Dantrium Intravenous 20 mg Powder for Solution for Injection
*Company:
Norgine LimitedStatus:
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Product subject to medical prescription which may be renewed (B)Active Ingredient(s):
*Additional information is available within the SPC or upon request to the company
Updated on 24 October 2024
File name
ie-pil-dan-iv-en.pdf
Reasons for updating
- Change to section 4 - possible side effects
Updated on 14 June 2022
File name
ie-smpc-dan-iv-en-clean.pdf
Reasons for updating
- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.7 - Effects on ability to drive and use machines
- Change to section 4.8 - Undesirable effects
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 5.3 - Preclinical safety data
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
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4.1 Therapeutic indication
For the treatment of malignant hyperthermia.
In combination with adequate support measures, Dantrium Intravenous is indicated in adults and children in the treatment of malignant hyperthermia.
4.2 Posology and method of administration
Posology
As soon as the MH reaction is recognised, all anaesthetic agents should be discontinued; the administration of 100 % oxygen is recommended. Dantrium Intravenous 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 Intravenous 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 crises and administration of treatment.
Dantrium Intravenous should be administered by rapid intravenous injection at least 2.5 mg/kg body weight (8-10 vials in adults). As long as the main clinical symptoms of tachycardia, hypoventilation, sustained hyperacidity (pH and pCO2 monitoring required) and hyperthermia persist, bolus injection should be repeated. In most cases, a total dose of 10 mg/kg body weight per 24h is sufficient. This dose (10 mg/kg) may need to be exceeded in individual cases. Safe uses up to 40 mg/kg have been described. Based on this experience, higher dosages can be administered in isolated cases if required.
Paediatric population
Experience to date indicates that the dose for children is the same as for adults. No dosage adjustment required.
Method of administration
Dantrium 20 mg powder for solution is available f For intravenous administration only.
After reconstitution, the solution must be filtered with the filtration device provided when drawing up the solution into the syringe ( see section 4.4). Remove the single–use filtration device from the syringe prior to attachment to an intravenous cannula or giving set.
Each vial should be prepared by adding 60 mL of sterile water for injection and the vial shaken until the solution is dissolved.
The reconstituted solution should be filtered using the single use filter provided
For instructions on use reconstitution and filtration of the medicinal product before administration, see section 6.6.
4.3 Contraindications
Hypersensitivity to dantrolene sodium or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
The use of Dantrium Intravenous in the management of MH malignant hyperthermic crisis is not a substitute for other supportive measures.
These must be individually continued in their various forms. Dantrium Intravenous may only be infused intravenously. Due to the high pH value of the solution (pH 9.5), extravascular injection/infusion must be avoided as it can lead to tissue necrosis. Due to the risk of vascular occlusion, intraarterial injections must be avoided. Spill of the solution on skin should be avoided. If solution gets on the skin, it must be removed with sufficient water.
In addition, due to the potential for undissolved crystals/particles to appear in the re-constituted product and the subsequent potential risk of exacerbation of injection site reactions/tissue necrosis from crystals within affected vials, use of the filtration device when drawing up the solution is required at all times.
Each vial of Dantrium Intravenous contains 3 g mannitol (for adjustment of isotonic solutions). This amount should be considered if mannitol is used to prevent and treat renal complications related to malignant hyperthermia.
Caution should be exercised if hyperkalaemia symptoms occur (muscular paralysis, ECG changes, bradycardic arrhythmias) or in cases of pre-existing hyperkalaemia (renal insufficiency, digitalis intoxication etc.), as an increase in serum potassium has been demonstrated in animal trials as a result of dantrolene.
Liver damage may occur during dantrolene therapy. This is dependent on the dosage and duration of therapy and may run a lethal course.
This medicine contains less than 1mmol sodium (23mg) per vial that is to say essentially “sodium free.
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, monitor urinary output, and monitor for electrolyte imbalance.
Since the effect of disease state and other drugs on dantrolene sodium related skeletal muscle weakness, including possible respiratory depression, cannot be predicted, patients who receive IV dantrolene sodium preoperatively should have vital signs monitored.
If patients judged with MHS are administered intravenous or oral dantrolene sodium preoperatively, anaesthetic preparation must still follow a standard MHS regimen, including the avoidance of known triggering agents. Monitoring for early clinical and metabolic signs of MH is indicated because attenuation of MH, rather than prevention, is possible. These signs usually call for the administration of additional IV dantrolene sodium.
When mannitol is used to prevent or treat the renal complications of malignant hyperthermia, the mannitol content in the Dantrium vial, i.e. 3000 milligrams of mannitol per 20mg of dantrolene sodium, should be taken into consideration.
Because of the high pH of Dantrium Intravenous and potential for tissue necrosis, care must be taken to prevent extravasation of the intravenous solution into the surrounding tissues. In addition, due to the potential for undissolved crystals/particles to appear in the re-constituted product and the subsequent potential risk of exacerbation of injection site reactions/tissue necrosis from crystals within affected vials, use of the filtration device when drawing up the solution is required at all times.
In some subjects as much as 10mg/kg of dantrolene sodium 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.
Information for Patients
Based upon data in human volunteers, it will sometimes be appropriate to tell patients who receive dantrolene sodium intravenous that decrease in grip strength and weakness of leg muscles, especially walking down stairs, can be expected postoperatively. Caution is also indicated at meals on the day of administration because difficulty in swallowing and choking has been reported. Caution should be exercised in the concomitant administration of tranquilizing agents.
Hepatotoxicity seen with dantrolene sodium capsules
Dantrolene has a potential for hepatotoxicity, and symptomatic hepatitis, sometimes fatal, has been reported. Factors that may be related to a poorer prognosis include higher daily doses, prolonged duration of therapy, female gender, and increasing patient age. Spontaneous reports also suggest a higher proportion of hepatic events with fatal outcome in elderly patients.
Hepatic dysfunction, including fatal hepatic failure, can occur with dantrolene use, and appears to be related to dose and duration of therapy. Fatal and non-fatal liver disorders of idiosyncratic or hypersensitivity type may also occur with dantrolene sodium therapy.
Evaluation of hepatic function should be done before initiating treatment, and hepatic function should be monitored at appropriate intervals throughout treatment. If monitoring reveals abnormal liver function, or if signs or symptoms of hepatotoxicity occur during therapy, dantrolene should be withdrawn. If a decision is made to restart treatment after recovery from hepatic dysfunction, liver function should be monitored and the drug discontinued if abnormal values are observed.
4.5 Interaction with other medicinal products and other forms of interaction
Isolated case reports and animal studies indicate an interaction between dantrolene and calcium channel blockers, such as verapamil and diltiazem, in the form of heart failure. It is recommended that Dantrium Intravenous and calcium channel blockers should not be used at the same time.
Concomitant administration of Dantrium Intravenous with non-depolarising muscle relaxants such as vecuronium can enhance their effect.
Dantrolene is metabolised by the liver, and it is theoretically possible that its metabolism may be enhanced by drugs known to induce hepatic microsomal enzymes. However, neither phenobarbital nor diazepam appears to affect dantrolene's metabolism. 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.
The combination of therapeutic doses of intravenous dantrolene sodium and verapamil in halothane/alpha-chloralose 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 sodium and concomitant calcium channel blockers. Hence, the use of Dantrium Intravenous and calcium channel blockers in combination is not recommended, until the relevance of these findings to humans is established.
Administration of dantrolene may potentiate vecuronium-induced neuromuscular block.
Pregnancy
The safety of Dantrium Intravenous in pregnant women has not been established: There are no or limited data from the use of dantrolene in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). Dantrolene crosses the placenta, and should be given only when the potential benefits have been weighed against the possible risk to mother and child.
Breast feeding
No information is available on use of dantrolene during breastfeeding. According to its safety profile, a risk to a breastfed infant cannot be excluded as dantrolene is excreted in breastmilk. Therefore, breastfeeding should be discontinued during administration of Dantrium Intravenous. Based on elimination half-life of dantrolene, breastfeeding can be restarted 60 hours after the last dose.
Dantrolene has been detected in human milk at low concentrations (less than 2 micrograms per milliliter) 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.
Fertility
Data on the effects of dantrolene on fertility in humans are not available.
There are no data on the effects of Dantrium on fertility in humans.
4.7 Effects on ability to drive and use machines
Dantrium Intravenous has major influence on the ability to drive and use machines, as it can lead to weakness, dizziness and light-headedness. This applies particularly in combination with alcohol or other medicines that depress the central nervous system.
A decrease in grip strength and weakness of leg muscles, especially walking down stairs, can be expected postoperatively. In addition, symptoms such as "light headedness" may be noted. Since some of these symptoms may persist for up to 48 hours, patients must not operate an automobile or engage in other hazardous activity during this time.
4.8 Undesirable effects
Summary of the safety profile
There have been occasional reports of death following MH crisis even when treated with intravenous dantrolene. Incidence figures are not available (the pre-dantrolene mortality of MH 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.
There are rare reports of fatality in MH crisis, despite initial satisfactory response to Dantrium Intravenous, which involve patients who could not be weaned from dantrolene after initial treatment. The administration of intravenous dantrolene to human volunteers is associated with loss of grip strength and weakness in the legs, as well as subjective CNS complaints.
The following adverse reactions are in approximate order of severity:
Tabulated list of adverse reactions.
Adverse Drug Reactions related to dantrolene sodium are presented below according to system organ class and frequency.
Frequencies are defined according to:
Very common (≥ 1/10)
Common (≥ 1/100 to < 1/10)
Uncommon (≥ 1/1000 to < 1/100)
Rare (≥ 1/10000 to < 1/1000)
Very rare (< 1/10000)
Not known: frequency could not be estimated due to the present data
System Organ Class
Frequency
Adverse Drug Reaction
Blood and lymphatic disorders
Unknown
Thrombophlebitis
Immune system disorder
Unknown rare
Allergic reactions, Aanaphylaxis
Metabolism and nutrition disorders
Unknown
Hyperkalaemia
Nervous system disorders
Unknown
Drowsiness, dizziness, general weakness, somnolence,
convulsion, speech disorder, headache
Cardiac disorders
Unknown
Cardiac failure, bradycardia, tachycardia
Vascular disorders
Unknown
Thrombophlebitis
Respiratory, thoracic and mediastinal disorders
Unknown
Rare
Pulmonary oedema,
Pleural effusion, respiratory failure, respiratory depression
Gastrointestinal disorders
Unknown
Abdominal pain/cramps, nausea, vomiting, gastrointestinal bleeding, diarrhoea
Hepatobiliary disorders
Unknown
Jaundice, hepatitis, hepatic dysfunction including fatal hepatic failure, idiosyncratic or hypertensive liver diseases
Skin and subcutaneous disorders
Rare
Unknown
Urticaria, erythema
Hyperhidrosis
Musculoskeletal and
connective tissue disorders
Unknown
Muscle weakness, muscle fatigue
Renal and urinary disorders
Unknown
Crystalluria
Reproductive system and breast disorders
Unknown
Uterine hypotonia
General disorders and administration site conditions
Unknown
common
Fatigue, administration Local injection site reactions
For orally administered dantrolene sodium the unwanted effects associated with the use of Dantrium are as follows:
System Organ Class
Frequency
Adverse Drug Reaction
Metabolism and nutrition disorders
Common
Anorexia
Psychiatric disorders:
Less common
Mental depression, mental confusion
Nervous system disorders:
Common
Seizure, speech disturbance, headache, drowsiness, dizziness
Eye disorders
Common
Visual disturbances
Cardiac disorders
Common
Less common
Pericarditis
Exacerbation of cardiac insufficiency, tachycardia
Vascular disorders
Less common
Labile blood pressure
Respiratory, thoracic and mediastinal disorders
Common:
Less Common
Pleural effusion with associated eosinophilia, respiratory depression
Dyspnoea
Gastrointestinal disorders
Common
Less common
Nausea and/or vomiting, abdominal pain, diarrhoea
Swallowing difficulties, constipation (rarely progressing to signs of intestinal obstruction)
Hepato-biliary disorders
Common
Hepatotoxicity (see section 4.4), liver function test disturbances
Skin and subcutaneous tissue disorders
Common
Less common
Acne-like rash, skin eruptions
Sweating
Renal and urinary disorders
Less common
Incontinence, increased urinary frequency, urinary retention, haematuria, crystalluria
General disorders and administration site conditions
Common
Common
weakness, general malaise, fatigue
Chills and /or fever
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: direct-acting muscle relaxants, ATC code: M03CA01.
Dantrolene decouples nerve impulse and contraction in skeletal muscle probably by interfering with calcium release from the sarcoplasmic reticulum. Its action is specific and has no influence on neuromuscular transmission or any measurable effect on the excitable surface membrane.
In anaesthetic-induced malignant hyperthermia, signs indicate a genetic-related anomaly of the muscle cell. It is assumed that the triggering agents cause a sudden rise in myoplasmic calcium, by increasing its release and preventing storage in the sarcoplasmic reticulum. The resulting increase in myoplasmic calcium leads to hypermetabolism, which is the cause of hyperthermia, metabolic acidosis and other symptoms of malignant hyperthermia.
Dantrolene can prevent acute catabolism within the muscle cell by inhibiting the release of calcium from the sarcoplasmic reticulum within the myoplasm. Thus, the physiologic, metabolic and biochemical changes associated with the crisis can be reversed or attenuated. However, dantrolene therapy can only work when calcium has not yet entirely been emptied from the sarcoplasmic reticulum, i.e. dantrolene should be used as early as possible, provided that muscle perfusion is still adequately assured.
Pharmacotherapeutic group: ATC code: M03CA01, muscle relaxants, directly acting agents.
Mechanism of action
Dantrolene is classified as a direct-acting skeletal muscle relaxant. In isolated nerve-muscle preparation, dantrolene sodium has been shown to produce relaxation by affecting the contractile response of the skeletal muscle at a site beyond the myoneural junction, directly on the muscle itself.
Pharmacodynamic effects
In skeletal muscle, dantrolene dissociates the excitation-contraction coupling, probably by interfering with the release of Ca++ from the sarcoplasmic reticulum. This effect appears to be more pronounced in fast muscle fibres as compared to slow ones, but generally affects both.
Clinical efficacy and safety
A central nervous system effect occurs, with drowsiness, dizziness, and generalised weakness occasionally present. Although dantrolene does not appear to directly affect the CNS, the extent of its indirect effect is unknown.
5.2 Pharmacokinetic properties
Distribution
Dantrolene is reversibly bound to plasma albumin; as an in vitro binding constant, a value of 4.3x104M 1 was established. For the transplacental passage of dantrolene, a factor of 0.4 was found.
Metabolism
Metabolism in the liver takes place through microsomal enzymes both via
5-hydroxylation at the hydantoin ring and via reduction of the nitro group to amine with subsequent acetylation. 5-hydroxydantrolene has similar activity to that of the parent substance, while the acetamino dantrolene does not have any muscle relaxant effect.
Elimination
Excretion is mainly renal and biliary, whereby renal excretion takes place,
even in long-term use, at a ratio of 79% 5-hydroxydantrolene, 17% acetylamino-dantrolene and 1 to 4% unchanged dantrolene. Renal clearance (5-OH-dantrolene) is 1.8 to 7.8 L/h.
Following intravenous administration, the average elimination half-life of dantrolene is variable, generally it is between 4 and 8 hours, in a malignant hyperthermia patient it is 12 hours. Pharmacokinetic studies in children have shown an average elimination half-life of approximately 7.4 to 12.6 hours.
Metabolism
Specific metabolic pathways for the degradation and elimination of dantrolene in humans have been established. Dantrolene is found in measurable amounts in blood and urine.
Its major metabolites in body fluids are 5-hydroxy dantrolene and an acetylamino metabolite of dantrolene. Another metabolite with an unknown structure appears related to the latter. Dantrolene may also undergo hydrolysis and subsequent oxidation forming nitrophenylfuroic acid.
Elimination
The mean biologic half-life of dantrolene after intravenous administration is variable, between 4 to 8 hours under most experimental conditions. 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.
5.3 Preclinical safety data
Acute toxicity
Non clinical data for intravenous administration are not available. Following
intraperitoneal administration, the LD50 is around 800 mg/kg body weight in rats (human equivalent dose 129 mg/kg) and following oral administration the LD50 is around 3 g/kg in newborn rats (human equivalent dose 484 mg/kg). No LD50 values could be determined following oral administration to adult animals, due to a lack of mortality.
With subacute intravenous administration of dantrolene at doses of up to 20 mg/kg/day, the sole observations were reduced body weight gain in rats (human equivalent dose 3.2 mg/kg) and hepatic changes in dogs (human equivalent dose 11.1 mg/kg).
Chronic toxicity
In chronic toxicity studies rats, dogs and monkeys oral administration of >30 mg/kg/day (human equivalent dose 4.8 mg/kg, 16.2 mg/kg and 9.6 mg/kg, respectively) for 12 months led to a reduction of growth or body weight gain. Hepatotoxic effects and possibly renal obstruction were observed, which were reversible.
Mutagenicity
Dantrolene yielded positive results in the Ames S. typhyimurium test both in the present and absence of a liver activating system.
Carcinogenicity
Dietary doses of dantrolene sodium in rats at doses of up to 60 mg/kg/day (human equivalent dose 9.6 mg/kg) for to 18 months resulted in increases in benign hepatic lymphatic neoplasms, increased hepatic lymphangiomas and hepatic angiosarcomas, and in females only, an increase in mammary tumours. The relevance of these data for clinical use of dantrolene is not known.
Reproductive toxicity
In male and female adult rats dantrolene up to an oral dose of 45 mg/bodyweight/day (human equivalent dose 7.3 mg/kg/day) did not have any adverse effects on fertility or general reproductive capability Administration of dantrolene to pregnant rabbits (45 mg/kg/day; human equivalent dose 14.5 mg/kg/day) led to increased formation of unilateral or bilateral supernumerary ribs in the pups.
Carcinogenicity
Dantrolene sodium showed some evidence of tumourgenicity at high dose levels in Sprague-Dawley female rats. These effects were not seen in other studies in Fischer 344 rats or HaM/ICR mice.
There is no clinical evidence of carcinogenicity in humans; however, this possibility cannot be absolutely excluded.
10. DATE OF REVISION OF THE TEXT
01 October 2021
10th June 2022
Updated on 14 June 2022
File name
ie-pil-dan-iv-en-clean.pdf
Reasons for updating
- Change to section 1 - what the product is used for
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 3 - dose and frequency
- Change to section 3 - overdose, missed or forgotten doses
- Change to section 4 - possible side effects
- Change to section 6 - date of revision
Free text change information supplied by the pharmaceutical company
Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
If you get any side effects, talk to your doctor or pharmacist.
This includes any possible side effects not listed in this leaflet. See section 4.
1.What Dantrium Intravenous is and what it is used for
Dantrium is a muscle relaxant. When given by intravenous injection, it is useful in controlling
malignant hyperthermia. This is a rare reaction to anaesthesia in which the body temperature rises
extremely quickly. This serious condition produces a variety of symptoms such as a fast heartbeat and breathing rate, stiff muscles, changes in the acidity of the body and rhythm of the heart as well as high
blood pressure. The reaction requires emergency treatment including oxygen, cooling the body,
controlling its acidity, stopping the anaesthetic and giving Dantrium Intravenous. This injection is
given to you by a doctor immediately when malignant hyperthermia is recognised.
Dantrium Intravenous belongs to the pharmacotherapeutic group of direct-acting muscle relaxants. It is used for the treatment of malignant hyperthermia. The ATC code is M03CA01.
Dantrium Intravenous is a medicine which will be administered to you by a doctor or nurse.
2. What you need to know before you are given Dantrium Intravenous
You will probably have been given Dantrium Intravenous before you see this leaflet. The urgent
need for treatment will have been more important than anything else at the time. Before you are given this injection, your doctor will try to find out if you have had a serious reaction to Dantrium Intravenous in the past.
Do not take Do not use Dantrium Intravenous-i
If you are allergic (hypersensitive) to dantrolene sodium the active ingredient or any of the other ingredients of Dantrium Intravenous this medicine (listed in see section 6).
Warning and precautions
Take special care with Dantrium Intravenous. You will probably have been given Dantrium Intravenous before you read this leaflet. The urgent need for treatment will have been more important than anything else at the time. Before you are given this injection, your doctor will try to find out if you have had a serious reaction to dantrolene sodium or any of the other ingredients of Dantrium Intravenous in the past.
Other medicines and Dantrium Intravenous
Tell your doctor if you are taking, have recently taken or might use any other medicines, including medicines obtained without a prescription.
Your doctor will also exercise caution if you are taking tranquilizing medicines.
Dantrium Intravenous contains sodium
This medicine contains less than 1 mmol sodium (23mg) per vial that is to say essentially “sodium free”.
3. How Dantrium Intravenous is given
This injection is given to you by a doctor into a vein. The dose of Dantrium Intravenous is based on
body weight; in most cases a total dose of up to 10 mg may be given for each kilogram of your body weight is sufficient however a total dose of up to 40mg for each kilogram of your body weight may be required in rare cases.
Based on experience to date, the dose for children is the same as for adults. Care should be taken that Dantrium Intravenous is not mixed with other intravenous infusion fluids.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
If you are given more Dantrium Intravenous than you should
Malignant hyperthermia is an emergency situation where rapid infusion of a high Dantrium Intravenous dose is necessary. There are no known specific symptoms of dantrolene overdose. Caution is required if there are any signs of hyperkalaemia.
If you stop using Dantrium Intravenous
If it should appear necessary to discontinue Dantrium Intravenous therapy, intensive care and supportive therapeutic measures which have been initiated should be continued on an individual basis.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects were observed:
Not known (Frequency cannot be estimated from the available data):
muscle weakness, tiredness, dizziness, headache, gastrointestinal complaints such as nausea, vomiting, diarrhoea, anaphylaxis, allergic reactions, mostly of the skin, as well as thrombophlebitis or reactions at the application site, somnolence, convulsion, speech disorder, bradycardia (slowed heartbeat), tachycardia (accelerated heartbeat), pleural effusion (fluid collection in the chest), respiratory failure, abdominal pain, gastrointestinal bleeding, jaundice, hepatitis, hyperhidrosis (increased sweat secretion), crystalluria (accumulation of crystals in urine sediment), heart failure.
You may suffer an allergic reaction, symptoms of which include rash, itching, difficulty in
breathing or swelling of the face, lips, throat or tongue (anaphylaxis).
Reactions at site of injection may occur.
Immediately inform your health care provider if you have liver problems, which may be serious (signs may include, yellowing of skin and eyes, feeling sick or abnormal blood tests)
Rare side effect reported include:
-Weakness of hand and leg muscles and light headedness in the first 48 hours following injection.
-red, swollen, irritated skin and tissue around the area
-extreme shortness of breath
-hives
-red painful lesions
Side effects of unknown frequency which cannot be estimated from the available data:
-dizziness
-drowsiness
-convulsions
-speech disorder
-decreased heart rate
-increased heart rate
-shortness of breath when you exert yourself or when lying down
-chest pain
-wheezing, bluish tint to the skin
-abnormal breathing
-abdominal pain
-nausea, vomiting
-blood in the stool
-yellowing of the skin, fever, loss of appetite
-increased sweating
-cloudy urine
-inflammation and/or redness, sometimes formation of a blood clot in the vein where Dantrium Intravenous was injected
6. Contents of the pack and other information
This leaflet was last revised in 0210/20212.
Updated on 05 October 2021
File name
ie-smpc-dan-iv-en-clean.pdf
Reasons for updating
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- Change to section 6.5 - Nature and contents of container
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
4.8 Undesirable effects
Reporting suspected adverse reactions after authorisation 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 via HPRA Pharmacovigilance, Earlsfor Terrace, IRL – Dublin 2; Tel:+353 1 6764971: FAX: +353 1 6762517. Website: www.hpra.ie.: Email:medsafety@hpra.ie.
6.5 Nature and contents of container
Clear 70 ml vials, glass Type I (Ph .Eur.), with siliconized chlorobutyl lyophilisation bromobutyl rubber stopper Type I (Ph. Eur.) and with an aluminium cap seal with a polypropylene flip-off disk. The vials are sealed with aluminium caps with polypropylene flip off disks. Each vial is provided with a single-use filtration device. Supplied in packs of 12 or 36 vials.
Not all pack sizes may be marketed.
10 DATE OF REVISION OF THE TEXT
May 2019 01 October 2021
Updated on 05 October 2021
File name
ie-pil-dan-iv-clean.pdf
Reasons for updating
- Change to section 4 - how to report a side effect
- Change to section 6 - date of revision
Free text change information supplied by the pharmaceutical company
4. Possible side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel:+353 1 6764971: FAX: +353 1 6762517. Website: www.hpra.ie.: Email:medsafety@hpra.ie.
By reporting side effects you can help provide more information on the safety of this medicine.
6. Contents of the pack and other information
This leaflet was last revised in 05/201910/2021.
Updated on 15 May 2019
File name
ie-pil-dantrium iv-5124-May 2019.pdf
Reasons for updating
- Change to further information section
Updated on 15 May 2019
File name
ie-spc-dantrium iv-5124-May 2019.pdf
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 6.5 - Nature and contents of container
- Change to section 6.6 - Special precautions for disposal and other handling
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 23 January 2019
File name
ie-pil-dantrium-iv-7890 Nov 2018.pdf
Reasons for updating
- Change to section 6 - marketing authorisation holder
- Change to section 6 - date of revision
Updated on 23 January 2019
File name
ie-spc-dantrium-iv-7890 Jan 2019.pdf
Reasons for updating
- Change to section 7 - Marketing authorisation holder
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 06 July 2017
Reasons for updating
- New SPC for new product
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 06 July 2017
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.8 - Undesirable effects
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- Change to section 10 - Date of revision of the text
- Correction of spelling/typing errors
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Section 4.8 has been updated with:
Cardiac disorders - Cardiac failure, bradycardia
Gastrointestinal disorders - gastrointestinal bleeding
Respiratory, thoracic and mediastinal disorders - respiratory failure
Hepatobiliary disorders - jaundice, hepatitis
Updated on 06 July 2017
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.8 - Undesirable effects
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- Change to section 10 - Date of revision of the text
- Correction of spelling/typing errors
Free text change information supplied by the pharmaceutical company
Section 4.8 has been updated with:
Cardiac disorders - Cardiac failure, bradycardia
Gastrointestinal disorders - gastrointestinal bleeding
Respiratory, thoracic and mediastinal disorders - respiratory failure
Hepatobiliary disorders - jaundice, hepatitis
Updated on 29 June 2017
File name
PIL_8592_648.pdf
Reasons for updating
- New PIL for new product
Updated on 12 May 2017
Reasons for updating
- Previous version of SPC reinstated
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Updated on 12 May 2017
Reasons for updating
- Previous version of SPC reinstated
Free text change information supplied by the pharmaceutical company
Updated on 30 December 2016
Reasons for updating
- Change to section 4.8 - Undesirable effects
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- Change to section 10 - Date of revision of the text
- Improved presentation of SPC
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 30 December 2016
Reasons for updating
- Change to section 4.8 - Undesirable effects
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- Change to section 10 - Date of revision of the text
- Improved presentation of SPC
Updated on 28 October 2014
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.6 - Pregnancy and lactation
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- Change to section 4.9 - Overdose
- Change to section 6.1 - List of excipients
- Change to section 6.3 - Shelf life
- Change to section 6.4 - Special precautions for storage
- Change to section 6.5 - Nature and contents of container
- Change to section 6.6 - Special precautions for disposal and other handling
- Change to section 7 - Marketing authorisation holder
- Change to section 8 - MA number
- Change to section 9 - Date of renewal of authorisation
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
4.2 Posology and method of administration
As soon as the malignant hyperthermia (MH) MH reaction is recognised, all anaesthetic agents should be discontinued; the administration of 100 % oxygen is recommended. Dantrium IV 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.
4.4 Special warnings and precautions for use
The use of Dantrium IV in the management of a 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, monitor urinary output, and monitor for electrolyte imbalance.
Since the effect of disease state and other drugs on dantrolene sodium related skeletal muscle weakness, including possible respiratory depression, cannot be predicted, patients who receive i.v.IV dantrolene sodium preoperatively should have vital signs monitored.
If patients judged MH-susceptible (with MHS) are administered intravenous or oral dantrolene sodium preoperatively, anesthetic preparation must still follow a standard MHS regimen, including the avoidance of known triggering agents. Monitoring for early clinical and metabolic signs of MH is indicated because attenuation of MH, rather than prevention, is possible. These signs usually call for the administration of additional i.v.IV dantrolene sodium.
Hepatic dysfunction, including fatal hepatic failure, can occur with dantrolene use, and appears to be related to dose and duration of therapy. Fatal and non-fatal liver disorders of an idiosyncratic or hypersensitivity type may also occur with dantrolene sodium therapy.
4.6 Pregnancy Fertility, pregnancy and lactation
4.8 Undesirable effects
Vasular Vascular disorders:
Less common: Labile blood pressure
4.9 Overdose
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, diarrhea diarrhoea, and crystalluria.
6.1 List of excipients
Mannitol
Sodium hydroxide (for pH adjustment)
6.3 Shelf life
Unopened: 3 years.
Reconstituted solution: Chemical and physical in-use stability has been demonstrated for 6 hours between 15 and at 25°Cc. From a microbiological point of view, the product should be used immediately.
6.4 Special precautions for storage
Unopened product: Do not store above 25°C.
Reconstituted solution: Do not store above 25°C. Do not refrigerate or freeze. Protect from direct light. Reconstitution should take place in controlled and validated aseptic conditions.
6.5 Nature and contents of container
Clear 70- ml vials, glass type Type I (Ph. Eur.), with siliconised chlorobutyl lyophilisation stoppers Type I (Ph. Eur.). The vials are sealed with aluminium caps with polypropylene flip-off disks. Supplied in packs of 12 or 36 vials.
6.6 Special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product
Each vial of Dantrium IV should be reconstituted by adding 60 ml of waterWater for injection Injection Ph. Eur. and shaking until the solution is clear. Any unused portion of the reconstituted solution should be discarded. There are no special requirements relating to the disposal of the container or contents.
7. MARKETING AUTHORISATION HOLDER
SpePharm Holding Norgine B.V.
Kingsfordweg 151
1043 GR Hogehilweg 7
1101CA Amsterdam ZO
The Netherlands
8. MARKETING AUTHORISATION NUMBER(S)
PA 1556/1/3 1336/004/003
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 022nd December 1980
Date of last renewal: 022nd December 22010005
10. DATE OF REVISION OF THE TEXT
December 2011 September 2014
Updated on 28 October 2014
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.6 - Pregnancy and lactation
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- Change to section 4.9 - Overdose
- Change to section 6.1 - List of excipients
- Change to section 6.3 - Shelf life
- Change to section 6.4 - Special precautions for storage
- Change to section 6.5 - Nature and contents of container
- Change to section 6.6 - Special precautions for disposal and other handling
- Change to section 7 - Marketing authorisation holder
- Change to section 8 - MA number
- Change to section 9 - Date of renewal of authorisation
- Change to section 10 - Date of revision of the text
Free text change information supplied by the pharmaceutical company
4.2 Posology and method of administration
As soon as the malignant hyperthermia (MH) MH reaction is recognised, all anaesthetic agents should be discontinued; the administration of 100 % oxygen is recommended. Dantrium IV 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.
4.4 Special warnings and precautions for use
The use of Dantrium IV in the management of a 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, monitor urinary output, and monitor for electrolyte imbalance.
Since the effect of disease state and other drugs on dantrolene sodium related skeletal muscle weakness, including possible respiratory depression, cannot be predicted, patients who receive i.v.IV dantrolene sodium preoperatively should have vital signs monitored.
If patients judged MH-susceptible (with MHS) are administered intravenous or oral dantrolene sodium preoperatively, anesthetic preparation must still follow a standard MHS regimen, including the avoidance of known triggering agents. Monitoring for early clinical and metabolic signs of MH is indicated because attenuation of MH, rather than prevention, is possible. These signs usually call for the administration of additional i.v.IV dantrolene sodium.
Hepatic dysfunction, including fatal hepatic failure, can occur with dantrolene use, and appears to be related to dose and duration of therapy. Fatal and non-fatal liver disorders of an idiosyncratic or hypersensitivity type may also occur with dantrolene sodium therapy.
4.6 Pregnancy Fertility, pregnancy and lactation
4.8 Undesirable effects
Vasular Vascular disorders:
Less common: Labile blood pressure
4.9 Overdose
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, diarrhea diarrhoea, and crystalluria.
6.1 List of excipients
Mannitol
Sodium hydroxide (for pH adjustment)
6.3 Shelf life
Unopened: 3 years.
Reconstituted solution: Chemical and physical in-use stability has been demonstrated for 6 hours between 15 and at 25°Cc. From a microbiological point of view, the product should be used immediately.
6.4 Special precautions for storage
Unopened product: Do not store above 25°C.
Reconstituted solution: Do not store above 25°C. Do not refrigerate or freeze. Protect from direct light. Reconstitution should take place in controlled and validated aseptic conditions.
6.5 Nature and contents of container
Clear 70- ml vials, glass type Type I (Ph. Eur.), with siliconised chlorobutyl lyophilisation stoppers Type I (Ph. Eur.). The vials are sealed with aluminium caps with polypropylene flip-off disks. Supplied in packs of 12 or 36 vials.
6.6 Special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product
Each vial of Dantrium IV should be reconstituted by adding 60 ml of waterWater for injection Injection Ph. Eur. and shaking until the solution is clear. Any unused portion of the reconstituted solution should be discarded. There are no special requirements relating to the disposal of the container or contents.
7. MARKETING AUTHORISATION HOLDER
SpePharm Holding Norgine B.V.
Kingsfordweg 151
1043 GR Hogehilweg 7
1101CA Amsterdam ZO
The Netherlands
8. MARKETING AUTHORISATION NUMBER(S)
PA 1556/1/3 1336/004/003
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 022nd December 1980
Date of last renewal: 022nd December 22010005
10. DATE OF REVISION OF THE TEXT
December 2011 September 2014
Updated on 14 August 2012
Reasons for updating
- Change to section 6.5 - Nature and contents of container
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Updated on 14 August 2012
Reasons for updating
- Change to section 6.5 - Nature and contents of container
Free text change information supplied by the pharmaceutical company
Updated on 25 March 2011
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 6.3 - Shelf life
- Change to section 6.4 - Special precautions for storage
- Change to section 6.5 - Nature and contents of container
- Change to section 7 - Marketing authorisation holder
- Change to section 8 - MA number
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
4.4 Special warnings and precautions for use
The use of Dantrium IV in the management of a 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, monitor urinary output, and monitor for electrolyte imbalance.
Since the effect of disease state and other drugs on dantrolene sodium related skeletal muscle weakness, including possible respiratory depression, cannot be predicted, patients who receive i.v. dantrolene sodium preoperatively should have vital signs monitored.
If patients judged MH-susceptible (MHS) are administered intravenous or oral dantrolene sodium preoperatively, anesthetic preparation must still follow a standard MHS regimen, including the avoidance of known triggering agents. Monitoring for early clinical and metabolic signs of MH is indicated because attenuation of MH, rather than prevention, is possible. These signs usually call for the administration of additional i.v. dantrolene sodium.
When mannitol is used to prevent or treat the renal complications of malignant hyperthermia, the mannitol content in the Dantrium vial, i.e. 3000 milligrams of mannitol per 20mg of dantrolene sodium, should be taken into consideration.
Because of the high pH of Dantrium IV and potential for tissue necrosis, care must be taken to prevent extravasation of the intravenous solution into the surrounding tissues.
In some subjects as much as 10mg/kg of dantrolene sodium 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.
Information for Patients
Based upon data in human volunteers, it will sometimes be appropriate to tell patients who receive dantrolene sodium intravenous that decrease in grip strength and weakness of leg muscles, especially walking down stairs, can be expected postoperatively. In addition, symptoms such as "lightheadedness" may be noted. Since some of these symptoms may persist for up to 48 hours, patients must not operate an automobile or engage in other hazardous activity during this time. Caution is also indicated at meals on the day of administration because difficulty in swallowing and choking has been reported. Caution should be exercised in the concomitant administration of tranquilizing agents.
Hepatotoxicity seen with dantrolene sodium capsules
Dantrolene has a potential for hepatotoxicity, and symptomatic hepatitis, sometimes fatal, has been reported. Factors that may be related to a poorer prognosis include higher daily doses, female gender, and increasing patient age. Spontaneous reports also suggest a higher proportion of hepatic events with fatal outcome in elderly patients.
Hepatic dysfunction, including fatal hepatic failure, can occur with dantrolene use, and appears to be related to dose and duration of therapy. Fatal and non-fatal liver disorders of an idiosyncratic or hypersensitivity type may also occur with dantrolene sodium therapy.
Evaluation of hepatic function should be done before initiating treatment, and hepatic function should be monitored at appropriate intervals throughout treatment. If monitoring reveals abnormal liver function, or if signs or symptoms of hepatotoxicity occur during therapy, dantrolene should be withdrawn. If a decision is made to restart treatment after recovery from hepatic dysfunction, liver function should be monitored and the drug discontinued if abnormal values are observed.
6.3 Shelf life
Unopened: 3 years.
Reconstituted solution: Chemical and physical in-use stability has been demonstrated for 6 hours between 15 and 25°C. From a microbiological point of view, the product should be used immediately.
6.4 Special precautions for storage
Unopened product: Do not store above 25°C.
Reconstituted solution: Do not store above 25°C. Do not refrigerate or freeze. Protect from direct light. Reconstitution should take place in controlled and validated aseptic conditions.
6.5 Nature and contents of container
Clear 70-ml vials, glass type III treated for type II (Ph. Eur.), with siliconised chlorobutyl lyophilisation stoppers Type I (Ph. Eur.). The vials are sealed with aluminium caps with polypropylene flip-off disks. Twelve vials per carton.
7. MARKETING AUTHORISATION HOLDER
SpePharm Holding B.V.
Kingsfordweg 151
1043 GR Amsterdam
The Netherlands
8. MARKETING AUTHORISATION NUMBER
PA 1556/1/3
10. DATE OF REVISION OF THE TEXT
April 2010
Updated on 25 March 2011
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 6.3 - Shelf life
- Change to section 6.4 - Special precautions for storage
- Change to section 6.5 - Nature and contents of container
- Change to section 7 - Marketing authorisation holder
- Change to section 8 - MA number
- Change to section 10 - Date of revision of the text
Free text change information supplied by the pharmaceutical company
4.4 Special warnings and precautions for use
The use of Dantrium IV in the management of a 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, monitor urinary output, and monitor for electrolyte imbalance.
Since the effect of disease state and other drugs on dantrolene sodium related skeletal muscle weakness, including possible respiratory depression, cannot be predicted, patients who receive i.v. dantrolene sodium preoperatively should have vital signs monitored.
If patients judged MH-susceptible (MHS) are administered intravenous or oral dantrolene sodium preoperatively, anesthetic preparation must still follow a standard MHS regimen, including the avoidance of known triggering agents. Monitoring for early clinical and metabolic signs of MH is indicated because attenuation of MH, rather than prevention, is possible. These signs usually call for the administration of additional i.v. dantrolene sodium.
When mannitol is used to prevent or treat the renal complications of malignant hyperthermia, the mannitol content in the Dantrium vial, i.e. 3000 milligrams of mannitol per 20mg of dantrolene sodium, should be taken into consideration.
Because of the high pH of Dantrium IV and potential for tissue necrosis, care must be taken to prevent extravasation of the intravenous solution into the surrounding tissues.
In some subjects as much as 10mg/kg of dantrolene sodium 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.
Information for Patients
Based upon data in human volunteers, it will sometimes be appropriate to tell patients who receive dantrolene sodium intravenous that decrease in grip strength and weakness of leg muscles, especially walking down stairs, can be expected postoperatively. In addition, symptoms such as "lightheadedness" may be noted. Since some of these symptoms may persist for up to 48 hours, patients must not operate an automobile or engage in other hazardous activity during this time. Caution is also indicated at meals on the day of administration because difficulty in swallowing and choking has been reported. Caution should be exercised in the concomitant administration of tranquilizing agents.
Hepatotoxicity seen with dantrolene sodium capsules
Dantrolene has a potential for hepatotoxicity, and symptomatic hepatitis, sometimes fatal, has been reported. Factors that may be related to a poorer prognosis include higher daily doses, female gender, and increasing patient age. Spontaneous reports also suggest a higher proportion of hepatic events with fatal outcome in elderly patients.
Hepatic dysfunction, including fatal hepatic failure, can occur with dantrolene use, and appears to be related to dose and duration of therapy. Fatal and non-fatal liver disorders of an idiosyncratic or hypersensitivity type may also occur with dantrolene sodium therapy.
Evaluation of hepatic function should be done before initiating treatment, and hepatic function should be monitored at appropriate intervals throughout treatment. If monitoring reveals abnormal liver function, or if signs or symptoms of hepatotoxicity occur during therapy, dantrolene should be withdrawn. If a decision is made to restart treatment after recovery from hepatic dysfunction, liver function should be monitored and the drug discontinued if abnormal values are observed.
6.3 Shelf life
Unopened: 3 years.
Reconstituted solution: Chemical and physical in-use stability has been demonstrated for 6 hours between 15 and 25°C. From a microbiological point of view, the product should be used immediately.
6.4 Special precautions for storage
Unopened product: Do not store above 25°C.
Reconstituted solution: Do not store above 25°C. Do not refrigerate or freeze. Protect from direct light. Reconstitution should take place in controlled and validated aseptic conditions.
6.5 Nature and contents of container
Clear 70-ml vials, glass type III treated for type II (Ph. Eur.), with siliconised chlorobutyl lyophilisation stoppers Type I (Ph. Eur.). The vials are sealed with aluminium caps with polypropylene flip-off disks. Twelve vials per carton.
7. MARKETING AUTHORISATION HOLDER
SpePharm Holding B.V.
Kingsfordweg 151
1043 GR Amsterdam
The Netherlands
8. MARKETING AUTHORISATION NUMBER
PA 1556/1/3
10. DATE OF REVISION OF THE TEXT
April 2010
Updated on 26 August 2008
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.8 - Undesirable effects
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Hepatic dysfunction, including fatal hepatic failure, can occur with dantrolene use, and appears to be related to dose and duration of therapy. Fatal and non-fatal liver disorders of an idiosyncratic or hypersensitivity type may also occur with dantrolene sodium therapy.
Updated on 26 August 2008
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.8 - Undesirable effects
- Change to section 10 - Date of revision of the text
Free text change information supplied by the pharmaceutical company
Hepatic dysfunction, including fatal hepatic failure, can occur with dantrolene use, and appears to be related to dose and duration of therapy. Fatal and non-fatal liver disorders of an idiosyncratic or hypersensitivity type may also occur with dantrolene sodium therapy.
Updated on 02 March 2006
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 02 March 2006
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
Updated on 18 August 2003
Reasons for updating
- Improved electronic presentation
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 18 August 2003
Reasons for updating
- Improved electronic presentation
Updated on 07 July 2003
Reasons for updating
- New SPC for medicines.ie
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 07 July 2003
Reasons for updating
- New SPC for medicines.ie