Ledevoni ®

Treatment-naive patients without cirrhosis or with compensated cirrhosis: Ledipasvir 90 mg/sofosbuvir 400 mg once daily for 12 weeks.

Decompensated cirrhosis: Ledipasvir 90 mg/sofosbuvir 400 mg once daily with concomitant ribavirin for 12 weeks; if ribavirin ineligible, ledipasvir 90 mg/sofosbuvir 400 mg once daily for 24 weeks.

Contraindications:

Hypersensitivity to any component of the formulation.

Interactions:

Amiodarone: Sofosbuvir may enhance the bradycardic effect of Amiodarone. Management: Use alternative to a sofosbuvir-containing combo or to amiodarone when possible. If alternatives not possible, monitor in inpatient setting for first 48 hours of coadministration with daily outpatient monitoring for at least 2 weeks. Risk D: Consider therapy modification

Antacids: May decrease the serum concentration of Ledipasvir. Management: Separate the administration of ledipasvir and antacids by 4 hours. Risk D: Consider therapy modification

Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider therapy modification

Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the serum concentration of Ledipasvir. Management: PPI or PCAB doses equivalent to omeprazole 20 mg or lower may be given with ledipasvir under fasted conditions. Use of ledipasvir with higher doses or with food, or 2 hours after these agents, may reduce ledipasvir bioavailability. Risk D: Consider therapy modification

Oxcarbazepine: May decrease the serum concentration of Sofosbuvir. Risk X: Avoid combination

Rosuvastatin: Ledipasvir may increase the serum concentration of Rosuvastatin. Risk X: Avoid combination

Pregnancy and Lactation:

Adverse events were not observed in animal reproduction studies using ledipasvir or sofosbuvir.

It is not known if ledipasvir or sofosbuvir are present in breast milk, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Warning and Precaution:

Diabetes: Rapid reduction in hepatitis C viral load during direct-acting antiviral (DAA) therapy for hepatitis C may lead to improvement in glucose metabolism in patients with diabetes, potentially resulting in symptomatic hypoglycemia if antidiabetic agents are continued at the same dose. Monitor for changes in glucose tolerance and inform patients of the risk of hypoglycemia during DAA therapy, particularly within the first 3 months. Modification of antidiabetic therapy may be necessary.

Hepatitis B virus (HBV) reactivation has been reported in hepatitis C virus (HCV)/HBV coinfected patients who were receiving or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy; some cases have resulted in fulminant hepatitis, hepatic failure, and death. Test all patients for evidence of current or prior HBV infection prior to initiation of ledipasvir/sofosbuvir; monitor HCV/HBV co-infected patients for hepatitis flare or HBV reactivation during treatment and post-treatment follow-up. Initiate treatment for HBV infection as clinically indicated.

Amiodarone: Symptomatic bradycardia (some requiring pacemaker intervention) and fatal cardiac arrest has occurred in patients receiving amiodarone and ledipasvir/sofosbuvir. Bradycardia generally occurred within hours to days following coadministration, however some cases have occurred 2 weeks following the initiation of HCV treatment. The risk of bradycardia may be increased in patients taking beta blockers or patients with underlying cardiac comorbidities and/or advanced liver disease.

Adverse Reactions:

Headache (11% to 29%), fatigue (10% to 18%), Asthenia (18% to 31%)

Storage:

Store below 30°C and protect from light and moisture.