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SOVALDI™ (sofosbuvir)

DESCRIPTION CLINICAL PHARMACOLOGY INDICATIONS AND USAGE
CONTRAINDICATIONS PRECAUTIONS ADVERSE REACTIONS
DOSAGE AND ADMINISTRATION HOW SUPPLIED  
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Drug Updates:  SOVALDI ® (sofosbuvir) tablets, for oral use
[Drug information  /  PDF]  
Dosing:  Click (+) next to Dosage and Administration section (drug info link)

Initial U.S. Approval:  2013
SOVALDI is indicated for the treatment of genotype 1, 2, 3 or 4 chronic hepatitis C virus (HCV) infection as a component of a combination antiviral treatment regimen

Mechanism of Action: Sofosbuvir is a direct-acting antiviral agent against the hepatitis C virus




WARNINGS  top of page

See warnings and precautions below.

DESCRIPTION  top of page

Description:
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.

CLINICAL PHARMACOLOGY: top of page

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  top of page

INDICATIONS AND USAGE:
SOVALDI is a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor indicated for the treatment of chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen.

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:

  • Monotherapy of SOVALDI is not recommended for treatment of CHC.
  • Treatment regimen and duration are dependent on both viral genotype and patient population.
  • Treatment response varies based on baseline host and viral factors.

 USE IN SPECIFIC POPULATIONS
Patients with HCV/HIV-1 co-infection: Safety and efficacy have been studied.
Patients with hepatocellular carcinoma awaiting liver transplantation: Safety and efficacy have been studied.

CONTRAINDICATIONS top of page

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.

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.

PRECAUTIONS top of page

WARNINGS AND PRECAUTIONS:
  1. Pregnancy: Ribavirin may cause birth defects and fetal death and animal studies have shown interferons have abortifacient effects; avoid pregnancy in female patients and female partners of male patients. Patients must have a negative pregnancy test prior to initiating therapy, use at least 2 effective non-hormonal methods of contraception and have monthly pregnancy tests.
  2. Drug interactions: Drugs that are potent intestinal P-gp inducers (e.g., rifampin, St. John's wort) may alter the concentrations of sofosbuvir. Consult the full prescribing information prior to use for potential drug-drug interactions.

ADVERSE REACTIONS top of page

ADVERSE REACTIONS:
  • 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.
See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide.

DOSAGE AND ADMINISTRATION  top of page

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.
  Treatment Duration
Patients with genotype 1 or 4 CHC SOVALDI + peginterferon alfa* + ribavirin† 12 weeks
Patients with genotype 2 CHC SOVALDI + ribavirin† 12 weeks
Patients with genotype 3 CHC SOVALDI + ribavirin† 24 weeks

*See peginterferon alfa prescribing information for dosing recommendation for patients with genotype 1 or 4 CHC.
†Dose of ribavirin is weight-based (<75 kg = 1000 mg and geq75 kg = 1200 mg). The daily dose of ribavirin is administered orally in two divided doses with food. Patients with renal impairment (CrCl leq 50 mL/min) require ribavirin dose reduction; refer to ribavirin prescribing information.


Patients with genotype 1 or 4 CHC SOVALDI + peginterferon alfa* + ribavirin† 12 weeks
Patients with genotype 2 CHC SOVALDI + ribavirin† 12 weeks
Patients with genotype 3 CHC SOVALDI + ribavirin† 24 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
SOVALDI 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.

Dose Modification
Dose reduction of SOVALDI is not recommended.

Genotype 1 and 4:
If a patient has a serious adverse reaction potentially related to peginterferon alfa and/or ribavirin, the peginterferon alfa and/or ribavirin dose should be reduced or discontinued. Refer to the peginterferon alfa and ribavirin prescribing information for additional information about how to reduce and/or discontinue the peginterferon alfa and/or ribavirin dose.

Genotype 2 and 3:
If a patient has a serious adverse reaction potentially related to ribavirin, the ribavirin dose should be modified or discontinued, if appropriate, until the adverse reaction abates or decreases in severity. Table 2 provides guidelines for dose modifications and discontinuation based on the patient's hemoglobin concentration and cardiac status.

Table 2 Ribavirin Dose Modification Guideline for Coadministration with SOVALDI
Laboratory Values Reduce Ribavirin Dose to 600 mg/day* If: Discontinue Ribavirin If:†
Hemoglobin in patients with no cardiac disease <10 g/dL <8.5 g/dL
Hemoglobin in patients with history of stable cardiac disease geq2 g/dL decrease in hemoglobin during any 4 week treatment period <12 g/dL despite 4 weeks at reduced dose
*The daily dose of ribavirin is administered orally in two divided doses with food.

† Once ribavirin has been withheld due to either a laboratory abnormality or clinical manifestation, an attempt may be made to restart ribavirin at 600 mg daily and further increase the dose to 800 mg daily. However, it is not recommended that ribavirin be increased to the original assigned dose (1000 mg to 1200 mg daily).

Discontinuation of Dosing
If the other agents used in combination with SOVALDI are permanently discontinued, SOVALDI should also be discontinued.

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

HOW SUPPLIED top of page

DOSAGE FORMS AND STRENGTHS:
Tablets: 400 mg.

REFERENCE

Reference(s):
Package insert data:  
Manufactured and distributed by:
Gilead Sciences, Inc.
Foster City, CA 94404

SOVALDI is a trademark of Gilead Sciences, Inc., or its related companies. ATRIPLA is a trademark of Bristol-Myers Squibb & Gilead Sciences, LLC. All other trademarks referenced herein are the property of their respective owners.

©2013 Gilead Sciences, Inc. All rights reserved.

204671-GS-000
Revised: 12/2013
 [Accessed: Jan 2014]
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