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 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. Acalabrutinib is a CYP3A4 and P-gp substrate which are not affected by sofosbuvir. 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 as acamprosate does not undergo significant metabolism.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant pharmacokinetic 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 activity and is metabolised by intestinal enzymes and by the microbial flora. 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. Aceclofenac is metabolised by CYP2C9 which is not affected by sofosbuvir. 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. Acenocoumarol is mainly metabolized by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19 and sofosbuvir does not affect CYP enzymes. 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 aciclovir is eliminated primarily unchanged in the urine via glomerular filtration and active renal secretion. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications.

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 should be separated by 4 hours. [Note: this interaction is not specific for sofosbuvir, 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 as adefovir is eliminated renally via glomerular filtration and active renal secretion by OAT1. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications.

Coadministration has not been studied. Based on metabolism and elimination there is little potential for a pharmacokinetic interaction as agomelatine is metabolised by CYP1A2 which is unlikely to be affected by sofosbuvir. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [Note, agomelatine is contraindicated in hepatic impairment as increases in exposure of up to 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. Albiglutide is a protein for which the expected metabolic pathway is degradation to small peptides and individual amino acids by ubiquitous proteolytic enzymes. Albiglutide slows gastric emptying, but this is unlikely to have a clinically relevant effect on sofosbuvir.

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. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications.

Coadministration has not been studied but alendronate can be administered with sofosbuvir 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 administration. [Note: this interaction is not specific for sofosbuvir, but for any medication taken with alendronic acid.]

Coadministration has not been studied. Based on metabolism and clearance a clinically significant interaction is unlikely as allopurinol is metabolised by xanthine oxidase and aldehyde oxidase which are unlikely to be affected by sofosbuvir. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [Note, the European and US product labels for allopurinol recommend a reduced dose of allopurinol in hepatic impairment.]

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alogliptin does not undergo extensive metabolism and is excreted mainly unchanged in the urine and metabolism by CYPs is minimal. No transporter interactions have been described. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications.

Coadministration has not been studied. Although a clinically significant pharmacokinetic interaction is unlikely, in the absence of further data, separating doses by 2 hours from sofosbuvir could be considered.

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 cannot be ruled out. Doses of sofosbuvir and alverine should be separated by 4 hours if possible. [Note: this interaction is not specific for sofosbuvir, 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. 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. Sofosbuvir is a prodrug and the formation of its active metabolite is unlikely to be affected by comedications.

Coadministration of amiodarone and sofosbuvir combined with another direct acting antiviral such as daclatasvir or simeprevir may result in serious symptomatic bradycardia and is not recommended. The mechanism of the effect is unknown.

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

Coadministration has not been studied. Although a clinically significant pharmacokinetic interaction is unlikely, in the absence of further data, separating doses by 2 hours from sofosbuvir could be considered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. These pathways are not affected by sofosbuvir. 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. Artesunate is hydrolysed and metabolised via UGT1A9 and 2B7 and has been shown to induce CYP3A4; these metabolic pathways are not affected by sofosbuvir. 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. Asenapine is metabolized by glucuronidation (UGT1A4) and oxidative metabolism (mainly CYP1A2, with minor contributions from CYP3A4 and CYP2D6), none of which is affected by sofosbuvir. 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. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by atazanavir.

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 atazanavir/cobicistat.

Coadministration with atazanavir/ritonavir alone 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 atazanavir/ritonavir. Coadministration of sofosbuvir (400 mg once daily) with atazanavir/ritonavir (300/100 mg once daily, with emtricitabine/tenofovir-DF 200/300 mg once daily) had no clinically significant effect on atazanavir, ritonavir, emtricitabine, tenofovir or sofosbuvir.

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. 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 as axitinib is metabolised by CYP3A4 which is not affected by sofosbuvir. 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 drug interaction is unlikely. Aztreonam is only minimally metabolised and is eliminated mainly unchanged in the urine. 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. Bedaquiline is metabolised by CYP3A4 and sofosbuvir does not affect CYP enzymes. 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. 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. 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. Benralizumab is a humanised IgG1 monoclonal antibody that is degraded by proteolytic enzymes widely distributed in the body and not restricted to hepatic tissue. 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. Benztropine is primarily metabolised by CYP2D6, which is not affected by sofosbuvir. 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 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. 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. Bevacizumab biotransformation involves proteolytic catabolism throughout the body, including endothelial cells, and does not rely primarily on elimination through the kidneys and liver. 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. Bezafibrate is metabolised by hydroxylation, glucuronidation and renal elimination (~50%). Due to the involvement of multiple metabolic pathways and renal elimination, a clinically significant interaction is not expected. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [Note, the European SmPC for bezafibrate contraindicates its use in significant hepatic disease.]

Coadministration of bictegravir/emtricitabine/tenofovir alafenamide and sofosbuvir alone has not been studied. Based on studies with sofosbuvir/ledipasvir and sofosbuvir/ledipasvir/voxilaprevir, bictegravir is unlikely to significantly impact sofosbuvir pharmacokinetics and sofosbuvir is unlikely to significantly impact bictegravir pharmacokinetics. Furthermore, no clinically significant interactions were observed when sofosbuvir was coadministered with emtricitabine or tenofovir alafenamide. Coadministration of emtricitabine (200 mg once daily with efavirenz and tenofovir) and sofosbuvir (400 mg single dose) was studied in 16 subjects. Sofosbuvir Cmax and AUC decreased by 19% and 6%, respectively, with Cmax and AUC of GS-331007 (the major circulating sofosbuvir metabolite) decreasing by 23% and 16%, respectively. Emtricitabine Cmax and AUC decreased by 3% and 1%, but Cmin increased by 4%. Coadministration of ledipasvir/sofosbuvir (90/400 mg once daily) and tenofovir alafenamide (25 mg once daily) increased tenofovir alafenamide AUC by 32%, the pharmacokinetics of ledipasvir/sofosbuvir was not significantly changed. 

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. 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. 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. 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 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. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. However, bisacodyl increases colonic mass movements and may affect absorption of sofosbuvir. The potential interaction can be resolved by giving bisacodyl at least 4 hours after sofosbuvir. [Note: this interaction is not specific for sofosbuvir, but for any medication taken with bisacodyl.]

Coadministration has not been studied. Bisoprolol is metabolised via CYP3A4 and 2D6 and a clinically significant interaction is unlikely as sofosbuvir does not affect CYP enzymes. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [Note, the European SmPC 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. 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. Bosutinib is metabolised principally by CYP3A4 which is not affected by sofosbuvir. 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. 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. 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. Brinzolamide is metabolised by CYP3A4 which is not affected by sofosbuvir. 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. Brodalumab is degraded into small peptides. 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. Bromperidol is metabolised by CYP3A4, which is not affected by sofosbuvir. 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. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). These pathways are not affected by sofosbuvir. 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. Calcium carbimide is a prodrug requiring catalase and hydrogen peroxide to generate the active metabolite. 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. Canagliflozin is primarily metabolised by UGTs 1A9 and 2B4 which are not affected by sofosbuvir. Canagliflozin is an inhibitor of P-gp and may increase sofosbuvir concentrations. However, increasing sofosbuvir concentrations has been shown not to increase the active component GS-331007 therefore no a priori dose modification is required. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely as candesartan is largely eliminated unchanged via urine and bile. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [Note, use of candesartan in severe hepatic impairment is contraindicated in the European SmPC; the US Prescribing Information recommends caution in moderate hepatic impairment.]

Coadministration with sofosbuvir is not currently recommended. Carbamazepine is a potent inducer of P-gp and may significantly decrease sofosbuvir concentrations; this may lead to reduced therapeutic effect and potential virological failure. Coadministration of sofosbuvir with carbamazepine decreased sofosbuvir Cmax and AUC by 48%. Cmax of GS-331007 increased by 4% and AUC decreased by 1%. 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) and achieved a sustained virologic response. Although every effort to prevent concomitant use of sofosbuvir and potent inducers should be made, these cases have demonstrated that clinical cure may still be achieved in patients where coadministration cannot be avoided. Therapeutic drug level monitoring could be considered, where available.

Coadministration has not been studied. As both carvedilol and sofosbuvir are substrates of P-gp, concentrations of sofosbuvir may be increased. However, increasing sofosbuvir concentrations has been shown not to increase the predominant metabolite GS-331007, therefore no dose change should be required. [Note, the US Prescribing Information contraindicates carvedilol in patients with severe hepatic impairment and the European SPC contraindicates it in patients with hepatic dysfunction.]

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely as caspofungin undergoes spontaneous chemical degradation and non-CYP mediated metabolism. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [Note, no dose adjustment is required in patients with normal hepatic function, but the European SmPC for caspofungin recommends a dose reduction of caspofungin daily dose to 35 mg for adults with moderate hepatic impairment. There is no clinical experience in adults with severe hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cat’s claw is a strong inhibitor of CYP3A4 which does not interact with sofosbuvir. 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 drug interaction is unlikely. Cefaclor is predominantly eliminated unchanged by the kidneys. 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 drug interaction is unlikely. Cefadroxil is not metabolised and is predominantly eliminated unchanged by the kidneys. 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 drug interaction is unlikely. Cefradine is not metabolised and is predominantly eliminated unchanged by the kidneys. 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 drug interaction is unlikely. Ceftaroline is not metabolised by CYP enzymes and is primarily eliminated by the kidneys. 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 as celecoxib is mainly metabolised by CYP2C9 which is not affected by sofosbuvir. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [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. Like other protein therapeutics, cetuximab is expected to be degraded into small peptides and amino acids via catabolic pathways. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications.

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. Chloroquine is mainly metabolised by CYP2C8 and CYP3A4/5. A clinically significant interaction is unlikely as sofosbuvir does not affect CYP enzymes. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. 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. Chlorpromazine is a substrate of CYPs 2D6 (major), 1A2, and 3A4 in vitro. Sofosbuvir does not affect CYP enzymes. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [Note, the European SmPC for chlorpromazine advises that its use should be avoided in patients with hepatic dysfunction.]

Coadministration 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. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [Note, although no interaction is anticipated, ECG monitoring is mandatory prior to treatment with chlorprothixene.]

Coadministration of sofosbuvir and ciclosporin (600 mg single dose) had no effect on ciclosporin (Cmax increased by 6%, AUC decreased by 2%). The Cmax and AUC of sofosbuvir increased by 2.54- and 4.53-fold, respectively. GS-331007 Cmax decreased by 40%, but AUC increased by 4%. No dose adjustment of sofosbuvir or ciclosporin is required. However, the pharmacokinetics of tacrolimus 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 pharmacokinetic interaction is unlikely. Cilazapril is rapidly converted to the active form, cilazaprilat, which is excreted unchanged in the urine. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [Note, in patients with cirrhosis, a maximum dose of 0.5 mg/day is recommended as significant hypotension may occur.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cisatracurium undergoes mainly (80% of overall elimination) spontaneous degradation in plasma and tissues at physiological pH and temperature (Hofmann elimination). 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 drug interaction is unlikely. Clavulanic acid is extensively metabolized (likely by a non-CYP mediated pathway) and excreted in the urine by glomerular filtration. 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. Clevidipine is rapidly metabolised by hydrolysis of the ester linkage and does not undergo CYP metabolism. 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. Clodronate is not metabolised and is primarily excreted unchanged by the kidney. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. 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, but for any medication taken with clodronate.]

Coadministration has not been studied. Clopidogrel is metabolised by CYP enzymes and a clinically significant interaction is unlikely as sofosbuvir does not affect CYP enzymes. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [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. The metabolism of clotiapine has not been well characterised but is likely to involve CYP450 enzymes. Sofosbuvir does not affect CYP enzymes. 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. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications.

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, but for any medication taken with colestyramine.]

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. 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 limited data for the metabolism and clearance of cyclizine, a clinically significant interaction is unlikely. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. Cyclizine undergoes hepatic metabolism which may include CYP2D6.

Coadministration of sofosbuvir (400 mg once daily) and daclatasvir (60 mg once daily) was studied in patients with chronic HCV infection. When compared to historical data, daclatasvir AUC, Cmax and Cmin decreased by 5%, 12% and 9%, respectively. There was no change in the AUC of GS-331007 (the major circulating metabolite of sofosbuvir), but Cmax decreased by 20% and Cmin increased by 40%. No dose adjustment of daclatasvir or sofosbuvir is required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as danaparoid is renally excreted and no hepatic involvement was shown in animal studies. 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. Dantron is absorbed from the small intestine and acts at the large intestine. 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 as dapagliflozin is metabolised by UGT1A9. 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. 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. 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. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by darunavir/cobicistat.

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 darunavir/cobicistat. No clinically significant interactions were observed when sofosbuvir was coadministered with emtricitabine or tenofovir alafenamide. Coadministration of emtricitabine (200 mg once daily with efavirenz and tenofovir) and sofosbuvir (400 mg single dose) was studied in 16 subjects. Sofosbuvir Cmax and AUC decreased by 19% and 6%, respectively, with Cmax and AUC of GS-331007 (the major circulating sofosbuvir metabolite) decreasing by 23% and 16%, respectively. Emtricitabine Cmax and AUC decreased by 3% and 1%, but Cmin increased by 4%. Coadministration of ledipasvir/sofosbuvir (90/400 mg once daily) and tenofovir alafenamide (25 mg once daily) increased tenofovir alafenamide AUC by 32%, the pharmacokinetics of ledipasvir/sofosbuvir was not significantly changed. No dose adjustment is required.

Coadministration of darunavir/ritonavir (800/100 mg once daily) and sofosbuvir (400 mg single dose) was studied in 18 subjects. Cmax and AUC of sofosbuvir increased by 45% and 34% respectively. Cmax of GS-331007 decreased by 3%, but AUC increased by 24%. Darunavir Cmax, AUC and Cmin decreased by 3%, 3% and 14%, respectively. No dose adjustment of sofosbuvir or darunavir/ritonavir is required.

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. 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. 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. A clinically significant interaction is unlikely as sofosbuvir does not affect CYP enzymes. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [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. 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. 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. Sofosbuvir does not affect CYP enzymes. 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 as desvenlafaxine is metabolised by CYP3A4 which is not affected by sofosbuvir. 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. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. Sofosbuvir is a substrate of P-gp and BCRP. Dexamethasone is a P-gp inducer in pre-clinical models but this is unlikely to be clinically relevant in this setting.

Coadministration has not been studied but based on 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.

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 is not expected to induce or inhibit UGTs or CYP2C8/2C9. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [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. Dienogest is a substrate of CYP3A4 which is not affected by sofosbuvir. 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. 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 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 as diphenhydramine is metabolised by CYP2D6 which is not affected by sofosbuvir. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [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. Dofetilide is eliminated in the kidney by cationic secretion and is metabolized to a small extent by CYP3A4. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications.

Coadministration with dolutegravir/rilpivirine 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. Dolutegravir is metabolised by UGT1A1 (major) and CYP3A (minor), neither of which is affected by sofosbuvir. Coadministration of rilpivirine (25 mg once daily) and sofosbuvir (400 mg single dose) was studied in 17 subjects. Sofosbuvir Cmax and AUC increased by 21% and 9%, whereas GS-331007 Cmax and AUC increased by 6% and 1%. Rilpivirine Cmax and AUC increased by 5% and 6%, but Cmin decreased by 1%. No dose adjustment of sofosbuvir or rilpivirine is required.

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. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications.

Coadministration with sofosbuvir alone has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Coadministration of doravirine (100 mg once daily) and ledipasvir/sofosbuvir (90/400 mg once daily) increased doravirine AUC, Cmax and Cmin by 15%, 11% and 24%, respectively. This small increase is not considered clinically meaningful. Doravirine did not significantly alter sofosbuvir exposure.

Coadministration with Delstrigo has not been studied. Coadministration of doravirine (100 mg once daily) and ledipasvir/sofosbuvir (90/400 mg once daily) increased doravirine AUC, Cmax and Cmin by 15%, 11% and 24%, respectively. This small increase is not considered clinically meaningful. Doravirine did not significantly alter sofosbuvir exposure. No clinically significant interaction is expected with lamivudine. Coadministration of tenofovir-DF (300 mg once daily with emtricitabine and efavirenz) and sofosbuvir (400 mg single dose) was studied in 16 subjects. Sofosbuvir Cmax and AUC decreased by 19% and 6%, respectively, with GS-331007 Cmax and AUC decreasing by 23% and 16%, respectively. Tenofovir Cmax increased by 25%, but AUC and Cmin decreased by 2% and 1%, respectively. No dose adjustment is required.

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 are not affected by sofosbuvir. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [Note: Dosulepin should be used with caution in mild to moderate hepatic impairment and avoided in severe hepatic impairment.]

Coadministration has not been studied. Doxazosin is extensively metabolised by CYP3A4 and to a lesser extent 2D6 and 2C19. A clinically significant interaction is unlikely as sofosbuvir does not affect CYP enzymes. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [Note, the European SmPC does not recommend doxazosin in severe hepatic impairment; the US Prescribing Information has a caution for use in hepatic impairment.]

Coadministration has not been studied. Doxepin is primarily metabolized by hepatic cytochrome P450 isozymes CYP2C19 and CYP2D6, and to a lesser extent, by CYP1A2 and CYP2C9. A clinically significant interaction is unlikely as sofosbuvir does not affect CYP enzymes. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [Note, the European and US product labels for doxepin advise caution and monitoring in patients with hepatic impairment as a dosage reduction may be required.]

Co-administration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Limited data available for doxylamine metabolism suggest involvement of CYP2B6 which is not affected by sofosbuvir. 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. Drospirenone is metabolised mainly without involvement of CYP enzymes. 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 as dulaglutide is presumed to be degraded by general protein catabolism pathways. Dulaglutide delays gastric emptying but interaction studies showed no clinically significant effect on the absorption of concomitantly administered oral medicinal products and no dose adjustment of comedications is recommended. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications.

Coadministration has not been studied. Duloxetine is metabolised via CYP1A2 and 2D6 and a clinically significant interaction is unlikely as sofosbuvir does not affect CYP enzymes. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [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. 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 as dutasteride is metabolised by CYP3A4 and CYP3A5, neither of which is not affected by sofosbuvir. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [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. Eblastine is metabolised by CYP450 which is not affected by sofosbuvir. 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. Although both drugs are substrates of P-gp, no effect on edoxaban or sofosbuvir concentrations is expected. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [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 efavirenz (600 mg once daily with emtricitabine and tenofovir) and sofosbuvir (400 mg single dose) was studied in 16 subjects. Sofosbuvir Cmax and AUC decreased by 19% and 6%, respectively, with GS-331007 Cmax and AUC decreasing by 23% and 16%, respectively. Efavirenz Cmax, AUC and Cmin decreased by 5%, 4% and 4% respectively. No dose adjustment of sofosbuvir or efavirenz is required.

The interaction between elbasvir/grazoprevir and sofosbuvir was evaluated in clinical studies, and no dose adjustments are needed. Coadministration of sofosbuvir (400 mg single dose) and elbasvir + grazoprevir (50 + 200 mg once daily) increased sofosbuvir AUC and Cmax by 2.43-fold and 2.27-fold. The AUC and Ctrough of GS-331007 (the predominant circulating metabolite of sofosbuvir) increased by 13% and 53%, but Cmax decreased by 13%.

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 does not inhibit or induce these CYP enzymes. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications.

Coadministration with sofosbuvir alone has not been studied, but a clinically significant interaction is unlikely based on studies with ledipasvir/sofosbuvir. Coadministration of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (150/150/200/10 mg once daily) and ledipasvir/sofosbuvir (90/400 mg once daily) increased ledipasvir and sofosbuvir AUC by 79% and 47%, respectively (most likely via inhibition of P-gp and/or BCRP by cobicistat). Ledipasvir/sofosbuvir increased elvitegravir and cobicistat AUC by 11% and 53%, respectively, but did not impact significantly the pharmacokinetics of tenofovir alafenamide (AUC decreased by 16%), tenofovir (AUC increased by 27%) or emtricitabine. The increase in ledipasvir and sofosbuvir are within the safety window. In addition, the increase in elvitegravir and cobicistat are considered as not clinically relevant based on the safety window. No dose adjustments are needed.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as elvitegravir is metabolised by CYP3A4 which is not affected by sofosbuvir. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. In addition, coadministration of emtricitabine/tenofovir-DF (with efavirenz) and sofosbuvir (400 mg single dose) was studied in 16 subjects. Sofosbuvir Cmax and AUC decreased by 19% and 6%, respectively, with GS-331007 Cmax and AUC decreasing by 23% and 16%, respectively. Tenofovir Cmax increased by 25%, but AUC and Cmin decreased by 2% and 1%, respectively. No dose adjustment of sofosbuvir or tenofovir-DF is required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although both drugs are substrates of P-gp, no effect on sofosbuvir concentrations is expected. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications.

Coadministration of emtricitabine (200 mg once daily with efavirenz and tenofovir) and sofosbuvir (400 mg single dose) was studied in 16 subjects. Sofosbuvir Cmax and AUC decreased by 19% and 6%, respectively, with GS-331007 Cmax and AUC decreasing by 23% and 16%, respectively. Emtricitabine Cmax and AUC decreased by 3% and 1%, but Cmin increased by 4%. No dose adjustment of sofosbuvir or emtricitabine is required.

Coadministration with sofosbuvir and emtricitabine/tenofovir alafenamide has not been studied. A clinically significant interaction is unlikely based on studies with sofosbuvir-containing regimens in combination with emtricitabine/tenofovir alafenamide-containing regimens.

Coadministration of tenofovir-DF (300 mg), emtricitabine (200 mg) with efavirenz (once daily) and sofosbuvir (400 mg single dose) was studied in 16 subjects. Sofosbuvir Cmax decreased by 19% and there was no change in AUC; GS-331007 (a metabolite of sofosbuvir) Cmax decreased by 23%, with no change in AUC. Tenofovir Cmax increased by 25%, but there was no change in AUC and Cmin. There was no change in emtricitabine AUC, Cmax or Cmin. No dose adjustment is required.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Entecavir is eliminated primarily in the urine by glomerular filtration and tubular secretion by OAT1. 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. 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 as ergometrine is metabolised by CYP3A4 which is not affected by sofosbuvir. 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. Although both drugs are substrates of P-gp, no effect on sofosbuvir concentrations is expected. 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. Sofosbuvir is a substrate for P-gp and BCRP but eslicarbazepine does not induce these transporters.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [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. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications.

Coadministration of sofosbuvir and an oral contraceptive containing ethinyl estradiol and norgestimate increased ethinyl estradiol Cmax and AUC by 14% and 8%. The Cmax and AUC of norgestromin (an active metabolite of norgestimate) increased by 6% and 5%, whereas the Cmax and AUC of norgestrel (an active metabolite of norgestimate) increased by 18% and 19%. No dose adjustment of ethinyl estradiol or norgestimate is required.

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. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications.

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 does not interact with these metabolic pathways. 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 as etoposide is mainly metabolised by CYP3A4 and UGT1A1 which are not affected by sofosbuvir. 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. 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 but based on metabolism and clearance a clinically significant interaction is unlikely as exemestance is metabolised by CYP3A4, which is not affected by sofosbuvir. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications.

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

Coadministration has not been studied, but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Ezetimibe is primarily metabolized in the small intestine and liver via glucuronidation. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [Note, use of ezetemibe is not recommended in moderate to severe hepatic dysfunction.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Febuxostat is extensively metabolised by multiple P450 (CYPs 1A1, CYP1A2, CYP2C8 and CYP2C9) and UGT enzymes (UGTs 1A1, 1A8, and 1A9). A clinically significant interaction is unlikely as febuxostat is metabolised by multiple pathways. 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 as fenofibrate is metabolised by multiple enzyme pathways (esterases, UGT2B7 and UGT1A1). Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [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. Flibanserin is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C19, neither of which are affected by sofosbuvir. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications.

Coadministration has not been studied. Flucloxacillin is mainly eliminated renally, partly by glomerular filtration and partly by active secretion via OAT1. Sofosbuvir is a substrate of P-gp. Flucloxacillin is thought to be a weak inducer of P-gp, particularly at higher doses (>2-3 g daily). A modest reduction in plasma concentrations of sofosbuvir 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 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. Fludarabine phosphate is rapidly hydrolyzed (non-CYP mediated) to 2F-ara-A, the principal metabolite, which is then eliminated renally.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. Fluinidone is metabolised by CYP2C9 (major) and CYP1A2 (minor) which are not affected by sofosbuvir. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. 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. Fluoxetine is mainly metabolised by CYP2D6 which is not affected by sofosbuvir. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. 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 as flurbiprofen is metabolised by CYP2C9 and UGT2B7 which are not affected by sofosbuvir. 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 as fluvastatin is metabolised by CYP3A4 which is not affected by sofosbuvir. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. Note, use of fluvastatin in active liver disease is contraindicated.

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Fosinopril is a prodrug metabolised in the liver by a non-CYP mechanism to the active metabolite. 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. Gefitinib is metabolised by CYP3A4, which is not affected by sofosbuvir. 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 pharmacokinetic interaction is unlikely. Gemfibrozil is metabolised via UGT2B7 and to date there is no evidence that sofosbuvir is involved in this pathway. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. [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. In vitro data show gingerols moderately inhibit CYP3A4. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. 

Coadministration of sofosbuvir (400 mg single dose) and glecaprevir/pibrentasvir increased sofosbuvir Cmax and AUC by 66% and 125%; there was no change in the Cmax and AUC of GS-33107 (the active metabolite of sofosbuvir) but Cmin increased by 85%. Cmax, AUC and Cmin of glecaprevir and pibrentasvir were unaltered. No dose adjustment is required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as glibenclamide is metabolised by CYP3A4 which is not affected by sofosbuvir. 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 as gliclazide is metabolized by CYPs 2C19 and 2C9 which are not affected by sofosbuvir. 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 as glimepiride is metabolised by CYP2C9 which is not affected by sofosbuvir. 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 as glipizide is metabolised by CYP2C9 which is not affected by sofosbuvir. 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. Glycerol phenylbutyrate is metabolised by pancreatic lipases, beta-oxidation, and glutamine conjugation, then eliminated in the urine. Glycerol phenylbutyrate has been shown to be a weak inducer of CYP3A4, but sofosbuvir does not undergo CYP metabolism. 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 concentration is unlikely. Goldenseal is a CYP3A4 inhibitor, however, 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 as there is minimal metabolism and no clinically relevant accumulation with higher doses of depot. Goserelin acetate is renally cleared with no dose alteration required in renal or hepatic impairment. 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. Granisetron is metabolised by CYP3A4 which is not affected by sofosbuvir. 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. Grape seed extract appears to mildly inhibit CYP3A4. 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. Studies have shown variable CYP involvement with green tea metabolism but the overall effect is likely negligible. 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. Heroin is metabolised mainly by deacetylation. 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. There is no evidence that homeopathic remedies interact with conventional medicines, provided they are from a reputable source, and of the strength stated. However, exercise caution, as some remedies termed ‘low potency’ are less dilute, and some remedies may contain alcohol.