SAFETY PROFILE OF THE COMBINATION OF VERAPAMIL AND TRANDOLAPRIL

Advantages of drug combinations The particular advantage usually sough t with antihypertensive drug combinations is an improvement in blood p ressure control. However, at least as important is a consideration of adverse reactions and the safety of the combination compared to monoth erapy. Verapamil and trandolapril The fixed-dose combination of the ca lcium antagonist verapamil and the angiotensin converting enzyme (ACE) inhibitor trandolapril consists of a sustained-release (SR) tablet fo rmulation of verapamil, and an instant-release granulation of trandola pril, 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 f or 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 combinat ion of 180 mg verapamil + 2 mg trandolapril per day. Constipation and cough, which are considered to be specific adverse effects, occurred i n 3.4% and 2.4% of patients on monotherapy with verapamil and trandola pril, respectively, but in only 2.9% and 1.9% of patients on combinati on therapy, respectively. Electrocardiograph recordings have not shown a prolongation of the P-Q interval to >200 ms (placebo 1.1%, verapami l 1.2%, trandolapril 1.8% combination 1.2%). No specific changes were found in the laboratory parameters. Conclusions In summary, the profil e of adverse drug reactions of the fixed-dose combination of verapamil and trandolapril consists the typical side effects of the monocompoun ds, The frequencies of adverse events were equal to or even lower than those far the monocompounds or of placebo.