Flexeril

Muscle Relaxants, Centrally Acting, Plain

Oral Administration

If gastric irritation occurs, may be administered with meals.

Oral Solid Formulations

Extended-release capsules (Amrix)
Swallow capsules intact.
Alternatively, capsule contents may be sprinkled onto a tablespoon of applesauce and consumed immediately without chewing. Rinse the mouth to ensure all contents have been swallowed. Other foods have not been tested and should not be substituted for applesauce. Discard any unused portion of the capsules.

Severe

seizures / Delayed / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
angioedema / Rapid / 0-1.0
anaphylactic shock / Rapid / 0-1.0
SIADH / Delayed / Incidence not known
stroke / Early / Incidence not known
myocardial infarction / Delayed / Incidence not known
ileus / Delayed / Incidence not known
serotonin syndrome / Delayed / Incidence not known

Moderate

palpitations / Early / 0-6.0
confusion / Early / 1.0-3.0
blurred vision / Early / 1.0-3.0
constipation / Delayed / 1.0-3.0
ataxia / Delayed / 0-1.0
excitability / Early / 0-1.0
hallucinations / Early / 0-1.0
psychosis / Early / 0-1.0
hypertonia / Delayed / 0-1.0
dysarthria / Delayed / 0-1.0
urinary retention / Early / 0-1.0
hypotension / Rapid / 0-1.0
sinus tachycardia / Rapid / 0-1.0
peripheral vasodilation / Rapid / 0-1.0
cholestasis / Delayed / 0-1.0
hepatitis / Delayed / 0-1.0
jaundice / Delayed / 0-1.0
gastritis / Delayed / 0-1.0
peripheral neuropathy / Delayed / Incidence not known
dyspnea / Early / Incidence not known
galactorrhea / Delayed / Incidence not known
impotence (erectile dysfunction) / Delayed / Incidence not known
testicular swelling / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
hypertension / Early / Incidence not known
edema / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known
stomatitis / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known

Mild

xerostomia / Early / 6.0-58.0
drowsiness / Early / 16.0-39.0
dizziness / Early / 3.0-19.0
headache / Early / 1.0-17.0
nausea / Early / 1.0-8.0
fatigue / Early / 1.0-6.0
tremor / Early / 0-6.0
dysgeusia / Early / 6.0-6.0
acne vulgaris / Delayed / 6.0-6.0
dyspepsia / Early / 1.0-4.0
asthenia / Delayed / 1.0-3.0
irritability / Delayed / 1.0-3.0
vertigo / Early / 0-1.0
agitation / Early / 0-1.0
diplopia / Early / 0-1.0
paresthesias / Delayed / 0-1.0
malaise / Early / 0-1.0
anxiety / Delayed / 0-1.0
insomnia / Early / 0-1.0
tinnitus / Delayed / 0-1.0
urticaria / Rapid / 0-1.0
pruritus / Rapid / 0-1.0
rash / Early / 0-1.0
increased urinary frequency / Early / 0-1.0
flatulence / Early / 0-1.0
abdominal pain / Early / 0-1.0
diarrhea / Early / 0-1.0
vomiting / Early / 0-1.0
anorexia / Delayed / 0-1.0
diaphoresis / Early / 0-1.0
weakness / Early / 0-1.0
paranoia / Early / Incidence not known
breast enlargement / Delayed / Incidence not known
gynecomastia / Delayed / Incidence not known
libido decrease / Delayed / Incidence not known
libido increase / Delayed / Incidence not known
syncope / Early / Incidence not known
weight gain / Delayed / Incidence not known
tongue discoloration / Delayed / Incidence not known
weight loss / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
photosensitivity / Delayed / Incidence not known
myalgia / Early / Incidence not known
purpura / Delayed / Incidence not known

Amrix, Fexmid, Flexeril

Rx

Skeletal muscle relaxant closely related to the antidepressant amitriptyline. Has some pharmacologic effects similar to antidepressants but not used clinically as an antidepressant.

For the treatment of muscle spasm associated with acute, painful musculoskeletal conditions as an adjunct to rest and physical therapy. Oral dosage (immediate-release) Adults

5 mg PO 3 times daily, initially. May increase the dose to 7.5 or 10 mg PO 3 times daily based on response. Treatment duration beyond 2 to 3 weeks is not recommended.

Adolescents 15 to 17 years

5 mg PO 3 times daily, initially. May increase the dose to 7.5 or 10 mg PO 3 times daily based on response. Treatment duration beyond 2 to 3 weeks is not recommended.

Oral dosage (extended-release) Adults 18 to 64 years

15 mg PO once daily. Up to 30 mg/day may be required. Treatment duration beyond 2 to 3 weeks is not recommended.

For the treatment of fibromyalgia†. Oral dosage (immediate-release oral tablets) Adults

Safety and efficacy have not been established; not FDA-approved. While initial studies used oral doses typical to those used for acute musculoskeletal conditions , more recent clinical trials are using low-dose cyclobenzaprine to investigate the effect of the drug on fibromyalgia pain, tenderness, fatigue, moods and sleep. Doses range from 1 mg to 4 mg PO once nightly. Overall, treated patients appear to experience some improvement in sleep and pain scores. Low-dose side effects include sedation and dry mouth. A sublingual form under investigation is reported to cause oral hypoesthesia. Overall the evidence is weak in favor of usage; some guidelines include as a potential modality for patients with sleep disturbance as a symptom.

†Indicates off-label use

Hepatic Impairment

Immediate-release tablets: Patients with hepatic impairment require lower doses and less frequent dosing of cyclobenzaprine.
Extended-release once-daily capsules: Use is not recommended in patients with mild, moderate, or severe hepatic impairment due to the limited dosing flexibility.

Renal Impairment

No dosage adjustment needed.

Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and diphenhydramine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with cyclobenzaprine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Acetaminophen; Chlorpheniramine: (Moderate) Cyclobenzaprine and sedating antihistamines such as chlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Cyclobenzaprine and sedating antihistamines such as chlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Cyclobenzaprine and sedating antihistamines such as chlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Cyclobenzaprine and sedating antihistamines such as chlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Cyclobenzaprine and sedating antihistamines such as chlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Acetaminophen; Codeine: (Major) Concomitant use of codeine with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and doxylamine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Additive CNS depression is possible if skeletal muscle relaxants are used concomitantly with other CNS depressants. Dosage adjustments of one or both medications may be necessary.
Acetaminophen; Diphenhydramine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and diphenhydramine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Acetaminophen; Hydrocodone: (Major) Concomitant use of hydrocodone with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Acetaminophen; Oxycodone: (Major) Concomitant use of oxycodone with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Alfentanil: (Major) Concomitant use of alfentanil with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death. Additionally, concomitant use may result in serotonin syndrome. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Alosetron: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like cyclobenzaprine, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Alprazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Amantadine: (Moderate) Amantadine exhibits significant anticholinergic activity. Medications with significant anticholinergic activity, like cyclobenzaprine, may potentiate the anticholinergic effects of amantadine and may increase the risk of antimuscarinic-related side effects, including constipation and urinary retention.
Amifampridine: (Major) Carefully consider the need for concomitant treatment with cyclobenzaprine and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Cyclobenzaprine may increase the risk of seizures.
Amitriptyline: (Moderate) Monitor for unusual drowsiness, sedation, signs of anticholinergic toxicity, and serotonin syndrome during coadministration of cyclobenzaprine and tricyclic antidepressants. Concomitant use may increase the risk for additive CNS depression, anticholinergic adverse events, and serotonin syndrome. If serotonin syndrome occurs, consider discontinuation of therapy.
Amobarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Amoxapine: (Major) Cyclobenzaprine shares structural similarity to amoxapine; concurrent use of cyclobenzaprine should generally be avoided in patients taking cyclic antidepressants due to the additive risk of similar pharmacology, and side effects such as sedation and anticholinergic effects. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive anticholinergic adverse effects, such as constipation or urinary retention. Additive CNS effects such as drowsiness or dizziness may also occur.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Cyclobenzaprine may cause additive CNS depression if used concomitantly with other CNS depressants, such as anxiolytics, sedatives, and hypnotics. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary.
Apomorphine: (Moderate) Monitor for additive CNS effects if apomorphine is used concurrently with tricyclic antidepressants. Apomorphine causes considerable somnolence, and concomitant administration of apomorphine and CNS agents like cyclobenzaprine could result in additive CNS effects.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Aspirin, ASA; Caffeine; Orphenadrine: (Major) Orphenadrine has mild anticholinergic activity. Additive anticholinergic effects may be seen when orphenadrine is used concomitantly with other antimuscarinics, such as cyclobenzaprine. Clinicians should note that anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of codeine with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of oxycodone with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Atropine: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Atropine; Difenoxin: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Azelastine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
Azelastine; Fluticasone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
Barbiturates: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Belladonna; Opium: (Major) Concomitant use of opioid agonists with cyclobenzaprine may cause respiratory depression, profound sedation, and death. Limit the use of opioid agonists with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use of opioid agonists and cyclobenzaprine increases the risk for serotonin syndrome. Avoid concomitant use if possible and monitor for serotonin syndrome if use is necessary. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and belladonna use. Concomitant use may result in additive anticholinergic adverse effects.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of benzhydrocodone with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death. Additionally, concomitant use may result in serotonin syndrome. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Benzodiazepines: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects.
Benztropine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Botulinum Toxins: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Brompheniramine: (Moderate) Cyclobenzaprine and sedating antihistamines such as brompheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Cyclobenzaprine and sedating antihistamines such as brompheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Brompheniramine; Phenylephrine: (Moderate) Cyclobenzaprine and sedating antihistamines such as brompheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Brompheniramine; Pseudoephedrine: (Moderate) Cyclobenzaprine and sedating antihistamines such as brompheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Cyclobenzaprine and sedating antihistamines such as brompheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Buprenorphine: (Major) Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Buprenorphine; Naloxone: (Major) Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Bupropion: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as cyclobenzaprine. Use low initial doses of bupropion and increase the dose gradually. Monitor patients for signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome.
Bupropion; Naltrexone: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as cyclobenzaprine. Use low initial doses of bupropion and increase the dose gradually. Monitor patients for signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome.
Butabarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Butalbital; Acetaminophen: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Butalbital; Acetaminophen; Caffeine: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of codeine with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of codeine with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Butorphanol: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as cyclobenzaprine, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and cyclobenzaprine. CNS depressants can potentiate the effects of cannabidiol.
Carbidopa; Levodopa; Entacapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Carbinoxamine: (Moderate) Cyclobenzaprine and sedating antihistamines such as carbinoxamine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Celecoxib; Tramadol: (Major) Concomitant use of tramadol with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome, seizures, and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and cyclobenzaprine. Concurrent use may result in additive CNS depression.
Cetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Cetirizine; Pseudoephedrine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Cyclobenzaprine and sedating antihistamines such as dexchlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Chlorcyclizine: (Moderate) Cyclobenzaprine and sedating antihistamines such as chlorcyclizine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Chlordiazepoxide: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Chlordiazepoxide; Amitriptyline: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation. (Moderate) Monitor for unusual drowsiness, sedation, signs of anticholinergic toxicity, and serotonin syndrome during coadministration of cyclobenzaprine and tricyclic antidepressants. Concomitant use may increase the risk for additive CNS depression, anticholinergic adverse events, and serotonin syndrome. If serotonin syndrome occurs, consider discontinuation of therapy.
Chlordiazepoxide; Clidinium: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Chlorpheniramine: (Moderate) Cyclobenzaprine and sedating antihistamines such as chlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Chlorpheniramine; Codeine: (Major) Concomitant use of codeine with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Cyclobenzaprine and sedating antihistamines such as chlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Chlorpheniramine; Dextromethorphan: (Moderate) Cyclobenzaprine and sedating antihistamines such as chlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Cyclobenzaprine and sedating antihistamines such as chlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Cyclobenzaprine and sedating antihistamines such as chlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of opioid agonists with cyclobenzaprine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. (Moderate) Cyclobenzaprine and sedating antihistamines such as chlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of hydrocodone with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Cyclobenzaprine and sedating antihistamines such as chlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Cyclobenzaprine and sedating antihistamines such as chlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Chlorpheniramine; Phenylephrine: (Moderate) Cyclobenzaprine and sedating antihistamines such as chlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Chlorpheniramine; Pseudoephedrine: (Moderate) Cyclobenzaprine and sedating antihistamines such as chlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Chlorpromazine: (Moderate) Additive anticholinergic effects may be seen when chlorpromazine is used concomitantly with other drugs with antimuscarinic activity such as cyclobenzaprine. Antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive sedation may also occur.
Chlorthalidone; Clonidine: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of clonidine and cyclobenzaprine; a clonidine dose adjustment may be necessary. Concomitant use may result in decreased clonidine efficacy and/or additive CNS depression. The hypotensive effect of clonidine may be reduced by tricyclic antidepressants, and cyclobenzaprine is structurally related to the tricyclic antidepressants.
Clemastine: (Moderate) Cyclobenzaprine and sedating antihistamines such as clemastine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Clomipramine: (Moderate) Monitor for unusual drowsiness, sedation, signs of anticholinergic toxicity, and serotonin syndrome during coadministration of cyclobenzaprine and tricyclic antidepressants. Concomitant use may increase the risk for additive CNS depression, anticholinergic adverse events, and serotonin syndrome. If serotonin syndrome occurs, consider discontinuation of therapy.
Clonazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Clonidine: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of clonidine and cyclobenzaprine; a clonidine dose adjustment may be necessary. Concomitant use may result in decreased clonidine efficacy and/or additive CNS depression. The hypotensive effect of clonidine may be reduced by tricyclic antidepressants, and cyclobenzaprine is structurally related to the tricyclic antidepressants.
Clorazepate: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Clozapine: (Moderate) Additive anticholinergic effects may be seen when clozapine is used concomitantly with other drugs with antimuscarinic activity such as cyclobenzaprine. Antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Particular attention should be paid to GI problems because of the possible development of paralytic ileus. Additive sedation may also occur.
Codeine: (Major) Concomitant use of codeine with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Codeine; Guaifenesin: (Major) Concomitant use of codeine with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of codeine with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of codeine with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and promethazine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Codeine; Promethazine: (Major) Concomitant use of codeine with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and promethazine. Concomitant use may result in additive CNS depression or anticholinergic effects.
COMT inhibitors: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Cyproheptadine: (Moderate) Cyclobenzaprine and cyproheptadine exhibit additive anticholinergic activity. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Desipramine: (Moderate) Monitor for unusual drowsiness, sedation, signs of anticholinergic toxicity, and serotonin syndrome during coadministration of cyclobenzaprine and tricyclic antidepressants. Concomitant use may increase the risk for additive CNS depression, anticholinergic adverse events, and serotonin syndrome. If serotonin syndrome occurs, consider discontinuation of therapy.
Deutetrabenazine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as cyclobenzaprine, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
Dexchlorpheniramine: (Moderate) Cyclobenzaprine and sedating antihistamines such as dexchlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Cyclobenzaprine and sedating antihistamines such as dexchlorpheniramine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Dexmedetomidine: (Moderate) Due to the anesthetic effects of dexmedetomidine, concurrent use with other CNS depressants, such as skeletal muscle relaxants, could result in additive sedative effects and possibly prolong recovery from anesthesia. Dosage adjustments of either or both medications may be necessary.
Dextromethorphan; Bupropion: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as cyclobenzaprine. Use low initial doses of bupropion and increase the dose gradually. Monitor patients for signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and diphenhydramine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Diazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Dicyclomine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and dicyclomine use. Concomitant use may result in additive anticholinergic adverse effects.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Dimenhydrinate: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant dimenhydrinate and cyclobenzaprine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Diphenhydramine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and diphenhydramine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Diphenhydramine; Ibuprofen: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and diphenhydramine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Diphenhydramine; Naproxen: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and diphenhydramine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Diphenhydramine; Phenylephrine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and diphenhydramine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Diphenoxylate; Atropine: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Disopyramide: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties like disopyramide and cyclobenzaprine are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation.
Donepezil: (Moderate) The use of cyclobenzaprine may result in significant anticholinergic activity, thereby interfering with the therapeutic effect of donepezil. Donepezil inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine.
Donepezil; Memantine: (Moderate) The use of cyclobenzaprine may result in significant anticholinergic activity, thereby interfering with the therapeutic effect of donepezil. Donepezil inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine.
Doxepin: (Moderate) Monitor for unusual drowsiness, sedation, signs of anticholinergic toxicity, and serotonin syndrome during coadministration of cyclobenzaprine and tricyclic antidepressants. Concomitant use may increase the risk for additive CNS depression, anticholinergic adverse events, and serotonin syndrome. If serotonin syndrome occurs, consider discontinuation of therapy.
Doxylamine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and doxylamine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Doxylamine; Pyridoxine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and doxylamine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Dronabinol: (Moderate) Concomitant use of skeletal muscle relaxants with dronabinol can result in additive CNS depression and dizziness, which can impair the ability to undertake tasks requiring mental alertness. Utilize appropriate caution if these drugs are given together.
Entacapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Escitalopram: (Major) Because of the potential risk and severity of serotonin syndrome, concurrent use of cyclobenzaprine with other drugs that have serotonergic properties, such as the selective serotonin reuptake inhibitors (SSRIs), should generally be avoided. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome is suspected, milnacipran and concurrent serotonergic agents should be discontinued.
Esketamine: (Major) Closely monitor patients receiving esketamine and skeletal muscle relaxants for sedation and other CNS depressant effects. Patients who receive a dose of esketamine should not drive or engage in other activities requiring alertness until the next day after a restful sleep.
Estazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Eszopiclone: (Moderate) Cyclobenzaprine may cause additive CNS depression if used concomitantly with other CNS depressants, such as anxiolytics, sedatives, and hypnotics. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Ethiodized Oil: (Major) Use of medications that lower the seizure threshold, such as cyclobenzaprine, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Cyclobenzaprine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Etomidate: (Moderate) General anesthetics, such as etomidate, potentiate the effects of other CNS depressants, including skeletal muscle relaxants like cyclobenzaprine.
Fenfluramine: (Moderate) Use fenfluramine and cyclobenzaprine with caution due to an increased risk of serotonin syndrome and additive CNS depression. Monitor for excessive sedation, somnolence, and serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Fentanyl: (Major) Concomitant use of fentanyl with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medication with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during tre

atment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Flavoxate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and flavoxate use. Concomitant use may result in additive anticholinergic adverse effects.
Fluoxetine: (Major) Because of the potential risk and severity of serotonin syndrome, concurrent use of cyclobenzaprine with other drugs that have serotonergic properties, such as the selective serotonin reuptake inhibitors (SSRIs), should generally be avoided. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome is suspected, milnacipran and concurrent serotonergic agents should be discontinued.
Fluphenazine: (Moderate) Cyclobenzaprine possesses antimuscarinic properties, which can cause dry mouth, urinary difficulties and slowing of gastrointestinal motility. If used with other drugs with antimuscarinic properties, such as most antipsychotic phenothiazines, anticholinergic side effects can be additive. Particular attention should be paid to GI problems because of the possible development of paralytic ileus. Additive CNS depression causing sedation and/or dizziness is also possible.
Flurazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Fluvoxamine: (Major) Because of the potential risk and severity of serotonin syndrome, concurrent use of cyclobenzaprine with other drugs that have serotonergic properties, such as the selective serotonin reuptake inhibitors (SSRIs), should generally be avoided. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome is suspected, milnacipran and concurrent serotonergic agents should be discontinued.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and cyclobenzaprine. Concomitant use of gabapentin with cyclobenzaprine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Galantamine: (Moderate) Concurrent use of certain muscle relaxants, such as cyclobenzaprine with galantamine should be avoided if possible. Galantamine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Use of cyclobenzaprine may result in significant anticholinergic activity, thereby interfering with the therapeutic effect of galantamine.
Glycopyrrolate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Glycopyrrolate; Formoterol: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Granisetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as cyclobenzaprine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome is suspected, granisetron and concurrent serotonergic agents should be discontinued and appropriate medical treatment should be initiated.
Guaifenesin; Hydrocodone: (Major) Concomitant use of hydrocodone with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Homatropine; Hydrocodone: (Major) Concomitant use of hydrocodone with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and homatropine use. Concomitant use may result in additive anticholinergic adverse effects.
Hydrocodone: (Major) Concomitant use of hydrocodone with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Hydrocodone; Ibuprofen: (Major) Concomitant use of hydrocodone with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Hydrocodone; Pseudoephedrine: (Major) Concomitant use of hydrocodone with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking cyclobenzaprine. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Hydromorphone: (Major) Concomitant use of opioid agonists with cyclobenzaprine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hydroxyzine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and hydroxyzine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Hyoscyamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects.
Ibuprofen; Oxycodone: (Major) Concomitant use of oxycodone with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Imipramine: (Moderate) Monitor for unusual drowsiness, sedation, signs of anticholinergic toxicity, and serotonin syndrome during coadministration of cyclobenzaprine and tricyclic antidepressants. Concomitant use may increase the risk for additive CNS depression, anticholinergic adverse events, and serotonin syndrome. If serotonin syndrome occurs, consider discontinuation of therapy.
Indacaterol; Glycopyrrolate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Iodixanol: (Major) Use of medications that lower the seizure threshold, such as cyclobenzaprine, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Cyclobenzaprine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iohexol: (Major) Use of medications that lower the seizure threshold, such as cyclobenzaprine, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Cyclobenzaprine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iomeprol: (Major) Use of medications that lower the seizure threshold, such as cyclobenzaprine, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Cyclobenzaprine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopamidol: (Major) Use of medications that lower the seizure threshold, such as cyclobenzaprine, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Cyclobenzaprine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopromide: (Major) Use of medications that lower the seizure threshold, such as cyclobenzaprine, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Cyclobenzaprine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ioversol: (Major) Use of medications that lower the seizure threshold, such as cyclobenzaprine, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Cyclobenzaprine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Isocarboxazid: (Contraindicated) Concurrent use of cyclobenzaprine and MAOIs is contraindicated. Further, use of cyclobenzaprine within 14 days of MAOI discontinuation is contraindicated. Hyperpyretic crisis, seizures and deaths have occurred in patients receiving cyclobenzaprine or structurally similar tricyclic antidepressants concomitantly with MAO inhibitor drugs. A patient taking phenelzine developed symptoms of serotonin syndrome including confusion, agitation, tremors, tachycardia, diaphoresis, hallucinations, delusions, and fever after the third oral dose of cyclobenzaprine 10 mg, which was prescribed every 8 hours. The patient remained symptomatic despite drug discontinuation. All of her symptoms progressively resolved over the next 3 days. Reinitiation of phenelzine was without consequences.
Isosulfan Blue: (Major) Use of medications that lower the seizure threshold, such as cyclobenzaprine, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Cyclobenzaprine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Lasmiditan: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and cyclobenzaprine. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and cyclobenzaprine. Dosage adjustments of lemborexant and cyclobenzaprine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Levocetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Levorphanol: (Major) Concomitant use of opioid agonists with cyclobenzaprine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial levorphanol dosage by 50% or more. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Linezolid: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. Hypertensive crises, severe convulsive seizures, coma, or circulatory collapse may occur in patients receiving cyclobenzaprine concomitantly.
Lofexidine: (Moderate) Monitor for excessive hypotension and sedation during coadministration of lofexidine and cyclobenzaprine. Lofexidine can potentiate the effects of CNS depressants.
Lorazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Loxapine: (Moderate) Loxapine and cyclobenzaprine both have anticholinergic activity. The concomitant use of these drugs can increase the risk of anticholinergic adverse reactions including exacerbation of glaucoma, constipation, and urinary retention. Loxapine is a central nervous system (CNS) depressant. The concurrent use of loxapine with other CNS depressants (e.g., muscle relaxants such as cyclobenzaprine) can increase the risk of respiratory depression, hypotension, profound sedation, and syncope. Therefore, consider reducing the dose of CNS depressants if used concomitantly with loxapine.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
Maprotiline: (Major) Concurrent use of cyclobenzaprine should generally be avoided in patients taking maprotiline due to the additive risk of similar pharmacology and side-effect profiles. Cyclobenzaprine possesses antimuscarinic properties, which can cause dry mouth, urinary difficulties and slowing of gastrointestinal motility. If used with other drugs with antimuscarinic properties, such as maprotiline, anticholinergic side effects can be additive. Particular attention should be paid to GI problems because of the possible development of paralytic ileus. Patients should be monitored for excessive adverse effects from either agent.
Meclizine: (Moderate) Cyclobenzaprine and sedating antihistamines such as meclizine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Meperidine: (Major) Concomitant use of opioid agonists with cyclobenzaprine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Meprobamate: (Moderate) Cyclobenzaprine may cause additive CNS depression if used concomitantly with other CNS depressants, such as anxiolytics, sedatives, and hypnotics. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary.
Methadone: (Major) Concomitant use of methadone with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death. Additionally, concomitant use may result in serotonin syndrome. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects.
Methohexital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Methscopolamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and methscopolamine use. Concomitant use may result in additive anticholinergic adverse effects.
Midazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Mirtazapine: (Moderate) Skeletal muscle relaxants like cyclobenzaprine may cause additive CNS depression if used concomitantly with other drugs with CNS depressant properties such as mirtazapine. Combination therapy may amplify sedation and dizziness, which can impair the patient's ability to perform tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary in some instances. In addition, anecdotal evidence from case reports suggests that cyclobenzaprine may possess serotonin augmenting effects that may be clinically relevant during administration of the drug with serotonin-enhancing medications. In theory, there is a remote possibility that serotonin syndrome may occur from concurrent administration of cyclobenzaprine and mirtazapine since mirtazapine increases central serotonin activity. In addition, cyclobenzaprine is closely related to the tricyclic antidepressants, which are known to decrease serotonin reuptake. Caution is advisable during concurrent use with mirtazapine until more information about cyclobenzaprine's effects on serotonin becomes available.
Molindone: (Moderate) Simultaneous use of skeletal muscle relaxants and other CNS depressants, such as molindone, can increase CNS depression. In addition, antipsychotics are associated with anticholinergic effects; therefore, additive effects may be seen during concurrent use of molindone and other drugs having anticholinergic activity. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Monoamine oxidase inhibitors: (Contraindicated) Concurrent use of cyclobenzaprine and MAOIs is contraindicated. Further, use of cyclobenzaprine within 14 days of MAOI discontinuation is contraindicated. Hyperpyretic crisis, seizures and deaths have occurred in patients receiving cyclobenzaprine or structurally similar tricyclic antidepressants concomitantly with MAO inhibitor drugs. A patient taking phenelzine developed symptoms of serotonin syndrome including confusion, agitation, tremors, tachycardia, diaphoresis, hallucinations, delusions, and fever after the third oral dose of cyclobenzaprine 10 mg, which was prescribed every 8 hours. The patient remained symptomatic despite drug discontinuation. All of her symptoms progressively resolved over the next 3 days. Reinitiation of phenelzine was without consequences.
Morphine: (Major) Concomitant use of morphine with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Morphine; Naltrexone: (Major) Concomitant use of morphine with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Nabilone: (Major) Avoid use together if possible. Use of nabilone with skeletal muscle relaxants can potentiate the CNS depressant effects of nabilone on sedation, dizziness and other side effects, which can impair the ability to undertake tasks requiring mental alertness.
Nalbuphine: (Major) Concomitant use of nalbuphine with cyclobenzaprine may cause excessive sedation and somnolence. Limit the use of nalbuphine with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Nefazodone: (Major) Coadministration of medications that increase central serotonergic activity, such as cyclobenzaprine and nefazodone, may increase the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical treatment should be implemented. In addition, in vitro data indicate that CYP3A4 and CYP1A2 are primarily responsible for the metabolism of cyclobenzaprine, and concurrent use of a CYP3A4 inhibitor such as nefazodone could theoretically result in elevated cyclobenzaprine plasma concentrations. Patients should be observed for enhanced side effects, such as CNS depression, if cyclobenzaprine and nefazodone are coadministered.
Neostigmine; Glycopyrrolate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold, such as cyclobenzaprine, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Cyclobenzaprine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Nortriptyline: (Moderate) Monitor for unusual drowsiness, sedation, signs of anticholinergic toxicity, and serotonin syndrome during coadministration of cyclobenzaprine and tricyclic antidepressants. Concomitant use may increase the risk for additive CNS depression, anticholinergic adverse events, and serotonin syndrome. If serotonin syndrome occurs, consider discontinuation of therapy.
Octreotide: (Moderate) Octreotide decreases GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Other drugs that also decrease GI motility, such as cyclobenzaprine, may produce additive effects with antidiarrheals if used concomitantly.
Olanzapine: (Moderate) When cyclobenzaprine and olanzapine are used concurrently, an increase in anticholinergic side effects may occur. Cyclobenzaprine possesses antimuscarinic properties, which can cause dry mouth, urinary difficulties and slowing of gastrointestinal motility. If used with other drugs with antimuscarinic properties, such as olanzapine, anticholinergic side effects can be additive. Particular attention should be paid to GI problems because of the possible development of paralytic ileus.
Olanzapine; Fluoxetine: (Major) Because of the potential risk and severity of serotonin syndrome, concurrent use of cyclobenzaprine with other drugs that have serotonergic properties, such as the selective serotonin reuptake inhibitors (SSRIs), should generally be avoided. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome is suspected, milnacipran and concurrent serotonergic agents should be discontinued. (Moderate) When cyclobenzaprine and olanzapine are used concurrently, an increase in anticholinergic side effects may occur. Cyclobenzaprine possesses antimuscarinic properties, which can cause dry mouth, urinary difficulties and slowing of gastrointestinal motility. If used with other drugs with antimuscarinic properties, such as olanzapine, anticholinergic side effects can be additive. Particular attention should be paid to GI problems because of the possible development of paralytic ileus.
Olanzapine; Samidorphan: (Moderate) When cyclobenzaprine and olanzapine are used concurrently, an increase in anticholinergic side effects may occur. Cyclobenzaprine possesses antimuscarinic properties, which can cause dry mouth, urinary difficulties and slowing of gastrointestinal motility. If used with other drugs with antimuscarinic properties, such as olanzapine, anticholinergic side effects can be additive. Particular attention should be paid to GI problems because of the possible development of paralytic ileus.
Oliceridine: (Major) Concomitant use of oliceridine with cyclobenzaprine may cause excessive sedation and somnolence. Limit the use of oliceridine with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Opicapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Orphenadrine: (Major) Orphenadrine has mild anticholinergic activity. Additive anticholinergic effects may be seen when orphenadrine is used concomitantly with other antimuscarinics, such as cyclobenzaprine. Clinicians should note that anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Oxazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Oxybutynin: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and oxybutynin use. Concomitant use may result in additive anticholinergic adverse effects.
Oxycodone: (Major) Concomitant use of oxycodone with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Oxymorphone: (Major) Concomitant use of opioid agonists with cyclobenzaprine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxymorphone dosage by one-third to one-half. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Ozanimod: (Contraindicated) Coadministration of ozanimod with cyclobenzaprine is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of cyclobenzaprine. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Cyclobenzaprine may increase blood pressure and serotonergic side effects by increasing norepinephrine and serotonin concentrations.
Paroxetine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant cyclobenzaprine and paroxetine use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Pentazocine: (Major) Concomitant use of pentazocine with cyclobenzaprine may cause respiratory depression, profound sedation, and death. Limit the use of pentazocine with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use of pentazocine and cyclobenzaprine increases the risk for serotonin syndrome. Avoid concomitant use if possible and monitor for serotonin syndrome if use is necessary.
Pentazocine; Naloxone: (Major) Concomitant use of pentazocine with cyclobenzaprine may cause respiratory depression, profound sedation, and death. Limit the use of pentazocine with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use of pentazocine and cyclobenzaprine increases the risk for serotonin syndrome. Avoid concomitant use if possible and monitor for serotonin syndrome if use is necessary.
Pentobarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Perphenazine: (Moderate) Additive anticholinergic effects may be seen when perphenazine is used concomitantly with other drugs with antimuscarinic activity such as cyclobenzaprine. Antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive sedation may also occur.
Perphenazine; Amitriptyline: (Moderate) Additive anticholinergic effects may be seen when perphenazine is used concomitantly with other drugs with antimuscarinic activity such as cyclobenzaprine. Antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive sedation may also occur. (Moderate) Monitor for unusual drowsiness, sedation, signs of anticholinergic toxicity, and serotonin syndrome during coadministration of cyclobenzaprine and tricyclic antidepressants. Concomitant use may increase the risk for additive CNS depression, anticholinergic adverse events, and serotonin syndrome. If serotonin syndrome occurs, consider discontinuation of therapy.
Phenelzine: (Contraindicated) Concurrent use of cyclobenzaprine and MAOIs is contraindicated. Further, use of cyclobenzaprine within 14 days of MAOI discontinuation is contraindicated. Hyperpyretic crisis, seizures and deaths have occurred in patients receiving cyclobenzaprine or structurally similar tricyclic antidepressants concomitantly with MAO inhibitor drugs. A patient taking phenelzine developed symptoms of serotonin syndrome including confusion, agitation, tremors, tachycardia, diaphoresis, hallucinations, delusions, and fever after the third oral dose of cyclobenzaprine 10 mg, which was prescribed every 8 hours. The patient remained symptomatic despite drug discontinuation. All of her symptoms progressively resolved over the next 3 days. Reinitiation of phenelzine was without consequences.
Phenobarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects. (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects. (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and scopolamine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and cyclobenzaprine. Concomitant use of pregabalin with cyclobenzaprine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Primidone: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Prochlorperazine: (Moderate) Additive anticholinergic effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity such as cyclobenzaprine. Antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive sedation may also occur.
Promethazine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and promethazine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Promethazine; Dextromethorphan: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and promethazine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Promethazine; Phenylephrine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and promethazine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Propantheline: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and propantheline use. Concomitant use may result in additive anticholinergic adverse effects.
Protriptyline: (Moderate) Monitor for unusual drowsiness, sedation, signs of anticholinergic toxicity, and serotonin syndrome during coadministration of cyclobenzaprine and tricyclic antidepressants. Concomitant use may increase the risk for additive CNS depression, anticholinergic adverse events, and serotonin syndrome. If serotonin syndrome occurs, consider discontinuation of therapy.
Pseudoephedrine; Triprolidine: (Moderate) Cyclobenzaprine and sedating antihistamines such as triprolidine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Quazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Ramelteon: (Moderate) Cyclobenzaprine may cause additive CNS depression if used concomitantly with other CNS depressants, such as anxiolytics, sedatives, and hypnotics. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary.
Rasagiline: (Contraindicated) Concurrent use of rasagiline and cyclobenzaprine is contraindicated. Cyclobenzaprine is structurally related to the class of tricyclic antidepressants, and severe CNS toxicity with hyperpyrexia has been reported during concurrent use of antidepressants and selective or non-selective MAOIs. At least 14 days should elapse between rasagiline discontinuation and cyclobenzaprine initiation.
Remifentanil: (Major) Concomitant use of remifentanil with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death. Additionally, concomitant use may result in serotonin syndrome. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Remimazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Rivastigmine: (Moderate) Concurrent use of certain muscle relaxants, such as cyclobenzaprine or orphenadrine, with rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Use of cyclobenzaprine or high doses of orphenadrine may result in significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Safinamide: (Contraindicated) Safinamide is contraindicated for use with cyclobenzaprine due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of cyclobenzaprine.
Scopolamine: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and scopolamine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Secobarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Selegiline: (Contraindicated) Cyclobenzaprine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with cyclobenzaprine. After stopping treatment with cyclobenzaprine, a time period equal to 4 to 5 half-lives of cyclobenzaprine or any active metabolite should elapse before starting therapy with selegiline.
Serotonin norepinephrine reuptake inhibitors: (Major) Cautious use of cyclobenzaprine and drugs that increase serotonin concentrations such as serotonin norepinephrine reuptake inhibitors (SNRIs) is advised because of the possibility of serotonin syndrome. If these drugs must be used together, closely monitor the patient for signs and symptoms of serotonin syndrome. If such a reaction develops, immediately discontinue cyclobenzaprine and the SSRI. A suspected case of serotonin syndrome was noted in a man who took duloxetine, opiates, and cyclobenzaprine. The man developed worsening confusion, hallucinations, diaphoresis, tachycardia, tremors, marked agitation, spontaneous sustained clonus, and multifocal myoclonus, but recovered after duloxetine and cyclobenzaprine discontinuation and cyproheptadine initiation.
Sertraline: (Major) Because of the potential risk and severity of serotonin syndrome, concurrent use of cyclobenzaprine with other drugs that have serotonergic properties, such as the selective serotonin reuptake inhibitors (SSRIs), should generally be avoided. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome is suspected, sertraline and concurrent serotonergic agents should be discontinued.
Sodium Iodide: (Moderate) Because medications that decrease salivation increase the time of sodium iodide I-131 induced radiation exposure to salivary glands, consider discontinuing medications with antimuscarinic activity including cyclobenzaprine prior to sodium iodide I-131 administration.
Sodium Oxybate: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and cyclobenzaprine. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Major) Concomitant use of sufentanil with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death. Additionally, concomitant use may result in serotonin syndrome. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Suvorexant: (Moderate) Cyclobenzaprine may cause additive CNS depression if used concomitantly with other CNS depressants, such as anxiolytics, sedatives, and hypnotics. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary.
Tapentadol: (Major) Concomitant use of opioid agonists with cyclobenzaprine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Tasimelteon: (Moderate) Cyclobenzaprine may cause additive CNS depression if used concomitantly with other CNS depressants, such as anxiolytics, sedatives, and hypnotics. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary.
Temazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Thalidomide: (Major) Avoid the concomitant use of thalidomide with other central nervous system depressants such as skeletal muscle relaxants due to the potential for additive sedative effects.
Thioridazine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like thioridazine and cyclobenzaprine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Thiothixene: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Tolcapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Tolterodine: (Moderate) Additive anticholinergic effects may be seen when tolterodine is concomitantly with other drugs with antimuscarinic activity such as cyclobenzaprine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive hypotension or CNS effects such as drowsiness may also occur.
Tramadol: (Major) Concomitant use of tramadol with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome, seizures, and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Tramadol; Acetaminophen: (Major) Concomitant use of tramadol with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome, seizures, and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Trandolapril; Verapamil: (Moderate) If concomitant treatment with cyclobenzaprine and verapamil is clinically warranted, careful observation is advised, particularly during treatment initiation or dose increases, due to the potential risk of serotonin syndrome. Discontinue all serotonergic agents and initiate supportive symptomatic treatment if serotonin syndrome occurs.
Tranylcypromine: (Contraindicated) Concurrent use of cyclobenzaprine and MAOIs is contraindicated. Further, use of cyclobenzaprine within 14 days of MAOI discontinuation is contraindicated. Hyperpyretic crisis, seizures and deaths have occurred in patients receiving cyclobenzaprine or structurally similar tricyclic antidepressants concomitantly with MAO inhibitor drugs. A patient taking phenelzine developed symptoms of serotonin syndrome including confusion, agitation, tremors, tachycardia, diaphoresis, hallucinations, delusions, and fever after the third oral dose of cyclobenzaprine 10 mg, which was prescribed every 8 hours. The patient remained symptomatic despite drug discontinuation. All of her symptoms progressively resolved over the next 3 days. Reinitiation of phenelzine was without consequences.
Trazodone: (Moderate) Increased CNS depressant effects, including sedation, may be seen if cyclcobenzaprine and trazodone are administered concurrently.
Triazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Tricyclic antidepressants: (Moderate) Monitor for unusual drowsiness, sedation, signs of anticholinergic toxicity, and serotonin syndrome during coadministration of cyclobenzaprine and tricyclic antidepressants. Concomitant use may increase the risk for additive CNS depression, anticholinergic adverse events, and serotonin syndrome. If serotonin syndrome occurs, consider discontinuation of therapy.
Trifluoperazine: (Moderate) Additive anticholinergic effects may be seen when trifluoperazine is used concomitantly with other drugs with antimuscarinic activity such as cyclobenzaprine. Antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Trihexyphenidyl: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and trihexyphenidyl use. Concomitant use may result in additive anticholinergic adverse effects.
Trimipramine: (Moderate) Monitor for unusual drowsiness, sedation, signs of anticholinergic toxicity, and serotonin syndrome during coadministration of cyclobenzaprine and tricyclic antidepressants. Concomitant use may increase the risk for additive CNS depression, anticholinergic adverse events, and serotonin syndrome. If serotonin syndrome occurs, consider discontinuation of therapy.
Triprolidine: (Moderate) Cyclobenzaprine and sedating antihistamines such as triprolidine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Trospium: (Moderate) Cyclobenzaprine possesses antimuscarinic properties, which can cause dry mouth, urinary difficulties and slowing of gastrointestinal motility. If used with other drugs with antimuscarinic properties, anticholinergic side effects can be additive.
Valerian, Valeriana officinalis: (Moderate) Cyclobenzaprine may cause additive CNS depression if used concomitantly with other CNS depressants, such as valerian, Valeriana officinalis. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary.
Verapamil: (Moderate) If concomitant treatment with cyclobenzaprine and verapamil is clinically warranted, careful observation is advised, particularly during treatment initiation or dose increases, due to the potential risk of serotonin syndrome. Discontinue all serotonergic agents and initiate supportive symptomatic treatment if serotonin syndrome occurs.
Vilazodone: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering vilazodone with other drugs that have serotonergic properties such as cyclobenzaprine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored closely for toxicity. Due to the CNS effects of vilazodone, caution should be used when vilazodone is given in combination with other centrally acting medications such as cyclobenzaprine. Patients should be advised to avoid driving or engaging in other tasks requiring mental alertness until they know how this combination affects them.
Zaleplon: (Moderate) Cyclobenzaprine may cause additive CNS depression if used concomitantly with other CNS depressants, such as anxiolytics, sedatives, and hypnotics. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary.
Zolpidem: (Moderate) Cyclobenzaprine may cause additive CNS depression if used concomitantly with other CNS depressants, such as anxiolytics, sedatives, and hypnotics. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary.

Amrix/Cyclobenzaprine/Cyclobenzaprine Hydrochloride Oral Cap ER: 15mg, 30mg
Cyclobenzaprine/Cyclobenzaprine Hydrochloride/Fexmid/Flexeril Oral Tab: 5mg, 7.5mg, 10mg

Adults

30 mg/day PO.

Geriatric

30 mg/day PO. Elderly are at higher risk for adverse effects.

Adolescents

15 years and older: 30 mg/day PO (immediate-release tablets only).
Less than 15 years: Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Since cyclobenzaprine is so closely similar to amitriptyline in chemical structure, some of its effects are similar to the tricyclic antidepressants, including anticholinergic activity, potentiation of norepinephrine, and antagonism of reserpine. Cyclobenzaprine relieves muscle spasms through a central action, possibly at the brain stem level, with no direct action on the neuromuscular junction or the muscle involved. It is not a peripheral neuromuscular blocker. Anecdotal evidence from case reports suggests that the drug may possess serotonin augmenting effects, which may be clinically relevant in some instances. Animal data indicate that inhibition of serotonergic descending systems in the spinal cord (e.g., 5-HT2 receptors) appears to be a significant component of the action of cyclobenzaprine as a muscle relaxant. Treatment with the drug reduces pain and tenderness and improves mobility. Unlike dantrolene, cyclobenzaprine is not effective for muscle spasm secondary to cerebral or spinal cord disease.

Cyclobenzaprine is administered orally. It is extensively metabolized and undergoes enterohepatic recirculation. Cyclobenzaprine exhibits linear pharmacokinetics at recommended doses, and reaches steady-state within 3 to 4 days. The onset of skeletal muscle relaxant action occurs in about 1 hour, and duration of action ranges from 12 to 24 hours. Spasmolytic effects may take 1 to 2 days to be fully manifest. Cyclobenzaprine is 93% protein-bound, and no evidence is available as to whether it crosses the placenta or is distributed into breast milk. It undergoes extensive metabolism in the liver and is excreted mainly as conjugated inactive metabolites in the urine and as unchanged drug via the bile in the feces. Hepatic cytochrome P-450 isoenzymes (CYP3A4, CYP1A2, and to a lesser extent CYP2D6) are primarily responsible for the N-demethylation pathway of cyclobenzaprine metabolism (one of the oxidative pathways). The half-life ranges from 8 to 37 hours (mean 18 hours).
 
Affected cytochrome P450 isoenzymes and drug transporter: CYP3A4, CYP1A2, CYP2D6

Oral Route

Cyclobenzaprine is well absorbed from the GI tract following oral administration. Estimates of mean oral bioavailability range from 33% to 55%. When the extended-release capsules were given to 15 healthy adults, Cmax and AUC increased in a dose-proportional manner from 15 mg to 30 mg; Tmax was 7 to 8 hours for both doses. When the contents of the extended-release capsules were administered by sprinkling on applesauce, it was found to be bioequivalent to the same dose administered as an intact capsule. A food effect study using a single dose of 30 mg extended-release capsule demonstrated a statistically significant increase in bioavailability when the capsule was given with food relative to a fasting state. Cmax increased by 35% and AUC by 20%, and Tmax was not affected.

Pregnancy

Case reports of cyclobenzaprine use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, decreased body weight and survival were reported among the offspring of pregnant rats who were given oral cyclobenzaprine at doses of 10 and 20 mg/kg/day (equivalent to 3 and 6 times the maximum recommended human dose on a mg/m2 basis) throughout pregnancy and lactation.[43354]

There are no data on the presence of cyclobenzaprine in human milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for cyclobenzaprine and any potential adverse effects on the breast-fed infant from cyclobenzaprine or the underlying maternal condition.[43354]