Report on New Patented Drugs - Tramacet

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: Tramacet

Generic Name: (tramadol HCl/acetaminophen)

DIN: 02264846 37.5 mg/325 mg tablet

Patentee: Janssen-Ortho Inc.

Indication - as per product monograph:

For the short-term management of acute pain (5 days or less).

Date of Issuance of First Patent(s) Pertaining to the Medicine: April 6, 1999

Notice of Compliance: July 22, 2005

Date of First Sale: July 22, 2005

ATC Class: N02AX52 Nervous System; Analgesics; Opioids; Other opioids.

APPLICATION OF THE GUIDELINES

Summary

The introductory price of Tramacet was found to be within the Guidelines because the cost of therapy did not exceed the cost of therapy of existing drugs in the therapeutic class comparison and the price did not exceed the range of prices in other comparator countries where Tramacet is sold.

Scientific Review

Tramacet is a combination of a new active substance, tramadol, and an existing substance, acetaminophen. The PMPRB's Human Drug Advisory Panel (HDAP) recommended that Tramacet be reviewed as a category 3 new medicine (provides moderate, little or no therapeutic advantage over comparable medicines).

The Therapeutic Class Comparison (TCC) test of the Guidelines provides that the price of a category 3 new drug product cannot exceed the prices of other drugs that treat the same disease or condition. Comparators are generally selected from among existing drug products in the same 4th level of the Anatomical Therapeutic Chemical (ATC) System that are clinically equivalent in addressing the approved indication. See the PMPRB's Compendium of Guidelines, Policies and Procedures for a more complete description of the Guidelines and the policies on TCCs.

The HDAP recommended codeine/acetaminophen combinations available on the Canadian market, oxycodone in combination with acetaminophen, a combination of codeine, acetaminophen and ibuprofen, and ibuprofen as comparators to Tramacet. These drugs and combination of drugs were compared in head-to-head trials with Tramacet and were found to have similar efficacy with respect to acute pain. Ibuprofen was also considered a comparator as it showed similar efficacy to Tramacet in direct clinical trials using a dental pain model.

The Guidelines provide that the dosage recommended for comparison purposes will normally not be higher than the maximum of the usual recommended dosage. The recommended comparable dosage regimens for Tramacet and the comparators are based on their respective product monographs and supported by clinical literature.

Price Review

Under the Guidelines, the introductory price of a new category 3 drug product will be presumed to be excessive if it exceeds the price of all of the comparable drug products in the TCC test, or if it exceeds the prices of the same medicine in the seven countries listed in the Patented Medicines Regulations. As shown in the table below, the price of Tramacet was within the Guidelines as the cost of therapy did not exceed the cost of therapy with the comparator medicines.

First 30-day sales (July to August 2005)

1 Publicly available price as per the Patented Medicines Regulations
2 Liste de médicaments, Régie de l'assurance maladie du Québec, February 2005
3 Ontario Drug Benefit Formulary, September 2005
4 Association québécoise des pharmaciens propriétaires, October 2005

Where comparators and dosage regimens are referred to in the Summary Reports, they have been selected by the PMPRB Staff and 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 - Tramacet

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15. Product monograph of Tramacet (tramadol hydrochloride/acetaminophen). Janssen-Ortho Inc., Toronto, ON, July 14, 2005.
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17. Rosenthal NR, Silverfield JC, Wu SC, et al. Tramadol/acetaminophen combination tablets for the treatment of pain associated with osteoarthritis flare in an elderly patient population. J Am Geriatr Soc 2004;52:374-80.
18. Ruoff GE, Rosenthal N, Jordan D, et al. Tramadol/acetaminophen combination tablets for the treatment of chronic lower back pain. A multicenter, randomized, double-blind, placebo-controlled outpatient study. Clin Ther 2003;25:1123-41.
19. Silverfield JC, Kamin M, Wu SC, et al. Tramadol/acetaminophen combination tablets for the treatment of osteoarthritis flare pain. A multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel group, add-on study. Clin Ther 2002;24;282-97.
20. Smith AB, Ravikumar TS, Kamin M, et al. Combination tramadol plus acetaminophen for postsurgical pain. Am J Surg 2004;187:521-7.
21. 21. U.K. Medicines Information. Tramacet (tramadol/paracetamol). October 2004. Available at: http://www.ukmi.nhs.uk/NewMaterial/html/docs/TramacetNMP1004.pdf