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
Corlopam Side Effects, and Drug Interactions - Fenoldopam Mesylate
Corlopam Side Effects, and Drug Interactions - Fenoldopam Mesylate
SIDE EFFECTS
Adult Patients: Fenoldopam causes a dose-related fall
in blood pressure and increase in heart rate (see Precautions,
Tachycardia, and Hypotension). In controlled clinical studies
of severe hypertension in patients with end-organ damage, 3% (4/137) of patients
withdrew because of excessive falls in blood pressure. Increased heart rate
could, in theory, lead to ischemic cardiac events or worsened heart failure,
although these events have not been observed. The most common events reported
as associated with fenoldopam use are headache, cutaneous dilation (flushing),
nausea, and hypotension, each reported in more than 5% of patients.
Adverse reactions in controlled trials in hypertensive adult
patients
Adverse events occurring more than once in any dosing group
(once if potentially important or plausibly drug-related) in the fixed-dose
constant-infusion studies are presented in the following Table by infusion-rate
group. There was no clear dose relationship, except possibly for headache, nausea,
flushing.
|
Table 4 ADVERSE EVENTS* FROM FIXED-DOSE INFUSION STUDIES
BY DOSAGE GROUP
|
|
Body System
|
Fenoldopam Dosage (mcg/kg/min) (Adults)
|
|
Event
|
Placebo
(n = 7)
|
0.01
(n = 26)
|
0.03-0.04
(n = 31)
|
0.1
(n = 28)
|
0.3-0.4
(n = 29)
|
0.6-0.8
(n = 11)
|
|
Body, General
|
Headache
|
1
|
5
|
4
|
7
|
8
|
6
|
|
Injection site reaction
|
0
|
1
|
3
|
0
|
3
|
2
|
|
Cardiovascular
|
ST-T
abnormalities
(primarily T-wave
inversion)
|
0
|
2
|
4
|
0
|
1
|
0
|
|
Flushing
|
0
|
0
|
0
|
0
|
1
|
3
|
|
Hypotension**
|
0
|
0
|
0
|
2
|
0
|
2
|
|
Postural hypotension
|
0
|
2
|
0
|
0
|
0
|
0
|
|
Tachycardia**
|
0
|
0
|
0
|
0
|
0
|
2
|
|
Digestive
|
Nausea
|
0
|
3
|
0
|
3
|
5
|
4
|
|
Vomiting
|
0
|
2
|
0
|
2
|
1
|
2
|
|
Abdominal pain/ fullness
|
0
|
2
|
0
|
0
|
2
|
1
|
|
Constipation
|
0
|
0
|
0
|
0
|
0
|
2
|
|
Diarrhea
|
0
|
0
|
0
|
0
|
2
|
0
|
|
Metabolic and Nutritional
|
Increased creatinine**
|
0
|
0
|
2
|
0
|
0
|
0
|
|
Hypokalemia**
|
0
|
2
|
2
|
0
|
1
|
0
|
|
Nervous
|
Nervousness/ anxiety
|
0
|
0
|
1
|
0
|
0
|
2
|
|
Insomnia
|
0
|
2
|
0
|
0
|
0
|
0
|
|
Dizziness
|
0
|
1
|
1
|
2
|
2
|
0
|
|
Respiratory
|
Nasal congestion
|
0
|
0
|
0
|
0
|
0
|
2
|
|
Skin and Appendages
|
Sweating
|
0
|
0
|
0
|
1
|
1
|
2
|
|
Urogenital
|
Urinary tract infection
|
0
|
2
|
0
|
1
|
0
|
0
|
|
Musculoskeletal
|
Back pain
|
0
|
1
|
0
|
1
|
2
|
2
|
|
*Includes events reported by 2
or more patients receiving fenoldopam treatment across all dose
groups.
|
|
**Investigator defined; no
protocol definition.
|
Adverse effects in overall database
The adverse event incidences listed below are based on observations
of over 1,000 fenoldopam treated adult patients and not listed in Table 4 above.
|
Events reported with a frequency between 0.5-5% in patients
treated with IV fenoldopam
|
|
Cardiovascular:
|
extrasystoles, palpitations,
bradycardia, heart failure, ischemic heart disease, myocardial
infarction, angina pectoris
|
|
Metabolic:
|
elevated BUN, elevated serum
glucose, elevated transaminase, elevated LDH
|
|
General Body:
|
non-specific chest pain,
pyrexia
|
|
Hematologic/Lymphatic:
|
leukocytosis, bleeding
|
|
Respiratory:
|
Dyspnea, upper respiratory
disorder
|
|
Genitourinary:
|
Oliguria
|
|
Musculoskeletal:
|
limb cramp
|
Pediatric Patients: In pediatric patients, the most
common adverse events reported during short term administration in controlled
trials (30 minutes) were hypotension and tachycardia. However, because of the
short exposure, there is limited experience with defining adverse events in
children. The long-term effects of fenoldopam on growth and development have
not been studied.
ANIMAL TOXICOLOGY
Unusual toxicologic findings (arterial lesions in the rat)
with fenoldopam are summarized below. These findings have not been observed
in mice or dogs. No evidence of a similar lesion in humans has been observed.
Arterial lesions characterized by medial necrosis and hemorrhage
have been seen in renal and splanchnic arteries of rats given fenoldopam mesylate
by continuous intravenous infusion at doses of 1 to 100 mcg/kg/min for 24 hours.
The incidence of these lesions is dose related. Arterial lesions morphologically
identical to those observed with fenoldopam have been reported in rats infused
with dopamine. Data suggest that the mechanism for this injury involves activation
of D1-like dopaminergic receptors. Such lesions have not been seen
in dogs given doses up to 100 mcg/kg/min by continuous intravenous infusion
for 24 hours, nor were they seen in dogs infused at the same dose for 6 hours
daily for 24 days. The clinical significance of this finding is not known.
Oral administration of fenoldopam doses of 10 to 15 mg/kg/day
or 20 to 25 mg/kg/day to rats for 24 months induced a higher incidence of polyarteritis
nodosa compared to controls. Such lesions were not seen in rats given 5 mg/kg/day
of fenoldopam or in mice given the drug at doses up to 50 mg/kg/day for 24 months.
DRUG INTERACTIONS
Drug Interactions with Beta-Blockers: Concomitant use
of fenoldopam with beta-blockers should be avoided. If the drugs are used
together, caution should be exercised because unexpected hypotension could
result from beta-blocker inhibition of the sympathetic reflex response to
fenoldopam.
Drug Interactions, General: Although there have been no formal interaction studies, intravenous
fenoldopam has been administered safely with drugs such as digitalis and
sublingual nitroglycerin. There is limited experience with concomitant
antihypertensive agents such as alpha-blockers, calcium channel-blockers,
ACE inhibitors, and diuretics (both thiazide-like and loop).
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