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Chlorzoxazone: Drug information

Chlorzoxazone: Drug information
(For additional information see "Chlorzoxazone: Patient drug information" and see "Chlorzoxazone: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Lorzone
Pharmacologic Category
  • Skeletal Muscle Relaxant
Dosing: Adult
Musculoskeletal conditions

Musculoskeletal conditions: Oral: 250 to 500 mg 3 or 4 times daily; for painful musculoskeletal conditions, may initiate therapy with 500 mg 3 or 4 times daily. May increase dose based on response and tolerability to 750 mg 3 or 4 times daily. Consider dose reductions as symptoms improve.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling. Use caution due to extensive hepatic metabolism; dose adjustments may be necessary (Lucas 1999; Ono 1995).

Dosing: Older Adult

Avoid use (Ref).

Dosing: Pediatric

(For additional information see "Chlorzoxazone: Pediatric drug information")

Muscle spasm

Muscle spasm: Limited data available, efficacy results variable (Losin 1966); Note: Chlorzoxazone not a routine treatment option for management of spasticity in pediatric patients (eg, cerebral palsy); use has been replaced by newer, more effective agents (Delgado 2010):

Children and Adolescents: 20 mg/kg/day in 3 to 4 divided doses; dosing based on generally recognized expert recommendations; published pediatric trial data is lacking; in reported experience, initial dose range: 125 to 250 mg 3 times daily (Berman 1964; Berman 1964a; Darienzo 1966; Gal 2007; Losin 1966); maximum dose: 750 mg/dose

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling.

Adverse Reactions

The following adverse drug reactions are derived from product labeling unless otherwise specified.

Postmarketing:

Dermatologic: Allergic skin rash, ecchymoses

Gastrointestinal: Gastrointestinal hemorrhage

Genitourinary: Urine discoloration

Hematologic & oncologic: Petechia

Hepatic: Hepatotoxicity (Chou 2004)

Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity angiitis (Chiu 2004)

Nervous system: Dizziness, drowsiness, malaise, paradoxical central nervous system stimulation

Neuromuscular & skeletal: Torticollis (spasmodic) (Rosin 1981)

Contraindications

Hypersensitivity to chlorzoxazone or any component of the formulation

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: Rare, serious (including fatal) idiosyncratic and unpredictable hepatocellular toxicity has been reported with use. Discontinue immediately if early signs/symptoms of hepatic toxicity arise (eg, fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, jaundice). Also discontinue if elevated liver enzymes (eg, AST, ALT, alkaline phosphatase, bilirubin) develop.

• Hypersensitivity reaction: Use caution in patients with known allergies or a history of allergic reactions to drugs; if sensitivity (itching, redness, urticaria) occurs, discontinue therapy.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP 1997; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.

Dosage Forms: US

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

Tablet, Oral:

Lorzone: 375 mg [contains sodium benzoate]

Lorzone: 750 mg [scored; contains sodium benzoate]

Generic: 250 mg, 375 mg, 500 mg, 750 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Chlorzoxazone Oral)

250 mg (per each): $24.88

375 mg (per each): $8.93

500 mg (per each): $1.08 - $1.10

750 mg (per each): $9.99

Tablets (Lorzone Oral)

375 mg (per each): $11.78

750 mg (per each): $13.17

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.

Administration: Adult

Administer orally.

Administration: Pediatric

Oral: Administer with or without food

Use: Labeled Indications

Musculoskeletal conditions: Adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions

Medication Safety Issues
Older Adult: High-Risk Medication:

Beers Criteria: Chlorzoxazone is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) because most muscle relaxants are poorly tolerated by older adults because of anticholinergic effects caused by some muscle relaxants, risk of sedation, and an increased risk of fracture. In addition, efficacy is questionable at doses tolerated by geriatric patients (Beers Criteria [AGS 2023]).

Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2A6 (minor), CYP2D6 (minor), CYP2E1 (major), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (weak)

Drug Interactions

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): May enhance the CNS depressant effect of Chlorzoxazone. Alcohol (Ethyl) may decrease the serum concentration of Chlorzoxazone. Specifically, chronic alcohol ingestion may decrease serum concentrations of chlorzoxazone. Risk C: Monitor therapy

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

ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. 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

Botulinum Toxin-Containing Products: Muscle Relaxants (Centrally Acting) may enhance the adverse/toxic effect of Botulinum Toxin-Containing Products. Specifically, the risk for increased muscle weakness may be enhanced. Risk C: Monitor therapy

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

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of Chlorzoxazone. Chlormethiazole may increase the serum concentration of Chlorzoxazone. Management: Consider reduced doses of chlorzoxazone when combined with chlormethiazole. Monitor patients for increased chlorzoxazone effects/toxicities (ie, CNS depression, sedation) if these agents are combined. 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

CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP2E1 Inhibitors (Strong): May increase the serum concentration of Chlorzoxazone. 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

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

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. 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

Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. 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

Isoniazid: May increase the serum concentration of Chlorzoxazone. Isoniazid may decrease the serum concentration of Chlorzoxazone. Specifically, it may decrease chlorzoxazone concentrations below baseline after isoniazid discontinuation. Risk C: Monitor therapy

Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. 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: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification

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

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification

Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification

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

Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. 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

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy

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

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination

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

Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy

Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy

Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: 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. Risk D: Consider therapy modification

Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

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

Tolperisone: May enhance the adverse/toxic effect of Muscle Relaxants (Centrally Acting). Management: Monitor for increased sedation or CNS effects if tolperisone is combined with other centrally acting muscle relaxants. Consider decreasing the tolperisone dose if these agents are combined. Risk D: Consider therapy modification

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy

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

Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification

Valerian: May enhance the CNS depressant effect of CNS Depressants. 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

Pregnancy Considerations

Animal reproduction studies have not been conducted.

Monitoring Parameters

Liver functions tests (periodic); signs/symptoms of hepatotoxicity

Mechanism of Action

Centrally acting agent; acts on the spinal cord and subcortical areas of the brain to inhibit polysynaptic reflex arcs involved in causing and maintaining skeletal muscle spasms

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Within 1 hour (Desiraju 1983).

Duration: Up to 6 hours (Desiraju 1983).

Absorption: Rapid (Desiraju 1983).

Metabolism: Extensively hepatic via glucuronidation by CYP2E1 (~98%) (Lucas 1999; Ono 1995).

Half-life elimination: ~1 hour (Desiraju 1983).

Time to peak: ~1 to 2 hours.

Excretion: Urine (predominately as conjugates; <1% as unchanged drug).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Solaxin;
  • (AR) Argentina: Paraflex;
  • (CZ) Czech Republic: Paraflex;
  • (HK) Hong Kong: Solaxin;
  • (HR) Croatia: Myoflex;
  • (HU) Hungary: Myoflexin;
  • (ID) Indonesia: Solaxin;
  • (IN) India: Actizone;
  • (JP) Japan: Chlorzon | Chlorzoxazone isei | Chlorzoxazone merck hoei | Chlorzoxazone towa | Chlozoxine | Framenco | Korispar s | Kuronkipal | Mesin | Palkizon | Slaxin | Solaxin | Troncrol;
  • (KR) Korea, Republic of: Benzolinon | Carbamol pro | Chlormezanone crown | Chlozoxine | Clodafen | Geunlax | Geunsokpeu | Hanmi relax | Puligen | Relaxel | Soxazone;
  • (LB) Lebanon: Paraflex;
  • (LT) Lithuania: Paraflex;
  • (LV) Latvia: Paraflex;
  • (PL) Poland: Paraflex;
  • (PR) Puerto Rico: Lorzone | Parafon forte dsc | Relax-ds | Remular-s;
  • (RO) Romania: Clorzoxazon | Clorzoxazona | Clorzoxazona arena;
  • (SA) Saudi Arabia: Relaxon forte;
  • (SE) Sweden: Klorzoxazon evolan | Klorzoxazon orifarm | Paraflex;
  • (TH) Thailand: Maselax | Solaxin;
  • (TN) Tunisia: Myoflex;
  • (TR) Turkey: Paraflex;
  • (TW) Taiwan: Anrokin | Chlozin | Matalmin | Meotin | Mesin | Muscol | Muslax | Muslax-a | Muslaxin | Ninlaxin | Penzin | Prolax | Rezoxin | Salalin | Shulijn | Solacon | Solaxin | Sonzin | Soraflex | Sorin | Sumenchiton | Tonipin | Transone | Xatone | Zikan
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