Sofosbuvir is a prescription antiviral medication for treating chronic hepatitis C. It belongs to a class of drugs known as direct-acting antivirals (DAAs), which target specific steps in a virus’s life cycle. As a foundational component of many treatment strategies, its introduction altered the standard of care by offering a more targeted approach compared to older, less specific treatments.
How Sofosbuvir Works
The primary function of sofosbuvir is to halt viral replication. It is a prodrug, meaning it is administered in an inactive form and must be metabolized within the body to become active. It is converted inside liver cells into its pharmacologically active form. This active molecule resembles uridine, one of the natural building blocks of RNA, the virus’s genetic material.
The hepatitis C virus (HCV) relies on an enzyme called NS5B RNA-dependent RNA polymerase to make copies of its genome. This enzyme assembles new RNA strands so the virus can multiply. The active form of sofosbuvir functions as a defective substrate for this machine. Because it mimics a natural nucleotide, the NS5B polymerase mistakenly incorporates it into the new, growing strand of viral RNA.
Once embedded in the chain, the unique chemical structure of the sofosbuvir molecule acts as a “chain terminator.” It creates a structural block that prevents any further nucleotides from being added. This termination of RNA elongation stops the virus from producing complete copies of its genetic material, thereby inhibiting its ability to replicate and generate new viral particles. This targeted action is specific to the viral enzyme, leaving the host’s cellular machinery unaffected.
Approved Medical Uses
Sofosbuvir is approved for the treatment of chronic hepatitis C virus (HCV) infection. It demonstrates a pan-genotypic effect, meaning it is active against multiple HCV genotypes, which are different genetic variations of the virus. Genotype 1 is the most common in the United States, but the drug is also effective as part of regimens targeting genotypes 2, 3, 4, 5, and 6.
Sofosbuvir is almost always administered as part of a combination therapy, as using it alone increases the risk of the virus developing resistance. Therefore, it is co-formulated or prescribed with other direct-acting antivirals that target different parts of the HCV life cycle. This multi-pronged attack helps to achieve high rates of sustained virologic response (SVR), which is considered a cure.
Commonly, sofosbuvir is found in single-pill, fixed-dose combinations. For example, it is combined with ledipasvir (sold as Harvoni), a treatment highly effective for genotype 1. Another combination product is sofosbuvir and velpatasvir (Epclusa), which was the first regimen approved for all six major HCV genotypes. For more difficult-to-treat cases or for patients who have failed previous therapies, it may be combined with velpatasvir and a third drug, voxilaprevir (Vosevi).
Potential Side Effects
The side effects associated with sofosbuvir often depend on the other medications it is combined with. When used in regimens containing only other direct-acting antivirals, the treatment is generally well-tolerated. The most commonly reported side effects include fatigue, headache, and nausea. Some people may also experience insomnia, and these effects are typically mild to moderate in intensity.
Less frequent side effects can include skin rash, diarrhea, decreased appetite, and irritability. For instance, when sofosbuvir is taken with ribavirin, a different type of antiviral drug, side effects like anemia (a low red blood cell count) become more common. The side effect profile can also vary in specific patient populations, such as those who have received a liver transplant.
While rare, more serious side effects can occur, including severe allergic reactions marked by hives, swelling, and difficulty breathing. Any indication of such a reaction requires immediate medical attention. It is important for patients to communicate with their healthcare provider about any adverse effects they experience, as the provider can offer ways to manage them.
Important Safety Information
Before starting treatment, it is important to be aware of specific safety warnings associated with sofosbuvir. The U.S. Food and Drug Administration (FDA) has issued a black box warning—its most serious type—regarding the risk of hepatitis B virus (HBV) reactivation. Patients who have a current or past HBV infection may experience a return of the virus while being treated for HCV. This reactivation can lead to severe liver problems, including liver failure and death, so all patients are tested for HBV before starting a sofosbuvir-containing regimen.
Another significant safety concern is a serious drug interaction with amiodarone, a medication used to treat irregular heartbeats. Co-administration of amiodarone with a sofosbuvir-containing regimen can lead to severe symptomatic bradycardia, a dangerously slow heart rate. This condition can cause fainting, dizziness, and shortness of breath and has, in rare instances, resulted in fatal cardiac arrest or the need for a pacemaker. The combination is not recommended unless no other treatment options are available, and it requires intensive cardiac monitoring.
Patients should inform their doctor of all medications they are taking, including over-the-counter drugs and herbal supplements. Certain substances, such as the antibiotic rifampin and the herbal supplement St. John’s wort, can significantly lower the concentration of sofosbuvir in the blood. This reduction can diminish the drug’s therapeutic effect, potentially leading to treatment failure.