Sofosbuvir, sold under the brand name Sovaldi among others, is a medication used to treat hepatitis C. It is taken by mouth. Common side effects include fatigue, headache, nausea, and trouble sleeping. Side effects are generally more common in interferon-containing regimens. Sofosbuvir may reactivate hepatitis B in those who have been previously infected. In combination with ledipasvir, daclatasvir or simeprevir, it is not recommended with amiodarone due to the risk of an abnormally slow heartbeat. Sofosbuvir is in the nucleotide analog family of medications and works by blocking the hepatitis C NS5B protein. Sofosbuvir was discovered in 2007 and approved for medical use in the United States in 2013. It is on the World Health Organization's List of Essential Medicines. In 2016, the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America jointly published a recommendation for the management of hepatitis C. In this recommendation, sofosbuvir used in combination with other drugs is part of all first-line treatments for HCV genotypes 1, 2, 3, 4, 5, and 6, and is also part of some second-line treatments. Sofosbuvir in combination with velpatasvir is recommended for all genotypes with a cure rate greater than 90%, and close to 100% in most cases. The duration of treatment is typically 12 weeks. Sofosbuvir is also used with other medications and longer treatment durations, depending on specific circumstances, genotype and cost-effectiveness–based perspective. For example, for the treatment of genotypes 1, 4, 5, and 6 hepatitis C infections, sofosbuvir can be used in combination with the viral NS5A inhibitor ledipasvir. In genotype 2 and 3 HCV infections, sofosbuvir can be used in combination with daclatasvir. For the treatment of cases with cirrhosis or liver transplant patients, weight-based ribavirin is sometimes added. Peginterferon with or without sofosbuvir is not recommended in an initial HCV treatment.

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