Epclusa® (sofosbuvir/velpatasvir)

Coadministration With Fentanyl

This document is in response to your request for information regarding Epclusa® (sofosbuvir/velpatasvir [SOF/VEL]) and coadministration with fentanyl.

Some data may be outside of the US FDA-approved prescribing information. In providing this data, Gilead Sciences, Inc. is not making any representation as to its clinical relevance or to the use of any Gilead product(s). For information about the approved conditions of use of any Gilead drug product, please consult the FDA-approved prescribing information.

The full indication, important safety information, and boxed warnings are available at:
www.gilead.com/-/media/files/pdfs/medicines/liver-disease/epclusa/epclusa_pi.

PK DDI Evaluation

Drug interaction studies have not been conducted between the single-tablet regimen SOF/VEL and fentanyl. Based on the PK profile of each active ingredient within SOF/VEL and fentanyl, a PK interaction would not be predicted. For more information about fentanyl, please refer to its product labeling.1-3

SOF/VEL PK1

Table 1. SOF/VEL PK1

Abbreviations: BCRP=breast cancer resistance protein; OATP=organic anion transporting polypeptide;
P-gp=p-glycoprotein.

Relevant SOF/VEL Label Information1

There is no information in the SOF/VEL product labeling about the coadministration of SOF/VEL and fentanyl.

Established and Potentially Significant Drug Interactions

Clearance of HCV infection with direct-acting antivirals may lead to changes in hepatic function, which may impact safe and effective use of concomitant medications. Frequent monitoring of relevant laboratory parameters (eg, INR in patients taking warfarin, blood glucose levels in diabetic patients) or drug concentrations of concomitant medications such as CYP substrates with a narrow therapeutic index (eg, certain immunosuppressants) is recommended to ensure safe and effective use. Dose adjustments of concomitant medications may be necessary.

Real-World Data on the Coadministration of Fentanyl With SOF/VEL

Multidisciplinary Care Center Study4

Study design and dmographics

A real-world study conducted through an inner-city outreach program evaluated the efficacy of HCV therapy (SOF/VEL, n=133; GLE/PIB, n=75) in patients who were actively using fentanyl at the time of HCV treatment initiation between March 2019 and May 2022. The primary endpoint was SVR12. Medication adherence was verified weekly, and HCV therapy was administered in conjunction with opiate agonist therapy as appropriate. Patients were included in this analysis if active street fentanyl use was identified either through documented fentanyl use within 1 week prior to HCV treatment initiation, or through a positive urine screen for fentanyl at the time of HCV treatment initiation.

Table 2. Baseline Demographics and Disease Characteristics (Truong et al)4

Results

Of the 208 eligible patients, 11 patients discontinued the study prematurely (non-adherent or lost to follow-up, n=7; withdrew from the study, n=3; death, n=1); discontinuation rates were similar in each treatment group. At the time data were reported, 154 patients completed treatment, 138 had SVR data (SOF/VEL, n=79), and 16 were awaiting post-treatment HCV RNA results. At the time of the analysis, 97.4% of the patients (76/79) who received SOF/VEL achieved SVR ≥12 weeks after end of treatment. All therapeutic failures were attributed to relapses (SOF/VEL, n=3). Safety data were not reported.

References

1. Enclosed. Gilead Sciences Inc, EPCLUSA® (sofosbuvir and velpatasvir) tablets, for oral use. US Prescribing Information. Foster City, CA.

2. Janssen Pharmaceuticals, Inc. DURAGESIC® (fentanyl transdermal system), for transdermal administration. US Prescribing Information. Titusville, NJ.

3. Akorn, Inc. Fentanyl citrate injection, for intravenous or intramuscular use. US Prescribing Information. Lake Forest, IL.

4. Truong D, Shawn S, Yung R, Liu G, Conway B. HCV Treatment Among Fentanyl Users: Toward Universal Across to Antiviral Therapy [Poster]. Paper presented at: AASLD: The Liver Meeting; 4-8 November, 2022; Washinton DC.

Abbreviations

DDI=drug-drug interaction
GLE=glecaprevir
PIB=pibrentasvir
PK=pharmacokinetic(s)
SOF=sofosbuvir
SVR=sustained virologic response
SVR12=sustained virologic response 12 weeks after end of treatment
VEL=velpatasvir
 

Product Label

For the full indication, important safety information, and boxed warning(s), please refer to the Epclusa US Prescribing Information available at:
www.gilead.com/-/media/files/pdfs/medicines/liver-disease/epclusa/epclusa_pi.

Follow-Up

For any additional questions, please contact Gilead Medical Information at:

☎1‐866‐MEDI‐GSI (1‐866‐633‐4474) or   www.askgileadmedical.com

Adverse Event Reporting

Please report all adverse events to:

Gilead Global Patient Safety ☎ 1-800-445-3235, option 3 or
 www.gilead.com/utility/contact/report-an-adverse-event

FDA MedWatch Program by ☎ 1-800-FDA-1088 or MedWatch, FDA, 5600 Fishers Ln, Rockville, MD 20852 or   www.accessdata.fda.gov/scripts/medwatch

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