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
Precedex Side Effects, and Drug Interactions - Dexmedetomidine hydrochloride
Precedex Side Effects, and Drug Interactions - Dexmedetomidine hydrochloride
SIDE EFFECTS
Adverse event information is derived from the placebo-controlled,
continuous infusion trials of dexmedetomidine for sedation in the ICU setting
in which 387 patients received PRECEDEX. Overall, the most frequently observed
treatment-emergent adverse events included hypotension, hypertension, nausea,
bradycardia, fever, vomiting hypoxia, tachycardia and anemia (see Table 5).
Table 5:Treatment-Emergent Adverse Events Occurring in >1%
of All Dexmedetomidine-Treated Patients in the Randomized Placebo-controlled
Continuous Infusion ICU Sedation Studies
|
Adverse Event
|
Dexmedetomidine (N=387)
|
Placebo (N=379)
|
|
Hypotension
|
30%
|
15%
|
|
Nausea
|
11%
|
10%
|
|
Bradycardia
|
8%
|
4%
|
|
Atrial Fibrillation
|
7%
|
6%
|
|
Hypoxia
|
6%
|
4%
|
|
Anemia
|
3%
|
2%
|
|
Pain
|
3%
|
2%
|
|
Pleural Effusion
|
3%
|
1%
|
|
Infection
|
2%
|
1%
|
|
Leukocytosis
|
2%
|
<1%
|
|
Oliguria
|
2%
|
1%
|
|
Pulmonary Edema
|
2%
|
<1%
|
|
Thirst
|
2%
|
<1%
|
The treatment-emergent adverse events in Table 6 were reported
in 1% of all dexmedetomidine-treated patients and are potentially clinically
relevant.
Table 6: Potentially Clinically Relevant Treatment-Emergent
Adverse Events to Dexmedetomidine Reported in £1%
Patients in the Continuous Infusion ICU Sedation Trials
|
Body System
|
Preferred Term
|
|
Body as a Whole
|
Fever, Hyperpyrexia, Hypovolemia, Light Anesthesia, Pain,
Rigors
|
|
Cardiovascular Disorders, General
|
Blood pressure fluctuation, Heart disorder, Aggravated
hypertension
|
|
Central and Peripheral Nervous System Disorders
|
Dizziness, Headache, Neuralgia, Neuritis, Speech disorder
|
|
Gastrointestinal System Disorders
|
Abdominal pain, Diarrhea, Vomiting,
|
|
Heart Rate and Rhythm Disorders
|
Arrhythmia, Ventricular arrhythmia, AV block, Cardiac
arrest, Extrasystoles, Atrial fibrillation, Heart block, T wave inversion,
Tachycardia, Supraventricular tachycardia, Ventricular tachycardia
|
|
Liver and Biliary System Disorders
|
Increased GGT, Increased SGOT, Increased SGPT,
|
|
Metabolic and Nutritional Disorders
|
Acidosis, Respiratory acidosis, Hyperkalemia, Increased
alkaline phosphatase, Thirst
|
|
Psychiatric Disorders
|
Agitation, Confusion, Delirium, Hallucination, Illusion,
Somnolence
|
|
Red Blood Cell Disorders
|
Anemia
|
|
Respiratory System Disorders
|
Apnea, Bronchospasm, Dyspnea, Hypercapnia, Hypoventilation,
Hypoxia, Pulmonary congestion
|
|
Skin and Appendages Disorders
|
Increased sweating
|
|
Vision Disorders
|
Photopsia, Abnormal vision
|
DRUG ABUSE AND DEPENDENCE
PRECEDEX (dexmedetomidine hydrochloride) is not a controlled
substance.
The dependence potential of dexmedetomidine has not been studied
in humans. However, since studies in rodents and primates have demonstrated
that dexmedetomidine exhibits pharmacologic actions similar to those of clonidine,
it is possible that PRECEDEX may produce a clonidine-like withdrawal syndrome
upon abrupt discontinuation (See PRECAUTIONS,
Withdrawal).
DRUG INTERACTIONS
General
In vitro studies in human liver microsomes demonstrated no
evidence of cytochrome P450-mediated drug interactions that are likely to be
of clinical relevance.
Anesthetics/Sedatives/Hypnotics/Opioids
Co-administration of PRECEDEX with anesthetics, sedatives,
hypnotics, and opioids is likely to lead to an enhancement of effects. Specific
studies have confirmed these effects with sevoflurane, isoflurane, propofol,
alfentanil, and midazolam. No pharmacokinetic interactions between dexmedetomidine
and isoflurane, propofol, alfentanil, and midazolam have been demonstrated.
However, due to possible pharmacodynamic interactions, when co-administered
with PRECEDEX, a reduction in dosage of PRECEDEX on the concomitant anesthetic,
sedative, hypnotic or opioid may be required.
Neuromuscular Blockers
In one study of 10 healthy volunteers, administration of PRECEDEX
for 45 minutes at a plasma concentration of 1 (one) ng/mL resulted in no clinically
meaningful increases in the magnitude or neuromuscular blockade associated with
rocuronium administration.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Animal carcinogenicity studies have not been performed with
dexmedetomidine.
Dexmedetomidine was not mutagenic in vitro, in either the bacterial
reverse mutation assay (E. coli and Salmonella typhimurium) or the mammalian
cell forward mutation assay (mouse lymphoma). Dexmedetomidine was clastogenic
in the in vitro human lymphocyte chromosome aberration test with, but not without,
metabolic activation. Dexmedetomidine was also clastogenic in the in vivo mouse
micronucleus test.
Fertility in male or female rats was not affected after daily
subcutaneous injections at doses up to 54 mcg/kg (less than the maximum recommended
human intravenous dose on a mcg/m2 basis). Dexmedetomidine was dosed
from 10 weeks prior to mating in males and 3 weeks prior to mating and during
mating in females.
Pregnancy: Teratogenic Effects. Pregnancy Category C
Teratogenic effects were not observed following administration
of dexmedetomidine at subcutaneous doses up to 200 mcg/kg in rats from day 5
to day 16 of gestation and intravenous doses up to 96 mcg/kg in rabbits from
day 6 to day 18 of gestation. The dose in rats is approximately 2 times the
maximum recommended human intravenous dose on a mcg/m2 basis. The
exposure in rabbits is approximately equal to that in humans at the maximum
recommended intravenous dose based on plasma area-under-the-curve values. However,
fetal toxicity, as evidenced by increased postimplantation losses and reduced
live pups, was observed in rats at a subcutaneous dose of 200 mcg/kg. The no-effect
dose was 20 mcg/kg (less than the maximum recommended human intravenous dose
on a mcg/m2 basis). In another reproductive study when dexmedetomidine
was administered subcutaneously to pregnant rats from gestation day 16 through
nursing, it caused lower pup weights at doses of 8 and 32 mcg/kg as well as
fetal and embryocidal toxicity of second generation offspring at a dose of 32
mcg/kg (less than the maximum recommended human intravenous dose on a mcg/m2
basis). Dexmedetomidine also produced delayed motor development in pups
at a dose of 32 mcg/kg (less than the maximum recommended human intravenous
dose on a mcg/m2 basis). No such effects were observed at a dose
of 2 mcg/kg (less than the maximum recommended intravenous dose on a mcg/m2
basis).
Placental transfer of dexmedetomidine was observed when radiolabeled
dexmedetomidine was administered subcutaneously to pregnant rats.
There are no adequate and well-controlled studies in pregnant
women.
Dexmedetomidine should be used during pregnancy only if the
potential benefits justify the potential risk to the fetus.
Labor and Delivery
The safety of PRECEDEX during labor and delivery has not been
studied. Therefore, PRECEDEX is not recommended during labor and delivery, including
cesarean section deliveries.
Nursing Mothers
It is not known whether PRECEDEX is excreted in human milk.
Radiolabeled dexmedetomidine administered subcutaneously to lactating female
rats was excreted in milk. Because many drugs are excreted in human milk, caution
should be exercised when PRECEDEX is administered to a nursing woman.
Pediatrics
There have been no clinical studies to establish the safety
and efficacy of PRECEDEX in pediatric patients below 18 years of age. Therefore,
PRECEDEX is not recommended for use in this population.
Geriatrics
A total of 531 subjects in the clinical studies were 65 years
of age and over. A total of 129 subjects in the clinical studies were 75 years
of age and over. In patients greater than 65 years of age, a higher incidence
of bradycardia and hypotension was observed following administration of PRECEDEX.
Therefore a dose reduction may be considered in patients over 65 years of age.
Dexmedetomidine is known to be substantially excreted by the
kidney, and the risk of adverse reactions to this drug may be greater in patients
with impaired renal function. Because elderly patients are more likely to have
decreased renal function, care should be taken in dose selection in elderly
patients, and it may be useful to monitor renal function.
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