Dantrium Information
Dantrium (Dantrolene sodium)
Dantrium (Dantrolene sodium) Description
The chemical formula of (dantrolene sodium) is hydrated 1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2, 4-imidazolidinedione sodium salt. It 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 (3-1/2 moles) and has a molecular weight of 399. The structural formula for the hydrated salt is:
Dantrium (Dantrolene sodium) Clinical Pharmacology
In isolated nerve-muscle preparation, 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. In skeletal muscle, 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 fibers as compared to slow ones, but generally affects both. A central nervous system effect occurs, with drowsiness, dizziness, and generalized weakness occasionally present. Although does not appear to directly affect the CNS, the extent of its indirect effect is unknown. The absorption of 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 biologic half-life of in adults is 8.7 hours after a 100-mg dose. Specific metabolic pathways in the degradation and elimination of in human subjects have been established. Metabolic patterns are similar in adults and pediatric patients. 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 analog and the acetamido analog. Since is probably metabolized by hepatic microsomal enzymes, enhancement of its metabolism by other drugs is possible. However, neither phenobarbital nor diazepam appears to affect metabolism.
Clinical experience in the management of fulminant human malignant hyperthermia, as well as experiments conducted in malignant hyperthermia susceptible swine, have revealed that the administration of intravenous dantrolene, combined with indicated supportive measures, is effective in reversing the hypermetabolic process of malignant hyperthermia. Known differences between human and swine malignant hyperthermia are minor. The prophylactic administration of oral or intravenous dantrolene to malignant hyperthermia susceptible swine will attenuate or prevent the development of signs of malignant hyperthermia in a manner dependent upon the dosage of dantrolene administered and the intensity of the malignant hyperthermia triggering stimulus. Limited clinical experience with the administration of oral dantrolene to patients judged malignant hyperthermia susceptible, when combined with clinical experience in the use of intravenous dantrolene for the treatment of malignant hyperthermia and data derived from the above cited animal model experiments, suggests that oral dantrolene will also attenuate or prevent the development of signs of human malignant hyperthermia, provided that currently accepted practices in the management of such patients are adhered to (see ); intravenous dantrolene should also be available for use should the signs of malignant hyperthermia appear.
Dantrium (Dantrolene sodium) Indications And Usage
If improvement occurs, it will ordinarily occur within the dosage titration (see ), and will be manifested by a decrease in the severity of spasticity and the ability to resume a daily function not quite attainable without
Occasionally, subtle but meaningful improvement in spasticity may occur with therapy. In such instances, information regarding improvement should be solicited from the patient and those who are in constant daily contact and attendance with him. Brief withdrawal of for a period of 2 to 4 days will frequently demonstrate exacerbation of the manifestations of spasticity and may serve to confirm a clinical impression.
A decision to continue the administration of on a long-term basis is justified if introduction of the drug into the patient's regimen:
Oral is also indicated 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. Currently accepted clinical practices in the management of such patients must still be adhered to (careful monitoring for early signs of malignant hyperthermia, minimizing exposure to triggering mechanisms and prompt use of intravenous dantrolene sodium and indicated supportive measures should signs of malignant hyperthermia appear); see also the package insert for (dantrolene sodium)
Oral should be administered following a malignant hyperthermic crisis to prevent recurrence of the signs of malignant hyperthermia.
Dantrium (Dantrolene sodium) Contraindications
Active hepatic disease, such as hepatitis and cirrhosis, is a contraindication for use of . is contraindicated where spasticity is utilized to sustain upright posture and balance in locomotion or whenever spasticity is utilized to obtain or maintain increased function.
Dantrium (Dantrolene sodium) Warnings
It is important to recognize that fatal and non-fatal liver disorders of an idiosyncratic or hypersensitivity type may occur with therapy.
At the start of therapy, it is desirable 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 hepatotoxicity could be enhanced, although such a possibility has not yet been established.
Liver function studies (e.g., SGOT or SGPT) should be performed at appropriate intervals during 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, should be discontinued. If caused by and detected early, the abnormalities in liver function characteristically have reverted to normal when the drug was discontinued.
Dantrium (Dantrolene sodium) Precautions
Dantrium (Dantrolene sodium) Adverse Reactions
The most frequently occurring side effects of have been drowsiness, dizziness, weakness, general malaise, fatigue, and diarrhea. These 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. Diarrhea may be severe and may necessitate temporary withdrawal of therapy. If diarrhea recurs upon readministration of , therapy should probably be withdrawn permanently.
Other less frequent side effects, listed according to system, are:
The published literature has included some reports of use in patients with Neuroleptic Malignant Syndrome (NMS). capsules are not indicated for the treatment of NMS and patients may expire despite treatment with capsules.
For medical advice about adverse reactions contact your medical professional. To report SUSPECTED ADVERSE REACTIONS, contact JHP at 1-866-923-2547 or MEDWATCH at 1-800-FDA-1088 (1-800-332-1088) or http://www.fda.gov/medwatch/.
Dantrium (Dantrolene sodium) Drug Abuse And Dependence
Drug abuse and dependency potential has not been evaluated in human or animal studies.
Dantrium (Dantrolene sodium) 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, and crystalluria. For acute overdose, general supportive measures should be employed along with immediate gastric lavage.
Intravenous fluids should be administered in fairly large quantities to avert the possibility of crystalluria. An adequate airway should be maintained and artificial resuscitation equipment should be at hand. Electrocardiographic monitoring should be instituted, and the patient carefully observed. To date, no experience has been reported with dialysis and its value in Dantrium (Dantrolene sodium) overdose is not known.
Dantrium (Dantrolene sodium) Dosage And Administration
Prior to the administration of , 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 . Refer to section for description of response to be anticipated.
It is important to establish a therapeutic goal (regain and maintain a specific function such as therapeutic exercise program, utilization of braces, transfer maneuvers, etc.) before beginning 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.
It is important that the dosage be titrated and individualized for maximum effect. The lowest dose compatible with optimal response is recommended.
The following gradual titration schedule is suggested. Some patients will not respond until higher daily dosage is achieved. 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.
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. (See .)
The following gradual titration schedule is suggested. Some patients will not respond until higher daily dosage is achieved. 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.
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. (See .)
Dantrium (Dantrolene sodium) How Supplied
Dantrium (Dantrolene sodium)
Dantrium (Dantrolene sodium)
Dantrium (Dantrolene sodium) Principal Display Panel - Mg Bottle
Dantrium (Dantrolene sodium) Principal Display Panel - Mg Bottle
Dantrium (Dantrolene sodium) Principal Display Panel - Mg Bottle
