Details About Overdose or Poisoning Generic Salt ::  Dantrolene

Dantrolene

    

Drug Pharmacology ::

I. Pharmacology. Dantrolenerelaxes skeletal muscle by inhibiting the release of calcium from thesarcoplasmic reticulum, thereby reducing actin-myosin contractileactivity. Dantrolene can help control hyperthermia that results fromexcessive muscle hyperactivity, particularly when hyperthermia iscaused by a defect within the muscle cell (eg, malignant hyperthermia).Dantrolene is not a substitute for other temperature-controllingmeasures (eg, sponging and fanning).

Drug Indications ::

Indications

   

The primary indication for dantrolene is malignant hyperthermia (see Malignant hyperthermia).

Dantrolenemay be useful in treating hyperthermia and rhabdomyolysis caused bydrug-induced muscular hyperactivity that is not controlled by usualcooling measures or neuromuscular paralysis.

Theoretically,dantrolene is not expected to be effective for hyperthermia caused byconditions other than muscular hyperactivity, such as increasedmetabolic rate (eg, salicylate or dinitrophenol poisoning), neurolepticmalignant syndrome (NMS), impaired heat dissipation (eg,anticholinergic syndrome),and environmental exposure (heat stroke).However, there is anecdotal evidence (case reports or case-controlstudies) of benefit for the management of NMS, MAO inhibitor(phenelzine poisoning)–induced hyperthermia, dinitrophenol-inducedhyperthermia, muscle rigidity from baclofen withdrawal, hypertonicityfrom carbon monoxide poisoning, tetanus, and black widow spiderenvenomation.

Drug Contra-Indications ::

III. Contraindications. Noabsolute contraindications exist. Patients with muscular weakness orrespiratory impairment must be observed closely for possiblerespiratory arrest.

Drug Adverse Effects ::

IV. Adverse effects

   

Muscle weakness, which may aggravate respiratory depression.

Drowsiness, fatigue, dizziness, photosensitivity, and diarrhea.

Black box warning. Potentialfor fatal hepatotoxicity (hypersensitivity hepatitis) reported afterchronic therapy. May also be dose-related (more common with 800mg/day). Transaminases are elevated in about 10% of patients treatedwith dantrolene.

IV administration associated with pulmonary edema (mannitol may contribute), phlebitis, and urticaria (avoid extravasation).

E. Use in pregnancy. FDAcategory C (indeterminate). This does not preclude its acute,short-term use for a seriously symptomatic patient (see Table III–1).

Drug Lab Interactions ::

Drug or laboratory interactions

   

Dantrolene may have additive CNS–depressant effects with sedative and hypnotic drugs.

Dantrolene and verapamil coadministration is associated with hyperkalemia (case report).

Each20-mg vial of Dantrium contains 3 g of mannitol; this should be takeninto consideration as it may have additive effects with any mannitolgiven to treat rhabdomyolysis. Use only sterile water (withoutbacteriostatic agent) to reconstitute. Incompatible with D5W and NS.

Drug Dose Management ::

Dosage and method of administration (adults and children)

   

Parenteral. Give1 mg/kg rapidly IV; this may be repeated as needed every 5–10 minutesto a maximum total dose of 10 mg/kg. Satisfactory response usually isachieved with an average total dosage of 2.5 mg/kg.

Oral. Toprevent recurrence of hyperthermia, administer 1–2 mg/kg intravenouslyor orally (up to 100 mg maximum) four times a day for 2–3 days. Dailydose not to exceed 400 mg (see Black box warning section, above). Forprevention (patients at risk for malignant hyperthermia), give 1–2 daysprior to surgery and give the last dose 3–4 hours before surgery orgive IV at 2.5-mg/kg infused over 1 hour and 1 hour prior toanesthesia.

Drug Chemical Formulations ::

Formulations

   

Parenteral. Dantrolenesodium (Dantrium), 20 mg of lyophilized powder for reconstitution(after reconstitution, protect from light and use within 6 hours toensure maximal activity). Each 20-mg vial contains 3 g of mannitol (seeadverse effects and interactions).

Oral. Dantrolene sodium (Dantrium) in 25-, 50-, and 100-mg capsules.

The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is thirty-five 20-mg vials.

Disclaimer ::

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