Yes

Vasodilator

Management of moderate to severe hypertension, congestive heart failure, hypertension secondary to pre-eclampsia/eclampsia; treatment of primary pulmonary hypertension

C

Clinical effects on the fetus: Crosses the placenta. One report of fetal arrhythmia; transient neonatal thrombocytopenia and fetal distress reported following late 3rd trimester use. A large amount of clinical experience with the use of these drugs for management of hypertension during pregnancy is available. Available evidence suggests safe use during pregnancy and breast-feeding.

Breast-feeding/lactation: Crosses into breast milk in extremely small amounts. American Academy of Pediatrics considers compatible with breast-feeding.

Hypersensitivity to hydralazine or any component; mitral valve rheumatic heart disease

May cause a drug-induced lupus-like syndrome (more likely on larger doses, longer duration). Adjust dose in severe renal dysfunction. Use with caution in CAD (increase in tachycardia may increase myocardial oxygen demand). Use with caution in pulmonary hypertension (may cause hypotension). Tartrazine may be in some products (do not use in sensitive individuals). Patients may be poorly compliant because of frequent dosing.

Incidence of reactions are not reported.

• Central nervous system: Increased intracranial pressure (I.V., in patient with pre-existing increased intracranial pressure), fever (rare), chills (rare), anxiety, disorientation, depression, coma

Dermatologic: Rash (rare), urticaria (rash), pruritus (rash)

Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, constipation, adynamic ileus

Genitourinary: Difficulty in micturition, impotence

Hematologic: Hemolytic anemia (rare), eosinophilia (rare), decreased hemoglobin concentration (rare), reduced erythrocyte count (rare), leukopenia (rare), agranulocytosis (rare), thrombocytopenia (rare)

Neuromuscular & skeletal: Rheumatoid arthritis, muscle cramps, weakness, tremors, peripheral neuritis (rare)

Ocular: Lacrimation, conjunctivitis

Respiratory: Nasal congestion, dyspnea

Miscellaneous: Drug-induced lupus-like syndrome (dose-related; fever, arthralgia, splenomegaly, lymphadenopathy, asthenia, myalgia, malaise, pleuritic chest pain, edema, positive ANA, positive LE cells, maculopapular facial rash, positive direct Coombs' test, pericarditis, pericardial tamponade), sweating

• Seen in uremic patients and severe hypertension where rapidly escalating doses may have caused hypotension leading to these effects.

Symptoms of overdose include hypotension, tachycardia, shock

Hypotension usually responds to I.V. fluid, Trendelenburg positioning or vasoconstrictors; treatment is primarily supportive and symptomatic

Beta-blockers (metoprolol, propranolol) serum concentrations and pharmacologic effects may be increased. Monitor cardiovascular status.

Propranolol increases hydralazine's serum concentrations. Acebutolol, atenolol, and nadolol (low hepatic clearance or no first-pass metabolism) are unlikely to be affected.

NSAIDs may decrease the hemodynamic effects of hydralazine; avoid use if possible or closely monitor cardiovascular status.

Intact ampuls/vials of hydralazine should not be stored under refrigeration because of possible precipitation or crystallization

Hydralazine should be diluted in NS for IVPB administration due to decreased stability in D₅W

Stability of IVPB solution in NS: 4 days at room temperature

Direct vasodilation of arterioles (with little effect on veins) with decreased systemic resistance

Onset of action: Oral: 20-30 minutes; I.V.: 5-20 minutes

Duration: Oral: 2-4 hours; I.V.: 2-6 hours

Distribution: Crosses placenta; appears in breast milk

Metabolism: Large first-pass effect orally, acetylated in liver

Protein binding: 85% to 90%

Bioavailability: 30% to 50%; enhanced by concurrent administration with food

Half-life: Normal renal function: 2-8 hours; End-stage renal disease: 7-16 hours

Elimination: 14% excreted unchanged in urine

Children:

Oral: Initial: 0.75-1 mg/kg/day in 2-4 divided doses; increase over 3-4 weeks to maximum of 7.5 mg/kg/day in 2-4 divided doses; maximum daily dose: 200 mg/day

I.M., I.V.: 0.1-0.2 mg/kg/dose (not to exceed 20 mg) every 4-6 hours as needed, up to 1.7-3.5 mg/kg/day in 4-6 divided doses

Adults:

Oral: Hypertension:

Initial dose: 10 mg 4 times/day for first 2-4 days; increase to 25 mg 4 times/day for the balance of the first week

Increase by 10-25 mg/dose gradually to 50 mg 4 times/day; 300 mg/day may be required for some patients

Oral: Congestive heart failure:

Initial dose: 10-25 mg 3 times/day

Target dose: 75 mg 3 times/day

Maximum dose: 100 mg 3 times/day

I.M., I.V.:

Hypertension: Initial: 10-20 mg/dose every 4-6 hours as needed, may increase to 40 mg/dose; change to oral therapy as soon as possible.

Pre-eclampsia/eclampsia: 5 mg/dose then 5-10 mg every 20-30 minutes as needed.

Elderly: Oral: Initial: 10 mg 2-3 times/day; increase by 10-25 mg/day every 2-5 days.

Dosing interval in renal impairment:

Cl_cr 10-50 mL/minute: Administer every 8 hours.

Cl_cr <10 mL/minute: Administer every 8-16 hours in fast acetylators and every 12-24 hours in slow acetylators.

Hemodialysis: Supplemental dose is not necessary.

Peritoneal dialysis: Supplemental dose is not necessary.

Food enhances bioavailability of hydralazine

Blood pressure (monitor closely with I.V. use), standing and sitting/supine, heart rate, ANA titer

May be combined with isosorbide dinitrate for the treatment of heart failure. This combination has shown to decrease cardiovascular morbidity and mortality in patients with heart failure. The combination of hydralazine and isosorbide dinitrate should be considered in ACE-inhibitor intolerant patients or in patients who develop symptoms regardless of maximal ACE-inhibitor therapy. One disadvantage of combination therapy includes the need for multidosing (TID).

May cause drowsiness

Concurrent use with MAOIs may result in significant decrease in blood pressure; use cautiously

No information available to require special precautions

No effects or complications reported

Take as directed, with meals. Do not use alcohol or OTC medication without consulting prescriber. Weigh daily at the same time, in the same clothes. Report weight gain >5 lb/week, swelling of feet or ankles. May cause dizziness or weakness; change position slowly when rising from sitting or lying position and avoid driving or activities requiring alertness until response to drug is known. You may experience nausea (small frequent meals may help), impotence (reversible), or constipation (fluids, exercise, dietary fiber may help). This medication does not replace other antihypertensive interventions; follow instructions for diet and lifestyle changes. Report flu-like symptoms, difficulty breathing, skin rash, blackened stool, or numbness and tingling of extremities. Pregnancy precautions: Use appropriate contraception and inform prescriber if you are or intend to be pregnant.

Aid with ambulation, rising may cause orthostasis

Injection, as hydrochloride: 20 mg/mL (1 mL)

Tablet, as hydrochloride: 10 mg, 25 mg, 50 mg, 100 mg

An oral solution (20 mg/5 mL) has been made from 20 mL of the hydralazine injection (20 mg/mL), 8 mL of propylene glycol and purified water USP qs ad 100 mL; expected stability: 30 days if refrigerated

Alexander KS, Pudipeddi M, and Parker GA, "Stability of Hydralazine Hydrochloride Syrup Compounded From Tablets," Am J Hosp Pharm, 1993, 50(4):683-6.

Nahata MC and Hipple TF, Pediatric Drug Formulations, 2nd ed, Cincinnati, OH: Harvey Whitney Books Co, 1992.

Birkenhager WH, "Choosing the Optimum Therapy for Older Hypertensive Patients," Drugs Aging, 1991, 1(1):36-47.

Smith BA and Ferguson DB, "Acute Hydralazine Overdose: Marked ECG Abnormalities in a Young Adult," Ann Emerg Med, 1992, 21(3):326-30.

Sproat TT and Lopez LM, "Hypertension," Therapeutics in the Elderly, 2nd ed, Delauente JC, Stewart RB, eds, Cincinnati, OH: Harvey Whitney Books, 1995, 228-46.