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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
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
(For additional information see "Cyclobenzaprine: Drug information")
Dosage guidance:
Safety: Patients more sensitive to sedating and other CNS adverse effects (eg, those who are older, debilitated patients, those with organ impairment) may better tolerate a reduced dose, less frequent administration, and/or more gradual titration (Ref).
Fibromyalgia (alternative agent) (off-label use):
Note: For mild to moderate symptoms, particularly with sleep disturbance (Ref).
Oral: Immediate release: Initial: 5 to 10 mg once daily before bedtime; may gradually titrate as needed and tolerated up to 10 to 40 mg daily in 1 to 3 divided doses (Ref). If excessive sedation occurs, may divide dose so larger portion is taken at bedtime (eg, 5 mg in morning and 10 or 15 mg at bedtime) (Ref).
Muscle spasm and/or musculoskeletal pain (adjunctive therapy):
Note: For skeletal muscle spasm and/or pain (eg, low back pain, neck pain) with muscle spasm, usually in combination with a nonsteroidal anti-inflammatory drug (NSAID) and/or acetaminophen (Ref). In general, muscle relaxants should be used temporarily (eg, for a few days or intermittently for a few days when needed) (Ref).
Oral: Immediate release: Initial: 5 mg 3 times daily scheduled or as needed with one of the doses administered at bedtime (Ref). May increase dose based on response and tolerability up to 10 mg 3 times daily as needed. Once-daily use at bedtime (with daytime NSAID and/or acetaminophen) may be better tolerated (Ref).
Oral: Extended release: Usual: 15 mg once daily; some patients may require up to 30 mg once daily.
Temporomandibular disorder, acute (adjunctive therapy) (off-label use):
Note: Adjunct to an NSAID in select patients with pain on palpation of the lower jaw muscle (Ref).
Oral: Immediate release: Usual: 5 to 10 mg once daily at bedtime for 10 to 14 days; some patients with persistent muscular pain may require an additional 7 days of therapy (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Mild to severe impairment: No dosage adjustment likely needed based on pharmacokinetic characteristics; however, use with caution due to limited safety and efficacy data (Ref).
Hemodialysis: Unlikely to be dialyzed (Ref): No dosage adjustment likely needed based on pharmacokinetic characteristics; however, use with caution due to limited safety and efficacy data (Ref). Increased risk of altered mental status and fractures has been observed (Ref).
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.
Similar to tricyclic antidepressants, reversible peripheral and central anticholinergic effects may occur with cyclobenzaprine use. These include CNS effects (eg, dizziness, drowsiness, confusion), GI effects (eg, constipation), and GU effects (eg, urinary retention). The anticholinergic CNS effects have been associated with an increased risk of injury and falls in older patients (Ref).
Mechanism: Dose-related; related to the pharmacologic action (ie, inhibition of acetylcholine action at muscarinic receptors; atropine-like effects).
Risk factors:
• Higher doses (Ref)
• Multiple daily dosing (Ref)
• Age ≥65 years (Ref)
• Concurrent administration with other anticholinergic agents
Cyclobenzaprine use is associated with reversible CNS effects such as dizziness, drowsiness, asthenia, and fatigue which may impair the ability to drive or operate machinery (Ref). These effects have been associated with an increased risk of injury and falls in older patients (Ref).
Mechanism: Dose-related; mechanism not fully understood. Sedation may be a result of anticholinergic and other CNS effects (Ref).
Onset: Rapid; typically occurs within the first 3 days of therapy (Ref).
Risk factors:
• Higher doses (Ref)
• Multiple daily dosing (Ref)
• Age ≥65 years (Ref)
• Concurrent administration with ethanol and/or other CNS depressants (Ref)
• Hepatic impairment
Serotonin syndrome has been reported rarely when cyclobenzaprine is concurrently administered with one or more serotonergic agents. Symptoms such as mental status changes (confusion, agitation, psychosis, hallucinations, delusions); autonomic instability (tachycardia, labile blood pressure, hyperthermia); neuromuscular effects (tremor, clonus, myoclonus, muscle rigidity); and GI effects (diaphoresis, nausea, vomiting, diarrhea) have been observed. These effects are typically reversible within 3 days after withdrawal of cyclobenzaprine and/or serotonergic agents and supportive care (Ref). Some reported cases have been life-threatening (Ref).
Mechanism: Non–dose-related; inhibition of serotonin transport and agonist action at serotonin receptors (Ref).
Onset: Rapid; generally occurs within the first 24 hours of concurrent administration with serotonergic agents (Ref).
Risk factors:
• Concurrent use of drugs that increase serotonin synthesis, block serotonin reuptake, and/or impair serotonin metabolism
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Xerostomia (6% to 32%) (table 1)
Drug (Cyclobenzaprine) |
Placebo |
Dose |
Dosage Form |
Number of Patients (Cyclobenzaprine) |
Number of Patients (Placebo) |
---|---|---|---|---|---|
32% |
7% |
10 mg 3 times daily |
Immediate-release tablets |
249 |
469 |
21% |
7% |
5 mg 3 times daily |
Immediate-release tablets |
464 |
469 |
27% |
N/A |
10 mg 3 times daily |
Immediate-release tablets |
N/A |
N/A |
14% |
2% |
30 mg once daily |
Extended-release capsules |
126 |
128 |
6% |
2% |
15 mg once daily |
Extended-release capsules |
127 |
128 |
Nervous system: Dizziness (3% to 11%) (table 2) , drowsiness (1% to 39%) (table 3)
Drug (Cyclobenzaprine) |
Placebo |
Dose |
Dosage Form |
Number of Patients (Cyclobenzaprine) |
Number of Patients (Placebo) |
---|---|---|---|---|---|
11% |
N/A |
10 mg 3 times daily |
Immediate-release tablets |
N/A |
N/A |
6% |
2% |
30 mg once daily |
Extended-release capsules |
126 |
128 |
3% |
2% |
15 mg once daily |
Extended-release capsules |
127 |
128 |
Drug (Cyclobenzaprine) |
Placebo |
Dose |
Dosage Form |
Number of Patients (Cyclobenzaprine) |
Number of Patients (Placebo) |
---|---|---|---|---|---|
39% |
N/A |
10 mg 3 times daily |
Immediate-release tablets |
N/A |
N/A |
38% |
10% |
10 mg 3 times daily |
Immediate-release tablets |
249 |
469 |
29% |
10% |
5 mg 3 times daily |
Immediate-release tablets |
464 |
469 |
2% |
0% |
30 mg once daily |
Extended-release capsules |
126 |
128 |
1% |
0% |
15 mg once daily |
Extended-release capsules |
127 |
128 |
1% to 10%:
Gastrointestinal: Abdominal pain (1% to 3%), acid regurgitation (1% to 3%), constipation (1% to 3%) (table 4) , diarrhea (1% to 3%), dyspepsia (4%), nausea (3%), unpleasant taste (1% to 3%)
Drug (Cyclobenzaprine) |
Placebo |
Dose |
Dosage Form |
Number of Patients (Cyclobenzaprine) |
Number of Patients (Placebo) |
---|---|---|---|---|---|
3% |
0% |
30 mg once daily |
Extended-release capsules |
126 |
128 |
1% |
0% |
15 mg once daily |
Extended-release capsules |
127 |
128 |
Nervous system: Confusion (1% to 3%), decreased mental acuity (1% to 3%), fatigue (3% to 6%) (table 5) , headache (1% to 3%), irritability (1% to 3%), nervousness (1% to 3%)
Drug (Cyclobenzaprine) |
Placebo |
Dose |
Dosage Form |
Number of Patients (Cyclobenzaprine) |
Number of Patients (Placebo) |
---|---|---|---|---|---|
6% |
3% |
5 mg 3 times daily |
Immediate-release tablets |
464 |
469 |
6% |
3% |
10 mg 3 times daily |
Immediate-release tablets |
249 |
469 |
3% |
2% |
15 mg once daily |
Extended-release capsules |
127 |
128 |
3% |
2% |
30 mg once daily |
Extended-release capsules |
126 |
128 |
Neuromuscular & skeletal: Asthenia (1% to 3%)
Ophthalmic: Blurred vision (1% to 3%)
Respiratory: Pharyngitis (1% to 3%), upper respiratory tract infection (1% to 3%)
Postmarketing:
Cardiovascular: Cardiac arrhythmia, facial edema, hypotension, palpitations, syncope, tachycardia (may be associated with serotonin syndrome; Keegan 2006), vasodilation
Dermatologic: Diaphoresis (may be associated with serotonin syndrome; Keegan 2006), pruritus, skin rash, urticaria
Endocrine & metabolic: Increased thirst
Gastrointestinal: Ageusia, anorexia, cholestasis, flatulence, gastritis, gastrointestinal pain, vomiting
Genitourinary: Urinary frequency, urinary retention (Cimolai 2009)
Hepatic: Hepatitis (rare), jaundice
Hypersensitivity: Anaphylaxis, angioedema, tongue edema
Nervous system: Abnormal dreams, abnormal sensory symptoms, abnormality in thinking, agitation (may be associated with serotonin syndrome; Keegan 2006), anxiety, ataxia, clonus (may be associated with serotonin syndrome; Keegan 2006), delusion (may be associated with serotonin syndrome; Keegan 2006), depressed mood, disorientation, dysarthria, excitement, hallucination (may be associated with serotonin syndrome; Keegan 2006), hyperthermia (may be associated with serotonin syndrome; Keegan 2006), hypertonia, insomnia, malaise, myoclonus (may be associated with serotonin syndrome; Keegan 2006), paresthesia, psychosis, seizure, serotonin syndrome (Keegan 2006), vertigo
Neuromuscular & skeletal: Muscle rigidity (may be associated with serotonin syndrome; Keegan 2006), muscle twitching, tremor (may be associated with serotonin syndrome; Keegan 2006)
Ophthalmic: Diplopia
Otic: Tinnitus
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
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• 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. ER capsules not recommended in patients with hepatic impairment of any severity (mild, moderate, or severe).
• Ophthalmic conditions: Use with caution in patients with certain ophthalmic conditions (eg, increased intraocular pressure, angle-closure glaucoma) as anticholinergic effects may exacerbate underlying condition.
• Urinary frequency/hesitancy: Use with caution in patients with urinary frequency/hesitancy as anticholinergic effects may exacerbate underlying condition.
Special populations:
• Older adult: ER capsules not recommended for use in older adults.
Other warnings/precautions:
• Appropriate use: Limit therapy to 2 to 3 weeks; efficacy has not been established for longer periods of use.
Not effective in the treatment of spasticity due to cerebral or spinal cord disease or in children with cerebral palsy.
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 (allura red ac dye), quinoline yellow (d&c yellow #10)]
Amrix: 30 mg [contains fd&c blue #1 (brilliant blue), fd&c blue #2 (indigotine,indigo carmine), fd&c red #40 (allura red ac dye), 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
Yes
Capsule ER 24 Hour Therapy Pack (Amrix Oral)
15 mg (per each): $69.65
30 mg (per each): $69.65
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 - $7.54
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Flexeril: 10 mg [contains corn starch, fd&c yellow #6(sunset yellow)alumin lake]
Generic: 10 mg
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.
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).
Treatment of muscle spasm associated with acute painful musculoskeletal conditions (immediate release tablets: FDA approved in ages ≥15 years and adults; extended release capsules: FDA approved in adults)
Cyclobenzaprine may be confused with cycloSERINE, cyproheptadine
Flexeril may be confused with Floxin
Beers Criteria: Cyclobenzaprine is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) because most muscle relaxants are poorly tolerated in older adults due to anticholinergic effects caused by some muscle relaxants, risk of sedation, and an increased risk of fracture. Cyclobenzaprine has strong anticholinergic properties. In addition, efficacy is questionable at doses tolerated by geriatric patients (Beers Criteria [AGS 2023]).
Pharmacy Quality Alliance (PQA): Cyclobenzaprine (as a single agent or as part of a combination product) is identified as a high-risk medication in patients 65 years and older on the PQA’s, Use of High-Risk Medications in the Elderly (HRM) performance measure, a safety measure used by the Centers for Medicare and Medicaid Services (CMS) for Medicare plans (PQA 2017).
Flexin: Brand name for cyclobenzaprine [Chile], but also the brand name for diclofenac [Argentina] and orphenadrine [Israel]
Flexin [Chile] may be confused with Floxin brand name for flunarizine [Thailand], norfloxacin [South Africa], ofloxacin [US, Canada], and pefloxacin [Philippines]; Fluoxine brand name for fluoxetine [Thailand]; Flexinol brand name for methocarbamol and paracetamol [India]
Substrate of CYP1A2 (minor), CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with 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
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. 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 at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. 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
Chlorprothixene: Anticholinergic Agents may enhance the anticholinergic effect of Chlorprothixene. Risk C: Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination
CloZAPine: Anticholinergic Agents may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. 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. 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
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. 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
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
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
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. 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 the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. 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 (Systemic): 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
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 X: Avoid combination
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
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
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
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
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
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
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. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form 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 X: Avoid combination
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
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
Rivastigmine: Anticholinergic Agents may diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Anticholinergic Agents. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
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
Serotonergic Agents (High Risk): Cyclobenzaprine may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
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
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
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
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
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
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.
Published information related to cyclobenzaprine use in pregnancy is limited (Flannery 1989; Moreira 2014).
Relief of muscle spasms and pain; improvement in physical activities; signs/symptoms of serotonin syndrome (patients receiving other serotonergic drugs)
Centrally-acting skeletal muscle relaxant pharmacologically related to tricyclic antidepressants; reduces tonic somatic motor activity influencing both alpha and gamma motor neurons
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
Hepatic function impairment: In mild-to-moderate hepatic impairment, AUC and Cmax increased approximately twofold with immediate-release cyclobenzaprine.
Older adult: 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.
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