Here’s the latest monogram everyone’s been working from to determine who gets the Sovaldi, how much and for how long. Additionally. they are still trying to pawn off the bug juice (Interferon) on those unsuspecting few with Genotype 1A&B who are gently described as “Interferon naive” or virgins. The good news is the the sickest get it first and those with Cryoglobulinemia even get to cut line to the front. Everything in red is as it appears on the circular.

“Sofosbuvir is indicated for the treatment of chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen. Sofosbuvir has established efficacy in subjects with HCV genotype 1, 2, 3 or 4 infection, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) and those with HCV/HIV-1 co-infection.

This document is meant to aid in deciding which patients are appropriate for simeprevir or sofosbuvir therapy during the preparation, discussion and vetting of the comprehensive drug monograph and criteria for use. The most important outcome of the current document is to ensure access to treatment with these agents for patients with advanced disease who are at higher risk for morbidity and mortality from their disease and liver status.”

 Sofosbuvir: Executive summary

Efficacy has been established in HCV GT 1, 2, 3 or 4, including those with HCC meeting Milan criteria (awaiting liver transplantation) and those with HCV/HIV-1 co-infection

Must not be used as monotherapy

Safety and efficacy not established in post-liver transplant patients

Regimen and duration dependent on both viral genotype and patient population

The efficacy of sofosbuvir in a treatment experienced population was done using modeling; a clinical trial was not conducted.

Candidates for all oral therapy with sofosbuvir and ribavirin include genotype 2 and 3 patients, HIV-HCV co-infected patients, persons who are not candidates for interferon-containing therapy and those awaiting a liver transplant

The safety and efficacy of simeprevir and sofosbuvir in combination in the treatment of HCV infection have not been established.

Patient Selection during interim period (prior to Drug Monograph and CFU approval/posting)

Patients with the highest risk of disease advancement should be prioritized to receive sofosbuvir. This group includes all HCV genotypes with compensated or decompensated cirrhosis and pre- liver transplant patients to prevent post-transplant HCV. Additionally, genotype 1 patients who are deemed interferon intolerant can be considered for a treatment regimen of sofosbuvir/ribavirin given for 24 weeks. Patients who have demonstrated documented ongoing nonadherence to prior medications, medical treatment or failure to complete HCV disease evaluation appointments and procedures are not appropriate candidates for therapy until those issues have been resolved.

Cirrhosis/ALD can be defined as

Biopsy proven cirrhosis

or

Clinical diagnosis based on defined events (i.e.,prior Child class B or C qualifying events) , Fib-4 > 3.25, APRI > 2.0

or

Platelet count  < 100,000 mm3

Or

Fibroscan score >12.5 kPa

In addition, consideration should be given to treating patients with serious extra-hepatic complications of HCV infection such as cryoglobulinemia

Interferon ineligible populations include;

·         Patients with severe thrombocytopenia (platelet count < 50,000 mm3)

·         Patients with severe depression not responsive to medical therapy (documented by mental health provider)

·         Patients with decompensated liver cirrhosis, i.e., Child class B or C

·         Patients with hepatocellular cancer awaiting liver transplant

·         Patients with auto-immune diseases that may be exacerbated by interferon-mediated immune modulation

Dosage and Administration for Sofosbuvir

One 400mg tablet QD with or without food

No response guided treatment

Eliminated primarily via renal clearance, safety/efficacy of sofosbuvir is not established in CrCl<30 ml/min

Hemodialysis removes 18% of the dose.

A dose recommendation cannot be made for patients with severe renal impairment (CrCl< 30 ml/min) or end stage renal disease requiring dialysis

No dose adjustment of sofosbuvir is required for patients with mild, moderate or severe hepatic impairment.

Drug Interactions

Sofosbuvir is a substrate of P-glycoprotein: inducers may decrease sofosbuvir plasma concentrations

No CYP450 involvement, fewer drug interactions would be anticipated

 Duration of Treatment with Sofosbuvir, Peginterferon and Ribavirin*

*Includes both HCV mono-infected and HCV/HIV co-infected patients