Report on New Patented Drug - Spriafil
Under its transparency initiative, the PMPRB publishes the results of the reviews of new patented drugs by Board Staff, for purposes of applying the PMPRB's Excessive Price Guidelines (Guidelines), for all new active substances introduced after January 1, 2002.
Brand Name: Spriafil
Generic Name: (posaconazole)
DIN: 02293404 (40mg/ml dose)
Patentee: Schering-Plough Canada Inc.
Indication – as per product monograph:
SPRIAFIL (posaconazole) is indicated for:
- prophylaxis of Aspergillus and Candida infections in patients, 13 years of age and older, who are at high risk of developing these infections, such as patients with prolonged neutropenia or hematopoietic stem cell transplant (HSCT) recipients.
- treatment of invasive aspergillosis in patients 13 years of age or older with disease that is refractory to amphotericin B or itraconazole, or in patients who are intolerant of these medicinal products. Refractoriness is defined as progression of infection or failure to improve after a minimum of 7 days of prior therapeutic doses of effective antifungal therapy.
- treatment of oropharyngeal candidiasis (OPC) in patients 13 years of age or older.
Date of Issuance of First Patent(s) Pertaining to the Medicine: January 23, 2007
Notice of Compliance: March 26, 2007
Date of First Sale: June 6, 2007
ATC Class: J02AC04
Antiinfectives for Systemic Use; Antimycotics for Systemic Use; Antimycotics for Systemic Use; Triazole Derivatives
Application of the Guidelines
The introductory price of Spriafil was found to be within the Guidelines because the price in Canada did not exceed the median of the prices of the same drug in those countries listed in the Patented Medicines Regulations, 1994 (Regulations) in which Spriafil was sold.
Spriafil is a new active substance and the PMPRB's Human Drug Advisory Panel (HDAP) recommended that Spriafil be classified as a category 2 new medicine. It provides a substantial improvement in the prevention of invasive fungal infections in immunocompromised patients, where current standard of prophylactic care confers inadequate protection.
The HDAP did not recommend any comparators for Spriafil; it is the first new active substance that offers significantly improved prophylactic coverage against invasive fungal infections.
Under the Guidelines, the introductory price of a new category 2 drug product will be presumed to be excessive if it exceeds the prices of all comparable drug products, based on a Therapeutic Class Comparison (TCC) test, and the median of the international prices identified in an International Price Comparison (IPC) test. See the PMPRB's Compendium of Guidelines, Policies and Procedures for a more complete description of the Guidelines.
It was not possible to conduct a TCC test as the HDAP did not identify any comparator drug products. At introduction, the price of Spriafil was within the Guidelines as it did not exceed the median of the international prices identified in an IPC test.
Introductory Period (June - July 2007)
|Country Price per Dose (CDN)
Source: Publicly available prices as per the Patented Medicines Regulations, 1994
Where comparators and dosage regimens are referred to in the Summary Reports, they have been selected by the HDAP for the purpose of carrying out the PMPRB's regulatory mandate, which is to review the prices of patented medicines sold in Canada to ensure that such prices are not excessive. The publication of these reports is also part of the PMPRB's commitment to make its price review process more transparent.
The information contained in the PMPRB's Summary Reports should not be relied upon for any purpose other than its stated purpose and is not to be interpreted as an endorsement, recommendation or approval of any drug nor is it intended to be relied upon as a substitute for seeking appropriate advice from a qualified health care practitioner.
References - Spriafil
1. Product Monograph of Spriafil, dated August 24, 2006.
2. Torres HA et al. Posaconazole: a broad-spectrum triazole antifungal. Lancet Infect Dis. 2005 Dec;5(12):775-85.
3. Greenberg RN, Mullane K, vanBurik JAH, Raad I, Abzug MJ, Anstead G et al. Posaconazole as salvage therapy for zygomycosis. Antimicrobial Agents and Chemotherapy 2006 Jan;50:126-33
4. Ullmann AJ, Cornely OA, Burchardt A, Hachem R, Kontoyiannis DP, Topelt K et al. Pharmacokinetics, safety and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection. Antimicrob Agents Chemother 2006 Feb;50(2) :658-666.
5. Raad II, Hachem RY, Herbrecht R, Graybill JR, Hare R, Corcoran G, Kontoyiannis DP. Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions. Clin Infect Dis 2006;42:1398-403.
6. Pitisuttithum P, Negroni R, Graybill JR, Bustamante B, Pappas P, Chapman S et al. Activity of posaconazole in the treatment of central nervous system fungal infections. J Antimicrob Chemother 2005;56:745 755.
7. Walsh TJ, Raad I, Patterson TF, Chandrasekar P, Donowitz GR, Graybill, Greene RE et al. Treatment of invasiv aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy : an externally controlled trial. CID 2007 January 1;442:2-12.
8. Schering Canada Inc. Spriafil product monograph. Pointe Claire, QC; 2006.
9. WHO Collaborating Centre for Drug Statistics Methodology [database on the Internet; cited April 4, 2007]. Available from: http://www.whocc.no/atcddd/
10. Health Canada. Notice of Compliance Search [database on the Internet; cited April 4, 2007]. Available from: http://www.nocdatabase.ca/
11. Sobel JD. Practice Guidelines for the treatment of fungal infections. Clin Infectious Diseases 2000;30:652.
12. Dodds Ashley ES. Treatment options for invasive fungal infections. Pharmacotherapy 2006;26(6 Pt 2): 55S - 60S.
13. Enoch DA, Ludlam HA, Brown NM. Invasive fungal infections: a review of epidemiology and management options. J Med Microbiol 2006;55:809-18.
14. Glasmacher A, Prentics AG. Evidence-based review of antifungal prophylaxis in neutropenic patients with haematological malignancies. J Antimicrob Chemother 2005;56 Suppl S1:i23-i32.
15. Keating GM. Posaconazole. Drugs 2005;65(11):1553-67.
16. Cornely OA, Maertens J, Winston DJ, Perfect J, Ullman AJ, Walsh TJ et al. Posaconacole vs fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 2007 Jan 25;356(4):348-59.
17. Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med 2007 Jan 25;356(4):335-47.
18. Vazquez JA, Skiest DJ, Nieto L, Northland R, Sanne I, Gogate J et al. A Multicenter Randomized Trial Evaluating Posaconazole versus Fluconazole for the Treatment of Oropharyngeal Candidiasis in Subjects with HIV/AIDS. CID 2006;42:1179-86.
19. Walsh TJ, Raad I, Patterson TF, Chandrasekar P, Donowitz GR, Graybill, Greene RE et al. Treatment of invasiv aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy : an externally controlled trial. CID 2007 January 1;442:2-12.
20. Skiest DJ, Vazquez JA, Anstead GM, Graybill JR, Reynes J, Ward D et al. Poraconazole for the treatment of azole-refractory oropharyngeal and esophageal candidiasis in subjects with HIV infection. Clin Infect Dis 2007;44:607-14.
21. Raad II, Hachem RY, Herbrecht R, Graybill JR, Hare R, Corcoran G, Kontoyiannis DP. Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions. Clin Infect Dis 2006;42:1398-403.
22. Greenberg RN, Mullane K, vanBurik JAH, Raad I, Abzug MJ, Anstead G et al. Posaconazole as salvage therapy for zygomycosis. Antimicrobial Agents and Chemotherapy 2006 Jan;50:126-33.
23. van Burik JAH, Hare RS, Solomon HF, Corrado ML, Kontoyiannis DP. Posaconazole is effective as salvage thaerpy in zygomycosis : a retrospective summary of 91 cases. Clin Infect Dis 2006;42:e61-65.
24. Ullmann AJ, Cornely OA, Burchardt A, Hachem R, Kontoyiannis DP, Topelt K et al. Pharmacokinetics, safety and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection. Antimicrob Agents Chemother 2006 Feb;50(2) :658-666.
25. Pitisuttithum P, Negroni R, Graybill JR, Bustamante B, Pappas P, Chapman S et al. Activity of posaconazole in the treatment of central nervous system fungal infections. J Antimicrob Chemother 2005;56:745 755.
26. Negroni R, Tobon A, Bustamante B, Shikanai-Yasuda MA, Patino H, Restrepo A. Posaconazole treatment of refractory eumycetoma and chromoblastomycosis. Rev. Inst. Med. trop. S. Pauolo 2005 Nov'Dec;47(6):339-46.
27. Segal BH, Barnhart LA, Anderson VL, Walsh TJ, Malech HL, Holland SM. Posaconazole as salvage therapy in patients with chronic granulomatous disease and invasive filamentous fungal infection. CID 2005 June 1; 40 :1684-1688.
28. Galgiani JN, Ampel NM, Blair JE, Catanzaro A, Johnson RH, Stevens DA et al. Coccidioidomycosis. (Guidelines issued on behalf of the Infectious Diseases Society of America) Clin Infectious Diseases 2005;41 :1217-23.
29. Pappas PG, Rex JH, Sobel JD, Filler SG, Dismukes WE, Walsh TJ et al. Guidelines for treatment of candidiasis. CID 2004 Jan 15;38:161-189.
30. Centers for Disease Control and Prevention. Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. MMWR2004;53(No. RR-15):1-112.
31. Cornely OA, Bohme A, Buchheidt D, Glasmacher A, Kahl C, Karthaus M et al. Prophylaxis of invasive fungal infections in patients with hematological malignancies and solid tumors. Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 2003; 82 Suppl 2:S186-200.
32. Centers for Disease Control and Prevention.Guidelines for Preventing Opportunistic Infections Among HIV-Infected Persons - 2002 Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR 2002;51(No. RR-8):1-52.
33. Buchner T, Fegeler W, Bernhardt H, Brockmeyer N, Duswald K-H, Herrmann M et al. Treatment of severe candida infections in high-risk patients in Germany: consensus formed by a panel of interdisciplinary investigators. Eur J Clin Microbiol Infect Dis 2002;21:337-352.
34. Centers for Disease Control and Prevention. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients: recommendations of CDC, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation. MMWR 2000;49(No. RR-10):1-128.
35. Stevens DA, Kan VL, Judson MA, Morrison VA, Dummer S, Denning DW et al. Practice guidelines for diseases caused by Aspergillus. Clin Infectious Diseases 2000;30:696-709.
36. Saag MS, Graybill RJ, Larsen RA, Pappas PG, Perfect JR, Powderly WG et al. Practice guidelines for the management of cryptococcal disease. (part of a series of guidelines from the IDSA) Clin Infectious Diseases 2000;30:710-8.
37. Bhatti Z, Shaukat A, Almyroudis NG, Segal BH. Review of epidemiology, diagnosis, and treatment of invasive mould infections in allogeneic hematopoietic stem cell transplant recipients. Mycopathologia 2006;162:1 15.
38. Ullmann AJ and Cornely OA. Antifungal prophylaxis for invasive mycoses in high risk patients. Curr Opin in Infect Diseases 2006;19:571-76.
39. Esterre P & Queiroz-Telles F. Management of chromoblastomycosis : novel perspectives. Curr Opin Infect Dis 2006;19 :148-152.
40. Brown J. Zygomycosis: an emerging fungal infection. Am J Health-Syst Pharm. 2005 Dec 15;62:2593-2596.
41. Spellberg B, Edwards, Jr J, Ibrahim A. Novel perspectives on mucormycosis: pathophysicology, presentation and management. Clin Microbiol Reviews 2005 July;18(3):556-559.
42. Health Canada. Drug Product Database [database on the Internet; cited March 2007]. Available from: http://cpe0013211b4c6d-cm0014e88ee7a4.cpe.net.cable.rogers.com/dpdq/
43. Canadian Pharmacists Association. e-CPS [database on the Internet; cited April 2007]. Ottawa: Canadian Pharmacists Association; 2007.
44. American Society of Health-System Pharmacists. AHFS Drug Information® (2007). In: STAT!Ref Online Electronic Medical Library [database on the Internet; cited April 2007]. Bethesda: American Society of Health-System Pharmacists; 2007.
45. DiCaudo DJ. Coccidioidomycosis: a review and update. J Am Acad Dermatol 2006;55:929-42.
46. Product Monograph of Vfend. E-CPS 2007.
47. Product Monograph of Fungizone Intravenous. E-CPS 2007.
48. Product Monograph of Abelcet. Electronic CPS 2005.
49. Product Monograph of AmBisome. E-CPS 2007.
50. Product Monograph of Sporanox Oral Solution. E-CPS 2007.
51. Product Monograph of Sporanox Capsules. E-CPS 2007.
52. Product Monograph of Cancidas. E-CPS 2007.
53. Product Monograph of Diflucan. E-CPS 2007.
54. Gilbert DN et al. The Sanford Guide to Antimicrobial Therapy 2006. pp 74-85.