Safety profile of the combination of verapamil and trandolapril

ADVANTAGES OF DRUG COMBINATIONS: The particular advantage usually sought with antihypertensive drug combinations is an improvement in blood pressure control. However, at least as important is a consideration of adverse reactions and the safety of the combination compared to monotherapy. VERAPAMIL AND TRANDOLAPRIL: The fixed-dose combination of the calcium antagonist verapamil and the angiotensin converting enzyme (ACE) inhibitor trandolapril consists of a sustained-release (SR) tablet formulation of verapamil, and an instant-release granulation of trandolapril, a prodrug of the active metabolite trandolaprilat. The two drugs are suitable for combined administration since the half-life, time to maximal plasma concentration and peak: trough ratio are very similar for each drug. ADVERSE EFFECT PROFILE: In randomized placebo-controlled studies adverse events were observed in 25.6% of patients on placebo, 34.2% on verapamil SR, 27.3% on trandolapril and 27.9% on the combination of 180 mg verapamil + 2 mg trandolapril per day. Constipation and cough, which are considered to be specific adverse effects, occurred in 3.4% and 2.4% of patients on monotherapy with verapamil and trandolapril, respectively, but in only 2.9% and 1.9% of patients on combination therapy, respectively. Electrocardiograph recordings have not shown a prolongation of the P-Q interval to > 200 ms (placebo 1.1%, verapamil 1.2%, trandolapril 1,8%, combination 1.2%). No specific changes were found in the laboratory parameters. CONCLUSIONS: In summary, the profile of adverse drug reactions of a fixed-dose combination of verapamil and trandolapril consists the typical side effects of the monocompounds. The frequencies of adverse events were equal to or even lower than those for the monocompounds or of placebo.