Dantrolene

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as sodium:

Dantrium: 25 mg, 50 mg [contains fd&c yellow #6 (sunset yellow)]

Generic: 25 mg, 50 mg, 100 mg

Solution Reconstituted, Intravenous, as sodium:

Dantrium: 20 mg (1 ea)

Revonto: 20 mg (1 ea)

Solution Reconstituted, Intravenous, as sodium [preservative free]:

Generic: 20 mg (1 ea)

Suspension Reconstituted, Intravenous, as sodium:

Ryanodex: 250 mg (1 ea) [contains polysorbate 80]

Pharmacology

Mechanism of Action

Acts directly on skeletal muscle by interfering with release of calcium ion from the sarcoplasmic reticulum; prevents or reduces the increase in myoplasmic calcium ion concentration that activates the acute catabolic processes associated with malignant hyperthermia

Pharmacokinetics/Pharmacodynamics

Absorption

Oral: 70% (Allen 1988)

Distribution

V_d: 36.4 ± 11.7 L

Metabolism

Hepatic; major metabolites are 5-hydroxy dantrolene and an acetylamino metabolite of dantrolene.

Excretion

Feces (45% to 50%); urine (25% as unchanged drug and metabolites)

Half-Life Elimination

Neonates (at birth): ~20 hours (Shime 1988)

Children 2 to 7 years: 10 hours (range: 8.1 to 14.8 hours) (Lerman 1989)

Adults: 4 to 11 hours

Use: Labeled Indications

Chronic spasticity: Oral: Treatment of spasticity associated with upper motor neuron disorders (eg, spinal cord injury, stroke, cerebral palsy, or multiple sclerosis).

Malignant hyperthermia:

IV: Management of malignant hyperthermia (MH) crisis.

Oral, IV: Following a malignant hyperthermic crisis to prevent recurrence.

Note: Dantrolene is not recommended for preoperative prophylaxis of MH, even in susceptible patients, provided non-triggering anesthetic agents are used.

Use: Off Label

Neuroleptic malignant syndromec

An analysis of 271 case reports of neuroleptic malignant syndrome (NMS) found that dantrolene monotherapy was associated with an increased rate of improvement in the first 24 hours, but a higher overall mortality rate compared to supportive therapy. Use of dantrolene in combination with other therapies (eg, bromocriptine) was associated with a lower mortality rate compared with dantrolene alone; therefore, combination therapy with dantrolene may be preferred over dantrolene monotherapy

Contraindications

IV: There are no contraindications listed within the manufacturer's labeling.

Oral: Active hepatic disease (eg, cirrhosis, hepatitis); when spasticity is used to maintain upright posture/balance in locomotion or to obtain/maintain increased function

Dosage and Administration

Dosing: Adult

Chronic spasticity: Oral:

Note: Dose should be titrated and individualized for maximum effect; use the lowest dose compatible with optimal response. Some patients may not respond until a higher daily dosage is achieved; each dose level should be maintained for 7 days to determine patient response. If no further benefit observed with the higher dose level, then decrease dosage to previous dose level. Because of the potential for hepatotoxicity, stop therapy if benefits are not evident within 45 days.

Initial: 25 mg once daily for 7 days; increase to 25 mg 3 times daily for 7 days, increase to 50 mg 3 times daily for 7 days, and then increase to 100 mg 3 times daily; some patients may require 100 mg 4 times daily; maximum dose: 400 mg/day

Malignant hyperthermia (MH):

Note: Discontinue all malignant hyperthermia (MH)-triggering agents (eg, volatile anesthetics gases, succinylcholine) once hyperthermia crisis is recognized and administer supportive care.

Crisis: IV: Initial: 2.5 mg/kg; monitor patient continuously and give repeat doses of 1 mg/kg until symptoms subside or a cumulative dose of 10 mg/kg is reached (Litman 2019a; MHAUS recommendation, available at www.mhaus.org)

24-hour MH Hotline (for emergencies only):

United States: 1-800-644-9737

Outside the US: 00-1-209-417-3722

Post crisis follow-up and to prevent recurrence:

MHAUS protocol recommendation: 1 mg/kg every 4 to 6 hours (route not specified).

Manufacturer's labeling: Oral: Dosing in the prescribing information may not reflect current clinical practice. 4 to 8 mg/kg/day in 4 divided doses for 1 to 3 days; IV dantrolene may be used when oral therapy is not practical; individualize dosage beginning with 1 mg/kg or more as the clinical situation dictates

Neuroleptic malignant syndrome (off-label use): IV: 1 to 2.5 mg/kg initially; if rapid resolution of hyperthermia and rigidity is observed, may follow with 1 mg/kg every 6 hours up to a maximum cumulative dose of 10 mg/kg/day, then switch to oral dosage (Bienvenu 2012; Pileggi 2016; Strawn 2007; Susman, 2001). Note: Based on an analysis of 271 case reports, the use of dantrolene in combination with other therapies (eg, bromocriptine) may be preferred over dantrolene alone due to lower mortality and longer complete time of remission (Reulbach 2007).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Malignant hyperthermia: Infants, Children, and Adolescents:

Preoperative prophylaxis: Note: Routine use of prophylaxis is not recommended provided that there is immediate availability of parenteral dantrolene and adequate perioperative patient management (eg, avoiding known trigger agents in susceptible patients) (MHAUS 2020):

Oral: 4 to 8 mg/kg/day in 3 to 4 divided doses for 1 to 2 days prior to surgery with the last dose administered approximately 3 to 4 hours before scheduled surgery.

IV: 2.5 mg/kg/dose administered approximately 1.25 hours prior to surgery; infuse over at least 1 minute (Ryanodex) or 1 hour (Dantrium, Revonto); may administer additional doses as needed for clinical signs of malignant hyperthermia during anesthesia and surgery.

Crisis: IV: 2.5 mg/kg IV bolus; continuously repeat bolus dose as frequently as needed until symptoms of hypermetabolism subside. Doses >10 mg/kg may be required for patients with persistent contractures or rigidity (MHAUS 2020).

24-hour MH Hotline (for emergencies only):

United States: 1-800-644-9737

Outside the US: 00-1-209-417-3722

Postcrisis follow-up:

IV: 1 mg/kg/dose every 4 to 6 hours (preferred) or a continuous IV infusion of 0.25 mg/kg/hour for at least 24 hours; further doses may be indicated. Treatment may be stopped or interval between doses increased to every 8 to 12 hours when the following criteria are met: metabolic stability for 24 hours, core temperature <38°C, creatinine kinase continues to decrease, no evidence of ongoing myoglobinuria, and muscle rigidity has resolved (Litman 2019b; MHAUS 2020).

Oral: 4 to 8 mg/kg/day in 4 divided doses for 1 to 3 days. Note: Oral dosing is not mentioned in the most current MHAUS guidelines (MHAUS 2020).

Spasticity, chronic: Note: Dosing should be individualized based on patient response and tolerability. Titrate to desired effect; if no further benefit is observed at a higher dosage, decrease dose to previous lower dose. Use of the lowest dose associated with the optimal response is recommended:

Children ≥5 years and Adolescents: Oral:

<50 kg: Initial: 0.5 mg/kg/dose once or twice daily for 7 days; increase to 0.5 mg/kg/dose 3 times daily for 7 days, then increase to 1 mg/kg/dose 3 times daily for 7 days, and then increase to 2 mg/kg/dose 3 times daily; some patients may require a dose 4 times daily; maximum daily dose: 12 mg/kg/day up to 400 mg/day (Kliegman 2020; Krause 2004; manufacturer's labeling).

≥50 kg: Initial: 25 mg once daily for 7 days; increase to 25 mg 3 times daily for 7 days, then increase to 50 mg 3 times daily for 7 days, and then increase to 100 mg 3 times daily; some patients may require a dose 4 times daily; maximum daily dose: 400 mg/day.

Reconstitution

Injection, powder for reconstitution:

Dantrium, Revonto: Reconstitute vial by adding 60 mL of sterile water for injection only (not bacteriostatic water for injection); avoid glass bottles for IV infusion due to potential for precipitate formation.

Ryanodex: Reconstitute vial by adding 5 mL of sterile water for injection only (not bacteriostatic water for injection); shake well (suspension is an orange color). Do not dilute or transfer the suspension to another container to infuse the product.

Extemporaneously Prepared

A 5 mg/mL oral suspension may be made with dantrolene capsules, a citric acid solution, and either simple syrup or syrup BP (containing 0.15% w/v methylhydroxybenzoate). Add the contents of five 100 mg dantrolene capsules to a citric acid solution (150 mg citric acid powder in 10 mL water); mix while adding the chosen vehicle in incremental proportions to almost 100 mL. Transfer to a calibrated bottle and add quantity of vehicle sufficient to make 100 mL. Label "shake well" and "refrigerate". Simple syrup suspension is stable for 2 days refrigerated; syrup BP suspension is stable for 30 days refrigerated.

Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.

Administration

IV: Therapeutic or emergency dose can be administered with rapid continuous IV push. Follow-up doses should be administered over at least 1 minute (Ryanodex) or 1 hour (Dantrium, Revonto).

Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity.

Storage

Capsules: Store at 20°C to 25°C (68°F to 77°F).

Injection, powder for reconstitution: Protect from light. Use reconstituted solution within 6 hours of preparation.

Dantrium: Store unreconstituted vials and reconstituted solutions at 15°C to 30°C (59°F to 86°F).

Revonto: Store unreconstituted vials and reconstituted solutions at 20°C to 25°C (68°F to 77°F).

Ryanodex: Store unreconstituted vials at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Store reconstituted solutions at 20°C to 25°C (68°F to 77°F).

Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Consider therapy modification

Calcium Channel Blockers (Nondihydropyridine): Dantrolene may enhance the hyperkalemic effect of Calcium Channel Blockers (Nondihydropyridine). Dantrolene may enhance the negative inotropic effect of Calcium Channel Blockers (Nondihydropyridine). Management: This interaction has only been described with intravenous dantrolene administration. Avoid combination

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Dexketoprofen: May enhance the adverse/toxic effect of Dantrolene. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Estrogen Derivatives: May enhance the hepatotoxic effect of Dantrolene. Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Lacidipine: May enhance the adverse/toxic effect of Dantrolene. Monitor therapy

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Consider therapy modification

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Vecuronium: Dantrolene may enhance the neuromuscular-blocking effect of Vecuronium. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Adverse Reactions

Frequency not always defined.

Cardiovascular: Flushing (intravenous: 27%), atrioventricular block (intravenous: 3%), tachycardia (3%), cardiac failure, phlebitis, variable blood pressure

Central nervous system: Drowsiness (17%; drowsiness may persist for 48 hours post dose), voice disorder (intravenous: 13%), feeling abnormal (intravenous: 10%), dizziness (3%), headache (3%), myasthenia (3%), chills, choking sensation, confusion, depression, fatigue, insomnia, malaise, nervousness, seizure, speech disturbance

Dermatologic: Acneiform eruption (capsules), diaphoresis, eczematous rash, erythema (intravenous), hair disease (abnormal growth), pruritus, urticaria

Gastrointestinal: Dysphagia (10%; use caution at meal time on day of administration as swallowing may be difficult), nausea (10%), vomiting (3%), abdominal cramps, anorexia, constipation, diarrhea, dysgeusia, gastric irritation, gastrointestinal hemorrhage, sialorrhea

Genitourinary: Crystalluria, difficulty in micturition, erectile dysfunction, hematuria, nocturia, urinary frequency, urinary incontinence, urinary retention

Hematologic & oncologic: Anemia, aplastic anemia, leukopenia, lymphocytic lymphoma, thrombocytopenia

Hepatic: Hepatitis

Hypersensitivity: Anaphylaxis

Local: Injection site reaction (intravenous: 3%; pain, erythema, swelling), local tissue necrosis (with extravasation due to high product pH)

Neuromuscular & skeletal: Limb pain (intravenous: 3%), back pain, myalgia

Ophthalmic: Blurred vision (intravenous: 3%), diplopia, epiphora, visual disturbance

Respiratory: Dyspnea (intravenous), pleural effusion (with pericarditis), pulmonary edema (rare), respiratory depression

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Decrease in forced vital capacity (intravenous), dyspnea (intravenous), hepatic disease, hepatotoxicity (oral), increased liver enzymes (oral), respiratory muscle failure (intravenous)

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
• Hepatotoxicity: [US Boxed Warning]: Oral: Has potential for hepatotoxicity; symptomatic hepatitis (fatal and nonfatal) has been reported. Higher doses (ie, ≥800 mg/day), even sporadic short courses, may increase the risk of severe hepatic injury although hepatic injury may occur at doses <400 mg/day. Overt hepatitis has been most frequently observed between the third and twelfth month of therapy. The risk of hepatic injury appears to be greater in females, in patients >35 years, and in those taking concurrent medications. A higher incidence of fatal hepatic events have been reported in the elderly, although concurrent disease states and concurrent use of potentially hepatotoxic drugs may have contributed. Idiosyncratic and hypersensitivity reactions (sometimes fatal) of the liver have also occurred. Monitor hepatic function at baseline and as clinically indicated during treatment. Discontinue therapy if symptoms compatible with hepatitis, accompanied with abnormal liver function tests or jaundice occur or benefits are not observed within 45 days when utilized for chronic spasticity. Hepatic function usually reverts to normal upon discontinuation; if reinstitution of therapy is necessary, patients should be hospitalized and the drug initiated in very small and gradual dose increases.
• Muscle weakness: Loss of grip strength, weakness in the legs, dyspnea, respiratory muscle weakness, dysphagia, and decreased inspiratory capacity has occurred with IV dantrolene. Patients should not ambulate without assistance until they have normal strength and balance. Monitor patients for the adequacy of ventilation and for difficulty swallowing/choking.
• Photosensitivity: Oral therapy may cause a photosensitivity reaction; use with caution during exposure to sunlight.
• Pleural effusion: Pleural effusion with associated eosinophilia may occur.

Disease-related concerns:

• Cardiovascular disease: Use oral therapy with caution in patients with severely impaired cardiac function due to myocardial disease.
• Hepatic disease: Use oral therapy with caution in patients with history of hepatic disease or dysfunction; use is contraindicated in patients with active hepatic disease (eg, cirrhosis, hepatitis).
• Respiratory disease: Use oral therapy with caution in patients with impaired pulmonary function (particularly in obstructive pulmonary disease).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Extravasation: Alkaline solution; may cause tissue necrosis if extravasated (vesicant); ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.
• Mannitol: Injection may contain mannitol.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.

Other warnings/precautions:

• Appropriate use: IV dantrolene is not the only therapeutic approach for management of malignant hyperthermia. Supportive measures, including discontinuing trigger agents (eg, anesthetic agents), administering oxygen, utilizing cooling methods, and monitoring blood gases, urinary output, urine color, and electrolytes, must also be utilized and individualized. Administer diuretics to prevent late kidney injury due to myoglobinuria.

Monitoring Parameters

Motor performance should be monitored for therapeutic outcomes; nausea, vomiting, and liver function tests (baseline and at appropriate intervals thereafter) should be monitored for potential hepatotoxicity; intravenous administration requires cardiac, blood pressure, and respiratory monitoring.

Malignant hyperthermia: During and post-acute phase: Per MHAUS protocol, patient should be observed in an ICU for at least 24 hours since recrudescence may occur; monitor for arrhythmias; monitor vital signs (including core temperature), electrolytes, ABG, CK, end tidal CO₂ (EtCO₂)/capnography, urine output, urine myoglobin

Pregnancy

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Dantrolene crosses the human placenta. Cord blood concentrations are similar to those in the maternal plasma at term. and dantrolene can be detected in the newborn serum at delivery. Adverse events were not observed in the newborn following maternal doses of 100 mg/day administered orally prior to delivery (Shime, 1988). Uterine atony has been reported following dantrolene injection after delivery; however, this may be due in part to the mannitol contained in the IV preparation (Shin, 1995; Weingarten, 1987). Prophylactic use of dantrolene is not routinely recommended in pregnant women susceptible to MH prior to obstetric surgery, if use is needed, close monitoring of the mother and newborn is recommended (Krause 2004; Norman 1995).

Patient Education

What is this drug used for?

• It is used to relax muscles.
• It is used to treat or prevent a health problem called malignant hyperthermia.

Frequently reported side effects of this drug

• Fatigue
• Dizziness
• Flushing
• Nausea
• Change in voice
• Loss of strength and energy
• Diarrhea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin
• Shortness of breath
• Chest pain
• Trouble swallowing
• Choking
• Severe injection site pain, burning, swelling, or irritation
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.