Isosorbide Dinitrate / Hydralazine Hydrochloride

Trade Names:
BiDil
- Tablets 20 mg isosorbide dinitrate plus 37.5 mg hydralazine hydrochloride

Pharmacology

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Mechanism of beneficial effects in treatment of heart failure have not been identified.

Isosorbide dinitrate relaxes vascular smooth muscle in arteries and veins by releasing nitric oxide with subsequent activation of guanylyl cyclase.

Hydralazine selectively dilates arterial smooth muscle. Animal studies suggest it may also mitigate tolerance to nitrates.

Pharmacokinetics

Special Populations

Isosorbide dinitrate concentrations increase in patients with cirrhosis.

Isosorbide dinitrate, its active metabolites, and hydralazine may be eliminated more slowly in elderly patients.

Indications and Usage

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; to improve patient-reported functional status.

Contraindications

Allergy to organic nitrates.

Dosage and Administration

PO Initial dose: 1 tablet 3 times daily; may be titrated to max tolerated dose not to exceed 2 tablets 3 times daily. Titration may occur as often as every 3 to 5 days, or less if patient experiences adverse reactions. Dose may be reduced by ½ tablet 3 times daily if intolerable adverse reactions occur.

General Advice

• Administer without regard to meals. Administer with food if GI upset occurs.
• If a dose is missed, administer it as soon as remembered unless it is nearing time for the next scheduled dose. If it is nearing time for the next scheduled dose, skip the missed dose and administer the next dose as scheduled. Do not double the dose to catch up.

Storage/Stability

Store at controlled room temperature (59° to 86°F). Protect from light.

Drug Interactions

The pharmacologic effects of hydralazine may be decreased.

Use with caution.

The risk of severe hypotension may be increased.

Monitor patient for several hours for excessive fall in BP.

Effects may be additive.

Laboratory Test Interactions

None well documented.

Adverse Reactions

The incidence stated for the following adverse reactions were reported with BiDil (isosorbide dinitrate/hydralazine hydrochloride) administration. Adverse reactions occurring with administration of isosorbide dinitrate or hydralazine hydrochloride are listed in their respective monographs.

Cardiovascular

Hypotension (8%); palpitations, ventricular tachycardia (4%); tachycardia (2%).

CNS

Headache (50%); dizziness (32%); asthenia (14%); paresthesia (4%); malaise, somnolence (less than 2%).

Dermatologic

Alopecia, angioedema, sweating (less than 2%).

EENT

Rhinitis (4%); amblyopia (3%).

GI

Nausea (10%); vomiting (4%); cholecystitis (less than 2%).

Metabolic-Nutritional

Hyperglycemia (4%); hyperlipidemia (3%); hypercholesteremia (less than 2%).

Musculoskeletal

Arthralgia, myalgia, tendon disorder (less than 2%).

Respiratory

Bronchitis (8%); sinusitis (4%).

Miscellaneous

Chest pain (16%); allergic reaction (less than 2%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Cautiously select dosage, usually starting at the lower end of the dosing range, reflecting the greater frequency of decreased hepatic and renal function, and comorbidity.

To avoid hazards of hypotension and tachycardia, closely monitor clinical and hemodynamic status when this product is administered to patients with acute MI.

Hydralazine can cause tachycardia, potentially leading to myocardial ischemia and angina attacks. Isosorbide dinitrate may aggravate angina associated with hypertrophic cardiomyopathy.

May cause symptomatic hypotension, especially with upright posture. Use with caution in patients who are volume depleted or are already hypotensive.

Hydralazine has been associated with peripheral neuritis (numbness, paresthesia, tingling) that may be caused by an antipyridoxine effect. Add pyridoxine to treatment regimen if symptoms develop.

Use with caution. Augmentation of the vasodilatory effects of isosorbide dinitrate by phosphodiesterase inhibitors (eg, sildenafil, tadalafil, vardenafil) could result in severe hypotension.

Treatment with hydralazine can produce a clinical picture simulating systemic lupus erythematosus, including glomerulonephritis. If symptoms suggestive of lupus develop, CBCs and antinuclear antibody titer determinations should be performed. If a positive antinuclear antibody titer is noted, do not discontinue therapy until after a thorough benefit-to-risk assessment has been completed.

Overdosage

Symptoms

Expected signs and symptoms include cardiac arrhythmia, coma, confusion, death, generalized skin flushing, headache, hypotension, MI, myocardial ischemia, profound shock, reduced cardiac output, syncope, tachycardia, vasodilatation.

Patient Information

• Advise patient to read patient information leaflet before starting therapy and with each refill.
• Advise patient to take 3 times daily as prescribed, without regard to meals, but to take with food if stomach upset occurs.
• Advise patient to try to take each dose at about the same time each day.
• Advise patient that if a dose is missed to take as soon as remembered unless it is nearing time for the next scheduled dose. If it is nearing time for the next scheduled dose, advise patient to skip the missed dose and take the next dose as scheduled. Caution patient not to double the dose to catch up.
• Caution patient not to change the dose or stop taking unless advised by health care provider.
• Instruct patient to continue taking other medications for heart failure as prescribed by health care provider.
• Caution patient to avoid taking phosphodiesterase-5 inhibitor (eg, sildenafil, tadalafil, vardenafil) for treatment of erectile dysfunction or pulmonary hypertension because of risk of causing an extreme drop in BP, which could result in fainting, precipitation of angina, or heart attack.
• Instruct patient in BP and pulse measurement skills.
• Advise patient to monitor and record BP and pulse, daily weights, and heart failure symptoms at home. Instruct patient to inform health care provider if abnormal BP measurements, weight gain of 5 lb in 1 wk, or worsening symptoms of heart failure are noted. Also advise patient to take record of BP and pulse, daily weights, and heart failure symptoms to each follow-up visit.
• Advise patient that headaches are a common adverse reaction of therapy, especially when first starting the medication or increasing the dose but that they tend to go away with continued treatment. Advise patient that acetaminophen may be used to reduce headache pain. Instruct patient to notify health care provider if intolerable headaches persist with continued therapy.
• Caution patient to avoid sudden position changes to prevent orthostatic hypotension.
• Instruct patient to lie or sit down if they experience dizziness or lightheadedness when standing. Advise patient to notify health care provider if dizziness or lightheadedness occurs frequently or appears to be getting worse.
• Caution patient that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to excessive fall in BP, resulting in lightheadedness or fainting.
• Advise patient that medication may cause dizziness or lightheadedness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
• Instruct patient to notify health care provider if any of the following occur: joint pain, new or worsening chest pain, unexplained fever, persistent general body discomfort, numbness or tingling in hands or feet, abnormal skin sensations, or any other unexplained symptoms or feelings.

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