Sofosbuvir

Brand Names: Sovaldi

Drug Class: Hepatitis C Virus Nucleotide Analog NS5B Polymerase Inhibitor

Overview

11 DESCRIPTION SOVALDI (sofosbuvir) is a nucleotide analog inhibitor of HCV NS5B polymerase. The IUPAC name for sofosbuvir is ( S )-isopropyl 2-(( S )-(((2 R ,3 R ,4 R ,5 R )-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2 H )-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)-(phenoxy)phosphorylamino)propanoate. It has a molecular formula of C 22 H 29 FN 3 O 9 P and a molecular weight of 529.45.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Sofosbuvir is a direct-acting antiviral agent against the hepatitis C virus [see Microbiology (12.4) ]. 12.2 Pharmacodynamics Cardiac Electrophysiology The effect of sofosbuvir 400 and 1200 mg (three times the recommended dosage) on QTc interval was evaluated in a randomized, single-dose, placebo- and active-controlled (moxifloxacin 400 mg) four period crossover thorough QT trial in 59 healthy subjects. At a dosage three times the maximum recommended dosage, SOVALDI does not prolong QTc to any clinically relevant extent. 12.3 Pharmacokinetics Absorption The pharmacokinetic properties of sofosbuvir and the predominant circulating metabolite GS-331007 have been evaluated in healthy adult subjects and in subjects with chronic hepatitis C.

Indications

  • 1 INDICATIONS AND USAGE SOVALDI is a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor indicated for the treatment of: Adult patients with genotype 1, 2, 3 or 4 chronic HCV infection without cirrhosis or with compensated cirrhosis as a component of a combination antiviral treatment regimen. ( 1 ) Pediatric patients 3 years of age and older with genotype 2 or 3 chronic HCV infection without cirrhosis or with compensated cirrhosis in combination with ribavirin.

Common Doses

  • 400 mg
  • 1000 mg
  • 1200 mg
  • 50 mL

Dosage

2 DOSAGE AND ADMINISTRATION Testing Prior to the Initiation of Therapy: Test all patients for HBV infection by measuring HBsAg and anti-HBc. ( 2.1 ) Recommended dosage in adults: One 400 mg tablet taken once daily with or without food. ( 2.2 ) Recommended dosage in pediatric patients 3 years of age and older: Recommended dosage of SOVALDI in pediatric patients 3 years of age and older with genotype 2 or 3 HCV using SOVALDI tablets or oral pellets is based on weight. Refer to Table 3 of the full prescribing information for specific dosing guidelines based on body weight. ( 2.

Black Box Warning

WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with SOVALDI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing 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.

Contraindications

  • 4 CONTRAINDICATIONS When SOVALDI is used in combination with ribavirin or peginterferon alfa/ribavirin, the contraindications applicable to those agents are applicable to combination therapies. Refer to the prescribing information of peginterferon alfa and ribavirin for a list of their contraindications. When used in combination with peginterferon alfa/ribavirin or ribavirin alone, all contraindications to peginterferon alfa and/or ribavirin also apply to SOVALDI combination therapy. ( 4 )

Side Effects

  • 6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: Serious Symptomatic Bradycardia When Coadministered with Amiodarone [see Warnings and Precautions (5.2) ] . The most common adverse events (incidence greater than or equal to 20%, all grades) observed with SOVALDI in combination with ribavirin were fatigue and headache. The most common adverse events observed with SOVALDI in combination with peginterferon alfa and ribavirin were fatigue, headache, nausea, insomnia and anemia. ( 6.1 ).

Interactions

  • 7 DRUG INTERACTIONS Coadministration of amiodarone with a sofosbuvir-containing regimen may result in serious symptomatic bradycardia. ( 5.2 , 6.2 , 7.1 ) Drugs that are intestinal P-gp inducers (e.g., rifampin, St. John's wort) may alter the concentrations of sofosbuvir. ( 5.3 , 7 , 12.3 ) Consult the full prescribing information prior to use for potential drug-drug interactions. ( 5.2 , 5.3 , 7 , 12.3 ) Clearance of HCV infection with direct acting antivirals may lead to changes in hepatic function, which may impact safe and effective use of concomitant medications.