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This is duplicated text of a letter from Janssen-Ortho Inc.
Contact the company for a copy of any references, attachments or enclosures.
Conditional marketing authorization (NOC/c)
for NATRECORNote de bas de page *(nesiritide)
Dear Health Professional(s),
Janssen-Ortho Inc. is pleased to announce that Health Canada has granted a Notice of Compliance with Conditions (NOC/c) for NATRECOR, a recombinant human B-type natriuretic peptide (rhBNP), for the treatment of hospitalized patients with symptomatic Acute Decompensated Heart Failure (ADHF). It is the first rhBNP indicated for the treatment of this condition. Health Canada has issued a conditional marketing authorization for NATRECOR under the NOC/c policy to reflect the promising nature of the clinical results in patients with this serious disease. A confirmatory international trial, Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND HF) is being conducted.
NATRECOR is indicated for the treatment of hospitalized symptomatic Acute Decompensated Heart Failure (ADHF) patients, presenting with moderate to severe dyspnea. These are patients who present with signs and symptoms of persistent heart failure despite 2 hours of treatment with intravenous loop diuretics.
Health Canada based the NOC/c for NATRECOR on the effect of NATRECOR on the Pulmonary Capillary Wedge Pressure (PCWP) in pivotal Study 339/VMAC, a double-blind, randomized, clinical trial. The study recruited 489 patients to evaluate the role of NATRECOR in addition to standard of care in ADHF compared to placebo in addition to standard of care. The reduction of PCWP achieved with nesiritide was greater compared to placebo and the results were statistically significant. For details pertaining to results of the VMAC trial, please refer to the Product Monograph.
The use of diuretics in the VMAC trial was not restricted; while there was no overall difference seen in net urine output between groups, concomitant diuretic use was shown to be less for NATRECOR (85% use) compared to nitroglycerin (94%).
The recommended dosing regimen of NATRECOR is a 2 μg/kg IV bolus followed by an IV infusion dose of 0.01 μg/kg/min. NATRECOR should not be initiated at a dose that is above the recommended dose. The use of NATRECOR at doses higher than recommended is not encouraged. However, in the few cases where further optimization of clinical status may be required, the NATRECOR infusion dose may be increased or decreased according to hemodynamic and clinical response. If an increase in dose is required, the infusion dose may be increased by 0.005 μg/kg/min (preceded by a bolus of 1 μg/kg) for no more than every 3 hours up to a maximum dose of 0.03 μg/kg/min. Blood pressure should be monitored closely during NATRECOR administration. There is limited experience with administering NATRECOR for longer than 48 hours. 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 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.
NATRECOR should not be used as primary therapy for patients with cardiogenic shock or in patients with a systolic blood pressure < 90 mm Hg. The potential for hypotension may be increased by combining NATRECOR with other drugs that cause hypotension.
NATRECOR should not be used in patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container.
NATRECOR is not recommended for patients for whom vasodilating agents are not appropriate, such as patients with significant valvular stenosis, restrictive or obstructive cardiomyopathy, constrictive pericarditis, pericardial tamponade, or other conditions in which cardiac output is dependent on venous return, or for patients suspected of having low cardiac filling pressures. NATRECOR should be administered only in settings where blood pressure can be monitored closely.
Although NATRECOR is eliminated in part through renal clearance, available clinical data suggest that dose adjustment is not required in patients with pre-existing renal insufficiency. 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. Close monitoring of renal function is recommended.
The most common side effects of NATRECOR include hypotension with or without symptoms, non-sustained ventricular tachycardia, headache, and nausea. NATRECOR may cause other possible side effects including extrasystoles, tachycardia, bradycardia, angina pectoris, dizziness, confusion, anxiety, vomiting, insomnia, increased creatinine, and increased perspiration. This is not a complete list of the side effects reported with NATRECOR; for more information refer to the NATRECOR Product Monograph.
NATRECOR is provided as a sterile lyophilized powder in 1.5 mg, single-use 5 mL vials.
The Product Monograph is available to physicians and pharmacists upon request.
A Fact Sheet on the use of NATRECOR in the treatment of ADHF is available to consumers on the Health Canada website.
Should you have medical enquiries regarding NATRECOR for the treatment of ADHF, please contact our Medical Information Department at 1-800-567-3331, or e-mail to firstname.lastname@example.org.
Original signed by
Regulatory Affairs, Quality, Drug Safety and Surveillance
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