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Nitrates, Package Inserts, and the Food and Drug Administration: Title and subTitle BreakA Clinical Paradox FREE

Jonathan Abrams, MD
[+] Author Affiliations

Reprint requests to Division of Cardiology, University of New Mexico School of Medicine, Albuquerque, NM 87131 (Dr Abrams).


JAMA. 1981;246(14):1557-1558. doi:10.1001/jama.1981.03320140045027
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A DILEMMA exists regarding the usefulness of long-acting nitrate preparations in patients with angina pectoris or congestive heart failure and the present Food and Drug Administration approved package inserts (regulatory monographs), outlining nitrate dosage regimens and clinical indications. This group of drugs, whether given orally or topically, has been documented to be bioavailable and clinically effective for four to six hours or longer.1 Yet the FDA continues to classify all oral long-acting nitrate preparations as being only "possibly effective." In addition, maximal dosages currently recommended by the pharmaceutical manufacturers are considerably smaller than the amounts found to be safe, necessary, and efficacious in a variety of recent investigations.2,3 Finally, promotional literature, including the package insert, may not recommend nitrates for use in vasodilator therapy of congestive heart failure. No pharmaceutical company has yet submitted a New Drug Application to the FDA for use of any long-acting nitrate in

REFERENCES

Abrams J:  Usefulness of long-acting nitrates in cardiovascular disease . Am J Med 1978;;64:183-186.
Franciosa JA, Nordstrom LA, Cohn JN:  Nitrate therapy for congestive heart failure . JAMA 1978;;240:443-446.
Danahy DT, Aronow WS:  Hemodynamics and antianginal effects of high dose oral isosorbide dinitrate after chronic use . Circulation 1977;; 56:205-212.
Archer J:  A guide into chaos: Resist it . JAMA 1974;;227:1397-1398.
Archer J:  Instrument or impediment? The regulatory monograph in medical communications . JAMA 1972;;220:1474-1477.
Needleman P, Lang S, Johnson FM:  Organic nitrates: Relationship between biotransformation and rational angina pectoris therapy . J Pharmacol Exp Ther 1972;;18:489-497.
Reichek N, Goldstein RE, Redwood DR, et al:  Sustained effects of nitroglycerin ointment in patients with angina pectoris . Circulation 1974;;50:348-352.
Abrams J:  Pharmacology of nitroglycerin and long-acting nitrates and their usefulness in the treatment of chronic congestive heart failure , in Gould L, Reddy CVR (eds): Vasodilator Therapy for Cardiac Disorders . Mount Kisco, NY, Futura Publishing Co Inc, 1979;, pp 129-167.
Abrams J:  Nitroglycerin and long-acting nitrates . N Engl J Med 1980;;302:1234-1237.

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Abrams J:  Usefulness of long-acting nitrates in cardiovascular disease . Am J Med 1978;;64:183-186.
Franciosa JA, Nordstrom LA, Cohn JN:  Nitrate therapy for congestive heart failure . JAMA 1978;;240:443-446.
Danahy DT, Aronow WS:  Hemodynamics and antianginal effects of high dose oral isosorbide dinitrate after chronic use . Circulation 1977;; 56:205-212.
Archer J:  A guide into chaos: Resist it . JAMA 1974;;227:1397-1398.
Archer J:  Instrument or impediment? The regulatory monograph in medical communications . JAMA 1972;;220:1474-1477.
Needleman P, Lang S, Johnson FM:  Organic nitrates: Relationship between biotransformation and rational angina pectoris therapy . J Pharmacol Exp Ther 1972;;18:489-497.
Reichek N, Goldstein RE, Redwood DR, et al:  Sustained effects of nitroglycerin ointment in patients with angina pectoris . Circulation 1974;;50:348-352.
Abrams J:  Pharmacology of nitroglycerin and long-acting nitrates and their usefulness in the treatment of chronic congestive heart failure , in Gould L, Reddy CVR (eds): Vasodilator Therapy for Cardiac Disorders . Mount Kisco, NY, Futura Publishing Co Inc, 1979;, pp 129-167.
Abrams J:  Nitroglycerin and long-acting nitrates . N Engl J Med 1980;;302:1234-1237.
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To understand the clinical management of acute heart failure syndromes.
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