Hydralazine and isosorbide dinitrate

Treatment of Heart Failure in Self-identified Black Patients

Hydralazine and isosorbide dinitrate 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.

Limitations of Use

There is little experience in patients with NYHA class IV heart failure.

Hydralazine and isosorbide dinitrate contains a combination of Hydralazine (Hydralazine and Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate)) and Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate). Hydralazine (Hydralazine and Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate)) is a vasodilator. It relaxes (widens) veins and arteries, which makes it easier for your heart to pump. Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate) is in a group of drugs called nitrates. Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate) dilates (widens) blood vessels, making it easier for blood to flow through them and easier for the heart to pump.

Hydralazine and isosorbide dinitrate is used to treat heart failure in certain patients.

Hydralazine and isosorbide dinitrate may also be used for purposes not listed in this medication guide.

Hydralazine and isosorbide dinitrate should be initiated at a dose of one Hydralazine and isosorbide dinitrate Tablet, three times a day. Titrate to a maximum of two tablets three times daily, if tolerated.

Although titration of Hydralazine and isosorbide dinitrate 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

Hydralazine and isosorbide dinitrate Tablet three times a day if intolerable side effects occur. Efforts should be made to titrate up as soon as side effects subside.

How supplied

Dosage Forms And Strengths

The Hydralazine and isosorbide dinitrate (20 mg Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate) and 37.5 mg Hydralazine (Hydralazine and Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate)) hydrochloride) tablets are orange, biconvex, approximately 8 mm in diameter, scored, film-coated, and debossed with “20” on one side over the score and “N” on the other side.

Storage And Handling

Hydralazine and isosorbide dinitrate Tablets contain 20 mg of Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate) and 37.5 mg of Hydralazine (Hydralazine and Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate)) hydrochloride. They are biconvex, approximately 8 mm in diameter, scored, film-coated, orange tablets debossed “20” on one side over the score and “N” on the other side.

NDC 24338-010-18: Bottles of 180

Store at 25°C (77°F), excursions permitted to 15-30°C (59-86°F). Keep bottles tightly closed.

Protect from light. Dispense in a light-resistant, tight container.

Manufactured for: Arbor Pharmaceuticals, LLC, Atlanta, GA 30328. Manufactured by: Kremers Urban Pharmaceuticals Inc., Seymour, IN 47274 USA. Revised: Mar 2015

See also:
What is the most important information I should know about Hydralazine and isosorbide dinitrate?

Hydralazine and isosorbide dinitrate is contraindicated in patients who are allergic to organic nitrates.

​Do not use Hydralazine and isosorbide dinitrate 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 Hydralazine and isosorbide dinitrate in patients who are taking the soluble guanylate cyclase (sGC) stimulator riociguat. Concomitant use can cause hypotension.

Use Hydralazine and isosorbide dinitrate as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Hydralazine and isosorbide dinitrate by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.
• Drinking extra fluids while you are taking Hydralazine and isosorbide dinitrate is recommended. Check with your doctor for instructions.
• Take Hydralazine and isosorbide dinitrate on a regular schedule to get the most benefit from it. Taking Hydralazine and isosorbide dinitrate at the same time each day will help you remember to take it.
• Continue to take Hydralazine and isosorbide dinitrate even if you feel well. Do not miss any doses.
• If you miss a dose of Hydralazine and isosorbide dinitrate, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Hydralazine and isosorbide dinitrate.

Use: Labeled Indications

Heart failure with reduced ejection fraction (HFrEF): Treatment of heart failure as an adjunct to standard therapy in self-identified African-American patients. Note: Based on the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines for the management of heart failure, Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate) in combination with Hydralazine (Hydralazine and Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate)) is effective and recommended as additional therapy to optimal medical therapy for self-identified African-American patients with persistent NYHA class III or IV HFrEF or for patients who do not tolerate an ACE inhibitor or an ARB (ACC/AHA [Yancy 2013]). Some experts recommend Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate) in combination with Hydralazine (Hydralazine and Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate)) in addition to optimal guideline-directed medical therapy for black and nonblack patients with persistent NYHA class III or IV HFrEF, particularly for those with low output states or hypertension, or for patients who do not tolerate an ACE inhibitor, ARB, or angiotensin II-neprilysin inhibitor (Colucci 2019).

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What other drugs will affect Hydralazine and isosorbide dinitrate?

Phosphodiesterase Inhibitors

Hydralazine and isosorbide dinitrate 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 Hydralazine and isosorbide dinitrate in patients who are taking the soluble guanylate cyclase (sGC) stimulator riociguat. Comcomitant use can cause hypotension.

See also:
What are the possible side effects of Hydralazine and isosorbide dinitrate?

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Hydralazine and isosorbide dinitrate has been evaluated for safety in 517 heart failure patients in A-HeFT. A total of 317 of these patients received Hydralazine and isosorbide dinitrate for at least 6 months, and 220 received Hydralazine and isosorbide dinitrate for at least 12 months. In A-HeFT, 21% of the patients discontinued Hydralazine and isosorbide dinitrate for adverse reactions compared to 12% who discontinued placebo. Overall, adverse reactions were more common in Hydralazine and isosorbide dinitrate -treated than in placebo-treated patients. Table 1 lists adverse reactions reported with an incidence, after rounding, ≥ 2% higher on Hydralazine and isosorbide dinitrate than on placebo in A-HeFT, regardless of causality. The most common reasons for discontinuing Hydralazine and isosorbide dinitrate in the A-HeFT trial was headache (7%).

Table 1: Advers e Reactions Occurring in the A-HeFT Study in ≥ 2% of Patients Treated with Hydralazine and isosorbide dinitrate.

In the V-HeFT I and II clinical studies, a total of 587 patients with heart failure were treated with the combination of Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate) and Hydralazine (Hydralazine and Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate)) hydrochloride. The type, pattern, frequency and severity of adverse reactions reported in these studies were similar to those reported in A-HeFT, described above and no unusual adverse reactions were reported.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Hydralazine and isosorbide dinitrate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Use Of Hydralazine and isosorbide dinitrate

The following adverse reactions have been identified with use of Hydralazine and isosorbide dinitrate.

Cardiac Disorders: Palpitations

Ear and labyrinth disorders: Tinnitus, vertigo

Eye Disorders: Eyelid edema, vision blurred

Gastrointestinal Disorders: Abdominal discomfort, constipation

General Disorders and Administration Site Conditions: Facial pain, flushing, chest discomfort, chest pain, peripheral edema

Musculoskeletal and Connective Tissue Disorders: Pain in extremity, myalgia

Nervous Disorders: Dysgeusia, hypoaesthesia, migraine, syncope

Renal and Urinary Disorders: Chromaturia, pulmonary renal syndrome

Respiratory, Thoracic and Mediastinal Disorders: Dyspnea

Reproductive System and Breast Disorders: Erectile dysfunction

Skin and Subcutaneous Tissue Disorders: Erythema, hyperhidrosis, pruritus, face swelling

Use of Hydralazine (Hydralazine and Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate)) Hydrochloride or Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate): The following reactions have been reported with use of either Hydralazine (Hydralazine and Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate)) hydrochloride or Isosorbide Dinitrate (Hydralazine and isosorbide dinitrate).