• HF with reduced ejection fraction in black patients.

Contraindicated in:

• Hypersensitivity to either component
• Concurrent use of PDE-5 inhibitor (avanafil, sildenafil, tadalafil, vardenafil) or riociguat.

Use Cautiously in:

• Severe renal impairment (dose modification may be necessary)
• Severe hepatic impairment (dose modification may be necessary)
• Head trauma or cerebral hemorrhage
• OB: Safety not established in pregnancy
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Pedi: Safety and effectiveness not established in children
• Geri: Start with lower doses in older adults.

Hydralazine

CV: tachycardia, angina, arrhythmias, edema, orthostatic hypotension.

Derm: rash.

GI: diarrhea, nausea, vomiting.

MS: arthralgias, arthritis.

Neuro: dizziness, headache, drowsiness, peripheral neuritis, weakness.

Misc: drug-induced lupus syndrome.

Isosorbide Dinitrate

CV: hypotension, tachycardia, paradoxical bradycardia, syncope.

GI: abdominal pain, nausea, vomiting.

Misc: flushing, tolerance.

Drug-Drug:

• Concurrent use of avanafil, sildenafil, tadalafil, or vardenafil may result in severe hypotension; concurrent use contraindicated.
• Concurrent use of riociguat may result in severe hypotension; concurrent use contraindicated.
• ↑ risk of hypotension with other antihypertensives, acute ingestion of alcohol, and phenothiazines.
• MAO inhibitors may exaggerate hypotension.
• May ↓ the pressor response to epinephrine.
• Beta blockers ↓ tachycardia from hydralazine (therapy may be combined for this reason).
• Metoprolol and propranolol may ↑ hydralazine levels and risk of toxicity.
• Hydralazine may ↑ levels and risk of toxicity of metoprolol and propranolol.

• Tablets: hydralazine 37.5 mg/isosorbide dinitrate 20 mg;

• PO (Adults): 1 tablet 3 times daily, may be ↑ to 2 tablets 3 times daily.

BiDil

• BiDil is a fixed-dose combination of isosorbide dinitrate, a vasodilator with effects on both arteries and veins, and hydralazine, a predominantly arterial vasodilator.

• Improved survival, increased time to hospitalization and decreased symptoms of HF in black patients.

Therapeutic Classification: vasodilators

Pharmacologic Classification: vasodilators, nitrates

Hydralazine

Absorption: 10–26% absorbed in patients with HF following oral administration; absorption can be saturated, leading to large ↑ in absorption with higher doses.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Mostly metabolized by GI mucosa and liver.

Half-life: 4 hr.

Isosorbide Dinitrate

Absorption: Variable absorption (10–90%) following oral administration, reflecting first-pass hepatic metabolism.

Distribution: Accumulates in muscle and venous wall.

Metabolism/Excretion: Undergoes extensive first-pass metabolism in the liver, mostly metabolized by the liver; some metabolites are vasodilators.

Half-life: 2 hr.

(effect on BP)

• Instruct patient to take medication as directed on a regular schedule.
• Caution patient to make position changes slowly to minimize orthostatic hypotension.
• May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Advise patient to avoid concurrent use of alcohol or medications for erectile dysfunction with this medication. Patient should also consult health care professional before taking Rx, OTC, or herbal products while taking this medication.
• Caution patient that inadequate fluid intake or excessive fluid loss from perspiration, diarrhea, or vomiting may lead to a fall in BP, dizziness, or syncope. If syncope occurs, discontinue medication and notify health care professional promptly.
• Inform patient that headache is a common side effect that should decrease with continuing therapy. Aspirin or acetaminophen may be ordered to treat headache. Notify health care professional if headache is persistent or severe. Do not alter dose to avoid headache.
• Advise patient to notify health care professional if symptoms of systemic lupus erythematosus occur (arthralgia, fever, chest pain, prolonged malaise, or other unexplained symptoms).
• Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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