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The following are discussed in more detail in other sections of the labeling:
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. A causal relationship for NATRECOR® cannot be reliably established in individual cases.
Adverse drug reactions that occurred at least ≥ 2% more frequently on NATRECOR® than on placebo during the first 24 hours of infusion (excluding the ASCEND-HF study) are shown in Table 3.
Table 3: Adverse Drug
Reactions* Reported at ≥ 2% Frequency During the First 24 Hours After the
Start of Infusion in Long Infusion Trials† of NATRECOR® at
the Recommended Dose excluding ASCEND-HF Results
|System Organ Class Adverse Reaction||NATRECOR®
|Hypotension||12 (41)||4 (7)|
|Nausea||3 (11)||1 (2)|
|Back pain||3 (11)||1 (2)|
|Nervous System Disorders|
|Headache||7 (24)||6 (11)|
|Dizziness||2 (8)||2 (3)|
|*Adverse drug reaction is defined as an adverse event with a
frequency in the NATRECOR® group ≥ 2% and occurred at a higher
frequency than in the placebo group.
† Trials in which NATRECOR® was administered as a continuous infusion for ≥ 12 hours.
‡704.339 [VMAC] and 704.341[PROACTION]
§704.311, 704.325 and 704.341 [PROACTION]
Laboratory adverse drug reactions that occurred in ≥ 2% of patients and collected during the first 14 days after the start of NATRECOR® infusion included: hypoglycemia.
Worsening Renal Function
In the ASCEND-HF trial, through Day 30, the incidence of renal impairment as measured by a > 25% decrease in glomerular filtration rate (calculated based on serum creatinine) was observed in 31.4% and 29.5% in the NATRECOR® and placebo groups, respectively. Other metrics of decompensated renal function such as an increase in creatinine of > 0.5 mg/dl, a 50% increase in creatinine or a value of ≥ 2 or 100% increase in creatinine were more frequent in the NATRECOR® group. At 30 days post enrollment, more subjects in the NATRECOR® group had elevated levels of creatinine of 50% greater than baseline compared to placebo 4.6% versus 3.3%. In the ASCEND-HF study there were relatively few subjects requiring either hemofiltration or dialysis.
In the PRECEDENT trial, the incidence of elevations in serum creatinine to > 0.5 mg/dL above baseline through Day 14 was higher in the NATRECOR® 0.015 mcg/kg/min group (17%) and the NATRECOR® 0.03 mcg/kg/min group (19%) than with standard therapy (11%). In the VMAC trial, through Day 30, the incidence of elevations in creatinine to > 0.5 mg/dL above baseline was 28% and 21% in the NATRECOR® (2 mcg/kg bolus followed by 0.01 mcg/kg/min) and nitroglycerin groups, respectively.
Neutral Effect on Mortality
A meta-analysis performed of seven clinical trials demonstrated NATRECOR® did not increase mortality in patients with acute decompensated heart failure (ADHF) at Day 30 or Day 180 (see Figures 1 and 2). Data from seven studies in which 30-day data were collected are presented in Figure 1. The data depict hazard ratios (HR) and confidence intervals (CI) of mortality data for randomized and treated patients with NATRECOR® relative to active or placebo controls through Day 30 for each of the seven individual studies along with the overall combined estimate (Studies 311, 325, 326, 329 [PRECEDENT], 339 [VMAC], 341 [PROACTION], and A093 [ASCEND-HF]).
Figure 1 (on logarithmic scale) also contains an estimate for the seven studies combined (n=8514). The results indicate that there is no increased mortality risk for NATRECOR® at Day 30 (seven studies pooled: HR=0.99; 95% CI: 0.80, 1.22). The percentages are the Kaplan-Meier estimates.
Figure 1 : 30-Day All-Cause
Mortality Hazard Ratios
*Studies 704.311, 704.325, 704.326, 704.329, 704.339, 704.341 and ASCEND-HF
Figure 2 presents 180-day mortality hazard ratios from all six individual studies where 180day data were collected (Studies 325, 326, 329, 339, 341 and A093 [ASCEND-HF]). The results indicate that with the addition of the ASCEND-HF data, there is no increased mortality risk for NATRECOR® at Day 180 (six studies pooled: HR=0.98; 95% CI: 0.88, 1.10).
Figure 2 : 180-Day All-Cause
Mortality Hazard Ratios
*Studies 704.325, 704.326, 704.329, 704.339, 704.341 and ASCEND-HF
The following adverse reactions have been identified during post-approval use of NATRECOR®. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.
- Hypersensitivity reactions
- Infusion site extravasation
Read the Natrecor (nesiritide) Side Effects Center for a complete guide to possible side effects
No trials specifically examining potential drug interactions with NATRECOR® were conducted, although many concomitant drugs (including IV nitroglycerin) were used in clinical trials [see Clinical Studies]. No drug interactions were detected except for an increase in symptomatic hypotension in patients receiving afterload reducers or affecting the renin-angiotensin system (i.e., ARBs and/or ACE inhibitors).
The co-administration of NATRECOR® with nitroprusside, milrinone, or IV ACE inhibitors has not been evaluated.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 9/4/2012
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