1. BiDil Prescribing Information
2. Isosorbide dinitrate Prescribing Information. Par Pharmaceuticals; February 2002.
3. Hydralazine hydrochloride Prescribing Information. Par Pharmaceuticals; June 2003.
4. Taylor AL, Ziesche S, Yancy C, et al, for the African-American Heart Failure Trial Investigators. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004;351:2049-2057.
5. Yancy CW. Heart failure in African Americans: a cardiovascular enigma. J Card Fail. 2000;6(3):183-186.
6. Dries DL, Exner DV, Gersh BJ, et al. Racial differences in the outcome of left ventricular dysfunction. N Engl J Med. 1999; 22:791-794.
7. Bourassa MG, Gurné O, Bangdiwala SI, et al, for the SOLVD Investigators. Natural history and patterns of current practice in heart failure. J Am Coll Cardiol. 1993;22(suppl A):14A-19A.
8. Thom T, Haase N, Rosamond W, et al. Heart disease and stroke statistics—2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2006:113;e85-e151.
9. U.S. Census Bureau. Statistical Abstract of the United States: 2000. 119th ed. Washington, DC: US Census Bureau; 2000.
10. Yancy CW. Heart failure in African Americans: pathophysiology and treatment. J Card Fail. 2003;9(suppl 3):S210-S215.
11. Rector TS, Cohn JN. Minnesota Living With Heart Failure® Questionnaire. Available at www.mlhfq.org.
12. Drexler H, Hasenfuss G. Physiology of the normal and failing heart. In: Crawford MH, DiMarco JP, Paulus WJ, eds. Cardiology. 2nd ed. Edinburgh: Mosby; 2004.
13. Pierpont GL, Cohn JN, Franciosa JA. Combined oral hydralazine-nitrate therapy in left ventricular failure. Chest. 1978;73:8-13.
14. Massie B, Chatterjee K, Werner J, Greenberg B, Hart R, Parmley WW. Hemodynamic advantage of combined administration of hydralazine orally and nitrates nonparenterally in the vasodilator therapy of chronic heart failure. Am J Cardiol. 1977;40:794-801.
15. Food and Drug Administration. Orange Book. http://www.accessdata.fda.gov/scripts/cder/ob/docs/tempai.cfm. Accessed March 9, 2007
16. NDA 20-727: FDA Clinical Pharmacology/Biopharmaceutics Review: Submission Date: July 3, 1996
17. Münzel T, et al. Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase: A new action for an old drug. J Clin Invest. 1996;98(6):1465-1470
18. Hare JM. Nitroso-redox balance in the cardiovascular system. N Engl J Med. 2004;351:2112-2114
Important information about BiDil®
(isosorbide dinitrate/hydralazine hydrochloride):
INDICATIONS AND USAGE
BiDil is indicated for the treatment of heart failure as an adjunct to standard therapy in self-identified black patients to improve survival, to prolong time to hospitalization for heart failure, and to improve patient-reported functional status. There is little experience in patients with NYHA class IV heart failure. Most patients in the clinical trial supporting effectiveness (A-HeFT) received a loop diuretic, an angiotensin converting enzyme inhibitor or an angiotensin II receptor blocker, and a beta blocker, and many also received a cardiac glycoside or an aldosterone antagonist.
IMPORTANT SAFETY INFORMATION
BiDil is contraindicated in patients who are allergic to organic nitrates.
WARNINGS AND PRECAUTIONS
Augmentation of the vasodilatory effects of isosorbide dinitrate by phosphodiesterase inhibitors such as sildenafil, vardenafil, or tadalafil could result in severe hypotension. The time course and dose dependence of this interaction have not been studied. Reasonable supportive care should consist of those measures used to treat a nitrate overdose with elevation of the extremities and central volume expansion.
Treatment with hydralazine hydrochloride may produce a clinical picture simulating systemic lupus erythematosus including glomerulonephritis. If systemic lupus erythematosus-like symptoms occur in patients treated with BiDil, discontinuation of BiDil should be considered only after a thorough benefit-to-risk assessment. Symptoms and signs of systemic lupus erythematosus usually regress when hydralazine hydrochloride is discontinued but residua have been detected many years later. Long-term treatment with steroids may be necessary.
Symptomatic hypotension, particularly with upright posture, may occur with even small doses of BiDil. BiDil should be used with caution in patients who may be volume depleted or who are already hypotensive.
Hydralazine hydrochloride can cause tachycardia potentially leading to myocardial ischemia and angina attacks. Careful clinical and hemodynamic monitoring is recommended when BiDil is administered to patients with acute myocardial infarction to avoid the hazards of hypotension and tachycardia.
Hydralazine hydrochloride has been associated with peripheral neuritis, evidenced by paresthesia, numbness, and tingling, which may be related to an antipyridoxine effect. Pyridoxine should be added to BiDil therapy if such symptoms develop.
Isosorbide dinitrate therapy may aggravate angina associated with hypertrophic cardiomyopathy.
Headache and dizziness were the most frequent adverse events occurring at an incidence greater than 2% in clinical studies compared to placebo. Others included chest pain, asthenia, nausea, bronchitis, hypotension, sinusitis, ventricular tachycardia, palpitations, hyperglycemia, rhinitis, paresthesia, vomiting, amblyopia, hyperlipidemia, and tachycardia.
The full Prescribing Information for BiDil is available here.