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NITROGLYCERIN PATCH LONG-TERM USE SHOULD INCLUDE TREATMENT-FREE INTERVAL

Executive Summary

NITROGLYCERIN PATCH LONG-TERM USE SHOULD INCLUDE TREATMENT-FREE INTERVAL in order to avoid patient tolerance to the drug, a clinical investigator from the German Heart Center in Munich, Germany recommended in a presentation at the American Heart Assn.'s four-day annual scientific meeting in Washington, D.C. Nov. 10-13. As part of a team presentation on nitroglycerin tolerance at the "Ischemic Heart Disease-Drug Therapy" session on Nov. 13, Dr. Kraus concluded that "effective long-term treatment requires an adequately long-term treatment-free interval." the German MD noted that even when using lower dose and short treatment-free intervals, "tolerance development cannot be avoided." In their study, "Nitroglycerin Patches in Coronary Artery Disease: Can Tolerance Development Be Avoided Through An Interval Therapy?" Kraus, et al, investigated the anti-ischemic effect of nitroglycerin patches at an intermediate dosage (15 mg/24 h) for a period of three days with a nightly therapy-free interval of 10 hours prior to the third application. In their study, the German investigators observed a "clear attenuation of action within 8-14 hours" after the first application of the 15 mg nitroglycerin patch. Kraus noted that a short-term 10-hour patch-free interval after two days of treatment was too short of a therapeutic holiday to allow for a return to initial efficacy. Other researchers reporting study results at the session generally accepted that, while nitroglycerin and nitrate treatment is clinically effective, tolerance can develop rapidly. "It is a drug tolerance problem," Udho Thadani, MD, (OUHSC, Oklahoma City, OK), said in response to questions on his study, "Dose Titration and Duration of Effects of Transdermal Nitroglycerin Patches in Angina Pectoris." Patches increased tradmill walking time at 4 hours but not at 24 hours, and there was no improvement after 48 hours, Thadani reported. In addition, three other presentations during the session demonstrated rapid patient tolerance to nitrate tablets. In conclusion, several investigators proposed sufficient drug-free intervals or lower doses to maintain treatment response. A daily "nitratefree" interval after two weeks administration of 80 mg slow release isosorbide dinitrate and a "daily valley" of drug plasma level were separate suggestions proposed by two different groups of investigators from the University of Munich, West Germany. In a second presentation, Thadani discussed the development of patient tolerance to an active metabolite of isosorbide dinitrate, isosorbide-5-mononitrate. During once-a-day therapy, slow release isosorbide-5-mononitrate did not exert any antianginal or anti-ischemic effects at 20 or 24 hours . . . despite adequate plasma levels," Thadani said. One nitrate presentation did not focus on problems with patient tolerance. John Parker, MD, Queen's University, Kingston, Canada, discussed the benefits of a nitroglycerin spray recently approved by FDA. Calling the spray an effective prophylaxis for exercise-induced angina, Parker said it will be marketed in the U.S. in .4 mg doses, "comparable to .4 sublingual dose." Parker touted the prompt action and several years' shelf life as advantages of the spray over sublingual administration. Rorer said its Nitrolingual aerosol spray will be launched in early 1986 ("The Pink Sheet" Nov. 11, In Brief).
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