Isosorbide Dinitrate And Hydralazine Hydrochloride
FDA Drug Information • Also known as: Isosorbide Dinitrate And Hydralazine Hydrochloride
- Brand Names
- Isosorbide Dinitrate And Hydralazine Hydrochloride
- Drug Class
- Nitrate Vasodilator [EPC]
- Route
- ORAL
- Dosage Form
- TABLET, FILM COATED
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Isosorbide dinitrate and hydralazine hydrochloride tablets are a fixed-dose combination of isosorbide dinitrate, a vasodilator with effects on both arteries and veins, and hydralazine hydrochloride, a predominantly arterial vasodilator. Isosorbide dinitrate is described chemically as 1,4:3,6-dianhydro-D-glucitol dinitrate and its structural formula is: Isosorbide dinitrate is a white to off-white, crystalline powder with the empirical formula C 6 H 8 N 2 O 8 and a molecular weight of 236.14. It is freely soluble in organic solvents such as alcohol, chloroform and ether, but is only sparingly soluble in water. Hydralazine hydrochloride is described chemically as 1-hydrazinophthalazine monohydrochloride, and its structural formula is: Hydralazine hydrochloride is a white to off-white, crystalline powder with the empirical formula C 8 H 8 N 4 ·HCl and a molecular weight of 196.64. It is soluble in water, slightly soluble in alcohol, and very slightly soluble in ether. Each isosorbide dinitrate and hydralazine hydrochloride tablet for oral administration contains 20 mg of isosorbide dinitrate and 37.5 mg of hydralazine hydrochloride. The inactive ingredients in isosorbide dinitrate and hydralazine hydrochloride tablets include: anhydrous lactose, microcrystalline cellulose, sodium starch glycolate, colloidal silicon dioxide, magnesium stearate, hypromellose, FD&C Yellow No. 6 aluminum lake, polyethylene glycol, titanium dioxide, polysorbate 80. isdn hcl
What Is Isosorbide Dinitrate And Hydralazine Hydrochloride Used For?
1 INDICATIONS AND USAGE Isosorbide dinitrate and hydralazine hydrochloride tablets are 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 ( 1.1 ) Limitations of use: There is little experience in patients with NYHA class IV heart failure ( 1.2 ) 1.1 Treatment of Heart Failure in Self-identified Black Patients Isosorbide dinitrate and hydralazine hydrochloride tablets are 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. 1.2 Limitations of Use There is little experience in patients with NYHA class IV heart failure.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Isosorbide dinitrate and hydralazine hydrochloride tablets should be initiated at a dose of one isosorbide dinitrate and hydralazine hydrochloride tablet, three times a day. Titrate to a maximum of two tablets three times daily, if tolerated. Although titration of isosorbide dinitrate and hydralazine hydrochloride tablets 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 isosorbide dinitrate and hydralazine hydrochloride 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 ( 2 ) Dosage may be decreased to as little as one-half tablet three times a day if intolerable side effects occur. Efforts should be made to titrate up as soon as side effects subside ( 2 )
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS Most common adverse reactions (≥ 5% more on Isosorbide dinitrate and hydralazine hydrochloride tablets than on placebo) were headache and dizziness ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact A2A Integrated Pharmaceuticals at 1-800-380-6709 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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. Isosorbide dinitrate and hydralazine hydrochloride tablets has been evaluated for safety in 517 heart failure patients in A-HeFT. A total of 317 of these patients received isosorbide dinitrate and hydralazine hydrochloride tablets for at least 6 months, and 220 received isosorbide dinitrate and hydralazine hydrochloride tablets for at least 12 months. In A-HeFT, 21% of the patients discontinued isosorbide dinitrate and hydralazine hydrochloride tablets for adverse reactions compared to 12% who discontinued placebo. Overall, adverse reactions were more common in isosorbide dinitrate and hydralazine hydrochloride tablets -treated than in placebo-treated patients. Table 1 lists adverse reactions reported with an incidence, after rounding, 2% higher on isosorbide dinitrate and hydralazine hydrochloride tablets than on placebo in A-HeFT, regardless of causality. The most common reasons for discontinuing isosorbide dinitrate and hydralazine hydrochloride tablets in the A-HeFT trial was headache (7%). Table 1. Adverse Reactions Occurring in the A-HeFT Study in 2% of Patients Treated with isosorbide dinitrate and hydralazine hydrochloride tablets. Isosorbide dinitrate and hydralazine hydrochloride tablets (N=517) % Placebo (N=527) % Headache 50 21 Dizziness 32 14 Asthenia 14 11 Nausea 10 6 Hypotension 8 4 Sinusitis 4 2 Ventricular tachycardia 4 2 Paresthesia 4 2 Vomiting 4 2 Amblyopia 3 1 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 and hydralazine 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. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of isosorbide dinitrate and hydralazine hydrochloride tablets. 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 isosorbide dinitrate and hydralazine hydrochloride tablets : The following adverse reactions have been identified with use of isosorbide dinitrate and hydralazine hydrochloride tablets. 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 Hydrochloride or Isosorbide Dinitrate: The following reactions have been reported with use of either hydralazine hydrochloride or isosorbide dinitrate. Blood and Lymphatic System Disorders: Blood dyscrasias, agranulocytosis, purpura, eosinophilia, splenomegaly. Eye Disorders: Lacrimation,...
Drug Interactions
7 DRUG INTERACTIONS 7.1 Phosphodiesterase Inhibitors Isosorbide dinitrate and hydralazine hydrochloride tablets 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 isosorbide dinitrate and hydralazine hydrochloride tablets in patients who are taking the soluble guanylate cyclase (sGC) stimulator riociguat. Concomitant use can cause hypotension [see Contraindications (4) ] .
Contraindications
4 CONTRAINDICATIONS Isosorbide dinitrate and hydralazine hydrochloride tablets are contraindicated in patients who are allergic to organic nitrates. Do not use isosorbide dinitrate and hydralazine hydrochloride tablets 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 [see Drug Interactions (7.1) ]. Do not use isosorbide dinitrate and hydralazine hydrochloride tablets in patients who are taking the soluble guanylate cyclase (sGC) stimulator riociguat. Concomitant use can cause hypotension. Patients who are allergic to organic nitrates ( 4 ) Use of phosphodiesterase type 5 (PDE5) inhibitors, such as avanafil, sildenafil, tadalafil, or vardenafil, or soluble guanylate cyclase (sGC) stimulator (riociguat). ( 4 )
Overdosage
10 OVERDOSAGE The signs and symptoms of overdosage with isosorbide dinitrate and hydralazine hydrochloride tablets are expected to be those of excessive pharmacologic effect, i.e., vasodilatation, reduced cardiac output and hypotension, and signs and symptoms include headache, confusion, tachycardia, and generalized skin flushing. Complications can include myocardial ischemia and subsequent myocardial infarction, cardiac arrhythmia, and profound shock. Syncope, coma and death may ensue without appropriate treatment. Human Experience: There are no documented cases of overdosage with isosorbide dinitrate and hydralazine hydrochloride tablets. No deaths from acute poisoning have been reported. Treatment: There is no specific antidote. Support of the cardiovascular system is of primary importance. Shock should be treated with plasma expanders, vasopressors, and positive inotropic agents. The gastric contents should be evacuated, taking adequate precautions to prevent aspiration. These manipulations have to be carried out after cardiovascular status has been stabilized, since they might precipitate cardiac arrhythmias or increase the depth of shock. In patients with renal disease or congestive heart failure, therapy resulting in central volume expansion is not without hazard. Treatment of isosorbide dinitrate overdose in these patients may be difficult, and invasive monitoring may be required. No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of the components of isosorbide dinitrate and hydralazine hydrochloride tablets. Dialysis is not effective in removing circulating isosorbide dinitrate. The dialyzability of hydralazine has not been determined. Methemoglobinemia: Nitrate ions liberated during metabolism of isosorbide dinitrate can oxidize hemoglobin into methemoglobin. There are case reports of significant methemoglobinemia in association with moderate overdoses of organic...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Isosorbide dinitrate and hydralazine hydrochloride tablets contain 20 mg of isosorbide dinitrate and 37.5 mg of hydralazine hydrochloride. They are orange, round, bisected film coated tablets, debossed with “I3” on one side and “1/2” (1 and 2 on each side of the bisect) on the bisected side. NDC 73141-012-03: Bottles of 90 NDC 73141-012-18: Bottles of 180 Store at 25°C (77°F), excursions permitted to 15-30°C (59-86°F). [See USP Controlled Room Temperature.] Keep bottles tightly closed. Protect from light. Dispense in a light-resistant, tight container.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.