Sofosbuvir is a direct-acting antiviral (DAA) medication and a nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. It is a prodrug that undergoes intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), which incorporates into HCV RNA by the NS5B polymerase and acts as a chain terminator. It revolutionized HCV treatment in India by offering high cure rates (SVR12 >90%), pan-genotypic activity, excellent tolerability, and all-oral, interferon-free regimens.
Adult: One 400 mg tablet orally, once daily, with or without food (administration with a high-fat meal is recommended to enhance bioavailability). Must be used in combination with other DAAs as per genotype and patient history. Typical duration: 12 or 24 weeks.
Note: Swallow tablet whole with a glass of water. Take at approximately the same time each day. For optimal absorption, take with a meal, preferably containing fats. If a dose is missed and it is less than 18 hours from the usual time, take it immediately with food. If more than 18 hours have passed, skip the missed dose and take the next dose at the regular time. Do not take a double dose.
Sofosbuvir is a prodrug. After oral administration, it is absorbed and transported to the liver. Within hepatocytes, it undergoes intracellular metabolic activation to form the pharmacologically active uridine analog triphosphate (GS-461203). This active form mimics the natural substrate uridine triphosphate (UTP) and is incorporated by the HCV NS5B RNA-dependent RNA polymerase into the elongating viral RNA chain. Once incorporated, it acts as a chain terminator because it lacks a 3'-hydroxyl group, preventing the addition of the next nucleotide. This halts viral replication.
Pregnancy: Category B: Animal studies have shown no risk, but no adequate and well-controlled studies in pregnant women. Use only if clearly needed. The risk-benefit must be evaluated, especially if used with ribavirin (which is Category X).
Driving: Sofosbuvir has not been shown to impair driving ability. However, patients experiencing fatigue or dizziness should exercise caution.
| Rifampin / Rifabutin / St. John's Wort | Strong P-gp inducers. Decrease sofosbuvir plasma concentration drastically, leading to treatment failure. | Contraindicated |
| Carbamazepine / Phenytoin / Phenobarbital | Strong P-gp and moderate CYP inducers. May decrease sofosbuvir levels. | Contraindicated / Not Recommended |
| Amiodarone | Risk of serious symptomatic bradycardia, especially with concomitant use of sofosbuvir and daclatasvir/velpatasvir. Can be fatal. | Contraindicated |
| Tipranavir / Ritonavir | Potent P-gp inducers. May decrease sofosbuvir levels. | Not Recommended |
| Antacids (Al, Mg, Ca) | May decrease sofosbuvir absorption. Separate administration by at least 4 hours. | Moderate |
| H2-Receptor Antagonists (e.g., Famotidine) | May decrease sofosbuvir absorption. Can be given simultaneously or 12 hours apart from sofosbuvir. | Mild |
| Proton Pump Inhibitors (e.g., Omeprazole) | May decrease sofosbuvir absorption. Administer sofosbuvir with food and take PPI simultaneously or 4 hours before sofosbuvir. | Mild |