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Pronunciation
(hye DRAL a zeen)
Generic Available (U.S.)
Yes
Index Terms
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Management of moderate-to-severe hypertension
Use: Unlabeled/Investigational
Heart failure; hypertension secondary to pre-eclampsia/eclampsia
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic effects were observed in animal studies at 20-30 times the maximun daily human dose. Hydralazine crosses the placenta. Hydralazine is recommended for use in the management of hypertension associated with pre-eclampsia.
Lactation
Enters breast milk/use caution (AAP rates “compatible”; AAP 2001 update pending)
Breast-Feeding Considerations
In a case report, following a maternal dose of hydralazine 50 mg three times daily, exposure to the infant was calculated to be 0.013 mg per 75mL breast milk.
Contraindications
Hypersensitivity to hydralazine or any component of the formulation; mitral valve rheumatic heart disease
Warnings/Precautions
Concerns related to adverse effects:
• Drug-induced lupus-like syndrome: May cause a drug-induced lupus-like syndrome (more likely on larger doses, longer duration).
• Fluid/sodium retention: Hydralazine-induced fluid and sodium retention may require addition or increased dosage of a diuretics.
• Peripheral neuritis: Hydralazine has been associated with peripheral neuritis (eg, paresthesia, numbness, and tingling), possibly due to an antipyridoxine effect. Pyridoxine therapy should be initiated with onset of such symptoms.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with coronary artery disease (CAD); increase in tachycardia may increase myocardial oxygen demand.
• Pulmonary hypertension: Use with caution in pulmonary hypertension; may cause hypotension.
• Renal impairment: Use with caution in patients with severe renal impairment; dosage adjustment recommended.
Other warnings/precautions:
• I.V. administration: Monitor blood pressure closely following I.V. administration. Response may be delayed and unpredictable in some patients; titrate cautiously to response.
• Patient compliance: Patients may be poorly compliant because of frequent dosing.
Adverse Reactions
Frequency not defined.
Cardiovascular: Angina pectoris, flushing, orthostatic hypotension, palpitations, paradoxical hypertension, peripheral edema, tachycardia, vascular collapse
Central nervous system: Anxiety, chills, depression, disorientation, dizziness, fever, headache, increased intracranial pressure (I.V.; in patient with pre-existing increased intracranial pressure), psychotic reaction
Dermatologic: Pruritus, rash, urticaria
Gastrointestinal: Anorexia, constipation, diarrhea, nausea, paralytic ileus, vomiting
Genitourinary: Dysuria, impotence
Hematologic: Agranulocytosis, eosinophilia, erythrocyte count reduced, hemoglobin decreased, hemolytic anemia, leukopenia, thrombocytopenia (rare)
Neuromuscular & skeletal: Muscle cramps, peripheral neuritis, rheumatoid arthritis, tremor, weakness
Ocular: Conjunctivitis, lacrimation
Respiratory: Dyspnea, nasal congestion
Miscellaneous: Diaphoresis, 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)
Metabolism/Transport Effects
Inhibits CYP3A4 (weak)
Drug Interactions
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of HydrALAZINE. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase CNS depression).
Food: Food enhances bioavailability of hydralazine.
Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid garlic (may have increased antihypertensive effect).
Storage
Intact ampuls/vials of hydralazine should not be stored under refrigeration because of possible precipitation or crystallization.
Reconstitution
Hydralazine should be diluted in NS for IVPB administration due to decreased stability in D5W. Stability of IVPB solution in NS is 4 days at room temperature.
Compatibility
Stable in dextran 6% in dextrose, dextran 6% in NS, D5LR, D51/4NS, D51/2NS, D5NS, D10W, LR, 1/2NS, NS; incompatible with D5W.
Y-site administration: Compatible: Heparin, hydrocortisone sodium succinate, potassium chloride, verapamil, vitamin B complex with C. Incompatible: Aminophylline, ampicillin, diazoxide, furosemide. Variable (consult detailed reference): Nitroglycerin.
Compatibility when admixed: Compatible: Dobutamine. Incompatible: Aminophylline, ampicillin, chlorothiazide, edetate calcium disodium, ethacrynate, hydrocortisone sodium succinate, mephentermine, methohexital, nitroglycerin, phenobarbital, verapamil.
Mechanism of Action
Direct vasodilation of arterioles (with little effect on veins) with decreased systemic resistance
Pharmacodynamics/Kinetics
Onset of action: Oral: 20-30 minutes; I.V.: 5-20 minutes
Duration: Oral: Up to 8 hours; I.V.: 1-4 hours; Note: May vary depending on acetylator status of patient
Protein binding: 85% to 90%
Metabolism: Hepatically acetylated; extensive first-pass effect (oral)
Bioavailability: 30% to 50%; increased with food
Half-life elimination: Normal renal function: 2-8 hours; End-stage renal disease: 7-16 hours
Excretion: Urine (14% as unchanged drug)
Dosage
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 (maximum: 300 mg/day); usual dose range (JNC 7): 25-100 mg/day in 2 divided doses
Congestive heart failure:
Initial dose: 10-25 mg 3-4 times/day
Adjustment: Dosage must be adjusted based on individual response
Target dose: 225-300 mg/day in divided doses; use in combination with isosorbide dinitrate
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:
Clcr 10-50 mL/minute: Administer every 8 hours.
Clcr <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.
Administration: I.V.
Solution for injection: Administer as a slow I.V. push; maximum rate: 5 mg/minute
Administration: I.V. Detail
pH: 3.4-4.0
Monitoring Parameters
Blood pressure (monitor closely with I.V. use), standing and sitting/supine, heart rate, ANA titer
Dietary Considerations
Administer tablet with meals.
Patient Education
Take with meals. Avoid alcohol. This medication does not replace other antihypertensive interventions; follow prescriber's instructions for diet and lifestyle changes. Weigh daily for the first 2 weeks and weekly thereafter. Report weight gain or swelling of feet or ankles. May cause dizziness, weakness, nausea, vomiting, or headache. Report skin rash, severe dizziness or loss of consciousness, significant weight gain, joint pain or swelling, or persistent GI problems.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: A common adverse event of intravenous hydralazine is unpredictable hypotension. Hypotension due to hydralazine may last longer (up to 12 hours) even though the circulating half-life is only ~3 hours. For this reason, intravenous hydralazine is not recommended for the treatment of hypertensive crisis (Marik, 2007). In patients with significant obstructive coronary disease, the use of intravenous hydralazine may be detrimental due to the production of reflex tachycardia; use with caution. Hydralazine is considered to be safe for the management of blood pressure during pregnancy (eg, pre-eclampsia); however, other agents may be considered.
Evidence-Based Information: May be combined with isosorbide dinitrate for the treatment of heart failure (HF) with ACE inhibitors, beta-blockers (eg, bisoprolol, carvedilol, metoprolol XL) and diuretics in patients who are self-identified as African-Americans. Hydralazine/isosorbide dinitrate combination may also be used in HF patients with reduced LVEF who are already on an ACE inhibitor and a beta-blocker for symptomatic heart failure and who have persistent symptoms or those unable to tolerate ACE inhibition or angiotensin II receptor blockade (Hunt, 2009).
Cardiovascular Considerations
Heart Failure: May be combined with isosorbide dinitrate for the treatment of heart failure (HF). This combination has shown to decrease cardiovascular morbidity and mortality in patients with HF (Cohn, 1986). The ACC/AHA 2009 Heart Failure Guidelines recommend that hydralazine/isosorbide dinitrate combination be used to improve outcomes in HF patients who are self-identified as African-Americans and receiving ACE inhibitors, beta-blockers (eg, bisoprolol, carvedilol, metoprolol XL), and diuretics (Class I recommendation). They also suggest that the combination of hydralazine and a nitrate is reasonable for patients with reduced LVEF who are already on an ACE inhibitor and a beta-blocker for symptomatic heart failure and who have persistent symptoms or in patients who cannot tolerate an ACE inhibitor or ARB due to intolerance, hypotension, or renal insufficiency (Hunt, 2009).
Hypertension: For the management of hypertension, hydralazine may be used alone or in combination with other agents. It is considered to be safe for the management of blood pressure during pregnancy.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause drowsiness
Mental Health: Effects on Psychiatric Treatment
Concurrent use with MAO inhibitors may result in significant decrease in blood pressure; use cautiously
Nursing: Physical Assessment/Monitoring
Orthostatic precautions should be observed and patient monitored closely during and following infusion. Monitor for hypotension and fluid retention periodically during therapy.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as hydrochloride: 20 mg/mL (1 mL)
Tablet, oral, as hydrochloride: 10 mg, 25 mg, 50 mg, 100 mg
Pricing: U.S. (www.drugstore.com)
Tablets (HydrALAZINE HCl)
25 mg (100): $27.99
50 mg (30): $19.98
Extemporaneously Prepared
A flavored suspension (1.25 mg/mL) may be made with tablets. Dissolve seventy-five 50 mg hydralazine hydrochloride tablets in 250 mL of distilled water with 2250 g of Lycasin® (75% w/w maltitol syrup vehicle). Add 3 g edetate disodium, then add 3 g sodium saccharin dissolved in 50 mL distilled water. Preserve solution with 30 mL of a solution containing methylparaben 10% (w/v) and propylparaben 2% (w/v) in propylene glycol. Flavor with 3 mL orange flavoring; add sufficient quantity of distilled water to make 3 L. Adjust to pH 3.7 with glacial acetic acid. Label "shake well" and "refrigerate". Stable for 5 days at room temperature and at least 2 weeks refrigerated (preferred).
Alexander KS, Pudipeddi M, and Parker GA, "Stability of Hydralazine Hydrochloride Syrup Compounded From Tablets," Am J Hosp Pharm, 1993, 50(4):683-6.
References
ACOG Committee on Practice Bulletins--Obstetrics, "ACOG Practice Bulletin. Diagnosis and Management of Preeclampsia and Eclampsia. Number 33, January 2002," Obstet Gynecol, 2002, 99(1):159-67.
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89.
Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
Cohn JN, Archibald DG, Ziesche S, et al, “Effect of Vasodilator Therapy on Mortality in Chronic Congestive Heart Failure. Results of a Veterans Administration Cooperative Study,” N Engl J Med, 1986, 314(24):1547-52.
Cohn JN, Johnson G, Ziesche S, et al, “A Comparison of Enalapril With Hydralazine-Isosorbide Dinitrate in the Treatment of Chronic Congestive Heart Failure,” N Engl J Med, 1991, 325(5):303-10.
Erstad BL and Barletta JF, “Treatment of Hypertension in the Perioperative Patient,” Ann Pharmacother, 2000, 34(1):66-79.
Hunt SA, Abraham WT, Chin MH, et al, “2009 Focused Update Incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation,” J Am Coll Cardiol, 2009, 53(15):e1-e90.
Liedholm H, Wåhlin-Boll E, Hanson A, et al, "Transplacental Passage and Breast Milk Concentrations of Hydralazine," Eur J Clin Pharmacol, 1982, 21(5):417-9.
Lindenfeld J, Albert NM, Boehmer JP, et al, “HFSA 2010 Comprehensive Heart Failure Practice Guideline,” J Card Fail, 2010, 16(6):e1-194.
Marik PE and Varon J, “Hypertensive Crises: Challenges and Management,” Chest, 2007, 131(6); 1949-62.
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents,” Pediatrics, 2004, 114(2 Suppl):555-76.
Taylor AL, Ziesche S, Yancy C, et al, “Combination of Isosorbide Dinitrate and Hydralazine in Blacks With Heart Failure,” N Engl J Med, 2004, 351(20):2049-57.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
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