[OP.4C.10] CLINICALLY IMPORTANT DIFFERENCES IN SYSTOLIC AMBULATORY BLOOD PRESSURE IN PATIENTS SWITCHED BETWEEN ALTERNATE NIFEDIPINE OSMOTIC DELIVERY FORMULATIONS

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Abstract

Objective:

Anecdotal evidence suggested clinically important systolic blood pressure (SBP) differences occurred in our patients whose nifedipine was being switched by pharmacies between AdN (Adalat XL – a formulation providing zero order release from the GastroIntestinal Therapeutic System - GITS) and MyN (Mylan-nifedipine ER - a formulation providing a delayed first-order release from the Osmotic Release Oral System - OROS). In vitro dissolution studies showed greater lag time to initial release from MyN and declining release at end of dosing interval. The objective of this study was to use Ambulatory Blood Pressure Monitoring (ABPM) to examine whether differences in overall effectiveness and duration of action exist between these two nifedipine formulations.

Design and method:

A randomized cross-over trial studied 20 patients receiving daily morning AdN vs. MyN 60 mg. After each 2-week period, 24-h ABPM was done. SBP data for 24 h and last 8 h (22:00 - 06:00 h) were examined using a Generalized Additive Mixed Model (GAMM). The software (R) used 2560 data points to model SBP population curves and compare them statistically.

Results:

GAMM of SBP over time showed MyN mean ± SE SBP was 2.59 ± 1.09 mmHg higher for 24 h (p = 0.0173) and 4.18 ± 1.6 mmHg higher for last 8 h (p = 0.0098). Mean 24-h SBP was >  = 2 mmHg higher, while taking MyN in 50% of patients while SBP for last 8 h ranged as high as 18 mmHg higher while taking MyN.

Conclusions:

Clinically meaningful differences in SBP were seen in a cohort of patients when taking MyN compared to when they were taking AdN. This was likely based on differences in release profiles. For nifedipine, a potent vasodilator with a steep dose-response relationship and a 2-hour half-life, differences in timing and/or extent of delivery over as little as 6 h could allow clinically important changes in SBP. These data support the conclusion that formulations using differing release technologies are not suitable for bioequivalence testing. Undisclosed switching of nifedipine formulations by pharmacies can lead to an undesirable increase in variability in BP control.

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