Sofosbuvir: Indications, Mechanism of Action and Side Effects

Indications

Sofosbuvir is a direct-acting antiviral drug primarily used in combination with other drugs to treat hepatitis C virus (HCV) infection. The combination of sofosbuvir and velpatasvir is used with or without ribavirin for the treatment of chronic hepatitis C genotype 1, 2, 3, 4, 5, or 6 infections, including those with or without cirrhosis. with or without cirrhosis). It is also used in combination with peginterferon or daclatasvir for the treatment of chronic (long term) hepatitis C.

Genotype 1 or 4: sofosbuvir plus peginterferon-alfa plus ribavirin for 12 weeks

Genotype 2: sofosbuvir plus ribavirin for 12 weeks

Genotype 3: sofosbuvir plus ribavirin for 24 weeks

For patients with genotype 1 HCV who are ineligible to receive interferon therapy: consider treatment with sofosbuvir plus ribavirin for 24 weeks.

For patients with HCV and hepatocellular carcinoma awaiting liver transplantation: Sofosbuvir plus ribavirin for up to 48 weeks or until liver transplantation, whichever occurs first.

Mechanism of Action

Sofosbuvir is a nucleotide analogue inhibitor of hepatitis C virus NS5B polymerase, a key enzyme that mediates HCV RNA replication. Therefore, Sofosbuvir exerts its therapeutic effect by inhibiting the proliferation of its hepatitis C virus. Sofosbuvir is converted into a pharmacologically active form of the uridine analogue, 5'-triphosphate (GS-461203), upon ingestion. This triphosphate mimics the natural cytosolic uridine nucleotide and is bound by HCV RNA polymerase to the extended RNA primer strand, resulting in chain termination.The active form of GS-461203 targets the NS5B catalytic site and is a non-negligible chain terminator. Most importantly, the active compound (GS-461203) does not inhibit host DNA polymerase, RNA polymerase or mitochondrial RNA polymerase.

Side Effects

Common side effects of Sofosbuvir include: fatigue, headache, nausea, and insomnia. Other side effects that may occur include: unusual tiredness, diarrhoea, loss of appetite, chest pain, light-headedness, dizziness or fainting, rash, sometimes with blisters or hive-like swelling. Severe allergic reactions are rare and may be accompanied by a slow or irregular heartbeat, difficulty breathing, hives-like swelling of the face, eyelids, lips, tongue, and throat. Contact your doctor if you experience any serious adverse reactions.