The BiDil Difference
BiDil is indicated for the treatment of heart failure as an adjunct to standard therapy in self-identified African American 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.
In 1997 the U.S. Food and Drug Administration (FDA) determined that the prospectively defined results of the Veteran's Affairs Vasodilator Heart Failure Trials (V-HeFT I and II) were not adequate to support approval of BiDil for the treatment of heart failure at that time because those studies did not show convincing evidence of a survival benefit. However, when NitroMed presented retrospective analyses of V-HeFT I and II to the FDA in 2000, indicating a positive survival signal in African Americans, the FDA indicated that a clearly positive trial in African Americans could provide a basis for approval of BiDil for this particular heart failure population.
The African American Heart Failure Trial (A-HeFT) - co-sponsored by NitroMed and the Association of Black Cardiologists, Inc. - was the first study conducted in a heart failure population in which all of the participants identified themselves as African American. This Phase III trial commenced in May 2001 and evaluated the effects of BiDil, a fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride, in self-identified African Americans when taken in addition to standard heart failure therapies. After a unanimous recommendation from the independent Data Safety Monitoring Board (DSMB) and Steering Committee in July 2004, A-HeFT was halted early due to a significant survival benefit seen with the drug plus standard therapy as compared to standard therapy alone.
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.