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Medication Safety Issues
Sound-alike/look-alike issues:
HydrALAZINE may be confused with hydrOXYzine
Pronunciation
(hye DRAL a zeen)
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Management of moderate to severe hypertension, congestive heart failure, hypertension secondary to pre-eclampsia/eclampsia; treatment of primary pulmonary hypertension
Pregnancy Risk Factor
C
Pregnancy Considerations
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 this drug for management of hypertension during pregnancy is available. Available evidence suggests safe use during pregnancy.
Lactation
Enters breast milk/compatible
Breast-Feeding Considerations
Crosses into breast milk in extremely small amounts. Available evidence suggests safe use during breast-feeding. AAP considers compatible with breast-feeding.
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.
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: Tachycardia, angina pectoris, orthostatic hypotension (rare), dizziness (rare), paradoxical hypertension, peripheral edema, vascular collapse (rare), flushing
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 (rare), pruritus (rare)
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, tremor, 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), diaphoresis
*Seen in uremic patients and severe hypertension where rapidly escalating doses may have caused hypotension leading to these effects.
Metabolism/Transport Effects
Inhibits CYP3A4 (weak)
Drug Interactions
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
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
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
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
Distribution: Crosses placenta; enters breast milk
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.
Inject over 1 minute. Hypotensive effect may be delayed and unpredictable in some patients.
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 with meals.
Patient Education
Do not take any new medication during therapy unless approved by prescriber. Take as directed, with meals. Avoid alcohol. This medication does not replace other antihypertensive interventions; follow prescriber's instructions for diet and lifestyle changes. Weigh daily at the same time, in the same clothes for the first 2 weeks and weekly thereafter. Report weight gain >5 lb/week or swelling of feet or ankles. May cause postural hypotension, dizziness, or weakness (change position slowly when rising from sitting or lying position, climbing stairs, and avoid driving or activities requiring alertness until response to drug is known); nausea or vomiting (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); impotence (reversible); diarrhea (boiled milk, buttermilk, or yogurt may help); or constipation (increased exercise, fluids, fruit, or fiber may help). Report chest pain, rapid heartbeat, or palpitations; flu-like symptoms; respiratory difficulty; skin rash; numbness and tingling of extremities; muscle cramps, weakness, or tremors; persistent GI problems; or other adverse reactions. Pregnancy precaution: Inform prescriber if you are or intend to become pregnant
Anesthesia and Critical Care Concerns/Other Considerations
May be combined with isosorbide dinitrate for the treatment of heart failure. It is considered to be safe for the management of blood pressure during pregnancy.
Cardiovascular Considerations
Heart Failure: 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 (Cohn JN, 1986). The ACC/AHA 2005 Heart Failure Guidelines suggest that the addition 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 (intolerance, hypotension, renal insufficiency).
Ethnic Considerations: Isosorbide dinitrate and hydralazine may be added to a medical regimen for heart failure (ACE inhibitors and beta-blockers) in black patients with NYHA functional Class III or IV (Taylor AL, 2004).
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
Assess potential for interactions with other pharmacological agents or herbal products patient may be taking (especially anything that may impact blood pressure). For infusion see Administration specifics. Orthostatic precautions should be observed and patient monitored closely during and following infusion. Assess results of laboratory tests, therapeutic effectiveness (decreased blood pressure), and adverse response (eg, hypotension, fluid retention) periodically during therapy. Teach patient proper use (oral), possible side effects/appropriate interventions, and adverse symptoms to report.
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, as hydrochloride: 10 mg, 25 mg, 50 mg, 100 mg
Pricing: U.S. (www.drugstore.com)
Tablets (HydrALAZINE HCl)
10 mg (30): $13.99
25 mg (100): $25.99
50 mg (30): $13.99
100 mg (30): $20.00
Extemporaneously Prepared
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
A flavored syrup (1.25 mg/mL) has been made using seventy-five hydralazine hydrochloride 50 mg tablets, dissolved in 250 mL of distilled water with 2250 g of Lycasin® (75% w/w maltitol syrup vehicle); edetate disodium 3 g and sodium saccharin 3 g dissolved in 50 mL distilled water was added; solution was preserved with 30 mL of a solution containing methylparaben 10% (w/v) and propylparaben 2% (w/v) in propylene glycol; flavored with 3 mL orange flavoring; qs ad to 3 L with distilled water and then pH adjusted to pH of 3.7 using glacial acetic acid; measured stability was 5 days at room temperature (25°C); less than 2% loss of hydralazine occurred at 2 weeks when syrup was stored at 5°C
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.
References
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, "ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure)," available at http://www.acc.org/qualityandscience/clinical/guidelines/failure/update/index.pdf.
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 August 2008
Content last modified August 2008
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