SUMMARY CMI

Dantrium^® Powder For Injection

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about treatment with this medicine, speak to your doctor or pharmacist.

1. Why am I being treated with Dantrium powder for injection?

Dantrium powder for Injection contains the active ingredient dantrolene sodium hemiheptahydrate. It is a muscle relaxant used to treat a condition known as malignant hyperthermia.

For more information, see Section 1. Why am I being treated with Dantrium powder for injection? in the full CMI.

2. What should I know before treatment with Dantrium powder for injection?

Talk to your doctor if you have ever had an allergic reaction to dantrolene or mannitol which are ingredients contained in this medicine.

Talk to your doctor if you have any medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before treatment with Dantrium powder for injection? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Dantrium powder for injection and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How is Dantrium powder for injection given?

Dantrium powder for Injection is made into a solution, which is given by injection into a vein by your doctor.

More instructions can be found in Section 4. How is Dantrium powder for injection given? in the full CMI.

5. What should I know during treatment with Dantrium powder for injection?

For more information, see Section 5. What should I know during treatment with Dantrium powder for injection? in the full CMI.

6. Are there any side effects?

Side effects of this medicine may include swelling or tenderness around a vein; itchy skin rash or reddening of the skin; breathlessness; chest tightness or pain; gasping for air; wheezing; drowsiness; dizziness; weakness in the legs or loss of grip strength; difficulty in swallowing.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

Dantrium^® Powder For Injection

Active ingredient(s): Dantrolene sodium hemiheptahydrate

Consumer Medicine Information (CMI)

This leaflet provides important information about treatment with Dantrium powder for injection. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about treatment with Dantrium powder for injection.

Where to find information in this leaflet:

1. Why am I being treated Dantrium powder for injection?
2. What should I know before treatment with Dantrium powder for injection?
3. What if I am taking other medicines?
4. How is Dantrium powder for injection given?
5. What should I know during or after treatment with Dantrium powder for injection?
6. Are there any side effects?
7. Product details

1. Why am I being treated Dantrium powder for injection?

Dantrium powder for injection contains the active ingredient dantrolene sodium hemiheptahydrate.

It is a muscle relaxant used to treat a condition known as malignant hyperthermia. This condition occurs rarely during or after surgery or anaesthesia. The tendency to develop malignant hyperthermia may be inherited.

Some of the symptoms of malignant hyperthermia are very high fever, fast and irregular heart-beat, difficulty breathing and rigid muscles.

Malignant hyperthemia may be fatal if not treated.

Your doctor may have prescribed Dantrium powder for injection for a purpose other than that listed above.

Ask your doctor if you have any questions about why Dantrium was prescribed for you.

2. What should I know before treatment with Dantrium powder for injection?

Warnings

Tell your doctor if you have ever had an allergic reaction to dantrolene sodium hemiheptahydrate or mannitol.

Some of the symptoms of an allergic reaction may include rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or troubled breathing.

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

3. What if I am taking other medicines?

Some medicines may interfere with Dantrium powder for injection and affect how it works.

Tell your doctor if you are taking any heart medicines or tranquillisers (medicines to reduce anxiety or help you sleep).

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Dantrium powder for injection.

4. How is Dantrium powder for injection given?

How much Dantrium powder for injection is given

The dose of Dantrium is calculated by your doctor according to your body weight.

How is Dantrium powder for injection given

Dantrium is given to you by your doctor as soon as malignant hyperthermia is recognised. It will be given by injection into a vein.

How long will I receive Dantrium powder for injection

Treatment must continue until all symptoms of malignant hyperthermia are gone.

Treatment may be repeated if symptoms return after initial recovery.

If you receive too much Dantrium powder for injection

As Dantrium powder for injection is given under the close supervision of your doctor, it is very unlikely that you will receive too much.

If you experience any side effects tell your doctor or nurse immediately.

Tell your doctor or nurse immediately if you are concerned that you may have been given too much Dantrium powder for injection.

5. What should I know during or after treatment with Dantrium powder for injection?

Things you should do

Driving or using machines

For 2 days after treatment, do not operate machinery or do anything else that could be dangerous when not fully alert.

Weakness, dizziness and drowsiness can continue for up to 48 hours after treatment.

Things to be careful of

Take care when getting out of bed or walking downstairs.

You may experience light-headedness, leg weakness or loss in grip strength after treatment with Dantrium.

Be careful when eating or drinking on the day you have been treated with Dantrium.

Some people have difficulty swallowing after treatment with Dantrium. Choking has been reported.

Drinking alcohol

Caution should be taken when drinking alcohol.

Looking after your medicine

Dantrium powder for injection is stored in the pharmacy or on the hospital ward under the correct conditions.

Disposal of the medicine

The hospital staff will dispose of any leftover Dantrium powder for injection.

6. Are there any side effects?

Tell your doctor as soon as possible if you have any concerns about being treated with Dantrium powder for injection.

All medicines can have side effects. You may need medical treatment if you get some of the side effects.

Tell your doctor, nurse or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

7. Product details

This medicine is only available with a doctor's prescription.

What Dantrium powder for injection contains

What Dantrium powder for injection looks like

Dantrium powder for injection is a powder which must be diluted with sterile water for injections before use.

Dantrium powder for injection: Aust R 14435.

Who distributes Dantrium powder for injection

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizermedicalinformation.com.au

This leaflet was prepared in November 2024.

Published by MIMS December 2024

1 Name of Medicine

Dantrolene sodium hemiheptahydrate.

2 Qualitative and Quantitative Composition

Dantrium Powder for Injection is a sterile lyophilised formulation of dantrolene sodium hemiheptahydrate and in this form provides a preparation for intravenous use. Each 65 mL vial contains 20 mg dantrolene sodium hemiheptahydrate, 3 g mannitol and sufficient sodium hydroxide to yield a pH of approximately 9.5 when reconstituted with 60 mL of sterile water for injections (without a bacteriostatic agent).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Dantrium Powder for Injection is light yellow lyophilised powder.

4 Clinical Particulars

4.1 Therapeutic Indications

Dantrium for injection is indicated, along with appropriate supportive measures, for the management of the fulminant hypermetabolism of skeletal muscle characteristic of malignant hyperthermia (MH) crisis. It should be administered by intravenous injection as soon as the MH reaction is recognised (i.e. tachycardia, tachypnea, central venous desaturation, hypercarbia, metabolic acidosis, skeletal muscle rigidity, increased utilisation of anaesthesia circuit carbon dioxide absorber, cyanosis and mottling of the skin and, in many cases, fever).

4.2 Dose and Method of Administration

As soon as the MH reaction is recognised, all anaesthetic agents should be discontinued. Dantrium for injection should be administered by continuous rapid intravenous push beginning at a minimum dose of 1 mg/kg, and continuing until symptoms subside or the maximum cumulative dose of 10 mg/kg has been reached. If the physiologic and metabolic abnormalities reappear, the regimen may be repeated.
It is important to note that administration of Dantrium for injection should be continuous until symptoms subside. The effective dose to reverse the crisis is directly dependent upon the individual's degree of susceptibility to MH, the amount and time of exposure to the triggering agent, and the time elapsed between onset of the crisis and initiation of treatment.
Please Note: In some subjects as much as 10 mg/kg of dantrolene sodium hemiheptahydrate has been needed to reverse MH. In a 70 kg man this dose would require about 36 vials. Such a volume has been administered in approximately 90 minutes.

Children's dose.

Preparation.

4.3 Contraindications

None.

4.4 Special Warnings and Precautions for Use

The use of Dantrium for injection in the management of MH crisis is not a substitute for previously known supportive measures. These measures must be individualised, 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, attend to urinary output, monitor for electrolyte imbalance.

General.

Hepatotoxicity.

With dantrolene sodium hemiheptahydrate capsules.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The combination of therapeutic doses of intravenous dantrolene sodium hemiheptahydrate and verapamil in halothane/ alpha-chloralose anaesthetised swine has resulted in ventricular fibrillation and cardiovascular collapse in association with marked hyperkalaemia. Myocardial depression and hyperkalaemia have also been reported rarely in MH susceptible patients receiving intravenous dantrolene and concomitant calcium channel blockers. It is recommended that the combination of intravenous dantrolene sodium hemiheptahydrate and calcium channel blockers, such as verapamil, not be used during reversal of a MH crisis.
Administration of dantrolene sodium hemiheptahydrate may potentiate the effects of nondepolarising muscle relaxants, such as vecuronium.
Caution should be exercised in the concomitant administration of tranquillising agents. Dantrolene causes dizziness, drowsiness and weakness; alcohol and other CNS depressants may intensify this effect.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

There have been occasional reports of death following MH crisis even when treated with intravenous dantrolene sodium hemiheptahydrate. 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 exclude therapeutic failure of dantrolene sodium hemiheptahydrate.
There are rare reports of fatality in MH crisis, despite initial satisfactory response to intravenous dantrolene sodium hemiheptahydrate, which involve patients who could not be weaned from dantrolene sodium hemiheptahydrate after initial treatment.
There are rare reports of pulmonary oedema developing during the treatment of MH crisis in which the diluent volume and mannitol needed to deliver intravenous dantrolene sodium hemiheptahydrate possibly contributed.
There have been reported cases of hepatotoxicity following the use of intravenous dantrolene products. Elevated liver enzymes have occurred hours to days following use of intravenous dantrolene, though many of these cases were observed in patients with comorbidities (e.g. critical illness).
There have been reports of thrombophlebitis following administration of dantrolene sodium hemiheptahydrate; the incidence of this complication is unknown.
There have been rare reports of urticaria and erythema possibly associated with administration of intravenous dantrolene sodium hemiheptahydrate and at least one case of anaphylaxis.
The administration of intravenous dantrolene sodium hemiheptahydrate to human volunteers is associated with loss of grip strength and weakness in the legs, as well as drowsiness and dizziness.
The serious reactions reported with chronic oral Dantrium use have been hepatitis, seizures and pleural effusion with associated eosinophilia, pericarditis. None of the reactions reported in patients taking oral Dantrium have been reported in patients treated with short-term Dantrium for injection therapy for MH.
The following additional events have been reported in patients receiving oral dantrolene: abdominal cramps, abnormal hair growth, acne-like rash, anorexia, alteration of taste, aplastic anaemia, anaphylaxis, backache, chills, constipation rarely progressing to signs of intestinal obstruction, crystalluria, diarrhoea, difficult erection, difficult urination and/or urinary retention, diplopia, eczematoid eruption, erratic blood pressure, exacerbation of cardiac insufficiency, excessive tearing, fatigue, feeling of suffocation, fever, gastric irritation, general malaise, myalgia, GI bleeding, haematuria, headache, heart failure, increased nervousness, increased urinary frequency, insomnia, leucopenia, lightheadedness, liver function test disturbances, lymphocytic lymphoma, mental confusion, mental depression, nausea, phlebitis, pruritus, speech disturbance, swallowing difficulty, sweating, tachycardia, transient lowering of G.F.R. and renal plasma flow after 8 weeks' therapy has been reported, urinary incontinence and/or nocturia, urticaria, visual disturbance and vomiting.

Reporting suspected adverse effects.

4.9 Overdose

Fatal poisoning with this agent is rare and lethal doses are not established. There is no known set of symptoms with acute overdose. Signs and symptoms are likely to be an extension of those under Adverse Effects (Undesirable Effects) (see Section 4.8 Adverse Effects (Undesirable Effects)). The primary toxic effect is CNS depression and, in severe cases, coma. Respiratory depression may occur in patients with significant CNS depression. Total skeletal paralysis is unlikely in conscious patients. Symptoms which may occur in case of overdose include, but are not limited to, muscular weakness and alterations in the state of consciousness (e.g. lethargy, coma), vomiting, diarrhoea and crystalluria. Mild tachycardia and hypotension may develop.
Monitor and support respiratory and cardiovascular function.
Intravenous fluids should be administered in fairly large quantities to avert the possibility of crystalluria. Consider central venous pressure monitoring to guide further fluid therapy. Fluids and electrolytes should be monitored closely. Monitor patients with significant CNS depression for respiratory insufficiency and rhabdomyolysis.
Excretion of the active compounds is not known to be enhanced by fluid diuresis.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

Dantrolene sodium hemiheptahydrate is classified as a direct-acting skeletal muscle relaxant.

5.1 Pharmacodynamic Properties

Mechanism of action.

Clinical trials.

5.2 Pharmacokinetic Properties

Specific metabolic pathways in the degradation and elimination of dantrolene sodium hemiheptahydrate in humans have been established. Dantrolene is found in measurable amounts in blood and urine. In addition, its major metabolites in body fluids are the 5-hydroxy analogue and the acetamido analogue. Another metabolite with an unknown structure appears related to acetylamino-dantrolene. Dantrolene sodium hemiheptahydrate may also undergo hydrolysis and subsequent oxidation forming nitrophenylfuroic acid. Since dantrolene sodium hemiheptahydrate is metabolised by the liver, enhancement of its metabolism by other drugs is possible. However, neither phenobarbitone nor diazepam appears to affect dantrolene sodium hemiheptahydrate metabolism.
The mean biologic half-life of dantrolene sodium hemiheptahydrate after intravenous administration is about 5 hours. Based on assays of whole blood and plasma, slightly greater amounts of dantrolene are associated with red blood cells than with the plasma fraction of blood. Significant amounts of dantrolene are bound to plasma proteins, mostly albumin, and this binding is readily reversible. Binding to plasma protein is not significantly altered by diazepam, diphenylhydantoin, or phenylbutazone. Binding to plasma proteins is reduced by warfarin and clofibrate and increased by tolbutamide.
In animals dantrolene sodium hemiheptahydrate given intravenously has no appreciable effect on the cardiovascular system or on respiratory function. A transient inconsistent effect on smooth muscles has been observed at high doses.
Because of the low drug concentration requiring the administration of large volumes of fluid, acute toxicity of a dantrolene sodium hemiheptahydrate intravenous formulation could not be assessed. In 14 day (subacute) studies, the intravenous formulation of dantrolene sodium hemiheptahydrate was relatively non toxic to rats at doses of 10 mg/kg/day and 20 mg/kg/day. While 10 mg/kg/day in dogs for 14 days evoked little toxicity, 20 mg/kg/day for 14 days caused hepatic changes of questionable biologic significance.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Mannitol, sodium hydroxide.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C, protect from light.
The contents of the vial must be protected from direct light and used within 6 hours after reconstitution. Store reconstituted solutions at controlled room temperature (15°C - 25°C). Store unreconstituted product below 25°C and avoid prolonged exposure to light.

6.5 Nature and Contents of Container

Dantrium Powder for Injection 20 mg type I clear glass vials, in packs of 6's.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

The hydrated salt contains approximately 15% water (3½ moles) and has a molecular weight of 399. The anhydrous salt has a molecular weight of 336.

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

Schedule 4 (Prescription Only Medicine).

Summary Table of Changes