Reports on New Patented Drugs – Ezetrol

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 Price Guidelines, for all new active substances introduced after January 1, 2002.

Brand Name: Ezetrol

Generic Name: ezetimibe

DIN: 02247521 10 mg tablet

Patentees: Merck Frosst and Schering Canada Inc.

Indication – as per product monograph:

As an adjunct to lifestyle changes, including diet at least equivalent to the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) TLC diet, when the response to diet and other non-pharmacological measures alone has been inadequate.

Notice of Compliance: May 12, 2003

Date of First Sale: June 11, 2003

ATC Class: C10AX09

Other cholesterol and triglyceride reducers



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

Scientific Review:

Ezetrol is a new active substance and the PMPRB´s Human Drug Advisory Panel (HDAP) recommended that Ezetrol 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 PMPRB´s Price 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. The Guidelines provide that it may, however, be appropriate to include products from other ATC classes if they are clinically equivalent for the appropriate indication to the drug product under review. See the PMPRB´s Compendium of Guidelines, Policies and Procedures for a more complete description of the Guidelines and the policies on TCCs.

Members of the same 4th level ATC class as Ezetrol include Probucol and Omega-3 fatty acids. However, none of these products share the same indication as Ezetrol.

In its review, the HDAP recommended the resins Questran and Colestid, niacin and the statins Lescol and Pravachol as appropriate TCC comparators for Ezetrol.

The PMPRB´s 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 Ezetrol and the comparators are based on their respective products monographs.

Price Review:

Under the PMPRB´s Price 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. The introductory price of Ezetrol was within the PMPRB´s Price Guidelines as it did not exceed the cost of therapy with the comparator medicines.

Brand Name Active Ingredient Strength Dosage Regimen Unit Price Cost Per Day
Ezetrol ezetimibe 10 mg tablet 10 mg/day $1.58001 $1.5800
Lescol Fluvastatin 20 mg capsule 20 mg/day $0.47432 $0.7500
Pravachol Pravastatin 10 mg tablet 10 mg/day $0.64073 $1.5133
Questran Cholestyramin 4 g / packet 4 to 24 g/day $0.64072 $0.4743 - 2.8458
Questran Light cholestyramine 4 g / packet 4 to 24 g/day $0.81832 $0.6407 - 3.8442
Questran cholestyramine 4 g / scoop 4 to 24 g/day $0.81832 $0.6407 - 3.8442
Colestid Orange colestipol 5 g / packet 5 to 30 g/day $0.75002 $0.8183 - 4.9098
Colestid Regular colestipol 5 g / packet 5 to 30 g/day $1.51332 $0.8183 - 4.9098
Niacin 500 mg * various DINs 500 mg tablet/caplet/ capsule 6 tablets/caplets/ capsules daily $0.0317 to $0.04563,4 $0.1902 -$0.2736

* Niacin is available from a number of different manufacturers. Price ranges for these are identified in the table above.
1 PPS Pharma, January 2004
2 Ontario Drug Benefit Formulary, April 2004
3 Liste de médicaments, Régie de l´assurance maladie du Québec, October 2003
4 Association québécoise des pharmaciens propriétaires (AQPP), April 2002

In 2003, Ezetrol was also being sold in Germany, Sweden, Switzerland, the United Kingdom and the United States. In compliance with the PMPRB´s Price Guidelines, the introductory prices of Ezetrol in Canada did not exceed the range of prices in those countries; the price in Canada was the lowest of these countries.

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.

Evidence / References:

Fodor JG, Frohlich JJ, Genest JJG, McPherson PR. Recommendations for the management and treatment of dyslipidemia. CMAJ 2000;162(10):1441-7. (electronic)

Anon. Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). National Institute of Health, May 2001, NIH Publication Number 01-3670.

Sudhop T, Tujohann D, Kodal A, et al. Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation 2002;106:1943-8.

Stein E. Results of phase I/II clinical trials with ezetimibe, a novel selective cholesterol absorption inhibitor. Eur Heart J Suppl 2001;(suppl E):E11-6.

Bays HE, Moore PB, Drehobl MA, et al. Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: Pooled analysis of two phase II studies. Clin Ther 2001;23(8):1209-30.

Dujovne CA, Ettinger MP, McNeer JF et al. Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia. Am J Cardiol 2002;90:1092-7.

Knopp RH, Gitter H, Truitt T et al. Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Eur Heart J 2003;24:729-41.

Kosoglou T, Meyer I, Veltri EP, et al. Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin. Br J Clin Pharmacol 2002;54:309-19.

Kosoglou T, Seiberling M, Statkevich P, et al. Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and atorvastatin (abstract). J Am Coll Cardiol 2001;37(suppl A):229A.

Kosoglou T, Meyer I, Musiol B, et al. Pharmacodynamic interaction between fluvastatin and ezetimibe had favourable clinical implications (abstract). Atherosclerosis Suppl 2001;2:89.

Kosoglou T, Fruchart JC, Guillaume M, et al. Coadministration of ezetimibe and fenofibrate leads to favorable effects on Apo CIII, and LDL subfractions. (abstract). Atherosclerosis Suppl 2001;2:89.

Gagne C, Bays HE, Weiss SR et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol 2002;90;1084-91.

Davidson MH, McGarry T, Bettis R et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol 2002;40:2125-34.

Ballantyne CM, Houri J, Notarbartolo A et al. Effect of ezetimibe coadministration with atorvastatin in 628 patients with primary hypercholesterolemia. Circulation 2003;107:2409-15.

Melani L, Mills R, Hassman D et al. Efficacy and safety of ezetimibe coadminstered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Eur Heart J 2003;24:717-28.

Kerzner B, Corbelli J, Sharp S et al. Efficacy and safety of ezetimibe coadministration with lovastatin in primary hypercholesterolemia. Am J Cardiol 2003;91:418-24.

Gagne C, Gaudet D, Brucket E et al. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation 2002;105:2469-75.

Von Bergmann K, Salen G, Lutjohann D, Musliner T, Musser B. Ezetimibe effectively reduces serum plant sterols in patients with sitosterolemia. (abstract). Presented at the 72nd European Atherosclerosis Society Congress, Salzburg, Austria, July 2002. Accessed July 15, 2003.

Worz CR, Bottorff M. Treating dyslipidemic patients with lipid-modifying and combination therapies. Pharmacotherapy 2003;23(5):625-37.

Rosenson RS. The rationale for combination therapy. Am J Cardiol 2002;90(suppl):2K-7K.

McKenney J. Combination therapy for elevated low-density lipoprotein cholesterol: the key to coronary artery disease risk reduction. Am J Cardiol 2002;90(suppl):8K-20K.

Xydakis AM, Ballantyne CM. Combination therapy for combined dyslipidemia. Am J Cardiol 2002;90(suppl):21K-29K.

Bays H. Existing and investigational combination drug therapy for high-density lipoprotein cholesterol. Am J Cardiol 2002;90(suppl):30K-43K.

Brown AS. Use of combination therapy for dyslipidemia a lipid clinic approach. Am J Cardiol 2002;90(suppl):44K-49K.

Davidson MH. Combination therapy for dyslipidemia: safety and regulatory considerations. Am J Cardiol 2002;90(suppl):50K-60K.

Gray J (ed). Therapeutic Choices (3rd ed). Canadian Pharmacists Association, 2000, Ottawa, ON.

Mauro VF, Tuckerman CE. Ezetimibe for management of hypercholesterolemia. Ann Pharmacother 2003;37:839-48.

CCOHTA. Ezetimibe for lowering blood cholesterol. Issues in Emerging Health Technologies 2003;49:1-4.

Date modified: