The FDA Center for Drug Evaluation and Research (CDER) has published a warning on the use of medicinal products containing sofosbuvir and velpatasvir (sofosbuvir / velpatasvir) based on the clinical studies conducted.
“Adverse reactions” section
Experience in clinical trials
Underlined additions and/or changes:
Adverse reactions in persons who inject drugs, including those receiving opioid agonist treatment (OAT) for opioid use disorder
The safety of sofosbuvir/velpatasvir in persons who inject drugs is based on an open-label phase 2 study (SIMPLIFY) that enrolled 103 adult subjects with chronic hepatitis C infection of genotypes 1, 2, 3 and 4.
Persons who self-reported injection drug use within 6 months before the start of treatment were eligible to participate and received sofosbuvir/velpatasvir for 12 weeks. The study included a subgroup of 58 subjects receiving medication-assisted treatment (MAT) for opioid use disorder.
The adverse reactions observed in SIMPLIFY, both overall and in individuals who received DAAs, were consistent with the known safety profile of sofosbuvir/velpatasvir. The most common adverse reactions overall were fatigue (18%), nausea (13%) and headache (11%) (see Use in Specific Populations (8.8) and Clinical Studies (14.7)). No adverse reactions leading to permanent discontinuation of treatment were observed in any patient.
Section “Interaction with medicinal products”
Drugs without clinically significant interactions with sofosbuvir/velpatasvir
Additions are underlined
Based on drug interaction studies conducted with the components sofosbuvir or velpatasvir, no clinically significant drug interactions were observed or expected with the following medicinal products [see Clinical Pharmacology (12.3)]:
Sofosbuvir/velpatasvir: atazanavir/ritonavir, buprenorphine/naloxone, cyclosporine, darunavir/ritonavir, dolutegravir, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, emtricitabine, methadone, naltrexone, or raltegravir.
Sofosbuvir: ethinylestradiol/norgestimate or tacrolimus.
Velpatasvir: ethinylestradiol/norgestimate, ketoconazole or pravastatin
Section “Use in specific population groups”
People who inject drugs, including those receiving supportive medication treatment (SMT) for opioid use disorder
A new subsection has been added
Based on data from phase 2 of the SIMPLIFY study, the safety and efficacy of sofosbuvir/velpatasvir in individuals who self-reported injection drug use, including those concurrently receiving MAT, were similar to the known safety and efficacy profile of [Trade name of the medicinal product]. Dose adjustment of [Trade name of the medicinal product] is not recommended for individuals who use injection drugs, including those on MAT for opioid use disorder (see Adverse reactions (6.1) and Clinical studies (14.7)).
The original text is available at the link https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=849
