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Nesiritide

Pronunciation

(ni SIR i tide)

Index Terms

  • B-type Natriuretic Peptide (Human)
  • hBNP
  • Natriuretic Peptide

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Natrecor: 1.5 mg (1 ea)

Brand Names: U.S.

  • Natrecor

Pharmacologic Category

  • Natriuretic Peptide, B-Type, Human

Pharmacology

Binds to guanylate cyclase receptor on vascular smooth muscle and endothelial cells, increasing intracellular cyclic GMP, resulting in smooth muscle cell relaxation. Has been shown to produce dose-dependent reductions in pulmonary capillary wedge pressure (PCWP) and systemic arterial pressure.

Distribution

Vss: 0.19 L/kg

Metabolism

Proteolytic cleavage by vascular endopeptidases and proteolysis following binding to the membrane bound natriuretic peptide (NPR-C) and cellular internalization

Excretion

Primarily eliminated by metabolism; also excreted in the urine

Onset of Action

PCWP reduction: 15 minutes (60% of 3-hour effect achieved within this time period); Peak effect: Within 1 hour

Duration of Action

>60 minutes (up to several hours) for systolic blood pressure; hemodynamic effects persist longer than serum half-life would predict

Half-Life Elimination

Initial (distribution) ~2 minutes; Terminal: ~18 minutes

Use: Labeled Indications

Treatment of acutely decompensated heart failure (HF) with dyspnea at rest or with minimal activity

Contraindications

Hypersensitivity to natriuretic peptide or any component of the formulation; cardiogenic shock (when used as primary therapy); hypotension (persistent systolic blood pressure <100 mm Hg) prior to therapy

Dosage

Adults: IV: Initial: 2 mcg/kg (bolus optional); followed by continuous infusion at 0.01 mcg/kg/minute. Note: Should not be initiated at a dosage higher than initial recommended dose. There is limited experience with increasing the dose >0.01 mcg/kg/minute; in one trial, a limited number of patients received higher doses that were increased no faster than every 3 hours by 0.005 mcg/kg/minute (preceded by a bolus of 1 mcg/kg), up to a maximum of 0.03 mcg/kg/minute. Increases beyond the initial infusion rate should be limited to selected patients and accompanied by close hemodynamic and renal function monitoring.

Patients experiencing hypotension during the infusion: Infusion dose should be reduced or discontinued. Other measures to support blood pressure should be initiated (eg, IV fluids, Trendelenburg position). Hypotension may be prolonged (up to hours); once patient is stabilized, may attempt to restart at a lower dose (reduce previous infusion dose by 30% and omit bolus).

Maximum dosing weight: According to the manufacturer, the PRECEDENT Trial capped dosing weight at 160 kg and the VMAC Trial capped dosing weight at 175 kg. There are no specific guidelines on maximum dosing weight and clinical judgment should be used.

Dosage adjustment in renal impairment: No dosage adjustment necessary. Use cautiously in patients with renal impairment or those patients who rely on the renin-angiotensin-aldosterone system for renal perfusion. Monitor renal function closely.

Dosage adjustment in hepatic impairment: No dosage adjustment provided in manufacturer’s labeling.

Reconstitution

Reconstitute 1.5 mg vial with 5 mL of diluent removed from a prefilled 250 mL plastic IV bag (compatible with D5W, D51/2NS, D51/4NS, NS). Do not shake vial to dissolve (roll gently). Withdraw entire contents of vial and add to 250 mL IV bag. Invert several times to mix. Resultant concentration of solution is ∼6 mcg/mL.

Administration

Do not administer through a heparin-coated catheter (concurrent administration of heparin via a separate catheter is acceptable, per manufacturer).

Prime IV tubing with 5 mL of infusion prior to connection with vascular access port and prior to administering bolus or starting the infusion. Withdraw bolus from the prepared infusion bag and administer over 60 seconds. Begin infusion immediately following administration of the bolus.

Compatibility

Stable in D5W, D51/2NS, D51/4NS, NS. Incompatible with injectable drugs containing sodium metabisulfite.

Y-site administration: Incompatible with bumetanide, enalaprilat, ethacrynate sodium, furosemide, heparin, hydralazine, insulin (regular), micafungin. Do not administer through the same catheter.

Storage

Vials may be stored below 25°C (77°F); do not freeze. Protect from light. Following reconstitution, vials are stable at 2°C to 25°C (36°F to 77°F) for up to 24 hours. Use reconstituted solution within 24 hours.

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Adverse Reactions

Note: Frequencies cited below were recorded in VMAC trial, unless otherwise noted, at dosages similar to approved labeling. Higher frequencies have been observed in trials using higher dosages of nesiritide. The percentages marked with an asterisk (*) indicate frequency less than or equal to placebo or other standard therapy.

>10%:

Cardiovascular: Hypotension (total: 11% [27% in ASCEND-HF trial]; symptomatic: 4% [7% in ASCEND-HF trial] at recommended dose, up to 17% at higher doses)

Renal: Increased serum creatinine (28% with >0.5 mg/dL increase over baseline)

1% to 10%:

Cardiovascular: Ventricular tachycardia (3%)*, ventricular extrasystoles (3%)*, angina (2%)*, bradycardia (1%), tachycardia, atrial fibrillation, AV node conduction abnormalities

Central nervous system: Headache (8%)*, dizziness (3%), insomnia (2%)*, anxiety (3%), confusion, fever, paresthesia, somnolence, tremor

Dermatologic: Pruritus, rash

Gastrointestinal: Nausea (4%)*, abdominal pain (1%)*, vomiting (1%)*

Hematologic: Anemia

Local: Injection site reaction, catheter pain

Neuromuscular & skeletal: Back pain (4%), leg cramps

Ocular: Amblyopia

Respiratory: Apnea, cough increased, hemoptysis

Miscellaneous: Diaphoresis

Postmarketing and/or case reports: Extravasation, hypersensitivity reactions (rare)

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactic/hypersensitivity reactions: Serious anaphylactic or hypersensitivity reactions may occur following administration; obtain careful history and use caution in patients with previous hypersensitivity to other recombinant peptides; nesiritide prepared through recombinant technology using E. coli.

• Hypotension: May cause hypotension; administer in clinical situations when blood pressure may be closely monitored. Effects may be additive with other agents capable of causing hypotension. Hypotensive effects may last for several hours.

• Renal effects: May be associated with development of azotemia; use caution in patients with renal impairment or in patients where renal perfusion is dependent on renin-angiotensin-aldosterone system (eg, severe heart failure); avoid initiation at doses higher than recommended; increases in serum creatinine may occur at an elevated rate.

Disease-related concerns:

• Cardiovascular disease: Should not be used in patients with low cardiac filling pressures, or in patients with conditions which depend on venous return including significant valvular stenosis, restrictive or obstructive cardiomyopathy, constrictive pericarditis, and pericardial tamponade.

• Renal impairment: Use with caution in patients with renal impairment.

Other warnings/precautions:

• Prolonged infusions: Use caution with prolonged infusions; limited experience with infusions >96 hours.

Monitoring Parameters

Blood pressure, hemodynamic responses (PCWP, RAP, CI), BUN, creatinine; urine output; consult individual institutional policies and procedures

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were not observed in an animal reproduction study. Nesiritide is a recombinant B-type natriuretic peptide (rhBNP). BNP and NT-proBNP (which has been used as a marker of BNP), are endogenous peptides and NT-proBNP is measurable in the umbilical cord serum of normal pregnancies. Information related to the administration of nesiritide during pregnancy has not been located.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache. Have patient report immediately to prescriber dyspnea, tachycardia, bradycardia, arrhythmia, severe dizziness, syncope, paresthesia, angina, illogical thinking, hemoptysis, urinary retention, oliguria, injection site pain or irritation, tremors, considerable asthenia, or vision changes (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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