n adverse effect on nursing infants. Consider the benefits of breast-feeding, the risk of infant drug exposure, and the risk of an untreated or inadequately treated condition. Boceprevir, simeprevir, or sofosbuvir may be considered as alternatives; however, their excretions into human breast milk are also unknown. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.
Renal failure, renal impairment
Safety and efficacy of sofosbuvir; velpatasvir have not been established in patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m2) or end stage renal failure. Compared to individuals with normal renal function, patients with mild, moderate, and severe renal impairment display increased exposure to the parent drug sofosbuvir (61%, 107%, and 171% higher, respectively) and the major metabolite, GS-331007, (55%, 88%, and 451% higher, respectively). Exposure to sofosbuvir and GS-331007 in patients with end stage renal failure, as compared to those with normal renal function, is 28% and 1,280% higher, respectively, when dosed 1 hour before hemodialysis and 60% and 2,070% higher, respectively, when dosed 1 hour after hemodialysis.
Hepatitis C and HIV coinfection
HIV treatment guidelines recommend all patients presenting with HIV infection undergo testing for hepatitis C, with continued annual screening advised for those persons considered high risk for acquiring hepatitis C. If hepatitis C and HIV coinfection is identified, consider treating both viral infections concurrently. For most patients, the benefits of concurrent therapy outweighs the potential risks (i.e., drug-induced hepatic injury, complex drug interactions, overlapping toxicities); therefore, it is recommended to initiate a fully suppressive antiretroviral (ARV) therapy and a hepatitis C regimen in all coinfected patients regardless of CD4 count. However, for antiretroviral naive patients with CD4 counts greater than 500 cells/mm3, consideration may be given to deferring ARV until the hepatitis C treatment regimen has been completed. Conversely, for patients with CD4 counts less than 200 cells/mm3, consider delaying initiation of the hepatitis C treatment regimen until the patient is stable on fully suppressive ARV regimen. Instruct coinfected patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate.
Hepatitis B exacerbation
Use of direct-acting antivirals (DAA), such as sofosbuvir and velpatasvir, to treat hepatitis C virus (HCV) infections in patients currently or previously infected with hepatitis B virus (HBV) has been associated with reactivation and exacerbation of the HBV infection. To decrease the risk of reactivating a HBV infection, screen all potential drug recipients for evidence of current or prior HBV infection by measuring HBsAg and anti-HBc concentrations. For those patients whose screening reveals serologic evidence of HBV infection, a baseline HBV DNA concentration should be obtained prior to starting sofosbuvir; velpatasvir. Continue to monitor coinfected patients during and after treatment for clinical and laboratory signs of hepatitis B exacerbation (i.e., HBsAg, HBV DNA, hepatic enzymes, bilirubin). In addition, instruct patients to immediately report any signs of liver toxicity (e.g., yellow eyes or skin, fatigue, weakness, loss of appetite, nausea, vomiting, or li |
