Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abiraterone has multiple metabolic pathways and is an inhibitor of CYP2D6.

Coadministration has not been studied but should be avoided. Acalabrutinib is a CYP3A4 and P-gp substrate. Acalabrutinib concentrations may increase due to inhibition of CYP3A4 by boceprevir. Itraconazole (a CYP3A4 inhibitor) increased acalabrutinib AUC and Cmax by 5.1- and 3.9-fold, respectively, and a similar effect could be expected with boceprevir.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely as acamprosate does not undergo significant metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aceclofenac is metabolised by CYP2C9 which is not affected by boceprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acenocoumarol is mainly metabolized by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19, but these enzymes are not affected by boceprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as aciclovir is eliminated primarily unchanged in the urine via active renal tubular secretion.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Boceprevir is metabolized by aldoketoreductase and CYP3A. The potential for hepatically metabolised interactions with adefovir is low. Adefovir is eliminated renally via glomerular filtration and active renal secretion by OAT1.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely as agomelatine is metabolised predominantly via CYP1A2. Note, agomelatine is contraindicated in hepatic impairment as increases in exposure of up to 140-times have been seen in cirrhotic patients.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Albiglutide is a protein for which the expected metabolic pathway is degradation to small peptides and individual amino acids by ubiquitous proteolytic enzymes. However, as albiglutide slows gastric emptying it is advisable to take boceprevir at least 1 hour before an albiglutide injection. [Note: this interaction is not specific for boceprevir, but for any medication taken with albiglutide.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as alemtuzumab is a protein for which the expected metabolic pathway is degradation to small peptides and individual amino acids by widely distributed proteolytic enzymes.

Coadministration has not been studied but alendronate can be administered with boceprevir and no dose alteration is required. Alendronate is not metabolised and is cleared from the plasma by uptake into bone and elimination via renal excretion. Although no pharmacokinetic interaction is expected, note that alendronate should be separated from food or other medicinal products and therefore should be separated from boceprevir administration. [Note: this interaction is not specific for boceprevir, but for any medication taken with alendronic acid.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Allopurinol is metabolised by xanthine oxidase and aldehyde oxidase which are not affected by boceprevir. However, both allopurinol and boceprevir can cause leucopenia, thrombocytopenia and anaemia so these parameters should be monitored. Note, the European SPC and US Prescribing Information for allopurinol recommend reduced dose in hepatic impairment.

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 does not undergo extensive metabolism and is excreted mainly unchanged in the urine and metabolism by CYPs is minimal. No transporter interactions have been described.

Coadministration has not been studied but based on limited understanding of metabolism and clearance a clinically significant interaction is unlikely. However as alverine citrate affects gastric motility, an effect on the absorption of boceprevir cannot be ruled out. Doses of boceprevir and alverine should be separated by 4 hours if possible. [Note: this interaction is not specific for boceprevir, but for any medication taken with alverine citrate.]

Coadministration has not been studied and is not recommended. Amobarbital induces CYP3A4 and P-gp and could decrease concentrations of boceprevir. This may result in loss of efficacy and potential virological failure.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as amphotericin B is mainly excreted in the urine.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asenapine is metabolized by glucuronidation (UGT1A4) and oxidative metabolism (mainly CYP1A2, with minor contributions from CYP3A4 and CYP2D6). As asenapine is metabolised by multiple pathways, a clinically significant effect is unlikely.

Coadministration has not been studied and is not recommended. Based on drug-drug interactions studies with ritonavir-boosted protease inhibitors, coadministration of boceprevir and atazanavir may decrease atazanavir concentrations.

Coadministration has not been studied and is not recommended. Based on drug-drug interactions studies with ritonavir-boosted protease inhibitors, coadministration of boceprevir and atazanavir/cobicistat may decrease atazanavir/cobicistat concentrations.

Coadministration of boceprevir (800 mg three times daily) and atazanavir/ritonavir (300/100 mg once daily) decreased atazanavir AUC, Cmax and Cmin by 35%, 25%, and 49%, respectively. Ritonavir AUC decreased by 34%, but coadministration did not alter boceprevir AUC. Coadministration is not recommended in the US Prescribing Information, but the European SmPC for atazanavir states it can be considered on a case by case basis if deemed necessary in patients with suppressed HIV viral loads and without any suspected viral resistance to the HIV regimen.

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

Coadministration has not been studied but would not be recommended. Axitinib is a metabolised by CYP3A and coadministration with strong CYP3A4/5 inhibitors such as boceprevir may increase axitinib plasma concentrations and an alternative should be considered. Coadministration of ketoconazole (another strong inhibitor of CYP3A4/5) increased axitinib AUC and Cmax by 2-fold and 1.5-fold, respectively. If coadministration cannot be avoided, a dose decrease of axitinib to approximately half the dose is recommended. If coadministration of the strong inhibitor is discontinued, a return to the axitinib dose used prior to initiation of the strong CYP3A4/5 inhibitor should be considered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant drug interaction is unlikely. Aztreonam is only minimally metabolised and is eliminated mainly unchanged in the urine.

Coadministration has not been studied. Bedaquiline is metabolized by CYP3A4 and concentrations may increase due to inhibition of CYP3A4 by boceprevir. In a parallel group interaction study, steady state coadministration bedaquiline (200 mg three times weekly, n=17) and ritonavir (as lopinavir/ritonavir, n=14) increased bedaquiline AUC by 62%. A similar effect may occur with boceprevir and coadministration should be avoided. If the benefit of coadministration outweighs the risk and coadministration is necessary, clinical monitoring including frequent ECG assessment and monitoring of transaminases 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, 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.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Benralizumab is a humanised IgG1 monoclonal antibody that is degraded by proteolytic enzymes widely distributed in the body and not restricted to hepatic tissue.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Benztropine is primarily metabolised by CYP2D6 which is not affected by boceprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Betahistine undergoes nearly complete metabolism by monoamine oxidase. Based on in-vitro data, no inhibition of cytochrome P450 enzymes by betahistine is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bevacizumab biotransformation involves proteolytic catabolism throughout the body, including endothelial cells, and does not rely primarily on elimination through the kidneys and liver.

Coadministration has not been studied. Bezafibrate is metabolised by hydroxylation, glucuronidation and renal elimination (~50%). Due to the involvement of multiple metabolic pathways and renal elimination, a clinically significant interaction is not expected. Note, the European SPC for bezafibrate contraindicates its use in significant hepatic disease.

Coadministration has not been studied and is not recommended. Coadministration with boceprevir has the potential to adversely affect the intracellular activation and clinical antiviral efficacy of tenofovir alafenamide based on in vitro data.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No interactions are anticipated since although the drug is metabolised, the systemic concentrations of bimatoprost are extremely low (less than 0.2 ng/ml) following ocular dosing with bimatoprost.

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 pharmacokinetic interaction is unlikely. Absorption of bisacodyl from the GI tract is minimal and the small amount absorbed is excreted in the urine as the glucuronide. However, bisacodyl increases colonic mass movements and may affect absorption of boceprevir. The potential interaction can be resolved by giving bisacodyl at least 4 hours after boceprevir. [Note: this interaction is not specific for boceprevir, but for any medication taken with bisacodyl.]

Coadministration has not been studied but bisoprolol concentrations may be increased through inhibition of CYP3A4 by boceprevir. The clinical significance of this is unknown. Monitor for signs of bradycardia and dizziness. Note, the European SPC for bisoprolol recommends a maximum of 10 mg in severe hepatic impairment; the US Prescribing Information for bisoprolol recommends an initial 2.5mg in hepatic impairment with caution in further dose titration.

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, a clinically relevant interaction is unlikely. The metabolic pathway of blinatumomab has not been characterised. Like other protein therapeutics, blinatumomab is expected to be degraded into small peptides and amino acids via catabolic pathways.

Coadministration has not been studied. Bosutinib is metabolised principally by CYP3A4. Data with ketoconazole showed a 8.6-fold increase in bosutinib AUC and a similar effect may occur with boceprevir. Coadministration is not recommended.

Coadministration has not been studied. Brentuximab vedotin releases the active species MMAE within the tumour cell; MMAE is a substrate of CYP3A4 and possibly CYP2D6 and a weak inhibitor of CYP3A4. Boceprevir is an inhibitor of CYP3A4 and may increase MMAE concentrations and the incidence of neutropenia. No a priori dose adjustment is recommended, however, patients who are receiving strong CYP3A4 inhibitors concomitantly with brentuximab vedotin should be closely monitored for adverse reactions. If neutropenia develops, refer to dosing recommendations for neutropenia.

Coadministration has not been studied. Brinzolamide is metabolised by CYP3A4 and concentrations may increase due to inhibition of CYP3A4 by boceprevir. Caution is advised, and a dose reduction could be considered at higher doses. Monitor for increased side effects such as blurred vision and consider intraocular pressure checks if co-prescribed within first week. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brodalumab is degraded into small peptides. Brodalumab may modulate serum levels of some cytokines and may modestly increase the exposure of CYP450 substrates such as boceprevir. However, based on data with midazolam (AUC increased by 24%), this is unlikely to be clinically significant.

Coadministration has not been studied. Bromperidol is metabolised by CYP3A4 and concentrations may increase due to inhibition of CYP3A4 by boceprevir. Monitor for signs and symptoms of increased concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Calcium carbimide is a prodrug requiring catalase and hydrogen peroxide to generate the active metabolite. Calcium carbimide is an inhibitor of ALDH but this enzyme is not involved in the metabolism of boceprevir.

Coadministration has not been studied. Canagliflozin concentrations may be increased due to inhibition of P-gp by boceprevir. Close monitoring of blood glucose is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely as candesartan is largely eliminated unchanged via urine and bile. Note, use of candesartan in severe hepatic impairment is contraindicated in the European SPC and the US Prescribing Information recommends caution in moderate hepatic impairment.

Coadministration has not been studied. As both carvedilol and boceprevir are inhibitors of P-glycoprotein, concentrations of both may be increased. Carvedilol can also commonly cause anaemia. Monitor for increased side effects and toxicities including anaemia, neutropenia and thrombocytopenia for boceprevir and dizziness, bradycardia and GI upset for carvedilol. note, the US Prescribing Information contraindicates carvedilol in patients with severe liver impairment and the European SPC contraindicates it in patients with hepatic dysfunction.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely as caspofungin undergoes spontaneous chemical degradation and non-CYP medicated metabolism. Note, no dose adjustment is required in patients with normal hepatic function but a dose reduction of caspofungin daily dose to 35 mg is recommended for adults with moderate hepatic impairment. There is no clinical experience in adults with severe hepatic impairment.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant drug interaction is unlikely. Cefadroxil is not metabolised and is predominantly eliminated unchanged by the kidneys.

Coadministration has not been studied but based on metabolism and clearance a clinically significant drug interaction is unlikely. Cefradine is not metabolised and is predominantly eliminated unchanged by the kidneys.

Coadministration has not been studied but based on metabolism and clearance a clinically significant drug interaction is unlikely. Ceftaroline is not metabolised by CYP enzymes and is primarily eliminated by the kidneys.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Celecoxib is mainly metabolised by CYP2C9 with CY 3A4 being involved to a lesser extent. Boceprevir is not a substrate or inhibitor of CYP2C9 and so a pharmacokinetic interaction is unlikely. However, celecoxib may uncommonly cause anaemia which may be exacerbated by boceprevir. Note, use in patients with severe liver impairment is contraindicated in the European SPC and not recommended in the US Prescribing Information. In patients with moderate liver impairment (serum albumin 25-35 g/L, Child-Pugh Class B), celecoxib treatment should be started at half the recommended dose.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Like other protein therapeutics, cetuximab is expected to be degraded into small peptides and amino acids via catabolic pathways.

Coadministration has not been studied but a clinically significant interaction is considered unlikely. Very little has been described about chlorambucil metabolism in humans but CYP450 enzymes are not involved.

Co-administration has not been studied. Boceprevir may increase chloroquine concentrations through CYP3A4 inhibition although the clinical significance is uncertain. Note, the European SPC and US Prescribing Information for chloroquine both recommend caution in impaired hepatic function.

Coadministration with boceprevir has not been studied, but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely as chlorpromazine is metabolised predominantly via CYP2D6 and to a lesser extent CYP1A2. Chlorpromazine can cause QT prolongation so if used in combination with boceprevir ECG monitoring should be performed to avoid risk of serious ventricular arrhythmias such as torsades de pointes. Both chlorpromazine and boceprevir can cause neutropenia. Note, the European SPC for chlorpromazine advises that its use should be avoided in patients with hepatic dysfunction.

Coadministration has not been studied but would not be recommended due to the cumulative risk of QT prolongation with boceprevir and chlorprothixene. If use cannot be avoided, strict adherence to maximum QTc intervals for males and females should be adhered to with regular ECG monitoring. 

Coadministration has not been studied, but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Cilazapril is rapidly converted to the active form, cilazaprilat, which is excreted unchanged in the urine. Note, in patients with cirrhosis, a maximum dose of 0.5 mg/day is recommended as significant hypotension may occur.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cisatracurium undergoes mainly (80% of overall elimination) spontaneous degradation in plasma and tissues at physiological pH and temperature (Hofmann elimination).

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clevidipine is rapidly metabolised by hydrolysis of the ester linkage and does not undergo CYP metabolism.

Coadministration has not been studied. Clobazam is metabolised primarily by CYP3A4 and to a lesser extent by CYP2C19. Boceprevir may increase clobazam concentrations due to inhibition of CYP3A4. Consider starting patient on the recommended dose with close clinical monitoring for side effects and toxicities associated with clobazam and decrease dose if necessary.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Clodronate is not metabolised and is primarily excreted unchanged by the kidney. However, if administered orally, clondronate should be taken more than two hours after and one hour before any other oral drugs. [Note: this interaction is not specific for boceprevir, but for any oral medication taken with clodronate.]

Coadministration has not been studied. Studies suggest clomiphene is metabolised by CYP3A4, CYP2D6 and UGTs and concentrations may increase due to inhibition of CYP3A4 by boceprevir. Monitoring may be required as clinically indicated.

Coadministration has not been studied. Clopidogrel is a prodrug and is converted to its active metabolites via CYPs 2C19, 3A4, 2B6, and 1A2. Boceprevir may decrease concentrations of the active metabolite and an alternative could be considered. Note, the European SPC for clopidogrel contraindicates clopidogrel in severe hepatic impairment but the US Prescribing Information states no dose alteration.

Coadministration has not been studied. The metabolism of clotiapine has not been well characterised but is likely to involve CYP450 enzymes. Boceprevir is a potent CYP3A4 inhibitor and may increase clotiapine exposure. In the absence of further data, use with caution. If coadministration is unavoidable, monitoring for side effects associated with increased concentrations of clotiapine is recommended. A clinically significant effect on boceprevir is unlikely. As with other antipsychotics, caution is advised with clotiapine and other medications which prolong the QT interval, ECG monitoring is recommended in combination with boceprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although colecalciferol levels may increase due to inhibition of CYP3A4 by boceprevir, this is unlikely to be clinically significant.

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 boceprevir, but for any medication taken with colestyramine.]

Co-administration has not been studied but based on limited data for the metabolism and clearance of cyclizine, a clinically significant interaction is unlikely. Cyclizine undergoes hepatic metabolism which may include CYP2D6.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dantron is absorbed from the small intestine and acts at the large intestine. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Like other protein therapeutics, daratumumab is expected to be degraded into small peptides and amino acids via catabolic pathways and is not anticipated to alter drug-metabolising enzymes.

Coadministration has not been studied and is not recommended. Based on drug-drug interaction studies with ritonavir-boosted protease inhibitors, coadministration of boceprevir and darunavir/cobicistat may result in decreased darunavir/cobicistat or boceprevir concentrations.

Coadministration has not been studied and is not recommended. Coadministration with boceprevir has the potential to adversely affect the intracellular activation and clinical antiviral efficacy of tenofovir alafenamide. Based on drug-drug interaction studies with ritonavir-boosted protease inhibitors, coadministration of boceprevir and darunavir/cobicistat may result in decreased darunavir, cobicistat or boceprevir concentrations. Emtricitabine does not interact with this metabolic pathway.

Coadministration is not recommended. Coadministration of boceprevir (800 mg three times daily) and darunavir/ritonavir (600/100 mg twice daily) decreased boceprevir AUC, Cmax and Cmin by 32%, 25% and 35% respectively. Decreases were observed for darunavir AUC, Cmax and Cmin (44%, 36%, and 59%, respectively) and ritonavir AUC, Cmax and Cmin (27%, 13%, and 45%, respectively).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Deferiprone is glucuronidated by UGT1A6 which is not affected by boceprevir.

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. Coadministration 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 boceprevir 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). Note, delamanid is not recommended in patients with moderate to severe hepatic impairment.

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 resulting in degradation to small peptides and individual amino acids.

Coadministration has not been studied. Desvenlafaxine is metabolised via CYP3A4 and concentrations may be increased via inhibition of this enzyme by boceprevir. Monitoring may be required as clinically indicated. A dose reduction of desvenlafaxine should be considered if appropriate. Note, a maximum dose of 50 mg is recommended in moderate hepatic impairment.

Coadministration has not been studied. The role of CYP450 in the metabolism of dexamfetamine has not been fully described and potent inhibitors of CYP3A4, such as boceprevir, should be used with caution.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Dexketoprofen is mainly glucuronidated, with CYP mediated metabolism (CYP2C8/9) playing only a minor role. Boceprevir is not expected to induce or inhibit UGTs or CYP2C8/2C9. Note, use in patients with severe hepatic impairment (Child Pugh class C) is contraindicated in the European product label for dexketoprofen.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diosmin is a naturally occurring flavonoid. Diosmin-containing products are available as dietary supplements or on prescription (in certain countries). Interaction studies suggest that diosmin may be a weak inhibitor of CYP3A4 and P-gp, but any effect on boceprevir is unlikely to be clinically relevant.

Coadministration has not been studied but, based on metabolism and clearance, a clinically significant interaction is unlikely as diphenhydramine is a substrate and inhibitor of CYP2D6 and boceprevir does not affect this pathway. Note, diphenhydramine should be used with caution in patients with moderate to severe hepatic impairment.

Coadministration with dolutegravir/rilpivirine has not been studied. Boceprevir had no clinically significant effect on the pharmacokinetics of dolutegravir alone. Coadministration of boceprevir (800 mg every 8 hours) and dolutegravir (50 mg once daily) increased dolutegravir Cmax, AUC and Ctrough by 5%, 7% and 8%, respectively. Using cross-study comparisons to historical pharmacokinetic data, dolutegravir did not appear to affect the pharmacokinetics of boceprevir. Coadministration of rilpivirine alone (25 mg once daily) and boceprevir (800 mg three times daily) increased rilpivirine AUC, Cmax and C24 by 39%, 15% and 51%, respectively, but these increases were not considered to be clinically significant. Boceprevir AUC and Cmax decreased by 6% and 2%, but C8 increased by 4%. No dose adjustment is required if boceprevir and dolutegravir/rilpivirine are coadministered.

Coadministration has not been studied. Donepezil is metabolised by CYP3A4 and CYP2D6 (minor). Concentrations may increase due to inhibition of CYP3A4 by boceprevir. No a priori dose modification is required but monitoring for increased side effects is recommended.

Coadministration has not been studied. Boceprevir inhibits CYP3A4 and is predicted to increase doravirine exposure by ~3-fold based on drug-drug interaction studies with ritonavir and ketoconazole. No dose adjustment of doravirine is required as phase I trials showed good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Boceprevir inhibits CYP3A4 and is predicted to increase doravirine exposure by ~3-fold based on drug-drug interaction studies with ritonavir and ketoconazole. No dose adjustment of doravirine is required as phase I trials showed good tolerability of doravirine with up to a 3-4 fold increase in exposure. No clinically relevant interaction is expected with lamivudine. Coadministration of boceprevir (800 mg three times daily) and tenofovir-DF (300 mg once daily) had no notable effect on boceprevir AUC and Cmax, nor on tenofovir AUC (5% increase) and renal clearance, but increased tenofovir Cmax by 32%. No dose adjustment of boceprevir is required.

Coadministration has not been studied but would not be recommended due to an additive effect on QT prolongation by both drugs. 

Coadministration has not been studied. Doxazosin is primarily metabolised by CYP3A4 and boceprevir is likely to increase doxazosin concentrations which may cause hypotension. Use with caution. Note, the European SPC does not recommend doxazosin in severe hepatic impairment; the US Prescribing Information has a caution for use in hepatic impairment.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Doxepin is metabolised to nordoxepin by CYP2CA9 and CYP2D6 and boceprevir is not involved in this pathway.Note, the European and US product labels for doxepin advise caution and monitoring in patients with hepatic impairment as a dosage reduction may be required.

Co-administration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Limited data available for doxylamine metabolism suggest involvement of CYP2B6 which is not affected by boceprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dulaglutide is presumed to be degraded into its component amino acids by general protein catabolism pathways. However, as dulaglutide slows gastric emptying it is advisable to take boceprevir at least 1 hour before a dulaglutide injection. [Note: this interaction is not specific for boceprevir, but for any medication taken with dulaglutide.]

Coadministration has not been studied. Duloxetine is metabolised by CYP1A2 and CYP2D6. Based on the known metabolic pathways boceprevir is not expected to alter duloxetine concentrations. A clinically significant effect on boceprevir exposure is unlikely. Note, duloxetine is contraindicated in patients with hepatic impairment as concentrations may increase due to decreased clearance of duloxetine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dupilimab is a protein and degrades to small peptides and individual amino acids. 

Coadministration has not been studied. Dutasteride is metabolised mainly by CYP3A4 and CYP3A5 and coadministration may increase dutasteride concentrations. Monitor for increased side effects such as impotence, decreased libido and dizziness. The European SPC for dutasteride suggests switching to 48 hourly dosing if side effects become problematic. Note, the European SPC (but not the US Prescribing Information) cautions against dutasteride use in mild to moderate hepatic impairment and contraindicates it in severe hepatic impairment.

Coadministration has not been studied. Ebastine is metabolised by CYP450 and concentrations may be increased due to CYP3A4 inhibition by boceprevir. Use with caution as increased concentrations of ebastine may prolong QT interval. Consider ECG monitoring.

Coadministration has not been studied. Eliglustat is metabolised primarily by CYP2D6 and to a lesser extent by CYP3A4. Concentrations of eliglustat may increase due to CYP3A4 inhibition by boceprevir. In the absence of knowledge of CYP2D6 genotyping (i.e., whether the patient is a CYP2D6 poor metabolizer), coadministration is contraindicated.

Coadministration has not been studied and is not recommended. Coadministration with boceprevir has the potential to adversely affect the intracellular activation and clinical antiviral efficacy of tenofovir alafenamide. In addition, based on drug-drug interactions studies with ritonavir-boosted protease inhibitors, coadministration of boceprevir and elvitegravir/cobicistat may result in decreased elvitegravir, cobicistat or boceprevir concentrations.

Coadministration has not been studied and is not recommended. Based on drug-drug interactions studies with boosted HIV protease inhibitors, coadministration of boceprevir and elvitegravir/cobicistat may result in decreased elvitegravir, cobicistat or boceprevir concentrations.

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 boceprevir is an inhibitor of P-gp, data with verapamil (also a P-gp inhibitor) suggest a clinically relevant effect on empagliflozin is unlikely.

Coadministration has not been studied and is not recommended. Coadministration with boceprevir has the potential to adversely affect the intracellular activation and clinical antiviral efficacy of tenofovir alafenamide.

Coadministration with emtricitabine/tenofovir-DF has not been studied.  Based on metabolism and clearance a clinically significant interaction is unlikely with emtricitabine as boceprevir is metabolized by aldo-keto reductase and CYP3A. Coadministration of boceprevir (800 mg three times daily) and tenofovir-DF (300 mg once daily) had no notable effect on boceprevir AUC and Cmax, nor on tenofovir AUC (5% increase) and renal clearance, but increased tenofovir Cmax by 32%.  No dose adjustment of emtricitabine/tenofovir-DF or boceprevir is required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Boceprevir is metabolized by aldoketoreductase and CYP3A. Entecavir is not hepatically metabolised and the potential for interactions via this route is low. Entecavir is eliminated primarily in the urine by glomerular filtration and tubular secretion by OAT1.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Epoprostenol is rapidly hydrolysed; there does not appear to be any involvement with CYP isoenzymes or transporter proteins.

Coadministration has not been studied. Erlotinib is mainly metabolized by CYP3A4 and coadministration could potentially increase erlotinib concentrations. Coadministration of a potent CYP3A4 inhibitor should be avoided, but if this is not possible, use with caution. Close monitoring for erlotinib mediated toxicity is necessary and a dose reduction may be required for erlotinib.

Coadministration has not been studied and is not recommended as eslicarbazepine is an inducer of CYP3A4 and coadministration may result in sub clinical boceprevir concentrations.

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

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Estramustine is dephosphorylated and minimal data show it not to undergo any form of CYP metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Note, there is a concern of hepatotoxic adverse events in patients with HCV receiving anti-TNF agents. Use with caution and monitor liver enzymes and HCV viral load.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data suggest etelcalcetide is not metabolised by CYP450 nor transported by common transporter proteins.

Coadministration with an etonogestrel-containing progestogen-only implant has not been studied. Etonogestrel is metabolized by CYP3A4 and boceprevir is an inhibitor of CYP3A4. Coadministration of lopinavir/ritonavir (also CYP3A4 inhibitors) and etonogestrel implants increased etonogestrel AUC, Cmax and Cmin by 52%, 61% and 34%, respectively, suggesting that lopinavir/ritonavir will not impair the efficacy of etonogestrel implants. Similarly, coadministration with boceprevir could potentially increase etonogestrel exposure. However, despite the higher levels a clinically significant interaction is not expected.

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. Boceprevir 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.

Coadministration has not been studied. Etoposide is partly metabolised by CYP3A4 to reactive catechol metabolites and partly metabolised by UGT1A1.  Concentrations of etoposide may increase due to CYP3A4 inhibition by boceprevir, increasing risk and severity of mucositis, myelosuppression and transaminitis. Use with caution.

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 boceprevir. No a priori dose adjustment is required.

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

Coadministration has not been studied, but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Ezetimibe is primarily metabolized in the small intestine and liver via glucuronidation. Note, use of ezetemibe is not recommended in moderate to severe hepatic dysfunction.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Febuxostat is extensively metabolised by multiple P450 (CYPs 1A1, CYP1A2, CYP2C8 and CYP2C9) and UGT enzymes (UGTs 1A1, 1A8, and 1A9). A clinically significant interaction is unlikely as febuxostat is metabolised by multiple pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as fenofibrate is metabolised by multiple enzyme pathways (esterases, UGT2B7 and UGT1A1). Note, fenofibrate is contraindicated in severe hepatic disease in its European SPC, and its US Prescribing Information contraindicates it in active liver disease.

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 boceprevir 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 and is contraindicated. Flibanserin is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C19. Inhibition of CYP3A4 by boceprevir is expected to increase flibanserin concentrations which can cause severe hypotension and syncope.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluinidone is metabolised by CYP2C9 (major) and CYP1A2 (minor) which are not affected by boceprevir.

Coadministration has not been studied. Fluoxetine is mainly metabolised by CYP2D6. Boceprevir is not expected to alter fluoxetine concentrations and a clinically significant effect on boceprevir is unlikely. Note, a lower or less frequent dose should be considered in cases of hepatic insufficiency.

Coadministration has not been studied. Fluvastatin is a substrate of CYPs 2C8, 2C9 and 3A4 and OATPs 1B1/3 and BCRP; concentrations could increase due to inhibition of CYP3A by boceprevir. Note, use of fluvastatin in active liver disease is contraindicated.

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Fosinopril is a prodrug metabolised in the liver by a non-CYP mechanism to the active metabolite.

Coadministration has not been studied. Gefitinib is metabolised by CYP3A4 and concentrations may increase significantly due to inhibition of CYP3A4 by boceprevir. A physiologically-based pharmacokinetic model recommended a gefitinib dose of 125 mg in the presence of ritonavir (a potent CYP3A4 inhibitor). A similar dose should be considered when given in combination with boceprevir.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Gemfibrozil is metabolised via UGT2B7 and to date there is no evidence that boceprevir is involved in this pathway. Note, use of gemfibrozil in hepatic impairment is contraindicated.

Co-administration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with standard doses (up to 240 mg) of Ginkgo biloba.

Glecaprevir/pibrentasvir is an NS3A containing regimen. There are no data to support the coadministration with boceprevir.

Coadministration has not been studied. Glycerol phenylbutyrate has been shown to be a weak inducer of CYP3A4. This is unlikely to be clinically significant but should be considered in the event of a suboptimal response to HCV treatment. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. There is minimal metabolism of goserelin and no clinically relevant accumulation with higher doses of the implant. Goserelin is renally cleared with no dose alteration required in renal or hepatic impairment. However, androgen deprivation therapy may prolong the QT interval and the benefit/risk ratio (including the potential for Torsade de pointes) should be assessed prior to initiating goserelin as boceprevir may cause QT prolongation.

Coadministration has not been studied. Granisetron is metabolised by CYP3A4 and concentrations may increase due to inhibition of CYP3A4 by boceprevir. As granisetron may prolong the QTc interval, ECG monitoring should be considered.

Coadministration has not been studied. Hydrocodone is metabolised by CYP2D6 to hydromorphone and by CYP3A4 to norhydrocodone, both of which have analgesic effects. Inhibition of CYP3A4 by boceprevir may increase hydrocodone concentrations but decrease concentrations of norhydrocodone and the clinical significance of this is unclear. Monitor the analgesic effect and for signs of opiate toxicity. Note, use with caution in patients with hepatic impairment.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydromorphone is extensively glucuronidated and excreted in the urine mainly as conjugated metabolites. Hydromorphone is a poor inhibitor of CYP450 enzymes and is not expected to alter boceprevir concentrations. Note, use of hydromorphone in patients with ANY degree of hepatic impairment is contraindicated in its European SPC, but the US Prescribing Information does not recommend it for patients with severe hepatic impairment and suggests a dose reduction for patients with moderate hepatic impairment.

Coadministration has not been studied. CYP3A4 is likely to have role in the metabolism of hydroxychloroquine. Boceprevir may increase hydroxychloroquine concentrations through CYP3A4 inhibition although the clinical significance of this is uncertain. Monitor for increased hydroxychloroquine side effects. Note, the European SPC for hydroxychloroquine recommends caution in impaired hepatic function.

Coadministration has not been studied but may increase concentrations of hydroxyzine. A clinically significant effect on boceprevir exposure is unlikely. Note, as hydroxyzine elimination is impaired in patients with hepatic dysfunction, daily dose or dose frequency should be reduced in patients with impaired liver function.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hyoscine acts predominantly locally and undergoes minimal absorption.