Natrecor

Other Cardiovascular Agents

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

For intravenous (IV) administration only.
Do not exceed the recommended initial bolus or maintenance doses for nesiritide; serious hypotension and associated complications can occur with higher doses.
Nesiritide is physically and/or chemically incompatible with injectable formulations of heparin, insulin, ethacrynic acid, bumetanide, enalapril; enalaprilat, hydralazine, and furosemide. These drugs should not be coadministered as infusions through the same IV catheter with nesiritide. The catheter must be flushed with a compatible solution between IV administration of nesiritide and incompatible drugs.
Sodium metabisulfite (a preservative) is incompatible with nesiritide. Injectable drugs that contain sodium metabisulfite should not be administered in the same infusion line as nesiritide.
Nesiritide must not be administered through a central heparin-coated catheter. Nesiritide binds to heparin and therefore could bind to the heparin lining of a heparin-coated catheter, decreasing the amount of nesiritide delivered to the patient for some period of time. Concomitant administration of a heparin infusion through a separate catheter from nesiritide is acceptable.
Reconstitution of nesiritide vials:
Reconstitute one 1.5-mg vial of nesiritide by adding 5 ml of diluent removed from a pre-filled 250-ml plastic infusion bag containing the diluent of choice for the final infustion preparation. The following sterile, preservative-free IV diluents are recommended for reconstitution: D5W injection; NS injection; D5W and 0.45% Sodium Chloride injection; or D5W and 0.2% Sodium Chloride injection.
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.
Store reconstituted vials at room temperature (or refrigerated) for up to 24 hours (vials are preservative-free).
Preparation of intravenous (IV) infusion bag:
Withdraw the entire contents of the reconstituted nesiritide vial and add to the 250-ml plastic IV bag (Final drug concentration: 6 mcg/ml).
Invert the IV bag several times to ensure complete mixing of the solution.
Use the reconstituted intravenous infusion solution within 24 hours, as the solution contains no preservative.
Administration of the IV bolus followed by continuous IV infusion:
Prime the IV tubing with 5 ml of the infusion solution prior to connecting to the patient's vascular access port and prior to administering the bolus or starting the infusion.
After preparation of the infusion bag as per the above instructions, calculate the required bolus volume based on the patient's weight as follows: bolus volume (in ml) = 0.33 x patient weight (kg). Then withdraw the appropriate bolus volume (e.g., 20 ml for 60 kg, 23.3 ml for 70 kg, 26.7 ml for 80 kg, 30 ml for 90 kg, 33.3 ml for 100 kg, or 36.7 ml for 110 kg) from the nesiritide infusion bag, and inject it over about 60 seconds through an IV port in the tubing.
Immediately following the administration of the IV bolus, infuse nesiritide solution at a flow rate of 0.1 ml/kg/hour (e.g., 6 ml/h for 60 kg, 7 ml/h for 70 kg, 8 ml/h for 80 kg, 9 ml/h for 90 kg, 10 ml/h for 100 kg, or 11 ml/h for 110 kg). The calculation for the infusion flow rate (ml/hr) = 0.1 x patient weight (kg). This will deliver the initial recommended nesiritide maintenance infusion rate of 0.01 mcg/kg/min.
Monitor blood pressure closely. If hypotension occurs, the dose should be reduced or discontinued. Prolonged hypotension may occur. If nesiritide is restarted following stabilization of blood pressure, a period of observation may be necessary before restarting the drug.
Nesiritide is generally administered at a fixed IV infusion rate. Due to a long onset and offset of action, nesiritide should be titrated upward no more frequently than every 3 hours. Do not titrate infusion rate at frequent intervals as is done with other IV agents that have a significantly shorter half-life (e.g., dobutamine, dopamine, nitroglycerin, nitroprusside). See adult dosage section for further dosing information.

ventricular tachycardia / Early / 3.0-3.0
bradycardia / Rapid / 1.0-1.0
apnea / Delayed / 1.0
atrial fibrillation / Early / 1.0
azotemia / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known

hypotension / Rapid / 7.1-11.0
premature ventricular contractions (PVCs) / Early / 3.0-3.0
angina / Early / 2.0-2.0
sinus tachycardia / Rapid / 1.0
anemia / Delayed / 1.0
hemoptysis / Delayed / 1.0
confusion / Early / 1.0
amblyopia / Delayed / 1.0
hypoglycemia / Early / 2.0
orthostatic hypotension / Delayed / Incidence not known

headache / Early / 7.0-7.0
nausea / Early / 3.0-3.0
back pain / Delayed / 3.0-3.0
anxiety / Delayed / 3.0-3.0
insomnia / Early / 2.0-2.0
vomiting / Early / 1.0-1.0
abdominal pain / Early / 1.0-1.0
cough / Delayed / 1.0
paresthesias / Delayed / 1.0
diaphoresis / Early / 1.0
tremor / Early / 1.0
drowsiness / Early / 1.0
fever / Early / 1.0
muscle cramps / Delayed / 1.0
injection site reaction / Rapid / 1.0
rash / Early / 1.0
pruritus / Rapid / 1.0
syncope / Early / Incidence not known
dizziness / Early / Incidence not known

Natrecor

Rx

Parenteral recombinant preparation of human B-type natriuretic peptide (hBNP)
Indicated only for acute decompensated heart failure
Augments the normal physiologic response in heart failure; improves PCWP and CHF symptoms

2 mcg/kg IV followed by 0.01 mcg/kg/minute continuous IV infusion. May titrate up no more frequently than every 3 hours. Do not exceed 0.03 mcg/kg/minute. The loading dose may not be appropriate for patients with low systolic blood pressure (less than 110 mm Hg) or patients recently treated with afterload reducers. If hypotension occurs, reduce dose or discontinue nesiritide. May restart at a dose that is reduced by 30% (with no bolus administration) after stabilization of hemodynamics. There is limited experience with administering nesiritide for longer than 96 hours.[51226] Guidelines suggest nesiritide as an adjuvant to diuretics for relief of dyspnea in patients with acutely decompensated heart failure if symptomatic hypotension is absent.[57101] [62661]

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
 
Intermittent hemodialysis:
It is not known whether nesiritide is removed by hemodialysis.

Acetaminophen; Butalbital; Caffeine; Codeine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Acetaminophen; Codeine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Acetaminophen; Hydrocodone: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Acetaminophen; Oxycodone: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Acetaminophen; Propoxyphene: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Alfentanil: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Alpha-blockers: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Amyl Nitrite: (Major) The potential for hypotension may be increased when coadministering nesiritide with other vasodilators or hypotensive drugs, such as nitrates.
Angiotensin II receptor antagonists: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Angiotensin-converting enzyme inhibitors: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Articaine; Epinephrine: (Major) Nesiritide may have additive inoptropic effects with cardiac glycosides.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Aspirin, ASA; Caffeine; Dihydrocodeine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Aspirin, ASA; Carisoprodol; Codeine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Aspirin, ASA; Oxycodone: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Belladonna; Opium: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Beta-adrenergic blockers: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Brompheniramine; Guaifenesin; Hydrocodone: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Calcium-channel blockers: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Carbinoxamine; Hydrocodone; Phenylephrine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Cardiac glycosides: (Major) Nesiritide may have additive inoptropic effects with cardiac glycosides.
Central-acting adrenergic agents: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Chlorpheniramine; Codeine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Chlorpheniramine; Hydrocodone: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Codeine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Codeine; Guaifenesin: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Codeine; Phenylephrine; Promethazine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Codeine; Promethazine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Dexmedetomidine: (Moderate) Concomitant administration of dexmedetomidine and nesiritide could lead to additive hypotension and bradycardia; use together with caution. In clinical trials where other vasodilators were co-administered with dexmedetomidine an additive pharmacodynamic effect was not observed. Nonetheless, both drugs may cause symptomatic hypotension. If hypotension occurs, dose reduction of one or both infusions may be needed and supportive measures instituted.
Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Diphenhydramine; Hydrocodone; Phenylephrine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Dobutamine: (Major) Nesiritide may have additive inoptropic effects with cardiac glycosides.
Dopamine: (Major) Nesiritide may have additive inoptropic effects with cardiac glycosides.
Epinephrine: (Major) Nesiritide may have additive inoptropic effects with cardiac glycosides.
Eplerenone: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Epoprostenol: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Fentanyl: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
General anesthetics: (Major) The potential for hypotension may be increased when coadministering nesiritide with other hypotensive drugs, including general anesthetics.
Ginger, Zingiber officinale: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of antiarrhythmics, inotropes and vasopressors; however, no clinical data are available.
Guaifenesin; Hydrocodone: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Homatropine; Hydrocodone: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Hydralazine; Isosorbide Dinitrate, ISDN: (Major) The potential for hypotension may be increased when coadministering nesiritide with other vasodilators or hypotensive drugs, such as nitrates.
Hydrocodone: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Hydrocodone; Ibuprofen: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Hydrocodone; Phenylephrine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Hydrocodone; Potassium Guaiacolsulfonate: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Hydrocodone; Pseudoephedrine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Hydromorphone: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Ibuprofen; Oxycodone: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Iloprost: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Isoproterenol: (Major) Although not identified during clinical trials, the potential for hypotension may be increased when coadministering nesiritide with other vasodilators or hypotensive drugs including isoproterenol.
Isosorbide Dinitrate, ISDN: (Major) The potential for hypotension may be increased when coadministering nesiritide with other vasodilators or hypotensive drugs, such as nitrates.
Isosorbide Mononitrate: (Major) The potential for hypotension may be increased when coadministering nesiritide with other vasodilators or hypotensive drugs, such as nitrates.
Levorphanol: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Loop diuretics: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Meperidine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Meperidine; Promethazine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Methadone: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Methohexital: (Major) The potential for hypotension may be increased when coadministering nesiritide with other hypotensive drugs, including general anesthetics.
Morphine: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Morphine; Naltrexone: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Nitrates: (Major) The potential for hypotension may be increased when coadministering nesiritide with other vasodilators or hypotensive drugs, such as nitrates.
Nitroglycerin: (Major) The potential for hypotension may be increased when coadministering nesiritide with other vasodilators or hypotensive drugs, such as nitrates.
Opiate Agonists: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Oxycodone: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Oxymorphone: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Potassium-sparing diuretics: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Prilocaine; Epinephrine: (Major) Nesiritide may have additive inoptropic effects with cardiac glycosides.
Propoxyphene: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Remifentanil: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Reserpine: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Sildenafil: (Major) No formal drug interaction trials have been conducted with nesiritide. Sildenafil use within 24 hours was an exclusion criteria for nesiritide treatment during clinical trials. Although not identified during clinical trials, the potential for symptomatic hypotension may be significantly increased when coadministering nesiritide with sildenafil. Sildenafil should be avoided within 24 hours before or after nesiritide use.
Sufentanil: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Thiazide diuretics: (Moderate) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Thiopental: (Major) The potential for hypotension may be increased when coadministering nesiritide with other hypotensive drugs, including general anesthetics.
Treprostinil: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Vasodilators: (Moderate) The potential for hypotension may be increased when coadministering nesiritide with vasodilators. Reduce the dose of or discontinue nesiritide in patients who develop hypotension. In clinical trials, no drug interactions were detected except for an increase in symptomatic hypotension in patients receiving afterload reducers, such as vasodilators.

Natrecor Intravenous Inj Pwd F/Sol: 1.5mg

0.03 mcg/kg/min IV continuous infusion, with cautious hemodynamic monitoring.

0.03 mcg/kg/min IV continuous infusion, with cautious hemodynamic monitoring.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Mechanism of Action: Nesiritide is an IV purified preparation of human B-type natriuretic peptide (hBNP). BNP is a naturally-occurring hormone produced in the ventricles of the heart. BNP should not be confused with ANP (atrial natriuretic peptide). ANP is produced in the atria while BNP is produced in the ventricles. BNP and ANP are endogenous hormones which cause natriuresis, diuresis, and vasodilation; however, the effects of BNP may be more potent and last longer.Endogenous concentrations of hBNP are elevated in patients with heart failure; the addition of nesiritide augments the body's normal physiologic response to heart failure. Nesiritide produces balanced arterial and venous dilation, evidenced by reductions in systemic vascular resistance, systemic arterial pressure, PCWP, right atrial pressure, and mean pulmonary arterial pressure. Nesiritide increases cardiac output and stroke volume, without increasing heart rate. It also has natriuretic actions and promotes diuresis.Human BNP binds to the particulate guanylate cyclase receptor of vascular smooth muscle and endothelial cells, leading to increased intracellular concentrations of guanosine 3'5'-cyclic monophosphate (cGMP) and smooth muscle cell relaxation. Cyclic GMP serves as a second messenger to dilate veins and arteries. Nesiritide has been shown to relax isolated human rhBNP arterial and venous tissue preparations that were precontracted with either endothelin-1 or the alpha-adrenergic agonist, phenylephrine. Intravenous nesiritide (0.015—0.06 mcg/kg/min) produces dose-dependent reductions in pulmonary capillary wedge pressure (PCWP) and systemic blood pressure (SBP) in patients with acute decompensated heart failure. Nesiritide, at IV doses ranging from 0.015 to 0.06 mcg/kg/min for 24 hours, produces significant decreases in PCWP (27—39%), mean right atrial pressure and systemic vascular resistance (SVR); these effects are accompanied by increased cardiac index (CI) and stroke volume index (SVI), without an associated increase in heart rate. Beneficial effects are sustained throughout the infusion. Nesiritide promotes diuresis due to a direct natriuretic action, increased cardiac output, and/or decreased aldosterone levels.Nesiritide causes potent, dose-related vasodilation that is rapid in onset and sustained for the duration of drug infusion. After initiating the recommended dosing, 60% of the 3-hour effect on PCWP reduction is achieved within 15 minutes, reaching 95% of the 3-hour effect within 1 hour. Approximately 70% of the 3-hour effect on SBP reduction is reached within 15 minutes. The pharmacodynamic half-life of the onset and offset of the hemodynamic effect of nesiritide is longer than that expected from the pharmacokinetic half-life. In patients who develop symptomatic hypotension at recommended doses, 50% recovery of SBP toward baseline is observed approximately 60 minutes following drug discontinuation or dosage reduction. When higher doses of nesiritide are infused, the duration of hypotension is sometimes prolonged for several hours.In animals, nesiritide had no effects on cardiac contractility or on measures of cardiac electrophysiology such as atrial and ventricular effective refractory times or atrioventricular node conduction. Naturally occurring atrial natriuretic peptide (ANP), a related peptide, increases vascular permeability in animals and humans and may reduce intravascular volume. The effect of nesiritide on vascular permeability has not been studied.

Nesiritide is administered intravenously. Nesiritide exhibits biphasic elimination from the plasma in heart failure patients. The mean initial elimination phase is about 2 minutes. The mean terminal elimination half-life of nesiritide is approximately 18 minutes; however, the pharmacodynamic onset and offset of the hemodynamic effect of nesiritide is longer than what would predict from the pharmacokinetic half-life. The volume of distribution of the central compartment (Vc) is estimated to be 0.073 L/kg; the mean steady-state volume of distribution (Vss) is approximately 0.19 L/kg. The average systemic clearance is 9.2 mL/kg/minute. The mechanism of elimination of nesiritide has not been studied in humans.
 
Affected cytochrome P450 isoenzymes and drug transporters: none

At steady-state, plasma brain natriuretic peptide (BNP) concentrations increase from baseline endogenous concentrations by approximately 3- to 6-fold with nesiritide infusion doses ranging from 0.01 to 0.03 mcg/kg/minute. At the recommended dosing regimen, 60% of the 3-hour effect on pulmonary capillary wedge pressure (PCWP) reduction is achieved within 15 minutes after the bolus, reaching 95% of the 3-hour effect within 1 hour. Approximately 70% of the 3-hour effect on systolic blood pressure reduction is reached within 15 minutes.

There are no data to assess the drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes with nesiritide use during human pregnancy. In animal studies, administration of nesiritide at 100 times the maximum recommended human dose (MRHD) during organogenesis did not result in maternal or fetal toxicity. Pregnant women with heart failure are at increased risk for preterm birth. Heart failure may worsen with pregnancy and lead to maternal death or stillbirth.[51226]

There are no data on the presence of nesiritide in human (or animal) breast milk, or regarding the effect on the breast-feeding child or milk production.[51226]