SOFOSBUVIR

Indications & Dose:

Treatment of adults with chronic hepatitis C virus (HCV) infection: · in combination with sofosbuvir in patients with HCV genotype 1 without cirrhosis or with compensated cirrhosis · in combination with peginterferon alfa (Peg-IFN-alfa) and ribavirin (RBV) in patients with HCV genotype 1 or 4 without cirrhosis or with compensated cirrhosis. (1) Limitations of Use: · Efficacy of sofosbuvir  in combination with Peg-IFN-alfa and RBV is substantially reduced in patients infected with HCV genotype 1a with an NS3 Q80K polymorphism · sofosbuvir  is not recommended in patients who have previously failed therapy with a treatment regimen that included sofosbuvir  or other HCV protease inhibitors.

BY MOUTH:

The recommended dose of Sofosbuvir is one 400 mg tablet, taken orally, once daily with or without food. Sofosbuvir should be used in combination with ribavirin or in combination with pegylated interferon and ribavirin for the treatment of CHC in adults. The recommended regimen and treatment duration for  Sofosbuvir combination therapy as under.

Recommended Regimens and Treatment Duration for  Sofosbuvir Combination Therapy in HCV Mono-infected and HCV/HIV-1 Coinfected Patients

Patients with genotype 1 or 4 CHC

Sofosbuvir + peginterferon alfaa + ribavirinb                                                   
                                                        12 weeks

Patients with genotype 2 CHC

Sofosbuvir + ribavirinb                     12 weeks

Patients with genotype 3 CHC

Sofosbuvir + ribavirinb                        24 weeks

a. See peginterferon alfa prescribing information for dosing recommendation for patients with genotype 1 or 4 CHC.

b. Dose of ribavirin is weight-based (<75 kg = 1000 mg and e”75 kg = 1200 mg). The daily dose of ribavirin is administered orally in two divided doses with food. Patients with renal impairment (CrCl d” 50 mL/min) require ribavirin dose reduction; refer to ribavirin prescribing information.

Sofosbuvir in combination with ribavirin for 24 weeks can be considered as a therapeutic option for CHC patients with genotype 1 infection who are ineligible to receive an interferon-based regimen. Treatment decision should be guided by an assessment of the potential benefits and risks for the individual patient. Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation

Sofosbuvir in combination with ribavirin is recommended for up to 48 weeks or until the time of liver transplantation, whichever occurs first, to prevent post-transplant HCV reinfection. Severe Renal Impairment and End Stage Renal Disease

No dose recommendation can be given for patients with severe renal impairment (estimated Glomerular Filtration Rate (eGFR) <30 mL/min/ 1.73m2) or with end stage renal disease (ESRD) due to higher exposures (up to 20-fold) of the predominant sofosbuvir metabolite

Contraindications:

Side Effects:

Cautions:

Precautions:

Interaction:

Co-administration of amiodarone with sofosbuvir in combination with sofosbuvir  may result in serious symptomatic bradycardia. · Co-administration of sofosbuvir  with drugs that are moderate or strong inducers or inhibitors of CYP3A may significantly affect the plasma concentrations of simeprevir. The potential for drug-drug interactions must be considered prior to and during treatment. 

Warnings:

Serious Symptomatic Bradycardia When Co-administered with Sofosbuvir and Amiodarone: Serious symptomatic bradycardia may occur in patients taking amiodarone with sofosbuvir in combination with sofosbuvir  particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Co-administration of amiodarone with sofosbuvir  in combination with sofosbuvir is not recommended. In patients without alternative treatment options, cardiac monitoring is recommended. · Hepatic Decompensation and Hepatic Failure: Hepatic decompensation and hepatic failure, including fatal cases have been reported in patients with advanced and/or decompensated cirrhosis. Monitor liver chemistry tests before and during sofosbuvir combination therapy.  · Photosensitivity: Serious photosensitivity reactions have been observed during sofosbuvir  combination therapy. Use sun protection measures and limit sun exposure during sofosbuvir  combination therapy. Consider discontinuation if a photosensitivity reaction occurs.  · Rash: Rash has been observed during sofosbuvir  combination therapy. Discontinue sofosbuvir  if severe rash occurs. 

Adverse Effects:

Lactations:

Special Precautions:

Counselling:

Side Effects Or Adverse Reactions:

Fatigue, headache and nausea. Most common adverse reactions reported with sofosbuvir with Peg-IFN-alfa and RBV during first 12 weeks of treatment: rash (including photosensitivity), pruritus and nausea

Patient And Carer Advice: