Important Clarification: Sovalteltide vs. Sofosbuvir (Sovaldi)
The evidence provided addresses sofosbuvir (Sovaldi), not sovalteltide. These are completely different medications. I will provide information on sofosbuvir based on the available evidence, but please confirm which medication you are asking about.
Sofosbuvir (Sovaldi): Mechanism of Action, Uses, and Side Effects
Mechanism of Action
Sofosbuvir is a hepatitis C virus (HCV)-specific uridine nucleotide NS5B polymerase inhibitor with potent pan-genotypic activity. 1
- Sofosbuvir acts as a direct-acting antiviral agent by inhibiting the NS5B RNA polymerase, which is essential for HCV replication 2
- The drug undergoes extensive hepatic metabolism through sequential hydrolysis catalyzed by cathepsin A (CatA) or carboxylesterase 1 (CES1), followed by phosphoramidate cleavage by HINT1, and subsequent phosphorylation to form the active triphosphate metabolite GS-461203 2, 1
- The active metabolite directly inhibits viral RNA synthesis, preventing HCV replication across all major genotypes 1, 3
Clinical Uses
Sofosbuvir is indicated for the treatment of chronic hepatitis C virus infection in combination with other antiviral agents. 2
Adult Patients:
- Genotype 1 or 4 infection (with or without compensated cirrhosis): Used in combination with pegylated interferon and ribavirin 2, 1
- Genotype 2 or 3 infection (with or without compensated cirrhosis): Used in combination with ribavirin 2, 1
- All genotypes (1-6): Can be used as part of newer combination regimens (e.g., with ledipasvir or velpatasvir) 4, 5
Pediatric Patients:
- Approved for chronic HCV genotype 2 or 3 infection in patients ≥12 years of age or weighing ≥35 kg, in combination with ribavirin 2
Dosing:
- 400 mg once daily (one tablet), taken with or without food 1
- Treatment duration typically ranges from 12-24 weeks depending on genotype, cirrhosis status, and treatment history 1, 6
Side Effects and Safety Profile
Sofosbuvir is associated with a well-tolerated safety profile, with adverse events occurring at rates only slightly higher than placebo. 1
Most Common Adverse Events (≥10%):
- Headache 1, 4, 5
- Fatigue 1, 4, 5
- Nausea 1
- Anemia (particularly when combined with ribavirin and/or pegylated interferon) 1
- Insomnia (when used with pegylated interferon and ribavirin) 1
- Nasopharyngitis 4
Serious Safety Concerns:
Renal Impairment:
- Sofosbuvir is predominantly renally eliminated (approximately 80% in urine), requiring caution in severe renal impairment 1
- No dosage adjustment needed for mild-to-moderate renal impairment (eGFR 30-80 mL/min/1.73 m²) 1
- No dosage recommendation available for severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease due to up to 20-fold higher exposures of the metabolite GS-331007 1
Cardiac Effects:
- Co-administration with amiodarone (and possibly dronedarone) is CONTRAINDICATED due to serious risk of symptomatic bradycardia, including one lethal case reported 1
- Bradycardia can occur within hours to days, but cases have been observed up to 2 weeks after initiating HCV treatment 1
- The mechanism of this interaction is unknown and requires investigation 1
Drug Interactions
Critical Contraindications:
- Potent P-glycoprotein (P-gp) inducers (rifampin, carbamazepine, phenytoin, St. John's wort) significantly decrease sofosbuvir plasma concentrations and should be avoided 1
- Amiodarone and dronedarone are contraindicated due to life-threatening bradycardia risk 1
Important Interactions:
- No CYP3A4 metabolism: Sofosbuvir is not metabolized by cytochrome P450 enzymes, reducing potential drug interactions 1
- No food effect: Can be administered without regard to meals 1, 2
- HIV antiretrovirals: Generally well-tolerated with most antiretroviral agents, though caution needed with tenofovir-containing regimens due to potential nephrotoxicity potentiation 1
Special Populations
Hepatic Impairment:
- No dosage adjustment required for any degree of hepatic impairment 1
HIV/HCV Coinfection:
- Treatment recommendations are the same as for HCV monoinfection, with attention to antiretroviral drug interactions 1
- Clinical trials demonstrated 92-100% cure rates in HIV-coinfected patients 4
Pregnancy:
- No data available on use in pregnant women 6
- Contraception is mandatory when combined with ribavirin due to ribavirin's teratogenic effects, potentially for several months after treatment discontinuation 6
Clinical Efficacy
Sustained virological response (SVR) rates with sofosbuvir-containing regimens range from 90-100% across different HCV genotypes and patient populations. 4, 5, 6, 7