Consumer medicine information

Dantrium Capsules

Dantrolene sodium hemiheptahydrate

BRAND INFORMATION

Brand name

Dantrium Capsules

Active ingredient

Dantrolene sodium hemiheptahydrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Dantrium Capsules.

What is in this leaflet

This leaflet answers some common questions about DANTRIUM capsules. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of treating you with DANTRIUM against the expected benefits it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What DANTRIUM is used for

DANTRIUM capsules are used to relax muscles which are in spasm as a result of spinal cord injury, stroke, cerebral palsy or multiple sclerosis. It is of particular help to those patients whose rehabilitation is being slowed down by muscle spasm.

Ask your doctor if you have any questions about why DANTRIUM has been prescribed for you. Your doctor may have prescribed it for another reason.

Before you take DANTRIUM

When you must not take it

Do not take DANTRIUM Capsules if you have an allergy to:

  • any medicine containing dantrolene sodium hemiheptahydrate
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not take DANTRIUM Capsules if you have or have had any of the following medical conditions:

  • liver disease such as hepatitis and cirrhosis
  • muscle spasm to allow you to keep an upright position, to balance during movement or for better physical function.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

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

Tell your doctor if you have or have had any of the following medical conditions:

  • you have liver problems
    It is essential to have your liver checked by your doctor before taking DANTRIUM, to determine if you have any existing problems with your liver.
  • you have problems with your breathing
  • you have heart problems
  • you have kidney problems
  • you are pregnant or intend to become pregnant
    Your doctor will discuss the possible risks and benefits of using DANTRIUM during pregnancy.
  • you are breastfeeding or intend to breastfeed
    DANTRIUM should not be used while breastfeeding.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including:

  • all prescription medicines
  • all medicines, vitamins, herbal supplements or natural therapies you buy without a prescription from a pharmacy, supermarket, naturopath or health food shop.

Some medicines may be affected by DANTRIUM or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines. Your doctor will advise you.

Tell your doctor or pharmacist if you are taking any of the following:

  • medicines containing oestrogen, which include oral contraceptives and medicines used to treat symptoms of menopause.
  • calcium channel blockers such as verapamil, used to treat high blood pressure.
  • other muscle relaxant medicines which work differently to DANTRIUM
  • CNS depressants (medicines to reduce anxiety or help you sleep).

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to take DANTRIUM

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the bottle, ask your doctor or pharmacist for help.

How much to take

Your doctor will decide how much DANTRIUM you should take each day and how long your treatment with DANTRIUM should continue.

Take the capsules exactly as instructed by your doctor or pharmacist.

When to take it

Your doctor will tell you how many times a day you should take DANTRIUM.

Always read the pharmacist's label to check the exact dose and how often to take it.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking it as you would normally.

Do not take a double dose to make up for the dose that you have missed.

If you are not sure whether to skip the dose, ask your doctor or pharmacist for advice.

If you take too much (overdose)

Immediately telephone your doctor, or the Australian Poisons Information Centre (telephone 131 126), or go to Accident and Emergency at your nearest hospital, if you think you or anyone else may have taken too much DANTRIUM.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are taking DANTRIUM

Things you must do

Keep all your doctor's appointments so that your progress and health can be monitored.

DANTRIUM can cause damage to your liver, so your liver function needs to be checked regularly by your doctor to detect any abnormalities.

If you become pregnant while being treated with DANTRIUM, tell your doctor immediately.

If you are about to be started on any new medicine, tell your doctor and pharmacist that you are being treated with DANTRIUM.

Tell all doctors, dentists and pharmacists who are treating you that you are taking DANTRIUM.

Things you must not do

Do not take DANTRIUM to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not drive or operate machinery while you are taking DANTRIUM.

DANTRIUM causes drowsiness, dizziness and weakness in some people and therefore may affect alertness.

Avoid drinking alcohol or taking medicines to reduce anxiety or help you sleep. These may increase the drowsiness and dizziness effects of DANTRIUM and should be avoided.

Things to be careful of

Be careful of exposure to sunlight while being treated with DANTRIUM. DANTRIUM may increase sensitivity of the skin to sun. Symptoms of sunburn (such as redness, itching, swelling or blistering) may occur more quickly than normal.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking DANTRIUM.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

It can be difficult to tell whether side effects are the result of taking DANTRIUM, effects of your condition or side effects of other medicines you may be taking. For this reason it is important to tell your doctor of any change in your condition.

Do not be alarmed by the list of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if…

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • drowsiness
  • dizziness
  • weakness
  • fatigue
  • diarrhoea
  • general feeling of being unwell
  • shortness of breath and chest pain
  • constipation
  • loss of appetite
  • difficulty swallowing
  • stomach cramps/pain
  • indigestion
  • dry mouth
  • vomiting
  • speech problems
  • headache
  • nausea
  • light-headedness
  • visual problems, including double vision
  • alteration of taste
  • trouble sleeping
  • depression
  • mental confusion
  • frequent urination
  • increased urination at night
  • abnormal colouration of the urine
  • difficulties in obtaining an erection
  • abnormal hair growth
  • rashes
  • bleeding or bruising more easily
  • sweating
  • backache
  • muscle pain
  • feeling of suffocation, excessive tearing, chills and fever.

Tell your doctor as soon as possible if…

Tell your doctor immediately if you notice any of the following:

  • swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing
  • swelling of the liver which can result in yellowing of the skin and eyes, lower back pain, dark urine, nausea, vomiting, loss of appetite, fever, itching and a general feeling of being unwell
  • gastrointestinal bleeding
  • fits or convulsions
  • fast heart rate
  • shortness of breath and swelling of the feet or legs
  • crystals or blood in the urine
  • loss of control of the bladder
  • difficulty passing or inability to pass urine.

These may be serious side effects of DANTRIUM. You may need urgent medical attention.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After using DANTRIUM

Storage

Keep your capsules in a cool dry place where the temperature stays below 30°C.

Do not store DANTRIUM or any other medicine in the bathroom or near a sink.

Do not leave it in the car or on a window sill on hot days. Heat and dampness can destroy some medicines.

Keep your DANTRIUM capsules where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking DANTRIUM, or the capsules have passed their expiry date, ask your pharmacist what to do with any capsules that are left over.

Product description

What it looks like

DANTRIUM capsules are available in 25 mg and 50 mg strengths.

DANTRIUM 25 mg capsules are orange and tan and marked in black with "Dantrium" "25 mg", "0149", "0030" and a single line. The 25 mg capsules are available in bottles of 100 capsules.

DANTRIUM 50 mg capsules are orange and tan and marked in black with "Dantrium" "50 mg", "0149", "0031" and a double line. The 50 mg capsules are available in bottles of 100 capsules.

Ingredients

The active ingredient in DANTRIUM capsules is dantrolene sodium.

DANTRIUM capsules also contain:

  • maize starch
  • purified talc
  • magnesium stearate
  • lactose monohydrate
  • gelatin
  • iron oxide red
  • iron oxide yellow
  • sunset yellow FCF
  • sodium lauryl sulfate
  • titanium dioxide
  • black printing ink (TekPrint SW-9008 or TekPrint SW-9010).

Supplier

DANTRIUM capsules are supplied in Australia by:

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

Australian registration numbers

25 mg capsule: AUST R 42975
50 mg capsule: AUST R 42976

Date of preparation

This leaflet was prepared in September 2020.

® = Registered Trademark

© Pfizer Australia Pty Ltd

Published by MIMS November 2020

BRAND INFORMATION

Brand name

Dantrium Capsules

Active ingredient

Dantrolene sodium hemiheptahydrate

Schedule

S4

 

1 Name of Medicine

Dantrolene sodium hemiheptahydrate.

2 Qualitative and Quantitative Composition

25 mg capsule.

Contains 25 mg dantrolene sodium hemiheptahydrate.

50 mg capsule.

Contains 50 mg dantrolene sodium hemiheptahydrate.

Excipient(s) with known effect.

Sugars (as lactose monohydrate).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

25 mg capsule.

Hard gelatin capsule with a tan opaque body and orange opaque cap, imprinted with "Dantrium" "25 mg" on the cap and "0149" "0030" and single coding bars on the body in black ink. Fill: deep orange cylindrical plug.

50 mg capsule.

Hard gelatin capsule with a tan opaque body and orange opaque cap, imprinted with the logo "Dantrium" "50 mg" on the cap and "0149" "0031" and single coding bars on the body in black ink. Fill: deep orange cylindrical plug.

4 Clinical Particulars

4.1 Therapeutic Indications

Dantrium is indicated in controlling the manifestations of clinical spasticity resulting from serious chronic disorders such as spinal cord injury, stroke, cerebral palsy, or multiple sclerosis. It is of particular benefit to the patient whose functional rehabilitation has been retarded by the sequelae of spasticity. Such patients must have presumably reversible spasticity where relief of spasticity will aid in restoring residual function. There is no evidence that patients with contractures will benefit. Dantrium is not indicated in the treatment of skeletal muscle spasm resulting from rheumatic disorders or electroconvulsive therapy.
If improvement occurs, it will ordinarily occur within the dosage titration schedule (see Section 4.2 Dose and Method of Administration), as manifested by a decrease in the severity of spasticity and the ability to resume a daily function not quite attainable without Dantrium.
Occasionally, subtle but meaningful improvements in spasticity may occur with Dantrium therapy. In such instances information regarding improvement should be solicited from the patient directly and from those who are in constant daily contact and attendance with the patient. Brief withdrawal of Dantrium for a period of 2 to 4 days will frequently demonstrate exacerbation of the manifestation of spasticity and may serve to confirm a clinical impression.
A decision to continue the administration of Dantrium on a long-term basis is justified if introduction of the drug into the patient's regimen produces a significant reduction in painful and/or disabling spasticity such as clonus, or permits a significant reduction in the intensity and/or degree of nursing care required, or rids the patient of an annoying manifestation of spasticity considered important by the patient themselves.

4.2 Dose and Method of Administration

Dosage.

Prior to the administration of Dantrium, consideration should be given to the potential response to treatment. A decrease in spasticity sufficient to allow a daily function not otherwise attainable should be the therapeutic goal of treatment with Dantrium. See Section 4.1 Therapeutic Indications for a description of the response to be anticipated.
It is important to establish a therapeutic goal (regain and maintain a specific function such as therapeutic exercise program, utilisation of braces, transfer manoeuvres, etc.) before beginning Dantrium therapy. Dosage should be increased until the maximum performance compatible with the dysfunction due to underlying disease is achieved. No further increase in dosage is then indicated.
Usual dosage. It is important that the dosage be titrated and individualised for maximum effect. The lowest dose compatible with optimal response is recommended.
In view of the potential for liver damage in long-term Dantrium use, therapy should be stopped if benefits are not evident within 45 days.

Adults.

Begin therapy with 25 mg once daily; increase to 25 mg two, three or four times daily and then by increments of 25 mg up to as high as 50 mg two, three or four times daily if necessary. The maximum recommended dose is 200 mg/day. As most patients will respond to this or a lower dose, and hepatotoxicity appears to be dose related above 200 mg/day, higher doses should be used only rarely and with close monitoring (see Section 4.4 Special Warnings and Precautions for Use). Doses higher than 400 mg/day should not be used.
Each dosage level should be maintained for four to seven days to determine the patient's response. The dose should not be increased beyond, and may even have be reduced to, the amount at which the patient received maximal benefit without adverse effects.

Children.

A similar approach should be utilised, starting with 0.5 mg/kg of bodyweight twice daily; this is increased to 0.5 mg/kg three or four times daily, and then by increments to a maximum of 2 mg/kg three times a day. Doses higher than 50 mg four times daily should not be used in children.

4.3 Contraindications

Active hepatic disease, such as acute hepatitis and active cirrhosis, is a contraindication for use of Dantrium. Dantrium is contraindicated where spasticity is utilised to sustain upright posture and balance in locomotion, or whenever spasticity is utilised to obtain or maintain increased function.

4.4 Special Warnings and Precautions for Use

If no observable benefit is derived from the administration of Dantrium after a total of 45 days, therapy should be discontinued. The lowest possible effective dose for the individual patient should be prescribed.

Hepatotoxicity.

Dantrium should be used with caution in patients with a history of previous liver disease or dysfunction.
It is important to recognise that Dantrium has a potential for hepatotoxicity, and should not be used in conditions other than those recommended. Symptomatic hepatitis (fatal and nonfatal) has been reported at various dose levels of the drug. Hepatotoxicity appears to be dose related above 200 mg/day and this is the maximum recommended dose. Patients receiving higher doses should be closely monitored. Even sporadic short courses of doses above 400 mg/day within a treatment regimen markedly increased the risk of serious hepatic injury. Liver dysfunction as evidenced by blood chemical abnormalities alone (liver enzyme elevations) has been observed in patients exposed to Dantrium for varying periods of time. Overt hepatitis has occurred at varying intervals after initiation of therapy, but has been most frequently observed between the third and twelfth month of therapy.
At the start of Dantrium therapy, it is essential to do liver function studies (SGOT, SGPT, alkaline phosphatase, total bilirubin) for a baseline or to establish whether there is pre-existing liver disease. If baseline liver abnormalities exist and are confirmed, there is a clear possibility that the potential for Dantrium hepatotoxicity could be enhanced. Dantrium should be used only in conjunction with appropriate monitoring of hepatic function. Liver function studies (e.g. SGOT or SGPT) should be performed at appropriate intervals during Dantrium therapy. If such studies reveal abnormal values, therapy should generally be discontinued. Only where benefits of the drug have been of major importance to the patient, should reinitiation or continuation of therapy be considered. Some patients have revealed a return to normal laboratory values in the face of continued therapy while others have not.
If symptoms compatible with hepatitis, accompanied by abnormalities in liver function tests or jaundice appear, Dantrium should be discontinued. If caused by Dantrium and detected early, the abnormalities in liver function characteristically have reverted to normal when the drug was discontinued. Dantrium therapy has been reinstituted in a few patients who have developed clinical and/or laboratory evidence of hepatocellular injury. If such reinstitution of therapy is done, it should be attempted only in patients who clearly need Dantrium and only after previous symptoms and laboratory abnormalities have cleared. The patient should be hospitalised and the drug should be restarted in very small and gradually increasing doses. Laboratory monitoring should be frequent and the drug should be withdrawn immediately if there is any indication of recurrent liver involvement. Some patients have reacted with unmistakable signs of liver abnormality upon administration of a challenge dose, while others have not.
Dantrium should be used with particular caution in females and in patients over 35 years of age in view of the apparently greater likelihood of drug induced, potentially fatal, hepatocellular disease in these groups. Careful consideration should be given to the possible risks involved in the concurrent use of hormonal oral contraceptives with Dantrium (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Impaired pulmonary function.

Dantrium should be used with caution in patients with impaired pulmonary function, particularly those with obstructive pulmonary disease, and in patients with severely impaired cardiac function due to myocardial disease. Dantrium is associated with pleural effusion with associated eosinophilia.

Photosensitivity.

Dantrium might possibly evoke a photosensitivity reaction; patients should be cautioned about exposure to sunlight while on therapy.

Neuroleptic malignant syndrome.

The published literature has included some reports of Dantrium use in patients with neuroleptic malignant syndrome (NMS). Dantrium capsules are not indicated for the treatment of NMS and patients may expire despite treatment with Dantrium capsules.

Long-term safety.

Long-term safety of Dantrium in humans has not been established. Chronic studies in rats, dogs and monkeys at dosages greater than 30 mg/kg/day showed growth or weight depression and signs of hepatopathy and possible occlusion nephropathy, all of which were reversible upon cessation of treatment. Sprague-Dawley female rats fed dantrolene sodium hemiheptahydrate for 18 months at dosage levels of 15, 30 and 60 mg/kg/day showed an increased incidence of benign and malignant mammary tumours compared with concurrent controls and, at the highest dosage an increase in the incidence of hepatic lymphangiomas and hepatic angiosarcomas. These effects were not seen in 2½ year studies in Sprague-Dawley or Fischer 344 rats or in 2 year studies in mice of the HaM/ICR strain.

Use in hepatic impairment.

See Section 4.4 Special Warnings and Precautions for Use, Hepatotoxicity; Section 4.3 Contraindications.

Use in renal impairment.

In patients with impaired renal function, dosage may have to be significantly reduced and the possibility of a drug related further impairment borne in mind (see Section 4.8 Adverse Effects (Undesirable Effects)).

Use in the elderly.

Spontaneous reports suggest a higher proportion of hepatic events with fatal outcome in elderly patients receiving Dantrium. 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. As with all patients receiving Dantrium, it is recommended that elderly patients receive the lowest dose compatible with the optimal response (see Section 4.2 Dose and Method of Administration).

Paediatric use.

The long-term safety of Dantrium in children under the age of 5 years has not been established. Because of the possibility that adverse effects of the drug could become apparent only after many years, a benefit-risk consideration of the long-term use of Dantrium is particularly important in paediatric patients.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

While a definite drug interaction with oestrogen therapy has not yet been established, caution should be observed if the two drugs are to be given concomitantly. Hepatotoxicity has occurred more often in women over 35 years of age receiving concomitant oestrogen therapy.
There are very rare reports of cardiovascular collapse in patients treated simultaneously with verapamil and dantrolene sodium hemiheptahydrate. The combination of therapeutic doses of intravenous dantrolene sodium hemiheptahydrate and verapamil in halothane/ α-chloralose anaesthetised swine has resulted in ventricular fibrillation and cardiovascular collapse in association with marked hyperkalaemia. Until the relevance of these findings to humans is established, the combination of dantrolene sodium hemiheptahydrate and calcium channel blockers, such as verapamil, is not recommended.
The effects of nondepolarising muscle relaxants may be potentiated in patients administered dantrolene.
Administration of Dantrium may potentiate vecuronium induced neuromuscular block.
Dantrolene causes dizziness, drowsiness, and weakness; alcohol and other CNS depressants such as sedatives and tranquilising agents may intensify this effect.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B2)
The safety of Dantrium for use in women who are or who may become pregnant has not been established; hence it should be given only when the potential benefits have been weighed against possible hazard to mother and child. Dantrolene crosses the placenta.
 Dantrium should not be used by nursing mothers. Dantrolene has been detected in human breast milk.

4.7 Effects on Ability to Drive and Use Machines

Patients should be cautioned against driving a motor vehicle or participating in hazardous occupations while taking Dantrium. Dantrolene causes dizziness, drowsiness and weakness; alcohol and other CNS depressants may intensify this effect.

4.8 Adverse Effects (Undesirable Effects)

The most frequently occurring adverse effects of Dantrium have been drowsiness, dizziness, weakness, general malaise, fatigue, and diarrhoea. These effects have been experienced by approximately 20% of patients. They are generally transient, occurring early in treatment, and can often be obviated by beginning with a low dose and increasing dosage gradually until an optimal regimen is established. Diarrhoea may be severe and may necessitate temporary withdrawal of Dantrium therapy. If diarrhoea recurs upon readministration of Dantrium, therapy should probably be withdrawn permanently.
Other less frequent adverse effects, listed according to system are:

Gastrointestinal.

Constipation, rarely progressing to signs of intestinal obstruction, GI bleeding, anorexia, gastric irritation, abdominal cramps, vomiting, nausea, dry mouth, saliva hypertension, dyspepsia, dysphagia.

Haematologic.

Aplastic anaemia, anaemia, leukopenia, lymphocytic lymphoma, thrombocytopenia.

Hepatobiliary.

Liver function test disturbances, hepatitis (see Section 4.4 Special Warnings and Precautions for Use, Hepatotoxicity).

Neurologic.

Speech disturbance, seizure, headache, lightheadedness, visual disturbance, diplopia, alteration of taste.

Cardiovascular.

Tachycardia, erratic blood pressure, heart failure, phlebitis, exacerbation of cardiac insufficiency.

Psychiatric.

Mental depression, mental confusion, increased nervousness, insomnia.

Urogenital.

Increased urinary frequency, crystalluria, haematuria, difficult erection, urinary incontinence and/or nocturia, difficult urination, chromaturia and/or urinary retention. A transient lowering of GFR and renal plasma flow after 8 weeks' therapy has been reported.

Integumentary.

Abnormal hair growth, acne-like rash, pruritus, urticaria, eczematoid eruption, sweating.

Musculoskeletal.

Myalgia, backache.

Respiratory.

Feeling of suffocation, respiratory depression, respiratory failure.

Special senses.

Excessive tearing.

Hypersensitivity.

Pleural effusion with associated eosinophilia, pericarditis, anaphylaxis.

Other.

Chills and fever.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

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 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 that may occur include, but are not limited to, muscular weakness, alterations in the state of consciousness (e.g. lethargy, coma), vomiting, diarrhoea and crystalluria. Mild tachycardia and hypotension may develop. Oral dantrolene may cause lethargy, but is likely to resolve uneventfully.
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.
Emesis is not recommended due to risk of CNS and respiratory depression.
Excretion of the active compounds is not known to be enhanced by fluid diuresis.
For information on the management of overdose, contact the Poison Information Centre on 13 11 126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

In isolated nerve muscle preparations, Dantrium has been shown to produce relaxation of the contractile state of the skeletal muscle by an effect beyond the myoneural junction and directly on the muscle itself. In these preparations Dantrium uncouples the excitation and contraction of the skeletal muscle, probably by interfering with the release of calcium ions from the sarcoplasmic reticulum. This effect appears to be more pronounced in fast muscle fibres as compared to slow ones, but generally affects both. A central nervous system effect occurs with drowsiness, dizziness and generalised weakness in some 20% of cases. The extent of the involvement of the CNS in Dantrium induced muscle relaxation is unknown.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

The absorption of Dantrium after oral administration in humans is incomplete and slow, but consistent and dose related blood levels are obtained. The duration and intensity of skeletal muscle relaxation is related to the dosage and blood levels. The mean biological half-life of Dantrium in adults is 8.7 hours after a 100 mg dose. Specific metabolic pathways in the degradation and elimination of Dantrium in human subjects have been established. Metabolic patterns are similar in adults and children. In addition to the parent compound, dantrolene, which is found in measurable amounts in blood and urine, the major metabolites noted in body fluids are the 5-hydroxy analogue and the acetamido analogue.
Approximately 20 to 25% of an oral dose appears in the urine in the metabolised form and 1% or less is excreted unchanged. About 45 to 50% of the same oral dose appears in the bile. Since Dantrium is probably metabolised by hepatic microsomal enzymes, enhancement of its metabolism by other drugs is possible. However, neither phenobarbital nor diazepam appears to affect Dantrium metabolism.
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.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

Carcinogenicity in humans cannot be fully excluded, so this possible risk of chronic administration must be weighed against the benefits of the drug (i.e. after a brief trial) for the individual patient.

6 Pharmaceutical Particulars

6.1 List of Excipients

Gelatin, iron oxide red, iron oxide yellow, lactose monohydrate, magnesium stearate, sodium lauryl sulfate, maize starch, sunset yellow FCF, purified talc, TekPrint SW-9008 black ink, TekPrint SW-9010 black ink, and titanium dioxide.

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 30°C.

6.5 Nature and Contents of Container

Dantrium capsules are available in HDPE bottles of 100.

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

Dantrolene sodium hemiheptahydrate is an orange powder, slightly soluble in water, but due to its slightly acidic nature the solubility increases somewhat in alkaline solution. The anhydrous salt has a molecular weight of 336. The hydrated salt contains approximately 15% water (3½ moles) and has a molecular weight of 399.
Dantrolene sodium hemiheptahydrate is 1-{[5-(p-nitrophenyl) furfurylidene]amino}hydantoin sodium hydrate. The chemical structure of hydrated dantrolene sodium is shown below.

Chemical structure.


CAS number.

14663-23-1.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (S4).

Summary Table of Changes