Generic nifedipine SR is not bioequivalent to Adalat GITS

Shorter lag time and less inter-individual variability

Mean plasma concentration versus time curves for Adalat GITS vs generic nifedipine extended release (Osmotica) show notable differences1.

Under fed administration
  • Lag time was shorter for Adalat GITS1
  • The overall concentration (AUC) for generic nifedipine was approximately 20% less than that of Adalat GITS1
  • Point estimates for the the ratios of AUC0-last and Cmax were determined to be around 80% – bioequivalence was thus not reached1
Adalat GITS has lower inter-individual variability than generic nifedipine SR2.

Individual time course profiles for plasma concentrations under fed conditions demonstrate much lower take over individual variability for Adalat GITS compared with the generic formulation2:

Switching from Adalat GITS to generic nifedipine adversely affects BP control

Several patients in a single clinic demonstrated a >10 mmHg increase in SBP following substitution of a generic nifedipine SR formulation for the previously used Adalat GITS3. Three patients agreed to participate in N of 1 studies to investigate this phenomenon3.

In each of seven switches from Adalat GITS to generic nifedipine, there was an increase in SBP ≥8 mmHg3. Of the 14 switches, 13 demonstrated lower SBP with Adalat GITS (a mean of 17.3 mmHg lower)3.

Generic nifedipine SR significantly increases norepinephrine after first dose

The effect of switching between Adalat GITS and generic nifedipine SR (Coracten XL) was investigated in an open-label, randomised, crossover study involving 44 patients4.

Initial administration of generic nifedipine
  • Significant rise in plasma norepinephrine concentrations (p=0.005 vs Adalat GITS)4
  • Increased heart rate4
Initial administration of Adalat GITS
  • No relevant change in plasma norepinephrine concentrations4
  • No relevant heart rate changes4

References

  1. Anschütz M, et al. Int J Clin Pharmacol Ther 2010;48:158-70.
  2. Wonnemann M, et al. Int J Clin Pharm Ther 2006;44:38-48.
  3. Pollak PT. Int J Clin Pharm Ther 2010;48:400-4.
  4. Brown MJ, et al. Br J Clin Pharmacol 2007;65:646-53.