The following changes have been made:

QRD updates throughout the SPC

Section 4.8 has been tabulated in line with QRD and additional ADRs have been listed as unknown

Revision date

The following changes have been made:

QRD updates throughout the SPC

Section 4.8 has been tabulated in line with QRD and additional ADRs have been listed as unknown

Revision date

2.            QUALITATIVE AND QUANTITATIVE COMPOSITION

Dantrium capsules 100 mg Capsules contains 100 mg dantrolene sodium per capsules capsule.

Excipients: Contains Lactose Monohydrate 189.0 mg and Sunset Yellow (E110).

For a full list of excipients, see section 6.1.

3.        PHARMACEUTICAL form

Capsule, hard

Dantrium capsules are presented in orange/light brown hard capsules. The 100 mg capsule carries the monogram ‘Dantrium 100 mg’ on the cap and ‘0149’, ‘0033’ and triple coding bars on the body. white/green hard capsules.

4.2      Posology and method of administration

Each dosage level should be maintained for seven days in order to determine the patient's response. The maximum daily dose should not exceed 400 mg. In view of the potential for hepatoxicity hepatotoxicity in long term use, if no observable benefit is derived from the administration of Dantrium after a total of 45 days, therapy should be discontinued.

4.4         Special warnings and precautions for use

At the start of Dantrium therapy, liver function tests should be performed in all patients to establish a base-line, and exclude pre-existing liver disease. These tests should be repeated upon hospital discharge or at 6 six weeks after staring starting therapy. Further tests should may be carried out at appropriate intervals throughout treatment. Generally, if these studies reveal abnormal values, therapy should not be commenced or should be discontinued. In patients with symptoms compatible with hepatitis or where jaundice appears, Dantrium should be discontinued. 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

The effects of non-depolarizing muscle relaxants may be potentiated in patients administered Dantrium. Hyperkalemia and myocardial depression have been observed in malignant hyperthermia-susceptible patients receiving intravenous dantrolene sodium and concomitant calcium channel blockers.

4.6      Pregnancy Fertility, pregnancy and lactation

Dantrolene sodium crosses the placenta, and has been detected in human milk. Although teratological studies in animals have proved satisfactory, the use of Dantrium is not advised in pregnant or nursing mothers.

4.8 Undesirable effects

Nervous system disorders:

Common: Seizure, visual disturbances, speech disturbance, headache

VasularVascular disorders:

Less common: Labile blood pressure

The colouring agent E110 can cause allergic-type reactions including asthma. Allergy is more common in those people who are allergic to aspirin.

5.2      Pharmacokinetic properties

The absorption of Dantrium after oral administration in humans in 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 biologic 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.

6.1    List of excipients

Capsule Fill:Maize starch

Talc

Magnesium Stearate

Lactose monohydrate Monohydrate

Capsule Shell:

Sunset Yellow (E110)

Gelatin

Indigo Carmine (E132)

Titanium Dioxide (E171)

Iron Oxide (E172)

Edible Black Ink (Shellac, Iron Oxide E172).

6.5         Nature and contents of container

Dantrium 100 mg Capsules are supplied in polypropylene or  polyethylene containers of 100 capsules, with a polyethylene screw cap and packaged in an outer carton.

7.        MARKETING AUTHORISATION HOLDER

SpePharm Holding Norgine B.V.

Kingsfordweg 1511043 GR Hogehilweg 7

1101CA  Amsterdam ZO

The Netherlands

8.        MARKETING AUTHORISATION NUMBER(S)

PA 1556/1/2 1336/004/002

10.      DATE OF REVISION OF THE TEXT

July 2010 September 2014

2.            QUALITATIVE AND QUANTITATIVE COMPOSITION

Dantrium capsules 100 mg Capsules contains 100 mg dantrolene sodium per capsules capsule.

Excipients: Contains Lactose Monohydrate 189.0 mg and Sunset Yellow (E110).

For a full list of excipients, see section 6.1.

3.        PHARMACEUTICAL form

Capsule, hard

Dantrium capsules are presented in orange/light brown hard capsules. The 100 mg capsule carries the monogram ‘Dantrium 100 mg’ on the cap and ‘0149’, ‘0033’ and triple coding bars on the body. white/green hard capsules.

4.2      Posology and method of administration

Each dosage level should be maintained for seven days in order to determine the patient's response. The maximum daily dose should not exceed 400 mg. In view of the potential for hepatoxicity hepatotoxicity in long term use, if no observable benefit is derived from the administration of Dantrium after a total of 45 days, therapy should be discontinued.

4.4         Special warnings and precautions for use

At the start of Dantrium therapy, liver function tests should be performed in all patients to establish a base-line, and exclude pre-existing liver disease. These tests should be repeated upon hospital discharge or at 6 six weeks after staring starting therapy. Further tests should may be carried out at appropriate intervals throughout treatment. Generally, if these studies reveal abnormal values, therapy should not be commenced or should be discontinued. In patients with symptoms compatible with hepatitis or where jaundice appears, Dantrium should be discontinued. 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

The effects of non-depolarizing muscle relaxants may be potentiated in patients administered Dantrium. Hyperkalemia and myocardial depression have been observed in malignant hyperthermia-susceptible patients receiving intravenous dantrolene sodium and concomitant calcium channel blockers.

4.6      Pregnancy Fertility, pregnancy and lactation

Dantrolene sodium crosses the placenta, and has been detected in human milk. Although teratological studies in animals have proved satisfactory, the use of Dantrium is not advised in pregnant or nursing mothers.

4.8 Undesirable effects

Nervous system disorders:

Common: Seizure, visual disturbances, speech disturbance, headache

VasularVascular disorders:

Less common: Labile blood pressure

The colouring agent E110 can cause allergic-type reactions including asthma. Allergy is more common in those people who are allergic to aspirin.

5.2      Pharmacokinetic properties

The absorption of Dantrium after oral administration in humans in 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 biologic 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.

6.1    List of excipients

Capsule Fill:Maize starch

Talc

Magnesium Stearate

Lactose monohydrate Monohydrate

Capsule Shell:

Sunset Yellow (E110)

Gelatin

Indigo Carmine (E132)

Titanium Dioxide (E171)

Iron Oxide (E172)

Edible Black Ink (Shellac, Iron Oxide E172).

6.5         Nature and contents of container

Dantrium 100 mg Capsules are supplied in polypropylene or  polyethylene containers of 100 capsules, with a polyethylene screw cap and packaged in an outer carton.

7.        MARKETING AUTHORISATION HOLDER

SpePharm Holding Norgine B.V.

Kingsfordweg 1511043 GR Hogehilweg 7

1101CA  Amsterdam ZO

The Netherlands

8.        MARKETING AUTHORISATION NUMBER(S)

PA 1556/1/2 1336/004/002

10.      DATE OF REVISION OF THE TEXT

July 2010 September 2014

4.4     Special warnings and precautions for use

There are isolated cases of possibly significant effects of Dantrium on cardiovascular and respiratory systems and therefore Dantrium should be used with caution in patients with cardiovascular or respiratory disease.

Fatal and non-fatal liver disorders of an idiosyncratic or hypersensitivity type may occur with Dantrium therapy.

Patients should be instructed to contact their physician should signs or symptoms of hepatotoxicity (e.g., discoloured faeces, generalized pruritus, jaundice, anorexia, nausea, vomiting) occur during therapy. 

Factors that may increase the risk of developing hepatotoxicity include:

-                 Higher daily doses (doses exceeding 400 mg daily)

-                 Duration of therapy (most frequently reported between 2 and 12 months of treatment)

-                 Female gender

-                 Age greater than 30 years

-                 Prior history of liver disease/dysfunction

-                 Receiving other hepatotoxic therapies concomitantly

Spontaneous reports also suggest a higher proportion of hepatic events with fatal outcome in elderly patients.

At the start of Dantrium therapy, liver function tests should be performed in all patients to establish a base-line, and exclude pre-existing liver disease.  These tests should be repeated upon hospital discharge or at 6 weeks after staring therapy.  Further tests should be carried out at appropriate intervals throughout treatment.  Generally, if these studies reveal abnormal values, therapy should not be commenced or should be discontinued.  In patients with symptoms compatible with hepatitis or where jaundice appears, Dantrium should be discontinued.  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.

Patients with rare hereditary problems of galactose intolerance, the lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

6.1     List of excipients

Maize starch

Talc

Magnesium Stearate

Lactose monohydrate

Capsule shell

Sunset Yellow (E110)

Gelatin

Titanium Dioxide (E171)

Iron Oxide (E172)

Edible Black Ink (Shellac, Iron Oxide E172).

6.5         Nature and contents of container

7.       MARKETING AUTHORISATION HOLDER

SpePharm Holding B.V.

Kingsfordweg 151

1043 GR Amsterdam

The Netherlands

8.       MARKETING AUTHORISATION NUMBER(S)

PA 1556/1/2

9.       DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 19 March 1975.

Date of last renewal: 19 March 2010.

10.     DATE OF REVISION OF THE TEXT

July 2010

4.4     Special warnings and precautions for use

There are isolated cases of possibly significant effects of Dantrium on cardiovascular and respiratory systems and therefore Dantrium should be used with caution in patients with cardiovascular or respiratory disease.

Fatal and non-fatal liver disorders of an idiosyncratic or hypersensitivity type may occur with Dantrium therapy.

Patients should be instructed to contact their physician should signs or symptoms of hepatotoxicity (e.g., discoloured faeces, generalized pruritus, jaundice, anorexia, nausea, vomiting) occur during therapy. 

Factors that may increase the risk of developing hepatotoxicity include:

-                 Higher daily doses (doses exceeding 400 mg daily)

-                 Duration of therapy (most frequently reported between 2 and 12 months of treatment)

-                 Female gender

-                 Age greater than 30 years

-                 Prior history of liver disease/dysfunction

-                 Receiving other hepatotoxic therapies concomitantly

Spontaneous reports also suggest a higher proportion of hepatic events with fatal outcome in elderly patients.

At the start of Dantrium therapy, liver function tests should be performed in all patients to establish a base-line, and exclude pre-existing liver disease.  These tests should be repeated upon hospital discharge or at 6 weeks after staring therapy.  Further tests should be carried out at appropriate intervals throughout treatment.  Generally, if these studies reveal abnormal values, therapy should not be commenced or should be discontinued.  In patients with symptoms compatible with hepatitis or where jaundice appears, Dantrium should be discontinued.  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.

Patients with rare hereditary problems of galactose intolerance, the lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

6.1     List of excipients

Maize starch

Talc

Magnesium Stearate

Lactose monohydrate

Capsule shell

Sunset Yellow (E110)

Gelatin

Titanium Dioxide (E171)

Iron Oxide (E172)

Edible Black Ink (Shellac, Iron Oxide E172).

6.5         Nature and contents of container

7.       MARKETING AUTHORISATION HOLDER

SpePharm Holding B.V.

Kingsfordweg 151

1043 GR Amsterdam

The Netherlands

8.       MARKETING AUTHORISATION NUMBER(S)

PA 1556/1/2

9.       DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 19 March 1975.

Date of last renewal: 19 March 2010.

10.     DATE OF REVISION OF THE TEXT

July 2010