sofosbuvir


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Related to sofosbuvir: simeprevir, daclatasvir, ribavirin

sofosbuvir

(soe-fos-bue-vir),

Solvadi

(trade name)

Classification

Therapeutic: antivirals
Pharmacologic: temporary class
Pregnancy Category: B (alone)
Pregnancy Category: X (in combination with ribavirin or ribavirin with interferon alfa)

Indications

Treatment of chronic hepatitis C (CHC) infection (genotypes 1, 2, 3 and 4) in combination with ribavirin or ribavirin plus peginterferon alfa, including patients with hepatocellular carcinoma awaiting transplantation and those with HCV/HIV co-infection.Not intended as monotherapy.

Action

Inhibits RNA-dependent RNA polymerase, resulting in inhibition of viral replication.

Therapeutic effects

Decreased HCV RNA levels with decreased severity and sequelae of HCV.

Pharmacokinetics

Absorption: Rapidly metabolized following absorption.
Distribution: Unknown.
Metabolism and Excretion: Extensively metabolized with much conversion to GS-461203, an active antiviral moiety, then converted GS-331007, which does not have antiviral activity. 80% excreted in urine mostly as GS-331007 (3.5% as unchanged drug), 14% excreted in feces, 2.5% excreted in expired air.
Half-life: Sofosbuvir—0.4 hr; GS-331007—27 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunknown0.5–2 hr†24 hr
† Sofosbuvir (2–4 hr for GS-331007).

Contraindications/Precautions

Contraindicated in: Contraindications for ribavirin and/or peginterferon alfa;Pregnant women or men whose partners are pregnant (ribavirin may cause fetal harm); Severe renal impairment/end-stage renal disease);Concurrent use of P-gp inducers, including rifampin and St. John's wort ; Lactation: Discontinue sofosbuvir or discontinue breastfeeding.
Use Cautiously in: Women with child-bearing potential and their male partners; Pediatric: Safe and effective use in children < 18 yr has not been established.

Adverse Reactions/Side Effects

In combination with ribavirin

Central nervous system

  • fatigue (most frequent)
  • headache (most frequent)
  • insomnia (most frequent)
  • irritability
  • weakness

Gastrointestinal

  • diarrhea
  • nausea

Dermatologic

  • pruritus (most frequent)

Musculoskeletal

  • myalgia

Miscellaneous

  • chills
  • fever

In combination with ribavirin and peginterferon alfa

Central nervous system

  • fatigue (most frequent)
  • headache (most frequent)
  • insomnia (most frequent)
  • irritability (most frequent)
  • weakness

Gastrointestinal

  • diarrhea (most frequent)
  • nausea (most frequent)

Dermatologic

  • rash (most frequent)
  • pruritus (most frequent)

Hematologic

  • anemia (most frequent)

Musculoskeletal

  • myalgia (most frequent)

Miscellaneous

  • chills (most frequent)
  • fever (most frequent)

Interactions

Drug-Drug interaction

Blood levels and effectiveness may be ↓ by concurrent use of carbamazepine, phenytoin, phenobarbital, oxcarbazepine, rifabutin, rifampin, rifapentine and tipranavir/ritonavir (concurrent use should be avoided).Blood levels and effectiveness may be ↓ by concurrent use of of P-gp inducers including St. John's wort.

Route/Dosage

Oral (Adults) Genotypes 1 or 4—400 mg once daily for 12 wk in combination with peginterferon alfa and ribavirin; Genotype 2—400 mg once daily for 12 wk in combination with ribavirin; Genotype 3—400 mg once daily for 24 wk in combination with ribavirin; Patients with hepatocellular carcinoma awaiting liver transplantation—400 mg once daily in combination with ribavirin for up to 48 wk or until transplantaion, whichever occurs first.

Availability

Tablets: 400 mg

Nursing implications

Nursing assessment

  • Monitor for signs and symptoms of chronic hepatitis C.
  • Lab Test Considerations: A negative pregnancy test must be obtained immediately before beginning therapy and monthly thereafter.
    • Monitor CBC periodically during therapy. If hemoglobin <10 g/dL in patients with no cardiac disease reduce ribavirin dose to 600 mg/day. If hemoglobin <8.5 g/dL, discontinue ribavirin. If ≥2 g/dL decrease in hemoglobin during any 4 wk treatment period in patient with history of stable cardiac disease, decrease ribavirin dose to 600 mg/day. If hemoglobin <12 g/dL despite 4 wk at reduced dose, discontinue ribavirin.
    • May cause pancytopenia and thrombocytopenia.
      • May cause ↑ bilirubin, creatine kinase, and serum lipase levels.

    Potential Nursing Diagnoses

    Risk for infection (Indications)

    Implementation

    • Must be administered in conjunction with ribavirin or ribavirin plus peginterferon alfa. If ribavirin or ribavirin plus peginterferon alfa is/are discontinued, sofosbuvir must be discontinued.
    • Oral: Administer once daily without regard to food.

    Patient/Family Teaching

    • Instruct patient to take sofosbuvir with ribavirin or ribavirin plus pegainterferon alfa as directed. Take missed doses on same day on one day as soon as remembered; do not double doses. Advise patient to read Patient Information before starting and with each refill in case of changes.
    • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. Johns Wort.
    • Advise female patients and male patients with female partners who are pregnant or may become pregnant to use effective contraception due to risks for birth defects and fetal death and avoid breastfeeding. Women and male partners must use 2 forms of non-hormonal contraception during and for at least 6 mo after discontinuation of therapy. Advise women who become pregnant to enroll in the Ribavirin Pregnancy Registry by calling 1–800–593–2214. For patients with HCV/HIV 1 co-infection taking antiretrovirals there is an Antiviral Pregnancy Registry at 1–800–258–4263.

    Evaluation/Desired Outcomes

    • Decreased HCV RNA levels with decreased severity and sequelae of HCV.
      • Patients with genotype 1 and 4 chronic hepatitis C (CHC) should be treated with sofosbuvir, peginterferon alfa, and ribavirin for 12 wk.
      • Patients with genotype 2 CHC should be treated with sofosbuvir and ribavirin for 12 wk.
      • Patients with genotype 3 CHC should be treated with sofosbuvir and ribavirin for 24 wk.
      • Patients with hepatocellular cancer awaiting liver transplantation may be treated with sofosbuvir and ribavirin for up to 48 wk.
    References in periodicals archive ?
    The subject of this public contract for a period of 48 months pursuant to Annex 1 to the Purchase Contract - List of Goods with Unit Price, in the scope and in accordance with the terms of reference, is the supply of a medicinal product containing Sofosbuvir 400 MG and Velpatasvir 100 MG.
    However recent EASL guidelines for treatment of HCV has not included this combination in treatment of genotype 3 infection.11 There are no studies previously published in Pakistan regarding efficacy of daclatasvir plus sofosbuvir in patients with hepatitis C genotype 3a up to best of our knowledge.
    Though the Sofosbuvir and Daclatasvir combination is not the preferred first line regimen for the treatment of chronic HCV infection currently but because of its low cost, easy availability and low rate of adverse effects, it is the most commonly used pan-genotypic regimen for the treatment of chronic HCV infection in our local set up these days.
    "In a 'real-life experience' of a Brazilian center, sofosbuvir therapy appears to guarantee renal safety for patients with chronic hepatitis C followed until one year after treatment," the authors write.
    We also aimed to compare the results obtained from patients receiving sofosbuvir with daclatasvir versus sofosbuvir with simeprevir.
    Sofosbuvir, which was prescribed by doctors instead of Interferon injections, has been purchased by the health department at Rs32.13, lower than its last year's price of Rs49.
    Daclatasvir: Generally used in combination with sofosbuvir. It should be not used as monotherapy.
    Our study aimed at screening and management of chronic hepatitis C genotype 4 infected patients in Bardeen village, Sharkeya Governorate, Egypt, with Sofosbuvir plus Daclatasvir, as well as estimating the safety and efficacy of that regimen.
    Denning et al., "Sofosbuvir compassionate use program for patients with severe recurrent hepatitis C after liver transplantation," Hepatology, vol.
    used the combination of pegylated interferon, sofosbuvir, and ribavirin [58].
    Summary: In vitro dissolution of sofosbuvir 400 mg tablets dosage form was performed, using USP dissolution apparatus type-II (paddle type), at 75rpm +- 4 %, and 900mL +- 1%, 0.05 M phosphate buffer pH 6.8 +- 0.05 equilibrated at 37.0 +- 0.5AoC as dissolution medium.
    has been cleared to market Vosevi (sofosbuvir 400 mg/ velpatasvir 100 mg/voxilaprevir 100 mg), a single-tablet regimen for the re-treatment of chronic hepatitis C virus (HCV) infection in adults.