Sofosbuvir

What is sofosbuvir

• sofosbuvir (SOVALDI) is a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor used with other antiviral medicines to treat adults with chronic (lasting a long time) hepatitis C virus (HCV).

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What are the uses of this medicine?

This medicine is used with other antiviral medicines to treat adults with chronic (lasting a long time) hepatitis C virus (HCV):

• genotype 1 or 4 infection without cirrhosis or with compensated cirrhosis in combination with peginterferon alfa and ribavirin
• genotype 2 or 3 infection without cirrhosis or with compensated cirrhosis in combination with ribavirin

• SOVALDI is used to treat children 3 years of age and older with chronic HCV genotype 2 or 3 infection without cirrhosis or with compensated cirrhosis in combination with ribavirin.

How does this medicine work?

• Sofosbuvir (soe fos' bue vir) is an orally available nucleotide analogue that has potent activity against the RNA-dependent RNA polymerase of the hepatitis C virus (HCV).
• Sofosbuvir is a monophosphorylated uracil derivative whose single phosphate is protected by an alaninate cap that allows for the absorption and uptake of the molecule by hepatocytes where it is hydrolyzed to sofosbuvir monophosphate.
• Intracellular host kinases then convert it to the active triphosphate moiety.
• In multiple clinical trials, sofosbuvir has been shown to cause a rapid and marked decline in serum HCV RNA levels and, in combination with other antiviral agents and with more prolonged therapy, to result in sustained clearance of HCV (sustained virological response: SVR) in a high proportion of patients.

Who Should Not Use this medicine ?

• When used in combination with peginterferon alfa/ribavirin or ribavirin alone, all contraindications to peginterferon alfa and/or ribavirin also apply to SOVALDI combination therapy.

What drug interactions can this medicine cause?

• Coadministration of amiodarone with SOVALDI is not recommended; if coadministration is required, cardiac monitoring is recommended.
• Coadministration of SOVALDI with carbamazepine, phenytoin, phenobarbital or oxcarbazepine is expected to decrease the concentration of sofosbuvir, leading to reduced therapeutic effect of SOVALDI. Coadministration is not recommended.
• Coadministration of SOVALDI with rifampin, an intestinal P-gp inducer, is not recommended.
• Coadministration of SOVALDI with St. John's wort, an intestinal P-gp inducer, is not recommended.
• Coadministration of SOVALDI with tipranavir/ritonavir is not recommended.

Is this medicine FDA approved?

• Sofosbuvir was approved for use in the United States in 2013 to be used in combination with ribavirin or with both peginterferon and ribavirin in patients with chronic hepatitis C, genotypes 1, 2, 3 or 4.
• Sofosbuvir is available in tablets of 400 mg under the brand name Solvaldi, the recommended dose being 400 mg once daily in combination with either ribavirin alone (1000 or 1200 mg daily for 12 weeks for genotype 2 and 24 weeks for genotype 3) or in combination with both ribavirin and peginterferon for 12 weeks for patients with genotype 1.
• Subsequently, a fixed combination of sofosbuvir (400 mg) and the HCV NS5A replication complex inhibitor ledipasvir (le dip' as vir: 90 mg) was approved for use in patients with chronic hepatitis C, genotype 1 in 2014 and for genotype 4 in 2015. This combination is available as a fixed dose, single tablet under the brand name Harvoni and the recommended dose is one tablet daily for 12 weeks, which can be shortened to 8 weeks in selected patients.
• In addition, sofosbuvir combined with NS5A inhibitors with broader activity against HCV genotypes, daclatasvir [dak lat' as vir: 2015] and velpatasvir [vel pat' as vir: 2016], has been shown to be effective in treating almost all HCV genotypes with sustained response rates of 95% or greater in response to 12 weeks of treatment in genotypes 1, 2, 4, 5 and 6. In 2016, the fixed combination of sofosbuvir (400 mg) and velpatasvir (100 mg) was approved for use in patients with all 6 genotypes of hepatitis C. This combination is available as a fixed dose, single tablet under the brand name Epclusa. The recommended dose is one tablet daily for 12 weeks. For patients with decompensated cirrhosis (Childs-Pugh Class B or C), ribavirin (1000 to 1200 mg in two divided doses daily) should be added to Epclusa for 12 weeks. Finally, the combination of sofosbuvir with an HCV specific NS3/4 protease inhibitor (such as simeprevir [2014]) was also shown to be highly effective in patients with genotype 1 infection generally in 12 week courses.

How should this medicine be used?

• Test all patients for evidence of current or prior HBV infection.

Recommended Dosage:

• Recommended dosage in adults: One 400 mg tablet taken once daily with or without food.
• Recommended dosage in pediatric patients 3 years of age and older: Recommended dosage of SOVALDI in pediatric patients 3 years of age and older with genotype 2 or 3 HCV using SOVALDI tablets or oral pellets is based on weight.
• HCV/HIV-1 coinfection: For adult and pediatric patients with HCV/HIV-1 coinfection, follow the dosage recommendations in the tables below, respectively.

Recommended adult treatment regimen and duration:

	Adult Patient Population	Regimen and Duration
Genotype 1 or 4	Treatment-naïve without cirrhosis or with compensated cirrhosis
(Child-Pugh A)	SOVALDI + peginterferon alfa + ribavirin
12 weeks
Genotype 2	Treatment-naïve and treatment-experienced without cirrhosis or with compensated cirrhosis
(Child-Pugh A)	SOVALDI + ribavirin
12 weeks
Genotype 3	Treatment-naïve and treatment-experienced without cirrhosis or with compensated cirrhosis
(Child-Pugh A)	SOVALDI + ribavirin
24 weeks

Recommended treatment regimen and duration for pediatric patients 3 years of age and older:

	Pediatric Patient Population 3 Years of Age and Older	Regimen and Duration
Genotype 2	Treatment-naïve and treatment-experienced without cirrhosis or with compensated cirrhosis
(Child-Pugh A)	SOVALDI + ribavirin
12 weeks
Genotype 3	Treatment-naïve and treatment-experienced without cirrhosis or with compensated cirrhosis
(Child-Pugh A)	SOVALDI + ribavirin
24 weeks

Administration:

• Take SOVALDI exactly as your healthcare provider tells you to take it. Do not change your dose unless your healthcare provider tells you to.
• Do not stop taking SOVALDI without first talking with your healthcare provider.
• Take SOVALDI tablets or oral pellets by mouth, with or without food.
• For adults the usual dose of SOVALDI is one 400 mg tablet each day.
• For children 3 years of age and older, your healthcare provider will prescribe the right dose of SOVALDI tablets or oral pellets based on your child's body weight.
• Tell your healthcare provider if your child has problems with swallowing tablets.
• If your healthcare provider prescribes SOVALDI pellets for your child, see "HOW SHOULD I GIVE SOVALDI ORAL PELLETS TO MY CHILD."
• Do not miss a dose of SOVALDI. Missing a dose lowers the amount of medicine in your blood. Refill your SOVALDI prescription before you run out of medicine.
• If you take too much SOVALDI, call your healthcare provider or go to the nearest hospital emergency room right away.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 400 mg and 200 mg of sofosbuvir.
• Oral Pellets: 200 mg and 150 mg of sofosbuvir.

This medicine is available in fallowing brand namesː

• SOVALDI

What side effects can this medication cause?

The most common side effects of SOVALDI when used in combination with ribavirin include:

• tiredness
• headache

The most common side effects of SOVALDI when used in combination with peginterferon alfa and ribavirin include:

• tiredness
• headache
• nausea
• difficulty sleeping
• low red blood cell count

SOVALDI can cause serious side effects, including:

• Hepatitis B virus reactivation
• Slow heart rate (bradycardia)

What special precautions should I follow?

• Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals, and who were not receiving HBV antiviral therapy. Test all patients for evidence of current or prior HBV infection before initiation of HCV treatment. Monitor HCV/HBV coinfected patients for HBV reactivation and hepatitis flare during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
• Serious symptomatic bradycardia may occur in patients taking amiodarone with a sofosbuvir-containing regimen, particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Coadministration of amiodarone with SOVALDI is not recommended. In patients without alternative, viable treatment options, cardiac monitoring is recommended.

What to do in case of emergency/overdose?

• The effects of higher dosages are not known.

Management of overdosage:

• No specific antidote is available for overdose with SOVALDI.
• If overdose occurs, the patient must be monitored for evidence of toxicity.
• Treatment of overdose with SOVALDI consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient. A 4-hour hemodialysis session removed 18% of the administered dose.

Can this medicine be used in pregnancy?

• If SOVALDI is administered with ribavirin or peginterferon alfa and ribavirin, the combination regimen is contraindicated in pregnant women and in men whose female partners are pregnant.

Can this medicine be used in children?

• The safety, pharmacokinetics, and efficacy of SOVALDI in pediatric patients 3 years of age and older with genotype 2 and 3 infection have been established.
• The safety and efficacy of SOVALDI have not been established in pediatric patients less than 3 years of age with HCV genotype 2 or 3. The safety and efficacy of SOVALDI have not been established in pediatric patients with HCV genotype 1 or 4.

What are the active and inactive ingredients in this medicine?

• Active ingredient: sofosbuvir
• Inactive ingredients, Tablets: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, mannitol, and microcrystalline cellulose. The tablet film-coat contains polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide, and yellow iron oxide.
• Inactive ingredients, Oral Pellets: amino methacrylate copolymer, colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, hypromellose, lactose monohydrate, microcrystalline cellulose, polyethylene glycol, silicon dioxide, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, and talc.

Who manufactures and distributes this medicine?

• Manufactured and distributed by:

Gilead Sciences, Inc. Foster City, CA SOVALDI and HARVONI are trademarks of Gilead Sciences, Inc., or its related companies.

What should I know about storage and disposal of this medication?

• Store SOVALDI tablets or pellets below 86°F (30°C).
• Keep SOVALDI tablets in the original container.
• Do not use SOVALDI tablets if the seal over the bottle opening is broken or missing.
• Do not use SOVALDI pellets if the carton tamper-evident seal, or the pellets packet seal, is broken or damaged.
• Keep SOVALDI and all medicines out of the reach of children.

• Dailymed label info on Sofosbuvir
• FDA Sofosbuvir

Sofosbuvir Resources
Latest articles Most recent articles Ongoing trials	Wikipedia

The following are drugs for Hepatitis C:

Interferon Based Therapies

• Alpha Interferon and Peginterferon, Ribavirin

HCV NS5A Inhibitors

• Daclatasvir, Elbasvir, Ledipasvir, Ombitasvir, Pibrentasvir, Velpatasvir

HCV NS5B (Polymerase) Inhibitors

• Dasabuvir, Sofosbuvir

HCV Protease Inhibitors

• Asunaprevir, Boceprevir, Glecaprevir, Grazoprevir, Paritaprevir, Simeprevir, Telaprevir, Voxilaprevir

Combination Therapies

• Epclusa, Harvoni, Mavyret, Technive, Viekira Pak, Vosevi, Zepatier

• Dailymed label info on Sofosbuvir
• FDA Sofosbuvir

Sofosbuvir Resources
Latest articles Most recent articles Ongoing trials	Wikipedia