Liverpool HEP Interactions

Potential Interaction

Sofosbuvir/Velpatasvir/Voxilaprevir

Atorvastatin

Summary:

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

Description:

The effect of Vosevi on atorvastatin has not been studied. Coadministration of atorvastatin (40 mg single dose) with sofosbuvir/velpatasvir (400/100 mg, once daily) has been studied. Atorvastatin Cmax and AUC increased by 70% and 50%, respectively. Atorvastatin may be administered with Vosevi at a dose that does not exceed atorvastatin 20 mg.

Vosevi Summary of Product Characteristics, Gilead Sciences Ltd, January 2021.

Coadministration with Vosevi may increase the concentrations of atorvastatin. Increased statin concentrations may increase the risk of myopathy, including rhabdomyolysis. Use the lowest approved statin dose. If higher doses are needed, use the lowest necessary statin dose based on a risk/benefit assessment.
Coadministration of atorvastatin (40 mg, single dose) with sofosbuvir/velpatasvir (400/100, once daily) was studied in 26 subjects. Atorvastatin Cmax and AUC increased by 68% and 54%, respectively.

Vosevi Prescribing Information, Gilead Sciences, Inc. November 2019.

No Interaction Expected

Sofosbuvir/Velpatasvir/Voxilaprevir

Buprenorphine

Summary:

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

Description:

One hundred and three patients with chronic HCV infection who also self-reported injected drug use were treated with sofosbuvir/velpatasvir 400/100 mg, once daily for 12 weeks. Of this study population, 4 were taking buprenorphine and 12 were taking buprenorphine/naloxone. The primary endpoint of this study was sustained virological response at 12 weeks (SVR12), which 97% of the study population achieved. No drug interaction events relating to overdose of buprenorphine were noted.

Sofosbuvir and velpatasvir for hepatitis C virus infection in people with recent injection drug use (SIMPLIFY): an open-label, single-arm, phase 4, multicentre trial. Grebely J, Dalgard O, Conway B, et al. Lancet Gastroenterol Hepatol, 2018, 3(3):153-161.

No Interaction Expected

Sofosbuvir/Velpatasvir/Voxilaprevir

Folic acid

Summary:

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

Description:

(See Summary)

No Interaction Expected

Sofosbuvir/Velpatasvir/Voxilaprevir

Gliclazide

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gliclazide is metabolized by CYPs 2C19 and 2C9 which are not affected by sofosbuvir/velpatasvir/voxilaprevir.

Description:

Diabetics may experience improved glucose control, potentially resulting in symptomatic hypoglycaemia, after initiating HCV DAA treatment. Glucose levels of diabetic patients initiating DAA therapy should be closely monitored, particularly within the first 3 months, and their diabetic medication modified when necessary. The physician in charge of the diabetic care of the patient should be informed when DAA therapy is initiated.

Vosevi Summary of Product Characteristics, Gilead Sciences Ltd, January 2021.

Clearance of HCV infection with direct acting antivirals may lead to changes in hepatic function, which may impact the safe and effective use of concomitant medications. For example, altered blood glucose control resulting in serious symptomatic hypoglycemia has been reported in diabetic patients in postmarketing case reports and published epidemiological studies. Management of hypoglycemia in these cases required either discontinuation or dose modification of concomitant medications used for diabetes treatment. Frequent monitoring of relevant laboratory parameters (e.g., blood glucose levels in diabetic patients) is recommended to ensure safe and effective use. Dose adjustments of concomitant medications may be necessary.

Vosevi Prescribing Information, Gilead Sciences, Inc. November 2019.

No Interaction Expected

Sofosbuvir/Velpatasvir/Voxilaprevir

Lisinopril

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lisinopril does not undergo metabolism and is excreted entirely unchanged into the urine. [Note, lisinopril exposure is increased in cirrhotic patients due to decreased clearance.]

Description:

(See Summary)

No Interaction Expected

Sofosbuvir/Velpatasvir/Voxilaprevir

Lithium

Summary:

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

Description:

(See Summary)

No Interaction Expected

Sofosbuvir/Velpatasvir/Voxilaprevir

Metformin

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Metformin is mainly excreted renally and is transported by OCT2 which is not inhibited by sofosbuvir/velpatasvir/voxilaprevir. [Note, metformin is contraindicated with hepatic insufficiency, acute alcohol intoxication, and alcoholism.]

Description:

Diabetics may experience improved glucose control, potentially resulting in symptomatic hypoglycaemia, after initiating HCV DAA treatment. Glucose levels of diabetic patients initiating DAA therapy should be closely monitored, particularly within the first 3 months, and their diabetic medication modified when necessary. The physician in charge of the diabetic care of the patient should be informed when DAA therapy is initiated.

Vosevi Summary of Product Characteristics, Gilead Sciences Ltd, January 2021.

Clearance of HCV infection with direct acting antivirals may lead to changes in hepatic function, which may impact the safe and effective use of concomitant medications. For example, altered blood glucose control resulting in serious symptomatic hypoglycemia has been reported in diabetic patients in postmarketing case reports and published epidemiological studies. Management of hypoglycemia in these cases required either discontinuation or dose modification of concomitant medications used for diabetes treatment. Frequent monitoring of relevant laboratory parameters (e.g., blood glucose levels in diabetic patients) is recommended to ensure safe and effective use. Dose adjustments of concomitant medications may be necessary.

Vosevi Prescribing Information, Gilead Sciences, Inc. November 2019.

No Interaction Expected

Sofosbuvir/Velpatasvir/Voxilaprevir

Olanzapine

Summary:

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

Description:

(See Summary)

No Interaction Expected

Sofosbuvir/Velpatasvir/Voxilaprevir

Pregabalin

Summary:

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

Description:

(See Summary)

No Interaction Expected

Sofosbuvir/Velpatasvir/Voxilaprevir

Salbutamol

Summary:

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

Description:

(See Summary)

No Interaction Expected

Sofosbuvir/Velpatasvir/Voxilaprevir

Daptomycin

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daptomycin is eliminated renally with minimal to no active tubular secretion. Sofosbuvir, velpatasvir, and voxilaprevir are substrates of P-gp and BCRP. Velpatasvir and voxilaprevir are also substrates of OATP1B. In vitro, slow metabolic turnover of velpatasvir primarily by CYP2B6, CYP2C8, and CYP3A4 and of voxilaprevir primarily by CYP3A4 was observed.

Description:

(See Summary)

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