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
DOSAGE AND ADMINISTRATION
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.
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 alfaa + ribavirinb
|
12 weeks
|
Patients with genotype 2 CHC
|
SOVALDI + ribavirinb
|
12 weeks
|
Patients with genotype 3 CHC
|
SOVALDI + 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 ≥75 kg = 1200 mg). The daily dose of ribavirin is administered orally in two divided doses with food. Patients with renal impairment (CrCl ≤ 50 mL/min) require ribavirin dose reduction; refer to ribavirin prescribing information.
b. Dose of ribavirin is weight-based (<75 kg = 1000 mg and ≥75 kg = 1200 mg). The daily dose of ribavirin is administered orally in two divided doses with food. Patients with renal impairment (CrCl ≤ 50 mL/min) require ribavirin dose reduction; refer to ribavirin prescribing information.
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. Treatment decision should be guided by an assessment of the potential benefits and risks for the individual patient.< p/>
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.
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.
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.
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.
WARNINGS AND PRECAUTIONS
Use with Potent P-gp Inducers
Drugs that are potent P-gp inducers in the intestine (e.g., rifampin, St. John’s wort) may significantly decrease sofosbuvir plasma concentrations and may lead to a reduced therapeutic effect of SOVALDI. Rifampin and St. John’s wort should not be used with SOVALDI.
Drugs that are potent P-gp inducers in the intestine (e.g., rifampin, St. John’s wort) may significantly decrease sofosbuvir plasma concentrations and may lead to a reduced therapeutic effect of SOVALDI. Rifampin and St. John’s wort should not be used with SOVALDI.
ADVERSE REACTIONS
The most common adverse events (≥ 20%) for SOVALDI + ribavirin combination therapy were fatigue and headache. The most common adverse events (≥ 20%) for SOVALDI + peginterferon alfa + ribavirin combination therapy were fatigue, headache, nausea, insomnia and anemia.
The most common adverse events (≥ 20%) for SOVALDI + ribavirin combination therapy were fatigue and headache. The most common adverse events (≥ 20%) for SOVALDI + peginterferon alfa + ribavirin combination therapy were fatigue, headache, nausea, insomnia and anemia.
DRUG INTERACTIONS
Potential for Drug Interactions
After oral administration of SOVALDI, sofosbuvir is rapidly converted to the predominant circulating metabolite GS-331007 that accounts for greater than 90% of drug related material systemic exposure, while the parent sofosbuvir accounts for approximately 4% of drug related material. In clinical pharmacology studies, both sofosbuvir and GS-331007 were monitored for purposes of pharmacokinetic analyses.
Potential for Drug Interactions
After oral administration of SOVALDI, sofosbuvir is rapidly converted to the predominant circulating metabolite GS-331007 that accounts for greater than 90% of drug related material systemic exposure, while the parent sofosbuvir accounts for approximately 4% of drug related material. In clinical pharmacology studies, both sofosbuvir and GS-331007 were monitored for purposes of pharmacokinetic analyses.
Sofosbuvir is a substrate of drug transporter P-gp and breast cancer resistance protein (BCRP) while GS-331007 is not. Drugs that are potent P-gp inducers in the intestine (e.g., rifampin or St. John’s wort) may decrease sofosbuvir plasma concentration leading to reduced therapeutic effect of SOVALDI and thus should not be used with SOVALDI. Coadministration of SOVALDI with drugs that inhibit P-gp and/or BCRP may increase sofosbuvir plasma concentration without increasing GS-331007 plasma concentration; accordingly, SOVALDI may be coadministered with P-gp and/or BCRP inhibitors. Sofosbuvir and GS-331007 are not inhibitors of P-gp and BCRP and thus are not expected to increase exposures of drugs that are substrates of these transporters.
The intracellular metabolic activation pathway of sofosbuvir is mediated by generally low affinity and high capacity hydrolase and nucleotide phosphorylation pathways that are unlikely to be affected by concomitant drugs.
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