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All about: Nesiritide

Big Image Pronouncation: (nih-SIR-ih-tide)
Class: Human B-type natriuretic peptide

Trade Names:
Natrecor
- Powder for injection, lyophilized 1.58 mg

Mechanism of Action

Pharmacology

Binds to the particulate guanylate cyclase receptor of vascular smooth muscle and endothelial cells, leading to dose-dependent reductions in pulmonary capillary wedge pressure and systemic arterial pressure in patients with heart failure.

Pharmacokinetics

Distribution

The mean Vd of the central compartment is estimated to be 0.073 L/kg and the mean Cl is approximately 9.2 mL/min/kg. Following IV administration to patients with CHF, disposition from the plasma is biphasic.

Elimination

The mean terminal elimination t ½ is approximately 18 min and is associated with approximately 2/3 of the AUC. The mean initial elimination phase is about 2 min.

Onset

With administration of the recommended dosing regimen of 2 mcg/kg IV bolus followed by 0.01 mcg/kg/min, 60% of the 3-hr effect on pulmonary capillary wedge pressure reduction is achieved within 15 min after the bolus. Approximately 70% of the 3-hr effect on standing BP reduction is reached within 15 min.

Peak

95% of the 3-hr effect is achieved within 1 hr.

Duration

The pharmacodynamic t ½ of the onset and offset of the hemodynamic effect is longer than predicted by the pharmacokinetic t ½ .

Indications and Usage

Treatment of patients with acutely decompensated CHF who have dyspnea at rest or with minimal activity.

Contraindications

Primary treatment for patients with cardiogenic shock; systolic BP less than 90 mm Hg; hypersensitivity to any component of the product.

Dosage and Administration

Adults

IV Recommended dose is 2 mcg/kg IV bolus over 60 sec followed by continuous infusion at a dose of 0.01 mcg/kg/min. If hypotension occurs during administration, reduce or discontinue the dose and start other measures to support BP.

General Advice

  • For IV administration only. Not for intradermal, IM, subcutaneous, or intra-arterial administration.
  • Follow manufacturer's instructions for reconstitution of powder and final dilution for infusion solution.
  • Do not shake or agitate vials during reconstitution or dilution. Do not use filter needles during preparation of infusion.
  • Do not administer if solution is cloudy, discolored, or contains particulate matter.
  • Prime IV tubing with infusion solution prior to connecting to patient's vascular access port and prior to administering bolus dose and starting infusion.
  • Infusion rate may be increased by 0.005 mcg/kg/min, no more often than q 3 hr up to a max of 0.03 mcg/kg/min. Increases in infusion rate should be preceded by a bolus dose of 1 mcg/kg.
  • Do not administer through a central heparin-coated catheter.
  • Flush catheter between administration of nesiritide and any incompatible injectable medication.

Storage/Stability

Store vials at controlled room temperature (68° to 77°F) in original carton. Use reconstituted solution immediately. If immediate use is not possible, the reconstituted solution may be stored for up to 24 hr in refrigerator (36° to 46°F) or at controlled room temperature.

Drug Interactions

ACE inhibitors (eg, captopril)

Coadministration may cause an increase in symptomatic hypotension.

Incompatibility

Physically and chemically incompatible with injectable formulations of bumetanide, enalaprilat, ethacrynate sodium, furosemide, hydralazine, heparin, and insulin. These agents should not be administered as infusions with nesiritide through the same IV catheter. Sodium metabisulfite preservative is incompatible with nesiritide. Since nesiritide binds with heparin, do not administer through a central heparin-coated catheter.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension (symptomatic and asymptomatic) (11%); ventricular tachycardia (3%); nonsustained ventricular tachycardia (3%); ventricular extrasystoles (3%); angina pectoris; bradycardia; tachycardia; atrial fibrillation; AV node conduction abnormalities.

CNS

Headache (8%); insomnia; dizziness (3%); anxiety (3%); confusion; paresthesia; somnolence; tremor.

Dermatologic

Sweating; pruritus; rash.

EENT

Amblyopia.

GI

Nausea (4%); vomiting.

Hematologic

Anemia.

Respiratory

Increased cough; hemoptysis; apnea.

Miscellaneous

Abdominal pain; back pain; catheter pain; fever; injection site reaction; increased creatinine; leg cramps.

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

Renal function may be affected in susceptible patients; azotemia may occur in patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system.

Cardiac

Avoid administration in patients suspected of having or known to have low cardiac filling pressures. Not recommended for use in patients for whom vasodilating agents are not approved (eg, significant valvular stenosis; restrictive or obstructive cardiomyopathy).

Hypotension

May occur at recommended or adjustable doses.

Overdosage

Symptoms

Hypotension

Patient Information

  • Explain name, action, dosing regimen, and potential side effects of drug.
  • Advise patient, family, or caregiver that medication will be prepared and administered by highly trained health care providers in an intensive care setting.

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