DANTRIUM

Posology Each patient should be slowly titrated to the required individual dose. For the individual patient the lowest dose compatible with optimal response is recommended. A recommended dosage increment scale is shown below.

Adults:

Dantrium should be titrated no more rapidly than as per the following schedule: Week 1: 25 mg once a day Week 2: 25 mg two times a day Week 3: 50 mg two times a day Week 4: 50 mg three times a day As soon as the optimal dose is reached, patients should receive their total daily dose divided over 2 to 4 individual doses to achieve as uniform plasma levels as possible and to minimise adverse reactions.

Doses higher than 200 mg should not be administered in long-term therapy with Dantrium. Temporarily, the dose can be gradually increased up to 400 mg per day if pressurised or stressful situations are anticipated in the patient.

The increased dose should be titrated as follows:

Week 5: 75 mg three times a day Week 6: 75 mg four times a day Week 7: 100 mg four times a day However, doses above 200 mg per day should not be given for more than 2 months. Paediatric Population Dosing table for children over 5 years (upwards of 25 kg body weight) For the individual patient the lowest dose compatible with optimal response is recommended.

A recommended dosage titration schedule is provided below. Week 1: 1 Dantrium 25 mg capsule once a day Week 2: 1 Dantrium 25 mg capsule two times a day Week 3: 1 Dantrium 25 mg capsule three times a day Week 4: 2 Dantrium 25 mg capsules two times a day Week 5: 2 Dantrium 25 mg capsules three times a day Week 6: 3 Dantrium 25 mg capsules three times a day For children weighing 50 kg or more, see dosage for adults.

The dose can be increased gradually up to 200 mg daily. Dantrium is intended for long-term therapy. If therapeutic success is still absent after 6 - 8 weeks of treatment, therapy should be discontinued. As there is insufficient experience with the use of Dantrium in children under 5 years to assess its tolerability, it should not be used in this patient group.

Method of administration For oral use.

Tabulated list of adverse reactions System Organ Class Frequency Adverse Drug Reactions Uncommon Lymphocytic lymphomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) Uncommon Lymphoma Uncommon Aplastic anaemia Uncommon Anaemia Uncommon Leukopenia Blood and lymphatic system disorders Uncommon Thrombocytopenia Uncommon HypersensitivityImmune system disorders Uncommon Anaphylactic reaction Metabolism and nutrition disorders Common Decreased appetite Common Depression Common Confusional state Common Nervousness Uncommon Hallucination Common Insomnia Psychiatric disorders Unknown Disorientation Very common Dizziness Very common Somnolence Common Headache Common Speech disorder Common Seizures Uncommon Enhanced paresis in cases of amyotrophic lateral sclerosis or in the presence of bulbar paralytic symptoms Uncommon Dysgeusia Nervous system disorders Unknown Hypotonia Uncommon Diplopia Uncommon Lacrimation increased Eye disorders Common Visual impairment Uncommon Tachycardia Uncommon Cardiac failure Common Pericarditis Uncommon Pleuropericarditis Cardiac disorders Unknown Bradycardia Uncommon PhlebitisVascular disorders Uncommon Blood pressure fluctuation Common Respiratory depression Common Respiratory failure Very rare Suffocation feeling Respiratory, thoracic and mediastinal disorders Uncommon Dyspnoea Very Common Diarrhoea Common Abdominal cramps Common Nausea Common Vomiting Uncommon Constipation (rarely progressing to signs of intestinal obstruction) Gastrointestinal disorders Uncommon Dysphagia Uncommon Gastrointestinal haemorrhage Uncommon Abdominal pain upper Uncommon Salivary hypersecretion Unknown Dyspepsia Unknown Dry Mouth Common Hepatotoxicity/hepatitis Common Jaundice Hepatobiliary disorders Common Cholestasis Common Rash Common Dermatitis acneiform/acne like rash/acne Uncommon Hyperhidrosis Uncommon Hair growth abnormal Uncommon Pruritus Uncommon Photosensitivity reaction Very rare Urticaria Skin and subcutaneous tissue disorders Very rare Eczema Common Muscular weakness Uncommon Back pain Musculoskeletal and connective tissue disorder Uncommon Myalgia Uncommon Urinary incontinence Uncommon Pollakiuria Uncommon Crystalluria Uncommon Haematuria Uncommon Urinary retention Unknown Nocturia Very rare Micturition disorder Renal and urinary disorders Unknown Chromaturia Reproductive system and breast disorders Very rare Erectile dysfunction Very common Fatigue Very common Malaise Common Chills Common Pyrexia General disorders and administration site conditions Very common Asthenia Investigations Common Liver function tests abnormal In addition, the following specific undesirable effects have been noticed with the use of Dantrium Capsules: - Precipitation of cerebral seizures, especially in children with cerebral palsy; - pleuropericarditis and pericardial effusion, (accompanied by eosinophilia) - pleural effusion (with associated eosinophilia), - Diarrhoea (may be severe and may necessitate temporary withdrawal of dantrolene therapy).

Dantrium must be used with caution in the following situations:

In cases of amyotrophic lateral sclerosis or in the presence of bulbar paralytic symptoms, as paresis can be enhanced by Dantrium. Patients with cardiac disease, especially in patients with myocardial damage and/or cardiac arrhythmias, must receive particular medical surveillance.

Dantrolene leads to mild to severe liver damage in about 9 out of 100,000 treated patients, in whom mortality affects 10 to 20%. The risk of liver damage seems to be particularly increased at daily doses higher than 300 mg, during prolonged therapy, in women, in patients over 30 years of age or with a history of liver damage and during concomitant use of other medicinal products that can damage the liver.

Liver damage may run a lethal course, especially in elderly patients. In patients suffering from multiple sclerosis, the risk of serious liver damage seems to be further increased. Before the start and during therapy with Dantrium, liver enzymes must be monitored at regular intervals; in particular, SGOT and SGPT must be monitored frequently.

Patients in whom the risk of liver damage is increased must receive particularly close monitoring. If values are outside the norm or if symptoms of liver damage occur, Dantrium must be discontinued. There are indications that, when liver damage occurs, high serum bilirubin levels correlate to severe progression.

To reduce the risk of liver damage, the lowest possible effective dantrolene dose must be used. Dantrium can cause photosensitisation; patients should therefore protect themselves against strong sunlight during treatment. Dantrium must be discontinued if patients have developed pleural or pericardial effusion or pleuropericarditis.

Patients with rare hereditary problems of galactose intolerance, the lactase deficiency or glucose-galactose malabsorption should not take Dantrium. At doses above 200 mg dantrolene per day, increased adverse reactions must be anticipated.

1. - Hepatic disorders, - Impaired respiratory function - Severe impaired cardiac function due to myocardial disease - In cases where abnormally increased tone is required to allow better function, an upright posture or balance during movement.

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