Muscle relaxers Other information





Drug Dosage forms Dosing Other
Baclofen Tablet
  • 10 mg
  • 20 mg
Adults
Muscle spasticity
  • Starting:
    • 5 mg three times a day for 3 days, then
    • 10 mg three times a day for 3 days, then
    • 15 mg three times a day for 3 days, then
    • 20 mg three times a day for 3 days

  • Maximum: 20 mg four times a day
Mechanism of action
  • Not completely understood
  • Inhibits reflexes at the spinal level possibly by hyperpolarization of afferent terminals
  • Baclofen is also a GABA analog, and this may contribute to its effects

Price
  • Generic (90 tablets) - $

Drug Dosage forms Dosing Other
Carisoprodol

(Soma®)
Tablet
  • 250 mg
  • 350 mg
Adults
Musculoskeletal aches and pains
  • 250 - 350 mg three times a day and at bedtime as needed
  • Maximum recommended duration of use is 2 - 3 weeks
Mechanism of action
  • Not completely understood
  • In animal studies, muscle relaxation induced by carisoprodol is associated with altered interneuronal activity in the spinal cord and in the descending reticular formation of the brain

Other
  • Carisoprodol is an FDA Schedule IV medication
  • Carisoprodol is metabolized to the active metabolite meprobamate. Meprobamate is a controlled substance used to treat anxiety.
  • Carisoprodol is a sensitive CYP2C19 substrate. Use caution with CYP2C19 inducers and inhibitors.

Price
  • Generic (30 tablets) - $
Tablet - Soma® compound
  • Carisoprodol : aspirin
    • 200 mg : 325 mg
Adults
Musculoskeletal aches and pains
  • 1 - 2 tablets four times a day as needed
  • Maximum daily dose is 8 tablets
  • Maximum recommended duration of use is 2 - 3 weeks
Mechanism of action - carisoprodol
  • Not completely understood
  • In animal studies, muscle relaxation induced by carisoprodol is associated with altered interneuronal activity in the spinal cord and in the descending reticular formation of the brain

Other
  • Soma compound is an FDA Schedule IV medication
  • Carisoprodol is metabolized to the active metabolite meprobamate. Meprobamate is a controlled substance used to treat anxiety.
  • Carisoprodol is a sensitive CYP2C19 substrate. Use caution with CYP2C19 inducers and inhibitors.
  • See also aspirin

Price
  • Generic (30 tablets) - $$
Tablet
  • Soma® compound with codeine
    • Codeine 16 mg, aspirin 325 mg, carisoprodol 200 mg per tablet
Adults
Musculoskeletal aches and pains
  • 1 - 2 tablets four times daily as needed
Mechanism of action - carisoprodol
  • Not completely understood
  • In animal studies, muscle relaxation induced by carisoprodol is associated with altered interneuronal activity in the spinal cord and in the descending reticular formation of the brain

Other
  • Soma compound with codeine is an FDA Schedule III medication
  • Carisoprodol is metabolized to the active metabolite meprobamate. Meprobamate is a controlled substance used to treat anxiety.
  • Carisoprodol is a sensitive CYP2C19 substrate. Use caution with CYP2C19 inducers and inhibitors.
  • See also codeine and aspirin

Price
  • Generic (30 tablets) - $$

Drug Dosage forms Dosing Other
Chlorzoxazone

(Parafon Forte® DSC)
Tablet - Parafon Forte® DSC
  • 500 mg
Adults
Musculoskeletal aches and pains
  • 1 tablet three to four times a day as needed
  • May increase to 1 ½ tablets (750 mg) three to four times a day if necessary
Mechanism of action
  • Chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex arcs involved in producing and maintaining skeletal muscle spasm of varied etiology

Price
  • Generic (30 tablets) - $

Drug Dosage forms Dosing Other
Cyclobenzaprine

(Flexeril®)
Tablet
  • 5 mg
  • 7.5 mg
  • 10 mg
Adults
Muscle spasm associated with acute musculoskeletal conditions
  • Starting: 5 mg three times a day as needed
  • Maintenance: 5 - 10 mg three times a day as needed
  • Maximum recommended duration of use is 2 - 3 weeks
Mechanism of action
  • Cyclobenzaprine acts primarily within the central nervous system at the brain stem as opposed to the spinal cord level, although an overlapping action on the latter may contribute to its overall skeletal muscle relaxant activity
  • Evidence suggests that the net effect of cyclobenzaprine is a reduction of tonic somatic motor activity, influencing both gamma (γ) and alpha (α) motor systems

Other
  • Cyclobenzaprine is structurally related to the tricyclic antidepressant amitriptyline

Price
  • Generic (30 tablets, 5 and 10 mg) - $
  • Generic (30 tablets, 7.5 mg) - $$$
Capsule - extended-release
  • Amrix®
    • 15 mg
    • 30 mg
Adults
Muscle spasm associated with acute musculoskeletal conditions
  • Starting: 15 mg once daily as needed
  • Maintenance: 15 - 30 mg once daily as needed
  • Maximum recommended duration of use is 2 - 3 weeks
  • Amrix capsules may be opened and sprinkled on applesauce. Contents should be swallowed immediately without chewing.
Mechanism of action
  • Cyclobenzaprine acts primarily within the central nervous system at the brain stem as opposed to the spinal cord level, although an overlapping action on the latter may contribute to its overall skeletal muscle relaxant activity
  • Evidence suggests that the net effect of cyclobenzaprine is a reduction of tonic somatic motor activity, influencing both gamma (γ) and alpha (α) motor systems

Other
  • Cyclobenzaprine is structurally related to the tricyclic antidepressant amitriptyline

Price
  • 30 capsules - $$$$
  • No generic available

Drug Dosage forms Dosing Other
Metaxalone

(Skelaxin®)
Tablet
  • 400 mg
  • 800 mg
Adults
Musculoskeletal aches and pains
  • 800 mg three to four times a day as needed
Mechanism of action
  • Not completely understood
  • Action may be due to general central nervous system depression
  • Metaxalone has no direct action on the contractile mechanism of striated muscle, the motor end plate, or the nerve fiber

Other
  • Taking metaxalone with a high fat meal greatly increase its absorption and may increase side effects

Price
  • Generic (30 tablets) - $$$-$$$$


Drug Dosage forms Dosing Other
Methocarbamol

(Robaxin®)
Tablet
  • 500 mg
  • 750 mg
Adults
Musculoskeletal aches and pains
  • Methocarbamol 500 mg
    • Starting: 1500 mg four times a day
    • Maintenance: 1000 mg four times a day

  • Methocarbamol 750 mg
    • Starting: 1500 mg four times a day
    • Maintenance: 750 mg every 4 hours or 1500 mg three times a day

  • 6000 mg/day is recommended for the first 48 to 72 hours of treatment. (For severe conditions 8000 mg/day may be administered)
  • Thereafter, the dosage can usually be reduced to approximately 4000 mg/day
Mechanism of action
  • Not completely understood
  • Effect may be due to general central nervous system (CNS) depression
  • Methocarbamol has no direct action on the contractile mechanism of striated muscle, the motor end plate or the nerve fiber

Price
  • Generic (90 tablets) - $

Drug Dosage forms Dosing Other
Orphenadrine

(Norflex®)
Extended-release tablet - Norflex®
  • 100 mg
Adults
Musculoskeletal aches and pains
  • 1 tablet twice daily as needed
Mechanism of action
  • Not completely understood
  • Mechanism may be related to analgesic properties and sedating effects
  • Does not directly relax tense skeletal muscles

Other
  • Orphenadrine has anticholinergic activity
  • Orphenadrine is structurally related to the antihistamine diphenhydramine (Benadryl®)

Price
  • Generic (60 tablets) - $
Tablet - Norgesic®
  • Orphenadrine : aspirin : caffeine
    • 25 mg : 385 mg : 30 mg
    • 50 mg : 770 mg : 60 mg
Adults
Musculoskeletal aches and pains
  • 25/385/30: 1 - 2 tablets three to four times daily as needed
  • 50/770/60: ½ - 1 tablet three to four times daily as needed
Mechanism of action
  • Not completely understood
  • Mechanism may be related to analgesic properties and sedating effects
  • Does not directly relax tense skeletal muscles

Other
Price
  • Generic (60 tablets) - $$


Drug Dosage forms Dosing Other
Tizanidine

(Zanaflex®)
Tablet
  • 2 mg
  • 4 mg

Capsule
  • 2 mg
  • 4 mg
  • 6 mg
Adults
Spasticity
  • Starting: 2 mg every 6 - 8 hours as needed. Do not exceed 3 doses in 24 hours
  • Increase by 2 - 4 mg/dose at intervals of 1 - 4 days
  • Maximum daily dose is 36 mg
  • Single doses > 16 mg have not been studied
  • When discontinuing after chronic therapy (20 - 36 mg/day for ≥ 9 weeks), dose should be tapered gradually (2 - 4 mg per day) to prevent withdrawal
Mechanism of action
  • Tizanidine is a central alpha-2-adrenergic receptor agonist and presumably reduces spasticity by increasing presynaptic inhibition of motor neurons

Other
  • Tablets and capsules have equivalent absorption when fasting. Under fed conditions, the tablets have increased absorption and the capsules have delayed absorption. The extent of absorption is increased by food for both the tablet and capsule.
  • Tizanidine is a CYP1A2 sensitive substrate. DO NOT USE with strong CYP1A2 inhibitors.
  • Check LFTs at baseline and 1 month after maximum dose is achieved

Price
  • Generic (4 mg, 90 tablets) - $
  • Generic (4 mg, 90 capsules) - $$$-$$$$




Muscle relaxer side effects
Baclofen
  • NOTE: strength of association not well-defined
  • Drowsiness, dizziness, weakness, fatigue
  • Confusion
  • Hypotension
  • Nausea
  • Constipation
  • Urinary frequency

Carisoprodol (Soma®)
  • NOTE: P = % of patients on placebo who experienced side effect. Information is for 350mg dose of carisoprodol
  • Drowsiness - 17%, P - 6%
  • Dizziness - 7%, P - 2%
  • Headache - 3%, P - 2%

Chlorzoxazone (Parafon Forte® DSC)
  • NOTE: strength of association not well-defined
  • Drowsiness, dizziness, lightheadedness
  • Malaise
  • Overstimulation
  • Discoloration of the urine - rare side effect caused by phenolic metabolite of chlorzoxazone

Cyclobenzaprine (Flexeril®)
  • NOTE: P = % of patients on placebo who experienced side effect. Information is for 10 mg dose of cyclobenzaprine
  • Drowsiness - 38%, P - 10%
  • Dry mouth - 32%, P - 7%
  • Dizziness - 11%
  • Fatigue - 6%, P - 3%

Metaxalone (Skelaxin®)
  • NOTE: strength of association not well-defined
  • Drowsiness, dizziness
  • Headache
  • Nervousness or irritability
  • Nausea, vomiting, gastrointestinal upset

Methocarbamol (Robaxin®)
  • Side effects of methocarbamol are not well-defined
  • In general, CNS depressive effects (ex. drowsiness, somnolence, lightheadedness) may be seen

Orphenadrine (Norflex®)
  • Side effects are not well-defined
  • Anticholinergic side effects - orphenadrine has anticholinergic activity and may cause anticholinergic side effects
  • Antihistaminergic side effects - orphenadrine is structurally related to the antihistamine diphenhydramine, and it may cause antihistaminergic side effects (ex. dry mouth, sedation, etc.)

Tizanidine (Zanaflex®)
  • NOTE: P = % of patients on placebo who experienced side effect
  • Dry mouth - 49%, P - 10%
  • Somnolence - 48%, P - 10%
  • Weakness/tired - 41%, P - 16%
  • Dizziness - 16%, P - 4%
  • Hypotension (single dose, 8 mg) - 16%, P - 0%
  • Hypotension (single dose, 16 mg) - 33%, P - 0%
  • Bradycardia (single dose, 16 mg) - 10%, P - 0%
  • Liver test abnormalities - 6%, P - 2%


Muscle relaxer precautions
All muscle relaxers
  • Decreased alertness - all muscle relaxers can depress CNS activity and may impair the ability to operate motor vehicles and other dangerous machinery

Baclofen
  • Abrupt withdrawal - hallucinations and seizures have been reported. Reduce dose slowly when discontinuing.
  • Seizure disorders - baclofen may lower the seizure threshold and increase the risk of seizures
  • Spasticity - baclofen should be used with caution where spasticity is utilized to sustain upright posture and balance in locomotion or whenever spasticity is utilized to obtain increased function
  • Stroke - baclofen has not been shown to benefit patients with stroke. Patients with stroke may not tolerate baclofen well.
  • Pregnancy - risks are uncertain. Use only when benefit justifies potential harm to fetus.
  • Ovarian cysts - baclofen may increase the incidence of ovarian cysts
  • Kidney disease - clearance is reduced. Use caution.

Carisoprodol (Soma®)
  • Porphyria - DO NOT USE
  • Carbamate sensitivity - DO NOT USE
  • Drug abuse and addiction - carisoprodol is both psychologically and physically addictive. Use caution in susceptible patients.
  • Abrupt withdrawal - abrupt withdrawal after prolonged use may cause symptoms including insomnia, vomiting, abdominal cramps, headache, tremors, muscle twitching, ataxia, hallucinations, and psychosis
  • Seizure disorders - carisoprodol may lower the seizure threshold and increase the risk of seizure
  • CYP2C19 poor metabolizers - CYP2C19 metabolizes carisoprodol to meprobamate, an active metabolite. CYP2C19 poor metabolizers may have increased exposure to carisoprodol and decreased exposure to meprobamate. The impact of these exposure changes is unknown. Use caution.

Chlorzoxazone (Parafon Forte® DSC)
  • Liver toxicity - rare cases of liver toxicity have been reported in patients taking chlorzoxazone. Discontinue drug if liver enzyme elevations occur.

Cyclobenzaprine (Flexeril®)
  • Heart conditions - the cyclobenzaprine PI states that it is contraindicated in "acute recovery phase of myocardial infarction, and patients with arrhythmias, heart block or conduction disturbances, or congestive heart failure." This warning likely arises from the fact that cyclobenzaprine is structurally related to tricyclic antidepressants. In the medical literature, we only found one article pertaining to cyclobenzaprine and heart arrhythmias. The article found no evidence for an association between the two. [2]
  • Anticholinergic side effects - cyclobenzaprine is structurally related to tricyclic antidepressants. Because of this, it may have similar anticholinergic side effects.
  • Elderly patients - clearance of cyclobenzaprine is decreased in elderly patients. Use starting dose of 5 mg. Titrate slowly.
  • Liver disease
    • Immediate-release: mild - start with 5 mg dose, titrate slowly; moderate-to-severe - not recommended
    • Extended-release product (Amrix®): not recommended in liver disease
  • Hyperthyroidism - listed as contraindication in PI. A search of medical literature found no information.

Metaxalone (Skelaxin®)
  • Anemia - the metaxalone PI states that it is contraindicated in "drug induced, hemolytic, or other anemias." A search of the medical literature found no information.
  • Food effects - taking metaxalone with a high fat meal greatly increases its absorption. Side effects may be increased.
  • Elderly patients - elderly patients may be at increased risk of side effects. Lower doses may be appropriate.
  • Serotonin syndrome - case reports of serotonin syndrome have occurred in overdose [3,4]
  • Kidney disease - contraindicated in significant kidney disease
  • Liver disease - contraindicated in significant liver disease

Methocarbamol (Robaxin®)
  • Myasthenia gravis - methocarbamol may inhibit the effect of anticholinesterase agents (ex. pyridostigmine) used to treat myasthenia gravis. Use caution.
  • Pheochromocytoma - methocarbamol may interfere with screening tests for pheochromocytoma including urinary vanillylmandelic acid (Gitlow method)
  • Elderly - clearance is decreased. Use caution.
  • Kidney disease - clearance is decreased. Use caution.
  • Liver disease - clearance is decreased. Use caution.

Orphenadrine (Norflex®)
  • Anticholinergic side effects - orphenadrine has anticholinergic activity. Use caution or avoid in patients with glaucoma, bowel obstruction, urinary hesitancy, and/or urinary obstruction.
  • Myasthenia gravis - orphenadrine has anticholinergic activity. Do not use in patients with myasthenia gravis.

Tizanidine (Zanaflex®)
  • Decreased blood pressure - tizanidine is an alpha-2 agonist, and it may lower blood pressure in some patients
  • Liver toxicity - tizanidine may cause liver injury in some patients. LFTs should be checked at baseline and 1 month after maximum dose is achieved.
  • Withdrawal reactions - withdrawal reactions including hypertension, tachycardia, and hypertonia may occur. When discontinuing after chronic therapy (20 - 36 mg/day for ≥ 9 weeks), dose should be tapered gradually (2 - 4 mg per day) to prevent withdrawal.
  • Hallucinations - some patients have reported hallucinations while taking tizanidine
  • Anaphylaxis - anaphylaxis and angioedema have been reported
  • Kidney disease - clearance is reduced. Use caution in patients with CrCl < 25 ml/min. During titration, increase dosage as opposed to dose frequency.
  • Liver disease - clearance is decreased. Not recommended.


Muscle relaxer drug interactions
All muscle relaxers
  • Central Nervous System (CNS) depressants - muscle relaxers may potentiate the effects of other CNS depressants (e.g. opiates, benzodiazepines, alcohol, anticonvulsants, antihistamines, etc.). Risk for adverse events may be increased. Use caution when combining.

Carisoprodol (Soma®)
  • CYP2C19 inhibitors and inducers - CYP2C19 metabolizes carisoprodol to meprobamate, an active metabolite. CYP2C19 inducers may increase exposure to meprobamate and decrease exposure to carisoprodol. CYP2C19 inhibitors may decrease exposure to meprobamate and increase exposure to carisoprodol. The impact of these exposure changes is unknown. Use caution.

Cyclobenzaprine (Flexeril®)
  • MAO inhibitors - DO NOT COMBINE. After discontinuing MAO inhibitor, wait 14 days before starting cyclobenzaprine.
  • Serotonergic drugs - cyclobenzaprine is structurally related to tricyclic antidepressants. Concomitant use with other serotonergic drugs may increase the risk of serotonin syndrome.
  • Anticholinergic medications - cyclobenzaprine is structurally related to tricyclic antidepressants. Because of this, it may potentiate the anticholinergic side effects of other anticholinergic medications.
  • Tramadol (Ultram®) - cyclobenzaprine may potentiate seizure risk in patients taking tramadol
  • Alpha-2 agonists - cyclobenzaprine is structurally related to tricyclic antidepressants. Because of this, it may inhibit the blood pressure-lowering effect of alpha-2 agonists.

Metaxalone (Skelaxin®)
  • Serotonergic drugs - case reports of serotonin syndrome have been reported in metaxalone overdose with concomitant SSRI use [3]

Methocarbamol (Robaxin®)
  • Pyridostigmine (Mestinon®) - methocarbamol may inhibit the effect of pyridostigmine. Use with caution in patients with myasthenia gravis who are receiving anticholinesterase agents.

Orphenadrine (Norflex®)
  • Anticholinergic medications - orphenadrine has anticholinergic activity, and it may potentiate the anticholinergic effects of other drugs
  • Antihistamines - orphenadrine is structurally related to diphenhydramine, and it may potentiate the effects of other antihistamines

Tizanidine (Zanaflex®)
  • CYP1A2 inhibitors
    • CYP1A2 strong inhibitors - DO NOT USE with CYP1A2 strong inhibitors (e.g. fluvoxamine, ciprofloxacin)
    • CYP1A2 moderate and weak inhibitors - CYP1A2 moderate and weak inhibitors may increase the risk of side effects with tizanidine. Use caution and start with 2 mg dose.
  • Oral contraceptives - concomitant use of tizanidine with oral contraceptives (moderate CYP1A2 inhibitors) is not recommended. If used together, use caution and start with 2 mg dose.
  • Alpha-2 agonists - tizanidine is an alpha-2 agonist and should not be combined with other alpha-2 agonists (e.g. clonidine)
  • Alcohol - alcohol increases the absorption of tizanidine