Bayer supports study showing generic nifedipine not bioequivalent to
Adalat(R) XL(R)

Letter to the editor published in International Journal of Clinical Pharmacology and Therapeutics

TORONTO, May 21 /CNW/ - Bayer Inc. today responded to Professor Marvin Meyer's letter to the editor, entitled: "Critical questions concerning the validity of the Bayer study report of differences in bioavailability between 60 mg of nifedipine osmotic push-pull systems after fasted and fed administration" and published in the online edition of the International Journal of Clinical Pharmacology and Therapeutics. Bayer responded to the clinical relevance of the differences in formulation and dissolution behaviour and the delayed absorption of Mylan's extended release nifedipine. Bayer supports the findings of the study, published in the February issue (Vol. 48 - No. 2/2010) of the International Journal of Clinical Pharmacology and Therapeutics(1), which demonstrate that the extended release generic nifedipine product is not bioequivalent to Adalat(R) XL(R) (nifedipine extended release tablets)(2).

"Patient safety is Bayer Inc.'s top priority", said Dr. Shurjeel Choudhri, Head, Medical and Scientific Affairs, Bayer Inc. "We strongly encourage health care providers to monitor their patients who switch to the generic nifedipine product."

The Anschutz et al study(1) shows that Bayer's nifedipine extended release 60 mg product and Mylan Nifedipine Extended Release 60 mg are not bioequivalent. Available safety and clinical data indicate that switching from Bayer's nifedipine 60 mg product to the generic product can lead to loss of efficacy and adverse events.(3)

Adalat(R) XL(R), a clinically proven blood pressure control medication, delivers a relatively constant plasma level of nifedipine over 24 hours. This helps patients maintain a stable blood pressure level while avoiding unwanted side effects that may be seen with shorter acting agents.(4) The generic nifedipine is also a time-release delivery product, but the study clearly demonstrated the existence of a lag time and reduced total nifedipine release. Safety and clinical data indicate that switching from Adalat(R) XL(R) 60 mg to the generic product can lead to loss of efficacy and adverse events.(3)

Bayer has a longstanding commitment to the cardiovascular health of Canadians and will continue to actively market Adalat(R) XL(R).

To view the online version of the International Journal of Clinical Pharmacology and Therapeutics, visit: http://www.dustri.com/nc/journals-in-english/mag/int-journal-of-clinical-pharmacology-and-therapeutics.html.

About Adalat(R) XL(R)

Adalat(R) (nifedipine) is a well-established calcium channel blocker (CCB) that has been widely used as an antihypertensive and anti-anginal agent for many years. The unique formulation, also known as GITS, means that Adalat(R) XL(R) consists of a drug reservoir surrounded by a semi-permeable membrane, which has a single precision-laser-drilled pore on the drug-reservoir side. The Adalat(R) XL(R) formulation delivers a constant plasma level of nifedipine over 24 hours, avoiding unwanted side effects that may be seen with shorter-acting agents. The clinical efficacy of Adalat(R) XL(R), including in patients with increased cardiovascular risk, has been demonstrated in a number of important clinical trials. ACTION(5) extends the evidence base for Adalat(R) XL(R) established by the INSIGHT(6) and the ENCORE trials.(7),(8) In addition to its blood pressure lowering effect, these studies confirmed that Adalat(R) XL(R) has vascular-protective properties that help further reduce cardiovascular risk, which translates into improved clinical outcomes. Recent research suggests that the results of studies like INSIGHT and ACTION, can only be applied to Adalat(R) XL(R) - generic long-acting formulations of nifedipine have different pharmacokinetic and pharmacodynamic properties(1),(9),(10) Adalat(R) XL(R) is also branded in some markets as Adalat(R) OROS (Oral Release Osmotic System) or Adalat(R) GITS (Gastro-Intestinal Therapeutic System).

Adalat(R) XL(R) is contraindicated in: pregnancy, during lactation, and in women of childbearing potential; in patients with severe hypotension or cardiovascular shock and in patients with hypersensitivity to Adalat(R) XL(R). Nifedipine must not be used in combination with rifampicin because insufficient plasma levels of nifedipine may result due to enzyme induction.

In hypertension, the most common adverse events reported with Adalat(R) XL(R) were edema, which was dose-related and ranged in frequency from approximately 10 to 30% in the 30 to 120 mg dose range, headache (16.6%), fatigue (6.2%), dizziness (4.4%), constipation (3.5%) and nausea (3.5%).

In angina, the most common adverse events reported were edema (10.1%), headache (3.1%), angina pectoris (3.1%).

For complete information, please see the Product Monograph.

About Bayer Inc.

Bayer Inc. (Bayer) is a Canadian subsidiary of Bayer AG, an international research-based group with core businesses in health care, crop science and innovative materials. Headquartered in Toronto, Ontario, Bayer Inc. operates the Bayer Group's HealthCare and MaterialScience businesses in Canada. Bayer CropScience Inc., headquartered in Calgary, Alberta operates as a separate legal entity in Canada. Together, the companies play a vital role in improving the quality of life for Canadians - producing products that fight diseases, protecting crops and animals, and developing high-performance materials for applications in numerous areas of daily life. Canadian Bayer facilities include the Toronto headquarters and offices in Montréal and Calgary.

Bayer Inc. has approximately 800 employees across Canada and had sales of $853 million CDN in 2009. Globally, the Bayer Group had sales of over 31 billion Euro in 2009. Bayer Inc. invested approximately $50 million CDN in research and development in 2009. Worldwide, the Bayer Group spent the equivalent of over 2.7 billion Euro in 2009 in R&D. For more information, go to www.bayer.ca.

Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer's public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

    
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(1) Anschutz et al. Differences in bioavailability between 60 mg of nifedipine osmotic push-pull systems after fasted and fed administration. International Journal of Clinical Pharmacology and Therapeutics; Vol. 48 - No. 2/2010 (158-170): http://www.dustri.com/nc/journals-in-english/mag/int-journal-of-clinical-pharmacology-and-therapeutics/vol/volume-48/issue/february-17.html

(2) Marketed in some countries as Adalat(R) OROS or Adalat(R)GITS (Gastro Intestinal Therapeutic System).

(3) Pollak PT. Therapeutically relevant blood pressure differences with two nifedipine (60 mg) osmotic delivery systems of differing design: three case reports. International Journal of Clinical Pharmacology and Therapeutics; 2010; Vol. 48: 400-404.

(4) Adalat(R) XL(R) Product Monograph, December 8, 2009.

(5) Poole-Wilson PA, Lubsen J, Kirwan BA, et al. Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial. Lancet 2004;364:849-57.

(6) Brown MJ, Palmer CR, Castaigne A, et al. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet 2000;356:366-72.

(7) ENCORE I Study Group. Effect of nifedipine and cerivastatin on coronary endothelial function in patients with coronary artery disease: the ENCORE I study (Evaluation of Nifedipine and Cerivastatin On Recovery of coronary Endothelial function). Circulation 2003;107:422-8.

(8) Luscher T, Pieper M, Tendera M, et al. A randomized placebo-controlled study on the effect of nifedipine on coronary endothelial function and plaque formation in patients with coronary artery disease: the ENCORE II study. Eur Heart J 2009;30:1590-7.

(9) Wonnemann M, Schug B, Anschutz M, et al. Comparison of two marketed nifedipine modified-release formulations: an exploratory clinical food interaction study. Clin Ther 2008;30:1-11.

(10) Brown M, Toal C. Formulation of long-acting nifedipine tablets influences the heart rate and sympathetic nervous system response in hypertensive patients. Br J Clin Pharmacol 2008;65:646-52.

For further information: Laura Burns, Senior Business Communications Partner, Bayer Inc., [phone], [email protected]; Martha Linton, Hill & Knowlton, [phone], [email protected]