Dantrium IV

Uses

In Chronic Spasticity: Dantrium IV is used for controlling the manifestations of clinical spasticity resulting from upper motor neuron disorders (e.g., 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. Dantrium IV is not used for the treatment of skeletal muscle spasm resulting from rheumatic disorders.

A decision to continue the administration of Dantrium IV 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 any annoying manifestation of spasticity considered important by the patient himself.

In Malignant Hyperthermia: Oral Dantrium IV is also used preoperatively to prevent or attenuate the development of signs of malignant hyperthermia in known, or strongly suspect, malignant hyperthermia susceptible patients who require anesthesia and/or surgery.

Dantrium IV is also used to associated treatment for these conditions: Malignant Hyperthermia, Spasticity

How Dantrium IV works

Dantrium IV depresses excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor 1, and decreasing intracellular calcium concentration. Ryanodine receptors mediate the release of calcium from the sarcoplasmic reticulum, an essential step in muscle contraction.

Dosage

Dantrium IV dosage

For Use in Chronic Spasticity: It is important that the dosage be titrated and individualized for maximum effect. The lowest dose compatible with optimal response is recommended.Each dosage level should be maintained for seven days to determine the patient’s response. If no further benefit is observed at the next higher dose, dosage should be decreased to the previous lower dose.

Adults: 25 mg once daily for seven days, then 25 mg t.i.d. for seven days, 50 mg t.i.d. for seven days, 100 mg t.i.d.

Pediatric Patients:0.5 mg/kg once daily for seven days, then 0.5 mg/kg t.i.d. for seven days, 1 mg/kg t.i.d. for seven days, 2 mg/kg t.i.d. Therapy with a dose four times daily may be necessary for some individuals. Doses higher than 100 mg four times daily should not be used.

The long-term safety of Dantrium IV in pediatric patients under the age of 5 years has not been established.

For Malignant Hyperthermia:

• Preoperatively: 4 to 8 mg/kg/day of oral Dantrium IV in 3 or 4 divided doses for one or two days prior to surgery, with the last dose being given approximately 3 to 4 hours before scheduled surgery with a minimum of water.
• Post Crisis Follow-up: Oral Dantrium IV should also be administered following a malignant hyperthermia crisis, in doses of 4 to 8 mg/kg per day in four divided doses, for a one to three day period to prevent recurrence of the manifestations of malignant hyperthermia.

Side Effects

The most frequently occurring side effects of Dantrium IV have been drowsiness, dizziness, weakness, general malaise, fatigue, and diarrhea. Other less frequent side effects are constipation, anorexia, abdominal cramps, nausea and/or vomiting, hepatitis, headache, visual disturbance, alteration of taste, insomnia, tachycardia, anemia, leukopenia, lymphocytic lymphoma, mental depression and mental confusion.

Toxicity

Oral LD₅₀ in rats is 7400 mg/kg. 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, and crystalluria.

Precaution

Dantrium IV 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 IV is associated with pleural effusion with associated eosinophilia.

Patients should be cautioned against driving a motor vehicle or participating in hazardous occupations while taking Dantrium IV. Caution should be exercised in the concomitant administration of tranquilizing agents. Dantrium IV might possibly evoke a photosensitivity reaction; patients should be cautioned about exposure to sunlight while taking it.

Interaction

Drowsiness may occur with Dantrium IV therapy and the concomitant administration of CNS depressants such as sedatives and tranquilizing agents may result in further drowsiness. Hepatotoxicity has occurred more often in women over 35 years of age receiving concomitant estrogen therapy. Administration of Dantrium IV may potentiate vecuronium-induced neuromuscular block.

Food Interaction

• Take with or without food. The absorption is unaffected by food.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Dantrium IV Drug Interaction

Moderate: diphenhydramine, diphenhydramine, duloxetine, duloxetine, levetiracetam, clonazepam, pregabalin, pregabalin, diazepam, diazepamUnknown: polyethylene glycol 3350, polyethylene glycol 3350, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol, ondansetron, ondansetron

Dantrium IV Disease Interaction

Major: hepatotoxicityModerate: cardiac disease, pulmonary impairment

Elimination Route

Bioavailability is 70%.

Half Life

The mean biologic half-life after intravenous administration is variable, between 4 to 8 hours under most experimental conditions, while oral is 8.7 hours for a 100mg dose.

Pregnancy & Breastfeeding use

Pregnancy Category C. Dantrium IV should not be used in nursing mothers.

Contraindication

Active hepatic disease, such as hepatitis and cirrhosis, is a contraindication for use of Dantrium IV.

Acute Overdose

Symptoms: muscular weakness, alterations in the state of consciousness (e.g. lethargy, coma), vomiting, diarrhoea and crystalluria.

Management: Treatment is supportive with ECG monitoring. Admin IV fluids to prevent crystalluria. Maintain an adequate airway and have artificial resuscitation equipment at hand.

Storage Condition

Store between 15-30°C

Innovators Monograph

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