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Dantrolene

Category: Pharmacology > Voiding & Outlet

Overview​

Dantrolene is a direct-acting skeletal-muscle relaxant. It weakens striated muscle contraction without acting on the nerves that drive it. That property made it attractive in the 1970s and 1980s for external urethral sphincter (EUS) hypertonicity and detrusor-sphincter dyssynergia (DSD), especially in suprasacral spinal cord injury (SCI), because the sphincter is striated and the detrusor is smooth muscle.[1][2]

The urologic role today is historical and off-label. The evidence is a handful of small uncontrolled series from 1976 to 1980. No randomized trial has tested it for DSD. A 2025 scoping review found that all muscle-relaxant studies for DSD were published in 1980 or earlier, and noted that guidelines no longer encourage muscle relaxants for this use.[3] It recommends alpha-blockers to lower outlet resistance and describes intrasphincteric botulinum toxin A for DSD.[4]

Practical points:

  • Dantrolene is rarely the right drug for outlet obstruction. Alpha-blockers, intrasphincteric botulinum toxin, sphincterotomy or a urethral stent, and catheterization are the working options (see below).
  • Its main limits are generalized muscle weakness and a boxed warning for fatal and non-fatal hepatotoxicity.
  • Reconstructive surgeons meet it mostly as a drug the patient is already taking for spasticity, or as the anesthesia drug for malignant hyperthermia (MH).

Mechanism of Action​

Dantrolene uncouples excitation from contraction in skeletal muscle. It suppresses calcium release from the sarcoplasmic reticulum through ryanodine receptors. RyR1 is the skeletal-muscle isoform.[5] The label describes relaxation at a site beyond the myoneural junction, "directly on the muscle itself", with a slightly greater effect on fast fibers than slow ones.[6]

  • Skeletal-muscle selectivity. In an in vitro canine detrusor preparation, dantrolene had no statistically significant inhibitory effect on acetylcholine-induced detrusor contractions.[7]
  • Weakness is not selective. Dantrolene relaxes all skeletal muscle, including limb, respiratory and pelvic-floor muscle. The label lists drowsiness, dizziness, weakness, malaise, fatigue and diarrhea as the commonest effects, and notes central effects of uncertain extent.[6]

The animal data on the sphincter are mixed. In normal and T10 paraplegic dogs with bladder-stimulation-induced DSD, dantrolene had little effect on electrically evoked urethral sphincter contraction, while baclofen reduced urethral resistance.[8] In a human sphincterometry study, IV dantrolene 0.5 mg/kg reduced external sphincter resistance measured by sphincterometry.[9]

Agents in This Class​

Generic nameBrand name(s)RouteNotes
Dantrolene sodiumDantriumOral capsule (25, 50, 100 mg)Labeled for chronic spasticity from upper motor neuron disease and, preoperatively, for MH prophylaxis. Not labeled for the urinary tract.[6]
Dantrolene sodiumDantrium IV, Revonto, RyanodexIntravenousMalignant hyperthermia. See Anesthesia for crisis management and the product-specific dosing.

Dantrolene is not labeled for neuroleptic malignant syndrome. The Dantrium capsule label states that it is not indicated for NMS and that patients may die despite treatment.[6]

Indications in Reconstructive Urology​

FDA-labeled uses (not urologic). Oral dantrolene is labeled for spasticity from upper motor neuron disorders such as SCI, stroke, cerebral palsy and MS, where relief should help restore residual function. It is contraindicated when spasticity is needed to sustain posture, balance or locomotion. It is also labeled for oral preoperative prophylaxis and post-crisis follow-up in MH-susceptible patients.[6] Intravenous dantrolene is the specific treatment for an MH crisis.

Urologic use (off-label, historical). Two urologic problems drew interest:

  • EUS hypertonicity or spasm with functional outlet obstruction. Murdock and colleagues reported benefit in selected patients with neurologic and non-neurologic external sphincter spasm identified by sphincter EMG, cystometry and voiding cystourethrography.[2]
  • DSD with high residual urine in SCI. Hackler's series is the most cited report (see Evidence Summary).[1]

A 2015 case report describes a woman with cerebral palsy and refractory neurogenic detrusor overactivity whose symptoms improved when dantrolene was added to an antimuscarinic and mirabegron. She had started dantrolene for spasticity after spinal surgery.[10] One case provides no efficacy estimate for detrusor overactivity.[10]

Current options for DSD and sphincter hypertonicity. No DSD-specific first-line oral drug sequence is established. EAU 2026 recommends alpha-blockers to decrease outlet resistance in neuro-urological patients generally . AUA/SUFU 2021 says clinicians may recommend alpha-blockers to improve voiding parameters in NLUTD patients who spontaneously void , whereas NICE CG148 says not to offer them for neurological bladder-emptying problems.[3][4][14][15]

OptionPositionWhere covered
Alpha-blockersEAU 2026: prescribe to decrease bladder outlet resistance . Effects on PVR and dysreflexia reported.[4] Evidence in DSD is low quality but more favorable than for muscle relaxants.[3]Alpha-Blockers
Intrasphincteric botulinum toxin ACan treat DSD, but the effect wears off within months and needs repeat injection. Dose and technique are not settled and use is off-label.[4]Botulinum Toxin
External sphincterotomy or urethral stentOptions for refractory DSD in men who can use a condom catheter. Sphincterotomy is irreversible and often repeated. Counsel about the high risk of urinary incontinence after outlet reduction.[4] Continence after urethral stenting depends on an adequately closing bladder neck; complications and reinterventions limit stent use.[4]Neurogenic Bladder
Intermittent catheterizationStandard emptying strategy when the outlet cannot be relaxed safely.Neurogenic Bladder
Baclofen and other systemic relaxantsLimited urologic evidence; agent-specific effects.Skeletal Muscle Relaxants

Dosing & Administration​

The label gives an oral schedule for spasticity only. No label or guideline gives a urologic regimen.

SettingRegimen
Labeled spasticity titration (adults)25 mg daily for 7 days, then 25 mg three times daily for 7 days, then 50 mg three times daily for 7 days, then 100 mg three times daily. Each level is held for 7 days. If no further benefit appears at the next dose, return to the previous dose. [6]
Labeled ceiling100 mg four times daily (400 mg/day). Higher doses are not to be used. [6]
Stop ruleDiscontinue if there is no observable benefit after a total of 45 days. Prescribe the lowest effective dose.
Historical urologic seriesHackler: five of the eight responders needed up to 600 mg/day, which is above the current label ceiling.[1]

Do not use the 1980 doses as a prescribing target. The boxed warning describes a markedly higher hepatic risk at 800 mg/day or more, and fatal cases in the manufacturer's reports had a higher mean dose than nonfatal ones.[6][13]

Although oral preoperative MH prophylaxis remains on the capsule label, MHAUS does not recommend routine pretreatment for most susceptible patients when a nontriggering anesthetic, monitoring and adequate dantrolene supply are available.[6][16] IV crisis treatment follows the product-specific anesthesia protocol; see Anesthesia.

Contraindications & Precautions​

Boxed warning (Dantrium capsules). The label states that dantrolene "has a potential for hepatotoxicity, and should not be used in conditions other than those recommended." Symptomatic hepatitis, fatal and non-fatal, has occurred at various doses. The incidence in patients taking up to 400 mg/day is much lower than at 800 mg/day or more, and even sporadic short courses at higher doses markedly increased risk. Overt hepatitis has most often appeared between the third and twelfth month. Risk appears greater in women, in patients over 35 and in patients taking other medications.[6]

The evidence behind the warning:

SourceFinding
Utili 1977Hepatic injury in 19 of 1,044 patients (1.8%) monitored for at least 60 days on long-term therapy; 6 with icteric hepatitis (0.6%); 3 deaths (0.3%). Analysis of 50 cases (those 19 plus 31 reported after marketing) found a 28% case fatality; 85% of the fatalities were at 300 mg/day or more.[11]
Chan 1990Of 122 analyzable manufacturer-reported cases through 1987: 47 asymptomatic transaminase rises, 36 with jaundice, 27 deaths. Mean dose was 582 mg/day in fatal cases and 263 mg/day in nonfatal cases.[13]
Pinder 1977 reviewLiver chemistry abnormalities in 0.7 to 1% of patients on long-term treatment, symptomatic hepatitis in 0.35 to 0.5% and fatal hepatitis in 0.1 to 0.2%.[12]

These reports are passive or early surveillance data with different denominators and definitions.

Monitoring. Obtain baseline liver function tests (AST, ALT, alkaline phosphatase, total bilirubin) and repeat at appropriate intervals. Generally discontinue for abnormal liver tests; discontinue if hepatitis symptoms occur with abnormal tests or jaundice.[6] After hepatocellular injury, consider reinitiation only for a major benefit once symptoms and liver tests resolve, with an inpatient restart at very small, gradually increasing doses and frequent laboratory monitoring. Withdraw immediately if liver involvement recurs.[6]

Contraindications and cautions from the label:[6]

  • Active hepatic disease such as hepatitis or cirrhosis is a contraindication.
  • Spasticity that supports posture, balance or locomotion is a contraindication. In an ambulatory patient with incomplete SCI, sphincter relaxation may cost limb function.
  • Use caution with impaired pulmonary function (especially obstructive disease), severely impaired cardiac function and prior liver disease. The Dantrium capsule label advises use during pregnancy only if clearly needed and says it should not be used while nursing.[6]
  • Additive drowsiness with sedatives and tranquilizers. Caution with estrogen therapy, because hepatotoxicity was more frequent in women over 35 receiving estrogen. Dantrolene may potentiate vecuronium-induced neuromuscular block.
  • Patients should not drive or do hazardous work while taking it. Photosensitivity is possible.[6]

Urogenital adverse effects listed on the label: increased urinary frequency, urinary incontinence and/or nocturia, difficult urination and/or urinary retention, crystalluria, hematuria and difficult erection.[6] New frequency, incontinence or retention after starting dantrolene for spasticity may be drug-related. A weak sphincter may also cause reflex incontinence in a man who relied on a high-tone sphincter with a condom catheter.

Perioperative Considerations​

  • Ask about dantrolene use in patients with SCI, MS or cerebral palsy scheduled for reconstruction. A long-term user needs a current LFT panel, and the label advises stopping if abnormal.
  • Dantrolene may potentiate vecuronium-induced neuromuscular block; tell the anesthesia team.[6]
  • Weakness from oral dantrolene can affect transfers, catheterization technique and respiratory reserve. Plan for this in a patient with high-level SCI.
  • Oral dantrolene is not a substitute for a sphincter procedure. If outlet obstruction threatens the upper tracts, use an established option from the table above.
  • Dantrolene is the specific treatment for MH. Reconstructive operating rooms should follow the institution's MH protocol.

Evidence Summary​

IndicationEvidence levelKey studyNotes
EUS hypertonicity with high PVR in SCIUncontrolled case series (15 patients)Hackler 1980: 8 of 15 benefited (PVR under 100 mL, maintained on condom drainage). Urethral pressure fell by a mean of 77 cm H₂O (49%) in responders and 21 cm H₂O (16%) in failures. Five of the eight needed up to 600 mg/day.[1]All had closure pressures above 100 cm H₂O and PVR above 150 mL. Detrusor hyporeflexia may have contributed to failures. The authors concluded it would not replace external sphincterotomy in complete male SCI, and that a low effective dose would be needed to avoid weakness.
External sphincter spasm, neurologic and non-neurologicSmall uncontrolled seriesMurdock 1976: reported benefit in a selected group.[2]The abstract gives no numbers.
Sphincter resistance, pharmacodynamicPhysiologic studyPedersen 1978: IV 0.5 mg/kg reduced external sphincter resistance on sphincterometry.[9]Clinical voiding outcomes were not assessed.
Detrusor effectIn vitro canine bathHarris 1980: no significant inhibition of acetylcholine-induced detrusor contraction.[7]—
DSD modelCanineTeague 1978: little effect on evoked sphincter contraction; baclofen was effective.[8]Conflicts with the human sphincterometry data.
Detrusor overactivitySingle case reportBulchandani 2015 (cerebral palsy, on antimuscarinic and mirabegron).[10]—
Overview of oral DSD therapyScoping review, 15 studies, 257 patientsTousignant 2025: alpha-blockers "promising", evidence lacking overall; all muscle-relaxant studies were 1980 or earlier.[3]The review lists four DSD patients for Hackler in Table 1 and a 50% success rate in Table 2, but its footnote says outcomes were not differentiated by DSD status. Hackler's primary series reports benefit in 8 of 15 SCI patients overall.[1]

Practical Pearls​

  • Dantrolene has no established role in current DSD care. Select catheterization, intrasphincteric botulinum toxin, an alpha-blocker trial or an outlet procedure according to storage pressure, residual urine and catheterization ability.[3][4]
  • If a patient is already on dantrolene for spasticity, check LFTs, and review new urinary symptoms against the label's urogenital adverse effects.
  • The capsule label reports hepatic injury at various doses, with much lower incidence at up to 400 mg/day than at 800 mg/day or more; overt hepatitis is most frequent in months 3–12. Risk appears greater in women and patients over 35. For chronic oral spasticity, stop at 45 days if there is no benefit.[6]
  • A patient with incomplete SCI who walks on spastic legs may lose function on dantrolene. That is a labeled contraindication.
  • The 1980 dose range (up to 600 mg/day) is above the label ceiling and should not be copied.[1][6]

See Also​

References​

1. Hackler RH, Broecker BH, Klein FA, Brady SM. "A clinical experience with dantrolene sodium for external urinary sphincter hypertonicity in spinal cord injured patients." J Urol. 1980;124(1):78–81. doi:10.1016/s0022-5347(17)55305-7

2. Murdock MM, Sax D, Krane RJ. "Use of dantrolene sodium in external sphincter spasm." Urology. 1976;8(2):133–137. doi:10.1016/0090-4295(76)90340-x

3. Tousignant A, Blais MA, Tu LM, Morin M, Ismail S. "A scoping review of the oral treatment options for the management of detrusor sphincter dyssynergia." Neurourol Urodyn. 2025;44(4):743–753. doi:10.1002/nau.25642

4. European Association of Urology. EAU Guidelines on Neuro-Urology (Limited Update March 2026). Sections 3.4.2.c–d (drugs) and 3.4.2 (botulinum toxin A for DSD). Official guideline.

5. Yang HS, Choi JM, In J, Sung TY, Kim YB, Sultana S. "Current clinical application of dantrolene sodium." Anesth Pain Med (Seoul). 2023;18(3):220–232. doi:10.17085/apm.22260

6. Dantrium (dantrolene sodium) capsules prescribing information. Par Health USA. DailyMed. Label version published September 9, 2026.

7. Harris JD, Benson GS. "Effect of dantrolene sodium on canine bladder contractility." Urology. 1980;16(2):229–231. doi:10.1016/0090-4295(80)90095-3

8. Teague CT, Merrill DC. "Effect of baclofen and dantrolene on bladder stimulator-induced detrusor-sphincter dyssynergia in dogs." Urology. 1978;11(5):531–535. doi:10.1016/0090-4295(78)90179-6

9. Pedersen E, Harving H, Klemar B. "Effect of dantrolene sodium on the spastic external urethral sphincter recorded by sphincterometry." J Urol. 1978;119(3):403–405. doi:10.1016/s0022-5347(17)57502-3

10. Bulchandani S, Toozs-Hobson P, Kennedy A, Sturman S. "Dantrolene an unusual option for detrusor overactivity: observations of a patient with cerebral palsy." Eur J Obstet Gynecol Reprod Biol. 2015;194:255–256. doi:10.1016/j.ejogrb.2015.08.012

11. Utili R, Boitnott JK, Zimmerman HJ. "Dantrolene-associated hepatic injury. Incidence and character." Gastroenterology. 1977;72(4 Pt 1):610–616. doi:10.1016/s0016-5085(77)80141-8. PMID 838213

12. Pinder RM, Brogden RN, Speight TM, Avery GS. "Dantrolene sodium: a review of its pharmacological properties and therapeutic efficacy in spasticity." Drugs. 1977;13(1):3–23. doi:10.2165/00003495-197713010-00002

13. Chan CH. "Dantrolene sodium and hepatic injury." Neurology. 1990;40(9):1427–1432. doi:10.1212/wnl.40.9.1427

14. Ginsberg DA, Boone TB, Cameron AP, et al. "The AUA/SUFU guideline on adult neurogenic lower urinary tract dysfunction: treatment and follow-up." J Urol. 2021;206(5):1106–1113. doi:10.1097/JU.0000000000002239

15. National Institute for Health and Care Excellence. Urinary incontinence in neurological disease: assessment and management (CG148). 2012; updated 2023. Recommendation 1.5.1. Official guideline.

16. Malignant Hyperthermia Association of the United States. "Should MHS Patients Be Pretreated With Dantrolene?" Official clinical FAQ.