Natrecor

Dosage Forms & Strengths

injectable solution

• 1.5mg/vial

Acutely Decompensated CHF with Dyspnea at Rest

2 mcg/kg IV bolus over 1 minute, THEN

0.01 mcg/kg/min IV infusion 

If hypotension, discontinue until stabilized, then restart at 30% lower dose

Limited data available for use longer than 48 hours

Renal Impairment

Use caution; monitor renal function closely

Hepatic Impairment

Dose adjustment not necessary

Safety and efficacy not established

Mechanism of Action

Recombinant human B-type natriuretic peptide; increases cGMP in vascular smooth muscle resulting in vasodilation, reduce pulmonary capillary wedge pressure (PCWP)

No effect on cardiac contractility

Pharmacokinetics

Duration: Several hours (for systolic blood pressure); hemodynamic effect may persist longer its half-life

Onset: 15 min (PCWP reduction);

Peak Plasma Time: 90-120 min

Vd: 0.19 L/kg

Metabolism: By neutral endopeptidases in proximal tubule brush border in the kidney

Excretion: Urine; metabolism

Half-Life: 18-23 min

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Tell your doctor about all other medicines you use, especially medication to treat high blood pressure (hypertension).

Other drugs may interact with nesiritide, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your healthcare providers about all medicines you use now, and any medicine you start or stop using.

NATRECOR® (nesiritide) is a sterile, purified preparation of human B-type natriuretic peptide (hBNP), and is manufactured from E. coli using recombinant DNA technology. Nesiritide has a molecular weight of 3464 g/mol and an empirical formula of C143H244N50O42S4. Nesiritide has the same 32 amino acid sequence as the endogenous peptide, which is produced by the ventricular myocardium.

NATRECOR® is formulated as the citrate salt of rhBNP, and is provided in a sterile, single-use vial. Each 1.5 mg vial contains a white- to off-white lyophilized powder for intravenous (IV) administration after reconstitution. The quantitative composition of the lyophilized drug per vial is: nesiritide 1.58 mg, citric acid monohydrate 2.1 mg, mannitol 20.0 mg, and sodium citrate dihydrate 2.94 mg.

Included as part of the PRECAUTIONS section.

Your doctor or pharmacist can provide more information about nesiritide.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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Natrecor is part of the drug class:

• Other vasodilators used in cardiac diseases

Serious side effects have been reported with Natrecor including the following: 

• Low blood pressure. Your doctor will monitor your blood pressure. 
• Worsening kidney problems. Your doctor will monitor how well your kidneys are working during treatment and after treatment. 
• Allergic reaction. 

Do not receive Natrecor if you:

• are allergic to Natrecor or to any of its ingredients
• have a systolic blood pressure of <100 mmHg before therapy
• are in cardiogenic shock 

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Natrecor falls into category C. There are no well-controlled studies that have been done in pregnant women. Natrecor should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Natrecor crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Natrecor.

Receive Natrecor exactly as prescribed.

Natrecor is available in an injectable form that is given directly into a vein (IV) by a healthcare professional.

In the U.S.

• Natrecor

Available Dosage Forms:

• Powder for Solution

Therapeutic Class: Cardiovascular Agent

Pharmacologic Class: Natriuretic Peptide

• If you have an allergy to nesiritide or any other part of Natrecor (nesiritide).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have low blood pressure.
• If you have heart problems.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Natrecor with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Have your blood pressure checked often. Talk with your doctor.
• If you are 65 or older, use Natrecor with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

Natrecor® is contraindicated in patients with:

• Persistent systolic blood pressure <100 mm Hg prior to therapy because of an increased risk of symptomatic hypotension [see Warnings and Precautions (5.1)]
• Known hypersensitivity to any of its components [see Warnings and Precautions (5.3)]
• Cardiogenic shock

The following are discussed in more detail in other sections of the labeling:

• Hypotension [see Warnings and Precautions (5.1)]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. A causal relationship for Natrecor® cannot be reliably established in individual cases.

Adverse drug reactions that occurred at least ≥2% more frequently on Natrecor® than on placebo during the first 24 hours of infusion (excluding the ASCEND-HF study) are shown in Table 3.

Laboratory adverse drug reactions that occurred in ≥2% of patients and collected during the first 14 days after the start of Natrecor® infusion included: hypoglycemia.

Worsening Renal Function

In the ASCEND-HF trial, through Day 30, the incidence of renal impairment as measured by a >25% decrease in glomerular filtration rate (calculated based on serum creatinine) was observed in 31.4% and 29.5% in the Natrecor® and placebo groups, respectively. Other metrics of decompensated renal function such as an increase in creatinine of > 0.5 mg/dl, a 50% increase in creatinine or a value of ≥ 2 or 100% increase in creatinine were more frequent in the Natrecor® group. At 30 days post enrollment, more subjects in the Natrecor® group had elevated levels of creatinine of 50% greater than baseline compared to placebo 4.6% versus 3.3%. In the ASCEND-HF study there were relatively few subjects requiring either hemofiltration or dialysis.

In the PRECEDENT trial, the incidence of elevations in serum creatinine to >0.5 mg/dL above baseline through Day 14 was higher in the Natrecor® 0.015 mcg/kg/min group (17%) and the Natrecor® 0.03 mcg/kg/min group (19%) than with standard therapy (11%). 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® (2 mcg/kg bolus followed by 0.01 mcg/kg/min) and nitroglycerin groups, respectively.

Neutral Effect on Mortality

A meta-analysis performed of seven clinical trials demonstrated Natrecor® did not increase mortality in patients with acute decompensated heart failure (ADHF) at Day 30 or Day 180 (see Figures 1 and 2). Data from seven studies in which 30-day data were collected are presented in Figure 1. The data depict hazard ratios (HR) and confidence intervals (CI) of mortality data for randomized and treated patients with Natrecor® relative to active or placebo controls through Day 30 for each of the seven individual studies along with the overall combined estimate (Studies 311, 325, 326, 329 [PRECEDENT], 339 [VMAC], 341 [PROACTION], and A093 [ASCEND-HF]).

Figure 1 (on logarithmic scale) also contains an estimate for the seven studies combined (n=8514). The results indicate that there is no increased mortality risk for Natrecor® at Day 30 (seven studies pooled: HR=0.99; 95% CI: 0.80, 1.22). The percentages are the Kaplan-Meier estimates.

Figure 2 presents 180-day mortality hazard ratios from all six individual studies where 180-day data were collected (Studies 325, 326, 329, 339, 341 and A093 [ASCEND-HF]). The results indicate that with the addition of the ASCEND-HF data, there is no increased mortality risk for Natrecor® at Day 180 (six studies pooled: HR=0.98; 95% CI: 0.88, 1.10).

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Natrecor®. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.

• Hypersensitivity reactions
• Infusion site extravasation
• Pruritus
• Rash

No trials specifically examining potential drug interactions with Natrecor® were conducted, although many concomitant drugs (including IV nitroglycerin) were used in clinical trials [see Clinical Studies (14)]. No drug interactions were detected except for an increase in symptomatic hypotension in patients receiving afterload reducers or affecting the renin-angiotensin system (i.e., ARBs and/or ACE inhibitors).

The co-administration of Natrecor® with nitroprusside, milrinone, or IV ACE inhibitors has not been evaluated.

Applies to nesiritide: intravenous powder for solution

Along with its needed effects, nesiritide (the active ingredient contained in Natrecor) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking nesiritide:

• Low blood pressure

• Bluish lips or skin
• chest pain, tightness, or discomfort
• cool, clammy skin
• difficulty in breathing or shortness of breath
• dizziness
• fainting
• lightheadedness
• fast, slow, or irregular heartbeat
• unusual tiredness or weakness

Some side effects of nesiritide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Headache

• Abdominal or stomach pain
• anxiety
• back pain
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings on the skin
• change in vision
• confusion
• coughing or spitting up blood
• fever
• increased cough
• itching skin
• leg cramps
• nausea
• pain or irritation at the injection site
• pale skin, unusual bleeding or bruising
• rash
• sleepiness or unusual drowsiness
• sleeplessness
• sweating
• trembling or shakiness
• vomiting

Caution is recommended. Excreted into human milk: Unknown Excreted into animal milk: Data not available Comments: The effects in nursing infant are unknown.