Sofosbuvir

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of sofosbuvir
General
Non-proprietary name Sofosbuvir
other names

Isopropyl- (2 S ) -2 - ({[(2 R , 3 R , 4 R , 5 R ) -5- (2,4-dioxopyrimidin-1-yl) -4-fluoro-3-hydroxy-4- methyl-tetrahydrofuran-2-yl] methoxy-phenoxy-phosphoryl} amino) propanoate

Molecular formula C 22 H 29 FN 3 O 9 P
Brief description

white crystalline solid

External identifiers / databases
CAS number 1190307-88-0
EC number 695-717-4
ECHA InfoCard 100.224.393
PubChem 45375808
ChemSpider 26286922
DrugBank DB08934
Wikidata Q2502747
Drug information
ATC code

J05 AX15

properties
Molar mass 529.453 g mol −1
Physical state

firmly

solubility
  • slightly soluble in water
  • soluble in ethanol
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Sofosbuvir is a medicinal substance that is indicated in combination with other medicines (ledipasvir, daclatasvir, peginterferon α , ribavirin ) for the treatment of chronic hepatitis C in adults. In clinical studies, up to 90 percent of the affected patients could be cured.

Sofosbuvir is listed as an essential medicine on the World Health Organization list. The drug was developed by Michael J. Sofia at Pharmasset (now Gilead Sciences ), clinically tested from 2010 and approved in the USA in 2013/14.

Mechanism of action

Sofosbuvir inhibits the RNA- dependent enzyme NS5B polymerase . This enzyme plays an important role in the reproduction ( replication ) of the hepatitis C virus (HCV). Sofosbuvir is a nucleotide - prodrug and after intracellular metabolism to the active form uridine converted analogue triphosphate. Its incorporation into the HCV RNA leads to chain termination. The active metabolite does not inhibit human DNA or RNA polymerases or mitochondrial RNA polymerase.

Sofosbuvir is the first pangenotypically effective inhibitor of the HCV RNA polymerase NS5B (regardless of the genotype in the same way for all genotypes). The US agency FDA had granted the active ingredient Break Through Therapy status.

However, combination therapy and the associated duration of treatment vary depending on the HCV genotype.

Side effects and interactions

Sofosbuvir has mainly been studied in combination with ribavirin with and without peginterferon α. No specific side effects related to sofosbuvir were found. The most common side effects occurring during combination therapy were fatigue, headache, nausea and insomnia. In laboratory tests, an increase in creatine kinase and pancreatic enzymes was observed without any symptoms. However, sofosbusvir has a very broad spectrum of interaction because it is a substrate for P-glycoprotein . Simultaneous administration of St. John's wort , various antibiotics, analeptics and anticonvulsants can lead to a decrease in the concentration of sofosbuvir in the blood. The active substance is excreted through the kidneys and can show significantly increased blood levels in patients with impaired kidney function. During normal hemodialysis, around 18% of the drug was removed from the plasma, so that this can also occur in patients who require dialysis.

Trade names

  • Sovaldi (EU, USA, CAN)
  • Combination with velpatasvir : Epclusa (USA, EU)
  • Combination with velpatasvir and voxilaprevir : Vosevi (USA)
  • Combination with ledipasvir : Harvoni (EU, USA)

costs

Sovaldi has been approved in Canada and the USA since December 2013 and in the EU since January 2014. The manufacturer Gilead Sciences sold the drug in Germany in 2014 for around € 700 per tablet (€ 19,999 for a jar with 28 tablets). German health insurance companies feared annual costs of over one billion euros if all of the estimated 300,000 people infected with hepatitis C are treated. A therapy duration of about 12 weeks would cost 60,000 euros for one patient. In February 2015, after negotiations with the German statutory health insurance companies , the manufacturer announced that the reimbursement contribution per package was € 14,500. According to Spiegel Online, this would be € 488 per tablet, € 43,500 for 12-week therapy and € 87,000 for 24-week therapy.

In Switzerland, the price of a tablet was CHF 686 in 2014, or CHF 57,624 for a 12-week therapy. The Swiss Federal Office of Public Health had therefore ordered that the cost of the drug would only be reimbursed by the basic insurance in cases in which patients already suffer from cirrhosis of the liver (approx. 1,500 patients nationwide). As of October 1, 2017, this remuneration restriction ceased. This means that Harvoni and Epclusa can be prescribed to all hepatitis C patients, regardless of liver damage. The lifting of the so-called Limitatio was accompanied by substantial price reductions, which are also expected for Gilead products.

Gilead is selling sofosbuvir under its own brand in 101 low-income countries with a suggested retail price of $ 900 for 12 weeks of therapy. The company has also licensed various Indian generic drug manufacturers to manufacture sofosbuvir for a 7% royalty. The licenses allow the active ingredient to be exported to the same 101 countries.

Web links

Individual evidence

  1. ↑ a b c FDA: SOVALDI (sofosbuvir) tablets
  2. ^ EU: Summary on compassionate use for Sofosbuvir
  3. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  4. ↑ Outdated standard? - Hepatitis C can be cured up to 90 percent even without interferon
  5. ↑ New drugs: Sofosbuvir, Sovaldi (Gilead) pharmische-zeitung.de
  6. ↑ G-BA: New hepatitis C drug gets good grades
  7. ↑ FDA approves Sovaldi for chronic hepatitis C . FDA news release, December 6, 2013.
  8. ↑ Christoph Sarrazin, Thomas Berg, Peter Buggisch, Matthias Dollinger, Holger Hinrichsen, Dietrich Hüppe, Michael Manns, Stefan Mauss, Jörg Petersen, Karl-Georg Simon, Heiner Wedemeyer, Stefan Zeuzem: Current recommendation of the DGVS and the bng for the therapy of chronic Hepatitis C , DGVS guidelines addendum published on March 5, 2015, p. 36; last accessed on March 8, 2015 ( Memento from April 2, 2015 in the Internet Archive )
  9. ↑ Why a pill can cost 700 euros . Spiegel.de
  10. ↑ kis / DPA: New hepatitis drug blows the budget. In: stern.de . August 6, 2014, accessed May 18, 2019 .
  11. ↑ Nicola Kuhrt: Hepatitis C drug Sovaldi: Manufacturer lowers pill price. In: Spiegel Online . February 12, 2015, accessed May 18, 2019 .
  12. ^ Rita Flubacher: A pack of pills for 19,000 francs. In: Tages-Anzeiger, August 7, 2014, p. 1.
  13. ↑ Hepatitis C: Harvoni is now also fully remunerated In: medinside.ch, September 12, 2017, accessed on November 20, 2017.
  14. ↑ Rapid Reductions in prices for generic sofosbuvir and Daclatasvir to treat hepatitis C . In: Journal of Virus Eradication . 2, No. 1, January 2016, pp. 28–31. PMID 27482432 . PMC 4946692 (free full text).