Hydralazine and Isosorbide dinitrate

BiDil is a combination of isosorbide dinitrate, a nitrate vasodilator, and hydralazine hydrochloride, an arteriolar vasodilator, indicated for: the treatment of heart failure as an adjunct therapy to standard therapy in self-identified black patients to improve survival, prolong time to hospitalization for heart failure and to improve patient-reported functional status. Limitations of use: There is little experience in patients with NYHA class IV heart failure

The mechanism of action underlying the beneficial effects of BiDil in the treatment of heart failure has not been established. Isosorbide dinitrate is a vasodilator affecting both arteries and veins. Its dilator properties result from the release of nitric oxide and the subsequent activation of guanylyl cyclase, and ultimate relaxation of vascular smooth muscle. Several well-controlled clinical trials have used exercise testing to assess the anti-anginal efficacy of chronically-delivered nitrates. In the large majority of these trials, active agents were no more effective than placebo after 24 hours (or less) of continuous therapy. Attempts to overcome nitrate tolerance by dose escalation, even to doses far in excess of those used acutely, have consistently failed. Only after nitrates have been absent from the body for several hours is response to nitrates restored.

BiDil should be initiated at a dose of one BiDil Tablet, three times a day. Titrate to a maximum of two tablets three times daily, if tolerated. Although titration of BiDil can be rapid (3-5 days), some patients may experience side effects and may take longer to reach their maximum tolerated dose. The dosage may be decreased to as little as one-half BiDil Tablet three times a day if intolerable side effects occur. Efforts should be made to titrate up as soon as side effects subside. One tablet three times a day titrated to a maximum tolerated dose up to two tablets three times a day. Dosage may be decreased to as little as one-half tablet three times a day if intolerable side effects occur.

BiDil is contraindicated in patients who are allergic to organic nitrates. Do not use BiDil in patients who are taking PDE-5 inhibitors, such as avanafil, sildenafil, tadalafil, or vardenafil. Concomitant use can cause severe hypotension, syncope, or myocardial ischemia. Do not use BiDil in patients who are taking the soluble guanylate cyclase (sGC) stimulator riociguat. Concomitant use can cause hypotension. Patients who are allergic to organic nitrates. Use of phosphodiesterase type 5 (PDE5) inhibitors, such as avanafil, sildenafil, tadalafil, or vardenafil, or soluble guanylate cyclase (sGC) stimulator (riociguat).

May cause symptomatic hypotension. Symptomatic Lupus Erythematosus Syndromes: Consider discontinuation if clinically appropriate. Myocardial ischemia and angina. Peripheral Neuritis: May be treated with Pyridoxine

Most common adverse reactions (≥ 5% more on BiDil than on placebo) were headache and dizziness

Phosphodiesterase Inhibitors BiDil is contraindicated in patients who are using a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), PDE5 inhibitors such as avanafil, sildenafil, vardenafil, and tadalafil have been shown to potentiate the hypotensive effects of organic nitrates. Do not use BiDil in patients who are taking the soluble guanylate cyclase (sGC) stimulator riociguat. Concomitant use can cause hypotension.

Store at 25°C (77°F), excursions permitted to 15-30°C (59-86°F). Protect from light.