Sovaldi (Sofosbuvir) is a direct-acting orally available antiviral drug that is used in the treatment of chronic hepatitis C infection.

Sofosbuvir (Sovaldi) Uses:

• Chronic hepatitis C:

  • In adults, treatment of genotype 1, 2, 3, or 4 chronic hepatitis C virus (HCV) infection and genotype 2 or 3 chronic HCV infection in pediatric patients ≥12 years or weighing ≥35 kg, without cirrhosis or with compensated cirrhosis, as a component of a combination antiviral treatment regimen.

• Use: Off-Label: Adult

  • Chronic hepatitis C, genotype 1, 2, 3, or 4 (decompensated cirrhosis).
  • Chronic hepatitis C, genotype 1, 2, 3, 4, 5, or 6 (liver transplant recipients).
  • Chronic hepatitis C, genotype 2, 3, 5, or 6 (renal transplant recipients)

See also: Sofosbuvir + Velpatasvir (Epclusa) 

1. Sofosbuvir (Sovaldi) Dose in Adults

Sofosbuvir (Sovaldi) Dose in the treatment of Chronic hepatitis C (CHC) infection (mono infection or coinfected with HIV-1): P/O:

Note:

• Treatment-experienced refers to patients who have failed prior treatment with peginterferon and ribavirin.
• With ribavirin, combination therapy alone or ribavirin/peginterferon is not a recommended regimen in HCV treatment guidelines for patients with HCV (treatment-naive or treatment-experienced), regardless of genotype.

• Genotype 1:

  • Treatment-naive or peginterferon + ribavirin treatment-experienced patients without cirrhosis (alternative regimen):

    • For 12 weeks, 400 mg once daily in combination with simeprevir or daclatasvir.

  • Patients with decompensated cirrhosis (Child-Pugh class B or C) (off-label use):

    • For 12 weeks, 400 mg once daily in combination with daclatasvir and ribavirin (if ribavirin-ineligible give in combination with daclatasvir only for 24 weeks).

  • Liver transplant recipients without cirrhosis or with compensated cirrhosis (Child-Pugh class A) (alternative regimen) (off-label use):

    • For 12 weeks, 400 mg once daily, in combination with daclatasvir and ribavirin or simeprevir with or without ribavirin.

  • Manufacturer’s labeling:

    • In the prescribing information, dosing may not reflect current clinical practice.

  • Treatment-naive patients without cirrhosis or with compensated cirrhosis (Child-Pugh class A):

    • For 12 weeks, 400 mg once daily with concomitant peginterferon alfa and ribavirin.
    • Administer with concomitant ribavirin for 24 weeks, for patients that cannot receive peginterferon alfa.

• Genotype 2:

  • Treatment-naive or peginterferon + ribavirin treatment-experienced patients (alternative regimen):

    • For 12 weeks (without cirrhosis) or 16 to 24 weeks (with compensated cirrhosis [Child-Pugh class A]), 400 mg once daily in combination with daclatasvir.

  • Patients with decompensated cirrhosis (Child-Pugh class B or C) (off-label use):

    • For 12 weeks, 400 mg once daily in combination with daclatasvir and ribavirin (if ribavirin-ineligible give in combination with daclatasvir only for 24 weeks) (AASLD/IDSA 2017)

  • Liver transplant recipients with or without cirrhosis, including decompensated cirrhosis (Child-Pugh class B or C) (off-label use):

    • For 12 weeks, 400 mg once daily in combination with daclatasvir and ribavirin.

  • Renal transplant recipients without cirrhosis or with compensated cirrhosis (Child-Pugh class A) (alternative regimen) (off-label use):

    • For 12 weeks, 400 mg once daily in combination with daclatasvir and ribavirin.

  • Manufacturer’s labeling:

    • Dosing in the prescribing information may not reflect current clinical practice.

  • Treatment-naive and treatment-experienced patients without cirrhosis or with compensated cirrhosis (Child-Pugh class A):

    • For 12 weeks, 400 mg once daily with concomitant ribavirin.

• Genotype 3:

  • Treatment-naive or peginterferon + ribavirin treatment-experienced patients without cirrhosis (alternative regimen):

    • For 12 weeks, 400 mg once daily in combination with daclatasvir.

  • Treatment-naive patients with compensated cirrhosis (Child-Pugh class A) (alternative regimen):

    • For 24 weeks, 400 mg once daily in combination with daclatasvir with or without ribavirin.

  • Patients with decompensated cirrhosis (Child-Pugh class B or C) (off-label use):

    • For 12 weeks, 400 mg once daily in combination with daclatasvir and ribavirin (if ribavirin-ineligible give in combination with daclatasvir only for 24 weeks).

  • Liver transplant recipients with or without cirrhosis, including decompensated cirrhosis (Child-Pugh class B or C) (off-label use):

    • For 12 weeks, 400 mg once daily in combination with daclatasvir and ribavirin.

  • Renal transplant recipients without cirrhosis or with compensated cirrhosis (Child-Pugh class A) (alternative regimen) (off-label use):

    • For 12 weeks, 400 mg once daily in combination with daclatasvir and ribavirin.

  • Manufacturer’s labeling:

    • Dosing in the prescribing information may not reflect current clinical practice.
  • Treatment-naive or treatment-experienced patients without cirrhosis or with compensated cirrhosis (Child-Pugh class A):
    • For 24 weeks, 400 mg once daily with concomitant ribavirin.

• Genotype 4:

  • Patients with decompensated cirrhosis (Child-Pugh class B or C) (off-label use):

    • For 12 weeks, 400 mg once daily in combination with daclatasvir and ribavirin (if ribavirin-ineligible give in combination with daclatasvir only for 24 weeks).

  • Liver transplant recipients without cirrhosis or with compensated cirrhosis (Child-Pugh class A) (alternative regimen) (off-label use):

    • For 12 weeks, 400 mg once daily, in combination with daclatasvir and ribavirin or simeprevir with or without ribavirin.

  • Manufacturer’s labeling:

    • Dosing in the prescribing information may not reflect current clinical practice.

  • Treatment-naive patients without cirrhosis or with compensated cirrhosis (Child-Pugh class A):

    • For 12 weeks, 400 mg once daily with concomitant peginterferon alfa and ribavirin.

• Genotypes 5 and 6 (AASLD/IDSA 2017):

  • Liver transplant recipients without cirrhosis or with compensated cirrhosis (Child-Pugh class A) (alternative regimen) (off-label use):

    • For 12 weeks, 400 mg once daily in combination with daclatasvir and ribavirin.

  • Renal transplant recipients without cirrhosis or with compensated cirrhosis (Child-Pugh class A) (alternative regimen) (off-label use):

    • For 12 weeks, 400 mg once daily in combination with daclatasvir and ribavirin.

Sofosbuvir (Sovaldi) Dose in Children

Sofosbuvir (Sovaldi) Dose in the treatment of Chronic hepatitis C infection (mono-infection or coinfected with HIV-1):

Treatment-naive or treatment-experienced without cirrhosis or with compensated cirrhosis (Child-Pugh class A):

Note:

• Treatment-experienced refers to patients who have failed prior treatment with an interferon-based regimen with or without ribavirin.

• Children ≥12 years or weighing ≥35 kg and Adolescents:

  • Genotype 2:

    • P/O:
      • For 12 weeks, 400 mg once daily with concomitant ribavirin.

  • Genotype 3:

    • P/O:
      • For 24 weeks, 400 mg once daily with concomitant ribavirin.

Sofosbuvir (Sovaldi) Pregnancy Risk Category: B

• Sofosbuvir should not be used as a monotherapy.
• Combination therapy with Ribavirin is not recommended for pregnant females or males whose partners are pregnant.
• If ribavirin is used together with it, all warnings regarding pregnancy and contraception must be observed.
• Refer to the ribavirin monograph for additional information.
• Treatment of hepatitis C during pregnancy is not recommended to treat maternal infections or reduce the chance of mother-to child transmission.
• HCV-infected women with childbearing potential who are not yet on treatment to reduce the risk of HCV transmission should postpone pregnancy.
• If HCV infection is discovered during pregnancy, treatment should be delayed until after delivery.
• Direct-acting antiviral medication should not be administered to pregnant women unless safety and efficacy data are available.

Sofosbuvir use during breastfeeding:

• It is unknown if sofosbuvir can be found in breast milk.
• When deciding whether to discontinue or continue breastfeeding during therapy, it is important to consider the risks to infants, the benefits to the mother, and the benefits to the mother.
• The spread of the hepatitis C viruses is not associated with breastfeeding.
• Breastfeeding is not recommended if the nipples crack or are bleeding. Milk should be expressed and discarded.
• Breastfeeding is not recommended in the case of HIV co-infection.

Sofosbuvir (Sovaldi) Dose in Kidney Disease:

• Estimated glomerular filtration rate (eGFR) ≥30 mL/min:

  • No dosage adjustment is necessary.

• eGFR <30 mL/min:

  • In the manufacturer's labeling, there are no dosage adjustments provided (has not been studied).
  • Predominant metabolite accumulates in impaired renal function.

• End-stage renal disease (ESRD), including hemodialysis patients:

  • In the manufacturer's labeling, there are no dosage adjustments provided (has not been studied).
  • Predominant metabolite accumulates in impaired renal function.

Sofosbuvir (Sovaldi) Dose in Liver disease:

• Mild, moderate, or severe impairment (Child-Pugh class A, B, or C):
  • No dosage adjustment is necessary.

Common Side Effects of Sofosbuvir (Sovaldi):

• Central Nervous System:

  • Fatigue
  • Headache
  • Insomnia
  • Chills
  • Irritability

• Dermatologic:

  • Pruritus
  • Skin Rash

• Gastrointestinal:

  • Nausea
  • Decreased Appetite
  • Diarrhea

• Hematologic & Oncologic:

  • Anemia
  • Neutropenia

• Neuromuscular & Skeletal:

  • Asthenia
  • Myalgia

• Respiratory:

  • Flu-Like Symptoms

• Miscellaneous:

  • Fever

Less Common Side Effects of Sofosbuvir (Sovaldi):

• Gastrointestinal:

  • Increased Serum Lipase

• Hematologic & Oncologic:

  • Thrombocytopenia

• Hepatic:

  • Increased Serum Bilirubin

• Renal:

  • Increased Creatine Phosphokinase

Contraindications to Sofosbuvir (Sovaldi):

• There are no contraindications in the manufacturer's labeling.
• When administered with ribavirin or peginterferon, the contraindications apply.
• See Ribavirin and Peginterferon Alfa monographs.

Canadian labeling:Additional contraindications not listed in the US labeling:

• Hypersensitivity to sofosbuvir and any component of the formulation
• Female partners who are male may fall pregnant with their female partners

Warnings and precautions

• Diabetes:

  • Rapid reduction in hepatitis C viral load during direct-acting antiviral (DAA) therapy for hepatitis C may lead to an improvement in glucose metabolism in patients with diabetes, potentially resulting in symptomatic hypoglycemia if antidiabetic agents are continued at the same dose.
  • Especially in the first three months, assess for changes in glucose tolerance. Inform patients about the possibility of hypoglycemia while on DAA therapy.
  • Modifications to anti-diabetic therapy might be required.

• Hepatitis B virus activation: [US-Boxed Warning]

  • Reactivation of the hepatitis B virus has been observed in HCV co-infected patients.
  • This was among those who had received or were about to receive direct-acting antivirals for HCV and were not on HBV antiviral therapy.
  • Some cases can lead to fulminant liver disease, hepatic failure and even death.
  • Before starting sofosbuvir treatment, all patients should be tested for evidence of HBV infection.
  • Monitor HCV/HBV coinfected patients during treatment and after-treatment follow up for flare-ups or reactivation of HBV.
  • If HBV infection is clinically indicated, you should start treatment.
  • HBV reactivation can occur in HBsAg-positive patients as well as patients with confirmed HBV infection (i.e. HBsAg nil and anti-HBc p).
  • This is characterized in part by an abrupt rise in HBV replication and a rapid rise in serum HBV DNA levels.
  • Patients with a resolved HBV infection may experience HBsAg recurrence.
  • Patients who are taking immunosuppressants and chemotherapeutic drugs may have a higher risk of HBV reactivation.

Sofosbuvir: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Manufacturer's labeling:

  • Bilirubin, liver enzymes, and serum creatinine at baseline and periodically when clinically indicated.
  • If used in combination with amiodarone & 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 two weeks of treatment.
  • During treatment, at the end of treatment, during treatment follow-up, and when clinically indicated, serum HCV-RNA at baseline.
  • Prior to initiation, Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc).
  • Monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during treatment and during post-treatment follow-up, in patients with serologic evidence of hepatitis B virus (HBV) infection.

Alternate recommendations:

• Baseline (within 12 weeks prior to starting antiviral therapy):

  • CBC, INR, hepatic function panel (albumin, total and direct bilirubin, ALT, AST & alkaline phosphatase), and calculated GFR.

• Baseline (at any time prior to starting antiviral therapy):

  • HCV genotype & subtype, quantitative HCV viral load.

During therapy:

• • CBC, serum creatinine, calculated GFR, hepatic function panel (after 4 weeks of therapy, and as clinically indicated).
  • Quantitative HCV viral load testing (after 4 weeks of therapy & at 12 weeks after completion of therapy).
  • Repeat testing is recommended after 2 additional weeks of treatment if quantitative HCV viral load is detectable at treatment week 4 (treatment week 6).
  • Monitor blood glucose and for signs/symptoms of hypoglycemia in patients with diabetes.

How to administer Sofosbuvir (Sovaldi)?

• Administer with or without food.

Mechanism of action of Sofosbuvir (Sovaldi):

• Sofosbuvir is an antiviral agent that acts directly against the hepatitis C viruses. It is a drug that has been converted via intracellular metabolism to its pharmacologically effective form (GS-4611203).
• It acts as a terminator and inhibits HCV-NS5B RNA dependent polymerase.

Notice:

• Pediatric patients aged >=12 years are similar to adults in terms of pharmacokinetic profiles.

Protein binding:

• ~61%-65%

Metabolism:

• Hepatic.
• Forms pharmacologically active nucleoside (uridine) analog triphosphate GS-461203.
• Dephosphorylation results in the formation of nucleoside inactive metabolite GS331007

Half-life elimination:

• 0.4 hours

Time to peak:

• ~0.5-2 hours

Excretion:

• Urine (80%; primarily as metabolite).
• Feces (14%).

International Brands of Sofosbuvir:

• Sovaldi
• Caprisofos
• Grateziano
• Gratisovir
• Hepcee
• Hepcinat
• Hepcivir
• Hopforhep
• HopSo
• Myhep
• Sofgen
• Soforal
• Sovaldi
• Soventa

Sofosbuvir Brand Names in Pakistan:

Sovaldi (Ferozsons)