FDA approves label changes for Natrecor

May 15, 2005

Scios Inc., a Johnson & Johnson company, has changed its package labeling to add data about deaths associated with its heart failure drug nesiritide (Natrecor) after studies in prominent medical journals raised questions about an increased risk of fatal renal problems. The Food & Drug Administration-approved label change, which stops short of an outright warning, indicated that in clinical trials 5.3% of the patients treated with nesiritide died, compared with 4.3% who took other agents, including diuretics and intravenous nitroglycerin. However, the new label states that the data might not be statistically significant because of the small number of patients involved.

Scios Inc., a Johnson & Johnson company, has changed its package labeling to add data about deaths associated with its heart failure drug nesiritide (Natrecor) after studies in prominent medical journals raised questions about an increased risk of fatal renal problems. The Food & Drug Administration-approved label change, which stops short of an outright warning, indicated that in clinical trials 5.3% of the patients treated with nesiritide died, compared with 4.3% who took other agents, including diuretics and intravenous nitroglycerin. However, the new label states that the data might not be statistically significant because of the small number of patients involved.

Nesiritide, given intravenously, has been used in more than 600,000 patients in the past four years. The drug's main benefit is decreasing shortness of breath in heart failure patients, frequently the most debilitating symptom of heart failure. Scios officials have asserted all along that the studies were done using higher doses than were indicated on the drug's label.

Prior to the addition of the mortality data, the package insert stated that nesiritide 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 nesiritide may be associated with azotemia (nitrogen retention). When nesiritide was initiated at doses higher than 0.01 mcg/kg/min (0.015 and 0.03 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. In the 30-day follow-up period in the VMAC (Vasodilation in the Management of Acute Congestive Heart Failure) trial, five patients in the nitroglycerin group (2%) and nine patients in the nesiritide group (3%) required first-time dialysis.

In the meantime, Laine commented, the potential risks on mortality need to be carefully weighed against the benefits of symptom relief and quality of life when deciding whether or not to utilize nesiritide, particularly as a first-line agent, since alternative therapy, such as diuretics and nitroglycerin, is available.