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sofosbuvir (Sovaldi)

Indications: - for use in combination with ledipasvir (Harvoni) for treatment of hepatitis C genotypes 1, 4, 5, or 6 - for use in combination with ribavirin for treatment of hepatitis C genotypes 2 & 3 - for use in combination with pegylated interferon & ribavirin for treatment of hepatitis C genotypes 1,4,5,6 - particularly useful for hepatitis C genotype 1 * FDA-approved for use in patients >- 12 years of age [16] Dosage: - oral agent - 12 weeks of therapy - in combination with ledipasvir, 8 weeks of therapy [7] - 95% effective in cirrhosis-free patients - equally effective among previously untreated as well as previously treated patients, many with cirrhosis [11] - 8 weeks of therapy equivalent to 12 weeks [7] - cost effective for genotype 1 infection - $12,825 more per quality-adjusted life year compared with standard of care [9] - cost-effective for genotype 2 or 3 infection with cirrhosis or previous treatment with interferon [10] Storage: - store in orginal container - original container has a desiccant [8] Adverse effects: - headache, fatigue (when used in combination with ribavirin) - also nausea, insomnia & anemia when used in combination with peginterferon-alfa) [5] - may exacerbate hepatitis B infection [13,14] - may cause liver injury & liver failure independent of hepatitis B [15] Mechanism of action: - nucleotide polymerase inhibitor Notes: - response rates (no detectable serum HCV RNA) at 24 weeks - 84% of previously untreated patients with HCV genotype 1 - ~100% of previously untreated patients with HCV genotype 2 or HCV genotype 3 - up to 68% patients with HCV genotype 1 [4] - 10% of patients with HCV genotype 1 not responding to previous therapy - resistance to sofosbuvir did not develop in 2 studies [3] - discontinuation of sofosbuvir only 1-2% [3] - $84,000 for a 12-week course of treatment (2014) [6]

Interactions

drug interactions

General

antiviral agent

References

  1. Gane EJ et al. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med 2013 Jan 3; 368:34. PMID: 23281974 - Poordad F et al. Exploratory study of oral combination antiviral therapy for hepatitis C. N Engl J Med 2013 Jan 3; 368:45 PMID: 23281975
  2. Sax PE HIV and ID Observations Simeprevir and Sofosbuvir Submitted to FDA - Clock Ticking on Boceprevir, Telaprevir, Even Interferon cited in: Physician's First Watch for April 11, 2013 Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org http://blogs.jwatch.org/hiv-id-observations/index.php/simeprevir-and-sofosbuvir-submitted-to-fda-clock-ticking-on-boceprevir-telaprevir-even-interferon/2013/04/10/?q=pfw-featured
  3. Lawitz E et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013 Apr 23; PMID: 23607594 http://www.nejm.org/doi/full/10.1056/NEJMoa1214853
  4. Osinusi A et al Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 in Patients With Unfavorable Treatment Characteristics. A Randomized Clinical Trial. JAMA. 2013;310(8):804-811 PMID: 23982366 http://jama.jamanetwork.com/article.aspx?articleid=1733720
  5. FDA News Release: Dec. 6, 2013 FDA approves Sovaldi for chronic hepatitis C http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm377888.htm
  6. Physician's First Watch, March 25, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
  7. Kowdley JV et al Ledipasvir and Sofosbuvir for 8 or 12 Weeks for Chronic HCV without Cirrhosis. N Engl J Med. April 11, 2014 PMID: 24720702 http://www.nejm.org/doi/full/10.1056/NEJMoa1402355
  8. Prescriber's Letter 21(6): 2014 Oral Meds to Keep in Original Containers Detail-Document#: 300622 (subscription needed) http://www.prescribersletter.com
  9. Najafzadeh M et al. Cost-effectiveness of novel regimens for the treatment of hepatitis C virus. Ann Intern Med 2015 Mar 17; 162:407. PMID: 25775313 http://annals.org/article.aspx?articleid=2197177 - Chhatwal J et al. Cost-effectiveness and budget impact of hepatitis C virus treatment with sofosbuvir and ledipasvir in the United States. Ann Intern Med 2015 Mar 17; 162:397. PMID: 25775312 http://annals.org/article.aspx?articleid=2197176
  10. Linas BP et al The Cost-Effectiveness of Sofosbuvir-Based Regimens for Treatment of Hepatitis C Virus Genotype 2 or 3 Infection. Ann Intern Med. Published online 30 March 2015 PMID: 25820703 http://annals.org/article.aspx?articleid=2212248 - Etzion O, Ghany MG A Cure for the High Cost of Hepatitis C Virus Treatment. Ann Intern Med. Published online 30 March 2015. PMID: 25820765 http://annals.org/article.aspx?articleid=2212249
  11. Afdhal N et al Ledipasvir and Sofosbuvir for Previously Treated HCV Genotype 1 Infection. N Engl J Med. April 12, 2014 PMID: 24725238 http://www.nejm.org/doi/full/10.1056/NEJMoa1316366 - Afdhal N et al Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection. N Engl J Med. April 12, 2014 PMID: 24725239 http://www.nejm.org/doi/full/10.1056/NEJMoa1402454 - Poordad F et al ABT-450/r - Ombitasvir and Dasabuvir with Ribavirin for Hepatitis C with Cirrhosis. N Engl J Med. April 12, 2014 PMID: 24725237 http://www.nejm.org/doi/full/10.1056/NEJMoa1402869 - Hoofnagle JH and Sherker JH Therapy for Hepatitis C - The Costs of Success. N Engl J Med. April 12, 2014 PMID: 24725236 http://www.nejm.org/doi/full/10.1056/NEJMe1401508
  12. Herper M. The Top Drug Launches Of All Time. Forbes. July 29, 2015 http://www.forbes.com/sites/matthewherper/2015/07/29/the-top-drug-launches-of-all-time
  13. Collins JM et al. Hepatitis B virus reactivation during successful treatment of hepatitis C virus with sofosbuvir and simeprevir. Clin Infect Dis 2015 Oct 15; 61:1304. PMID: 26082511 http://cid.oxfordjournals.org/content/61/8/1304 - Balagopal A and Thio CL. Another call to cure hepatitis B. Clin Infect Dis 2015 Oct 15; 61:1307 PMID: 26082512 http://cid.oxfordjournals.org/content/61/8/1307
  14. FDA Drug Safety Communication: Oct 4, 2016 FDA warns about the risk of hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis C. http://www.fda.gov/Drugs/DrugSafety/ucm522932.htm
  15. PERSPECTIVES FROM NEW ADVERSE EVENT REPORTS Institute for Safe Medication Practices. Jan 25, 2017 http://www.ismp.org/quarterwatch/pdfs/2016Q2.pdf
  16. Kelley KJ, Sadoughi S, Sofair A FDA Approves Two Antivirals to Treat HCV in Pediatric Patients. Physician's First Watch, April 10, 2017 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - FDA News Release. April 7, 2017 FDA approves two hepatitis C drugs for pediatric patients. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm551407.htm

Component-of

ledipasvir/sofosbuvir (Harvoni) sofosbuvir/velpatasvir (Epclusa) sofosbuvir/velpatasvir/voxilaprevir (Vosevi)