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  1. Pharmacology. Dantrolene relaxes skeletal muscle by inhibiting the release of calcium from the sarcoplasmic reticulum, thereby reducing actin-myosin contractile activity. Dantrolene can help control hyperthermia that results from excessive muscle hyperactivity, particularly when hyperthermia is caused by a defect within the muscle cells (eg, malignant hyperthermia). Dantrolene is not a substitute for other temperature-controlling measures (eg, sponging and fanning).

  2. Indications

    1. The primary indication for dantrolene is malignant hyperthermia (See Hyperthermia).

    2. Dantrolene may be useful in treating hyperthermia and rhabdomyolysis caused by drug-induced muscular hyperactivity that is not controlled by usual cooling measures or neuromuscular paralysis.

    3. Theoretically, dantrolene is not expected to be effective for hyperthermia caused by conditions other than muscular hyperactivity, such as increased metabolic rate (eg, salicylate or dinitrophenol poisoning), neuroleptic malignant syndrome (NMS), impaired heat dissipation (eg, anticholinergic syndrome), and environmental exposure (heat stroke). However, there is anecdotal evidence (case reports or case-control studies) of benefit for the management of several conditions: NMS; monoamine oxidase (MAO) inhibitor–induced hyperthermia (phenelzine poisoning); dinitrophenol-induced hyperthermia; muscle rigidity from baclofen withdrawal; hypertonicity from carbon monoxide poisoning; tetanus; and black widow spider envenomation.

  3. Contraindications. No absolute contraindications exist. Patients with muscular weakness or respiratory impairment must be observed closely for possible respiratory arrest.

  4. Adverse effects

    1. Muscle weakness, which may aggravate respiratory depression.

    2. Drowsiness, fatigue, dizziness, photosensitivity, and diarrhea.

    3. Black box warning. Potential for fatal hepatotoxicity (hypersensitivity hepatitis) reported after chronic therapy. May also be dose-related (more common with 800 mg/d). Transaminases are elevated in about 10% of patients treated with dantrolene.

    4. Intravenous administration has been associated with pulmonary edema (mannitol may contribute), phlebitis (avoid extravasation), and urticaria.

    5. Use in pregnancy. FDA Category C (indeterminate). This does not preclude acute, short-term use of dantrolene for a seriously symptomatic patient (See Introduction in Section III).

  5. Drug or laboratory interactions

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

    2. Dantrolene and verapamil co-administration is associated with hyperkalemia (case report).

    3. Each 20-mg vial of Dantrium contains 3 g of mannitol; this should be taken into consideration, as it may have additive effects with any mannitol given to treat rhabdomyolysis. Use only sterile water (without bacteriostatic agent) to reconstitute. Incompatible with D5W and NS.

  6. Dosage and method of administration (adults and children)

    1. Parenteral. Give a minimum of 1 mg/kg and up to 2.5 mg/kg rapidly IV through a secure, free-flowing peripheral or central line; this may be repeated as needed every 5–10 minutes to a cumulative total dose of 10 mg/kg (up to 30 mg/kg has been used). Satisfactory response usually is achieved with an average total dose of 2.5 mg/kg.

    2. Oral. To prevent recurrence of hyperthermia, administer 1–2 mg/kg intravenously or orally (up to 100 mg maximum) 4 times a day for 2–3 days. Daily dose not to exceed 400 mg (see black box warning). For prevention (patients at risk for malignant hyperthermia), give 1–2 days before surgery (with the last dose given 3–4 hours before surgery), or give IV at 2.5 mg/kg infused over 1 hour before ...

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