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HBV reactivation, including cases resulting in fulminant hepatitis, hepatic failure, and death, reported in patients coinfected with HCV and HBV who were receiving or had completed treatment with HCV direct-acting antivirals (DAAs) and were not receiving HBV antiviral therapy.Test all patients for evidence of current or prior HBV infection before initiating fixed combination of sofosbuvir and velpatasvir (sofosbuvir/velpatasvir).Monitor patients coinfected with HCV and HBV for hepatitis flare or HBV reactivation during and after HCV treatment.Treatment of chronic HCV genotype 1, 2, 3, 4, 5, or 6 infection in treatment-naive (have not previously received HCV treatment) or previously treated adults and pediatric patients ≥6 years of age weighing ≥17 kg without cirrhosis or with compensated or decompensated cirrhosis (Child-Pugh class A, B, or C), including those with HIV coinfection.Used alone for treatment of chronic HCV infection in patients without cirrhosis or with compensated cirrhosis (Child-Pugh class A);Treatment of chronic HCV infection is complex and rapidly evolving; consult a specialist to obtain the most up-to-date information.For treatment of chronic HCV infection, sofosbuvir/velpatasvir is used alone or in conjunction with ribavirin.Specific regimen depends on certain patient factors (e.g., presence of decompensated cirrhosis).Prior to initiating HCV treatment, test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc).Administer orally once daily without regard to food.Available as fixed-combination tablets containing 200 mg of sofosbuvir and 50 mg of velpatasvir and fixed-combination tablets containing 400 mg of sofosbuvir and 100 mg of velpatasvir.Treatment-naive or previously treated pediatric patients ≥6 years of age weighing ≥17 kg: Dosage is based on weight.Pediatric patients ≥6 years of age weighing ≥17 kg without cirrhosis or with compensated cirrhosis (Child-Pugh class A): Use alone for a treatment duration of 12 weeks.Pediatric patients ≥6 years of age weighing ≥17 kg with decompensated cirrhosis (Child-Pugh class B or C): Use in conjunction with ribavirin.One tablet containing sofosbuvir 200 mg/velpatasvir 50 mg once dailyOne tablet containing sofosbuvir 400 mg/velpatasvir 100 mg once dailyTwo tablets containing sofosbuvir 200 mg/velpatasvir 50 mg once dailyUse same dosage, treatment regimen, and treatment duration recommended for HCV-infected patients without HIV coinfection.Treatment-naive or previously treated adults: 1 tablet (sofosbuvir 400 mg and velpatasvir 100 mg) once daily.Noncirrhotic or with compensated cirrhosis (Child-Pugh class A): Use alone for treatment duration of 12 weeks.Decompensated cirrhosis (Child-Pugh class B or C): Use in conjunction If sofosbuvir/velpatasvir (without ribavirin) used for treatment of HCV genotype 1, 4, 5, or 6 infection in patients who cannot receive ribavirin, some experts recommend treatment duration of 24 weeks.In clinical trials, previously treated adults had received regimens containing peginterferon alfa and ribavirin with or without an HCV nonstructural 3/4A (NS3/4A) protease inhibitor (boceprevir, simeprevir, or telaprevir; drugs no longer available in US).Use weight-based ribavirin dosage in adults (1 g daily for patients <75 kg or 1.2 g daily for those ≥75 kg); give ribavirin daily dosage in 2 divided doses with food.Use same dosage, treatment regimen, and treatment duration recommended for HCV-infected patients without HIV coinfection.Mild, moderate, or severe hepatic impairment (Child-Pugh class A, B, or C): Dosage adjustments not needed.Mild, moderate, or severe renal impairment, including end-stage renal disease (ESRD) requiring dialysis: Dosage adjustments not needed.If sofosbuvir/velpatasvir used in conjunction with ribavirin, the contraindications to ribavirin also apply.Postmarketing reports of reactivation of HBV infection when DAAs were used for treatment of HCV infection in patients with HBV coinfection;HBV reactivation (abrupt increase in HBV replication manifested as rapid increase in serum HBV DNA levels or detection of HBsAg in an individual who was previously HBsAg negative and anti-HBc positive) reported in patients with HCV and HBV coinfection receiving HCV treatment with a regimen that included HCV DAAs without interferon alfa.Patients with HBV reactivation heterogeneous in terms of HCV genotype and baseline HBV disease.HBV reactivation also reported in patients receiving certain immunosuppressant or chemotherapeutic drugs;Mechanism for HBV reactivation in coinfected patients receiving HCV DAAs unknown.Prior to initiating treatment with an HCV DAA, including sofosbuvir/velpatasvir, screen all patients for evidence of current or prior HBV infection by measuring HBsAg, anti-HBs, and anti-HBc.In all patients with evidence of current or prior HBV infection, monitor for clinical and laboratory signs (i.e., HBsAg, HBV DNA levels, serum aminotransferase and bilirubin concentrations) of hepatitis flare or HBV reactivation during and after treatment with HCV DAAs.Advise coinfected patients to immediately contact a clinician if they develop any signs or symptoms of serious liver injury.When making decisions regarding HBV monitoring or HBV treatment in coinfected patients, consult a clinician with expertise in managing HBV infection.Postmarketing reports of symptomatic bradycardia, including cases requiring pacemaker intervention, in patients receiving amiodarone concomitantly with HCV treatment regimen containing sofosbuvir in conjunction with another HCV DAA (e.g., daclatasvir, simeprevir; drugs no longer available in US).In most reported cases, bradycardia occurred within hours to days after HCV treatment initiated in patients receiving amiodarone (also has been observed up to 2 weeks after initiation of HCV treatment) and resolved after HCV treatment discontinued.Patients who may be at increased risk for symptomatic bradycardia if amiodarone used concomitantly with sofosbuvir/velpatasvir include those also receiving a β-adrenergic blocking agent, those with underlying cardiac comorbidities, and/or those with advanced liver disease.Concomitant use of amiodarone with sofosbuvir/velpatasvir If there are no alternative HCV treatment options and regimen of sofosbuvir/velpatasvir must be used in a patient receiving amiodarone, advise patient about the risk of serious bradycardia before initiating HCV treatment.Advise patients receiving amiodarone concomitantly with sofosbuvir/velpatasvir to immediately contact a clinician if signs or symptoms of bradycardia (e.g., near-fainting or fainting, dizziness or lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pain, confusion, memory problems) develop.Concomitant use of sofosbuvir/velpatasvir and inducers of the P-glycoprotein (P-gp) transport system and/or moderate to potent inducers of CYP2B6, 2C8, or 3A4 (e.g., carbamazepine and other anticonvulsants, rifampin, St. John's wort) not recommended.Consider cautions, precautions, contraindications, and drug interactions associated with both drugs in the fixed combination (i.e., sofosbuvir, velpatasvir).When used in conjunction with ribavirin, consider that ribavirin may cause fetal toxicity and/or death.Adequate data not available regarding use in pregnant women.When used in conjunction with ribavirin, consider that ribavirin is contraindicated in pregnant women and male partners of pregnant women.Not known whether sofosbuvir/velpatasvir and metabolites distributed into human milk.Predominant metabolite of sofosbuvir (GS-331007) distributed into milk in rats;Consider benefits of breast-feeding and importance of the drug to the woman;Safety and efficacy not established in pediatric patients <6 years of age.Safety and efficacy for treatment of HCV genotype 1, 2, 3, 4, or 6 infection in treatment-naive and previously treated pediatric patients ≥6 years of age weighing ≥17 kg without cirrhosis or with compensated cirrhosis (Child-Pugh class A) have been established based on an open-label, phase 2 study.Safety and efficacy for treatment of HCV genotype 5 infection in pediatric patients ≥6 years of age weighing ≥17 kg without cirrhosis or with compensated cirrhosis (Child-Pugh class A) are supported by similar sofosbuvir, GS-331007 (predominant metabolite of sofosbuvir), and velpatasvir exposures in adults and pediatric patients.Adverse effects reported in pediatric patients ≥6 years of age are similar to those observed in adults.Data not available regarding safety of sofosbuvir/velpatasvir in pediatric patients with renal impairment.No overall differences in safety and efficacy in patients ≥65 years of age compared with younger adults, but increased sensitivity in some older individuals cannot be ruled out.HCV-infected individuals with moderate or severe hepatic impairment (Child-Pugh class B or C): Increased sofosbuvir and GS-331007 exposures compared with those in individuals with normal hepatic function.Moderate or severe hepatic impairment (Child-Pugh class B or C) without HCV infection: Velpatasvir exposure similar to exposure in individuals with normal hepatic function.When velpatasvir/sofosbuvir used in conjunction with ribavirin in patients with decompensated cirrhosis (Child-Pugh class B or C), clinical and hepatic laboratory monitoring (including direct bilirubin) recommended as clinically indicated.Data not available regarding safety of sofosbuvir/velpatasvir in patients with decompensated cirrhosis Mild, moderate, or severe renal impairment without HCV infection: Increased sofosbuvir and GS-331007 exposures compared with those in individuals with normal renal function.ESRD without HCV infection: Increased sofosbuvir and GS-331007 exposures when administered 1 hour before or 1 hour after hemodialysis compared with exposures in individuals with normal renal function.Severe renal impairment without HCV infection: Velpatasvir exposure similar to exposure in healthy individuals.HCV-infected with ESRD requiring dialysis: Increased sofosbuvir, GS-331007, and velpatasvir exposures compared with those with normal renal function.Data not available regarding safety of sofosbuvir/velpatasvir in patients with severe renal impairment (including those with ESRD requiring dialysis) who also have decompensated cirrhosis.Sofosbuvir/velpatasvir in patients without cirrhosis or with compensated cirrhosis: Headache,In vitro studies indicate slow metabolic turnover of velpatasvir by CYP2B6, 2C8, and 3A4.Velpatasvir inhibits breast cancer resistance protein (BCRP);Velpatasvir transported by organic anion transporting polypeptide (OATP) 1B1 and 1B3;The following drug interactions are based on studies using sofosbuvir/velpatasvir, sofosbuvir alone, or velpatasvir alone, or are predicted to occur.Moderate or potent CYP2B6, 2C8, or 3A4 inducers: Possible decreased sofosbuvir and/or velpatasvir plasma concentrations leading to reduced therapeutic effect;CYP2B6, 2C8, or 3A4 inhibitors: Possible increased velpatasvir plasma concentrations;P-gp substrates: Intestinal absorption may be affected resulting in increased exposure of such substrates.P-gp inducers: Possible decreased sofosbuvir and/or velpatasvir plasma concentrations leading to reduced therapeutic effect;P-gp inhibitors: Possible increased sofosbuvir and/or velpatasvir concentrations;BCRP substrates: Intestinal absorption may be affected resulting in increased exposure of such substrates.BCRP inhibitors: Possible increased sofosbuvir and/or velpatasvir concentrations;OATP1B1, 1B3, or 2B1 substrates: Intestinal absorption may be affected resulting in increased exposure of such substrates.Take antacids 4 hours before or after sofosbuvir/velpatasvirAmiodarone: Concomitant use with sofosbuvir/velpatasvir may result in serious symptomatic bradycardia;Amiodarone: Concomitant use with sofosbuvir/velpatasvir Anticonvulsants (carbamazepine, phenobarbital, phenytoin)Carbamazepine, phenobarbital, phenytoin: Decreased sofosbuvir and velpatasvir concentrations expectedCarbamazepine, phenobarbital, phenytoin: Concomitant use with sofosbuvir/velpatasvir not recommendedAltered blood glucose control resulting in serious symptomatic hypoglycemia reported when HCV DAAs used in diabetic patients receiving antidiabetic agentsKetoconazole: No clinically important pharmacokinetic interactions with velpatasvirAntimycobacterial agents (rifabutin, rifampin, rifapentine)Rifabutin: Decreased sofosbuvir concentrations and AUC;Rifampin: Decreased sofosbuvir and velpatasvir concentrations and AUCsRifapentine: Decreased sofosbuvir and velpatasvir concentrations expectedRifabutin, rifampin, rifapentine: Concomitant use with sofosbuvir/velpatasvir not recommendedFixed combination of bictegravir, emtricitabine, and tenofovir alafenamide fumarate (bictegravir/emtricitabine/TAF): No clinically important pharmacokinetic interactions with sofosbuvir/velpatasvirIncreased digoxin concentrations and AUC when used concomitantly with velpatasvirDigoxin therapeutic concentration monitoring recommended if used concomitantly with sofosbuvir/velpatasvirNo clinically important pharmacokinetic interactions with sofosbuvir/velpatasvirHIV antiretroviral regimens that include dolutegravir Doravirine: Clinically important pharmacokinetic interactions not expected with sofosbuvir/velpatasvirFixed combination of doravirine, lamivudine, and TDF (doravirine/lamivudine/TDF): Increased tenofovir concentrations if used with sofosbuvir/velpatasvirDoravirine: Dosage adjustments not needed if used with sofosbuvir/velpatasvirDoravirine/lamivudine/TDF: Monitor for tenofovir-associated adverse effectsEfavirenz: Decreased velpatasvir concentrations and AUCFixed combination of efavirenz, emtricitabine, and TDF (efavirenz/emtricitabine/tenofovir DF): No clinically important effect on sofosbuvir pharmacokinetics;Efavirenz: Concomitant use with sofosbuvir/velpatasvir not recommendedFixed combination of elvitegravir, cobicistat, emtricitabine, and TAF (EVG/c/FTC/TAF): No clinically important pharmacokinetic interactionsFixed combination of elvitegravir, cobicistat, emtricitabine, and TDF (EVG/c/FTC/TDF): No clinically important effect on sofosbuvir, velpatasvir, elvitegravir, cobicistat, or emtricitabine pharmacokinetics;EVG/c/FTC/TDF: Monitor for tenofovir-associated adverse effectsNo clinically important pharmacokinetic interactions with sofosbuvir/velpatasvirOral contraceptive containing ethinyl estradiol and norgestimate: No clinically important effects on pharmacokinetics of ethinyl estradiol or norgestimate and its active metabolites (norelgestromin, norgestrel)Concomitant use with sofosbuvir/velpatasvir not recommendedAtorvastatin: Increased atorvastatin concentrations expected; increased risk of myopathy and rhabdomyolysisRosuvastatin: Increased rosuvastatin concentrations; increased risk of myopathy and rhabdomyolysisAtorvastatin: Closely monitor for statin-associated adverse effects (e.g., myopathy, rhabdomyolysis)Rosuvastatin: Do not exceed rosuvastatin dosage of 10 mg dailyImmunosuppressive agents (cyclosporine, tacrolimus)Cyclosporine: No clinically important pharmacokinetic interactions with sofosbuvir or velpatasvirTacrolimus: No clinically important pharmacokinetic interactions with sofosbuvirInterferon alfa: No in vitro evidence of antagonistic anti-HCV effects with sofosbuvir or velpatasvirFixed combination of lopinavir and ritonavir (lopinavir/ritonavir): No clinically important effect on sofosbuvir or velpatasvir pharmacokineticsLopinavir/ritonavir: Dosage adjustments not needed if used with sofosbuvir/velpatasvirHIV antiretroviral regimens that include lopinavir/ritonavir Clinically important pharmacokinetic interactions not expectedNo clinically important pharmacokinetic interactions with sofosbuvirConcomitant use with sofosbuvir/velpatasvir not recommendedConcomitant use with sofosbuvir/velpatasvir not recommendedIf concomitant use necessary, administer sofosbuvir/velpatasvir with food 4 hours before omeprazole 20 mg;Raltegravir: Clinically important pharmacokinetic interactions not expectedHIV antiretroviral regimen of raltegravir in conjunction with emtricitabine/TDF: No clinically important effect on raltegravir or emtricitabine pharmacokinetics;Raltegravir: Dosage adjustments not needed if used with sofosbuvir/velpatasvirHIV antiretroviral regimens that include raltegravir No in vitro evidence of antagonistic anti-HCV effects with sofosbuvir or velpatasvirRilpivirine: Clinically important pharmacokinetic interactions not expectedFixed combination of emtricitabine, rilpivirine, and TDF (emtricitabine/rilpivirine/TDF): No clinically important effect on emtricitabine or rilpivirine pharmacokinetics;HIV antiretroviral regimens that include rilpivirine Possible decreased sofosbuvir and velpatasvir concentrationsConcomitant use with sofosbuvir/velpatasvir not recommendedTenofovir alafenamide fumarate (TAF): No clinically important pharmacokinetic interactionsTenofovir disoproxil fumarate (TDF): Increased tenofovir concentrations and AUC if used with sofosbuvir/velpatasvirTAF: Dosage adjustments not needed if used with sofosbuvir/velpatasvirTDF: Monitor for tenofovir-associated adverse effects if used with sofosbuvir/velpatasvirExperts state consider using TAF (instead of TDF) in patients at risk for TDF-associated adverse effectsConcomitant use with sofosbuvir/velpatasvir not recommendedSubtherapeutic INR reported after initiation of sofosbuvir-containing regimens in patients receiving warfarinFollowing oral administration of sofosbuvir/velpatasvir, peak plasma concentrations of sofosbuvir occur approximately 0.5–1 hour after the dose.Following oral administration of sofosbuvir/velpatasvir, peak plasma concentrations of velpatasvir occur 3 hours after the dose.Administration of sofosbuvir/velpatasvir with moderate-fat (approximately 600 kcal, 30% fat) or high-fat (approximately 800 kcal, 50% fat) meal increased sofosbuvir exposures by 60 or 78%, respectively,Sofosbuvir: In HCV-infected individuals with moderate or severe hepatic impairment (Child-Pugh class B or C), sofosbuvir AUC is 126 or 143% higher, respectively, compared with individuals with normal hepatic function;Velpatasvir: In individuals with moderate or severe hepatic impairment (Child-Pugh class B or C) without HCV infection, AUC of velpatasvir after single 100-mg dose is similar to that observed in individuals with normal hepatic function.Sofosbuvir: In individuals with mild, moderate, or severe renal impairment without HCV infection, sofosbuvir AUC after single 400-mg dose is 61, 107, or 171% higher, respectively, compared with individuals with normal renal function;Velpatasvir: In individuals with severe renal impairment without HCV infection, no clinically important differences in velpatasvir pharmacokinetics after single 100-mg dose compared with healthy individuals.Sofosbuvir/velpatasvir: In HCV-infected individuals with ESRD requiring dialysis, AUCs of sofosbuvir, GS-331007, and velpatasvir are 81, 1719, and 418% higher, respectively, than AUCs in HCV-infected patients with normal renal function.Population pharmacokinetic analysis in HCV-infected individuals indicates cirrhosis does not substantially affect sofosbuvir, GS-331007, or velpatasvir exposures.Population pharmacokinetic analysis in HCV-infected individuals indicates that sex and race do not affect sofosbuvir, GS-331007, or velpatasvir exposures.Pediatric patients ≥6 years of age weighing ≥17 kg: No clinically important differences in pharmacokinetics compared with adults.Sofosbuvir: Prodrug that undergoes intracellular metabolic activation in the liver (hydrolysis by human cathepsin A [CatA] or carboxylesterase 1 [CES1], phosphoramidate cleavage by histidine triad nucleotide-binding protein 1 [HINT1], and phosphorylation by pyrimidine nucleotide biosynthesis pathway).Sofosbuvir: Major route of elimination is renal clearance.Velpatasvir: Major route of elimination is biliary excretion (approximately 77% of a dose eliminated as parent drug).Sofosbuvir: Hemodialysis (4-hour session) removes approximately 18% of dose.Sofosbuvir/velpatasvir is a fixed combination of 2 HCV antivirals.Sofosbuvir and velpatasvir are both DAAs with activity against HCV.Sofosbuvir is a prodrug that undergoes metabolic activation in the liver to a pharmacologically active uridine analog triphosphate (GS-461203), which can be incorporated into HCV RNA by NS5B polymerase;Velpatasvir inhibits the HCV NS5A protein, which is required for viral replication.Certain amino acid substitutions in NS5B polymerase of HCV genotypes 1b, 2a, 2b, 3a, 4a, 5a, and 6a have been selected in cell culture and have been associated with reduced susceptibility to sofosbuvir in vitro in replicon studies.Certain amino acid substitutions in NS5A of HCV genotype 1a (e.g., L31V, Y93H/N), genotype 1b (e.g., L31V, Y93H), genotype 2a (e.g., F28S, Y93H), genotype 3a (e.g., Y93H/S), genotype 4a (e.g., Y93H), and genotype 6 (e.g., L31V, P32A/L/Q/R) have been selected in cell culture and have been associated with reduced susceptibility to velpatasvir in vitro in replicon studies.Sofosbuvir and velpatasvir are active against HCV with substitutions associated with resistance to other HCV DAAs with different mechanisms of action (e.g., HCV NS5B polymerase inhibitors, HCV NS3 protease inhibitors).Importance of reading patient information provided by the manufacturer.Advise patients to take sofosbuvir/velpatasvir once daily (with or without food) on a regular dosing schedule.Importance of taking the recommended dosage of sofosbuvir/velpatasvir for the recommended duration of treatment;Inform patients that reactivation of HBV infection has occurred in coinfected patients being treated for HCV infection.If sofosbuvir/velpatasvir is used in a patient receiving amiodarone, advise the patient about the risk of serious symptomatic bradycardia and the importance of immediately contacting a clinician if signs or symptoms of bradycardia (e.g., near-fainting or fainting, dizziness, lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pain, confusion, memory problems) occur.Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.Importance of informing patients of other important precautionary information.2.