Study: Generic nifedipine product not bioequivalent to Adalat XL

BAYER INC.Feb 4 2010

- Total exposure to generic nearly 20 per cent lower when taken after meal

An extended release generic nifedipine product (Mylan-Nifedipine extended release 60 mg formerly Gen-Nifedipine extended release 60mg, Genpharm ULC) is not bioequivalent to the Canadian originator product, Adalat(R) XL(R), according to the results of a study recently published in the International Journal of Clinical Pharmacology and Therapeutics. Based on the study results from in vitro and in vivo tests, the generic extended release nifedipine product has a delayed onset of drug release compared to the originator which is especially noticeable in the fed state. When the tablet is taken after a standard high fat meal, the total exposure to the generic nifedipine is almost 20 per cent lower than with Adalat(R) XL(R).

"With drugs like nifedipine, we see a close relationship between plasma concentration and efficacy. A change in bioavailability could impact blood pressure," said principal investigator Dr. Frank Donath from SocraTec R&D, Oberursel, Germany. "Since it is widely accepted that small reductions in blood pressure can reduce long-term mortality, these findings may be relevant to physicians treating hypertensive patients."

The single centre, open-label, randomized phase I study was carried out with 26 healthy male subjects. Using a 4-period crossover study design, the participants were given 60 mg of either a Canadian marketed batch of the generic product (Mylan-Nifedipine extended release 60 mg formerly Gen-Nifedipine extended release 60mg, Genpharm ULC) or Bayer's once-daily nifedipine product (marketed in Canada as Adalat(R) XL(R)) either in a fed or a fasting state. Blood sampling was conducted regularly throughout the study to determine the plasma concentration of nifedipine. An in vitro dissolution test was carried out prior to the study. The in vitro dissolution curves show a later onset and considerably lower quantity of nifedipine release from the generic nifedipine compared to Bayer's once-daily nifedipine product. These differences in the completeness of drug release were also observed in the pharmacokinetic study. The total exposure of the generic nifedipine was nearly 20 per cent lower than with Bayer's once-daily nifedipine product in the fed state and almost 10 per cent lower in the fasting state.

"It is fairly common to assume that prescription medicines that become available on a generic basis can automatically be used in place of the original product," said Shurjeel Choudhri, Head, Medical and Scientific Affairs, Bayer Inc. "These study results indicate that the generic version does not match the unique pharmacokinetic properties of Adalat(R) XL(R). As a company, we encourage health care providers to carefully evaluate their patients who switch to this generic medication to determine if optimal results are being achieved."

While a number of previous studies have shown that several generic nifedipine products are not bioequivalent to Adalat(R) XL(R), this study is the first and only published one to compare the originator head to head with a generic nifedipine formulation based on the gastro intestinal intestinal therapeutic system (GITS) principle.