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Nesiritide

Generic name: nesiritide systemic

Brand names: Natrecor

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution Reconstituted, Intravenous:

Natrecor: 1.5 mg (1 ea [DSC])

Pharmacology

Mechanism of Action

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.

Pharmacokinetics/Pharmacodynamics

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

Acutely decompensated heart failure (HF): 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 and Administration

Dosing: Adult

Note: Natrecor is no longer available in the US.

Acute decompensated heart failure: 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.

Dosing: Geriatric

Refer to adult dosing. Older individuals may be more sensitive to the effect of nesiritide than younger patients.

Dosing: Pediatric

Note: Natrecor is no longer available in the US.

Heart failure, decompensated: Limited data available: Note: Nesiritide is not recommended for first-line therapy; may be considered when other treatment options have failed to lower central venous pressure (CVP) (ISHLT [Kirk 2014]): Infants, Children, and Adolescents:

Continuous IV infusion: Initial bolus (optional): 1 mcg/kg, followed by continuous infusion of 0.01 mcg/kg/minute; titrate by 0.005 mcg/kg/minute based on clinical response; manufacturer's labeling recommends titrating not more frequently than every 3 hours in adults; usual reported dose range: 0.005 to 0.02 mcg/kg/minute; maximum infusion rate: 0.03 mcg/kg/minute (Jefferies 2007; Mahle 2005). Dosing is based on a retrospective study and an observational study. The retrospective study included 30 pediatric patients (age: median: 4.6 months, range: 5 days to 16.7 years) with heart failure and worsening symptoms despite receiving conventional therapy (eg, inotropic and diuretic therapy). Most patients (80%) received a bolus dose of 1 mcg/kg and all patients received a continuous infusion of 0.005 to 0.02 mcg/kg/minute. Fluid balance and urine output significantly increased after 24 hours of treatment. Minimal effects on blood pressure were reported during infusion; however, one patient required discontinuation due to hypotension (Mahle 2005). Similar results were reported in the observational study of 63 patients (age: 11.97 ± 4.76 years; range: 0.01 to 20.5 years); patients were treated with an initial infusion rate of 0.01 mcg/kg/minute (without bolus dose); if necessary based on clinical response, rate was titrated by 0.005 mcg/kg/minute to a maximum rate of 0.03 mcg/kg/minute. Urine output improved on days 1 and 3 of therapy and only two patients required discontinuation due to hypotension (Jefferies 2007). If hypotension occurs during nesiritide administration, consider reducing dose or discontinuing infusion; if necessary, other measures to support blood pressure should be initiated.

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

IV: 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.

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

Benperidol: 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

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination

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

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

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

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

Nicergoline: 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

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. 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

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. 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

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

Adverse Reactions

Note: Incidences of adverse reactions include unapproved dosing regimens as well as combination therapy data.

>10%:

Cardiovascular: Hypotension (4% to 12%)

Renal: Increased serum creatinine (28% with >0.5 mg/dL above baseline; 5% with 50% greater serum creatinine levels than at baseline), renal insufficiency (>25% decrease in glomerular filtration rate: 31%)

1% to 10%:

Central nervous system: Headache (7%)

Endocrine & metabolic: Hypoglycemia (≥2%)

Gastrointestinal: Nausea (3%)

Neuromuscular & skeletal: Back pain (3%)

<1%, postmarketing and/or case reports: Extravasation, hypersensitivity reactions, pruritus, skin rash

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

Pregnancy Considerations

Adverse events were not observed in an animal reproduction study.

Data in humans are inadequate to make recommendations for use in pregnancy (ESC [Regitz-Zagrosek 2018]).

Patient Education

What is this drug used for?

  • It is used to treat heart failure (weak heart).

Frequently reported side effects of this drug

  • Headache
  • Nausea
  • Back pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

  • Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain
  • Severe dizziness
  • Passing out
  • Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Source: Wolters Kluwer Health. Last updated February 6, 2020.