Hydralazine Hydrochloride

Vasodilating agent.134 e

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).134

Not considered a preferred agent for initial management of hypertension, but may be used as add-on therapy if BP not adequately controlled with the recommended antihypertensive drug classes (i.e., ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, thiazide diuretics).501 502 503 504

Severe Hypertension and Hypertensive Crises

One of several recommended parenteral agents for use in the hospital setting to urgently lower BP in severely hypertensive pregnant women, including those with preeclampsia†.112 139 500 540

Historically considered the agent of choice for management of hypertensive emergencies associated with pregnancy (e.g., preeclampsia, eclampsia);542 however, some clinicians prefer IV labetalol for its more rapid onset, shorter duration of action, and more predictable hypotensive effect.502 542

Parenteral management of severe hypertension when the drug cannot be given orally or when BP must be lowered immediately;e other parenteral antihypertensive agents (e.g., labetalol, esmolol, fenoldopam, nicardipine, sodium nitroprusside) usually are preferred for these indications.500 502 542 b

Not recommended for the management of severe hypertension or hypertensive emergencies associated with cerebrovascular accidents or in patients with cerebral edema and encephalopathy.b

Although some manufacturers have not established pediatric dosage recommendations, some clinicians suggest the IV or IM use of hydralazine for rapid reduction of BP in pediatric patients 1–17 years of age† with severe hypertension†.133

Heart Failure

Used in fixed combination with isosorbide dinitrate as adjunct to standard therapy for the treatment of heart failure in self-identified black patients to improve survival, decrease rate of hospitalization for worsened heart failure, and improve patient-reported functional status.135 136 137

Current guidelines recommend a combination of drug therapies (e.g., ACE inhibitors, angiotensin II receptor antagonists, angiotensin receptor-neprilysin inhibitors [ARNIs], β-adrenergic blocking agents [β-blockers], aldosterone receptor antagonists) in adults with heart failure to reduce morbidity and mortality.524 701 703 800

Combination of hydralazine and isosorbide dinitrate recommended by ACCF and AHA for self-identified black patients with NYHA class III or IV heart failure and reduced ejection fraction who are receiving optimal therapy with ACE inhibitors and β-blockers, unless contraindicated.524

ACCF and AHA state that combined therapy with hydralazine and isosorbide dinitrate also can be useful in patients with current or prior symptomatic heart failure with reduced ejection fraction who cannot receive an ACE inhibitor or angiotensin II receptor antagonist† because of drug intolerance, hypotension, or renal insufficiency.524

Absorption

Bioavailability

Absorption from GI tract is rapid;b 66% of an oral dose may be absorbed.135

Onset

Following oral administration, antihypertensive effect occurs in 20–30 minutes.b

Following IM administration, hypotensive effect occurs within 10–30 minutes.b

Following IV administration, hypotensive effect occurs within 5–20 minutes, is maximum in 10–80 minutes.b

Duration

Following oral administration, antihypertensive effect lasts 2–4 hours.b

Following IM administration, hypotensive effect lasts 2–6 hours.b

Following IV administration, hypotensive effect lasts 2–6 hours.b

Food

Food increases plasma hydralazine concentrations.134 The effect of food on the bioavailability of hydralazine when administered in fixed combination with isosorbide dinitrate is not known.135

Distribution

Extent

Widely distributed into body tissues in animals;b highest concentrations in kidneys, plasma, and liver; high affinity for arterial walls;b lower concentrations in the brain, lungs, muscle, heart, and fat.b

Readily crosses the placenta.b

Distributed into milk.b

Plasma Protein Binding

85–87%.b

Elimination

Metabolism

Metabolized extensively in the GI mucosa during absorption and in the liver by acetylation, hydroxylation, and conjugation with glucuronic acid.b

Acetylation rate is genetically determined; slow acetylators have higher plasma hydralazine concentrations than rapid acetylators at the same oral dose.b

Elimination Route

Excreted principally in urine as metabolites and in feces (10%).b

Half-life

Plasma half-life: approximately 2–4 hours.b

Special Populations

Not known whether hydralazine is dialyzable.b

Not known whether impaired renal or hepatic function has an effect on the pharmacokinetics of hydralazine.135

Hydralazine may be eliminated more slowly in geriatric patients.135

• Importance of informing clinician about occurrence of SLE symptoms (e.g., joint or chest pain or fever).134 e

• Potential to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual are known.134 e

• Importance of consulting clinician if headache continues with repeated dosing.135

• Importance of informing patients receiving hydralazine in fixed combination with isosorbide dinitrate that inadequate fluid intake or excessive fluid loss due to diarrhea, vomiting, or perspiration may result in excessive hypotension, possibly leading to lightheadedness or syncope; if syncope occurs, discontinue treatment and notify clinician immediately.135

• Importance of taking hydralazine regularly and continuously as prescribed.134 e

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.134 e

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.134 e

• Importance of informing patients of other important precautionary information.134 e (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name