Natrecor

nesiritide

Natrecor

Pharmacologic class: Human B-type natriuretic peptide

Therapeutic class: Vasodilator

Pregnancy risk category C

Action

Binds to receptors on vascular smooth muscle and endothelial cells, causing smooth muscle relaxation and vasodilation. As a result, systemic and pulmonary pressures decrease and diuresis occurs.

Availability

Injection: 1.5 mg in single-use vials

Indications and dosages

Acutely decompensated heart failure in patients who have dyspnea at rest or with minimal activity

Adults: 2 mcg/kg I.V. bolus, followed by continuous I.V. infusion of 0.01 mcg/kg/minute

Contraindications

• Hypersensitivity to drug or its components

• Systolic pressure below 90 mm Hg

• Primary therapy for cardiogenic shock

Precautions

Use cautiously in:

• restrictive or obstructive cardiomyopathy, constrictive pericarditis, pericardial tamponade, renal dysfunction, hypotension

• pregnant or breastfeeding patients.

Administration

Know that nesiritide is a high-alert drug.

• For I.V. use, prime tubing before connecting to patient. Withdraw bolus and infuse over 60 seconds into I.V. port of tubing. Follow immediately with constant infusion delivering 0.01 mcg/kg/minute.

• Know that drug should be mixed and infused in dextrose 5% in water, normal saline solution, or dextrose in half-normal saline solution.

Don't mix with other drug solutions. Always administer through separate line.

• Know that nesiritide therapy beyond 48 hours has not been studied.

Adverse reactions

CNS: dizziness, headache, insomnia, anxiety

CV: hypotension, angina pectoris, bradycardia, ventricular extrasystole, ventricular tachycardia

GI: nausea, vomiting, abdominal pain

Musculoskeletal: leg cramps, back pain

Respiratory: cough, hemoptysis, apnea

Other: injection site reactions

Interactions

Drug-drug. Angiotensin-converting enzyme inhibitors, nitrates: increased hypotension

Bumetanide, enalaprilat, ethacrynate sodium, furosemide, heparin, hydralazine, insulin: physical and chemical incompatibility with nesiritide

Drug-diagnostic tests. Hematocrit, hemoglobin: decreased values

Patient monitoring

• Monitor vital signs and pulmonary artery wedge pressure continuously during and for several hours after infusion.

• Assess cardiovascular status closely.

Patient teaching

• Tell patient he'll be monitored closely during and for several hours after infusion.

• Inform patient that drug may cause serious adverse effects. Reassure him that he'll receive appropriate interventions to relieve symptoms.

• Instruct patient to report chest pain, dizziness, palpitations, and other uncomfortable symptoms.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

nesiritide

(ne-sir-i-tide) ,

Natrecor

(trade name)

Classification

Therapeutic: none assigned
Pharmacologic: vasodilators
Pregnancy Category: C

Indications

Acutely decompensated HF in hospitalized patients who have dyspnea at rest or with minimal activity; has been used with digoxin, diuretics, and ACE inhibitors. Should not be used for intermittent outpatient infusion, scheduled repetitive use, as a diuretic or to improve renal function.

Action

Binds to guanyl cyclase receptors in vascular smooth muscle and endothelial cells, producing increased intracellular guanosine 3′5′-cyclic monophosphate (cGMP) and smooth muscle cell relaxation. cGMP acts as a "second messenger" to dilate veins and arteries.

Therapeutic effects

Dose-dependent reduction in pulmonary capillary wedge pressure (PCWP) and systemic arterial pressure in patients with heart failure with resultant decrease in dyspnea.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Cleared from circulation by binding to cell surface clearance receptors resulting in cellular internalization and proteolysis, proteolytic breakdown by endopeptidases, and renal filtration.
Half-life: 18 min.

Time/action profile (effects on cardiovascular parameters)

ROUTEONSETPEAKDURATION
IV15 min1 hr60 min†
†Longer with higher than recommended doses

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Cardiogenic shock;Systolic BP <100 mm Hg;Low cardiac filling pressure, significant valvular stenosis, restrictive/subtractive cardiomyopathy, constrictive pericarditis/cardiac tamponade, or other conditions in which cardiac output is dependent on venous return.
Use Cautiously in: Heart failure where renal function is dependent on activity of the renin/angiotensin/aldosterone system (may cause azotemia);Cardiogenic shock (should not be used as primary therapy); Obstetric / Lactation / Pediatric: Pregnancy, lactation, or children (safety not established); Geriatric: May have ↑ sensitivity to effects.

Adverse Reactions/Side Effects

Central nervous system

  • anxiety
  • confusion
  • dizziness
  • headache
  • hypotension (dose related)
  • insomnia
  • drowsiness

Ear, Eye, Nose, Throat

  • amblyopia

Respiratory

  • apnea (life-threatening)
  • cough
  • hemoptysis

Cardiovascular

  • hypotension (most frequent)
  • arrhythmias
  • bradycardia

Gastrointestinal

  • abdominal pain
  • nausea
  • vomiting

Genitourinary

  • ↑ serum creatinine
  • renal failure

Dermatologic

  • itching
  • rash
  • sweating

Hematologic

  • anemia

Local

  • injection site reactions

Musculoskeletal

  • back pain
  • leg cramps

Neurologic

  • paresthesia
  • tremor

Miscellaneous

  • allergic reactions (life-threatening)
  • fever

Interactions

Drug-Drug interaction

None reported.

Route/Dosage

Intravenous (Adults) 2 mcg/kg bolus followed by 0.01 mcg/kg/min as a continuous infusion. May ↑ by 0.005 mcg/kg/min every 3 hr up to a maximum infusion rate of 0.03 mcg/kg/min (based on response).

Availability

Powder for injection: 1.5 mg/vial

Nursing implications

Nursing assessment

  • Monitor BP, pulse, ECG, respiratory rate, cardiac index, PCWP, and central venous pressure frequently during administration. May cause hypotension, especially in patients with a BP <100 mm Hg. Reduce dose or discontinue nesiritide if patient develops hypotension. Hypotension may cause renal compromise. Use IV fluids and changes in body position to support BP if symptomatic hypotension occurs. Nesiritide may be restarted at a dose reduced by 30% with no bolus administration once patient is stabilized. Hypotension may be prolonged for hours, requiring a period of monitoring prior to restarting administration.
  • Monitor intake and output and weigh daily. Assess for decrease in signs of HF (dyspnea, rales/crackles, peripheral edema, weight gain).
  • Obtain history for reactions to recombinant peptides; may increase risk of allergic reaction. Observe patient for signs and symptoms of allergic reactions (rash, pruritus, laryngeal edema, wheezing). Discontinue the drug and notify health care professional immediately if these occur. Keep epinephrine, an antihistamine, IV fluids, pressure amines, and resuscitation equipment close by in the event of an anaphylactic reaction.
  • Lab Test Considerations: Monitor BUN and serum creatinine. May cause ↑ in serum creatinine; ↑ serum creatinine may be dose-related.

Potential Nursing Diagnoses

Decreased cardiac output (Indications)
Activity intolerance (Indications)
Excess fluid volume (Indications)

Implementation

  • high alert: Intravenous vasoactive medications have an increased potential for causing harm. Have second practitioner independently check original order, dose calculations, and infusion pump settings. Administer only in settings where BP can be closely monitored.
    • Prime the IV tubing with an infusion of 25 mL prior to connecting to the patient’s vascular access port and prior to administering bolus or infusion. Flush catheter between administration of nesiritide and other medications. Do not administer through a central heparin-coated catheter as nesiritide binds to heparin. Concomitant administration of a heparin infusion through a separate catheter is acceptable.
  • Intravenous Administration
  • pH: 4.0–6.0.
  • Diluent: Reconstitute 1.5-mg vial of nesiritide by adding 5 mL of diluent removed from a pre-filled 250-mL plastic IV bag containing D5W, 0.9% NaCl, D5/0.45% NaCl, or D5/0.2% NaCl. Do not shake vial; rock gently so all surfaces including stopper are in contact with diluent to ensure complete reconstitution. Withdraw entire content of reconstituted vial and add back to 250-mL plastic IV bag. Invert IV bag several times to ensure complete mixing of solution. Infusion stable for 24 hr. After preparation of infusion bag, withdraw bolus volume from infusion bag. To calculate amount: bolus volume (mL) = 0.33 × patient weight (kg).Concentration: 6 mcg/mL.
  • Rate: Administer bolus over 60 seconds through a port in the IV tubing.
  • Intermittent Infusion: Diluent: See Diluent section under Direct IV section above for preparation instructions for infusion bag. Immediately follow bolus with infusion.Concentration: 6 mcg/mL.
  • Rate: Based on patient's weight (see Route/Dosage section).
  • Y-Site Compatibility: acyclovir, alemtuzumab, alfentanil, allopurinol, amifostine, aminophylline, amiodarone, amphotericin B colloidal, amphotericin C lipid complex, amphotericin B liposome, anidulafungin, argatroban, atracurium, azithromycin, aztreonam, bivalirudin, bleomycin, buprenorphine, busulfan, butorphanol, calcium acetate, calcium chloride, calcium gluconate, carboplatin, carmustine, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaoxone, cefuroxime, chloramphenicol, ciprofloxacin, cisatracurium, cisplatin, clindamycin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, dactinomycin, daunorubicin hydrochloride, dexmedetomidine, dexrazoxane, digoxin, diltiazem, diphenhydramine, docetaxel, dolasetron, doxacurium, doxorubicin, doxorubicin liposomal, doxycycline, droperidol, ephedrine, epirubicin, ertapenem, erythromycin, esmolol, etoposide, etoposide phosphate, famotidine, fentanyl, filgrastim, fluconazole, fludarabine, fluorouracil, foscarnet, fosphenytoin, ganciclovir, gemcitabine, glycopyrrolate, granisetron, haloperidol, hydrocortisone, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, irinotecan, ketorolac, leucovorin calcium, levofloxacin, linezolid, lorazepam, magnesium sulfate, mannitol, mechlorethamine, melphalan, meropenem, mesna, metaraminol, methohexital, methotrexate, methylprednisolone, metoclopramide, metronidazole, midazolam, milrinone, mitomycin, mitoxantrone, moxifloxacin, mycophenolate, nalbuphine, naloxone, nicardipine, nitroglycerin, nitroprusside, octreotide, ondansetron, oxaliplatin, oxytocin, paclitaxel, palonosetron, pamidronate, pancuronium, pemetrexed, pentamidine, pentobarbital, pheobarbital, phentolamine, potassium acetate, potassium chloride, potassium phosphates, prochlorperazine, propranolol, quinupristin/dalfopristin, ranitidine, remifentanil, rocuronium, sodium acetate, sodium bicarbonate, sodium phosphates, streptozocin, succinylcholine, sufentanil, tacrolimus, teniposide, theophylline, thiotepa, tigecycline, tirofiban, tolazoline, topotecan, torsemide, vancomycin, vasopressin, vecuronium, verapamil, vinblastine, vincristine, vinorelbine, zidovudine, zolendronic acid
  • Y-Site Incompatibility: ampicillin, ampicillin/sulbactam, cefepime, cefoperazone, dantrolene, daptomycin, diazepam, furosemide, insulin, micafungin, nafcillin, pantoprazole, phenytoin, piperacillin/tazobactam, sargramostim, thiopental

Patient/Family Teaching

  • Explain purpose of nesiritide to patient and family.
  • Advise patient to notify health care professional immediately if signs and symptoms of allergic reaction occurs.

Evaluation/Desired Outcomes

  • Improvement in dyspnea and reduction in mean PCWP in patients with decompensated HF.

Natrecor

A recombinant brain (B-type) natriuretic peptide given intraveinously to patients with acutely decompensated heart failure and dyspnoea at rest. Natrecor relaxes blood vessels, increases natriuresis and diuresis, and decreases neurohormones. 

Adverse effects
Hypotension, ventricular tachycardia, headache, nausea, back pain, decreased renal function. It has been linked to increased mortality or renal damage; it is to be used only on severely ill patients.
References in periodicals archive ?
His prior responsibilities include sales and marketing, commercial planning, product launch, healthcare economics, reimbursement, advocacy development, life cycle management, and business development for brands such as CERETEC, TAXUS, NATRECOR, RANEXA and OFIRMEV.
[to continue] promoting Risperdal to treat symptoms and behavioral disturbances of dementia which were not within Risperdal's indication." Criminal fines and forfeiture of profits totaled $485 million, including a fine of $85 million relating to a similar case involving the congestive heart failure drug Natrecor.
Johnson & Johnson agreed to pay $2.2 billion to resolve charges that it improperly marketed the antipsychotic drugs Risperdal and Invega and the heart medication Natrecor for unappreved uses and paid kickbacks to physicians and a long-term care pharmacy provider.
The civil accord covered off-label marketing of Risperdal; Invega, another antipsychotic; and Natrecor, a heart drug.
The allegations include paying kickbacks to physicians and pharmacies to recommend and prescribe Risperdal and Invega, both antipsychotic drugs, and Natrecor, which is used to treat heart failure.
Darelene Horton was also the clinical lead for Natrecor, a commercial product indicated to treat acute heart failure, during her 12 year tenure at Scios.
In June 2012, the company added $600 million to its legal reserves for settlements involving Risperdal, Invega and Natrecor (J&J settled a federal criminal charge of mismarketing that for $85 million last October), as well as Omnicare, the nursing home pharmacy company.
government is joining two lawsuits against Johnson & Johnson (New Brunswick NJ) and its Scios unit, accusing the companies of promoting heart failure drug Natrecor for unapproved uses, the Department of Justice said Thursday.
The company also offers Risperdal and Risperdal Consta for the treatment of schizophrenia; Procrit, which stimulates red blood cell production; Remicade for the treatment of Crohn's disease, ankylosing spondylitis, psoriatic arthritis, ulcerative colitis, chronic severe plaque psoriasis and rheumatoid arthritis; Topamax, an antiepileptic and migraine prevention treatment; Levaquin and Floxin anti-infective products; Duragesic for chronic pain; Ortho Evra contraceptive patch and Ortho Tri-Cyclen Lo oral contraceptive; Concerta for treating hyperactivity disorder; and Natrecor for decompensated congestive heart failure.
The remaining three reported deaths involved mix-ups between the anticonvulsant primidone and prednisone; the antiepileptic drug phenytoin sodium and the barbiturate phenobarbital; and Norcuron and the heart failure treatment Natrecor (nesiritide recombinant).
Avorn, "The Rise and Fall of Natrecor for Congestive Heart Failure: Implications for Drug Policy," Health Affairs 25 (2006): 1095-1102.
The problem with using surrogate endpoints in short trials has been demonstrated in cardiovascular medicine with the experience using antiarrhythmics to prevent premature ventricular contractions (later discovered to lead to increased mortality), inotropics to improve ejection fraction (no long-term benefit) and, most recently, with nesiritide (Natrecor) for heart failure.