Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Abacavir can be administered with sofosbuvir/velpatasvir/voxilaprevir and no dose alteration is required. Abacavir is metabolised by UGTs which are not affected by sofosbuvir/velpatasvir/voxilaprevir.

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. Sofosbuvir/velpatasvir/voxilaprevir is not involved with this pathway.

Coadministration has not been studied. Acalabrutinib is a CYP3A4 and P-gp substrate. Acalabrutinib concentrations may increase due to inhibition of P-gp by velpatasvir and voxilaprevir 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 sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acenocoumarol is metabolised by CYP2C9 and CYP1A2 which are not affected by sofosbuvir/velpatasvir/voxilaprevir. However, close monitoring of INR is recommended as this may change as a result of improved liver function.

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 and sofosbuvir/velpatasvir/voxilaprevir do not inhibit or induce this pathway.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely as acitretin undergoes isomerisation and glucuronidation which are not affected by sofosbuvir/velpatasvir/voxilaprevir.

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 sofosbuvir/velpatasvir/voxilaprevir should be separated by 4 hours. [Note: this interaction is not specific for sofosbuvir/velpatasvir/voxilaprevir 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. Sofosbuvir/velpatasvir/voxilaprevir 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. Adefovir is not expected to inhibit or induce any relevant metabolic enzymes or transporters of sofosbuvir/velpatasvir/voxilaprevir. Adefovir is eliminated renally via glomerular filtration and active renal secretion by OAT1. Sofosbuvir/velpatasvir/voxilaprevir do not inhibit this transporter.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as agomelatine is metabolized predominantly by CYP1A2 which is not affected by sofosbuvir/velpatasvir/voxilaprevir. [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 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

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.  GLP-1 agonists such as albiglutide also have the potential to inhibit gastric secretion and thereby impact drugs whose absorption is gastric dependent, such as velpatasvir. A reduction in velpatasvir exposure is possible with albiglutide, however, this is unlikely to be clinically significant. Albiglutide slows gastric emptying, but this is unlikely to have a clinically relevant effect on sofosbuvir/velpatasvir/voxilaprevir.

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. Velpatasvir/voxilaprevir are CYP3A4 substrates but no clinically significant interaction is expected. Sofosbuvir 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 sofosbuvir/velpatasvir/voxilaprevir and no dose alteration is required. Alendronate is not metabolised and is cleared from the plasma by uptake into bone and elimination via renal excretion. Although no pharmacokinetic interaction is expected, note that alendronate should be separated from food or other medicinal products and therefore should be separated from sofosbuvir/velpatasvir/voxilaprevir administration. [Note: this interaction is not specific for sofosbuvir/velpatasvir/voxilaprevir, but for any medication taken with alendronic acid.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfentanil is metabolised by CYP3A4 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfuzosin is metabolised by CYP3A4 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied. Aliskiren is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by velpatasvir and voxilaprevir. Monitor for side effects and aliskiren toxicities. Although both drugs are substrates of P-gp, no effect on sofosbuvir/velpatasvir/voxilaprevir concentrations is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Allopurinol is metabolised by xanthine oxidase which is not affected by sofosbuvir/velpatasvir/voxilaprevir. [Note, the European Summary of Product Characteristics 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 but these pathways are not affected by sofosbuvir/velpatasvir/voxilaprevir.

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 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but may decrease velpatasvir concentrations due the increase in gastric pH. Administration of an antacid and sofosbuvir/velpatasvir/voxilaprevir should be separated by 4 hours.

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 sofosbuvir/velpatasvir/voxilaprevir cannot be ruled out. Doses of sofosbuvir/velpatasvir/voxilaprevir and alverine should be separated by 4 hours if possible. [Note: this interaction is not specific for sofosbuvir/velpatasvir/voxilaprevir, 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 as 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 is 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 the inhibition of OATP1B1 by voxilaprevir and velpatasvir. 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 metabolised by the liver with approximately 50% of an oral dose excreted in urine.

Coadministration has not been studied and is not recommended. Coadministration of amiodarone and sofosbuvir combined with another direct acting antiviral such as velpatasvir and voxilaprevir may result in serious symptomatic bradycardia. As cases are potentially life threatening, amiodarone should only be used in patients on sofosbuvir/velpatasvir/voxilaprevir when other alternative anti-arrhythmic treatments are not tolerated or are contraindicated.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as 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 affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied. Amlodipine is metabolized by CYP3A4 and is a mild inhibitor of CYP3A4. Sofosbuvir/velpatasvir/voxilaprevir is metabolised by CYP3A4 and transported by P-gp. Although amlodipine may increase sofosbuvir/velpatasvir/voxilaprevir concentrations, this is unlikely to be of clinically significance. 

Coadministration has not been studied and is not recommended. Amobarbital induces CYP3A4 and P-gp and could decrease concentrations of sofosbuvir/velpatasvir/voxilaprevir. 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 affected by sofosbuvir/velpatasvir/voxilaprevir.

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 affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Anagrelide is metabolised by CYP1A2 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. Velpatasvir is metabolized by CYPs 2B6, 2C8 and 3A4; voxilaprevir is metabolized by CYPs 3A4, 1A2 and 2C8. Anakinra does not interact with these pathways. 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.

Coadministration has not been studied but may decrease velpatasvir concentrations due the increase in gastric pH. Administration of an antacid and sofosbuvir/velpatasvir/voxilaprevir should be separated by 4 hours.

Concentrations of apixaban may increase due to inhibition of P-gp and BCRP by velpatasvir and voxilaprevir. However, a large, retrospective, multi-centre cohort study of patients coadministered HCV DAAs and DOACs, including sofosbuvir/velpatasvir/voxilaprevir 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. Although aprepitant is an inhibitor of CYP3A4, no clinically significant effect on sofosbuvir/velpatasvir/voxilaprevir is expected. Note, following cessation of aprepitant, sofosbuvir/velpatasvir/voxilaprevir concentrations may decrease due to transient mild induction of CYP3A4, though this is unlikely to be clinically significant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aripiprazole is metabolized by CYP3A4 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Artemether is metabolised by CYP3A4 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

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. Dihydroartemisinin may potentially decrease sofosbuvir/velpatasvir/voxilaprevir concentrations although the clinical significance of this is uncertain. Caution is advised with close monitoring for therapeutic effect.

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. Dihydroartemisinin may potentially decrease sofosbuvir/velpatasvir/voxilaprevir concentrations although the clinical significance of this is uncertain. Caution is advised with close monitoring for therapeutic effect.

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. Aspirin is metabolised by deacetylation and UGT2B7 conjugation.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Astemizole is metabolised by CYP3A4 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration is not recommended as concentrations of voxilaprevir may increase by ~4-fold due to OATP1B1 and P-gp inhibition by atazanavir. Coadministration of atazanavir/ritonavir (300/100 mg single dose) and sofosbuvir/velpatasvir/voxilaprevir (400/100/100 mg single dose was studied in 15 subjects. Sofosbuvir Cmax and AUC increased by 29% and 40%; GS-331007 Cmax and AUC increased by 5% and 25%; velpatasvir Cmax and AUC increased by 29% and 93%; voxilaprevir Cmax and AUC increased by 4.42- and 4.31-fold.

Coadministration with atazanavir alone has not been studied and is not recommended as concentrations of voxilaprevir may increase by ~4-fold due to OATP1B1 and P-gp inhibition by atazanavir. Coadministration of atazanavir/ritonavir (300/100 mg single dose) and sofosbuvir/velpatasvir/voxilaprevir (400/100/100 mg single dose was studied in 15 subjects. Sofosbuvir Cmax and AUC increased by 29% and 40%; GS-331007 Cmax and AUC increased by 5% and 25%; velpatasvir Cmax and AUC increased by 29% and 93%; voxilaprevir Cmax and AUC increased by 4.42- and 4.31-fold.

Coadministration with atazanavir/cobicistat has not been studied and is not recommended as concentrations of voxilaprevir may increase by ~4-fold due to OATP1B1 and P-gp inhibition by atazanavir. Coadministration of atazanavir/ritonavir (300/100 mg single dose) and sofosbuvir/velpatasvir/voxilaprevir (400/100/100 mg single dose was studied in 15 subjects. Sofosbuvir Cmax and AUC increased by 29% and 40%; GS-331007 Cmax and AUC increased by 5% and 25%; velpatasvir Cmax and AUC increased by 29% and 93%; voxilaprevir Cmax and AUC increased by 4.42- and 4.31-fold.

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 sofosbuvir/velpatasvir/voxilaprevir.

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 affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance, exposure to atorvastatin may increase due to inhibition of OATP1B1 resulting in increased side effects. Coadministration of atorvastatin with sofosbuvir/velpatasavir increased atorvastatin Cmax and AUC by 68% and 54%, respectively.  The European Summary of Product Characteristics for Vosevi recommends not exceeding a dose of 20 mg of atorvastatin. The US Prescribing Information for Vosevi recommends using the lowest approved dose following a risk/benefit assessment.

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 sofosbuvir/velpatasvir/voxilaprevir 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Axitinib is metabolised by CYP3A4 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

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 affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Data suggest that azithromycin may be a substrate for P-gp and concentrations may increase due to inhibition of P-gp by velpatasvir and voxilaprevir. 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. Sofosbuvir is a prodrug and the formation of its active metabolite is unlikely to be affected by comedications. Velpatasvir is metabolised by CYPs 2B6, 2C8 and 3A4; voxilaprevir is metabolised by CYPs 3A4, 1A2 and 2C8. 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. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. Velpatasvir is metabolised by CYPs 2B6, 2C8 and 3A4; voxilaprevir is metabolised by CYPs 3A4, 1A2 and 2C8. Baricitinib is not expected to have a clinically relevant effect on drugs metabolised by CYP enzymes.

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. Beclometasone is metabolised by hydrolysis to beclometasone 17-monopropionate in vivo although it is a substrate of CYP3A4 in vitro.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bedaquiline is metabolised by CYP3A4 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

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 metabolised by CYP2D6 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

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 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

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 involvement of multiple metabolic pathways and renal elimination, a clinically significant interaction is not expected with sofosbuvir/velpatasvir/voxilaprevir. [Note, the European Summary of Product Characteristics for bezafibrate contraindicates its use in significant hepatic disease.]

Based on drug interaction studies conducted with Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) or the components of Biktarvy, no clinically significant drug interactions have been observed when Biktarvy is combined with sofosbuvir/velpatasvir/voxilaprevir. Coadministration of bictegravir/emtricitabine/tenofovir alafenamide (50/200/25 mg once daily) and sofosbuvir/velpatasvir/voxilaprevir (400/100/100 once daily, plus 100 mg voxilaprevir to approximate systemic voxilaprevir exposure in HCV-infected subjects) was studied in healthy volunteers (n=30). There was no significant effect on exposure of bictegravir, emtricitabine, sofosbuvir, GS-331007 (the major circulating sofosbuvir metabolite), velpatasvir and voxilaprevir, but AUC of tenofovir alafenamide increased by ~58% and AUC of tenofovir increased by ~67%.

Coadministration has not been studied but may increase concentrations of bilastine due to inhibition of P-gp and OATP1A2 by velpatasvir and voxilaprevir. No effect on sofosbuvir concentrations is expected. 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 sofosbuvir/velpatasvir/voxilaprevir. The potential interaction can be resolved by giving bisacodyl at least 4 hours after sofosbuvir/velpatasvir/voxilaprevir. [Note: this interaction is not specific for sofosbuvir/velpatasvir/voxilaprevir, 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 which is not clinically affected by sofosbuvir/velpatasvir/voxilaprevir. [Note, the European product label for bisoprolol recommends a maximum of 10 mg in severe hepatic impairment; 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. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. 

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 CYPs 1A2, 2C9, 2C19, 2D6 and 3A4 which are not clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied. Bosentan, a moderate CYP3A inducer, may decrease sofosbuvir/velpatasvir/voxilaprevir concentrations, leading to reduced therapeutic effect of sofosbuvir/velpatasvir/voxilaprevir. Coadministration is not recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bosutinib is metabolised principally by CYP3A4 but sofosbuvir/velpatasvir/voxilaprevir does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Concentrations of velpatasvir and voxilaprevir may increase slightly due to weak inhibition of CYP3A4 by MMAE, but this is unlikely to be clinically relevant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brinozolamide is metabolised by CYP3A4 which is not affected sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as 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, but no clinically significant effect on sofosbuvir/velpatasvir/voxilaprevir is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromazepam is metabolised by CYP1A2 and CYP2D6 which are not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromocriptine is metabolised by CYP3A4 which is not clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromperidol is metabolised by CYP3A4 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Budesonide is metabolised by CYP3A4 which is not clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied. Sofosbuvir/velpatasvir/voxilaprevir is a substrate of P-gp, BCRP 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 OATP1B1/3 and/or NTCP substrates is considered low. However, it should be noted that the product label recommends clinical monitoring if bulevirtide is coadministered with voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as bumetanide is mainly excreted in the urine and is not transported by P-gp or BCRP.

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, none of which is affected by sofosbuvir/velpatasvir/voxilaprevir to a clinically significant extent.

Coadministration has not been studied but based on limited data a clinically significant interaction is unlikely. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Buprenorphine is also a substrate of P-gp. Concentrations of buprenorphine may increase due to mild inhibition of P-gp by velpatasvir, however, this is unlikely to be of clinical significance. Post hoc analysis of multiple clinical trials has revealed no impact on the occurrence of adverse effects in patients receiving buprenorphine with sofosbuvir-based therapies, including sofosbuvir/velpatasvir/voxilaprevir. No effect on sofosbuvir/velpatasvir/voxilaprevir concentrations is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupropion is metabolised by CYP2B6, as is sofosbuvir/velpatasvir/voxilaprevir in part; however, neither drugs inhibit or induce this enzyme.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buspirone is metabolised by CYP3A4 which is not clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

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 has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sofosbuvir, velpatasvir, and voxilaprevir are inhibitors of intestinal P-glycoprotein and BCRP, but this is not relevant with intramuscular administration of cabotegravir and rilpivirine. Coadministration of oral rilpivirine (25 mg once daily with emtricitabine and tenofovir-alafenamide) and sofosbuvir/velpatasvir/voxilaprevir had no clinically significant effect on pharmacokinetic parameters.

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 sofosbuvir, velpatasvir or voxilaprevir.

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 sofosbuvir/velpatasvir/voxilaprevir. Canagliflozin is a substrate and inhibitor of P-gp and concentrations may increase due to mild inhibition of P-gp by velpatasvir and voxilaprevir, however, this is unlikely to be of clinical significance. Although canagliflozin is an inhibitor of P-gp, no clinically significant effect on velpatasvir or voxilaprevir is expected. Concentrations of sofosbuvir, but not the main circulating metabolite GS-331007, may increase and no a priori dose modification is recommended.

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, but 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 sofosbuvir/velpatasvir/voxilaprevir is unlikely. However, monitoring for ALT elevations may be required. [Note, use of candesartan in severe hepatic impairment is contraindicated in the European Summary of Product Characteristics; 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. Sofosbuvir/velpatasvir/velpatasvir does not interact with these pathways.

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 which are not clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

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 affected by sofosbuvir/velpatasvir/voxilaprevir.

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 has not been studied and is not recommended. Concentrations of sofosbuvir, velpatasvir and voxilaprevir may decrease due to induction of P-gp and/or CYPs 2B6, 2C8 and 3A4 by carbamazepine; this may lead to reduced therapeutic effect and potential virological failure.

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 based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Carfentanil is expected to be metabolized by CYP3A4/5. Sofosbuvir/velpatasvir/voxilaprevir does not interact with this pathway. However, 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. 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 affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied. Carvedilol is glucuronidated by UGTs 1A1, 2B4 and 2B7 with additional metabolism by CYP2D6 (and to a lesser extent CYPs 2C9 and 1A2), none of which is affected by sofosbuvir/velpatasvir/voxilaprevir. However, carvedilol is substrate of P-gp and concentrations may increase due to mild inhibition of P-gp by velpatasvir and voxilaprevir. Caution is warranted as carvedilol has a narrow therapeutic index. [Note, the US Prescribing Information contraindicates carvedilol in patients with severe liver impairment and the European Summary of Product Characteristics contraindicates it in patients with hepatic dysfunction.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. Velpatasvir is metabolised by CYPs 2B6, 2C8 and 3A4; voxilaprevir is metabolised by CYPs 3A4, 1A2 and 2C8. 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 as 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 with sofosbuvir/velpatasvir/voxilaprevir has not been studied. No clinically significant drug interactions were observed between velpatasvir and ketoconazole (another strong CYP3A4 inhibitor). Coadministration of ketoconazole (200 mg, twice daily) and velpatasvir (100 mg, single dose) increased velpatasvir Cmax and AUC by 29% and 71%, respectively (n=12). Based on this, no clinically significant drug interactions with cat’s claw are expected.

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 affected by sofosbuvir/velpatasvir/voxilaprevir.

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. 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 inhibited by sofosbuvir/velpatasvir/voxilaprevir.

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, approximately 60% of the dose being excreted in the urine predominantly by glomerular filtration and the remainder by 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 metabolised by CYP2C9 which is not affected by sofosbuvir/velpatasvir/voxilaprevir. [Note, use in patients with severe liver impairment is contraindicated in the European Summary of Product Characteristics 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. 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Chloramphenicol is metabolised by CYP3A4 which is not affected by sofosbuvir/velpatasvir/voxilaprevir. Although chloramphenicol is an inhibitor of CYP3A4, no clinically significant effect on sofosbuvir/velpatasvir/voxilaprevir is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chloroquine is rapidly metabolised by CYPs 2C8, 3A and 2D6 to the pharmacologically active desethylchloroquine and bisdesethylchloroquine and is also renally eliminated. These pathways are not affected by sofosbuvir/velpatasvir/voxilaprevir. Note, the European Summary of Product Characteristics 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 metabolised by CYP2D6 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

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 affected by sofosbuvir/velpatasvir/voxilaprevir. [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 sofosbuvir/velpatasvir/voxilaprevir. [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. 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 which are not affected by sofosbuvir/velpatasvir/voxilaprevir.

Co-administration has been studied with sofosbuvir, velpatasvir or voxilaprevir and coadministration with sofosbuvr/velpatasvir/voxilaprevir would not be recommended. Concentrations of voxilaprevir increased by 19.0-fold due to OATP1B1 inhibition by ciclosporin. The safety of this increase has not been established.

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 inhibited by sofosbuvir/velpatasvir/voxilaprevir.

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 which are not clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but may decrease velpatasvir concentrations. H2-receptor antagonists may be administered simultaneously with or 12 hours apart from sofosbuvir/velpatasvir/voxilaprevir at a dose that does not exceed doses comparable to famotidine 40 mg twice daily.

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 which is not inhibited by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but a clinically significant interaction is unlikely. Cisapride is metabolised by CYP3A4 which is not clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

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 which are not inhibited by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Citalopram is metabolized by CYP2C19 (38%), 2D6 (31%) and 3A4 (31%) which are not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied. Clarithromycin is a substrate and inhibitor of P-gp. Concentrations of clarithromycin may increase due to inhibition of P-gp by velpatasvir and voxilaprevir. The significance of this is unknown and monitoring for increased clarithromycin concentrations is recommended. Any increase in velpatasvir and voxilaprevir is likely to be within the upper clinical bounds and not clinically significant. Concentrations of sofosbuvir, but not the main circulating metabolite GS-331007, may increase. No a priori dose modification is recommended. 

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 which is not clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

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 which are not clinically affected by sofosbuvir/velpatasvir/voxilaprevir. Clobazam is a weak CYP3A4 inducer and could potentially decrease velpatasvir/voxilaprevir 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. Clobetasol is metabolized by CYP3A4 which is not clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

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. Clobetasone is metabolised by CYP3A4 which is not clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

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 sofosbuvir/velpatasvir/voxilaprevir, 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 a moderate inhibitor of CYP3A4 and may increase velpatasvir/voxilaprevir concentrations to a modest extent however this margin of increase is unlikely to be relevant. [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, none of which is clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

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 affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clonazepam is metabolised by CYP3A4 which is not clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

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 which are not clinically affected by sofosbuvir/velpatasvir/voxilaprevir. [Note, the European Summary of Product Characteristics 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 which is not clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of clotiapine has not been well characterised but is likely to involve CYP450 enzymes. Sofosbuvir/velpatasvir/voxilaprevir do not affect CYP enzymes. 

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 which are not clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

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, none of which are likely to be clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely Codeine is metabolised by CYP2D6 and CYP3A4, which are not clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but may increase colchicine concentrations due to mild inhibition of P-gp by velpatasvir and voxilaprevir. As colchicine has a narrow therapeutic window, dose reduction should be considered in patients with normal hepatic function and should be used with caution in those with hepatic or renal impairment.

Coadministration has not been studied but a clinically significant interaction is unlikely as colecalciferol undergoes extensive metabolism by multiple pathways, none of which is significantly affected by sofosbuvir/velpatasvir/voxilaprevir.

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 sofosbuvir/velpatasvir/voxilaprevir, 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, but no clinically significant effect on conivaptan or sofosbuvir/velpatasvir/voxilaprevir is expected.

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. Sofosbuvir/velpatasvir/voxilaprevir is only a weak inhibitor of CYP3A4 and is unlikely to affect these pathways to any clinically significant extent. However, sofosbuvir/velpatasvir/voxilaprevir 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, none of which are clinically affected by sofosbuvir/velpatasvir/voxilaprevir.

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. Sofosbuvir/velpatasvir/voxilaprevir does not interact with these pathways.

Coadministration has not been studied and the pharmacokinetics of cytisine are 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.

Dabigatran exposure may increase due to mild inhibition of P-gp by velpatasvir and voxilaprevir Coadministration of dabigatran etexilate (75 mg single dose) and sofosbuvir/velpatasvir/voxilaprevir (400/100/100 mg single dose) plus voxilaprevir (100 mg single dose) increased dabigatran Cmax and AUC by 2.87-fold and 2.61-fold. No effect on sofosbuvir/velpatasvir/voxilaprevir is expected. If coadministration is clinically necessary, close monitoring (for signs of bleeding and anaemia) is recommended as dabigatran has as a narrow therapeutic window. 

Sofosbuvir/velpatasvir/voxilaprevir is a complete regimen. There are no data to support 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 affected by sofosbuvir/velpatasvir/voxilaprevir.

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.

Clinically significant interactions are not expected with once-daily darunavir/ritonavir. Twice daily darunavir/ritonavir has not been studied and should be used with caution as voxilaprevir concentrations may increase more than with once daily darunavir (this would be of further significance in cirrhotic patients). Based on drug interaction studies conducted with sofosbuvir/velpatasvir/voxilaprevir, no clinically significant drug interactions have been observed with darunavir/ritonavir administered once daily. Coadministration of darunavir/ritonavir (800/100 mg once daily), emtricitabine/tenofovir disoproxil fumarate (200/300 mg once daily) and sofosbuvir/velpatasvir/voxilaprevir (400/100/100 mg once daily) plus voxilaprevir (100 mg once daily) was studied (n=29). There was no change in darunavir Cmax or AUC, but Cmin decreased by 34%; ritonavir Cmax and AUC increased by 60% and 45%, but there was no change in Cmin. Sofosbuvir Cmax decreased by 30%, but there was no change in AUC; there was no change in velpatasvir Cmax, AUC or Cmin; voxilaprevir Cmax, AUC and Cmin increased by 1.72-, 2.43- and 4.00-fold.

Coadministration with Symtuza has not been studied, but a clinically significant interaction is unlikely. No clinically significant drug interactions have been observed in drug interaction studies conducted with sofosbuvir/velpatasvir/voxilaprevir and darunavir/ritonavir administered once daily. Coadministration of darunavir/ritonavir (800/100 mg once daily), emtricitabine/tenofovir disoproxil fumarate (200/300 mg once daily) and sofosbuvir/velpatasvir/voxilaprevir (400/100/100 mg once daily) plus voxilaprevir (100 mg once daily) was studied. There was no change in darunavir Cmax or AUC, but Cmin decreased by 34%; ritonavir Cmax and AUC increased by 60% and 45%, but there was no change in Cmin. Sofosbuvir Cmax decreased by 30%, but there was no change in AUC; there was no change in velpatasvir Cmax, AUC or Cmin; voxilaprevir Cmax, AUC and Cmin increased by 1.72-, 2.43- and 4.00-fold. Coadministration of sofosbuvir/velpatasvir/voxilaprevir (400/100/100 once daily, plus 100 mg voxilaprevir to approximate systemic voxilaprevir exposure in HCV-infected subjects) was studied in groups (n=30) of healthy volunteers receiving emtricitabine/tenofovir alafenamide (200/25 mg once daily with bictegravir or rilpivirine) or emtricitabine/tenofovir alafenamide (200/10 mg once daily with elvitegravir/cobicistat). Coadministration with emtricitabine, tenofovir alafenamide and bictegravir or rilpivirine had no significant effect on the exposure of sofosbuvir, GS-331007 (the major circulating sofosbuvir metabolite), velpatasvir, voxilaprevir and emtricitabine. In the bictegravir and rilpivirine groups, coadministration increased the AUCs of tenofovir alafenamide by 52-58% and of tenofovir by 67-79%. Coadministration with emtricitabine, tenofovir alafenamide and elvitegravir/cobicistat had no significant effect on the AUCs of emtricitabine, tenofovir, tenofovir alafenamide, sofosbuvir and velpatasvir, but increased GS-331007 AUC by 43% and increased voxilaprevir AUC by 171%.

Coadministration with darunavir/cobicistat has not been studied, but a clinically significant interaction is unlikely. No clinically significant drug interactions have been observed in drug interaction studies conducted with sofosbuvir/velpatasvir/voxilaprevir and darunavir/ritonavir administered once daily. Coadministration of darunavir/ritonavir (800/100 mg once daily), emtricitabine/tenofovir disoproxil fumarate (200/300 mg once daily) and sofosbuvir/velpatasvir/voxilaprevir (400/100/100 mg once daily) plus voxilaprevir (100 mg once daily) was studied. There was no change in darunavir Cmax or AUC, but Cmin decreased by 34%; ritonavir Cmax and AUC increased by 60% and 45%, but there was no change in Cmin. Sofosbuvir Cmax decreased by 30%, but there was no change in AUC; there was no change in velpatasvir Cmax, AUC or Cmin; voxilaprevir Cmax, AUC and Cmin increased by 1.72-, 2.43- and 4.00-fold.

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. No clinically significant effect on concentrations of dasatinib or sofosbuvir/velpatasvir/voxilaprevir is expected.

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 sofosbuvir/velpatasvir/voxilaprevir.

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. Sofosbuvir/velpatasvir/voxilaprevir does not affect CYP enzymes so a clinically significant interaction is unlikely. [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 affected by sofosbuvir/velpatasvir/voxilaprevir.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as desmopressin undergoes no significant metabolism.

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. These enzymes are not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration of sofosbuvir/velpatasvir/voxilaprevir and ethinylestradiol is contraindicated in the European Summary of Product Characteristics for Vosevi as concomitant use with ethinylestradiol-containing medicinal products may increase the risk of alanine aminotransferase (ALT) elevations. Note: the US Prescribing Information for Vosevi states no clinically significant drug interactions have been observed.

Coadministration of sofosbuvir/velpatasvir/voxilaprevir and ethinylestradiol is contraindicated in the European Summary of Product Characteristics for Vosevi as concomitant use with ethinylestradiol-containing medicinal products may increase the risk of alanine aminotransferase (ALT) elevations. Note: the US Prescribing Information for Vosevi states no clinically significant drug interactions have been observed.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desvenlafaxine is a substrate of CYP3A4 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied and should be avoided if possible. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. Velpatasvir is metabolized by CYPs 2B6, 2C8 and 3A4; voxilaprevir is metabolized by CYPs 3A4, 1A2 and 2C8. Sofosbuvir, velpatasvir and voxilaprevir are also substrates of P-gp and BCRP. Dexamethasone is a moderate inducer of CYP3A4 at doses above 16mg and, thus, coadministration may decrease sofosbuvir/velpatasvir/voxilaprevir concentrations, possibly leading to reduced therapeutic effect. Dexamethasone is also a P-gp inducer in pre-clinical models although the clinically relevance of this is unclear.

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. Sofosbuvir/velpatasvir/voxilaprevir is not expected to induce or inhibit UGTs or CYP2C8/2C9. [Note, use in patients with severe hepatic impairment (Child Pugh class C) is contraindicated in the European product label for dexketoprofen.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextromethorphan is metabolized by CYP2D6 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextropropoxyphene is metabolised by CYP3A4 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diazepam is metabolised by CYP3A4 and CYP2C19 which are not affected by sofosbuvir/velpatasvir/voxilaprevir.

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, UGT2B7 and is an inhibitor of the renal transporter MRP4. These pathways are not affected by sofosbuvir/velpatasvir/voxilaprevir.

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 metabolised by CYP3A4 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

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 sofosbuvir/velpatasvir/voxilaprevir.

Coadministration with sofosbuvir/velpatasvir/voxilaprevir has not been studied. Coadministration of digoxin (0.25 mg single dose) and velpatasvir (100 mg single dose) increased digoxin Cmax and AUC by 88% and 34%, respectively. Voxilaprevir is also an inhibitor of P-gp and the additive effect is unknown. Therapeutic concentration monitoring of digoxin is recommended when coadministered with sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied. Dihydroartemisinin (the active metabolite of artesunate) has been shown to induce CYP3A4 and may potentially decrease sofosbuvir/velpatasvir/voxilaprevir concentrations although the clinical significance of this is uncertain. Caution is advised with close monitoring for therapeutic effect.

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 by UGT2B7 (major pathway) and to nordihydrocodeine by CYP3A4. These pathways are not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dihydroergotamine is metabolised by CYP3A4 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration with diltiazem has not been studied. Although diltiazem is an inhibitor of CYP3A4 and P-gp, a clinically significant effect on sofosbuvir/velpatasvir/voxilaprevir is unlikely. Diltiazem is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by velpatasvir and voxilaprevir. Caution is warranted as diltiazem has a narrow therapeutic index.

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 sofosbuvir/velpatasvir/voxilaprevir 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 metabolised by CYP2D6 which is not affected by sofosbuvir/velpatasvir/voxilaprevir. [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 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

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 sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dofetilide is eliminated in the kidney by cationic secretion and is metabolized to a small extent by CYP3A4 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No clinically significant drug interactions have been observed with dolutegravir and sofosbuvir/velpatasvir and no additional effect is likely with the addition of voxilaprevir.

Coadministration with dolutegravir/lamivudine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No clinically significant drug interactions have been observed with dolutegravir and sofosbuvir/velpatasvir and no additional effect is likely with the addition of voxilaprevir. Lamivudine is not expected to inhibit or induce any relevant metabolic enzymes or transporters of sofosbuvir/velpatasvir/voxilaprevir. The likelihood of metabolic interactions with lamivudine and other medicinal products is low due to the small extent of lamivudine hepatic metabolism (5-10%) and low plasma protein binding.

Coadministration with dolutegravir/rilpivirine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No clinically significant drug interactions have been observed with dolutegravir and sofosbuvir/velpatasvir and no additional effect is likely with the addition of voxilaprevir. Coadministration of rilpivirine (25 mg once daily with emtricitabine and tenofovir-alafenamide) and sofosbuvir/velpatasvir/voxilaprevir had no clinically significant effect on pharmacokinetic parameters.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Domperidone is predominantly metabolised by CYP3A4 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

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) which are not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doravirine is not expected to inhibit or induce any relevant metabolic enzymes or transporters of sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied. Doravirine and lamivudine are not expected to inhibit or induce any relevant metabolic enzymes or transporters of sofosbuvir/velpatasvir/voxilaprevir. However, sofosbuvir/velpatasvir/voxilaprevir has been shown to increase tenofovir exposure due to inhibition of P-gp inhibition by velpatasvir and voxilaprevir. Tenofovir exposure (AUC and Cmax) increased by ~40% during co-treatment with sofosbuvir/velpatasvir/voxilaprevir and tenofovir-DF (with darunavir/ritonavir/emtricitabine). Patients receiving sofosbuvir/velpatasvir/voxilaprevir concomitantly with tenofovir-DF should be monitored for tenofovir-associated adverse reactions.

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 these enzymes are not affected by sofosbuvir/velpatasvir/voxilaprevir. [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 which are not affected by sofosbuvir/velpatasvir/voxilaprevir. Note, the European Summary of Product Characteristics 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 is affected by sofosbuvir/velpatasvir/voxilaprevir. [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 but based on metabolism and clearance, a clinically significant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely 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. Sofosbuvir/velpatasvir/voxilaprevir does not interact with these pathways.

Coadministration of dronedarone and sofosbuvir combined with another direct acting antiviral such as velpatasvir and voxilaprevir may result in serious symptomatic bradycardia and is not recommended. The mechanism of the effect is unknown.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Droperidol is metabolised by CYP3A4 and CYP1A2 which are not affected by sofosbuvir/velpatasvir/voxilaprevir.

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. These pathways are not affected by sofosbuvir/velpatasvir/voxilaprevir. However, sofosbuvir/velpatasvir/voxilaprevir 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 sofosbuvir/velpatasvir/voxilaprevir and ethinylestradiol is contraindicated in the Vosevi European Summary of Product Characteristics, as concomitant use with ethinylestradiol-containing medicinal products may increase the risk of alanine aminotransferase (ALT) elevations. Note, the US Prescribing Information for Vosevi states no clinically significant drug interactions have been observed.

Coadministration with sofosbuvir/velpatasvir/voxilaprevir and ethinylestradiol is contraindicated in the Vosevi European Summary of Product Characteristics, as concomitant use with ethinylestradiol-containing medicinal products may increase the risk of alanine aminotransferase (ALT) elevations. Note, the US Prescribing Information for Vosevi states no clinically significant drug interactions have been observed.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dulaglutide is degraded by general protein catabolism pathways therefore no metabolic interaction is expected. Dulaglutide delays gastric emptying but interaction studies showed no clinically significant effect on the absorption of concomitantly administered oral medicinal products. GLP-1 agonists such as dulaglutide also have the potential to inhibit gastric secretion and thereby impact drugs whose absorption is gastric dependent, such as velpatasvir. A reduction in velpatasvir exposure is possible with dulaglutide, 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. Duloxetine is metabolized by CYP2D6 and CYP1A2 which are not affected by sofosbuvir/velpatasvir/voxilaprevir. [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 which is not affected by sofosbuvir/velpatasvir/voxilaprevir. [Note, the European Summary of Product Characteristics (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). Sofosbuvir/velpatasvir/voxilaprevir is only a weak inhibitor of CYP3A4 and is unlikely to affect these pathways to any clinically significant extent. However, sofosbuvir/velpatasvir/voxilaprevir 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Ebastine is metabolised by CYP450 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

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 sofosbuvir/velpatasvir/voxilaprevir.

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 affected by sofosbuvir/velpatasvir/voxilaprevir.

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.

Coadministration has not been studied but would not be recommended. Edoxaban is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by velpatasvir and voxilaprevir. The active metabolite of edoxaban is a substrate of OATP1B1 and its concentrations may increase due to inhibition of OATP1B1 by velpatasvir and voxilaprevir. No effect on sofosbuvir, velpatasvir or voxilaprevir concentrations is expected. The European SPC for Vosevi suggests that should direct Xa inhibitor use be deemed necessary, apixaban or rivaroxaban may be considered. [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 of sofosbuvir, velpatasvir and voxilaprevir with efavirenz-containing regimens is not recommended due to decreased concentrations of velpatasvir. Voxilaprevir in combination has not been studied. Coadministration of efavirenz (600 mg once daily with emtricitabine and tenofovir-DF) and sofosbuvir/velpatasvir (400/100 mg once daily) increased sofosbuvir Cmax by 38% but decreased AUC by 3%; velpatasvir Cmax, AUC and Cmin decreased by 47%, 53% and 57%, respectively (n=14). Efavirenz Cmax, AUC and Cmin decreased by 19%, 15% and 10%, respectively (n=15).

Sofosbuvir/velpatasvir/voxilaprevir is a complete regimen. There are no data to support coadministration with elbasvir/grazoprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eletriptan is primarily metabolised by CYP3A4 which is not affected by sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eliglustat is metabolised primarily by CYP2D6 and to a lesser extent by CYP3A4. Sofosbuvir/velpatasvir/voxilaprevir does not inhibit or induce these CYP enzymes.

Coadministration has not been studied but would not be recommended. Eltrombopag is metabolised by cleavage, conjugation and to a minor extent by CYP1A2 and CYP2C8, which are not affected by sofosbuvir/velpatasvir/voxilaprevir. However both velpatasvir and voxilaprevir are substrates of OATP1B1 and concomitant use of sofosbuvir/velpatasvir/voxilaprevir with eltrombopag, an inhibitor of OATP1B1, may increase the risk of ALT elevations due to a significant increase in voxilaprevir plasma concentrations. 

No clinically significant drug interactions have been observed with sofosbuvir/velpatasvir/voxilaprevir and elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide.  Coadministration of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate (150/150/200/10 mg once daily) and sofosbuvir/velpatasvir/voxilaprevir (400/100/100 mg once daily) and voxilaprevir (100 mg once daily) was studied (n=29). There was no change elvitegravir Cmax or AUC, but Cmin increased by 32%. There was no change cobicistat Cmax, but AUC and Cmin increased by 1.50- and 3.50-fold. Tenofovir Cmax decreased by 21%, but there was no change in AUC. Sofosbuvir Cmax increased by 27% but there was no change in AUC. There was no change in velpatasvir Cmax or AUC, but Cmin increased by 46%. Voxilaprevir Cmax, AUC and Cmin increased by 1.92-, 2.71- and 4.50-fold.

Coadministration has not been studied. Sofosbuvir/velpatasvir/voxilaprevir has been shown to increase tenofovir exposure when used together with an HIV regimen containing tenofovir disoproxil fumarate and a pharmacokinetic enhancer (ritonavir or cobicistat). The safety of tenofovir-DF in the setting of sofosbuvir/velpatasvir/voxilaprevir and a pharmacokinetic enhancer has not been established. Close monitoring for tenofovir-associated adverse reactions is recommended. 

Coadministration has not been studied. Empagliflozin is metabolised by UGTs and is a substrate of P-gp, BCRP, OAT3 and OATP1B1/1B3. Although velpatasvir and voxilaprevir are inhibitors of P-gp and OATP1B1/1B3, data with verapamil (a P-gp inhibitor) and rifampicin (an OATP1B1/1B3 inhibitor) suggest a clinically relevant effect on empagliflozin is unlikely. However, concentrations of empagliflozin may further increase due to inhibition of BCRP by velpatasvir and voxilaprevir and this combination should be used with caution.

No effect on the pharmacokinetic parameters of sofosbuvir, GS-331007, velpatasvir, voxilaprevir or emtricitabine was observed when sofosbuvir/velpatasvir/voxilaprevir was administered with various emtricitabine containing regimens.

Coadministration with emtricitabine/tenofovir alafenamide alone has not been studied. Coadministration of sofosbuvir/velpatasvir/voxilaprevir (400/100/100 once daily, plus 100 mg voxilaprevir to approximate systemic voxilaprevir exposure in HCV-infected subjects) was studied in groups (n=30) of healthy volunteers receiving emtricitabine/tenofovir alafenamide (200/25 mg once daily with bictegravir or rilpivirine) or emtricitabine/tenofovir alafenamide (200/10 mg once daily with elvitegravir/cobicistat). Coadministration with emtricitabine, tenofovir alafenamide and bictegravir or rilpivirine had no significant effect on exposure of sofosbuvir, GS-331007 (the major circulating sofosbuvir metabolite), velpatasvir, voxilaprevir and emtricitabine. In the bictegravir and rilpivirine groups, coadministration increased the AUCs of tenofovir alafenamide by 52-58% and of tenofovir by 67-79%. Coadministration with emtricitabine, tenofovir alafenamide and elvitegravir/cobicistat had no significant effect on the AUCs of emtricitabine, tenofovir, tenofovir alafenamide, sofosbuvir and velpatasvir, but increased GS-331007 AUC by 43% and increased voxilaprevir AUC by 171%.