Coadministration has not been studied with abacavir alone but based on metabolism and clearance a clinically significant interaction is unlikely. Abacavir is metabolised by alcohol dehydrogenase and UGT, which is not expected to be affected by glecaprevir/pibrentasvir, and is renally cleared.  Glecaprevir/pibrentasvir and abacavir was evaluated as part of a Phase 1 study with Triumeq (abacavir/dolutegravir/lamivudine) and showed no clinically significant interactions.

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. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and data from ketoconazole have shown a negligible effect of CYP3A4 inhibitors on abiraterone.

Coadministration has not been studied. Acalabrutinib is a CYP3A4 and P-gp substrate. Acalabrutinib concentrations may increase due to mild inhibition of CYP3A4 and inhibition of P-gp by glecaprevir/pibrentasvir which may result in increased toxicity. On treatment monitoring is recommended.

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. After ingestion of acarbose the majority of active unchanged drug remains in the lumen of the gastrointestinal tract to exert its pharmacological effect and is metabolised by intestinal enzymes and by the gut microflora.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acebutolol is mainly excreted in the urine as the diacetol metabolite, which is not mediated by CYP450.

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 glecaprevir/pibrentasvir.

Coadministration has not been studied. Acenocoumarol is metabolised by CYP2C9 (major) and CYP1A2. Glecaprevir/pibrentasvir is a mild inhibitor of CYP1A2 and clinically significant interactions are unlikely. However, as acenocoumarol has a narrow therapeutic index and concentrations may increase, close monitoring of INR and other adverse effects is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aciclovir is eliminated primarily unchanged in the urine via glomerular filtration and active renal secretion. It is transported by OCT3 which is not expected to be affected by glecaprevir/pibrentasvir

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acitretin undergoes isomerisation and glucuronidation which are not expected to be affected by glecaprevir/pibrentasvir.

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 glecaprevir/pibrentasvir should be separated by 4 hours. [Note: this interaction is not specific for glecaprevir/pibrentasvir, 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. Adalimumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Glecaprevir/pibrentasvir is not expected to interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glecaprevir/pibrentasvir is metabolised by and is a weak inhibitor of CYP3A4. The potential for hepatically metabolised interactions with adefovir is low. Adefovir is largely excreted unchanged via renal glomerular filtration and active renal secretion by OAT1, which are not expected to be affected by glecaprevir/pibrentasvir. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Agomelatine is metabolized predominantly by CYP1A2 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP1A2 and is unlikely to affect the exposure of agomelatine to any clinically significant extent. [Note, agomelatine is contraindicated in hepatic impairment as increases in exposure of 140-fold have been seen in cirrhotic patients.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Albendazole is metabolized in part by CYP3A4, but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of albendazole to any clinically significant extent.

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.  Albiglutide slows gastric emptying, but this is unlikely to have a clinically relevant effect on glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alcohol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase. Acute alcohol use inhibits CYP2E1. Chronic use may induce CYP2E1 and to a lesser extent CYP3A4 but this is unlikely to be clinically relevant. Glecaprevir/pibrentasvir does not interact with these pathways. Additionally, a study of over 15,000 veterans treated with DAAs found no association between alcohol use and SVR12, suggesting that alcohol does not affect the efficacy of DAAs.

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 glecaprevir/pibrentasvir 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, alendronate should be separated from food or other medicinal products and therefore should be separated from glecaprevir/pibrentasvir administration. [Note: this interaction is not specific for glecaprevir/pibrentasvir, but for any medication taken with alendronic acid.]

Coadministration has not been studied. Concentrations of alfentanil may increase due to mild CYP3A4 inhibition by glecaprevir/pibrentasvir. Due to the narrow therapeutic index of alfentanil, patients should be monitored closely for adverse effects including respiratory depression. Dose reduction may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfuzosin is metabolised by CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of alfuzosin to any clinically significant extent.

Coadministration has not been studied. Aliskiren is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by glecaprevir/pibrentasvir. Concomitant use with aliskiren is not recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as allopurinol is metabolised by xanthine oxidase. [Note, the European SmPC and US Prescribing Information for allopurinol recommend a reduced dose in hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies indicate a minor role for CYP3A4 and CYP2D6 in the metabolism of almotriptan. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of almotriptan to any clinically significant extent.

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 metabolism and clearance a clinically significant interaction is unlikely. Alprazolam is mainly metabolised by CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of alprazolam to any clinically significant extent.

Antacids can be administered with glecaprevir/pibrentasvir and no dose alteration is required. 

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 glecaprevir/pibrentasvir cannot be ruled out. Doses of glecaprevir/pibrentasvir and alverine should be separated by 4 hours if possible. [Note: this interaction is not specific for glecaprevir/pibrentasvir, but for any medication taken with alverine citrate.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amantadine is only metabolized to a minor extent (principally N-acetylation) and is largely excreted unchanged in urine.

Coadministration has not been studied. Ambrisentan is glucuronidated by several UGT isoenzymes and metabolised to a lesser extent by CYP3A4. Ambrisentan is also a substrate of P-gp and OATP1B1. Coadministration with ciclosporin resulted in a 2-fold increase in ambrisentan exposure (possibly due to OATP1B1 inhibition). A similar effect may occur due to inhibition of OATP1B1 by glecaprevir. Advise patient to be aware of the potential for increased side effects during coadministration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as amikacin is largely excreted unchanged renally via glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amiloride is not metabolized by the liver but is excreted unchanged by the kidneys, with approximately 50% of an oral dose excreted in urine. 

Coadministration has not been studied. Concentrations of amiodarone may increase due to weak inhibition of CYP3A4 by glecaprevir/pibrentasvir. As amiodarone has a narrow therapeutic index and unpredictable therapeutic levels, monitor patients closely for signs and symptoms of toxicity. Use with caution and consider therapeutic drug monitoring and/or ECGs during treatment. Concentrations of glecaprevir/pibrentasvir may be increased due to P-gp inhibition by amiodarone. However, this is unlikely to be clinically significant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amisulpride is largely excreted unchanged in urine and undergoes relatively little metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19 which are not expected to be affected by glecaprevir/pibrentasvir.

Coadministration has not been studied. Amlodipine is metabolized by CYP3A4 and is a mild inhibitor of CYP3A4. Glecaprevir/pibrentasvir are metabolised by CYP3A4 and transported by P-gp. Although amlodipine may increase glecaprevir/pibrentasvir concentrations, this is unlikely to be of clinical significance. Increased concentrations of amlodipine may be seen by weak inhibition of CYP3A4 by glecaprevir/pibrentasvir but this is also unlikely to be clinically significant.

Coadministration has not been studied and is not recommended. Amobarbital induces CYP3A4 and P-gp and could decrease concentrations of glecaprevir/pibrentasvir. 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. Amodiaquine is metabolised by CYP2C8 which is not expected to be affected by glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amoxicillin is renally excreted unchanged by glomerular filtration and tubular secretion.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amphetamine is metabolised by CYP2D6 which is not expected to be affected by glecaprevir/pibrentasvir. 

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 interaction is unlikely. Ampicillin is renally excreted unchanged by glomerular filtration and tubular secretion.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Angarelide is metabolised by CYP1A2 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP1A2 and is unlikely to affect the exposure of anagrelide to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glecaprevir and pibrentasvir are mainly eliminated by biliary/faecal excretion. Anakinra does not interact with this pathway. Anakinra is an IL-1 receptor antagonist and is eliminated by glomerular filtration and subsequent tubular metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anastrozole is metabolized by multiple enzyme pathways and a clinically significant interaction is not expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as anidulafungin is not hepatically metabolized and there are no known transporter interactions.

Antacids can be administered with glecaprevir/pibrentasvir and no dose alteration is required. 

Apixaban is metabolized mainly by CYP3A4/5 (with minor contributions from CYPs 1A2, 2C8, 2C9, 2C19, and 2J2) and is a substrate of P-gp and BCRP. Concentrations of apixaban may increase due to inhibition of P-gp and BCRP by glecaprevir/pibrentasvir. However, a large, retrospective, multi-centre cohort study of patients coadministered HCV DAAs and DOACs, including glecaprevir/pibrentasvir and apixaban, reported a low incidence of bleeding which was similar to historic controls of patients with liver disease on DOACs alone, providing reassurance that any increase in apixaban levels is unlikely to be clinically relevant. Patients should be reminded to promptly report any signs of bleeding or bruising as with anyone who is prescribed DOACs. [Note: Product labels state that apixaban is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk. It is not recommended in severe hepatic impairment and should be used with caution in patients with mild or moderate hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aprepitant is a substrate, a moderate inhibitor, and an inducer of CYP3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and no significant effect on aprepitant is likely. During treatment with aprepitant, CYP3A4 is inhibited although this is unlikely to have a clinically significant effect on glecaprevir/pibrentasvir due to the large therapeutic safety margins. Note, following cessation of aprepitant, glecaprevir/pibrentasvir concentrations may decrease due to short-term mild induction of CYP2C9, CYP3A4 and glucuronidation, though any effect should be transient.

Coadministration has not been studied. Aripiprazole is metabolised by CYP3A4 and concentrations may increase due to weak inhibition of CYP3A4 by glecaprevir/pibrentasvir. As aripiprazole has a narrow therapeutic index and unpredictable therapeutic levels, monitor patients closely for signs and symptoms of toxicity.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Artemether is metabolised by CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of artemether to any clinically significant extent.

Coadministration has not been studied. Artemisinins undergo rapid metabolism via several CYP450 (CYPs 3A4, 2A6, 2B6). The active metabolite (dihydroartemisinin, which has greater potency than the parent drug) is further metabolized via UGTs 1A9 and 2B7 and has been shown to induce CYP3A4. This is unlikely to have a clinically significant effect on glecaprevir/pibrentasvir due to the large therapeutic safety margins.

Coadministration has not been studied. Dihydroartemisinin (the active metabolite of artesunate) is further metabolised via UGTs 1A9 and 2B7 and has been shown to induce CYP3A4. This is unlikely to have a clinically significant effect on glecaprevir/pibrentasvir due to the large therapeutic safety margins.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ascorbic acid is largely hydrolysed to salicylic acid followed by conjugation with either glycine or glucuronic acid.

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 but based on metabolism and clearance a clinically significant interaction is unlikely as aspirin is metabolised by deacetylation and UGT2B7 conjugation.

Coadministration has not been studied. Astemizole is metabolised by CYP3A4 and glecaprevir/pibrentasvir is only a weak inhibitor CYP3A4. Although clinically significant interaction is unlikely, use with caution as astemizole has a narrow therapeutic index and has been discontinued in many countries.

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atenolol is mainly eliminated unchanged in the kidney, predominantly by glomerular filtration with some involvement of OAT1 which is not affected by glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atomoxetine is metabolised by CYP2D6 which is not expected to be affected by glecaprevir/pibrentasvir.

Coadministration of glecaprevir/pibrentasvir and atorvastatin (10 mg single dose) increased atorvastatin AUC by 8.28-fold and increased Cmax by 22-fold. Coadministration is not recommended due to increased levels of atorvastatin, caused by inhibition of OATP1B1, P-gp and BCRP by glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as atovaquone is mainly eliminated unchanged in the faeces.

Coadministration has not been studied. Atropine metabolism has not been well described but is thought to be by oxidation and conjugation to inactive metabolites and up to 50% is excreted unchanged by the kidneys. A clinically significant interaction is unlikely; however, atropine may alter the absorption of glecaprevir/pibrentasvir by possibly delaying gastric emptying but the clinical significance of this is unknown.

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. Axitinib is metabolised by CYP3A4. Glecaprevir is a mild inhibitor of CYP3A4 and therefore could potentially increase axitinib exposure. The clinical relevance of this interaction is unknown. No a priori dosage adjustment is recommended for axitinib.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. (Note, azathioprine interacts with ribavirin and if ribavirin is part of the regimen it is important to refer to the product information for ribavirin and azathioprine.)

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azilsartan is predominantly metabolised by CYP2C9 which is not expected to be affected by glecaprevir/pibrentasvir.

Coadministration has not been studied. Data suggest that azithromycin may be a substrate for P-gp and concentrations may increase due to inhibition of P-gp by glecaprevir/pibrentasvir. However, this is unlikely to be clinically significant due to azithromycin’s wide therapeutic index.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Baclofen is mainly excreted in the urine or deaminated.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glecaprevir and pibrentasvir are mainly eliminated by biliary/faecal excretion and are substrates of CYP3A4 and P-gp. Bamlanivimab and etesevimab are IgG1 monoclonal antibodies and are likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Bamlanivimab and etesevimab are not metabolized by CYP enzymes. Interactions with concomitant medications that are substrates, inducers, or inhibitors of CYP enzymes are unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glecaprevir and pibrentasvir are mainly eliminated by biliary/faecal excretion. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Basiliximab is an immunoglobulin and no metabolic drug-drug interactions are expected. Extensive studies have been carried out with concomitant medication showing no adverse effects.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Beclomethasone is metabolised by hydrolysis to beclomethasone 17-monopropionate in vivo although it is a substrate of CYP3A4 in vitro. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of beclometasone to any clinically significant extent.

Coadministration has not been studied. Bedaquiline is metabolized by CYP3A4 and concentrations may increase due to weak inhibition of CYP3A4 by glecaprevir/pibrentasvir. Caution is advised due to the narrow therapeutic index of bedaquiline and risk of serious adverse effects. If coadministration is required, more frequent ECG monitoring and monitoring of transaminases is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as benazepril is glucuronidated and renally cleared.

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 glecaprevir/pibrentasvir.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bepridil is metabolised by CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of bepridil to any clinically significant extent.

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. Betamethasone is metabolised by CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of betamethasone to any clinically significant extent.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. 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 with glecaprevir/pibrentasvir. [Note, the European SmPC for bezafibrate contraindicates its use in significant hepatic disease.]

Coadministration has not been studied. Bictegravir is a substrate of P-gp and concentrations may increase, but to a modest extent, as glecaprevir/pibrentasvir inhibits P-gp. Coadministration of bictegravir with darunavir/cobicistat (a strong CYP3A4 and P-gp inhibitor) increased bictegravir exposure by 74%. This increase is unlikely to be clinically significant; available dose exposure data, as well as data from phase 2 and phase 3 studies (48 weeks treatment), have shown a good safety profile with up to a 2.4 fold increase in bictegravir AUC. Studies performed with emtricitabine or tenofovir alafenamide showed no clinically significant interactions with glecaprevir/pibrentasvir. Note, the European product label for Biktarvy (bictegravir/FTC/TAF) indicates that coadministration of glecaprevir may increase bictegravir plasma concentrations and recommends caution.

Coadministration has not been studied but may increase concentrations of bilastine due to inhibition of P-gp by glecaprevir/pibrentasvir. No a priori dose modification is recommended but monitoring for signs and symptoms of increased bilastine exposure is recommended.

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 glecaprevir/pibrentasvir. The potential interaction can be resolved by giving bisacodyl at least 4 hours after glecaprevir/pibrentasvir. [Note: this interaction is not specific for glecaprevir/pibrentasvir, but for any medication taken with bisacodyl.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisoprolol is metabolised by CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of bisoprolol to any clinically significant extent. [Note, the European product label for bisoprolol recommends a maximum of 10 mg in severe hepatic impairment whereas the US Prescribing Information recommends an initial 2.5 mg 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. Black cohosh does not appear to be involved in drug metabolism to a clinically significant effect. Standardized black cohosh supplements, when taken at recommended doses, pose little risk for herb-drug interactions.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Bortezomib is metabolized by and is a weak inhibitor of CYPs 1A2, 2C9, 2C19, 2D6 and 3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of bortezomib to any clinically significant extent.

Coadministration is not recommended. Coadministration of glecaprevir/pibrentasvir with bosentan, a moderate CYP3A inducer, may decrease concentrations of glecaprevir/pibrentasvir, leading to reduced therapeutic effect.

Coadministration has not been studied. Bosutinib is metabolised principally by CYP3A4 and concentrations may increase as glecaprevir is a weak inhibitor of CYP3A4. This may result in adverse effects. Use with caution.

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. Glecaprevir is a mild inhibitor of CYP3A4 and may increase concentrations of MMAE and the incidence of neutropenia, but this is unlikely to be clinically relevant. No a priori dose adjustment is recommended but patients should be monitored for adverse reactions.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brinzolamide is metabolised by CYP3A4 which is not expected to be affected by glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brivudine is an analog of thymidine and is incorporated into viral DNA. The metabolism of brivudine is poorly described but to date there is no evidence of CYP or transporter involvement.

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 glecaprevir/pibrentasvir. However, based on data with midazolam (AUC increased by 24%), this is unlikely to be clinically significant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromazepam is a substrate of CYP1A2 and CYP2D6 which are not expected to be affected by glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromocriptine is metabolised by CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of bromocriptine to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromperidol is a metabolized by CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of bromperidol to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Budesonide is metabolised via CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of budesonide to any clinically significant extent.

Coadministration has not been studied. Glecaprevir/pibrentasvir is a substrate and mild inhibitor of CYP3A4 and is transported via P-gp and OATP1B1. A clinical interaction study of high-dose bulevirtide (administered at 5 mg twice daily) showed a 1.34 fold increase of Cmax and AUC of pravastatin (40 mg single dose) a substrate of OATP1B1/3 and NTCP. When bulevirtide is prescribed at the recommended dose of 2 mg, the risk for clinically relevant interactions with OATP1B1/OATP1B3 and/or NTCP substrates is considered low. However, it should be noted that the product label recommends clinical monitoring if bulevirtide is coadministered with glecaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bumetanide is mainly excreted in the urine and is not transported by OATP.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupivacaine is metabolised by UGT, CYPs 1A2 and 3A4, and amide hydrolysis which are not expected to be affected by glecaprevir/pibrentasvir.

Coadministration of glecaprevir/pibrentasvir (300/120 mg once daily) and buprenorphine/naloxone was studied in 12 subjects on individualized regimens of buprenorphine/naloxone. Dose normalized Cmax, AUC and C24 were slightly increased for buprenorphine (8%, 17% and 24%) and norbuprenorphine (25%, 30% and 21%). Naloxone dose-normalised Cmax and AUC were minimally affected (12% change or less). These changes were not considered clinically significant. Exposures of glecaprevir and pibrentasvir were similar to the observed values in previous studies. No dose adjustment is required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupropion is metabolised by CYP2B6 which is not expected to be affected by glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buspirone is metabolised by CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of buspirone to any clinically significant extent.

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

Coadministration with intramuscular cabotegravir and rilpivirine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of oral rilpivirine and glecaprevir/pibrentasvir was shown to increase rilpivirine Cmax, AUC and Cmin by 105%, 84% and 77%, respectively (n=12); this was deemed within safety limits thus no dose adjustment is required for rilpivirine. Glecaprevir and pibrentasvir inhibit intestinal P-glycoprotein but this is not problematic with intramuscular administration of cabotegravir and rilpivirine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Calcitonin is metabolised primarily via proteolysis in the kidney and to date no clinically significant interactions have been published that would be of concern.

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 glecaprevir/pibrentasvir.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Canagliflozin is primarily metabolised by UGTs 1A9 and 2B4 which are not affected by glecaprevir/pibrentasvir. Canagliflozin is a substrate and inhibitor of P-gp. Canagliflozin concentrations may increase due to inhibition of P-gp by glecaprevir/pibrentasvir but this is unlikely to be of clinical significance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glecaprevir and pibrentasvir are mainly eliminated by biliary/faecal excretion. Canakinumab is eliminated via intracellular catabolism.

Coadministration has not been studied. Although candesartan inhibits OATP1B1 in vitro there is no human data. Data shows that candesartan is a P-gp inhibitor however repeated oral dosing of candesartan did not alter steady state pharmacokinetics of digoxin (a probe P-gp substrate) in healthy volunteers and an interaction with glecaprevir/pibrentasvir is unlikely. However, monitoring for ALT elevations may be required. [Note, use of candesartan in severe hepatic impairment is contraindicated in the European SmPC; the US Prescribing Information recommends caution in moderate hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cannabidiol is mainly metabolized by CYP3A4 and CYP2C19. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of cannabidiol to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tetrahydrocannabinol (THC, the psychoactive component of cannabis) is metabolised by CYP2C9 and CYP3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of cannabis to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Capecitabine is metabolised by CYP2C9 which is not expected to be affected by glecaprevir/pibrentasvir.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Captopril is metabolised by sulfation and approximately 40-50% is excreted in the urine.

Coadministration is not recommended. Induction of CYP3A4 and/or P-gp by carbamazepine is expected to significantly decrease plasma concentrations of glecaprevir/pibrentasvir; this may lead to reduced therapeutic effect and potential virological failure. Coadministration of glecaprevir/pibrentasvir (single dose) and carbamazepine (200 mg twice daily) decreased glecaprevir Cmax and AUC by 67% and 66% and decreased pibrentasvir Cmax and AUC by 50% and 51%. Note - there are a small number of cases reported of patients who have remained on an inducing antiepileptic during HCV DAA therapy (including with glecaprevir/pibrentasvir) and achieved a sustained virologic response. Although every effort to prevent concomitant use of glecaprevir/pibrentasvir and potent inducers should be made, these cases have demonstrated that clinical cure may still be achieved in patients where coadministration cannot be avoided. Therapeutic drug level monitoring could be considered, where available.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carbimazole is a pro-drug which undergoes rapid and virtually complete metabolism to the active metabolite, thiamazole (methimazole). There is little evidence of marked interactions with this drug.

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

Coadministration has not been studied but carfentanil concentrations may be increased due to weak CYP3A4 inhibition by glecaprevir/pibrentasvir. The impact of weak CYP3A4 inhibition is unclear since carfentanil is only present at very low concentrations. However, even modest increases of carfentanil levels may lead to an increased risk of severe toxicities, including potentially fatal respiratory depression. Since carfentanil is an extremely strong opiate, reported to be up to 10,000 times more potent than morphine, and multiple deaths have resulted from its use, we would advise patients to avoid.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carisoprodol is metabolised by CYP2C19 which is not expected to be affected by glecaprevir/pibrentasvir.

Coadministration has not been studied. Carvedilol is a substrate and an inhibitor of P-gp. Concentrations of both carvedilol and glecaprevir/pibrentasvir may increase. Due to the potential increase in carvedilol concentrations, close monitoring for side effects including heart rate and blood pressure is recommended. [Note, the US Prescribing Information contraindicates carvedilol in patients with severe liver impairment and the European SmPC contraindicates it in patients with hepatic dysfunction.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glecaprevir and pibrentasvir are mainly eliminated by biliary/faecal excretion and are substrates of CYP3A4 and P-gp. Casirivimab and imdevimab are IgG1 monoclonal antibodies and are likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Casirivimab and imdevimab are not metabolized by CYP enzymes. Interactions with concomitant medications that are substrates, inducers, or inhibitors of CYP enzymes are unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caspofungin undergoes spontaneous chemical degradation and non-CYP mediated 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 interaction is unlikely. Cat’s claw is an inhibitor of CYP3A4, any increase of glecaprevir/pibrentasvir levels via this enzyme are unlikely to be clinically significant. Mild CYP3A4 inhibition of glecaprevir is unlikely to affect cat’s claw.

Coadministration has not been studied but based on metabolism and clearance a clinically significant 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 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 interaction is unlikely. Cefalexin is predominantly eliminated unchanged renally by glomerular filtration and tubular secretion via OAT1 and MATE1 which are not expected to be affected by glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefazolin is predominantly excreted unchanged in the urine, mainly by glomerular filtration with some renal tubular secretion.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies indicate that OATs participate in the renal elimination of cefotaxime but OAT1 and OAT3 are not expected to be affected by glecaprevir/pibrentasvir.

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Celecoxib is a substrate of CYP2C9 which is not expected to be affected by glecaprevir/pibrentasvir. [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 as celiprolol is mainly excreted unchanged in urine and faeces.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cetirizine is metabolised only to a limited extent and is eliminated unchanged in the urine through both glomerular filtration and tubular secretion.

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.

Coadministration has not been studied. Chloramphenicol is metabolised by CYP3A4 and is an inhibitor of CYPs 2C19 and 3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of chloramphenicol to any clinically significant extent. Inhibition of CYP3A4 by chloramphenicol is unlikely to have a clinically significant effect on glecaprevir/pibrentasvir due to the large therapeutic safety margins.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chloroquine is rapidly metabolised by CYPs 2C8, 3A4 and 2D6 to the pharmacologically active desethylchloroquine and bisdesethylchloroquine and is also renally eliminated. These pathways are not expected to be affected by glecaprevir/pibrentasvir. Note, the European SPC and US Prescribing Information for chloroquine both recommend caution in impaired hepatic function.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorothiazide is not metabolised and is eliminated rapidly by renal excretion.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolized by CYP2D6 which is not expected to be affected by glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorpromazine is a substrate of CYPs 2D6 (major), 1A2, and 3A4 in vitro, which are not expected to be affected by glecaprevir/pibrentasvir. [Note, the European SmPC for chlorpromazine advises that its use should be avoided in patients with hepatic dysfunction.]

Co-administration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorprothixene is metabolised by CYP2D6 which is not affected by glecaprevir/pibrentasvir. [Note, although no interaction is anticipated, ECG monitoring is mandatory prior to treatment with chlorprothixene.]

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciclesonide is metabolised by CYP3A4 and CYP2D6 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of ciclesonide to any clinically significant extent.

Concomitant use of glecaprevir/pibrentasvir with ciclosporin requires close monitoring of doses as concentrations of glecaprevir/pibrentasvir may increase due to inhibition of OATP1B. Coadministration of glecaprevir/pibrentasvir and ciclosporin (100 mg) increased glecaprevir/pibrentasvir concentrations within acceptable parameters (glecaprevir Cmax, AUC and Cmin by 30%, 37% and 34%, respectively; no change in pibrentasvir Cmax and AUC, but Cmin increased by 26%). However at higher doses of ciclosporin (400 mg), glecaprevir concentrations increased significantly (Cmax 4.51-fold, AUC 5.08-fold). Glecaprevir/pibrentasvir is not recommended for use in patients requiring stable ciclosporin doses >100 mg per day.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cidofovir is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3 which are not expected to be affected by glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cilazapril is metabolised by esterases to the active cilazaprilat which is excreted unchanged in 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. Cilostazol is extensively metabolised by CYP3A4 and CYP2C19. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of cilostazol to any clinically significant extent.

Coadministration has not been studied but may result in decreased concentrations of glecaprevir. Coadministration with the proton pump inhibitor omeprazole (40 mg once daily) decreased glecaprevir AUC by ~50%. A reduction in glecaprevir exposure is possible with cimetidine, however, this is unlikely to be clinically significant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciprofloxacin is primarily renally eliminated unchanged by glomerular filtration and tubular secretion by OAT3. These pathways are not expected to be affected by glecaprevir/pibrentasvir.

Coadministration has not been studied. Cisapride is metabolised by CYP3A4 and glecaprevir/pibrentasvir is a weak inhibitor of CYP3A4 and clinically significant interaction cannot be ruled out. Use with caution and close monitoring due to cisapride’s narrow therapeutic index.

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 interaction is unlikely. Cisplatin is eliminated renally by OCT2 and MATE1 but glecaprevir/pibrentasvir is not expected to inhibit these transporters

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Citalopram is metabolized by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect these pathways to any clinically significant extent.

Coadministration has not been studied. Clarithromycin is a substrate and inhibitor of both CYP3A4 and P-gp; glecaprevir is an inhibitor of P-gp and a mild inhibitor of CYP3A4. Coadministration could increase glecaprevir, pibrentasvir and clarithromycin concentrations due to CYP3A4 and P-gp inhibition. Any increase in glecaprevir or pibrentasvir is likely to be within the upper clinical bounds and not clinically significant. The significance of increased clarithromycin concentrations is unknown and monitoring may be required.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Clindamycin is metabolised by CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of clindamycin to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clobazam is metabolised primarily by CYP3A4 and to a lesser extent by CYP2C19. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of clobazam to any clinically significant extent. Clobazam is a weak CYP3A4 inducer and could potentially decrease glecaprevir exposure to a very limited extent. However, this is unlikely to be clinically relevant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following topical application to most areas of normal skin, only minimal amounts of the drug reach the dermis and subsequently the systemic circulation. Although clobetasol is a substrate of CYP3A4, glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of clobetasol to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following topical application to most areas of normal skin, only minimal amounts of the drug reach the dermis and subsequently the systemic circulation. Although clobetasone is a substrate of CYP3A4, glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of clobetasone to any clinically significant extent.

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, clodronate should be taken more than two hours after and one hour before any other oral drugs. [Note: this interaction is not specific for glecaprevir/pibrentasvir, but for any oral medication taken with clodronate.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. Glecaprevir/pibrentasvir does not interact with these pathways. [Note, the US Prescribing Information for clofazimine recommends to avoid clofazimine in patients with hepatic impairment (Child-Pugh Class A, B, and C) unless the benefit outweighs the risk.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Studies suggest clomifene is metabolised by CYP3A4, CYP2D6 and UGTs. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of clomifene to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolised mainly by CYP2D6 which is not expected to be affected by glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clonazepam is metabolised by CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of clonazepam to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as 70% of clonidine is excreted in the urine, largely in the form of unchanged parent drug.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug that is converted to its active metabolites by CYPs 2C19, 3A4, 2B6, and 1A2. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of clopidogrel to any clinically significant extent. Based on a preliminary drug interaction study with the probe CYP2C19 substrate, omeprazole, no clinically significant interaction is expected when glecaprevir/pibrentasvir is co-administered with CYP2C19 substrates. [Note, the European SmPC for clopidogrel contraindicates it use in severe hepatic impairment but the US Prescribing Information states no dose alteration.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clorazepate is rapidly converted to nordiazepam which is then metabolized to oxazepam by CYP3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of clorazepate to any clinically significant extent.

Coadministration has not been studied. The metabolism of clotiapine has not been well characterised but is likely to involve CYP450 enzymes. Clotiapine concentrations may increase due to mild inhibition of CYP3A4 by glecaprevir/pibrentasvir but the clinical significance is unclear. No a priori dose modification is recommended but, in the absence of data, monitoring may be required. A clinically significant effect on glecaprevir/pibrentasvir is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cloxacillin is metabolised to a limited extent and the unchanged drug and metabolites are excreted in the urine by glomerular filtration and renal tubular secretion. The transporters that facilitate this have not been described.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clozapine is metabolised by CYP1A2 and CYP3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYPs 3A4 and 1A2 and interactions via these enzymes are not deemed clinically significant in the product labels. However, as clozapine is associated with significant toxicities, and in the absence of further data, close monitoring is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cocaine is metabolised via multiple pathways including serum and hepatic cholinesterases, spontaneous hydrolysis, hepatic carboxyesterase and CYP3A4 to norcocaine. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of cocaine to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Codeine is metabolised by CYP2D6 and CYP3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of codeine to any clinically significant extent.

Coadministration has not been studied but may increase colchicine concentrations due to inhibition of P-gp by glecaprevir/pibrentasvir. As colchicine has a narrow therapeutic window, consider alternatives. If coadministration is necessary, dose reduction should be considered in patients with normal hepatic function and coadministration should be used with caution in those with hepatic or renal impairment. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of colecalciferol 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 colecalciferol and introduction of 6',7'-dihydroxybergamottin (a CYP3A4 inhibitor in grapefruit juice) reversed the effects of rifampicin on colecalciferol clearance. Weak inhibition of CYP3A by glecaprevir/pibrentasvir is not expected to reduce the effect of colecalciferol, but the consequence of CYP3A inhibition on the clinical effect of colecalciferol is not known. Glecaprevir and pibrentasvir are metabolized by CYP3A4 and are substrates of P-gp and/or BCRP. Colecalciferol does not interact with these pathways.

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 glecaprevir/pibrentasvir, but for any medication taken with colestyramine.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Conivaptan is a substrate and inhibitor of CYP3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of conivaptan to any clinically significant extent. Inhibition of CYP3A4 by conivaptan is unlikely to have a clinically significant effect on glecaprevir/pibrentasvir due to the large therapeutic safety margins.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of conjugated estrogens is complex and involves CYP3A4 isoenzymes and glucuronidation in the liver. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect these pathways to any clinically significant extent. However, glecaprevir/pibrentasvir is an inhibitor of OATP and in vitro studies have shown conjugated estrogens are transported via OATP: the clinical significance of this is unknown. An OATP-mediated interaction is possible, which may increase exposure of conjugated estrogens to a limited extent. This is unlikely to be clinically relevant with short durations of treatment for hepatitis C.

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.

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. Cyclobenzaprine undergoes a complex metabolic process involving glucuronidation and several CYP enzymes including CYPs 3A4 and 1A2. Glecaprevir/pibrentasvir is only a weak inhibitor of CYPs 3A4 and 1A2 and is unlikely to affect the exposure of cyclobenzaprine to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyclophosphamide is activated (major pathway) to 4-hydroxycyclophosphamide by CYPs 2B6 (major), 2C9 and 3A4. Inactivation (minor, 10%) to the neurotoxic chloroacetaldehyde metabolite is performed mainly by CYP3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect this pathway to any clinically significant extent.

Coadministration has not been studied and the pharmacokinetics of cytisine is poorly described. There are no reports of drug interactions or CYP involvement. Based on limited data for metabolism and clearance a clinically significant interaction is unlikely.

Coadministration increased dabigatran exposure due to P-gp inhibition by glecaprevir/pibrentasvir. Coadministration of dabigatran (150 mg single dose) and glecaprevir/pibrentasvir increased dabigatran Cmax and AUC by 2.05-fold and 2.38-fold. Coadministration is contraindicated in the European SPC for glecaprevir/pibrentasvir. However, the US Prescribing Information for glecaprevir/pibrentasvir refers to the dabigatran Prescribing Information which suggests no dose adjustment is needed in subjects with normal renal function, but to reduce dabigatran to 75 mg twice daily in subjects with creatinine clearance 30-50 mL/min (or avoid use) and does not recommend coadministration in subjects with creatinine clearance <30 mL/min.

Glecaprevir/pibrentasvir is a complete regimen. There are no data to support the coadministration with another NS5A agent such as daclatasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as dalteparin is mainly excreted unchanged by the kidney.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Danaparoid is renally excreted and no hepatic involvement was shown in animal studies.

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. Dapagliflozin is metabolised by UGT1A9 which is not expected to be affected by glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of dapsone is largely by N-acetylation and multiple CYP enzymes have been described.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Darbepoetin is not hepatically metabolized and to date no clinically significant interactions have been published that would be of concern.

Coadministration with darunavir/ritonavir is not recommended as it may substantially increase glecaprevir exposure. Medicinal products that inhibit OATP1B1/3 (e.g. darunavir) increase systemic concentrations of glecaprevir. Coadministration of darunavir/ritonavir (800/100 mg) increased glecaprevir AUC, Cmax and Cmin by 4.97-fold, 3.09-fold and 8.24-fold, respectively (n=12).

Coadministration with Symtuza has not been studied and is not recommended as it may substantially increase glecaprevir exposure. Medicinal products that inhibit OATP1B1/3 (e.g. darunavir/cobicistat increase systemic concentrations of glecaprevir. Coadministration of darunavir/ritonavir (800/100 mg) increased glecaprevir AUC, Cmax and Cmin by 4.97-fold, 3.09-fold and 8.24-fold, respectively. A similar interaction may occur with darunavir/cobicistat. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway.

Coadministration with darunavir/cobicistat has not been studied and is not recommended as it may substantially increase glecaprevir exposure. Medicinal products that inhibit OATP1B1/3 (e.g. darunavir) increase systemic concentrations of glecaprevir. Coadministration of darunavir/ritonavir (800/100 mg) increased glecaprevir AUC, Cmax and Cmin by 4.97-fold, 3.09-fold and 8.24-fold, respectively. A similar interaction may occur with darunavir/cobicistat.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dasatinib is a substrate and an inhibitor of cytochrome CYP3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of dasatinib to any clinically significant extent. Inhibition of CYP3A4 by dasatinib is unlikely to affect glecaprevir/pibrentasvir exposure due to the large therapeutic safety margins.

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 glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Glecaprevir is only a weak inhibitor of CYP3A4 and is unlikely to affect this pathway to any clinically significant extent.  [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 but based on metabolism and clearance a clinically significant interaction is unlikely. Desipramine is mainly metabolised by CYP2D6 which is not expected to be affected by glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of desloratadine is poorly characterised and no clinically relevant interactions have been observed with other inhibitors of CYP enzymes.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of desogestrel to any clinically significant extent. No dose adjustment is required when glecaprevir/pibrentasvir is co administered with progestin only contraception.

Coadministration of glecaprevir/pibrentasvir and doses of >20 μg ethinylestradiol is contraindicated. In interaction studies evaluating ethinylestradiol and glecaprevir/pibrentasvir in healthy female subjects, ALT elevations were observed in some subjects during coadministration. Based on increased ALT levels, coadministration of ethinylestradiol-containing hormonal contraceptives or hormone replacement therapies is not recommended. 

Coadministration with doses of 20 μg ethinylestradiol or less is permitted in the US Prescribing Information. In a phase 1 study, no adverse effects (AEs) of grade ≥ 2 ALT elevation and no serious or grade ≥ 3 AEs were reported in 66 healthy volunteers who were coadministered glecaprevir/pibrentasvir and ethinylestradiol/levonorgestrel (20/100 µg). PK parameters were within the expected ranges. However, coadministration with any dose of ethinylestradiol is contraindicated in the European Summary of Product Characteristics, due to increased ALT levels. 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. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of desogestrel to any clinically significant extent. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desvenlafaxine is a substrate of CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of desvenlafaxine to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexamethasone is a substrate and moderate inducer of CYP3A4 at doses above 16 mg. Glecaprevir undergoes minimal metabolism by CYP3A4. Glecaprevir and pibrentasvir are mainly eliminated by biliary/faecal excretion and are transported by P-gp and BCRP. Dexamethasone is a P-gp inducer in pre-clinical models but this is unlikely to be clinically relevant in this setting.

Coadministration has not been studied but based on limited data for metabolism and clearance a clinically significant interaction is unlikely. Note, the role of CYP450 in the metabolism of dexamfetamine has not been fully described.

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. Glecaprevir/pibrentasvir 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 of dextromethorphan (30 mg single dose) and glecaprevir/pibrentasvir (300/120 mg once daily) decreased dextromethorphan Cmax and AUC by 30% and 25% (n=12). This was not clinically significant and no dose adjustment is required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextropropoxyphene is metabolised by CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of dextropropoxyphene to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as diamorphine is metabolised mainly by deacetylation with multiple small pathway involvement.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diazepam is metabolised by CYP3A4 and CYP2C19 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of diazepam to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diclofenac is a substrate of CYP2C9, CYP3A4, UGT1A9 and UGT2B7, and is an inhibitor of the renal transporter MRP4. No effect of glecaprevir/pibrentasvir on diclofenac is expected due to the involvement of multiple enzyme pathways

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Didanosine is phosphorylated to its active triphosphate form and is not a substrate of any CYP isoenzyme. It is renally excreted.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dienogest is a substrate of CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of dienogest to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diflunisal is an aldoketoreductase inhibitor but this pathway is not involved in the metabolism of glecaprevir/pibrentasvir.

Coadministration with glecaprevir/pibrentasvir increased digoxin AUC by 1.48-fold and Cmax by 1.72-fold due to P-gp inhibition by glecaprevir/pibrentasvir. Use with caution. Therapeutic concentration monitoring of digoxin is recommended before initiating and during glecaprevir/pibrentasvir therapy. The US Prescribing Information for glecaprevir/pibrentasvir suggests reducing digoxin concentrations if required by decreasing the dose by approximately 50% or by modifying the dosing frequency.

Coadministration has not been studied. Dihydroartemisinin (the active metabolite of artesunate) induces CYP3A4 and may decrease exposure of glecaprevir/pibrentasvir but this is unlikely to be of clinical significance due to the large therapeutic safety margins.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dihydrocodeine is converted to dihydromorphine (active metabolite) by CYP2D6, to dihydrocodeine-6-glucuronide via UGT2B7 (major pathway) and to nordihydrocodeine by CYP3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of dihydrocodeine to any clinically significant extent.

Coadministration has not been studied. Dihydroergotamine is metabolised by CYP3A4. Although glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4, there is the potential for serious adverse events such as ergot toxicity due to the narrow therapeutic index of dihydroergotamine.

Coadministration has not been studied. Diltiazem is a substrate of CYP3A4 and P-gp. Concentrations may increase due to inhibition of P-gp and weak inhibition of CYP3A4 by glecaprevir/pibrentasvir. Close monitoring of heart rate and blood pressure is recommended and consider dose reduction if required.

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 glecaprevir/pibrentasvir is unlikely to be clinically relevant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diphenhydramine is a substrate (and inhibitor) of CYP2D6 which is not expected to be affected by glecaprevir/pibrentasvir. [Note, diphenhydramine should be used with caution 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 as dipyridamole is glucuronidated and does not appear to be metabolised by cytochrome P450s.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Disopyramide is a substrate of CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of disopyramide to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Disulfiram is an inhibitor of ALDH but this pathway is not involved in the metabolism of glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dofetilide is eliminated in the kidney by active secretion and is metabolized to a small extent by CYP3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of dofetilide to any clinically significant extent.

Coadministration with dolutegravir alone has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of dolutegravir and glecaprevir/pibrentasvir was evaluated as part of a Phase 1 study with Triumeq (abacavir/dolutegravir/lamivudine) and showed no clinically significant interaction with glecaprevir/pibrentasvir. No dose adjustment is required when glecaprevir/pibrentasvir is co administered with dolutegravir.

Coadministration of dolutegravir/abacavir/lamivudine and glecaprevir/pibrentasvir was evaluated as part of a Phase 1 study. Cmax and AUC for glecaprevir and pibrentasvir decreased by 25-28%, which is not clinically significant. No dose adjustment is required when glecaprevir/pibrentasvir is coadministered with dolutegravir/abacavir/lamivudine .

Coadministration with dolutegravir/lamivudine alone has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of dolutegravir and glecaprevir/pibrentasvir was evaluated as part of a Phase 1 study with Triumeq (abacavir/dolutegravir/lamivudine) and showed no clinically significant interaction with glecaprevir/pibrentasvir. No dose adjustment is required when glecaprevir/pibrentasvir is coadministered with dolutegravir/lamivudine.

Coadministration with dolutegravir/rilpivirine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of dolutegravir and glecaprevir/pibrentasvir was evaluated as part of a Phase 1 study with Triumeq (abacavir/dolutegravir/lamivudine) and showed no clinically significant interaction with glecaprevir/pibrentasvir. Coadministration of rilpivirine and glecaprevir/pibrentasvir increased rilpivirine Cmax, AUC and Cmin by 105%, 84% and 77%, respectively (n=12); this was deemed within safety limits. No dose adjustment is required when glecaprevir/pibrentasvir is coadministered with dolutegravir/rilpivirine.

Coadministration has not been studied. Domperidone is predominantly metabolised by CYP3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and may increase domperidone concentrations but to a modest extent. However, as domperidone has a narrow therapeutic index and is associated with QTc prolongation any modest increase could be clinically relevant. Use with caution and close monitoring. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Donepezil is metabolised by CYP3A4 and CYP2D6 (minor) but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of donepezil to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doravirine is metabolized by CYP3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 therefore is unlikely to affect the exposure of doravirine to any clinically significant extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doravirine is metabolized by CYP3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 therefore is unlikely to affect the exposure of doravirine to any clinically significant extent. No clinically significant interactions were observed when tenofovir-DF (with efavirenz and emtricitabine) and glecaprevir/pibrentasvir were coadministered or when lamivudine was coadministered with glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as dorzolamide undergoes minimal metabolism and is mainly excreted unchanged by the kidney.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dosulepin is extensively metabolised in the liver, likely by CYP2D6 (major) and CYP3A4, but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of dosulepin to any clinically significant extent. [Note: Dosulepin should be used with caution in mild to moderate hepatic impairment and avoided in severe hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxazosin is extensively metabolised by CYP3A4 and to a lesser extent CYP2D6 and CYP2C19. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of doxazosin to any clinically significant extent. [Note, the European SmPC for doxazosin does not recommend its use in severe hepatic impairment; the US Prescribing Information has a caution in hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxepin is primarily metabolized by CYP2C19 and CYP2D6, and to a lesser extent, by CYP1A2 and CYP2C9, none of which are expected to be affected by glecaprevir/pibrentasvir. [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.]

Coadministration has not been studied. Doxorubicin is metabolised by CYP enzymes and is a substrate for P-gp. Since glecaprevir/pibrentasvir inhibits P-gp and is a mild inhibitor of CYP3A4 there is the potential for increased doxorubicin exposure and a clinically significant interaction has to be considered. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxylamine is metabolized primarily by CYP2D6, CYP1A2, and CYP2C9. Glecaprevir/pibrentasvir does not interact with these pathways.

Coadministration has not been studied. Dronedarone is metabolised by CYP3A4 and concentrations may increase as glecaprevir/pibrentasvir is a weak inhibitor of CYP3A4. As dronedarone has a narrow therapeutic index and unpredictable therapeutic levels, monitor patients closely for signs and symptoms of toxicity. Use with caution and consider therapeutic drug monitoring and/or ECGs during treatment. The European Summary of Product Characteristics for Maviret states that dronedarone may increase plasma exposure of glecaprevir and pibrentasvir due to inhibition of P-gp and BCRP.

Coadministration has not been studied. Droperidol is metabolised by CYP3A4 and CYP1A2 and concentrations may increase as glecaprevir/pibrentasvir is a weak inhibitor of CYP3A4 and CYP1A2. Use with caution.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolised mainly without involvement of CYP enzymes with little known involvement of transporters.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolized by CYP3A4 and CYP1A2 and is glucuronidated. Drospirenone is metabolised in part by CYP3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect these pathways to any clinically significant extent. However, glecaprevir/pibrentasvir is an inhibitor of OATP and in vitro studies have shown estradiol to be a high-affinity OATP substrate: the clinical significance of this is unknown. An OATP-mediated interaction is possible, which may increase exposure of estradiol to a limited extent. This is unlikely to be clinically relevant with short durations of treatment for hepatitis C.

Coadministration with glecaprevir/pibrentasvir and doses of >20 μg ethinylestradiol is contraindicated. In interaction studies evaluating ethinylestradiol and glecaprevir/pibrentasvir in healthy female subjects, ALT elevations were observed in some subjects during coadministration. Based on increased ALT levels, coadministration of ethinylestradiol-containing hormonal contraceptives or hormone replacement therapies is not recommended.

Coadministration with doses of 20 μg ethinylestradiol or less is permitted in the US Prescribing Information. In a phase 1 study, no adverse effects (AEs) of grade ≥ 2 ALT elevation and no serious or grade ≥ 3 AEs were reported in 66 healthy volunteers who were coadministered glecaprevir/pibrentasvir and ethinylestradiol/levonorgestrel (20/100 µg). PK parameters were within the expected ranges. However, coadministration with any dose of ethinylestradiol is contraindicated in the European Summary of Product Characteristics, due to increased ALT levels. Drospirenone is metabolised mainly without the involvement of CYP enzymes with little known involvement of transporters so a clinically significant interaction with glecaprevir/pibrentasvir is not anticipated.

Coadministration has not been studied. Dulaglutide is degraded by general protein catabolism pathways therefore no metabolic interaction is expected. 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Duloxetine is metabolized by CYP2D6 and CYP1A2 which are not expected to be affected by glecaprevir/pibrentasvir. [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 but based on metabolism and clearance a clinically significant interaction is unlikely. Dutasteride is metabolised mainly by CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of dutasteride to any clinically significant extent. [Note, the European SmPC (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 but based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolized by CYP3A4 and CYP1A2 and is glucuronidated. Dydrogesterone is metabolized to dihydrodydrogesterone (possibly via CYP3A4). Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect these pathways to any clinically significant extent. However, glecaprevir/pibrentasvir is an inhibitor of OATP and in vitro studies have shown estradiol to be a high-affinity OATP substrate: the clinical significance of this is unknown. An OATP-mediated interaction is possible, which may increase exposure of estradiol to a limited extent. This is unlikely to be clinically relevant with short durations of treatment for hepatitis C.

Coadministration has not been studied. Ebastine is metabolised by CYP450 and concentrations may be increased due to mild CYP3A4 inhibition by glecaprevir. ECG monitoring should be considered as increased concentrations of ebastine can prolong the QT interval.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Studies using a cocktail of probe drugs showed Echinacea inhibited CYP1A2 and intestinal CYP3A activity, and induced hepatic CYP3A activity. The overall effect of Echinacea on CYP3A4 is unlikely to have a clinically significant effect on glecaprevir/pibrentasvir due to the large therapeutic safety margins.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. MDMA is mainly metabolized by CYP2D6 which is not expected to be affected by glecaprevir/pibrentasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eculizumab contains only naturally occurring amino acids and has no known active metabolites. Human antibodies are predominately catabolized by lysosomal enzymes to small peptides and amino acids. No drug interactions have been described to date.

Edoxaban is a substrate of P-gp and its active metabolite is a substrate of OATP1B1. Edoxaban concentrations may increase due to inhibition of P-gp and OATP1B1 by glecaprevir/pibrentasvir. No a priori dose modification is recommended. A large, retrospective, multi-centre cohort study of patients coadministered HCV DAAs and DOACs, including glecaprevir/pibrentasvir and edoxaban, reported a low incidence of bleeding which was similar to historic controls of patients with liver disease on DOACs alone, providing reassurance that the interaction is unlikely to be clinically relevant in the majority of patients. Patients should be reminded to promptly report any signs of bleeding or bruising as with anyone who is prescribed DOACs. [Note: product labels state that edoxaban is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk. It is not recommended in severe hepatic impairment and should be used with caution in patients with mild or moderate hepatic impairment.]

Coadministration is not recommended as efavirenz may reduce glecaprevir/pibrentasvir concentrations and this may lead to reduced therapeutic effect. Coadministration of glecaprevir/pibrentasvir and efavirenz/emtricitabine/tenofovir-DF (600/200/300 mg once daily) was studied to determine the effect on tenofovir concentrations. The effect on glecaprevir and pibrentasvir was not directly quantified within this study, but glecaprevir and pibrentasvir exposures were significantly lower than historical controls.

Coadministration of glecaprevir/pibrentasvir with other directly acting antivirals has not been studied and therefore cannot be recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eletriptan is primarily metabolised by CYP3A4 but glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 and is unlikely to affect the exposure of eletriptan to any clinically significant extent.

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 mild inhibition of CYP3A4 by glecaprevir/pibrentasvir. Caution and monitoring of adverse effects associated with increased eliglustat concentrations is recommended

Coadministration is contraindicated. Concomitant use of glecaprevir/pibrentasvir with OATP1B inhibitors, such as eltrombopag, may increase the risk of ALT elevations due to a significant increase in pibrentasvir plasma concentrations caused by OATP1B1/3 inhibition.

Coadministration of glecaprevir/pibrentasvir and elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide increased glecaprevir Cmax, AUC and Cmin by 2.50-fold, 3.05-fold and 4.58-fold, respectively; there was no change in pibrentasvir Cmax, but AUC and Cmin increased by 57% and 89%. However these increases were deemed to be within safety limits and no dose adjustment is required.