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)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	0.5–2 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.