DIFFERENCES IN 24-H AMBULATORY BLOOD PRESSURE MONITORING (ABPM) IN PATIENTS SWITCHED BETWEEN DIFFERING EXTENDED-RELEASE FORMULATIONS OF NIFEDIPINE: DOSE SCALING BETWEEN 30-MG VS. 60-MG DOSES

Abstract

Pharmacies frequently switch patients between the two once-daily osmotic pump formulations of nifedipine-extended-release (nifedipine-XL) deemed to be bioequivalent in Canada. We recently demonstrated statistically significant and clinically important differences in 24-h systolic blood pressures (SBP) when patients are switched between the two 60-mg versions of nifedipine-XL (the original two-compartment pump sold under the brand name Adalat XL = AdN and the newer one-compartment pump sold as Mylan-nifedipine-XL = MyN). We report the comparison of SBP results from ABPM studies on patients switched between the two 30-mg versions of nifedipine-XL (AdN and MyN), and contrast with the 60-mg results using the same protocol. Using a randomized-block, cross-over design, 40 patients receiving morning-dosed AdN or MyN 30 mg were studied using 24-h ABPM at the end of each 2-wk daily dosing period. We compared 24-h SBP (06:00 h - 06:00 h) and terminal 8-h SBP (22:00 h - 06:00 h) for each formulation. Mean ± SE 24-h SBP was 132.6 ± 1.6 mmHg with AdN, and 133.5 ± 1.6 mmHg with MyN (p=0.16). For the terminal 8 h, mean ± SE nocturnal SBP was 123.7 ± 2.0 mmHg with AdN and 125.4 ± 1.9 mmHg with MyN (p=0.18). Plots of the SBP 30-mg curves followed the same pattern as the 60-mg formulations. Some patients had terminal 8-h SBP 22 mmHg higher while taking MyN than while receiving AdN. Patients taking the MyN version of 30-mg nifedipine tended to have less blood pressure control. Although this difference was not statistically significant for the 30-mg group as a whole, some individuals experienced large differences when switched. The lesser overall difference seen when switching between the 30-mg versions (vs. with the 60-mg versions) could be due to: a halving of dose effects on SBP at the lower dose; or improvements in the MyN formulation characteristics made in the interval following the prior release of the 60-mg tablet. However, differences in the release pattern between the first vs. zero-order delivery technologies are conserved in the new MyN tablet, although less apparent at the smaller dose size. While not important on a population basis, switching between the 30-mg formulations of nifedipine-XL by pharmacies can still cause unexplained variability in SBP control in some patients, with unintended management consequences. Both nifedipine formulations work, but given the lack of cost differential, avoiding potential SBP inconsistencies from switches between different delivery technologies remains a reasonable precaution.