Limited reciprocal pharmacokinetic interaction between milnacipran and CYP isoenzymes would confer flexibility in the therapeutic use of the drug when combined with antidepressants. Drug-drug interaction risk would be low, even if the combined treatments were likely to inhibit CYP2D6 and CYP2C19 isoenzyme activities.

Rofecoxib increased plasma concentrations of the biologically less active R(+) warfarin, which accounted for a small increase in INR. The approximately 8% increase in INR at steady state with warfarin co-administered with 25 mg of rofecoxib is not likely to be clinically important in most patients taking warfarin. However, standard monitoring of INR values should be conducted when therapy with rofecoxib is initiated or changed, particularly in the first few days, for patients receiving warfarin.

Simultaneous oral administration of 10 mg manidipine and 30 mg delapril does not significantly alter the pharmacokinetics of either drug or that of their principal metabolites.

The fixed combination tablet of 10 mg manidipine and 30 mg delapril is bioequivalent to mono-ingredient tablets. At steady-state, the pharmacokinetic and pharmacodynamic profiles in young and elderly subjects undergo minor changes and indicate negligible accumulation. Drug exposure is higher in elderly subjects.