SOVALDI™ (sofosbuvir) tablets
|See warnings and precautions below.|
SOVALDI is the brand name for sofosbuvir, a nucleotide analog inhibitor of HCV NS5B polymerase.
The IUPAC name for sofosbuvir is (S)-Isopropyl 2-((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)-(phenoxy)phosphorylamino)propanoate. It has a molecular formula of C22H29FN3O9P and a molecular weight of 529.45.
| Mechanism of Action:
Sofosbuvir is a direct-acting antiviral agent against the hepatitis C virus.
Sofosbuvir is an inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication. Sofosbuvir is a nucleotide prodrug that undergoes intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), which can be incorporated into HCV RNA by the NS5B polymerase and acts as a chain terminator. In a biochemical assay, GS-461203 inhibited the polymerase activity of the recombinant NS5B from HCV genotype 1b, 2a, 3a and 4a with IC50 values ranging from 0.7 to 2.6 µM. GS-461203 is not an inhibitor of human DNA and RNA polymerases nor an inhibitor of mitochondrial RNA polymerase.
Indications and usage
INDICATIONS AND USAGE:
SOVALDI efficacy has been established 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.
The following points should be considered when initiating treatment with SOVALDI:
USE IN SPECIFIC POPULATIONS
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.
Because ribavirin may cause birth defects and fetal death, SOVALDI in combination with peginterferon alfa/ribavirin or ribavirin is contraindicated in pregnant women and in men whose female partners are pregnant.
| WARNINGS AND PRECAUTIONS:
| ADVERSE REACTIONS:
See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide.
Dosage and administration
| DOSAGE AND ADMINISTRATION:
Recommended Dose in Adults:
The recommended dose of SOVALDI is one 400 mg tablet, taken orally, once daily with or without food.
SOVALDI 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 SOVALDI combination therapy is provided in Table 1.
Table 1 Recommended Regimens and Treatment Duration for SOVALDI Combination Therapy in HCV Mono-infected and HCV/HIV-1 Co-infected Patients.
*See peginterferon alfa prescribing information for dosing recommendation for patients with genotype 1 or 4 CHC.
Patients with genotype 1 or 4 CHC SOVALDI + peginterferon alfa* + ribavirin† 12 weeks
SOVALDI 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 [See Use in Specific Populations and Clinical Studies - package insert]. 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
Genotype 1 and 4:
Genotype 2 and 3:
Table 2 Ribavirin Dose Modification Guideline for Coadministration with SOVALDI
Discontinuation of Dosing
Severe Renal Impairment and End Stage Renal Disease
National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
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