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Class: Vasodilating Agents, Miscellaneous
VA Class: CV900
Chemical Name: Natriuretic factor-32 (human brain clone λhBNP57)
Molecular Formula: C143H244N50O42S4
CAS Number: 124584-08-3
Brands: Natrecor


Vasodilator; a biosynthetic (recombinant DNA origin) form of human B-type natriuretic peptide (BNP).1 4 7 8

Uses for Nesiritide

Acute Decompensated Heart Failure

Treatment of acutely decompensated heart failure in patients with dyspnea at rest or with minimal activity.1 2 5 7 8 9

Evidence demonstrating improved outcomes with IV vasodilator therapy in hospitalized patients with heart failure is lacking.524

May be considered an adjunct to diuretic therapy for relief of dyspnea in patients hospitalized for acutely decompensated heart failure who do not have symptomatic hypotension.524

FDA-approved labeling for treatment of dyspnea in patients with acutely decompensated heart failure based on clinical trials showing reductions in pulmonary capillary wedge pressure (PCWP) and improvement in dyspnea when assessed 3 hours after initiation of the IV infusion.1 17 20 21 A subsequent placebo-controlled trial in >7000 patients (ASCEND-HF) failed to show meaningful improvement in dyspnea at 6 or 24 hours or meaningful short-term reductions in rates of death or rehospitalization for heart failure when nesiritide was used in conjunction with standard therapy.17 20

Some clinicians state that routine use cannot be recommended in the broad population of patients with acutely decompensated heart failure.16 17 20 22

Use of intermittent, serial, or scheduled repetitive infusions in an outpatient setting for treatment of severe decompensated heart failure not recommended.14 18 21 23 A randomized, placebo-controlled trial failed to establish efficacy of serial outpatient nesiritide infusions for treatment of severe heart failure.18

Manufacturer recommends strictly limiting use to patients with acutely decompensated heart failure whose manifestations warrant hospitalization or management in emergency department.14

Manufacturer does not recommend use as replacement therapy for diuretics, to improve renal function, and/or to enhance diuresis.14 (See Renal Effects under Cautions.)

Nesiritide Dosage and Administration


  • Administer only in settings where BP can be closely monitored and hypotension treated aggressively.1

  • Concomitant use of other cardiovascular agents including IV nitroglycerin, but excluding certain IV vasodilators (e.g., sodium nitroprusside, milrinone) and IV ACE inhibitors, was allowed in clinical studies.1


Administer IV loading dose followed by continuous IV infusion.1 7

IV Administration

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

Reconstituted solutions contain no preservatives; solutions preferably should be prepared immediately before use.7

Prime IV tubing with 5 mL of diluted nesiritide solution prior to connecting the tubing to the patient’s vascular access port and prior to administering the loading dose or starting the infusion.1 7

Withdraw loading dose from the infusion bag containing diluted nesiritide solution and administer through port in IV infusion set; continuous infusion should follow immediately.1 7

Do not administer through a central catheter coated with heparin, since nesiritide binds to heparin.1


Remove 5 mL of a preservative-free diluent (see Solution Compatibility under Stability) from a prefilled 250-mL infusion bag and add the 5 mL of diluent to a vial labeled as containing 1.5 mg of nesiritide.1 7 Swirl vial gently to ensure dissolution; do not shake.1 7


Following reconstitution, add entire contents of the vial to the original 250-mL infusion bag, to yield a final nesiritide concentration of approximately 6 mcg/mL; invert bag several times to ensure complete mixing.1 7

Rate of Administration

Administer loading dose over approximately 60 seconds followed immediately by continuous IV infusion of nesiritide (6 mcg/mL) at a rate of 0.1 mL/kg per hour (approximately 0.01 mcg/kg per minute).1 7

The volume of diluted (6 mcg/mL) solution needed to administer a 2-mcg/kg loading dose can be calculated by using the following formula or can be obtained from the following table:1 7

Loading dose volume (in mL) = patient weight (in kg) / 3

Patient Weight (kg)

Loading Dose Volume (mL)













The rate (in mL/hr) at which the diluted (6 mcg/mL) solution must be infused to deliver a dosage of 0.01 mcg/kg per minute can be calculated by using the following formula or can be obtained from the following table:1 7

Continuous infusion rate (in mL/hr) = patient weight (in kg) × 0.1

Patient Weight (kg)

Continuous Infusion Rate (mL/hr)














Because of the possibility of dose-related episodes of severe and/or protracted hypotension, do not initiate nesiritide at higher than recommended dosages.1 7

Do not titrate at frequent intervals.1 7 10


Acute Decompensated Heart Failure

Loading dose of 2 mcg/kg over approximately 60 seconds, followed immediately by continuous infusion of 0.01 mcg/kg per minute.1 7 Loading dose may not be appropriate for patients with SBP <110 mm Hg or for those who recently received cardiac afterload-reducing agents (e.g., nitroglycerin).1

Increase infusion rate no more frequently than every 3 hours with central hemodynamic monitoring, up to maximum dosage of 0.03 mcg/kg per minute.1

Dosage Modification for Hypotensive Episodes

If hypotension occurs, reduce dosage or discontinue drug and institute supportive measures (e.g., IV fluids, changes in body position).1 7 10 If symptomatic hypotension occurs, discontinue drug.1

May reinitiate nesiritide without loading dose and with 30% reduction in infusion rate once patient has been stabilized.1 Because hypotension may be prolonged (up to hours), a period of observation may be necessary before infusion is restarted.1

Prescribing Limits



Maximum 0.03 mcg/kg per minute with central hemodynamic monitoring.1 7

Limited experience with infusions lasting >96 hours.1 In clinical studies, 28% of patients received nesiritide for >48 hours.1

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations.1

Renal Impairment

Clinical data (e.g., hemodynamic effects) suggest that dosage adjustment not required.1

Geriatric Patients

Manufacturer makes no specific dosage recommendations.1

Cautions for Nesiritide


  • Persistent SBP <100 mm Hg prior to initiation of therapy.1 (See Hypotensive Effects under Cautions.)

  • Cardiogenic shock.1

  • Known hypersensitivity to nesiritide or any ingredient in the formulation.1


Hypotensive Effects

In ASCEND-HF trial, incidence of symptomatic hypotension was increased with nesiritide compared with placebo (approximately 7 versus 4%).1 17

In VMAC trial, incidence of symptomatic hypotension in initial 24 hours of therapy was similar with nesiritide or IV nitroglycerin (4 or 5%, respectively), but more prolonged with nesiritide (mean duration: 2.2 hours) than with nitroglycerin (mean duration: 0.7 hour).1 5 7 9 10

Higher dosages have been associated with increased risk of hypotension.7 10 14 16 19

Concomitant use of agents that reduce cardiac afterload or affect renin-angiotensin-aldosterone system (e.g., ACE inhibitors, angiotensin II receptor antagonists) increases risk of symptomatic hypotension.1 (See Interactions.)

Administer only in settings where BP can be monitored closely and hypotension treated aggressively.1 If hypotension occurs, institute supportive measures.1 Dosage reduction or drug discontinuance may be required.1 7 10 (See Dosage Modification for Hypotensive Episodes under Dosage and Administration.)

Contraindicated in patients with persistent SBP <100 mm Hg prior to initiation of therapy.1

Concomitant Cardiac Disorders

Use not recommended in patients with known or suspected low cardiac filling pressures or in those for whom vasodilating agents are not appropriate (e.g., patients with substantial valvular stenosis, restrictive or obstructive cardiomyopathy, constrictive pericarditis, pericardial tamponade, or other conditions in which cardiac output depends on venous return).1 10

Risk of Mortality

Pooled analyses of data from initial controlled clinical trials (approximately 1500–1700 patients) indicated numerical, but not statistically significant, increases in 30-day mortality with nesiritide compared with other therapies (generally nitroglycerin and diuretics).10 11 14 19

Subsequent pooled analysis of data from 7 clinical trials (approximately 8500 patients), including ASCEND-HF, indicated no increase in 30-day mortality with nesiritide compared with active or placebo controls.1 Pooled analysis of data from 6 of these studies (approximately 8400 patients) indicated no increase in 180-day mortality with nesiritide compared with active or placebo controls.1

Renal Effects

Possible increased Scr.1 10 12 13 14 Monitor Scr during and after completion of therapy until concentrations are stable.1

Possible azotemia in patients with severe heart failure whose renal function depends on activity of the renin-angiotensin-aldosterone system.1 10 12 13 14

Risk of elevated Scr increased in patients receiving nesiritide infusions initiated at rates >0.01 mcg/kg per minute compared with those receiving standard therapies.1

Initial pooled analysis of data from 5 clinical trials (1269 patients) suggested 1.5-fold increase in risk of worsening renal function (Scr increase of >0.5 mg/dL) with nesiritide (up to 0.03 mcg/kg per minute) compared with active controls.12 However, in ASCEND-HF (>7000 patients), incidence of worsening renal function (decrease in estimated GFR of >25%) was similar with nesiritide (0.01 mcg/kg per minute) or placebo.17

Sensitivity Reactions

Hypersensitivity Reactions

Serious hypersensitivity reactions reported.1 More likely to occur in patients with history of sensitivity to recombinant peptides.1 Prior to initiation of nesiritide therapy, ask patients about previous hypersensitivity reactions to other recombinant peptides.1

If hypersensitivity reaction occurs, discontinue drug and provide appropriate treatment (e.g., epinephrine, oxygen, IV fluids, antihistamines, corticosteroids, pressor amines, airway management) as clinically indicated.1

Specific Populations


Category C.1


Not known whether nesiritide is distributed into milk.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 7

Geriatric Use

No substantial differences in efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1

Common Adverse Effects

Hypotension,1 5 7 10 17 headache,1 5 7 10 back pain,1 7 nausea.1 5 7 10

Interactions for Nesiritide

No formal drug interaction studies to date.1 7

Cardiovascular Agents

Cardiac afterload-reducing agents may increase risk of hypotension.1 (See also General under Dosage and Administration.)

Specific Drugs



ACE inhibitors (oral)

Increased incidence of symptomatic hypotension1

Pharmacokinetic interaction unlikely1

Angiotensin II receptor antagonists

Increased incidence of symptomatic hypotension1

Pharmacokinetic interaction unlikely1

Antiarrhythmic agents (class III)

Pharmacokinetic interaction unlikely1


Pharmacokinetic interaction unlikely1

β-Adrenergic blocking agents

May increase risk of hypotension1

Calcium-channel blocking agents

May increase risk of hypotension1


Pharmacokinetic interaction unlikely1


May increase risk of hypotension1


Pharmacokinetic interaction unlikely1

HMG-CoA reductase inhibitor [statin] antilipemic agents

Pharmacokinetic interaction unlikely1


May increase risk of hypotension1

Pharmacokinetic interaction with oral nitrates unlikely; potential for pharmacokinetic interaction with IV nitroglycerin not established1

Nesiritide Pharmacokinetics


Elimination Route

Binding to cell surface clearance receptors with subsequent cellular internalization and lysosomal proteolysis; proteolytic cleavage of the peptide by endopeptidases (e.g., neutral endopeptidase) on the vascular lumenal surface; and renal filtration.16 19

Mechanisms involved in elimination not specifically studied in humans.1


Biphasic; mean initial-phase and terminal-phase half-lives of approximately 2 and 18 minutes, respectively.1

Special Populations

Renal impairment does not substantially alter pharmacokinetics.16

Age, gender, race/ethnicity, concentration of endogenous BNP, and severity of heart failure do not substantially affect clearance.1 16




Powder for Injection

<25°C; do not freeze.1 Store in carton to protect from light.1

Store reconstituted solution at 2–25°C; use up to 24 hours after reconstitution.1


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


Solution Compatibility

Compatible1 HID

Dextrose 5% in water

Dextrose 5% and 0.2 or 0.45% sodium chloride

Sodium chloride 0.9%

Drug Compatibility

Incompatible with drugs that contain the preservative sodium metabisulfite.1

Y-site CompatibilityHID


Amiodarone HCl



Diltiazem HCl

Fentanyl citrate

Milrinone lactate

Nicardipine HCl


Propranolol HCl

Quinidine gluconate

Sodium nitroprusside


Verapamil HCl




Ethacrynate sodium1


Heparin sodium1

Hydralazine HCl1

Insulin, regular1

Micafungin sodium


Metoprolol tartrate


  • A vasodilator that is structurally and pharmacologically identical to endogenous BNP,1 4 7 8 the principal natriuretic peptide responsible for maintaining normal fluid and sodium homeostasis in patients with heart failure.8

  • Produces dose-dependent reductions in pulmonary capillary wedge pressure and systemic arterial pressure and has modest diuretic and natriuretic effects in patients with heart failure.2 4 7 8 9

  • Proarrhythmic effects have not been observed in patients with decompensated heart failure receiving nesiritide.3 4 7

Advice to Patients

  • Importance of advising patient of potential risks and benefits of nesiritide therapy.1

  • Importance of informing clinician if symptoms of hypotension occur.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (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.



Dosage Forms


Brand Names



For injection, for IV infusion

1.5 mg



AHFS DI Essentials. © Copyright 2017, Selected Revisions January 31, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.


1. Scios Inc. Natrecor (nesiritide) for injection prescribing information. Fremont, CA; 2012 Jul.

2. Colucci WS, Elkayam U, Horton DP et al. Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. N Engl J Med. 2000; 343:246-53. [PubMed 10911006]

3. Burger AJ, Horton DP, LeJemtel T et al. Effect of nesiritide (B-type natriuretic peptide) and dobutamine on ventricular arrhythmias in the treatment of patients with acutely decompensated congestive heart failure: the PRECEDENT study. Am Heart J. 2002; 144:1102-8. [PubMed 12486437]

4. Colucci WS. Nesiritide for the treatment of decompensated heart failure. J Card Fail. 2001; 7:92-100. [PubMed 11264555]

5. Publication Committee for the VMAC Investigators (Vasodilatation in the Management of Acute CHF). Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA. 2002; 287:1531-40. [PubMed 11911755]

6. Silver MA, Horton DP, Ghali JK et al. Effect of nesiritide versus dobutamine on short-term outcomes in the treatment of patients with acutely decompensated heart failure. J Am Coll Cardiol. 2002; 39:798-803. [PubMed 11869844]

7. Scios, Sunnyvale, CA: Personal communication.

8. Hobbs RE, Mills RM, Young JB. An update on nesiritide for treatment of decompensated heart failure. Exp Opin Invest Drugs. 2001; 10:935-42.

9. Anon. Nesiritide for decompensated congestive heart failure. Med Lett Drugs Ther. 2001; 43:100-1.

10. Horton DP. Dear healthcare professional letter regarding important drug warning on Natrecor and possible adverse effects on survival and kidney function compared to control agents (e.g., nitroglycerin and diuretics). Scios Inc: Fremont, CA; 2005 May 6. From FDA web site. Accessed May 20, 2005.

11. Sackner-Bernstein JD, Kowalski M, Fox M et al. Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials. JAMA. 2005; 293:1900-5.

12. Sackner-Bernstein JD, Skopicki HA, Aaronson KD. Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation. 2005; 111:1487-91.

13. Teerlink JR, Massie BM. Nesiritide and worsening of renal function: the emperor’s new clothes? Circulation. 2005; 111:1459-61.

14. Horton DP. Dear healthcare professional letter regarding recommendations of an expert panel of cardiology and heart failure clinicians on the appropriate use of Natrecor (nesiritide) and the drug’s effect on mortality and kidney function. Scios Inc: Fremont, CA; 2005 July 13. From FDA web site. Accessed Oct. 20, 2005.

15. Yancy CW. Treatment with B-type natriuretic peptide for chronic decompensated heart failure: insights learned from the follow-up serial infusion of nesiritide (FUSION) trial.Heart Fail Rev. 2004;9:209-16.

16. Gassanov N, Biesenbach E, Caglayan E et al. Natriuretic peptides in therapy for decompensated heart failure. Eur J Clin Pharmacol. 2012; 68:223-30. [PubMed 21901345]

17. O'Connor CM, Starling RC, Hernandez AF et al. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med. 2011; 365:32-43. [PubMed 21732835]

18. Yancy CW, Krum H, Massie BM et al. Safety and efficacy of outpatient nesiritide in patients with advanced heart failure: results of the Second Follow-Up Serial Infusions of Nesiritide (FUSION II) trial. Circ Heart Fail. 2008; 1:9-16. [PubMed 19808265]

19. Scios Inc. Natrecor (nesiritide) for injection prescribing information. Fremont, CA; 2005 Apr.

20. Kociol RD, Konstam MA. Nesiritide ASCENDs the ranks of unproven treatments for acute heart failure. Am J Kidney Dis. 2012; 60:8-11. [PubMed 22305860]

21. Topol EJ. Nesiritide - not verified. N Engl J Med. 2005; 353:113-6. [PubMed 16014879]

22. Dandamudi S, Chen HH. The ASCEND-HF trial: an acute study of clinical effectiveness of nesiritide and decompensated heart failure. Expert Rev Cardiovasc Ther. 2012; 10:557-63. [PubMed 22651831]

23. Pleister AP, Baliga RR, Haas GJ. Acute study of clinical effectiveness of nesiritide in decompensated heart failure: nesiritide redux. Curr Heart Fail Rep. 2011; 8:226-32. [PubMed 21695395]

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.

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:848-9.