MUSCLE RELAXERS








Baclofen | Ozobax® | Fleqsuvy® | Lyvispah®

Dosage forms

Tablet
  • 10 mg
  • 20 mg
Solution (Ozobax®)
  • 5 mg/5 ml (1 mg/ml)
  • Comes in 473 ml bottle
  • Keep refrigerated
Suspension (Fleqsuvy®)
  • 25 mg/5 ml (5 mg/ml)
  • Comes in 120 and 300 ml bottles
  • Store at room temp
Granules (Lyvispah®)
  • 5 mg
  • 10 mg
  • 20 mg
  • Comes in carton with 90 packets

Dosing

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
Kidney disease
  • Baclofen is primarily excreted unchanged in the urine. Kidney disease increases exposure and caution should be used.

Generic / Price

  • Tablet (90 tablets) - YES/$
  • Ozobax Solution (473 ml) - NO/$$$$
  • Fleqsuvy Suspension (120 ml) - NO/$$$$
  • Lyvispah Granules (90 packets) - NO/$$$$

Efficacy

Low back pain Alcohol abuse

Mechanism of action

  • Mechanism of action is not entirely understood. Baclofen inhibits reflexes at the spinal level, possibly by hyperpolarization of afferent terminals. It is also a GABA analog, which may contribute to its effects.

Side effects

NOTE: no placebo comparator is reported, so strength of association is not well-defined

Side effect % of patients
Drowsiness 10 - 63%
Dizziness 5 - 15%
Weakness 5 - 15%
Nausea 4 - 12%
Confusion 1 - 11%
Hypotension 0 - 9%
Headache 4 - 8%
Insomnia 2 - 7%
Constipation 2 - 6%
Urinary Frequency 2 - 6%
Fatigue 2 - 4%

Drug interactions

  • 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.

Contraindications / Precautions

  • Decreased alertness - muscle relaxers can depress CNS activity and impair the ability to operate motor vehicles and other dangerous machinery
  • 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.
  • Encephalopathy - an observational study published in 2019 found that the risk of encephalopathy was increased in older patients (≥ 66 years) with chronic kidney disease (GFR < 60 ml/min) who initiated baclofen at doses ≥ 20 mg/day. [PMID 31705755]
  • 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 - baclofen is primarily excreted unchanged in the urine. Kidney disease increases exposure and caution should be used.

Carisoprodol (Soma®)

Dosage forms

Tablet
  • 250 mg
  • 350 mg

Dosing

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
  • Carisoprodol is an FDA Schedule IV medication
CYP2C19 inhibitors, inducers, and poor metabolizers
  • Carisoprodol is metabolized by CYP2C19 to meprobamate, an active metabolite that is also a controlled substance used to treat anxiety
  • CYP2C19 inhibitors may decrease meprobamate exposure and increase carisoprodol exposure, and CYP2C19 inducers may have the opposite effect. CYP2C19 poor metabolizers also have increased carisoprodol exposure and decreased meprobamate exposure. The clinical significance of these alterations in exposure is unknown, and caution should be used.
Kidney disease
  • Carisoprodol is excreted by the kidneys. Kidney disease likely increases exposure and caution should be used.
Liver disease
  • Carisoprodol is metabolized by the liver. Liver disease likely increases exposure and caution should be used.

Mechanism of action

  • The mechanism of carisoprodol is 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.

Generic / Price

- YES/$ (90 tablets)

Side effects



Side effect Carisoprodol 350 mg
3 times a day		 Placebo
Drowsiness 17% 6%
Dizziness 7% 2%
Headache 3% 2%

Drug interactions

  • Central nervous system (CNS) depressants - muscle relaxers can potentiate the effects of CNS depressants (e.g. opiates, benzodiazepines, alcohol, anticonvulsants, antihistamines) and increase the risk for adverse events. Use caution when combining.
  • CYP2C19 inhibitors and inducers - carisoprodol is metabolized by CYP2C19 to meprobamate, an active metabolite that is also a controlled substance used to treat anxiety. CYP2C19 inhibitors may decrease meprobamate exposure and increase carisoprodol exposure, and CYP2C19 inducers may have the opposite effect. The clinical significance of these alterations in exposure is unknown, and caution should be used.

Contraindications / Precautions

  • Porphyria - DO NOT USE
  • Carbamate sensitivity - DO NOT USE. Carisoprodol is metabolized to meprobamate, which is a carbamate.
  • Decreased alertness - muscle relaxers can depress CNS activity and impair the ability to operate motor vehicles and other dangerous machinery
  • 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 - carisoprodol is metabolized by CYP2C19 to meprobamate, an active metabolite that is also a controlled substance used to treat anxiety. CYP2C19 poor metabolizers have increased carisoprodol exposure and decreased meprobamate exposure. The clinical significance of these alterations in exposure is unknown, and caution should be used.
  • Kidney disease - carisoprodol is excreted by the kidneys. Kidney disease likely increases exposure and caution should be used.
  • Liver disease - carisoprodol is metabolized by the liver. Liver disease likely increases exposure and caution should be used.

Carisoprodol + aspirin (Soma® compound)

Dosage forms

Tablet
  • Carisoprodol 200 mg and aspirin 325 mg per tablet

Dosing

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
  • See carisoprodol and aspirin for prescribing information
  • Soma compound is an FDA Schedule IV medication

Generic / Price

- YES/$ (30 tablets)

Carisoprodol + aspirin + codeine (Soma® compound with codeine)

Dosage forms

Tablet
  • Codeine 16 mg, aspirin 325 mg, carisoprodol 200 mg per tablet

Dosing

Musculoskeletal aches and pains
  • 1 - 2 tablets four times daily as needed
  • See carisoprodol, aspirin, and codeine for prescribing information
  • Soma compound with codeine is an FDA Schedule III medication

Generic / Price

- YES/$ (30 tablets)

Chlorzoxazone (Parafon Forte® DSC)

Dosage forms

Tablet
  • 250 mg
  • 375 mg
  • 500 mg
  • 750 mg

Dosing

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

Generic / Price

  • 250 mg (40 tablets) - YES/$$$$
  • 375 mg (40 tablets) - YES/$
  • 500 mg (40 tablets) - YES/$
  • 750 mg (40 tablets) - YES/$$$$

Side effects

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

Drug interactions

  • Central nervous system (CNS) depressants - muscle relaxers can potentiate the effects of CNS depressants (e.g. opiates, benzodiazepines, alcohol, anticonvulsants, antihistamines) and increase the risk for adverse events. Use caution when combining.

Contraindications / Precautions

  • Decreased alertness - muscle relaxers can depress CNS activity and impair the ability to operate motor vehicles and other dangerous machinery
  • Liver toxicity - rare cases of liver toxicity have been reported in patients taking chlorzoxazone. Discontinue drug if liver enzyme elevations occur.

Cyclobenzaprine (Flexeril®)

Dosage forms

Tablet
  • 5 mg
  • 7.5 mg
  • 10 mg

Dosing

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
  • Elderly patients: clearance is decreased. Use starting dose of 5 mg and titrate slowly.
  • Maximum recommended duration of use is 2 - 3 weeks
Liver disease
  • Mild (Child-Pugh A): start with 5 mg dose and titrate slowly
  • Moderate-severe (Child-Pugh B/C): not recommended

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
  • Cyclobenzaprine is structurally related to the tricyclic antidepressant amitriptyline

Generic / Price

- YES/$

Side effects



Side effect Cyclobenzaprine 10 mg Placebo
Drowsiness 38% 10%
Dry mouth 32% 7%
Fatigue 6% 3%
Headache 5% 8%

Drug interactions

  • MAO inhibitors - DO NOT COMBINE. MAO inhibitors and cyclobenzaprine should not be taken within 14 days of each other.
  • Serotonergic drugs - cyclobenzaprine is structurally related to tricyclic antidepressants. Concomitant use with other serotonergic drugs may increase the risk of serotonin syndrome.
  • Central nervous system (CNS) depressants - muscle relaxers can potentiate the effects of CNS depressants (e.g. opiates, benzodiazepines, alcohol, anticonvulsants, antihistamines) and increase the risk for adverse events. Use caution when combining.
  • Anticholinergic medications - cyclobenzaprine has anticholinergic properties and can potentiate the effects of other anticholinergic medications
  • Tramadol (Ultram®) - cyclobenzaprine may potentiate the seizure-inducing effects of tramadol
  • Alpha-2 agonists - cyclobenzaprine is structurally related to tricyclic antidepressants, which can inhibit the blood pressure-lowering effect of alpha-2 agonists

Contraindications / Precautions

  • Hyperthyroidism - DO NOT USE
  • Decreased alertness - muscle relaxers can depress CNS activity and impair the ability to operate motor vehicles and other dangerous machinery
  • Heart conditions - cyclobenzaprine is structurally related to tricyclic antidepressants, which can adversely affect cardiac conduction. Cyclobenzaprine should not be used in patients with acute myocardial infarction, arrhythmias, congestive heart failure, heart block, or conduction disturbances.
  • Anticholinergic side effects - cyclobenzaprine has anticholinergic properties
  • Elderly patients - clearance is decreased in elderly patients. Use starting dose of 5 mg and titrate slowly.
  • Liver disease
    • Mild (Child-Pugh A): start with 5 mg dose and titrate slowly
    • Moderate-severe (Child-Pugh B/C): not recommended

Cyclobenzaprine (Amrix®)

Dosage forms

Capsule, extended-release
  • 15 mg
  • 30 mg

Dosing

Muscle spasm associated with acute musculoskeletal conditions
  • Starting: 15 mg once daily as needed
  • Maintenance: 15 - 30 mg once daily as needed
  • Elderly patients: not recommended
  • Liver disease: not recommended
  • 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
  • Cyclobenzaprine is structurally related to the tricyclic antidepressant amitriptyline

Generic / Price

- YES/$$-$$$$ (#30)

Side effects



Side effect Amrix 30 mg once daily Placebo
Dry mouth 14% 2%
Dizziness 6% 2%
Dyspepsia 4% 1%
Fatigue 3% 2%
Constipation 3% 0%
Nausea 3% 1%
Somnolence 2% 0%

Drug interactions

  • MAO inhibitors - DO NOT COMBINE. MAO inhibitors and cyclobenzaprine should not be taken within 14 days of each other.
  • Serotonergic drugs - cyclobenzaprine is structurally related to tricyclic antidepressants. Concomitant use with other serotonergic drugs may increase the risk of serotonin syndrome.
  • Central nervous system (CNS) depressants - muscle relaxers can potentiate the effects of CNS depressants (e.g. opiates, benzodiazepines, alcohol, anticonvulsants, antihistamines) and increase the risk for adverse events. Use caution when combining.
  • Anticholinergic medications - cyclobenzaprine has anticholinergic properties and can potentiate the effects of other anticholinergic medications
  • Tramadol (Ultram®) - cyclobenzaprine may potentiate the seizure-inducing effects of tramadol
  • Alpha-2 agonists - cyclobenzaprine is structurally related to tricyclic antidepressants, which can inhibit the blood pressure-lowering effect of alpha-2 agonists

Contraindications / Precautions

  • Elderly patients (≥ 65 years) - DO NOT USE. Plasma levels of Amrix are increased by 40% and half-life is increased by 56% in elderly patients.
  • Hyperthyroidism - DO NOT USE
  • Decreased alertness - muscle relaxers can depress CNS activity and impair the ability to operate motor vehicles and other dangerous machinery
  • Heart conditions - cyclobenzaprine is structurally related to tricyclic antidepressants, which can adversely affect cardiac conduction. Cyclobenzaprine should not be used in patients with acute myocardial infarction, arrhythmias, congestive heart failure, heart block, or conduction disturbances.
  • Anticholinergic side effects - cyclobenzaprine has anticholinergic properties
  • Liver disease - not recommended in patients with any degree of hepatic impairment

Metaxalone (Skelaxin®)

Dosage forms

Tablet
  • 400 mg
  • 800 mg

Dosing

Musculoskeletal aches and pains
  • Dosing: 800 mg three to four times a day as needed
  • Elderly: use lower doses. Risk of adverse effects is increased.
  • Taking metaxalone with a high-fat meal enhances its absorption, possibly increasing the risk of side effects
Kidney disease
  • Has not been studied. Use caution and do not give to patients with significant impairment.
Liver disease
  • Has not been studied. Use caution and do not give to patients with significant impairment.

Mechanism of action

  • The mechanism of action of metaxalone in humans has not been established, but may be due to general central nervous system (CNS) depression. Metaxalone has no direct action on the contractile mechanism of striated muscle, the motor end plate, or the nerve fiber.

Generic / Price

- YES/$ (30 tablets)

Efficacy

Low back pain

Side effects

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

Drug interactions

  • Central nervous system (CNS) depressants - muscle relaxers can potentiate the effects of CNS depressants (e.g. opiates, benzodiazepines, alcohol, anticonvulsants, antihistamines) and increase the risk for adverse events. Use caution when combining.
  • Serotonergic drugs - metaxalone has serotonergic activity, and cases of serotonin syndrome have been reported in patients receiving other serotonergic drugs with metaxalone. Use caution when combining.

Contraindications / Precautions

  • Anemia - metaxalone is contraindicated in patients with tendency to drug-induced, hemolytic, or other anemias
  • Decreased alertness - muscle relaxers can depress CNS activity and impair the ability to operate motor vehicles and other dangerous machinery
  • Food effects - taking metaxalone with a high-fat meal enhances its absorption, possibly increasing the risk of side effects
  • Elderly patients - elderly patients may be at increased risk of side effects, and lower doses may be appropriate
  • Serotonin syndrome - metaxalone has serotonergic activity, and cases of serotonin syndrome have been reported in patients receiving other serotonergic drugs with metaxalone. Serotonin syndrome has also occurred in patients taking higher doses of metaxalone than what is recommended. Use caution in susceptible patients.
  • Kidney disease - has not been studied. Use caution and do not give to patients with significant impairment.
  • Liver disease - has not been studied. Use caution and do not give to patients with significant impairment.

Methocarbamol (Robaxin®)

Dosage forms

Tablet
  • 500 mg
  • 750 mg

Dosing

Musculoskeletal aches and pains
  • Methocarbamol 500 mg
    • Starting: 1500 mg four times a day
    • Maintenance: 1000 mg four 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
  • 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
Kidney disease
  • Exposure is increased. Use caution.
Liver disease
  • Exposure is increased. Use caution.

Mechanism of action

  • The mechanism of action of methocarbamol in humans has not been established, but may be due to general central nervous system (CNS) depression. It has no direct action on the contractile mechanism of striated muscle, the motor end plate or the nerve fiber.

Efficacy

Low back pain

Generic / Price

- YES/$ (90 tablets)

Side effects

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

Drug interactions

  • Central nervous system (CNS) depressants - muscle relaxers can potentiate the effects of CNS depressants (e.g. opiates, benzodiazepines, alcohol, anticonvulsants, antihistamines) and increase the risk for adverse events. Use caution when combining.
  • Pyridostigmine (Mestinon®) - methocarbamol may inhibit the effect of pyridostigmine. Use with caution in patients with myasthenia gravis who are receiving anticholinesterase agents.

Contraindications / Precautions

  • Decreased alertness - muscle relaxers can depress CNS activity and impair the ability to operate motor vehicles and other dangerous machinery
  • 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 - exposure is increased. Use caution.
  • Liver disease - exposure is increased. Use caution.

Orphenadrine (Norflex®)

Dosage forms

Tablet, extended-release
  • 100 mg

Dosing

Musculoskeletal aches and pains
  • 1 tablet twice daily as needed

Mechanism of action

  • The mode of therapeutic action has not been clearly identified, but may be related to its analgesic properties. Orphenadrine citrate does not directly relax tense skeletal muscles in man.

Efficacy

Low back pain

Generic / Price

- YES/$ (60 tablets)

Side effects

  • The incidence of side effects with orphenadrine is not well-defined
  • Anticholinergic side effects - orphenadrine has anticholinergic activity
  • Antihistaminergic side effects - orphenadrine is structurally related to the antihistamine diphenhydramine and may cause similar side effects (e.g. dry mouth, sedation, constipation)

Drug interactions

  • Central nervous system (CNS) depressants - muscle relaxers can potentiate the effects of CNS depressants (e.g. opiates, benzodiazepines, alcohol, anticonvulsants, antihistamines) and increase the risk for adverse events. Use caution when combining.
  • Anticholinergic medications - orphenadrine has anticholinergic activity and may potentiate the effects of other anticholinergics
  • Antihistamines - orphenadrine is structurally related to diphenhydramine and may potentiate the effects of antihistamines

Contraindications / Precautions

  • Myasthenia gravis - DO NOT USE. Orphenadrine has anticholinergic activity and should not be used in patients with myasthenia gravis
  • Decreased alertness - muscle relaxers can depress CNS activity and impair the ability to operate motor vehicles and other dangerous machinery
  • Anticholinergic side effects - orphenadrine has anticholinergic activity and should be used cautiously or avoided in patients with glaucoma, bowel obstruction, urinary hesitancy, or urinary obstruction.

Tizanidine (Zanaflex®)

Dosage forms

Tablet
  • 2 mg
  • 4 mg
Capsule
  • 2 mg
  • 4 mg
  • 6 mg

Dosing

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), taper dose gradually (2 - 4 mg per day) to prevent withdrawal
  • 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.
Kidney disease
  • Exposure is increased. In patients with CrCl < 25 ml/min, clearance is reduced by more than 50%. Start with lower doses and titrate by increasing the dosage as opposed to dose frequency.
Liver disease
  • Tizanidine is extensively metabolized by the liver, and caution should be used. Start with lower doses and titrate by increasing the dosage as opposed to dose frequency.

Lab monitoring

  • Check LFTs at baseline, one month after maximum dose is achieved, and as needed for signs of liver disease

Mechanism of action

  • Tizanidine is a central alpha-2-adrenergic receptor agonist and presumably reduces spasticity by increasing presynaptic inhibition of motor neurons

Efficacy

Low back pain

Generic / Price

  • Generic 90 tablets - $
  • Generic 90 capsules - $-$$

Side effects



Side effect Tizanidine (multiple doses)
(N=264)		 Placebo
(N=261)
Dry mouth 49% 10%
Somnolence 48% 10%
Weakness/tired 41% 16%
Dizziness 16% 4%
UTI 10% 7%
Liver test abnormalities 6% 2%
Infection 6% 5%
In a single-dose study (N=142) of MS patients with spasticity, the following was observed:
  • Hypotension: Tizanidine 8 mg - 16%, Tizanidine 16 mg - 33%
  • Bradycardia: Tizanidine 8 mg - 2%, Tizanidine 16 mg - 10%

Drug interactions

  • CYP1A2 inhibitors - tizanidine is a CYP1A2 sensitive substrate
    • 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. Use caution and start with 2 mg dose.
  • Central nervous system (CNS) depressants - muscle relaxers can potentiate the effects of CNS depressants (e.g. opiates, benzodiazepines, alcohol, anticonvulsants, antihistamines) and increase the risk for adverse events. Use caution when combining.
  • 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 enhances the absorption of tizanidine, increasing the risk of side effects

Contraindications / Precautions

  • Decreased alertness - muscle relaxers can depress CNS activity and impair the ability to operate motor vehicles and other dangerous machinery
  • Hypotension - tizanidine is an alpha-2 agonist, a drug class that reduces sympathetic outflow and can lower blood pressure. In a single-dose study, hypotension occurred in 16% and 33% of patients given tizanidine 8 mg and 16 mg, respectively. In order to avoid significant hypotension, tizanidine should be titrated slowly while monitoring for symptoms of low blood pressure (e.g. lightheadedness, fatigue). Concomitant CYP1A2 inhibitors increase the risk of hypotension.
  • Bradycardia - tizanidine can slow the heart rate. In a single-dose study, bradycardia occurred in 2% and 10% of patients given tizanidine 8 mg and 16 mg, respectively.
  • Liver toxicity - hepatotoxicity has been reported in patients receiving tizanidine. Check LFTs at baseline, one month after maximum dose is achieved, and as needed for signs of liver disease.
  • Withdrawal reactions - if tizanidine is stopped abruptly, withdrawal reactions, including hypertension, tachycardia, and hypertonia, may occur. When discontinuing after chronic therapy (20 - 36 mg/day for ≥ 9 weeks), taper dose gradually (2 - 4 mg per day) to prevent withdrawal.
  • Hallucinations - some patients have reported hallucinations while taking tizanidine
  • Hypersensitivity reactions - hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with tizanidine
  • Kidney disease - exposure is increased. In patients with CrCl < 25 ml/min, clearance is reduced by more than 50%. Start with lower doses and titrate by increasing the dosage as opposed to dose frequency.
  • Liver disease - tizanidine is extensively metabolized by the liver, and caution should be used. Start with lower doses and titrate by increasing the dosage as opposed to dose frequency.





Pricing legend
  • $ = 0 - $50
  • $$ = $51 - $100
  • $$$ = $101 - $150
  • $$$$ = > $150
  • Pricing based on one month of therapy at standard dosing in an adult
  • Pricing based on information from GoodRX.com®
  • Pricing may vary by region and availability