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DANTRIUM INTRAVENOUS 20G

Active substance(s): DANTROLENE SODIUM

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PHYSICIAN LEAFLET

DANTRIUM® Intravenous 20 mg Powder for Solution for Injection
(dantrolene sodium)
Indications
For the treatment of malignant hyperthermia.
Mode of Action
In isolated muscle preparations, dantrolene sodium uncouples the
excitation and contraction of skeletal muscle, probably by interfering
with the release of calcium from sarcoplasmic reticulum. In the
malignant hyperthermia syndrome, evidence points to an intrinsic
abnormality of muscle tissue. It has been postulated that “triggering
agents” (i.e. skeletal muscle relaxants and inhalation anaesthetics)
induce a sudden rise in myoplasmic calcium either by preventing the
sarcoplasmic reticulum from accumulating calcium adequately, or by
accelerating its release. This rise in myoplasmic calcium activates the
acute catabolic processes involved in the malignant hyperthermia
crisis. Dantrolene sodium may prevent the increases in myoplasmic
calcium and the acute catabolism within the muscle cell by interfering
with the release of calcium from the sarcoplasmic reticulum to the
myoplasm. Thus the physiological, metabolic and biochemical changes
associated with the crisis may be reversed or attenuated.
Dosage and Administration
As soon as the malignant hyperthermia syndrome is recognised all
anaesthetic agents should be discontinued. An initial Dantrium IV dose
of 1 mg/kg should be given rapidly directly into the vein.
It must not be mixed with other intravenous infusions. If the
physiological and metabolic abnormalities persist or reappear, this
dose may be repeated up to a cumulative dose of 10 mg/kg. Clinical
experience to date has shown that the average dose of Dantrium IV
required to reverse the manifestations of malignant hyperthermia has
been 2.5 mg/kg. If a relapse or recurrence occurs, Dantrium IV should
be readministered at the last effective dose.
For intravenous use only.
Mixing Instructions
Each vial of Dantrium IV should be reconstituted by adding 60 ml Water
for Injections and shaking until the solution is clear.
Precautions and Warnings
a. In some subjects as much as 10 mg/kg of Dantrium IV has been
needed to reverse the crisis. In a 70 kg man this dose would require
approximately 36 vials. Such a volume has been administered in
approximately one and a half hours.
b. Contraindication: Hypersensitivity to dantrolene sodium or to any of
the excipients.
c. When mannitol is used for prevention or treatment of renal
complication of malignant hyperthermia the 3000 mg of mannitol
needed to dissolve each vial of intravenous dantrolene sodium
(20mg) should be taken into consideration.
d. Because of the high pH of the intravenous formulation of Dantrium
and potential for tissue necrosis, care must be taken to prevent
extravasation of the intravenous solution into the surrounding
tissues.
e. Pregnancy: the safety of Dantrium Intravenousin pregnant women
has not been established; Dantrolene sodium crosses the placenta
and it should be given only when the potential benefits have been
weighed against the possible risk to mother and child.
f. Dantrolene has been detected in human milk at low concentrations
(less than 2 micrograms per millilitre) during repeat intravenous
administration over 3 days. Dantrium Intravenous should be used by
nursing mothers only if the potential benefit justifies the potential
risk to the infant.

g. The use of Dantrium Intravenous in the management of malignant
hyperthermia is not a substitute for previously known supportive
measures. It will be necessary to discontinue the suspected
triggering agents, attend to increased oxygen requirements and
manage the metabolic acidosis. When necessary institute cooling,
attend to urinary output and monitor for electrolyte imbalance.
h Hepatic dysfunction, including hepatitis and fatal hepatic failure, has
been reported with dantrolene sodium therapy. Whilst the licensed
indications of intravenous dantrolene sodium do not generally
necessitate prolonged therapy, the risk of hepatic dysfunction may
increase with dose and duration of treatment, based on experience
with oral therapy. However in some patients it is of an idiosyncratic
or hypersensitivity type, and could occur after a single dose.
i. A decrease in grip strength and weakness of leg muscles, especially
walking down stairs,can be expected post-operatively. In addition,
symptoms such as “lightheadedness” may be noted. Since some of
these symptoms may persist for up to 48 hours, the patient must not
operate an automobile or engage in other hazardous activity during
this time.
Interactions with Other Drugs
The combination of therapeutic doses of intravenous dantrolene
sodium and verapamil in halothane/-alphachloralose anaesthetised
swine has resulted in ventricular fibrillation and cardiovascular collapse
in association with marked hyperkalaemia. Hyperkalaemia and
myocardial depression have also been reported rarely in malignant
hyperthermia-susceptible patients receiving intravenous dantrolene
and concomitant calcium channel blockers. Hence, the use of Dantrium
IV and calcium channel blockers in combination is not recommended.
Administration of dantrolene sodium may potentiate vecuroniuminduced neuromuscular block.
Side Effects and Adverse Reactions
There have been occasional reports of death following malignant
hyperthermia crisis even when treated with intravenous dantrolene
sodium; incidence figures are not available (the pre-dantrolene sodium
mortality of malignant hyperthermia crisis was approximately 50 %).
Most of these deaths can be accounted for by late recognition, delayed
treatment, inadequate dosage, lack of supportive therapy, intercurrent
disease and/or the development of delayed complications such as
renal failure or disseminated intravascular coagulopathy. In some cases
there are insufficient data to completely rule out therapeutic failure of
dantrolene sodium.
The administration of intravenous dantrolene sodium to human
volunteers is associated with loss of grip strength and weakness in the
legs, as well as subjective central nervous system complaints.
There are rare reports of pulmonary oedema developing during the
treatment of malignant hyperthermia crisis in which the diluent volume
and mannitol needed to deliver intravenous dantrolene sodium
possibly contributed.
Extravasation may lead to tissue necrosis.
Hepatic dysfunction may occur, including fatal hepatic failure
(see section “Precautions and warnings”).
Tabulated list of adverse other reactions
Frequency cannot be estimated from available data.

309517

System Organ Class Frequency
Nervous system
Unknown
disorders
Cardiac disorders
Unknown
Respiratory, thoracic
and mediastinal
disorders

Unknown

Gastrointestinal
disorders

Unknown

Hepatobiliary
disorders

Unknown

Skin and
subcutaneous
disorders
Renal and urinary
disorders
General disorders
and administration
site conditions

Unknown

Adverse drug Reactions
Dizziness, somnolence,
convulsion speech disorder
Cardiac failure, bradycardia,
tachycardia
Pulmonary oedema
(dilutent volume and
mannitol needed to
deliver dantrolene IV may
contribute to the event),
Pleural effusion, respiratory
failure, respiratory
depression
Abdominal pain, nausea,
vomiting, gastrointestinal
bleeding
Hepatic dysfunction
including fatal hepatic
failure (see section 4.4),
jaundice, hepatitis
Hyperhidrosis

Unknown

Crystalluria

Unknown

Rash, erythema, localised
pain and thrombophlebitis

Shelf-Life
Three years. The reconstituted solution should be used within six hours.
Excipients
Mannitol
Sodium hydroxide
Storage Precautions
Unopened product: Do not store above 25°C. Reconstituted product:
Store between 15 and 25°C.
Do not refrigerate or freeze. Protect from direct light.
Marketing Authorisation Holder and Manufacturer:
Norgine BV
Hogehilweg 7
1101 CA Amsterdam
The Netherlands
DANTRIUM is a registered trademark of the SpePharm AG group of
companies, licensed to the Norgine group of companies.
Legal Category: POM
This leaflet was last revised in 04/2016

22200502
309517

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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