hydralazine/isosorbide dinitrate

General

Pronunciation:
hye-dral-a-zeen eye-so-sor-bide di-ni-trate

Trade Name(s)

BiDil

Ther. Class.

vasodilators

Pharm. Class.

vasodilators

nitrates

Indications

HF with reduced ejection fraction in Black patients.

Action

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

Therapeutic Effect(s):

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

Pharmacokinetics

Hydralazine

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

Distribution: Widely distributed to tissues.

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

Half-life: 2 hr.

TIME/ACTION PROFILE (effect on BP)

ROUTE	ONSET	PEAK	DURATION
hydralazine (PO)	45 min	2 hr	2–4 hr
isosorbide (PO)	15–40 min	unknown	4 hr

Contraindication/Precautions

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.

Adverse Reactions/Side Effects

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

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

Avanafil, sildenafil, tadalafil, vardenafil, or riociguat may ↑ risk of 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.

Route/Dosage

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

Availability

Tablets: hydralazine 37.5 mg/isosorbide dinitrate 20 mg

Assessment

Monitor BP and HR routinely during period of dose adjustment. Symptomatic hypotension may occur even with small doses. Use caution with patients who are volume or sodium depleted or hypotensive.
Assess for signs and symptoms of peripheral neuritis (paresthesia, numbness, tingling) periodically during therapy. Adding pyridoxine may cause symptoms to ↓.

Lab Test Considerations:

If symptoms of systemic lupus erythematosus (SLE) occur, obtain a CBC and ANA titer. If positive for SLE, carefully weigh risks/benefits of continued therapy.

Implementation

Dose may be titrated rapidly over 3–5 days, but may need to ↓ if side effects occur. May ↓ to one-half tablet 3 times daily if intolerable side effects occur. Titrate up as soon as side effects subside.

Patient/Family Teaching

Explain the purpose and side effects of hydralazine/isosorbide dinitrate. Instruct patient to take as directed on a regular schedule. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
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 notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications. Advise patient to avoid concurrent use of alcohol or medications for erectile dysfunction with this medication.
Caution patient that inadequate fluid intake or excessive fluid loss from perspiration, diarrhea, or vomiting may lead to a ↓ in BP, dizziness, or syncope. If syncope occurs, discontinue medication and notify health care provider promptly.
Inform patient that headache is a common side effect that should ↓ with continuing therapy. Aspirin or acetaminophen may be ordered to treat headache. Notify health care provider if headache is persistent or severe. Do not alter dose to avoid headache.
Advise patient to notify health care provider if symptoms of SLE occur (arthralgia, fever, chest pain, prolonged malaise, other unexplained symptoms).
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes