Interactive Dosing

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Indications and Usage

NATRECOR^® is indicated for the intravenous treatment of patients with acutely decompensated congestive heart failure who have dyspnea at rest or with minimal activity. In this population, the use of NATRECOR^® reduced pulmonary capillary wedge pressure and improved dyspnea.

Contraindications

NATRECOR^® is contraindicated in patients who are hypersensitive to any of its components. NATRECOR^® should not be used as primary therapy for patients with cardiogenic shock or in patients with a systolic blood pressure <90 mm Hg.

Warnings

Administration of NATRECOR^® should be avoided in patients suspected of having, or known to have, low cardiac filling pressures.

The NATRECOR^® bolus must be drawn from the prepared infusion bag.
NATRECOR^® is for intravenous use only. There is limited experience with administering NATRECOR^® for longer than 48 hours. Blood pressure should be monitored closely during NATRECOR^® administration.
If hypotension occurs during the administration of NATRECOR^®, the dose should be reduced or discontinued and other measures to support blood pressure should be started (IV fluids, changes in body position). In the VMAC (Vasodilation in the Management of Acute Congestive Heart Failure) trial, when symptomatic hypotension occurred, NATRECOR^® was discontinued and subsequently could be restarted at a dose that was reduced by 30% (with no bolus administration) once the patient was stabilized. Because hypotension caused by NATRECOR^® may be prolonged (up to hours), a period of observation may be necessary before restarting the drug.

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Preparation
The NATRECOR^® bolus must be drawn from the prepared infusion bag.

Reconstitute one 1.5 mg vial of NATRECOR^® by adding 5 mL of diluent removed from a pre-filled 250 mL plastic IV bag containing the diluent of choice. After reconstitution of the vial, each mL contains 0.32 mg of nesiritide. The following preservative-free diluents are recommended for reconstitution: 5% Dextrose Injection (D5W), USP; 0.9% Sodium Chloride Injection, USP; 5% Dextrose and 0.45% Sodium Chloride Injection, USP, or 5% Dextrose and 0.2% Sodium Chloride Injection, USP.
Do not shake the vial. Rock the vial gently so that all surfaces, including the stopper, are in contact with the diluent to ensure complete reconstitution. Use only a clear, essentially colorless solution.
Withdraw the entire contents of the reconstituted NATRECOR^® vial and add to the 250 mL plastic IV bag. This will yield a solution with a concentration of NATRECOR^® of approximately 6 mcg/mL. The IV bag should be inverted several times to ensure complete mixing of the solution.
Use the reconstituted solution within 24 hours, as NATRECOR^® contains no antimicrobial preservative. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Reconstituted vials of Natrecor^® may be stored at 2-25°C (36-77°F) for up to 24 hours.

Dosing Instructions
The NATRECOR^® bolus must be drawn from the prepared infusion bag.
The recommended dose of NATRECOR^® is an IV bolus of 2 mcg/kg followed by a continuous infusion of 0.01 mcg/kg/min. NATRECOR^® should not be initiated at a dose that is above the recommended dose.

Prime the IV tubing with 5 mL of the solution for infusion prior to connecting to the patient's vascular access port and prior to administering the bolus or starting the infusion.
The administration of the recommended dose of NATRECOR^® is a two step process:

Step 1: Administration of the IV Bolus

After preparation of the infusion bag, as described previously, withdraw the bolus volume (see Weight-Adjusted Bolus Volume table) from the NATRECOR^® infusion bag, and administer it over approximately 60 seconds through an IV port in the tubing.

Bolus Volume (mL) = Patient Weight (kg) / 3

NATRECOR^® Weight-Adjusted Bolus Volume
Administered Over 60 Seconds
(Final Concentration = 6 mcg/mL)

Click here to use the Interactive NATRECOR^® Dosing Calculator

Patient Weight (kg)	Volume of Bolus (mL = kg/3)
60	20.0
70	23.3
80	26.7
90	30.0
100	33.3
110	36.7

Step 2: Administration of the Continuous Infusion
Immediately following the administration of the bolus, infuse NATRECOR^® at a flow rate of 0.1 mL/kg/hr. This will deliver a NATRECOR^® infusion dose of 0.01 mcg/kg/min.
To calculate the infusion flow rate to deliver a 0.01 mcg/kg/min dose, use the following formula (see the following Weight-Adjusted Infusion Flow Rate for Dosing table):

Infusion Flow Rate (mL/hr) = Patient Weight (kg) x 0.1

NATRECOR^® Weight-Adjusted Infusion Flow Rate
for a 0.01 mcg/kg/min Dose following Bolus
(Final Concentration = 6 mcg/mL)

Click here to use the Interactive NATRECOR^® Dosing Calculator

Patient Weight (kg)	Infusion Flow Rate(mL/hr)
60	6
70	7
80	8
90	9
100	10
110	11

Dose Adjustments
The dose-limiting side effect of NATRECOR^® is hypotension. Do not initiate NATRECOR^® at a dose that is higher than the recommended dose of a 2 mcg/kg bolus followed by an infusion of 0.01 mcg/kg/min. In the VMAC trial there was limited experience with increasing the dose of NATRECOR^® above the recommended dose (23 patients, all of whom had central hemodynamic monitoring). In those patients, the infusion dose of NATRECOR^® was increased by 0.005 mcg/kg/min (preceded by a bolus of 1 mcg/kg), no more frequently than every 3 hours up to a maximum dose of 0.03 mcg/kg/min. NATRECOR^® should not be titrated at frequent intervals as is done with other IV agents that have a shorter half-life (see Clinical Trials section of NATRECOR^® Full Prescribing Information).

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Chemical/Physical Interactions
NATRECOR^® is physically and/or chemically incompatible with injectable formulations of heparin, insulin, ethacrynate sodium, bumetanide, enalaprilat, hydralazine, and furosemide. These drugs should not be co-administered as infusions with NATRECOR^® through the same IV catheter. The preservative sodium metabisulfite is incompatible with NATRECOR^®. Injectable drugs that contain sodium metabisulfite should not be administered in the same infusion line as NATRECOR^®. The catheter must be flushed between administration of NATRECOR^® and incompatible drugs.

NATRECOR^® binds to heparin and therefore could bind to the heparin lining of a heparin-coated catheter, decreasing the amount of NATRECOR^® delivered to the patient for some period of time. Therefore, NATRECOR^® must not be administered through a central heparin-coated catheter. Concomitant administration of a heparin infusion through a separate catheter is acceptable.

Indication

NATRECOR^® (nesiritide) is indicated for the intravenous treatment of patients with acutely decompensated heart failure who have dyspnea (difficulty breathing) at rest or with minimal activity.

Important Safety Information

HYPOTENSION

NATRECOR^® may cause hypotension and should be administered only in settings where blood pressure can be monitored closely. If hypotension occurs during administration of NATRECOR^®, the dose should be reduced or discontinued. At the recommended dose of NATRECOR^®, the incidence of symptomatic hypotension (4%) was similar to that of IV nitroglycerin (5%). Asymptomatic hypotension occurred in 8% of patients treated with either drug. In some cases, hypotension that occurs with NATRECOR^® may be prolonged. The mean duration of symptomatic hypotension was longer with NATRECOR^® than IV nitroglycerin (2.2 versus 0.7 hours, respectively). NATRECOR^® should not be used in patients with systolic blood pressure <90 mm Hg or as primary therapy in patients with cardiogenic shock. The rate of symptomatic hypotension may be increased in patients with a baseline blood pressure <100 mm Hg, and NATRECOR^® should be used cautiously in these patients. In earlier trials, when NATRECOR^® was initiated at doses higher than the 2 mcg/kg bolus followed by a 0.01 mcg/kg/min infusion, the frequency, intensity, and duration of hypotension were increased. The hypotensive episodes were also more often symptomatic and/or more likely to require medical intervention.

NATRECOR^® is not recommended for patients for whom vasodilating agents are not appropriate and should be avoided in patients with low cardiac filling pressures.

RENAL

NATRECOR^® may affect renal function in susceptible individuals. In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with NATRECOR^® may be associated with azotemia. In the VMAC trial, through day 30, the incidence of elevations in creatinine to >0.5 mg/dL above baseline was 28% and 21% in the NATRECOR^® and nitroglycerin groups, respectively. When NATRECOR^® was initiated at doses higher than 0.01 mcg/kg/min, there was an increased rate of elevated serum creatinine over baseline compared with standard therapies, although the rate of acute renal failure and need for dialysis were not increased.

MORTALITY

In 7 NATRECOR^® clinical trials, through 30 days, 5.5% in the NATRECOR^® treatment group died as compared with 4.3% in the group treated with other standard medications. In 5 clinical trials, through 180 days, 21.5% in the NATRECOR^® treatment group died as compared with 20.7% in the group treated with other medications. There is not enough information to know if there is an increased risk of death after treatment with NATRECOR^®.

Please click here to see Full Prescribing Information for NATRECOR^®.

© Scios Inc. 2009.

This site is published by Scios Inc. which is solely responsible for its contents. Last Updated:May 06 2009 at 16:13:23 EDT.

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