Version May 2024
Dantrolene has a potential for hepatotoxicity; do not use in conditions other than those recommended. Symptomatic hepatitis (fatal and nonfatal) has been reported at various dose levels of the drug. The incidence reported in patients taking dosages of up to 400 mg/day is much lower than in those taking dosages of 800 mg or more per day. Even sporadic short courses of these higher dose levels within a treatment regimen markedly increase the risk of serious hepatic injury. Liver dysfunction as evidenced by blood chemical abnormalities alone (liver enzyme elevations) has been observed in patients exposed to dantrolene for varying periods of time. Overt hepatitis has occurred at varying intervals after initiation of therapy, but has been most frequently observed between the third and twelfth month of therapy. The risk of hepatic injury appears to be greater in females, patients >35 years of age, and patients taking other medication(s). Spontaneous reports suggest a higher proportion of hepatic events with fatal outcome in elderly patients receiving dantrolene; however, the majority of these cases were complicated with confounding factors such as concurrent illnesses and/or concomitant potentially hepatotoxic medications. Use dantrolene only in conjunction with appropriate monitoring of hepatic function, including frequent determination of AST or ALT. If no observable benefit is derived from dantrolene after a total of 45 days, discontinue therapy. Prescribe the lowest possible effective dose for the individual patient.
Malignant hyperthermia:
Note: Utilize actual body weight (Ref) for dosing calculations. There is no recommended maximum total dose. Although FDA approved, routine dantrolene for the prevention of malignant hyperthermia is not recommended (Ref).
If questions, contacting the MH Hotline (see below) may be helpful.
24-hour MH Hotline (for emergencies only):
United States: 1-800-644-9737
Outside the United States: 001-209-417-3722
Crisis: Infants, Children, and Adolescents: IV: Initial: 2.5 mg/kg, then 1 or 2.5 mg/kg every 5 minutes as frequently as needed until treatment goals reached (Ref). Doses >10 mg/kg may be required for patients with persistent contractures or rigidity; however, if no resolution, reassess diagnosis (Ref).
Postcrisis follow-up:
IV: Infants, Children, and Adolescents: IV: 1 mg/kg/dose every 4 to 6 hours (preferred to minimize extravasation risk) if within 6 hours of initial reaction; if outside of 6-hour window, a higher dose of 2 or 3 mg/kg/dose may be needed. 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 (Ref).
Oral: Note: Although FDA approved for this indication, expert guidelines do not recommend use (Ref): Infants, Children, and Adolescents: Oral: 4 to 8 mg/kg/day in 4 divided doses for 1 to 3 days.
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 (Ref).
≥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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling.
Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; use of oral dantrolene in patients with active liver disease (hepatitis or cirrhosis) is contraindicated.
(For additional information see "Dantrolene: Drug information")
Malignant hyperthermia:
Note: Administer dantrolene as soon as possible after the identification of clinical symptoms/crisis. Discontinue all malignant hyperthermia–triggering agents (eg, volatile anesthetics gases, succinylcholine) once hyperthermia crisis is recognized and administer supportive care. General treatment goals: end tidal CO2 <45 mm Hg, normal minute ventilation, core temperature <38ºC (100.4ºF), heart rate stable and decreasing, muscular rigidity resolved (Ref).
Malignant hyperthermia crisis: IV: Initial: 2.5 mg/kg; monitor patient continuously and administer repeat doses of 2.5 mg/kg every 5 minutes until symptoms subside and treatment goals are reached. Most patients will respond to a cumulative dose of ≤10 mg/kg; however, >10 mg/kg may be necessary in patients with persistent contractures or rigidity (Ref).
Recurrence of malignant hyperthermia after initial treatment: Note: Monitor for recurrence (eg, increased muscular rigidity, inappropriate hypercarbia, unexplained metabolic acidosis, inappropriate temperature increase) in PACU/ICU for at least 24 hours (Ref).
IV: 1 mg/kg every 4 to 6 hours or 0.25 mg/kg/hour continuous infusion for 24 hours or longer if clinically indicated; stop therapy or change dosing interval to every 8 to 12 hours when all of the following are met: metabolic stability for 24 hours, core temperature <38ºC (100.4ºF), decrease CK, myoglobinuria absent, no muscle rigidity (Ref).
MHAUS 24-hour MH Hotline (for emergencies only):
United States: 1-800-644-9737.
Outside the United States: 001-209-417-3722.
Neuroleptic malignant syndrome, moderate to severe (off-label use):
Note: Consider for use in combination with supportive care, benzodiazepines, and/or dopaminergic agents (eg, bromocriptine) in patients with severe symptoms at presentation (eg, hyperthermia, evidence of rhabdomyolysis) and for those not responding to initial withdrawal of medication and supportive care (Ref).
IV: Initial: 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 (maximum cumulative daily dose: 10 mg/kg/day) (Ref). After the patient is stabilized and symptoms have resolved, consider taper over days to weeks rather than abrupt discontinuation (Ref).
Spasticity, chronic: 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
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling; use of oral dantrolene in patients with active liver disease (eg, hepatitis and cirrhosis) is contraindicated.
The following adverse drug reactions are derived from product labeling unless otherwise specified.
Postmarketing:
Cardiovascular: Atrioventricular block, flushing, heart failure, phlebitis (including superficial thrombophlebitis) (Brandom 2011), tachycardia, variable blood pressure
Dermatologic: Acneiform eruption (Mowbray 2009), diaphoresis, eczematous rash, hair disease (abnormal growth), pruritus, urticaria
Endocrine & metabolic: Hyperkalemia (Brandom 2011)
Gastrointestinal: Abdominal cramps, anorexia, constipation, diarrhea (including severe diarrhea), dysgeusia, dysphagia, gastric irritation (Brandom 2011), gastrointestinal hemorrhage, nausea (Brandom 2011), sialorrhea (Brandom 2011), vomiting
Genitourinary: Crystalluria, difficulty in micturition, erectile dysfunction, hematuria, nocturia, urinary frequency, urinary incontinence, urinary retention
Hematologic & oncologic: Anemia, aplastic anemia, leukopenia, malignant lymphoma (lymphocytic) (Wan 1980), thrombocytopenia
Hepatic: Hepatitis (Wilkinson 1979), hepatotoxicity (including hepatic necrosis) (Wilkinson 1979), increased liver enzymes (Wilkinson 1979)
Hypersensitivity: Anaphylaxis
Local: Injection-site reaction (including erythema at injection site, injection-site phlebitis, pain at injection site, swelling at injection site)
Nervous system: Asthenia (Brandom 2011), chills, confusion, depression, dizziness (Brandom 2011), drowsiness, fatigue (Brandom 2011), feeling abnormal, headache, insomnia, malaise, myasthenia (Brandom 2011), nervousness, seizure, speech disturbance, voice disorder
Neuromuscular & skeletal: Back pain, dystonia, limb pain, myalgia
Ophthalmic: Blurred vision, diplopia, epiphora, visual disturbance (Brandom 2011)
Respiratory: Dyspnea (including a feeling of suffocation) (Brandom 2011), oropharyngeal spasm (Locatelli 2014), pleural effusion (with eosinophilia or pericarditis) (Miller 1984), pulmonary edema (Brandom 2011), respiratory depression, respiratory failure (Brandom 2011), respiratory insufficiency (including respiratory muscle weakness and decreased inspiratory capacity) (Javed 2010)
Miscellaneous: Fever
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.
Canadian labeling (additional contraindications not in US labeling): Hypersensitivity to dantrolene or any component of the formulation; compromised pulmonary function (eg, obstructive pulmonary disease).
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: Oral: Has potential for hepatotoxicity; symptomatic hepatitis (fatal and nonfatal) has been reported. Idiosyncratic and hypersensitivity reactions (sometimes fatal) of the liver have also occurred; monitor hepatic function. Discontinue therapy if symptoms compatible with hepatitis, accompanied with abnormal LFTs or jaundice, occur or benefits are not observed within 45 days. 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).
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral, as sodium:
Dantrium: 25 mg, 50 mg [DSC] [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 [DSC])
Solution Reconstituted, Intravenous, as sodium [preservative free]:
Revonto: 20 mg (1 ea)
Generic: 20 mg (1 ea)
Suspension Reconstituted, Intravenous, as sodium:
Ryanodex: 250 mg (1 ea) [contains polysorbate 80]
May be product dependent
Capsules (Dantrium Oral)
25 mg (per each): $1.28
Capsules (Dantrolene Sodium Oral)
25 mg (per each): $0.96 - $1.07
50 mg (per each): $1.56 - $1.73
100 mg (per each): $1.95 - $2.17
Solution (reconstituted) (Dantrium Intravenous)
20 mg (per each): $106.37
Solution (reconstituted) (Dantrolene Sodium Intravenous)
20 mg (per each): $85.09
Solution (reconstituted) (Revonto Intravenous)
20 mg (per each): $84.00
Suspension (reconstituted) (Ryanodex Intravenous)
250 mg (per each): $3,752.10
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as sodium:
Dantrium: 25 mg [contains fd&c yellow #6 (sunset yellow)]
Solution Reconstituted, Intravenous, as sodium:
Dantrium: 20 mg (1 ea)
Generic: 20 mg (1 ea)
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.
Oral: Administer liquid formulation (extemporaneously prepared) using an accurate measuring device; do not use household tablespoon.
Parenteral:
Dantrium, Revonto: Administer crisis doses by rapid IV injection, preferably in large-bore IV or central line.
Ryanodex: Administer crisis doses by rapid IV injection; follow-up doses should be administered over ≥1 minute.
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. 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.
IV:
Malignant hyperthermia crisis/recurrence: Administer as a rapid continuous IV push, through a large bore IV if possible (do not delay administration if large bore IV is not available) (Ref).
Other indications: Administer over at least 1 minute (Ryanodex) or 1 hour (Dantrium, Revonto) (Ref).
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.
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).
Parenteral: Management of the fulminant hypermetabolism of skeletal muscle characteristic of malignant hyperthermia (Dantrium, Revonto, Ryanodex: FDA approved in all ages); prevention of malignant hyperthermia in susceptible individuals (preoperative/postoperative administration) (Dantrium, Revonto, Ryanodex: FDA approved in all ages). Note: Although FDA approved, routine dantrolene for the prevention of malignant hyperthermia is not recommended (Hopkins 2021; MHAUS 2023).
Oral: Treatment of spasticity associated with upper motor neuron disorders such as spinal cord injury, stroke, cerebral palsy, or multiple sclerosis (FDA approved in ages ≥5 years and adults); preoperative prevention or attenuation of malignant hyperthermia in susceptible individuals who require anesthesia and/or surgery (FDA approved in ages ≥5 years and adults).
Note: Dantrolene prophylaxis is not routinely recommended for most malignant hyperthermia susceptible patients, provided there is immediate availability of parenteral dantrolene and adequate perioperative patient management (eg, avoiding known trigger agents [eg, anesthetics] in susceptible patients).
Dantrium may be confused with danazol, Daraprim
Revonto may be confused with Revatio
Substrate of CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: 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. Risk D: Consider therapy modification
Calcium Channel Blockers: Dantrolene may enhance the hyperkalemic effect of Calcium Channel Blockers. Dantrolene may enhance the negative inotropic effect of Calcium Channel Blockers. Risk X: Avoid combination
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: 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. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Dexketoprofen: May enhance the adverse/toxic effect of Dantrolene. Risk C: Monitor therapy
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: 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. Risk D: Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Estrogen Derivatives: May enhance the hepatotoxic effect of Dantrolene. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
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. Risk D: Consider therapy modification
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: 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 the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
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. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Vecuronium: Dantrolene may enhance the neuromuscular-blocking effect of Vecuronium. Risk C: 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. Risk D: Consider therapy modification
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
Dantrolene crosses the human placenta.
Cord blood concentrations of dantrolene 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). Untreated malignant hyperthermia (MH) is a medical emergency; treatment should not be withheld due to pregnancy. Prophylactic use of dantrolene is not routinely recommended in pregnant patients susceptible to MH prior to obstetric surgery; if use is needed, close monitoring of the mother and newborn is recommended (Krause 2004; Norman 1995; Urman 2019).
Spasticity: 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.
Malignant hyperthermia: Cardiac, respiratory, and blood pressure monitoring; during and postacute 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.
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
Absorption: Oral: 70% (Allen 1988)
Distribution: Vd: 36.4 ± 11.7 L
Metabolism: Hepatic; major metabolites are 5-hydroxy dantrolene and an acetylamino metabolite of dantrolene.
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
Time to peak: IV: 1 minute post-dose (dantrolene); 24 hours post-dose (5-hydroxy dantrolene)
Excretion: Feces (45% to 50%); urine (25% as unchanged drug and metabolites)
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