Usage
- Medical Conditions: Sofosbuvir is prescribed for chronic hepatitis C virus (HCV) infection in adults and children 3 years and older, including patients with or without cirrhosis. It is used in combination with other antiviral medications, and the specific combination depends on the HCV genotype and the patient’s condition. It is not used as monotherapy.
- Pharmacological Classification: Antiviral, specifically a nucleotide analog inhibitor of HCV NS5B polymerase.
- Mechanism of Action: Sofosbuvir is a prodrug that is metabolized in the liver to its active form, GS-461203. GS-461203 acts as a chain terminator, inhibiting the RNA polymerase NS5B, which is essential for HCV replication.
Alternate Names
- International or Regional Variations: No widely recognized variations exist.
- Brand Names: Sovaldi
How It Works
- Pharmacodynamics: Sofosbuvir’s active metabolite, GS-461203, directly targets the HCV NS5B polymerase, effectively stopping viral replication. It exhibits a high barrier to resistance development.
- Pharmacokinetics:
- Absorption: Sofosbuvir is rapidly absorbed after oral administration, with peak plasma concentrations reached within approximately 0.5 to 2 hours. Taking sofosbuvir with food may increase its bioavailability.
- Metabolism: Sofosbuvir undergoes intracellular metabolism in the liver to form the active triphosphate GS-461203, the pharmacologically active agent. This occurs via a series of hydrolysis and phosphorylation steps.
- Elimination: Primarily renal excretion, with about 80% of the dose eliminated in the urine (primarily as GS-331007, an inactive metabolite). The remainder is eliminated in feces.
Dosage
Standard Dosage
Adults:
- 400 mg orally once daily, with or without food.
- The duration of treatment depends on the HCV genotype and whether other antiviral medications are used in combination. It generally ranges from 12 to 24 weeks.
Children (3 years and older):
- Dosage is weight-based and should be determined by a physician.
- <17 kg: 150 mg (oral pellets) once daily
- 17 to <35 kg: 200 mg (tablet or oral pellets) once daily
- ≥35 kg: 400 mg (tablet or oral pellets) once daily
- Treatment duration is similar to adults.
Special Cases:
- Elderly Patients: No specific dose adjustments are necessary based on age alone.
- Patients with Renal Impairment: Dose adjustments may be needed for patients with severe renal impairment (creatinine clearance < 30 mL/min). Check the specific prescribing information.
- Patients with Hepatic Dysfunction: Dose adjustments may be necessary. Caution is advised in patients with decompensated cirrhosis (Child-Pugh B or C).
- Patients with Comorbid Conditions: Exercise caution and consider potential drug interactions with medications for conditions like diabetes and cardiovascular disease.
Clinical Use Cases Sofosbuvir is not typically used in situations like intubation, surgical procedures, mechanical ventilation, intensive care unit (ICU) use, or emergency situations like cardiac arrest. Its primary indication is chronic HCV infection.
Dosage Adjustments Dosage adjustments may be required in patients with renal or hepatic impairment, as well as those on interacting medications.
Side Effects
Common Side Effects: Fatigue, headache, nausea, insomnia, anemia (when used in combination with ribavirin), diarrhea
Rare but Serious Side Effects: Severe allergic reactions, reactivation of hepatitis B virus infection (in patients with co-infection), symptomatic bradycardia (when used with amiodarone), worsening of hepatic decompensation (in patients with advanced liver disease)
Long-Term Effects: Generally, sofosbuvir is well-tolerated. However, long-term monitoring for liver function is important in patients with pre-existing liver disease.
Adverse Drug Reactions (ADR): Severe allergic reactions, significant bradycardia (with amiodarone), hepatic decompensation.
Contraindications
- Hypersensitivity to sofosbuvir
- Co-administration with certain drugs like amiodarone (without specialized cardiac monitoring), potent inducers of P-glycoprotein (e.g., rifampin, St. John’s wort)
- Pregnancy (when used with ribavirin), due to the teratogenic effects of ribavirin
Drug Interactions
- CYP450 Interactions: Sofosbuvir is not a significant inhibitor or inducer of CYP450 enzymes.
- Other Interactions:
- Potent inducers of P-gp (e.g., rifampin, St. John’s wort) can decrease sofosbuvir concentrations.
- Amiodarone can cause significant bradycardia when combined with sofosbuvir.
- Interactions with other drugs may occur, so careful review of concomitant medications is important.
Pregnancy and Breastfeeding
- Pregnancy: Sofosbuvir is contraindicated during pregnancy when used in combination with ribavirin. Sofosbuvir monotherapy is not recommended for HCV treatment. The safety of sofosbuvir monotherapy in pregnancy has not been fully established.
- Breastfeeding: The safety of sofosbuvir during breastfeeding is not well established. The decision to breastfeed should be made after careful consideration of the risks and benefits.
Drug Profile Summary
- Mechanism of Action: HCV NS5B polymerase inhibitor
- Side Effects: Fatigue, headache, nausea, insomnia, anemia (with ribavirin)
- Contraindications: Hypersensitivity, co-administration with specific drugs (e.g., amiodarone without appropriate monitoring, P-gp inducers), pregnancy (when used with ribavirin)
- Drug Interactions: P-gp inducers, amiodarone, various other potential interactions
- Pregnancy & Breastfeeding: Contraindicated with ribavirin in pregnancy; caution advised during breastfeeding.
- Dosage: Adults: 400 mg once daily; children: weight-based dosing.
- Monitoring Parameters: HCV RNA levels, liver function tests, ECG (if co-administered with amiodarone), complete blood count (if co-administered with ribavirin).
Popular Combinations
- Sofosbuvir/Ledipasvir
- Sofosbuvir/Velpatasvir
- Sofosbuvir/Daclatasvir
- Sofosbuvir/Ribavirin (with or without peginterferon alfa)
The choice of combination depends on HCV genotype and patient characteristics.
Precautions
- General Precautions: Assess for pre-existing liver disease, HCV genotype, and potential drug interactions. Monitor liver function and HCV RNA levels during treatment. Rule out or manage co-infection with hepatitis B before starting therapy.
- Specific Populations:
- Pregnant Women: Contraindicated when used with ribavirin.
- Breastfeeding Mothers: Exercise caution and assess potential risks and benefits.
- Children & Elderly: Weight-based dosing for children; no specific age-based adjustments for elderly patients.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sofosbuvir?
A: Adults: 400 mg once daily. Children: weight-based dosing (150mg, 200mg or 400mg daily, depending on weight).
Q2: Can Sofosbuvir be used alone to treat HCV?
A: No, Sofosbuvir is not used as monotherapy. It should always be used in combination with other antiviral medications.
Q3: Which HCV genotypes does Sofosbuvir treat?
A: Sofosbuvir is effective against various HCV genotypes (genotypes 1-6), but the specific combination regimen used will depend on the genotype.
Q4: What are the most common side effects of Sofosbuvir?
A: Fatigue, headache, nausea, and insomnia are common. Anemia is also common when used with ribavirin.
Q5: What are the serious drug interactions with Sofosbuvir?
A: Co-administration with amiodarone can cause serious bradycardia. Certain drugs like rifampin can reduce sofosbuvir levels and efficacy. Always check for potential drug interactions.
Q6: Can Sofosbuvir be used in patients with cirrhosis?
A: Yes, but dosage adjustments may be needed, particularly in patients with decompensated cirrhosis.
Q7: Can pregnant women take Sofosbuvir?
A: Sofosbuvir is contraindicated in pregnancy when used with ribavirin due to ribavirin’s teratogenic effects. The safety of sofosbuvir monotherapy during pregnancy has not been established.
Q8: Is Sofosbuvir safe for breastfeeding mothers?
A: Limited data exists regarding the safety of sofosbuvir during breastfeeding. The decision to breastfeed should be made after carefully weighing potential risks and benefits.
Q9: How is Sofosbuvir administered?
A: Orally as a tablet or as oral pellets, once daily with or without food.
