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
Dantrium Warnings, Precautions, Pregnancy, Nursing, Abuse - Dantrolene Sodium
Dantrium Warnings, Precautions, Pregnancy, Nursing, Abuse - Dantrolene Sodium
WARNINGS
The use of Dantrium Intravenous in the management of malignant hyperthermia
crisis is not a substitute for previously known supportive measures. These
measures must be Individualized, but it will usually be necessary to discontinue
the suspect triggering agents, attend to increased oxygen requirements,
manage the metabolic acidosis, institute cooling when necessary, monitor
urinary output, and monitor for electrolyte imbalance.
Since the effect of disease state and other drugs on the consequences
of Dantrium related skeletal muscle weakness, including possible respiratory
depression, can not be predicted, patients who receive i.v. Dantrium preoperatively
should have vital signs monitored.
If patients judged malignant hyperthermia susceptible are administered
intravenous or oral Dantrium preoperatively, anesthetic preparation must
still follow a standard malignant hyperthermia susceptible regimen, including
the avoidance of known triggering agents. Monitoring for early clinical
and metabolic signs of malignant hyperthermia is indicated because attenuation
of malignant hyperthermia, rather than prevention, is possible. These
signs usually call for the administration of additional iv. dantrolene.
PRECAUTIONS
General
Care must be taken to prevent extravasation of Dantrium solution into
the surrounding tissues due to the high pH of the intravenous formulation.
When mannitol is used for prevention or treatment of late renal complications
of malignant hyperthermia, the 3 g of mannitol needed to dissolve each
20 mg vial of iv. Dantrium should be taken into consideration.
Information for Patients
See PATIENT INFORMATION section.
Drug Interactions
See DRUG INTERACTIONS section.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Sprague-Dawley female rats fed Dantrium for 18-months at dosage levels
of 15, 30, and 60 mg/kg/day showed an increased incidence of benign and
malignant mammary tumors compared with concurrent controls. At the highest
dose levels (approximately the same as the maximum recommended daily dose
on a mg/m² basis), there was an increase in the incidence of benign hepatic
lymphatic neoplasms. In a 30-month study in Sprague-Dawley rats fed dantrolene sodium,
the highest dose level (approximately the same as the maximum recommended daily dose
on a mg/m² basis) produced a decrease in the time of onset of mammary neoplasms.
Female rats at the highest dose level showed an increased incidence of
hepatic lymphangiomas and hepatic angiosarcomas.
The only drug-related effect seen in a 30-month study in Fischer-344
rats was a dose-related reduction in the time of onset of mammary and
testicular tumors. A 24-month study in HaM/ICR mice revealed no evidence
of carcinogenic activity.
The significance of carcinogenicity data relative to use of Dantrium
in humans is unknown.
Dantrolene sodium has produced positive results in the Ames S. Typhimurium
bacterial mutagenesis assay in the presence and absence of a liver activating
system.
Dantrolene sodium administered to male and female rats at dose levels
up to 45 mg/kg/day (approximately 1.4 times the maximum recommended daily dose on a mg/m² basis)
showed no adverse effects on fertility or general reproductive performance.
Usage in Pregnancy
Pregnancy Category C: Dantrium has been shown to be embryocidal
in the rabbit and has been shown to decrease pup survival in the rat when
given at doses seven times the human oral dose. There are no adequate
and well-controlled studies in pregnant women. Dantrium Intravenous should
be used during pregnancy only if the potential benefit justifies the potential
risk to the fetus.
Labor and Delivery
In one uncontrolled study, 100 mg per day of prophylactic oral Dantrium
was administered to term pregnant patients awaiting labor and delivery.
Dantrolene readily crossed the placenta, with maternal and fetal whole
blood levels approximately equal at delivery: neonatal levels then fell
approximately 50% per day for 2 days before declining sharply. No neonatal
respiratory and neuromuscular side effects were detected at low dose.
More data, at higher doses, are needed before more definitive conclusions
can be made.
Geriatric Use
Clinical studies of Dantrium Intravenous did not include sufficient numbers of subjects aged 65 and over
to determine whether they respond differently from younger subjects. Other reported clinical experience has
not identified differences in responses between the elderly and younger patients. In general, dose selection
for an elderly patient should be cautious reflecting the greater frequency of decreased hepatic, renal, or
cardiac function, and of concomitant disease or other drug therapy.
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