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Hydralazine Hydrochloride

Pronunciation

Class: Direct Vasodilators
VA Class: CV490
CAS Number: 304-20-1
Brands: BiDil

Introduction

Vasodilating agent.134 e

Uses for Hydralazine Hydrochloride

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

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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

In fixed combination with isosorbide dinitrate as adjunct to standard therapy for the treatment of CHF 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 Recommended by the American College of Cardiology Foundation (ACCF) and AHA for all such patients with NYHA class III or IV heart failure with 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 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

Hydralazine Hydrochloride Dosage and Administration

General

Hypertension

  • Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.500 501

    Adjust dosage carefully according to individual requirements and BP response.500

  • Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501

  • Tolerance to antihypertensive effect develops during prolonged therapy, especially if a diuretic is not administered concurrently.b

Hypertensive Crises

  • Monitor BP closely when parenteral hydralazine is used.e

  • Avoid excessive BP decreases in any hypertensive crisis since they may precipitate renal, cerebral, or coronary ischemia.500 542

  • Avoid abrupt discontinuance in patients with a marked reduction in BP.109 To minimize risk for sudden BP increase, reduce dosage gradually.b

Administration

Administer orally or by IM or IV injection.b Usually administer orally; may be administered IM or IV if patient unable to take drug orally or if a rapid decrease in BP is required.b

Oral Administration

Administer orally 2–4 times daily.134 b

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by rapid IV injection directly into the vein.e

Replace parenteral therapy with oral therapy as soon as possible.b

Dosage

Available as hydralazine hydrochloride; dosage expressed in terms of the salt.b

20–25 mg of IV hydralazine hydrochloride was approximately equal to 75–100 mg of oral hydralazine hydrochloride in one study.b

Pediatric Patients

Hypertension
Oral

Initially, 0.75 mg/kg daily (or 25 mg/m2 daily) given in 4 divided doses;133 134 b initial dose should not exceed 25 mg.b

Dosages may be increased gradually (over 3–4 weeks) up to a maximum of 7.5 mg/kg daily (or 200 mg daily).133 134 b

IM or IV

Usual dosage: 1.7–3.5 mg/kg daily or 50–100 mg/m2 daily given in 4–6 divided doses; initial dose should not exceed 20 mg.b e

If administered with reserpine, hydralazine hydrochloride dosages may be reduced to 0.15 mg/kg or 4 mg/m2 every 12–24 hours.b

Severe Hypertension
Rapid Reduction of BP
IV or IM

Children and adolescents 1–17 years of age: 0.2–0.6 mg/kg IV or IM per dose; administer every 4 hours when given by IV (“bolus”) injection.133

Adults

Hypertension
Oral

Initially, 10 mg 4 times daily for 2–4 days.134 Dosage then can be increased to 25 mg 4 times daily for the remainder of the week.134 If necessary, dosage can be increased for the second and subsequent weeks to 50 mg 4 times daily.134

Some experts recommend usual dosage of 12.5–50 mg twice daily.500

Severe Hypertension and Hypertensive Crises

In hypertensive emergency, initial goal of therapy is to reduce mean arterial BP by no more than 25% (within minutes to 1 hour), then, if stable, to 160/100 to 110 mm Hg within the next 2–6 hours.500

If this BP is well tolerated and the patient is clinically stable, implement further gradual reductions toward normal in the next 24–48 hours.500 In patients with aortic dissection, reduce SBP to <100 mm Hg if tolerated.500

IV

Usual dose: 10–20 mg.500 b Parenteral doses are repeated as necessary and may be increased within this range according to the BP response.b

IM

Usual dose: 10–40 mg.500 b Parenteral doses are repeated as necessary and may be increased within this range according to the BP response.b

Urgent Reduction of BP during Pregnancy
IV

Usual initial dose is 5 mg,101 103 105 108 112 500 540 followed by 5–10 mg every 20–40 minutes as necessary to achieve an adequate BP reduction.101 102 103 104 105 108 112 500 540 Maximum total dose of 20 or 25 mg has been recommended.500 540

Heart Failure
Fixed-combination Therapy with Isosorbide Dinitrate in Self-identified Black Patients
Oral

Initially, hydralazine hydrochloride 37.5 mg and isosorbide dinitrate 20 mg (1 tablet of BiDil) 3 times daily.135 524 May titrate dosage to a maximum tolerated dosage not to exceed 2 tablets (a total of 75 mg of hydralazine hydrochloride and 40 mg of isosorbide dinitrate) 3 times daily.135 524 Rapid titration (over 3–5 days) may be possible; however, slower titration may be needed due to adverse effects.135 May decrease dosage to as little as one-half of the fixed-combination tablet 3 times daily in patients who experience intolerable effects, but attempt to titrate dosage up once adverse effects subside.135

Hydralazine Therapy
Oral

ACCF and AHA recommend initial dosage of hydralazine hydrochloride 25–50 mg 3 or 4 times daily; give concomitantly with isosorbide dinitrate 20–30 mg 3 or 4 times daily.524 Titrate dosages to levels similar to those recommended for the fixed-combination preparation and administer both drugs at least 3 times daily.524

Prescribing Limits

Pediatric Patients

Hypertension
Oral

Maximum 7.5 mg/kg daily (or 200 mg daily).133 134 b

Adults

Heart Failure
Fixed-combination Therapy with Isosorbide Dinitrate in Self-identified Black Patients
Oral

Maximum 75 mg of hydralazine hydrochloride and 40 mg of isosorbide dinitrate (2 tablets of BiDil) 3 times daily.135

Hydralazine Therapy
Oral

Maximum 300 mg daily administered concomitantly with isosorbide dinitrate (maximum 120 mg daily).524

Special Populations

Renal Impairment

Lower dosage may be required in severe renal failure.b

Geriatric Patients

The manufacturer of the fixed combination of hydralazine hydrochloride and isosorbide dinitrate states that dosage should be selected with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.135

Cautions for Hydralazine Hydrochloride

Contraindications

  • CAD.134 e

  • Mitral valvular rheumatic heart disease.134 e

  • Hypersensitivity to hydralazine hydrochloride or any ingredient in the formulation.134 e

Warnings/Precautions

Warnings

Systemic Lupus Erythematosus (SLE)

May cause SLE (e.g., glomerulonephritis) or rheumatoid arthritis,134 e particularly in patients receiving >200 mg daily dosage for prolonged periods, in slow acetylators of hydralazine, or in those with decreased renal function.b

If unexplained signs and symptoms (e.g., arthralgia, fever, chest pain, continued malaise) occur, perform appropriate laboratory studies (e.g., CBCs, ANA titer determinations).b

If test results confirm SLE, discontinue hydralazine unless benefit outweighs risk.b Signs and symptoms usually regress with hydralazine discontinuance, but residual effects may be detected after many years.134 b Long-term corticosteroid treatment may be necessary if symptoms do not regress.b

Sensitivity Reactions

Sulfite Sensitivity

Some formulations contain sulfites that may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.b

General Precautions

Cardiovascular Effects

Possible precipitation of angina attacks and/or MI; 134 b use with caution in patients with suspected coronary artery disease.134 e

May increase pulmonary artery pressure in patients with mitral valvular disease.134 e (See Contraindications.)

Possible orthostatic hypotension; use with caution in patients with cerebrovascular accidents,134 135 those who may be volume-depleted, those with preexisting hypotension, or those receiving other hypotensive agents.135 b

Drug Interaction

May paradoxically reduce pressor response to epinephrine.134 b

Peripheral Neuritis

Possible peripheral neuritis (e.g., paresthesia, numbness, tingling);134 e may be caused by pyridoxine deficiency.b

If such symptoms occur, use concomitantly with pyridoxine.b

Hematologic Effects

Possible blood dyscrasias (e.g., decreased hemoglobin and erythrocytes, leukopenia, agranulocytosis, thrombocytopenia with or without purpura).134 e

If such abnormalities occur, discontinue therapy.134 e

Adequate Patient Monitoring

Perform CBCs and ANA titer determinations before initiation and then periodically thereafter during prolonged therapy (even in asymptomatic patients).134 b e

Manufacturers state that a positive ANA titer requires that the implications of the test result be weighed against the benefits from therapy with the drug,134 e whereas some experts state that an increase in ANA titer requires immediate discontinuance of the drug.b

Carefully monitor hemodynamic and clinical status in patients with acute MI.135

Use of Fixed Combinations

When hydralazine is used in fixed combination with isosorbide dinitrate, consider the cautions, precautions, and contraindications associated with isosorbide dinitrate.135

Specific Populations

Pregnancy

Category C.134 e

Lactation

Distributed into milk.b Use caution.134 e

Pediatric Use

Safety and efficacy alone or in fixed combination with isosorbide dinitrate not established.134 135 e Use is based on clinical experience.134 e

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.135 (See Geriatric Patients under Dosage.)

Renal Impairment

Generally considered to be safe; manufacturers state to use with caution in severe renal impairment.b

Common Adverse Effects

Headache, palpitation, tachycardia.b

Interactions for Hydralazine Hydrochloride

Specific Drugs

Drug

Interaction

Comments

β-Adrenergic blocking agents

Additive hypotensive effectb

Concomitant use may minimize adverse cardiac effects (e.g., tachycardia, precipitation of angina) associated with hydralazineb

Usually used to therapeutic advantage; adjust dosages carefully and monitor for excessive BP reductionb

Diazoxide, IV (no longer commercially available in US)

Possibly profound hypotensive episodesb

Diuretics

Additive hypotensive effectb

Concomitant use may prevent tolerance to hydralazine and also prevent sodium retention and increased plasma volume that may occur after prolonged hydralazine therapyb

Usually used to therapeutic advantage; adjust dosage carefully and monitor for excessive BP reductionb

Epinephrine

Decreased pressor response to epinephrine134 e

Hypotensive agents

Additive hypotensive effectb

Usually used to therapeutic advantage; adjust dosage carefully and monitor for excessive BP reductionb

MAO inhibitors

Synergistic effect, resulting in marked BP decreaseb

Use concomitantly with cautionb

Phosphodiesterase (PDE) inhibitors, selective when using hydralazine in fixed combination with isosorbide dinitrate

Sildenafil and other selective PDE inhibitors (e.g., tadalafil, vardenafil) profoundly potentiate the vasodilatory effects of isosorbide dinitrate and potentially life-threatening hypotension and/or hemodynamic compromise can result135

Because of the serious risk of concurrent use of isosorbide dinitrate and selective PDE inhibitors, such combined use is contraindicated135

Hydralazine Hydrochloride Pharmacokinetics

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

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at 15–30°C.134 b

Tablets (Hydralazine Hydrochloride and Isosorbide Dinitrate)

Tight, light-resistant containers at 25°C (may be exposed to 15–30°C).135

Parenteral

Injection

15–30°;e avoid freezing.b

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Color change develops after dilution with most IV infusion solutions.b Color changes that occur over 8–12 hours generally do not indicate loss of potency when stored at ≤30°C.b

Solution CompatibilityHID

Compatible

Dextrose–Ringer’s injection combinations

Dextrose 5% in Ringer’s injection, lactated

Dextrose 2.5% in half-strength Ringer’s injection, lactated

Dextrose–saline combinations

Dextrose 2.5 or 10% in water

Ionosol products

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Sodium lactate (1/6) M

Incompatible

Dextrose 5% in water

Dextrose 10% in Ringer’s injection, lactated

Drug Compatibility
Admixture CompatibilityHID

Compatible

Dobutamine HCl

Incompatible

Aminophylline

Ampicillin sodium

Chlorothiazide sodium

Edetate calcium disodium

Ethacrynate sodium

Hydrocortisone sodium succinate

Methohexital sodium

Nitroglycerin

Phenobarbital sodium

Verapamil HCl

Y-Site CompatibilityHID

Compatible

Caspofungin acetate

Heparin sodium

Hydrocortisone sodium succinate

Potassium chloride

Verapamil HCl

Incompatible

Aminophylline

Ampicillin sodium

Furosemide

Nesiritide

Variable

Nitroglycerin

Actions

  • Mechanism of action as an antihypertensive agent is presumed to be a result of a direct vasodilatory effect on vascular smooth muscle.134 e

Advice to Patients

  • 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.)

Preparations

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

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

Hydralazine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

10 mg*

Hydralazine Hydrochloride Tablets

25 mg*

Hydralazine Hydrochloride Tablets

50 mg*

Hydralazine Hydrochloride Tablets

100 mg*

Hydralazine Hydrochloride Tablets

Parenteral

Injection

20 mg/mL*

Hydralazine Hydrochloride Injection

Hydralazine Hydrochloride Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

37.5 mg with Isosorbide Dinitrate 20 mg

BiDil (scored)

NitroMed

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2015. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

HydrALAZINE HCl 10MG Tablets (CAMBER PHARMACEUTICALS): 30/$14.99 or 60/$19.98

HydrALAZINE HCl 100MG Tablets (CAMBER PHARMACEUTICALS): 30/$25.99 or 90/$66.97

HydrALAZINE HCl 25MG Tablets (PAR): 100/$27.99 or 200/$52.98

HydrALAZINE HCl 50MG Tablets (CAMBER PHARMACEUTICALS): 30/$20.99 or 60/$28.97

AHFS DI Essentials. © Copyright, 2004-2015, Selected Revisions February 15, 2015. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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102. Pritchard JA, Pritchard SA. Standardized treatment of 154 consecutive cases of eclampsia. Am J Obstet Gynecol. 1975; 123:543-51. [PubMed 1180300]

103. Nissen JC. Treatment of hypertensive emergencies of pregnancy. Clin Pharm. 1982; 1:334-43. [IDIS 155091] [PubMed 6764393]

104. Lubbe WF. Hypertension in pregnancy: pathophysiology and management. Drugs. 1984; 28:170-88. [IDIS 188451] [PubMed 6147240]

105. Lindheimer MD, Katz AI. Current concepts: hypertension in pregnancy. N Engl J Med. 1985; 313:675-80. [IDIS 204305] [PubMed 3894964]

108. National High Blood Pressure Education Program Working Group. National High Blood Pressure Education Program Working Group report on high blood pressure in pregnancy. Am J Obstet Gynecol. 1990; 163:1689-1712.

109. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health; 1997 Nov. (NIH publication No. 98-4080.)

110. Kaplan NM. Choice of initial therapy for hypertension. JAMA. 1996; 275:1577-80. [IDIS 365188] [PubMed 8622249]

111. Rey E, LeLorier J, Burgess E et al. Report of the Canadian Hypertension Society consensus conference: 3. pharmacologic treatment of hypertensive disorders in pregnancy. CMAJ. 1997; 157:1245-54. [IDIS 396283] [PubMed 9361646]

112. ACOG task force on hypertension in pregnancy: hypertension in pregnancy. Washington, DC: American College of Obstetricians and Gynecologists; 2013.

113. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: approaches to the prevention of heart failure. Am J Cardiol. 1999; 83:9A-38A.

114. 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; 314:1547-52. [IDIS 216898] [PubMed 3520315]

115. Cohn JN, Johnson G, Ziesche et al. A comparison of enalapril with hydralazine—isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med. 1991; 325:303-10. [IDIS 283294] [PubMed 2057035]

116. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. [PubMed 10818056]

117. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. [PubMed 10818055]

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122. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-60. [IDIS 490723] [PubMed 12479770]

123. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288:2981-97. [IDIS 490721] [PubMed 12479763]

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125. Whelton PK, Appel LJ, Espeland MA et al. for the TONE Collaborative Research Group. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). JAMA. 1998; 279:839-46. [PubMed 9515998]

127. Psaty BM, Smith NL, Siscovick DS et al. Health outcomes associated with antihypertensive therapies used as first-line agents: a systematic review and meta-analysis. JAMA. 1997; 277:739-45. [IDIS 380501] [PubMed 9042847]

130. The Guidelines Subcommittee of the WHO/ISH Mild Hypertension Liaison Committee. 1999 guidelines for the management of hypertension. J Hypertension. 1999; 17:392-403.

132. Carter B for the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Personal communication.

133. National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004; 114(Suppl 2):555-76. [PubMed 15286277]

134. Par Pharmaceutical, Inc. Hydralazine hydrochloride tablets prescribing information. Spring Valley, NY; 2003 Jun.

135. NitroMed, Inc. BiDil (isosorbide dinitrate and hydralazine hydrochloride) tablets prescribing information. Lexington, MA; 2005 Jun 23.

136. Taylor AL, Ziesche S, Yancy C et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004; 351:2049-57. [IDIS 523647] [PubMed 15533851]

137. Anon. BiDil for heart failure. Med Lett Drugs Ther. 2005; 47:77-8.

139. Duley L, Meher S, Jones L. Drugs for treatment of very high blood pressure during pregnancy. Cochrane Database Syst Rev. 2013; 7:CD001449. [PubMed 23900968]

500. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). Bethesda, MD: National Institutes of Health; 2004 Aug. (NIH publication No. 04-5230.)

501. James PA, Oparil S, Carter BL et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014; 311:507-20. [PubMed 24352797]

502. Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013; 31:1281-357. [PubMed 23817082]

503. Go AS, Bauman MA, Coleman King SM et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension. 2014; 63:878-85. [PubMed 24243703]

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524. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013; 128:e240-327. [PubMed 23741058]

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HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:618-20.

b. AHFS drug information 2015. McEvoy GK, ed. Hydralazine. Bethesda, MD: American Society of Health-System Pharmacists; 2015: .

e. American Regent. Hydralazine hydrochloride injection prescribing information. Shirley, NY; 2002 Jun.

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