(sye kloe BEN za preen)
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.
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
Muscle spasm: Oral: Note: Do not use longer than 2 to 3 weeks
Capsule, extended release: Usual: 15 mg once daily; some patients may require up to 30 mg once daily
Tablet, immediate release: Initial: 5 mg 3 times daily; may increase up to 10 mg 3 times daily if needed
Capsule, extended release: Use not recommended.
Tablet, immediate release: Initial: 5 mg; titrate dose slowly and consider less frequent dosing.
Muscle spasm: Oral: Tablet, immediate release: Children ≥15 years: Refer to adult dosing.
There are no dosage adjustment provided in the manufacturers labeling.
Capsule, extended release: Mild to severe impairment: Use not recommended.
Tablet, immediate release:
Mild impairment: Initial: 5 mg; use with caution; titrate slowly and consider less frequent dosing
Moderate to severe impairment: Use not recommended.
Oral: Extended release capsules: Swallow capsule 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.
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).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule Extended Release 24 Hour, Oral, as hydrochloride:
Amrix: 15 mg
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)]
Cream, Transdermal, as hydrochloride:
Active-Cyclobenzaprine: 5% (120 g) [contains chlorocresol (chloro-m-cresol)]
Cyclophene RapidPaq: 5% (100 g) [contains cetearyl alcohol, disodium edta]
EnovaRX-Cyclobenzaprine HCl: 20 mg/g (120 g) [contains cetearyl alcohol]
Suspension, Oral, as hydrochloride:
Tabradol FusePaq: 1 mg/mL (250 mL) [contains saccharin sodium, sodium benzoate]
Tabradol RapidPaq: 1 mg/mL (250 mL) [dye free, paraben free, sugar free; contains saccharin sodium, sodium benzoate]
Tablet, Oral, as hydrochloride:
Fexmid: 7.5 mg
Flexeril: 5 mg [DSC], 10 mg [DSC]
Generic: 5 mg, 7.5 mg, 10 mg
Abiraterone Acetate: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy
AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy
Analgesics (Opioid): Anticholinergic Agents may enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy
Analgesics (Opioid): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy
Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. 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. Monitor therapy
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
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. Consider therapy modification
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Monitor therapy
CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Consider therapy modification
Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination
Deferasirox: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy
Dimethindene: May enhance the CNS depressant effect of CNS Depressants. 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. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
MAO Inhibitors: Cyclobenzaprine may enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. 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. Consider therapy modification
Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination
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. Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy
Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy
Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Obeticholic Acid: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy
Ombitasvir, Paritaprevir, and Ritonavir: May decrease the serum concentration of Cyclobenzaprine. Monitor therapy
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May decrease the serum concentration of Cyclobenzaprine. Monitor therapy
OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
Peginterferon Alfa-2b: May increase the serum concentration of CYP1A2 Substrates. 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. Consider therapy modification
Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. 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. Avoid combination
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy
RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to secretin. 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. Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. 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. 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. Consider therapy modification
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy
TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Vemurafenib: May increase the serum concentration of CYP1A2 Substrates. Management: Consider alternatives to such combinations whenever possible, particularly if the CYP1A2 substrate has a relatively narrow therapeutic index. 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. Consider therapy modification
Signs/symptoms of serotonin syndrome (patients receiving other serotonergic drugs)
May cause false-positive serum TCA screen (Wong, 1995)
>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% (Limited to important or life-threatening): Anaphylaxis, angioedema, cardiac arrhythmia, convulsions, hepatitis (rare), hypertonia, hypotension, paresthesia, psychosis, seizure, serotonin syndrome, skin rash, syncope, tachycardia
In mild-to-moderate hepatic impairment, AUC and Cmax increased approximately twofold with immediate-release cyclobenzaprine.
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 capsules.
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.
B
Adverse events have not been observed in animal reproduction studies. The manufacturer recommends avoiding use during pregnancy unless clearly needed.
Centrally-acting skeletal muscle relaxant pharmacologically related to tricyclic antidepressants; reduces tonic somatic motor activity influencing both alpha and gamma motor neurons
Hepatic via CYP3A4, 1A2, and 2D6; may undergo enterohepatic recirculation
Urine (primarily as glucuronide metabolites); feces (as unchanged drug; Hucker, 1978); Clearance: 0.7 L/minute
Immediate release tablet: Within 1 hour
Immediate release tablet: ~4 hours (Winchell 2002); Extended release capsule: 7 to 8 hours
Immediate release tablet: 12 to 24 hours
Normal hepatic function: Range: 8 to 37 hours; Immediate release tablet: 18 hours; Extended release capsule: 32 hours; Impaired hepatic function: 46.2 hours (range: 22.4 to 188 hours) (Winchell 2002)
- 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, constipation, or nausea. Have patient report immediately to prescriber severe loss of strength and energy, lack of sweat, tachycardia, arrhythmia, or signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, arrhythmia, 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.