Is nesiritide FDA-approved, and what does the research show?

What is nesiritide?

Nesiritide is a laboratory-made copy of a hormone the heart itself produces, human B-type natriuretic peptide, or BNP ¹. A peptide is a short chain of amino acids, and this one is 32 amino acids long ¹. The label says it has the same sequence as the natural hormone, which comes from the muscle of the ventricles, the heart's main pumping chambers ¹. "Natriuretic" describes a substance that makes the kidneys pass sodium into the urine.

The approved product, Natrecor, was made in E. coli bacteria by recombinant DNA technology, in which bacteria are given the instructions to build a human peptide ¹. It was for intravenous use only, meaning it was given into a vein ¹.

Nesiritide is not a wellness, weight-loss or performance peptide. Its label covered heart failure that had suddenly worsened, heart failure being a condition in which the heart pumps too weakly for the body's needs ¹. Neither the label nor the largest trial's abstract reports any effect on body weight ⁴, ¹.

Is nesiritide FDA-approved?

Not any longer: FDA approved nesiritide in 2001 and withdrew the approval in 2020 at the company's request, and Drugs@FDA lists Natrecor as "Discontinued" ², ³. The approval of Natrecor (nesiritide) came on August 10, 2001, under new drug application (NDA) 020920, held by Scios LLC ². An NDA is the file a company submits to FDA to have a drug approved.

Its last label carried one indication: "for the treatment of patients with acutely decompensated heart failure who have dyspnea at rest or with minimal activity" ¹. Dyspnea is the medical word for shortness of breath, and "acutely decompensated" means the condition has suddenly worsened. The label adds that in these patients the drug "reduced pulmonary capillary wedge pressure and improved short term (3 hours) symptoms of dyspnea" ¹. Wedge pressure is a reading taken through a catheter in the heart, and it reflects the pressure backing up toward the lungs.

In a Federal Register notice published May 14, 2020, FDA withdrew approval of 16 applications, NDA 020920 among them, "as of June 15, 2020" ³. The notice says the applicants "have informed FDA that these drug products are no longer marketed and have requested that FDA withdraw approval of the applications" ³. A withdrawal by this route "is without prejudice to refiling," so a company may apply again ³.

Drugs@FDA, the agency's database of approved drugs, lists Natrecor with the marketing status "Discontinued" as of November 9, 2026, the date of the record's data ². The record carries a note: "Federal Register determination that product was not discontinued or withdrawn for safety or effectiveness reasons" ². In a notice of January 8, 2021, FDA determined that the listed products, Natrecor among them, "were not withdrawn from sale for reasons of safety or effectiveness" ⁵. That notice keeps Natrecor on the Orange Book's "Discontinued Drug Product List"; its approval had been withdrawn as of June 15, 2020 ³, ⁵. Drugs@FDA's data of November 9, 2026, lists one nesiritide application, NDA 020920 ².

The 2020 notice says in general terms that "Introduction or delivery for introduction into interstate commerce of products without approved new drug applications violates section 301(a) and (d) of the Federal Food, Drug, and Cosmetic Act" ³. The notice allowed stock already in inventory on June 15, 2020, to "continue to be dispensed until the inventories have been depleted or the drug products have reached their expiration dates or otherwise become violative, whichever occurs first" ³.

While it was approved, the label told clinicians to give nesiritide "only in settings where blood pressure can be monitored closely and hypotension aggressively treated" ¹. Hypotension is low blood pressure.

See the FDA status of every peptide, updated weekly.

How does nesiritide work?

The label says the ventricles release the body's own BNP when they are stretched ¹. Raised levels, it says, "have been associated with advanced heart failure and are considered to be a compensatory mechanism in this disease," meaning the body's response to the strain ¹.

BNP binds a receptor on the muscle cells in blood-vessel walls and on the cells that line the vessels ¹. That raises the level of cyclic GMP, a chemical messenger inside the cell, and the muscle relaxes ¹. In the label's words, cyclic GMP "serves as a second messenger to dilate veins and arteries" ¹. A drug that widens blood vessels in this way is called a vasodilator.

In patients, the label reports the effect as a fall in wedge pressure and in blood pressure ¹. Shown in isolated human artery and vein tissue: nesiritide relaxed samples that had first been made to contract ¹. Studied in animals: it had no effect on the force of the heart's contraction or on measures of its electrical conduction ¹.

Nesiritide leaves the blood quickly. Its mean terminal elimination half-life, the time for the blood level to fall by half in the final phase, is about 18 minutes ¹. The label says its effect on the circulation lasts longer than that half-life would predict ¹. It also says the way the body eliminates nesiritide "has not been studied specifically in humans" ¹.

What does the research show?

The label counts 11 clinical trials in which 4,505 patients with heart failure received nesiritide ¹. Their mean age was 64, and 32 percent were women ¹.

The label's three-hour results come from VMAC, a randomized, double-blind study ¹. Randomized means patients were assigned to a treatment by chance, and double-blind means neither they nor their doctors knew which one they received. It enrolled 489 patients hospitalized for shortness of breath at rest due to acutely decompensated heart failure ¹. They received nesiritide, intravenous nitroglycerin (another drug that widens blood vessels) or a placebo, a dummy infusion, added to their usual treatment ¹. The placebo comparison lasted three hours, after which the placebo patients were switched to one of the two active drugs ¹.

The two main measures were wedge pressure and the patients' own rating of their breathlessness, both at three hours ¹. Among patients with a heart catheter, mean wedge pressure fell by 5.8 mm Hg (millimeters of mercury, the unit of pressure) in the 124 given nesiritide ¹. It fell by 3.8 in the 60 given nitroglycerin and by 2.0 in the 62 given placebo ¹. The label marks the nesiritide result as statistically different from placebo (p<0.05) ¹.

Patients on nesiritide also "reported greater improvement in their dyspnea at 3 hours than patients receiving placebo (p=0.034)" ¹. A p value is the probability of a difference at least that large if the drug had no effect. The label does not give the breathlessness ratings themselves, only that comparison ¹.

A far larger trial followed, after earlier meta-analyses, studies that pool trials, "raised questions regarding renal toxicity and the mortality associated with this agent" ⁴. Renal toxicity is harm to the kidneys. The trial, ASCEND-HF, was published on July 7, 2011, and was funded by Scios ⁴. It randomly assigned 7,141 patients hospitalized with acute heart failure to nesiritide or placebo, given for 24 to 168 hours on top of standard care ⁴.

At 6 hours, 44.5 percent of the nesiritide group and 42.1 percent of the placebo group reported markedly or moderately improved breathlessness (P=0.03) ⁴. At 24 hours the figures were 68.2 and 66.1 percent (P=0.007) ⁴. Neither difference met the stricter significance level the trial had set in advance ⁴. The authors called it "a small, nonsignificant effect on dyspnea" ⁴.

Death from any cause or rehospitalization for heart failure within 30 days occurred in 9.4 percent with nesiritide and 10.1 percent with placebo ⁴. The absolute difference was -0.7 percentage points, with a 95 percent confidence interval of -2.1 to 0.7 (P=0.31) ⁴. A confidence interval is the range in which the true difference plausibly lies, and this one includes zero. Deaths at 30 days were 3.6 percent with nesiritide and 4.0 percent with placebo, which was not a significant difference ⁴. The authors concluded that nesiritide "cannot be recommended for routine use in the broad population of patients with acute heart failure" ⁴.

The label reports the same trial out to 180 days ¹. Of the 7,141 patients randomized, 7,007 took at least one dose ¹. By day 180, 429 patients (12.3 percent) in the nesiritide group and 447 (12.7 percent) in the placebo group had died, with no significant difference (p=0.5) ¹.

The label also pools seven trials with 8,514 patients, comparing nesiritide with placebo or another active drug, and reports "no increased mortality risk" at day 30 ¹. The hazard ratio, the death rate with nesiritide relative to the comparison groups, was 0.99, where 1 means no difference ¹. Its 95 percent confidence interval ran from 0.80 to 1.22 ¹. Across the six trials with 180-day data, the ratio was 0.98, with an interval of 0.88 to 1.10 ¹.

The label notes "limited experience" with infusions longer than 96 hours ¹. It says safety and effectiveness in children "have not been established" ¹.

What are the side effects?

The label calls hypotension the drug's "dose-limiting side effect" ¹. In ASCEND-HF, symptomatic hypotension, low pressure that the patient feels, occurred in 7.1 percent of nesiritide patients and 4.0 percent of placebo patients ¹. In VMAC the rate over the first 24 hours was 4 percent with nesiritide and 5 percent with nitroglycerin ¹. When it occurred, it lasted a mean of 2.2 hours with nesiritide and 0.7 hours with nitroglycerin ¹.

For other reactions, the label pools trials apart from ASCEND-HF in which the infusion ran 12 hours or longer ¹. Over the first 24 hours it compares 331 patients given nesiritide at the dose the label recommended with 188 given placebo ¹. Hypotension was reported in 12 percent against 4 percent, and headache in 7 percent against 6 percent ¹. Nausea and back pain were each reported in 3 percent against 1 percent ¹. The label also lists hypoglycemia, low blood sugar, as a laboratory finding in at least 2 percent of patients in the 14 days after the infusion began ¹.

The second warning concerns the kidneys. The label says nesiritide "may decrease renal function as judged by increases in serum creatinine," a blood marker of how well the kidneys filter ¹. In ASCEND-HF, the kidneys' estimated filtration rate fell by more than 25 percent in 31.4 percent of the nesiritide group and 29.5 percent of the placebo group ⁴, ¹. The trial's authors reported that difference as not significant, with an odds ratio of 1.09 and a 95 percent confidence interval of 0.98 to 1.21 ⁴. An odds ratio compares the odds of an event in two groups, and 1 means no difference.

The label adds that other creatinine-based measures of kidney decline "were more frequent in the NATRECOR group" ¹. At 30 days, 4.6 percent of the nesiritide group and 3.3 percent of the placebo group had creatinine 50 percent above baseline ¹. In VMAC, creatinine rose more than 0.5 mg/dL (milligrams per deciliter) above baseline through day 30 in 28 percent with nesiritide and 21 percent with nitroglycerin ¹.

The label contraindicated nesiritide in three situations ¹. They were "Persistent systolic blood pressure <100 mm Hg prior to therapy because of an increased risk of symptomatic hypotension," "Known hypersensitivity to any of its components," and "Cardiogenic shock" ¹. Systolic pressure is the upper number of a blood-pressure reading, and cardiogenic shock is a state in which the heart pumps too little blood to supply the body. The label also reports serious "hypersensitivity/allergic reactions," which it says are more likely in people with "a history of sensitivity to recombinant peptides" ¹.

The label called nesiritide "not recommended for patients for whom vasodilating agents are not appropriate" ¹. Its examples were patients with "significant valvular stenosis, restrictive or obstructive cardiomyopathy, constrictive pericarditis, pericardial tamponade" ¹. These are structural conditions of the heart's valves, its muscle and the sac around it. No trial was run specifically to test drug interactions ¹. The one the label reports is more symptomatic hypotension in patients also taking afterload reducers or drugs acting on the renin-angiotensin system, such as ACE inhibitors or ARBs ¹.

There are no data on use in pregnancy or on nesiritide in breast milk ¹. Of the 4,505 trial patients, 52 percent were 65 or older, and the label cautions: "Some older individuals may be more sensitive to the effect of NATRECOR than younger individuals" ¹. Reports after approval added hypersensitivity reactions, leakage of the infusion into nearby tissue, itching and rash, at a frequency the label says cannot be reliably estimated ¹.

In sport

Nesiritide is not named on the 2026 Prohibited List of WADA, the World Anti-Doping Agency, and neither are natriuretic peptides as a class ⁶. Section S5 prohibits "All diuretics and masking agents" ⁶. Nesiritide is not among the examples S5 names, and that list ends with "other substances with a similar chemical structure or similar biological effect(s)" ⁶.

Section S0 covers substances that the later sections do not address ⁶. It reads: "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use (e.g. drugs under pre-clinical or clinical development or discontinued, designer drugs, substances approved only for veterinary use) is prohibited at all times" ⁶. Outside the United States, no regulator's record is cited here.

Nesiritide was given as an intravenous infusion ¹. Method rule M2.2 prohibits "Intravenous infusions and/or injections of more than a total of 100 mL per 12-hour period except for those legitimately received in the course of hospital treatments, surgical procedures or clinical diagnostic investigations" ⁶.

What JumpstartMD offers

JumpstartMD does not prescribe nesiritide. Our peptide library covers it so you have the facts on its FDA status and the evidence, current as of November 10, 2026.

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Compounded medications are not FDA-approved, and FDA does not review their safety, effectiveness, or quality before they are marketed. A licensed clinician decides after an evaluation whether a peptide is appropriate for you, and not every patient will qualify.