Sofosbuvir is a nucleotide analog NS5B polymerase inhibitor used for the treatment of chronic hepatitis C (CHC) infection. It is administered as part of a combination antiviral therapy, not as a single drug.

The effectiveness of Sofosbuvir has been proven in patients infected with HCV genotypes 1, 2, 3, or 4. It is also effective in patients who have hepatocellular carcinoma that meets the Milan criteria and are waiting for liver transplantation, as well as in patients with HCV/HIV-1 coinfection.

When starting treatment with Sofosbuvir, the following points should be considered:

• Sofosbuvir should not be used alone for the treatment of chronic hepatitis C.
• The treatment regimen and duration depend on the viral genotype and the patient’s clinical condition.
• The treatment response may vary depending on baseline host factors and viral characteristics.

Sofosbuvir is a nucleotide analog inhibitor that selectively targets the HCV NS5B (non-structural protein 5B) RNA-dependent RNA polymerase, an essential enzyme required for hepatitis C virus replication.After entering the cell, Sofosbuvir undergoes intracellular metabolism to produce the pharmacologically active uridine analog triphosphate (GS-461203). This active metabolite is incorporated into the viral RNA by the NS5B polymerase during RNA synthesis and acts as a chain terminator, thereby stopping further RNA elongation.More specifically, Sofosbuvir inhibits viral replication by binding to the two Mg²⁺ ions located in the GDD active site motif of the NS5B polymerase, which blocks the replication of the hepatitis C viral genetic material.

One 400 mg tablet taken once daily with or without food. Should be used in combination with Ribavirin or in combination with Pegylated Interferon and Ribavirin for the treatment of CHC.

Recommended combination therapy: (HCV Mono-infected and HCV/HIV-1 Co-infected)

• Genotype 1 or 4: Sofosbuvir + Peginterferon alfa + Ribavirin for 12 weeks
• Genotype 2: Sofosbuvir + Ribavirin for 12 weeks
• Genotype 3: Sofosbuvir + Ribavirin for 24 weeks

Sofosbuvir in combination with Ribavirin for 24 weeks can be considered for CHC patients with genotype 1 infection who are Interferon ineligible

Should be used in combination with Ribavirin for treatment of CHC in patients with hepatocellular carcinoma awaiting liver transplantation for up to 48 weeks or until liver transplantation whichever occurs first A dose recommendation cannot be made for patients with severe renal impairment or end stage renal disease

The therapeutic effectiveness of Sofosbuvir may be reduced when it is used together with medicines that strongly induce P-glycoprotein (P-gp) in the intestine. Examples include rifampicin, St. John’s wort, carbamazepine, phenytoin, modafinil, phenobarbital, oxcarbazepine, rifabutin, and rifapentine. These drugs can decrease the concentration of Sofosbuvir in the body and may reduce its antiviral effect.Drugs that inhibit P-gp and/or BCRP (Breast Cancer Resistance Protein) may also affect the levels of Sofosbuvir.Co-administration of Sofosbuvir with amiodarone, particularly when used together with another direct-acting antiviral (DAA), may lead to serious symptomatic bradycardia (dangerously slow heart rate). Therefore, caution and close monitoring are recommended.

When Sofosbuvir is used together with Ribavirin or Peginterferon alfa/Ribavirin, the contraindications related to those medicines also apply to the combination therapy.Treatment with Sofosbuvir in combination with Ribavirin or Peginterferon alfa/Ribavirin is contraindicated in pregnant women, women who may become pregnant, and men whose female partners are pregnant. This is because Ribavirin is associated with a high risk of birth defects and fetal death.

The most frequently reported side effects (occurring in 20% or more of patients) when Sofosbuvir is used together with Ribavirin are fatigue and headache.When Sofosbuvir is used in combination with Peginterferon alfa and Ribavirin, the commonly reported adverse effects include fatigue, headache, nausea, insomnia, anemia, itching (pruritus), weakness (asthenia), skin rash, reduced appetite, chills, flu-like symptoms, fever (pyrexia), diarrhea, neutropenia, muscle pain (myalgia), and irritability.

Pregnancy Category B: There are no adequate and well-controlled studies of Sofosbuvir in pregnant women. Therefore, it should be used during pregnancy only if clearly needed and under medical supervision.

Nursing Mothers: It is not known whether Sofosbuvir or its metabolites are excreted in human breast milk. Caution should be exercised when Sofosbuvir is administered to breastfeeding mothers.

Bradycardia with amiodarone co-administration: Serious symptomatic bradycardia (slow heart rate) may occur in patients who take amiodarone together with Sofosbuvir and another direct-acting antiviral (DAA). The risk may be higher in patients who are also taking beta-blockers or those who have underlying heart disease and/or advanced liver disease.Co-administration of amiodarone with Sofosbuvir and another DAA is generally not recommended. If no suitable alternative treatment options are available, close cardiac monitoring is advised during therapy.

Pediatric Use: The safety and effectiveness of Sofosbuvir in children under 18 years of age have not yet been established.

Geriatric Use: Sofosbuvir has been studied in 90 patients aged 65 years and older. The treatment response in these older patients was similar to that seen in younger patients across different treatment groups. Therefore, no dose adjustment is required for elderly patients.

The highest studied dose of Sofosbuvir is a single 1200 mg dose. There is no specific antidote available for Sofosbuvir overdose. In case of overdose, treatment should include general supportive care, such as monitoring vital signs and carefully observing the patient’s clinical condition.

Hepatic viral infections (Hepatitis C)

Keep Sofosbuvir out of the reach of children. Store in a cool, dry place and protect from light.