Chlorzoxazone - a centrally acting muscle relaxant

Chlorzoxazone is a centrally acting muscle relaxant that is used as an adjunct to physcical therapy, exercise/ rest, and analgesics to treat spasticity and acute painful musculoskeletal conditions.

Chlorzoxazone Dose in Adults

For the treatment of spasticity and painful Musculoskeletal conditions:

250 to 500 mg 3 or 4 times a day to a maximum of 750 mg 3 - 4 times daily.
The dose should be reduced when the symptoms improve.

Chlorzoxazone Dose in Childrens

For the treatment of Muscle spasm in children and adolescents:

20 mg/kg/day in 3 or 4 divided doses.
The usual initial dose ranges between 125 to 250 mg thrice daily to a maximum daily dose of 750 mg/dose

Note: It is not routinely used in the treatment of spasticity in children as in patients with cerebral palsy because of the availability of more safe and effective agents.

Pregnancy Risk Factor: C

It has not yet been tested in pregnant women.

Use while breastfeeding

It is unknown whether chlorzoxazone can be excreted into breastmilk.
It is best to use it with caution.
The nneonate should be monitored for somnolence, liver toxicities and other symptoms.

Chlorzoxazone Dose in Renal Disease:

The manufacturer has not recommended any dose adjustment in patients with renal disease.

Chlorzoxazone Dose in Liver Disease:

The manufacturer has not recommended any dose adjustment in patients with liver disease.

Common Side Effects of Chlorzoxazone:

- Central nervous system:
- Dizziness
- Drowsiness
- Malaise
- Paradoxical central nervous system stimulation
Genitourinary:
- Urine discoloration

Contraindication to Chlorzoxazone include:

Allergy to any drug or component of the formulation

Warnings and Precautions

Depression in the CNS:
- Chlorzoxazone can cause CNS depression and physical and mental impairments. Patients who need mental alertness for tasks should not use chlorzoxazone.
Hepatotoxicity
- It has been reported that liver toxicity can sometimes prove fatal.
- If symptoms of liver toxicities like anorexia and jaundice, fever, fatigue, dark urine color or right upper quadrant pain, it should be stopped immediately
- If liver enzymes become abnormal, therapy should be stopped.
Hypersensitivity reaction
- Itching and rash caused by allergic reactions should be stopped immediately.

Chlorzoxazone: Drug Interaction

Note: Drug Interaction Categories:

Risk Factor C: Monitor When Using Combination
Risk Factor D: Consider Treatment Modification
Risk Factor X: Avoid Concomitant Use

Notice: Drug Interaction Categories

Risk Factor C (Monitor therapy).
Alcohol (Ethyl).	CNS Depressants can increase the CNS depressant effects of Alcohol (Ethyl).
Alizapride	CNS Depressants may increase the CNS depressant effects.
ARIPiprazole	CYP3A4 Inhibitors, Weak, may increase serum levels of ARIPiprazole. Monitoring for increased aripiprazole-pharmacologic effects is important. Aripiprazole dosage adjustments may be necessary depending on the indication and/or concomitant therapy. For more information, consult the full interaction monograph.
Botulinum Toxin-Containing Product	The adverse/toxic effects of Botulinum Toxin-Containing products may be exacerbated by centrally acting muscle relaxants. In particular, increased muscle weakness could be a possibility.
Brexanolone	CNS Depressants can increase the CNS depressant effects of Brexanolone.
Brimonidine	CNS Depressants may increase the CNS depressant effects.
Bromopride	CNS Depressants may increase the CNS depressant effects.
Cannabidiol	CNS Depressants may increase the CNS depressant effects.
Cannabis	CNS Depressants may increase the CNS depressant effects.
Chlorphenesin Carbamate	CNS Depressants may have an adverse/toxic effect that can be exacerbated by them.
CNS Depressants	Can increase the toxic/adverse effects of CNS Depressants.
Dimethindene (Topical)	CNS Depressants may increase the CNS depressant effects.
Disulfiram	Might increase serum Chlorzoxazone concentrations.
Dofetilide	Dofetilide may be increased by CYP3A4 inhibitors (Weak).
Doxylamine	CNS Depressants may have a greater depressant effect on the brain. Management: Diclegis (doxylamine/ pyridoxine), which is intended for pregnancy, clearly states that it should not be used with any other CNS depressants.
Dronabinol	CNS Depressants may increase the CNS depressant effects.
Esketamine	CNS Depressants may increase the CNS depressant effects.
Flibanserin	Flibanserin may be increased by CYP3A4 inhibitors (Weak).
HydrOXYzine	CNS Depressants may increase the CNS depressant effects.
Isoniazid	Could increase serum levels of Chlorzoxazone. Isoniazid can decrease the serum level of Chlorzoxazone. It may also decrease the baseline chlorzoxazone concentrations after discontinuation of isoniazid.
Kava Kava	CNS Depressants may have an adverse/toxic effect that can be exacerbated by them.
Lofexidine	CNS Depressants may have a greater depressant effect on the brain. Management: Separate drug interaction monographs are available for drugs listed as an exception to this monograph.
Magnesium Sulfate	CNS Depressants may increase the CNS depressant effects.
MetyroSINE	MetyroSINE may have a sedative effect that can be enhanced by CNS depressants.
Minocycline	CNS Depressants may increase the CNS depressant effects.
Mirtazapine	CNS Depressants can increase the CNS depressant effects of Mirtazapine.
Nabilone	CNS Depressants may increase the CNS depressant effects.
NiMODipine	CYP3A4 Inhibitors, Weak may increase NiMODipine serum concentrations.
Piribedil	CNS Depressants could increase the CNS depressant effects of Piribedil.
Pramipexole	Pramipexole may have a greater sedative effect if it is combined with CNS depressants.
ROPINIRole	CNS Depressants can increase the sedative effects of ROPINIRole.
Rotigotine	CNS Depressants can increase the sedative effects of Rotigotine.
Rufinamide	CNS Depressants may have an adverse/toxic effect that can be exacerbated by this. Particularly, dizziness and sleepiness may be increased.
Selective Serotonin Reuptake inhibitors	CNS Depressants can increase the toxic/adverse effects of Selective Serotonin Resuptake Inhibitors. Particularly, psychomotor impairment could be increased.
Tetrahydrocannabinol	CNS Depressants may increase the CNS depressant effects.
Tetrahydrocannabinol, and Cannabidiol	CNS Depressants may increase the CNS depressant effects.
Trimeprazine	CNS Depressants may increase the CNS depressant effects.
Risk Factor D (Consider therapy modifications)
Blonanserin	CNS Depressants can increase the CNS depressant effects of Blonanserin.
Buprenorphine	CNS Depressants can increase the CNS depressant effects of buprenorphine. Management: Reduced doses of CNS depressants should be considered and avoidance of such drugs for patients at high risk of buprenorphine self-injection/overuse. Buprenorphine patches (Butrans) should be initiated at 5 mg/hr for adults, when taken with other CNS depression drugs.
Chlormethiazole	Chlorzoxazone may have a depressant effect on the CNS. Chlormethiazole can increase Chlorzoxazone serum concentrations. When combined with chlormethiazole, reduce the dose of chlorzoxazone. If these agents are used together, monitor patients for elevated chlorzoxazone toxicities/effects (i.e. CNS depression, sedation).
Droperidol	CNS Depressants may increase the CNS depressant effects. Management: Droperidol and other CNS agents, such as opioids, may be reduced or used in combination with droperidol. Separate drug interaction monographs provide more detail on exceptions to this monograph.
Flunitrazepam	CNS Depressants can increase the CNS depressant effects of Flunitrazepam.
HYDROcodone	CNS Depressants can increase the CNS depressant effects of HYDROcodone. When possible, avoid concomitant use with hydrocodone and other CNS depressants. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
Lomitapide	Lomitapide may be increased by CYP3A4 inhibitors (Weak). Management: Patients taking lomitapide 5 mg/day can continue to take this dose. Patients who are taking lomitapide 10mg/day or more must reduce their lomitapide dosage by half. You can then adjust the lomitapide dose to 30 mg/day for adults.
Methotrimeprazine	Methotrimeprazine may have a higher CNS depressant activity than CNS Depressants. Methotrimeprazine can increase the CNS depressant effects of CNS Depressants. Management: Lower the adult dose of CNS Depressants by 50% and start concomitant methotrimeprazine treatment. After clinically proven efficacy of methotrimeprazine, further CNS depressant dose adjustments should only be made.
Opioid Agonists	CNS Depressants can increase the CNS depressant effects of Opioid Aggonists. Management: When possible, avoid concomitant use opioid agonists, benzodiazepines, or other CNS depressionants. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
OxyCODONE	CNS Depressants can increase OxyCODONE's CNS depressant effects. When possible, avoid the simultaneous use of oxycodone and other CNS depressants. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
Perampanel	CNS Depressants may have a greater CNS depressant effect. Perampanel and any other CNS depressant drug should be used in combination. Patients who take perampanel together with any other drug should not engage in complex or high-risk activities until they have had experience with the combination.
Sodium Oxybate	CNS Depressants may have a greater depressant effect if taken in combination. Management: Look for alternatives to the combination use. If you must combine use, reduce the doses of any one or more drugs. It is not recommended to combine sodium oxybate and alcohol, or any sedative hypnotics.
Suvorexant	CNS Depressants can increase the CNS depressant effects of Suvorexant. Management: Suvorexant or any other CNS depressionant can be reduced in doses. Suvorexant should not be taken with alcohol. It is also not recommended to take suvorexant along with any other drugs for insomnia.
Tapentadol	CNS Depressants may increase the CNS depressant effects. Tapentadol, benzodiazepines and other CNS depressants should be avoided when possible. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
Tolperisone	The adverse/toxic effects of centrally acting Muscle Relaxants may be increased. Monitoring: Watch for an increase in sedation or CNS effects when tolperisone is used with centrally acting muscle relaxants. If these agents are combined, you may need to reduce the dose of tolperisone.
Zolpidem	CNS Depressants can increase the CNS depressant effects of Zolpidem. Management: For men who also take CNS depressants, reduce the adult Intermezzo brand sublingual Zolpidem dose to 1.75mg. For women, no dose adjustment is advised. Avoid using CNS depressants at night; do not use alcohol.
Risk Factor X (Avoid the combination)
Azelastine - Nasal	CNS Depressants could increase the CNS depressant effects of Azelastine.
Bromperidol	CNS Depressants may increase the CNS depressant effects.
Orphenadrine	Orphenadrine may be more effective against CNS depression than other drugs.
Oxomemazine	CNS Depressants may increase the CNS depressant effects.
Paraldehyde	Paraldehyde may be enhanced by CNS depressants.
Pimozide	Pimozide may be increased by CYP3A4 inhibitors (Weak).
Thalidomide	CNS Depressants can increase Thalidomide's CNS depressant effects.

Monitoring Parameters:

Monitor for clinical features of hepatotoxicity and periodic liver function tests.

How to Administer Chlorzoxazone?

Administer the drug orally after meals.

Mechanism of action of Chlorzoxazone:

It acts centrally on the spinal cord and subcortical brain areas.
It works by inhibiting the polysynaptic reflexes that are involved in skeletal muscle contractions and is used to treat muscle spasms.

The Beginning of ActionIt takes less than an hour and can last up to six hours.

It happens quicklyIntakeAndMetabolizedThe liver is the main source of this substance.

It has a half life of approximately one hour, and peak plasma concentration takes 1-2 hours. It is excreted through urine

International Brands of Chlorzoxazone: