A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Natrecor Side Effects, and Drug Interactions - Nesiritide
Natrecor Side Effects, and Drug Interactions - Nesiritide
SIDE EFFECTS
Adverse events that occurred with at least a 3% frequency during
the first 24 hours of Natrecor infusion are shown in the following table.
|
Adverse Event
|
VMAC Trial
|
Other Long Infusion Trials
|
|
Nitroglycerin(n = 216)
|
Natrecor Recommended Dose (n = 273)
|
Control*
(n = 256)
|
Natrecor µg/kg/min
|
|
0.015
(n = 253)
|
0.03
(n = 246)
|
|
Cardiovascular
|
|
|
|
|
|
|
Hypotension
|
25 (12%)
|
31 (11%)
|
20 (8%)
|
56 (22%)
|
87 (35%)
|
|
Symptomatic Hypotension
|
10 (5%)
|
12 (4%)
|
8 (3%)
|
28 (11%)
|
42 (17%)
|
|
Asymptomatic Hypotension
|
17 (8%)
|
23 (8%)
|
13 (5%)
|
31 (12%)
|
49 (20%)
|
|
Ventricular Tachycardia (VT)
|
11 (5%)
|
9 (3%)
|
25 (10%)
|
25 (10%)
|
10 (4%)
|
|
Non-sustained VT
|
11 (5%)
|
9 (3%)
|
23 (9%)
|
24 (9%)
|
9 (4%)
|
|
Ventricular Extrasystoles
|
2 (1%)
|
7 (3%)
|
15 (6%)
|
10 (4%)
|
9 (4%)
|
|
Angina Pectoris
|
5 (2%)
|
5 (2%)
|
6 (2%)
|
14 (6%)
|
6 (2%)
|
|
Bradycardia
|
1 (< 1%)
|
3 (1%)
|
1 (< 1%)
|
8 (3%)
|
13 (5%)
|
|
Body as a Whole
|
|
|
|
|
|
|
Headache
|
44 (20%)
|
21 (8%)
|
23 (9%)
|
23 (9%)
|
17 (7%)
|
|
Abdominal Pain
|
11 (5%)
|
4 (1%)
|
10 (4%)
|
6 (2%)
|
8 (3%)
|
|
Back Pain
|
7 (3%)
|
10 (4%)
|
4 (2%)
|
5 (2%)
|
3 (1%)
|
|
Nervous
|
|
|
|
|
|
|
Insomnia
|
9 (4%)
|
6 (2%)
|
7 (3%)
|
15 (6%)
|
15 (6%)
|
|
Dizziness
|
4 (2%)
|
7 (3%)
|
7 (3%)
|
16 (6%)
|
12 (5%)
|
|
Anxiety
|
6 (3%)
|
8 (3%)
|
2 (1%)
|
8 (3%)
|
4 (2%)
|
|
Digestive
|
|
|
|
|
|
|
Nausea
|
13 (6%)
|
10 (4%)
|
12 (5%)
|
24 (9%)
|
33 (13%)
|
|
Vomiting
|
4 (2%)
|
4 (1%)
|
2 (1%)
|
6 (2%)
|
10 (4%)
|
* Includes dobutamine, milrinone, nitroglycerin, placebo, dopamine,
nitroprusside, or amrinone.
Adverse events that are not listed in the above table that
occurred in at least 1% of patients who received any of the above Natrecor doses
included: Tachycardia, atrial fibrillation, AV node conduction abnormalities,
catheter pain, fever, injection site reaction, confusion, paresthesia, somnolence,
tremor, increased cough, hemoptysis, apnea, increased creatinine, sweating,
pruritus, rash, leg cramps, amblyopia, anemia. All reported events (at least
1%) are included except those already listed, those too general to be informative,
and those not reasonably associated with the use of the drug because they were
associated with the condition being treated or are very common in the treated
population.
In placebo and active-controlled clinical trials, Natrecor
has not been associated with an increase in atrial or ventricular tachyarrhythmias.
In placebo-controlled trials, the incidence of VT in both Natrecor and placebo
patients was 2%. In the PRECEDENT (Prospective Randomized Evaluation of Cardiac
Ectopy with Dobutamine or Natrecor Therapy) trial, the effects of Natrecor (n
= 163) and dobutamine (n = 83) on the provocation or aggravation of existing
ventricular arrhythmias in patients with decompensated CHF was compared using
Holter monitoring. Treatment with Natrecor (0.015 and 0.03 µg/kg/min without
an initial bolus) for 24 hours did not aggravate pre-existing VT or the frequency
of premature ventricular beats, compared to a baseline 24-hour Holter tape.
Clinical Laboratory
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-µg/kg/min group (17%) and the Natrecor 0.03-µg/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 µg/kg bolus followed by 0.010 µg/kg/min) and nitroglycerin
groups, respectively.
Effect on Mortality
In the VMAC trial, the mortality rates at six months in the
patients receiving Natrecor and nitroglycerin were 25.1% (95% confidence interval,
20.0% to 30.5%) and 20.8% (95% confidence interval, 15.5% to 26.5%), respectively.
In all controlled trials combined, the mortality rates for Natrecor and active
control (including nitroglycerin, dobutamine, nitroprusside, milrinone, amrinone,
and dopamine) patients were 21.5% and 21.7%, respectively.
DRUG INTERACTIONS
:
No trials specifically examining potential drug interactions with Natrecor were
conducted, although many concomitant drugs were used in clinical trials. No
drug interactions were detected except for an increase in symptomatic hypotension
in patients receiving oral ACE inhibitors (see PRECAUTIONS,
Cardiovascular).
The co-administration of Natrecor with IV vasodilators such
as nitroglycerin, nitroprusside, milrinone, or IV ACE inhibitors has not been
evaluated (these drugs were not co-administered with Natrecor in clinical trials).
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Long-term studies in animals have not been performed to evaluate the carcinogenic
potential or the effect on fertility of
Natrecor. Natrecor did not increase the frequency of mutations
when used in an in vitro bacterial cell assay (Ames test). No other genotoxicity
studies were performed.
Pregnancy: Category C: Animal reproductive studies have
not been conducted with Natrecor. It is also not known whether Natrecor can
cause fetal harm when administered to pregnant women or can affect reproductive
capacity. Natrecor should be used during pregnancy only if the potential benefit
justifies any possible risk to the fetus.
Nursing Mothers: It is not known whether this drug is
excreted in human milk. Therefore, caution should be exercised when Natrecor
is administered to a nursing woman.
Pediatric Use: The safety and effectiveness of Natrecor
in pediatric patients has not been established.
Geriatric Use: Of the total number of subjects in clinical
trials treated with Natrecor (n = 941), 38% were 65 years or older and 16% were
75 years or older. No overall differences in effectiveness were observed between
these subjects and younger subjects, and other reported clinical experience
has not identified differences in responses between the elderly and younger
patients. Some older individuals may be more sensitive to the effect of Natrecor
than younger individuals.
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