Cyclobenzaprine (Lexi-Drugs)

Pronunciation

(sye kloe BEN za preen)

Brand Names: US

Amrix; Fexmid

Brand Names: Canada

APO-Cyclobenzaprine; Auro-Cyclobenzaprine; DOM-Cyclobenzaprine; JAMP-Cyclobenzaprine; MYLAN-Cyclobenzaprine [DSC]; PHL-Cyclobenzaprine [DSC]; PMS-Cyclobenzaprine; Q-Cyclobenzaprine [DSC]; RATIO-Cyclobenzaprine [DSC]; RIVA-Cyclobenzaprine; TEVA-Cyclobenzaprine

Pharmacologic Category

Skeletal Muscle Relaxant

Dosing: Adult

Jaw pain due to temporomandibular disorder, acute (off-label): Immediate release: Usual: 10 mg once daily administered 1 to 2 hours before bedtime (Alencar 2014; Herman 2002)

Muscle spasm: Oral: Note: Do not use longer than 2 to 3 weeks.

Extended release: Usual: 15 mg once daily; some patients may require up to 30 mg once daily

Immediate release: Initial: 5 mg 3 times daily; may increase up to 10 mg 3 times daily if needed

Dosing: Geriatric

Extended release: Use not recommended.

Immediate release: Initial: 5 mg; titrate dose slowly and consider less frequent dosing.

Dosing: Renal Impairment: Adult

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

Dosing: Hepatic Impairment: Adult

Extended release: Mild to severe impairment: Use not recommended.

Immediate release:

Mild impairment: Initial: 5 mg; use with caution; titrate slowly and consider less frequent dosing

Moderate to severe impairment: Use not recommended.

Dosing: Pediatric

Muscle spasm, treatment: Adolescents ≥15 years: Oral: Immediate release tablet: Initial: 5 mg 3 times daily; may increase up to 10 mg 3 times daily if needed. Do not use longer than 2 to 3 weeks.

Dosing: Renal Impairment: Pediatric

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

Dosing: Hepatic Impairment: Pediatric

Immediate release tablet: Adolescents ≥15 years:

Mild impairment: Initial: 5 mg; use with caution; titrate slowly and consider less frequent dosing

Moderate to severe impairment: Use not recommended

Use: Labeled Indications

Muscle spasm: As an adjunct to rest and physical therapy for short-term (2 to 3 weeks) relief of muscle spasm associated with acute, painful musculoskeletal conditions.

Use: Off-Label: Adult

  Jaw pain due to temporomandibular disorder, acuteLevel of Evidence [C]

Data from two randomized, double-blind, placebo-controlled trials in patients experiencing myofascial jaw pain upon awakening suggest that cyclobenzaprine at bedtime may have some benefit for the treatment of acute jaw pain due to temporomandibular disorder Ref. Of note, one study demonstrated significant improvement in pain scores with treatment; however, no significant differences were seen when compared to placebo Ref.

Level of Evidence Definitions
  Level of Evidence Scale
Administration: Oral

Extended release: Swallow whole and administer at the same time each day. Alternatively, the contents of the capsule may be sprinkled onto a tablespoon of applesauce and consume immediately without chewing; rinse mouth to ensure all contents have been swallowed; discard any unused portion of capsule.

Storage/Stability

Capsules: Store at 25°C (77°F); excursions are permitted to 15°C to 30°C (59°F to 86°F).

Tablets: Store between 20°C and 25°C (68°F and 77°F).

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, dizziness, dry mouth, constipation, or nausea. Have patient report immediately to prescriber severe loss of strength and energy, lack of sweating, tachycardia, abnormal heartbeat, or signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
  Geriatric Patients: High-Risk Medication:
  International issues:
Contraindications

Hypersensitivity to cyclobenzaprine or any component of the formulation; during or within 14 days of MAO inhibitors; hyperthyroidism; heart failure; arrhythmias; heart block or conduction disturbances; acute recovery phase of MI

Warnings/Precautions

Concerns related to adverse effects:

• Anticholinergic effects: Use with caution in patients with angle-closure glaucoma, increased intraocular pressure, or urinary frequency/hesitancy.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; ethanol and/or other CNS depressants may enhance these effects. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Serotonin syndrome: Potentially life-threatening serotonin syndrome has occurred with cyclobenzaprine when used in combination with other serotonergic agents (eg, SSRIs, SNRIs, TCAs, buspirone, meperidine, tramadol, MAO inhibitors), bupropion, and verapamil. Monitor patients closely especially during initiation/dose titration for signs/symptoms of serotonin syndrome such as mental status changes (eg, agitation, hallucinations); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue cyclobenzaprine and any concomitant serotonergic agent immediately if signs/symptoms arise. Concomitant use or use within 14 days of discontinuing an MAO inhibitor is contraindicated.

• Toxicity: Cyclobenzaprine shares the toxic potentials of the tricyclic antidepressants, including prolongation of conduction time, arrhythmias, and tachycardia; the usual precautions of tricyclic antidepressant therapy should be observed.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with mild hepatic impairment; plasma concentrations increased twofold in presence of mild impairment. Not recommended in moderate-to-severe hepatic impairment. Extended release capsules not recommended in patients with hepatic impairment of any severity (mild, moderate, or severe).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Extended release capsules not recommended for use in elderly.

Other warnings/precautions:

• Appropriate use: Limit therapy to 2-3 weeks; efficacy has not been established for longer periods of use.

Geriatric Considerations

High doses in the elderly cause drowsiness and dizziness; therefore, use the lowest dose possible. Because cyclobenzaprine causes anticholinergic effects, it may not be the skeletal muscle relaxant of choice in the elderly.

Warnings: Additional Pediatric Considerations

Not effective in the treatment of spasticity due to cerebral or spinal cord disease or in children with cerebral palsy.

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. The manufacturer recommends avoiding use during pregnancy unless clearly needed.

Breast-Feeding Considerations

It is not known if cyclobenzaprine is excreted in breast milk. Because cyclobenzaprine is closely related to tricyclic antidepressants, some of which are excreted in breast milk, the manufacturer recommends that caution be exercised when administering cyclobenzaprine to breastfeeding women.

Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

>10%:

Central nervous system: Drowsiness (1% to 39%), dizziness (1% to 11%)

Gastrointestinal: Xerostomia (6% to 32%)

1% to 10%:

Central nervous system: Fatigue (1% to 6%), headache (1% to 5%), confusion (1% to 3%), decreased mental acuity (1% to 3%), irritability (1% to 3%), nervousness (1% to 3%)

Gastrointestinal: Dyspepsia (≤4%), abdominal pain (1% to 3%), acid regurgitation (1% to 3%), constipation (1% to 3%), diarrhea (1% to 3%), nausea (1% to 3%), unpleasant taste (1% to 3%)

Neuromuscular & skeletal: Weakness (1% to 3%)

Ophthalmic: Blurred vision (1% to 3%)

Respiratory: Pharyngitis (1% to 3%), upper respiratory tract infection (1% to 3%)

<1%, postmarketing, and/or case reports: Abnormal dreams, abnormal hepatic function tests, abnormality in thinking, ageusia, agitation, anaphylaxis, angioedema, anorexia, anxiety, ataxia, cardiac arrhythmia, cholestasis, convulsions, depression, diaphoresis, diplopia, disorientation, dysarthria, excitement (paradoxical, children), facial edema, flatulence, gastritis, gastrointestinal pain, hallucination, hepatitis (rare), hypertonia, hypotension, increased thirst, insomnia, jaundice, malaise, muscle twitching, palpitations, paresthesia, pruritus, psychosis, seizure, serotonin syndrome, skin rash, syncope, tachycardia, tinnitus, tongue edema, tremor, urinary frequency, urinary retention, urticaria, vasodilation, vertigo, vomiting

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

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

Drug Interactions 

Abiraterone Acetate: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

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

Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Risk D: Consider therapy modification

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

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

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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants.Risk D: Consider therapy modification

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

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

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Risk X: Avoid combination

Deferasirox: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. 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. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination

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

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone 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

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

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

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

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. 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 adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification

Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk X: Avoid combination

Methylphenidate: May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. Risk C: Monitor therapy

Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

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

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors: Cyclobenzaprine may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

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

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy

Obeticholic Acid: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Ombitasvir, Paritaprevir, and Ritonavir: May decrease the serum concentration of Cyclobenzaprine. Risk C: Monitor therapy

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May decrease the serum concentration of Cyclobenzaprine. Risk C: Monitor therapy

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

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

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

Peginterferon Alfa-2b: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Risk X: Avoid combination

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk D: Consider therapy modification

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy

Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination

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

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid.Risk C: Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. 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

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol 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

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

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. 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

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy

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

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Vemurafenib: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Management: Consider alternatives to such combinations whenever possible, particularly if the CYP1A2 substrate has a relatively narrow therapeutic index. Drugs listed as exceptions to this monograph are discussed in separate drug interaction monographs.Risk D: Consider therapy modification

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

Food Interactions

Food increases bioavailability (peak plasma concentrations increased by 35% and area under the curve by 20%) of the extended release capsule. Management: Monitor for increased effects if taken with food.

Test Interactions

May cause false-positive serum TCA screen (Wong, 1995)

Advanced Practitioners Physical Assessment/Monitoring

May cause significant CNS depression. Caution patients about sedation.

Nursing Physical Assessment/Monitoring

May cause significant CNS depression. Caution patients about sedation.

Dosage Forms: US

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

Capsule Extended Release 24 Hour, Oral, as hydrochloride:

Amrix: 15 mg [contains fd&c red #40, fd&c yellow #10 (quinoline yellow)]

Amrix: 30 mg [contains brilliant blue fcf (fd&c blue #1), fd&c blue #2 (indigotine), fd&c red #40, fd&c yellow #6 (sunset yellow)]

Generic: 15 mg, 30 mg

Tablet, Oral, as hydrochloride:

Fexmid: 7.5 mg

Generic: 5 mg, 7.5 mg, 10 mg

Dosage Forms: Canada

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

Tablet, Oral, as hydrochloride:

Generic: 10 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • M03BX08
Generic Available (US)

Yes

Pricing: US

Capsule ER 24 Hour Therapy Pack (Amrix Oral)

15 mg (per each): $47.66

30 mg (per each): $47.66

Capsule ER 24 Hour Therapy Pack (Cyclobenzaprine HCl ER Oral)

15 mg (per each): $39.71 – $45.28

30 mg (per each): $39.71 – $45.28

Tablets (Cyclobenzaprine HCl Oral)

5 mg (per each): $0.07 – $1.73

7.5 mg (per each): $4.81

10 mg (per each): $0.07 – $2.98

Tablets (Fexmid Oral)

7.5 mg (per each): $8.32

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.

Mechanism of Action

Centrally-acting skeletal muscle relaxant pharmacologically related to tricyclic antidepressants; reduces tonic somatic motor activity influencing both alpha and gamma motor neurons

Pharmacodynamics/Kinetics

Onset of action: Immediate release: Within 1 hour

Duration of action: Immediate release: 12 to 24 hours

Metabolism: Hepatic via CYP3A4, 1A2, and 2D6; may undergo enterohepatic recirculation

Bioavailability: 33% to 55%

Half-life elimination: Normal hepatic function: Range: 8 to 37 hours; Immediate release: 18 hours; Extended release: 32 hours; Impaired hepatic function: 46.2 hours (range: 22.4 to 188 hours) (Winchell 2002)

Time to peak, serum: Immediate release: ~4 hours (Winchell 2002); Extended release: 7 to 8 hours

Excretion: Urine (primarily as glucuronide metabolites); feces (as unchanged drug; Hucker 1978)

Clearance: 0.7 L/minute

Pharmacodynamics/Kinetics: Additional Considerations

Hepatic function impairment: In mild-to-moderate hepatic impairment, AUC and Cmax increased approximately twofold with immediate-release cyclobenzaprine.

Geriatric: AUC increased ~2.4-fold in elderly males and ~1.2-fold in elderly females with immediate-release cyclobenzaprine. AUC increased 40% and the plasma half-life is prolonged (50 hours) in elderly subjects with extended-release cyclobenzaprine.

Dental Use

Treatment of muscle spasm associated with acute temporomandibular joint pain (TMJ)

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation).

Effects on Bleeding

No information available to require special precautions

Dental Usual Dosing

Treatment of muscle spasm associated with acute TMJ pain (Burket 2008) (Note: Do not use longer than 2-3 weeks): Oral:

Adults: Initial: 5 mg 3 times/day; may increase to 7.5-10 mg 3 times/day if needed

Elderly: 5 mg 3 times/day; plasma concentration and incidence of adverse effects are increased in the elderly; dose should be titrated slowly

Index Terms

Cyclobenzaprine HCl; Cyclobenzaprine Hydrochloride; Flexeril

FDA Approval Date
August 26, 1977
References

Alencar FG Jr, Viana PG, Zamperini C, Becker A. Patient education and self-care for the management of jaw pain upon awakening: a randomized controlled clinical trial comparing the effectiveness of adding pharmacologic treatment with cyclobenzaprine or tizanidine. J Oral Facial Pain Headache. 2014;28(2):119-127.[PubMed 24822235]

American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227-2246. doi:10.1111/jgs.13702.[PubMed 26446832]

Amrix (cyclobenzaprine) [prescribing information]. North Wales, PA: Teva Pharmaceuticals, Inc; May 2018.

Burket LW, Burket’s Oral Medicine, 11th ed, Greenberg MS, Glick M, and Ship JA, eds, Shelton, CT: PMPH-USA, 2008.

Cyclobenzaprine [prescribing information]. East Windsor, NJ: Aurobindo Pharma USA, Inc; December 2018.

Fexmid (cyclobenzaprine) [prescribing information]. East Brunswick, NJ: Casper Pharma LLC; January 2018.

Herman CR, Schiffman EL, Look JO, Rindal DB. The effectiveness of adding pharmacologic treatment with clonazepam or cyclobenzaprine to patient education and self-care for the treatment of jaw pain upon awakening: a randomized clinical trial. J Orofac Pain. 2002;16(1):64-70.[PubMed 11889661]

Hucker HB, Stauffer SC, Balletto AJ, et al, “Physiological Disposition and Metabolism of Cyclobenzaprine in the Rat, Dog, Rheses Monkey, and Man,” Drug Metab Dispos, 1978, 6(6):659-72.[PubMed 33029]

Pharmacy Quality Alliance. Use of high-risk medications in the elderly (HRM). http://pqaalliance.org/images/uploads/files/HRM2015.pdf. Published 2015. Accessed October 26, 2015.

Winchell GA, King JD, Chavez-Eng CM, et al, “Cyclobenzaprine Pharmacokinetics, Including the Effects of Age, Gender, and Hepatic Insufficiency,” J Clin Pharmacol, 2002, 42(1):61-9.[PubMed 11808825]

Wong EC, Koenig J, and Turk J, “Potential Interference of Cyclobenzaprine and Norcyclobenzaprine With HPLC Measurement of Amitriptyline and Nortriptyline: Resolution by GC-MS Analysis,” J Anal Toxicol, 1995, 19(4):218-24.[PubMed 8531466]

Brand Names: International

Bencoprim (CR, DO, GT, HN, NI, PA, SV); Benzamin (KR); Binelax ER (KR); Ciclamil (CL); Cybens (KR); Cycloflex (EG, IL); Cyrin (BD); Flexer (PE, TW); Flexerin (BD); Flexiban (AE, AR, IT, PT); Flexor (BD); Flogomax (EC); Miosan (BR); Mitrul (EC); Moveasy (EG); Multirelax (EG); Musgud (TW); Prinorelax (EG); Prolax (KW); Tensodox (EC, PE, PY); Yuredol (MX); Yurelax (ES, MX)

Cyclobenzaprine (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(sye kloe BEN za preen)

Brand Names: US

Amrix; Fexmid

What is this drug used for?
  • It is used to calm muscles.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to cyclobenzaprine or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have any of these health problems: Heart block or other heartbeat that is not normal, heart failure (weak heart), liver disease, or an overactive thyroid gland.
  • If you have had a recent heart attack.
  • If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson’s disease like selegiline or rasagiline in the last 14 days. Taking this drug within 14 days of those drugs can cause very bad high blood pressure.
  • If you are taking any of these drugs: Linezolid or methylene blue.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • All products:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
  • Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
  • Do not take this drug for longer than you were told by your doctor.
  • This drug is used with rest, PT (physical therapy), pain drugs, and other therapies.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
  • Tablets:
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Long-acting capsules:
  • Do not take this drug if you are 65 or older. Talk with your doctor.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Feeling very tired or weak.
  • Not sweating during activities or in warm temperatures.
  • A fast heartbeat.
  • A heartbeat that does not feel normal.
  • A very bad and sometimes deadly health problem called serotonin syndrome may happen if you take this drug with drugs for depression, migraines, or certain other drugs. Call your doctor right away if you have agitation; change in balance; confusion; hallucinations; fever; fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; very bad diarrhea, upset stomach, or throwing up; or very bad headache.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Feeling sleepy.
  • Dizziness.
  • Dry mouth.
  • Feeling tired or weak.
  • Constipation.
  • Upset stomach.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Take with or without food.
  • Long-acting capsules:
  • Take this drug at the same time of day.
  • Swallow whole. Do not chew or crush.
  • If you cannot swallow this drug whole, you may sprinkle the contents on applesauce. If you do this, swallow the mixture right away without chewing.
  • Rinse mouth to make sure all contents have been swallowed.
  • Throw away any part of opened capsule left over after the dose is given.
What do I do if I miss a dose?
  • Tablets:
  • If you take this drug on a regular basis, take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • Many times this drug is taken on an as needed basis. Do not take more often than told by the doctor.
  • Long-acting capsules:
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Cyclobenzaprine (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(sye kloe BEN za preen)

Brand Names: US

Amrix; Fexmid

What is this drug used for?
  • It is used to calm muscles.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child has any of these health problems: Heart block or other heartbeat that is not normal, heart failure (weak heart), liver disease, or an overactive thyroid gland.
  • If your child has had a recent heart attack.
  • If your child has taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for certain other health problems in the last 14 days. Taking this drug within 14 days of those drugs can cause very bad high blood pressure.
  • If your child is taking any of these drugs: Linezolid or methylene blue.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • To lower the chance of feeling dizzy or passing out, have your child rise slowly if your child has been sitting or lying down. Have your child be careful going up and down stairs.
  • Have your child be careful in hot weather or while your child is being active. Have your child drink lots of fluids to stop fluid loss.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • Talk with the doctor before giving your child other drugs and natural products that may slow your child’s actions.
  • Do not give this drug to your child for longer than you were told by the doctor.
  • This drug is used with rest, PT (physical therapy), pain drugs, and other therapies.
  • If your child is pregnant or breast-feeding a baby:
  • Talk with the doctor if your child is pregnant, becomes pregnant, or is breast-feeding a baby. You will need to talk about the benefits and risks to your child and the baby.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Feeling very tired or weak.
  • Not sweating during activities or in warm temperatures.
  • A fast heartbeat.
  • A heartbeat that does not feel normal.
  • A very bad and sometimes deadly health problem called serotonin syndrome may happen if your child takes this drug with drugs for depression, migraines, or certain other drugs. Call the doctor right away if your child has agitation; change in balance; confusion; hallucinations; fever; fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; very bad diarrhea, upset stomach, or throwing up; or very bad headache.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • Feeling sleepy.
  • Dizziness.
  • Dry mouth.
  • Feeling tired or weak.
  • Constipation.
  • Upset stomach.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Give this drug with or without food.
  • Long-acting capsules:
  • Give at the same time of day.
  • Have your child swallow whole. Do not let your child chew or crush.
  • If your child cannot swallow this drug whole, you may sprinkle the contents on applesauce. If you do this, have your child swallow the mixture right away without chewing.
  • Have your child rinse mouth to make sure all contents have been swallowed.
  • Throw away any part of opened capsule left over after the dose is given.
What do I do if my child misses a dose?
  • Tablets:
  • If your child takes this drug on a regular basis, give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
  • Many times this drug is given on an as needed basis. Do not give to your child more often than told by the doctor.
  • Long-acting capsules:
  • Give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.