/ritonavir could potentially decrease dronabinol exposure although to a moderate extent. 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. When used in a combined pill, the estrogen component is reduced. Given the lack of clinical data on the contraceptive efficacy, caution is recommended and additional contraceptives measures should be used.

Coadministration with drospirenone as hormone replacement therapy (HRT) has not been studied. CYP3A4 contributes to drospirenone metabolism. Coadministration is predicted to increase drospirenone exposure. 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 with a drospirenone progestogen-only pill (POP) has not been studied. CYP3A4 contributes to drospirenone metabolism. Coadministration is predicted to increase drospirenone and therefore, based on studies with norethisterone used as a progestogen only pill, the contraceptive efficacy of a drospirenone POP is unlikely to be compromised by indinavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as dulaglutide is presumed to be degraded by general protein catabolism pathways. Dulaglutide delays gastric emptying and has the potential to impact the rate of absorption of concomitantly administered oral medicinal products. However, interaction studies did not result in any clinically relevant effects and no dose adjustment of comedications is recommended.

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 required. Indinavir alone is unlikely to alter duloxetine concentrations.

Coadministration has not been studied. Dutasteride is mainly metabolized by CYP3A4. Indinavir/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. 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 of efavirenz with indinavir alone decreases indinavir concentrations; increasing indinavir to 1000 mg three times daily did not compensate for the increased indinavir metabolism due to efavirenz. Coadministration with indinavir/ritonavir (800/100 twice daily) had no effect on efavirenz AUC or Cmin, but decreased the AUC and Cmin of indinavir and ritonavir. No specific dose recommendation can be given for indinavir alone. Dose increases of indinavir/ritonavir when given in combination with efavirenz have not been studied.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Eflornithine is predominantly eliminated unchanged via the kidneys.

Coadministration has not been studied and is not recommended. Eletriptan is metabolised by CYP3A4 and concentrations may increase due to inhibition of CYP3A4 by indinavir. Coadministration with ketoconazole (a strong CYP3A4 inhibitor) increased eletriptan Cmax and AUC by 2.7 and 5.9 fold, respectively. The US product label for eletriptan contraindicates its use with potent CYP3A4 inhibitors whereas the European product label advises that it should not be used with potent CYP3A4 inhibitors.

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Genvoya should not be used in conjunction with protease inhibitors due to potential drug-drug interactions including altered and/or suboptimal pharmacokinetics of cobicistat, elvitegravir and/or the coadministered antiretroviral products. Genvoya should not be administered concurrently with products containing ritonavir or regimens containing ritonavir due to similar effects of cobicistat and ritonavir on CYP3A.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products.Stribild should not be used in conjunction with protease inhibitors inhibitors due to potential drug-drug interactions including altered and/or suboptimal pharmacokinetics of cobicistat, elvitegravir, and/or the coadministered antiretroviral products. Stribild should not be administered concurrently with products containing ritonavir or regimens containing ritonavir due to similar effects of cobicistat and ritonavir on CYP3A.

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 indinavir/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.

No data with indinavir/ritonavir. No change in the AUC or Cmax values for emtricitabine or indinavir when coadministered.

Coadministration has not been studied and therefore there are no data available to make dosing recommendations. 

Emtricitabine and tenofovir alafenamide used as PrEP are not expected to be coadministered with antiretrovirals. Coadministration has not been studied and therefore there are no data available to make dosing recommendations.

Coadministration with indinavir/ritonavir has not been studied. Coadministration of emtricitabine or tenofovir-DF with indinavir alone showed no clinically significant interactions. Indinavir in combination with emtricitabine resulted in no change in AUC or Cmax of either drug. Coadministration of tenofovir-DF (300 mg once daily) and indinavir (800 mg three times daily for 7 days) resulted in no change in AUC or Cmin of tenofovir and a 14% increase in Cmax. There was no change in indinavir AUC or Cmin, and an 11% decrease in Cmax. A higher risk of renal impairment has been reported in patients receiving tenofovir-DF in combination with a ritonavir boosted protease inhibitor. Close monitoring of renal function is required in these patients.

Coadministration has not been studied but is not recommended. Enzalutamide is primarily metabolized by CYP2C8 and to a lesser extent by CYP3A4. Enzalutamide concentrations may increase to a limited extent as indinavir inhibits CYP3A4 (minor pathway). However, indinavir is metabolized by CYP3A4 and enzalutamide is a strong inducer of CYP3A4 and may significantly decrease indinavir exposure leading to loss of therapeutic effect and possible development of resistance.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Ephedrine is predominantly eliminated unchanged via the kidneys.

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 is contraindicated as it may increase ergometrine concentrations, which could result in serious and/or life-threatening reactions such as acute ergot toxicity.

Coadministration is contraindicated as it may increase ergotamine concentrations, which could result in serious and/or life-threatening reactions such as acute ergot toxicity.

The interaction with indinavir/ritonavir has not been studied, but may increase the plasma concentrations of erythromycin. Careful monitoring of therapeutic and adverse effects is recommended.

Coadministration has not been studied. Escitalopram is metabolized by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Indinavir and indinavir/ritonavir could potentially increase escitalopram concentrations although to a moderate extent. No a priori dosage adjustment 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 indinavir 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 indinavir plasma concentrations (when possible).

Indinavir/ritonavir should not be administered with estazolam.

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 of an oral contraceptive (ethinylestradiol 35 µg and norethindrone 1 mg) and indinavir (800 mg three times daily) increased ethinylestradiol Cmax, AUC and Cmin by 2%, 22% and 37% respectively. Norethindrone AUC increased by 26% and Cmin increased by 44%. Although the interaction with indinavir alone is not clinically significant, caution should be exercised if coadministering with indinavir/ritonavir - additional or alternative contraceptive methods should be considered. Note, use of ethinylestradiol as part of gender affirming treatment is not recommended due to thrombotic risks.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Ethionamide is extensively metabolized in the liver, animal studies suggest involvement of flavin-containing monooxygenases. Ethionamide does not affect metabolism mediated by CYP450 enzymes in vitro.

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

Coadministration with an etonogestrel-containing progestogen-only implant has not been studied. Etonogestrel is metabolized by CYP3A4. Coadministration of lopinavir/ritonavir and etonogestrel implants increased etonogestrel AUC, Cmax and Cmin by 52%, 61% and 34%, respectively, suggesting that lopinavir/ritonavir may not impair the efficacy of etonogestrel implants. Similarly, coadministration with indinavir could potentially increase etonogestrel exposure and therefore is not expected to impair the contraceptive efficacy of etonogestrel when administered as an implant.

Coadministration with the etonogestrel as a combined vaginal ring (CVR) has not been studied. Etonogestrel is metabolized by CYP3A4 and is coformulated in the CVR with ethinylestradiol which is released at a dose of 0.015 mg/day. Indinavir is predicted to increase etonogestrel but to reduce ethinylestradiol concentrations. Since no dosage adjustment of ethinylestradiol is possible with the CVR, alternative forms of contraception should be used.

Etravirine and indinavir/ritonavir can be coadministered, however, unboosted indinavir should not be coadministered with etravirine. Coadministration of etravirine (1600 mg twice daily, phase II formulation) and indinavir (800 mg three times daily) increased etravirine AUC and Cmax both by 51%, however, indinavir AUC and Cmax decreased by 46% and 28%, respectively.

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 indinavir in the presence of ritonavir is unlikely.

Coadministration of 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 indinavir/ritonavir. Coadministration is not recommended as there are currently insufficient data to allow dosing recommendations with potent CYP3A4 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 indinavir/ritonavir. No a priori dose adjustment is required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as exenatide is primarily eliminated by glomerular filtration. However, as exenatide slows gastric emptying it is advisable to take indinavir at least 1 hour before an exenatide injection. [Note: this interaction is not specific for indinavir, but for any medication taken with exenatide.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fampridine is metabolized by CYP2E1 but is predominantly eliminated unchanged by the kidney with active secretion by OCT2. Indinavir does not interfere with fampridine elimination pathway.

Coadministration may increase concentrations of felodipine. Caution is warranted and clinical monitoring is recommended.

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 indinavir 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 but based on metabolism and clearance a clinically significant interaction is unlikely.

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 ritonavir.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Filgrastim is eliminated mainly by neutrophil-mediated clearance and renal excretion.

Indinavir/ritonavir should not be administered with flecanide.

No data with indinavir/ritonavir. Coadministration with indinavir alone (1000 mg three times daily) decreased indinavir AUC by 24% with no effect on fluconazole concentrations. A decrease of 20% is likely to be relevant in a non-boosted regimen. However, in a boosted regimen fluconazole is not expected to alter indinavir pharmacokinetics.