(soe FOS bue vir)
Chronic hepatitis C: Treatment of genotype 1, 2, 3, or 4 chronic hepatitis C (CHC) as a component of a combination antiviral treatment regimen.
All contraindications also applicable to ribavirin and peginterferon alfa including women who are pregnant or who may become pregnant and use by male partners of pregnant women.
Also refer to Peginterferon Alfa and Ribavirin monographs for individual product contraindications.
Canadian labeling: Additional contraindications (not in U.S. labeling): Hypersensitivity to sofosbuvir or any component of the formulation; males whose female partners may become pregnant
Chronic hepatitis C (CHC) infection in monoinfected (HCV) or coinfected (HCV/HIV-1) patients: Oral: 400 mg daily with concomitant ribavirin and with or without peginterferon alfa (maximum: 400 mg daily). Note: Treatment regimen and duration based on HCV genotype and/or clinical scenario as noted below:
Treatment-naive patients:
Genotype 1:
Patients who can receive interferon: 400 mg once daily with concomitant ribavirin and peginterferon alfa for 12 weeks. Note: A recommended regimen (AASLD/IDSA, 2014)
Patients who cannot receive interferon:
Manufacturer 's labeling: 400 mg once daily with concomitant ribavirin for 24 weeks. Note: A recommended regimen (AASLD/IDSA, 2014)
Alternative dosing (off-label regimen): 400 mg once daily with simeprevir and with or without ribavirin for 12 weeks. Note: A recommended regimen (AASLD/IDSA, 2014)
Genotype 2: 400 mg once daily with concomitant ribavirin for 12 weeks. Note: A recommended regimen (AASLD/IDSA, 2014)
Genotype 3:
Regardless of patient eligibility for peginterferon: Manufacturer 's labeling: 400 mg once daily with concomitant ribavirin for 24 weeks. Note: A recommended regimen (AASLD/IDSA, 2014)
Patients who can receive interferon: Alternative dosing (off-label regimen): 400 mg once daily with concomitant ribavirin and peginterferon alfa for 12 weeks. Note: A recommended regimen (AASLD/IDSA, 2014)
Genotype 4:
Patients who can receive interferon: Manufacturer 's labeling: 400 mg once daily with concomitant ribavirin and peginterferon alfa for 12 weeks. Note: A recommended regimen (AASLD/IDSA, 2014)
Patients who cannot receive interferon: Alternative dosing (off-label regimen): 400 mg once daily with concomitant ribavirin for 24 weeks. Note: A recommended regimen (AASLD/IDSA, 2014)
Genotype 5 or 6 (off-label use): Patients who can receive interferon: 400 mg once daily with concomitant ribavirin and peginterferon alfa for 12 weeks. Note: A recommended regimen (AASLD/IDSA, 2014)
Relapser patients (nonresponders to a previous regimen of ribavirin and peginterferon alfa without an HCV protease inhibitor):
Regardless of patient eligibility for peginterferon:
Genotype 1 (off-label regimen): 400 mg once daily with simeprevir and with or without ribavirin for 12 weeks. Note: A recommended regimen (AASLD/IDSA, 2014)
Relapser patients (nonresponders to a previous regimen of ribavirin and peginterferon alfa with or without an HCV protease inhibitor):
Patients who can receive interferon:
Genotype 1 (off-label regimen): 400 mg once daily for 12 weeks with ribavirin and peginterferon alfa for 12-24 weeks. Note: A recommended regimen (AASLD/IDSA, 2014)
Genotype 4: 400 mg once daily with concomitant ribavirin and peginterferon alfa for 12 weeks. Note: A recommended regimen (AASLD/IDSA, 2014)
Genotype 5 or 6 (off-label use): 400 mg once daily with concomitant ribavirin and peginterferon alfa for 12 weeks. Note: A recommended regimen (AASLD/IDSA, 2014)
Regardless of patient eligibility for peginterferon:
Genotype 2 (off-label regimen): 400 mg once daily with concomitant ribavirin for 12 weeks. Note: A recommended regimen; also patients with cirrhosis may benefit from a total of 16 weeks of treatment (AASLD/IDSA, 2014)
Genotype 3: 400 mg once daily with concomitant ribavirin for 24 weeks. Note: A recommended regimen (AASLD/IDSA, 2014)
Patients with hepatocellular carcinoma awaiting liver transplantation: 400 mg once daily with concomitant ribavirin for 48 weeks or until the time of liver transplantation, whichever occurs first
Missed dose: If a dose is missed within the calendar day it is usually taken, take as soon as possible. If the calendar day when the dose is usually taken has passed, do not take the missed dose and resume the usual dosing schedule. Do not take >400 mg daily. The Canadian labeling recommends that patients who vomit <2 hours after administration take another dose but if > 2 hours, take dose at the next regularly scheduled time.
Refer to adult dosing.
Sofosbuvir:
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in manufacturer 's labeling (has not been studied). Predominant metabolite accumulates in impaired renal function.
End stage renal disease (ESRD), including those requiring intermittent hemodialysis (IHD): There are no dosage adjustments provided in manufacturers labeling (has not been studied). Predominant metabolite accumulates in impaired renal function.
Peginterferon Alfa and Ribavirin: Refer to individual monographs.
Child-Pugh class A, B, or C: No dosage adjustment necessary.
Decompensated cirrhosis: There are no dosage adjustments provided in manufacturer 's labeling (has not been studied).
Peginterferon Alfa and Ribavirin: Refer to individual monographs; peginterferon alfa is contraindicated in hepatic decompensation.
Administer with or without food.
Store below 30 ‚ °C (86 ‚ °F). Dispense only in original container.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Sovaldi: 400 mg
Amiodarone: Sofosbuvir may enhance the bradycardic effect of Amiodarone. Avoid combination
Lumacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Modafinil: May decrease the serum concentration of Sofosbuvir. Avoid combination
OXcarbazepine: May decrease the serum concentration of Sofosbuvir. Avoid combination
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Sofosbuvir. Avoid combination
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Rifabutin: May decrease the serum concentration of Sofosbuvir. Avoid combination
Rifapentine: May decrease the serum concentration of Sofosbuvir. Avoid combination
Bilirubin, liver enzymes, and serum creatinine at baseline and periodically when clinically indicated. If used in combination with amiodarone and another direct acting antiviral (DAA) (or in patients who discontinued amiodarone just prior to initiating sofosbuvir in combination with a DAA), inpatient cardiac monitoring for the first 48 hours of coadministration, then daily outpatient or self monitoring of heart rate through at least the first 2 weeks of treatment.
Serum HCV-RNA at baseline, during treatment, at the end of treatment, during treatment follow-up, and when clinically indicated.
Pretreatment and monthly pregnancy tests up to 6 months following discontinuation of therapy for women of childbearing age.
Adverse reactions reported with combination therapy.
>10%:
Central nervous system: Fatigue (30% to 59%), headache (24% to 36%), insomnia (15% to 25%), chills (2% to 17%), irritability (10% to 13%)
Dermatologic: Pruritus (11% to 27%), skin rash (8% to 18%)
Gastrointestinal: Nausea (22% to 34%), decreased appetite (18%), diarrhea (9% to 12%)
Hematologic & oncologic: Decreased hemoglobin (<10 g/dL: 6% to 23%; <8.5 g/dL: ≤2%), anemia (6% to 21%), neutropenia (<1% [interferon-free regimen] to 17% [interferon-containing regimen]), decreased neutrophils ( ≥0.5 to <0.75 times 109/L: <1% [interferon-free regimen] to 15%; <0.5 times 109/L: ≤5%)
Neuromuscular & skeletal: Weakness (5% to 21%), myalgia (6% to 14%)
Respiratory: Flu-like symptoms (6% to 16%)
Miscellaneous: Fever (4% to 18%)
1% to 10%:
Gastrointestinal: Increased serum lipase (>3 times ULN: ≤2%)
Hematologic & oncologic: Thrombocytopenia ( ≤1%)
Hepatic: Increased serum bilirubin (>2.5 times ULN: 3%)
Renal: Increased creatine kinase ( ≥10 times ULN: 1% to 2%)
<1% (Limited to important or life-threatening): Bradycardia, pancytopenia, severe depression, suicidal ideation
AUC0-inf was higher in mild (eGFR ≥50 and <80 mL/minute/1.73 m2), moderate (eGFR ≥30 and <50 mL/minute/1.73 m2), and severe (eGFR <30 mL/minute/1.73 m2) renal impairment. A 4 hour hemodialysis session removed approximately 18% of administered dose.
AUC0-24 was higher in moderate and severe hepatic impairment
Concurrent drug therapy issues:
- Amiodarone: Symptomatic bradycardia (some requiring pacemaker intervention) has occurred in patients receiving amiodarone and sofosbuvir in combination with simeprevir or an investigational NS5A inhibitor. Fatal cardiac arrest occurred when a patient took the ledipasvir/sofosbuvir combination product. Bradycardia generally occurred within hours to days following coadministration, however some cases have occurred 2 weeks following the initiation of sofosbuvir. The risk of bradycardia may be increased in patients taking beta blockers or patients with underlying cardiac comorbidities and/or advanced liver disease. Bradycardia generally resolves following discontinuation of sofosbuvir. Coadministration of amiodarone and sofosbuvir in combination with another direct acting antiviral (DAA) is not recommended. However, if patients have no treatment alternatives, patients should have in-patient cardiac monitoring for the first 48 hours, followed by daily outpatient or self-monitoring of heart rate for at least the first 2 weeks of treatment. Due to the long half-life of amiodarone, cardiac monitoring (as described) is also recommended if amiodarone was discontinued just prior to beginning treatment with sofosbuvir. Patients should seek medical attention immediately if they experience fainting or near-fainting, dizziness, lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pains, confusion or memory problems.
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy, including use with potent P-gp inducers (eg, rifampin, St John 's wort) or amiodarone in combination with an additional direct acting antihepaciviral. Consult drug interactions database for more detailed information.
Special populations:
- Pregnancy: Combination therapy with ribavirin may cause birth defects and/or death of the exposed fetus; avoid pregnancy in females and female partners of male patients during therapy and for at least 6 months following treatment; two nonhormonal forms of effective contraception must be used. Combination therapy with ribavirin is contraindicated in pregnancy.
Other warnings/precautions:
- Appropriate use: Do not use as monotherapy; use only in combination with ribavirin (with or without peginterferon alfa depending upon the clinical indication). Alternative recommendations also use in combination with simeprevir in select patients (AASLD/IDSA, 2014).
B (sofosbuvir)/X (in combination with ribavirin or peginterferon alfa/ribavirin)
Adverse events were not observed in animal reproduction studies using sofosbuvir. However, sofosbuvir is only to be used in combination with ribavirin or peginterferon alfa/ribavirin for the treatment of hepatitis C virus (HCV), therefore use is contraindicated in pregnancy. A negative pregnancy test is required before initiation and monthly thereafter. Avoid pregnancy in female patients and female partners of male patients during therapy by using two effective forms of nonhormonal contraception; continue contraceptive measures for at least 6 months after completion of therapy. Also refer to the peginterferon alfa and ribavirin monographs for additional information.
If pregnancy occurs during use or within 6 months after treatment with ribavirin, report to the ribavirin pregnancy registry (800-593-2214). In addition, because sofosbuvir may be used for the treatment of HCV infection in women coinfected with HIV, inadvertent administration of sofosbuvir in women with HCV/HIV coinfection during pregnancy should also be reported to the Antiretroviral Pregnancy Registry (1-800-258-4263).
Sofosbuvir, a direct-acting antiviral agent against the hepatitis C virus, is a prodrug converted to its pharmacologically active form (GS-461203) via intracellular metabolism. It inhibits HCV NS5B RNA-dependent RNA polymerase, essential for viral replication, and acts as a chain terminator.
Hepatic; forms pharmacologically active nucleoside (uridine) analog triphosphate GS-461203; dephosphorylation results in the formation of nucleoside inactive metabolite GS-331007
Urine (80%)
~0.5 to 2 hours
0.4 hours
~61% to 65%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache, nausea, or insomnia. Have patient report immediately to prescriber severe loss of strength and energy (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.