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 interaction is unlikely. Carisoprodol is metabolised by CYP2C19 which is not affected by sofosbuvir/velpatasvir.

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. However, carvedilol is substrate of P-gp and concentrations may increase due to mild inhibition of P-gp by velpatasvir. 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 SmPC contraindicates it in patients with hepatic dysfunction.]

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

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

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

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.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely 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. [Note, use in patients with severe liver impairment is contraindicated in the European SmPC 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. Although chloramphenicol is an inhibitor of CYP3A4, no clinically significant effect on sofosbuvir/velpatasvir 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. Note, the European SPC and US Prescribing Information for chloroquine both recommend caution in impaired hepatic function.

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

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

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. [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. [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.

Coadministration with sofosbuvir/velpatasvir has not been studied. Based on drug interaction studies conducted with sofosbuvir alone or velpatasvir alone, no clinically significant drug interactions have been observed with ciclosporin. Coadministration of ciclosporin (600 mg single dose) and sofosbuvir (400 mg single dose, n=19) increased sofosbuvir Cmax and AUC by 154% and 353%. Coadministration of ciclosporin (600 mg single dose) and velpatasvir (100 mg single dose, n=12) increased velpatasvir Cmax and AUC by 56% and 103% (n=12). No effect on the pharmacokinetic parameters of ciclosporin was observed with sofosbuvir or velpatasvir. However, the pharmacokinetics of ciclosporin may be impacted by changes in liver function during DAA therapy and monitoring of ciclosporin levels is recommended.

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. 

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 affected by sofosbuvir/velpatasvir.

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 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.

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

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.

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.

Coadministration has not been studied. Clarithromycin is a substrate and inhibitor of P-gp. Although clarithromycin concentrations may increase due to mild inhibition of P-gp by velpatasvir, this is unlikely to be of clinical significance. Inhibition of P-gp by clarithromycin is not expected to have a clinically significant effect on velpatasvir. 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 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 affected by sofosbuvir/velpatasvir.

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 affected by sofosbuvir/velpatasvir. Clobazam is a weak CYP3A4 inducer and could potentially decrease velpatasvir 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 affected by sofosbuvir/velpatasvir.

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 affected by sofosbuvir/velpatasvir.

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, 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. Studies suggest clomifene is metabolised by CYP3A4, CYP2D6 and UGTs, none of which is affected by sofosbuvir/velpatasvir.

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.

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 affected by sofosbuvir/velpatasvir.

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 affected by sofosbuvir/velpatasvir. [Note, the European SmPC for clopidogrel contraindicates it use in severe hepatic impairment but the US Prescribing Information states no dose alteration.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clorazepate is rapidly converted to nordiazepam which is then metabolized to oxazepam by CYP3A4 which is not affected by sofosbuvir/velpatasvir.

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 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 affected by sofosbuvir/velpatasvir.

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

carboxylesterase and CYP3A4 to norcocaine, none of which is affected by sofosbuvir/velpatasvir.

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 affected by sofosbuvir/velpatasvir.

Coadministration has not been studied but may increase colchicine concentrations due to mild inhibition of P-gp by velpatasvir. 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.

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, 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 is expected.

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 is affected by sofosbuvir/velpatasvir.

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.

Coadministration has not been studied. Dabigatran exposure may increase due to mild inhibition of P-gp by velpatasvir. Close monitoring (for signs of bleeding and anaemia) is recommended due to the narrow therapeutic window. No effect on sofosbuvir/velpatasvir concentrations is expected.

Sofosbuvir/velpatasvir (with or without ribavirin) 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.

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

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

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

Coadministration with darunavir/cobicistat has not been studied. Based on drug interaction studies with sofosbuvir/velpatasvir and various cobicistat-containing regimens, a clinically significant interaction is unlikely. Note, velpatasvir has been shown to increase tenofovir exposure, especially when used with an HIV regimen containing tenofovir-DF and a pharmacokinetic enhancer (ritonavir or cobicistat). As the safety of tenofovir-DF in the setting of sofosbuvir/velpatasvir and a pharmacokinetic enhancer has not been established, monitor for tenofovir-associated adverse reactions.

Coadministration with Symtuza has not been studied. Based on drug interaction studies with sofosbuvir/velpatasvir and various cobicistat-containing regimens, a clinically significant interaction is unlikely. Drug interaction studies conducted with velpatasvir/sofosbuvir and emtricitabine/tenofovir alafenamide/elvitegravir/cobicistat (where emtricitabine/tenofovir alafenamide were dosed at 200/10 mg once daily), showed no clinically significant drug interactions with emtricitabine or tenofovir alafenamide.

Based on drug interaction studies conducted with sofosbuvir/velpatasvir, no clinically significant drug interactions have been observed with darunavir/ritonavir administered once daily. Coadministration of darunavir/ritonavir (800/100 mg once daily with emtricitabine and tenofovir-DF, n=29) decreased darunavir Cmax, AUC and Cmin by 10%, 8% and 13%, respectively but increased ritonavir Cmax, AUC and Cmin by 7%, 12% and 9%, respectively. Cmax and AUC of sofosbuvir decreased by 38% and 28%; velpatasvir Cmax and AUC decreased by 24% and 16%, but Cmin increased by 1%. Note, velpatasvir has been shown to increase tenofovir exposure, especially when used with an HIV regimen containing tenofovir-DF and a pharmacokinetic enhancer (ritonavir or cobicistat). As the safety of tenofovir-DF in the setting of sofosbuvir/velpatasvir and a pharmacokinetic enhancer has not been established, monitor for tenofovir-associated adverse reactions.

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 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.

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 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.

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.

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.

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. Sofosbuvir and velpatasvir 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 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 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.

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.

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.

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.

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.

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.

Coadministration with sofosbuvir/velpatasvir 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. The effect on velpatasvir exposure was not studied but no change is expected. No effect on sofosbuvir exposure is expected. Therapeutic concentration monitoring of digoxin is recommended when coadministered with sofosbuvir/velpatasvir.

Coadministration has not been studied. Dihydroartemisinin (the active metabolite of artesunate) has been shown to induce CYP3A4 and may potentially decrease sofosbuvir/velpatasvir 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.

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.

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

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.

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.

Based on drug interaction studies conducted with sofosbuvir/velpatasvir, no clinically significant drug interactions have been observed with dolutegravir. No effect on the pharmacokinetic parameters of sofosbuvir, GS-331007, velpatasvir or dolutegravir was observed.

Coadministration with dolutegravir/rilpivirine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Based on drug interaction studies conducted with velpatasvir/sofosbuvir, no clinically significant drug interactions have been observed with dolutegravir. No effect on the pharmacokinetic parameters of sofosbuvir, GS-331007, velpatasvir or dolutegravir was observed. Based on drug interaction studies conducted with velpatasvir/sofosbuvir, no clinically significant drug interactions have been observed with rilpivirine. Coadministration of rilpivirine (25 mg once daily with emtricitabine and tenofovir-DF) and sofosbuvir/velpatasvir (400/100 mg once daily) decreased rilpivirine Cmax, AUC and Cmin by 7%, 5% and 4%, respectively (n=24). No effect on the pharmacokinetic parameters of sofosbuvir, GS-331007 or velpatasvir was observed.

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.

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.

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.

Coadministration has not been studied. Doravirine and lamivudine are not expected to inhibit or induce any relevant metabolic enzymes or transporters of sofosbuvir/velpatasvir. However, sofosbuvir/velpatasvir increased tenofovir AUC by ~30-80% when administered with various regimens containing tenofovir-DF. No effect on the pharmacokinetic parameters of sofosbuvir, GS-331007 or velpatasvir was observed. Monitor 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. [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. [Note, the European SmPC for doxazosin does not recommend its use in severe hepatic impairment; the US Prescribing Information has a caution in hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxepin is primarily metabolized by CYP2C19 and CYP2D6, and to a lesser extent, by CYP1A2 and CYP2C9, none of which is affected by sofosbuvir/velpatasvir. [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 does not interact with these pathways.

Coadministration of dronedarone and sofosbuvir combined with another direct acting antiviral such as velpatasvir 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.

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. 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. [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. [Note, the European SmPC (but not the US Prescribing Information) cautions against dutasteride use in mild to moderate hepatic impairment and contraindicates it in severe hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ebastine is metabolised by CYP450 which is not affected by sofosbuvir/velpatasvir.

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.

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.

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

Edoxaban is a substrate of P-gp and its active metabolite is a substrate of OATP1B1. Edoxaban concentrations may increase due to inhibition of P-gp and OATP1B1 by velpatasvir. A large, retrospective, multi-centre cohort study of patients coadministered HCV DAAs and DOACs, including sofosbuvir/velpatasvir and edoxaban, reported a low incidence of bleeding which was similar to historic controls of patients with liver disease on DOACs alone, providing reassurance the interaction is unlikely to be clinically relevant in the majority of patients. Patients should be reminded to promptly report any signs of bleeding or bruising as with anyone who is prescribed DOACs. [Note: product labels state that edoxaban is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk. It is not recommended in severe hepatic impairment and should be used with caution in patients with mild or moderate hepatic impairment.]

Coadministration of sofosbuvir/velpatasvir with efavirenz-containing regimens is not recommended due to decreased concentrations of velpatasvir. 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).

The safety and efficacy of velpatasvir and sofosbuvir have been established in combination with ribavirin. Coadministration with other directly acting antivirals has not been studied and therefore cannot be recommended.

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

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 does not inhibit or induce these CYP enzymes.

Coadministration has not been studied. Eltrombopag is metabolised by cleavage, conjugation and to a minor extent by CYP1A2 and CYP2C8, which are not affected by velpatasvir/sofosbuvir. However, velpatasvir is a substrate of OATP1B1 and concentrations may increase due to inhibition of OATP1B1 by eltrombopag.

No clinically significant drug interactions have been observed with sofosbuvir/velpatasvir and elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. Coadministration increased sofosbuvir Cmax and AUC by 23% and 37% and increased velpatasvir Cmax, AUC and Cmin by 30%, 50% and 60%, respectively. Elvitegravir Cmax and AUC decreased by 13% and 6%, but Cmin increased by 8%. Cobicistat Cmax, AUC and Cmin increased by 16%, 30% and 103%, respectively. Emtricitabine Cmax, AUC and Cmin increased by 2%, 1% and 2%, respectively. Tenofovir Cmax and AUC decreased by 20% and 13%.

Velpatasvir has been shown to increase tenofovir exposure, especially when used with an HIV regimen containing tenofovir-DF and a pharmacokinetic enhancer (ritonavir or cobicistat). The safety of tenofovir-DF in the setting of sofosbuvir/velpatasvir and a pharmacokinetic enhancer has not been established. Close monitoring for tenofovir-associated adverse reactions is recommended. Coadministration of elvitegravir/cobicistat/emtricitabine/tenofovir-DF and sofosbuvir/velpatasvir (400/100 mg once daily) increased tenofovir Cmax, AUC and Cmin by 36%, 35% and 45%, respectively. Elvitegravir Cmax, AUC and Cmin decreased by 7%, 7% and 3%; cobicistat Cmax, AUC and Cmin increased by 11%, 23% and 71%; emtricitabine Cmax, AUC and Cmin increased by 2%, 1% and 6%, respectively. Cmax and AUC of sofosbuvir increased by 1% and 24%; Cmax, AUC and Cmin of GS-331007 increased by 13%, 35% and 45% respectively. Velpatasvir Cmax, AUC and Cmin increased by 5%, 19% and 37%, respectively.

Coadministration has not been studied. Empagliflozin is metabolised by UGTs and is a substrate of P-gp, BCRP, OAT3 and OATP1B1/1B3. Although velpatasvir is a mild inhibitor 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 this combination should be used with caution.

Based on drug interaction studies conducted with sofosbuvir/velpatasvir, no clinically significant drug interactions have been observed with emtricitabine. No effect on the pharmacokinetic parameters of sofosbuvir, GS-331007, velpatasvir or emtricitabine was observed when sofosbuvir/velpatasvir was administered with various emtricitabine containing regimens.

Coadministration with emtricitabine/tenofovir alafenamide alone has not been studied but no clinically significant interaction is expected. Drug interaction studies conducted with velpatasvir/sofosbuvir and emtricitabine/tenofovir alafenamide/elvitegravir/cobicistat (where emtricitabine/tenofovir alafenamide were dosed at 200/10 mg once daily), showed no clinically significant drug interactions with emtricitabine or tenofovir alafenamide.

Velpatasvir/sofosbuvir increased tenofovir AUC by ~30-80% when administered with various regimens containing tenofovir-DF due to inhibition of intestinal P-gp and BCRP. No effect on the pharmacokinetic parameters of sofosbuvir, GS-331007, or velpatasvir was observed. The increased exposure of tenofovir could potentiate adverse reactions associated with tenofovir disoproxil fumarate, including renal disorders and renal function should be closely monitored.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enalapril is a prodrug hydrolysed in the liver to enalaprilat. It is a substrate but not an inhibitor of OATP1B1. Although concentrations may increase due to mild inhibition of OATP1B1 by velpatasvir, this is unlikely to be of clinical significance.

Coadministration has not been studied but based on metabolism and clearance an interaction is unlikely. Enoxaparin does not undergo CYP metabolism but is desulphated and depolymerised in the liver and is then excreted predominantly renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Entecavir is not expected to inhibit or induce any relevant metabolic enzymes or transporters of sofosbuvir/velpatasvir. Entecavir is eliminated primarily in the urine by glomerular filtration and tubular secretion by OAT1.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. There is no evidence that treatment with epoetin-alfa alters the metabolism of other medicinal products.

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

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

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

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

Coadministration has not been studied. Erlotinib is a substrate for CYP3A4 and P-gp and concentrations may increase due to mild inhibition of P-gp by velpatasvir. Use with caution and with close monitoring for erlotinib mediated toxicity. A dose reduction may be required for erlotinib, particularly if toxicity is observed.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Erythromycin is a substrate and inhibitor of CYP3A4 but no significant effect on concentration of erythromycin and sofosbuvir/velpatasvir is expected. Erythromycin is transported by OATP1B1 and concentrations may increase due to mild inhibition of OATP1B1 by velpatasvir, however, this is unlikely to be of clinical significance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Escitalopram is metabolised by CYP2C19, CYP2D6 and CYP3A4 which are not affected by sofosbuvir/velpatasvir.

Coadministration has not been formally studied and is not currently recommended. Concentrations of velpatasvir may decrease due to induction of CYP3A4 by eslicarbazepine; this may lead to reduced therapeutic effect and potential virological failure. Note - there are a small number of cases reported of patients who have remained on an inducing antiepileptic during HCV DAA therapy (including with sofosbuvir/velpatasvir) and achieved a sustained virologic response. Although every effort to prevent concomitant use of sofosbuvir/velpatasvir and inducers should be made, these cases have demonstrated that clinical cure may still be achieved in patients where coadministration cannot be avoided. Therapeutic drug level monitoring could be considered, where available.

Coadministration has not been studied and is not recommended as concentrations of velpatasvir may decrease. If use of a proton pump inhibitor is considered medically necessary, the US Prescribing Information recommends sofosbuvir/velpatasvir to be administered with food and taken 4 hours before omeprazole 20 mg but does not recommend the use of other proton pump inhibitors. The European Summary of Product Characteristics states that sofosbuvir/velpatasvir could be administered with food and taken 4 hours before a proton pump inhibitor at a dose not to exceed that comparable to omeprazole 20 mg.

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

Coadministration has not been studied. Estradiol is metabolized by CYPs 3A4 and 1A2, and is glucuronidated. None of these pathways is affected by sofosbuvir/velpatasvir. However, velpatasvir 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 appears unlikely as estramustine is dephosphorylated and minimal data show it not to undergo any form of CYP metabolism.

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

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

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

Coadministration with sofosbuvir/velpatasvir has not been studied. Based on drug interaction studies conducted with sofosbuvir alone and velpatasvir alone, no clinically significant drug interactions have been observed with ethinyl estradiol/norgestimate. Coadministration of a once daily triphasic oral contraceptive containing ethinyl estradiol (0.025 mg) and norgestimate (0.180/0.215/0.25 mg) with sofosbuvir (400 mg once daily) or velpatasvir (100 mg once daily) was studied. When administered with sofosbuvir, ethinyl estradiol Cmax and AUC increased by 15% and 9%, but Cmin decreased by 1% (n=15). When administered with velpatasvir, ethinyl estradiol Cmax and AUC increased by 39% and 4%, but Cmin decreased by 17% (n=12).

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

Coadministration with an etonogestrel-containing progestogen-only implant has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4 which is not affected by sofosbuvir/velpatasvir.

Coadministration with etonogestrel as a combined vaginal ring (CVR) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4 and is coformulated in the CVR with ethinylestradiol which is released at a dose of 0.015 mg/day. Ethinylestradiol is mainly metabolized by hydroxylation. Sofosbuvir/velpatasvir does not interact with these metabolic pathways.

Coadministration has not been studied but based on metabolism and clearance an interaction is unlikely. Etoposide is partly metabolised by CYP3A4 to reactive catechol metabolites and partly metabolised by UGT1A1. These pathways are not affected by sofosbuvir/velpatasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etoricoxib is metabolised by multiple CYP enzymes (including CYP3A4) which are not affected by sofosbuvir/velpatasvir.

Coadministration has not been studied and is not recommended. Concentrations of velpatasvir and sofosbuvir may decrease due to induction of CYP3A4 by etravirine, resulting 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. Eucalyptus is a mild to moderate inhibitor of CYP3A4, however, a clinically relevant effect is unlikely at doses used for supplementation. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. 

Coadministration has not been studied. Everolimus concentrations may increase due to mild inhibition of P-gp by velpatasvir. If coadministration cannot be avoided, therapeutic drug monitoring of everolimus should be performed due to its narrow therapeutic index. No effect on sofosbuvir/velpatasvir concentrations is expected.

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

Coadministration with exenatide has not been studied but based on metabolism and clearance a metabolic interaction is unlikely as exenatide is eliminated by glomerular filtration. GLP-1 agonists such as exenatide 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 exenatide, however, this is unlikely to be clinically significant. However, as exenatide slows gastric emptying it is advisable to take sofosbuvir/velpatasvir at least 1 hour before immediate-release exenatide injection. [Note: this interaction is not specific for sofosbuvir/velpatasvir, but for any medication taken with exenatide.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ezetimibe is primarily metabolized in the small intestine and liver by glucuronidation and ezetimibe glucuronide is a substrate of OATP1B1. Any increase in concentrations of ezetimibe glucuronide due to inhibition of OATP1B1 by velpatasvir is unlikely to be of clinical significance. [Note, use of ezetimibe is not recommended in moderate to severe hepatic dysfunction.]

Famotidine may be administered simultaneously with or 12 hours apart from sofosbuvir/velpatasvir at a dose that does not exceed famotidine 40 mg twice daily. Simultaneously coadministration of famotidine decreased sofosbuvir Cmax and AUC by 8% and 18%, and decreased velpatasvir Cmax and AUC by 20% and 19%. When administered 12 hours apart, Cmax and AUC of sofosbuvir decreased by 23% and 20%, and those of velpatasvir decreased by 13% and 15%.

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

Coadministration has not been studied. Felodipine is a substrate of CYP3A4 and P-gp, and concentrations may increase due to mild inhibition of P-gp by velpatasvir, however, this is unlikely to be of clinical significance. No effect on sofosbuvir/velpatasvir concentrations is expected.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fentanyl undergoes extensive CYP3A4 metabolism (which is not affected by sofosbuvir/velpatasvir) and is a high hepatic extraction drug and therefore is less vulnerable to drug interactions.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fexofenadine is a substrate of P-gp and OATP, and concentrations may increase due to mild inhibition of these transporters by velpatasvir, however, this is unlikely to be of clinical significance. No effect on sofosbuvir/velpatasvir concentrations is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. CYP involvement has not been displayed with filgrastim and it is mainly eliminated by neutrophil-mediated clearance, such that the serum concentration of pegfilgrastim declines rapidly with neutrophil recovery.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fingolimod is metabolised mainly by CYP4F2 and is unlikely to interact with substrates of CYP enzymes or the main transporter proteins.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although cytochrome P450 enzymes are involved in the hydroxylation of omega-3 there is no human data to indicate any clinical significance.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flibanserin is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C19 which are not affected by sofosbuvir/velpatasvir.

Coadministration has not been studied. Flucloxacillin is mainly eliminated renally, partly by glomerular filtration and partly by active secretion by OAT1. Sofosbuvir and velpatasvir are substrates of P-gp and BCRP. Velpatasvir is also a substrate of OATP1B and CYP2B6, 2C8, and 3A4. Flucloxacillin is thought to be a weak inducer of CYP3A4 and P-gp, particularly at higher doses (>2-3 g daily). A modest reduction in plasma concentrations of sofosbuvir/velpatasvir may be observed but this is unlikely to be clinically relevant unless flucloxacillin is prescribed at higher doses for a prolonged course (>10-14 days).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluconazole is mainly excreted in urine. Sofosbuvir and velpatasvir are substrates of P-gp and BCRP. Velpatasvir is also a substrate of OATP1B and CYP2B6, 2C8, and 3A4. Fluconazole is a moderate inhibitor of CYP3A4, but no clinically relevant effect on velpatasvir is expected.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Flucytosine is metabolised to 5-fluorouracil which undergoes further metabolism by dihydropyrimidine dehydrogenase.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluinidone is metabolised by CYP2C9 (major) and CYP1A2 (minor) which are not affected by velpatasvir. 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. Flunisolide is metabolized primarily by CYP3A4 which is not affected by sofosbuvir/velpatasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluoxetine is metabolised by CYP2D6 which is not affected by sofosbuvir/velpatasvir. Note, a lower or less frequent dose of fluoxetine should be considered in cases of hepatic insufficiency.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of flupentixol has been poorly described but is likely to involve CYP2D6 and potentially CYP3A4, but these pathways are not affected by sofosbuvir/velpatasvir.

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

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

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Flurbiprofen is metabolised by CYP2C9 and UGT2B7 which are not affected by sofosbuvir/velpatasvir.

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

Coadministration has not been studied. Fluvastatin is a substrate of CYPs 2C8, 2C9 and 3A4 and OATPs 1B1/3 and BCRP. Coadministration may increase fluvastatin concentrations due to inhibition of BCRP by velpatasvir. Statin-associated adverse events such as myopathy should be closely monitored. The lowest necessary dose should be used when coadministered with sofosbuvir/velpatasvir. Note, use of fluvastatin in active liver disease is contraindicated.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvoxamine is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2, but these pathways are not affected by sofosbuvir/velpatasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as folic acid undergoes deconjugation and reduction

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as formoterol is eliminated primarily by glucuronidation and O-demethylation (multiple CYP involvement). 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although fosamprenavir is an inhibitor of OATP1B, no clinically significant effect on sofosbuvir/velpatasvir is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely as foscarnet is mainly renally eliminated.  

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as furosemide is a substrate of UGTs 1A1, 1A9 and 2B7 (which are not affected by sofosbuvir/velpatasvir) and is excreted in urine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. There is no evidence of gabapentin metabolism in humans and it is eliminated unchanged solely by renal excretion with few data on transporters involved.

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely as gadopentetate is mainly renally eliminated.  

Coadministration has not been studied but a clinically significant interaction is unlikely. Garlic extract has no known effect on enzymes or transporters involved in sofosbuvir/velpatasvir disposition.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as gemcitabine is metabolised by cytidine deaminase. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although gemfibrozil inhibits OATP1B1 in vitro, no clinically significant effect on sofosbuvir/velpatasvir is expected. [Note, use of gemfibrozil in hepatic impairment is contraindicated.]

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although in vitro data show gingerols moderately inhibit CYP3A4, a clinically relevant effect on DAA exposure is unlikely at standard dietary/supplement dosage. 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 with standard doses (up to 240 mg) of Ginkgo biloba.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant pharmacokinetic interaction is unlikely. In vitro data show no effect on a number of CYP isoforms including CYP3A4, 1A2, 2E1 and 2D6.