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  • CLASSES

    Compounding Kits Miscellaneous
    Muscle Relaxants, Centrally Acting, Plain

    DEA CLASS

    Rx

    DESCRIPTION

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

    COMMON BRAND NAMES

    Active - Cyclobenzaprine, Amrix, EnovaRX, Fexmid, Flexeril

    HOW SUPPLIED

    Active - Cyclobenzaprine Topical Pwd: 5%
    Amrix/Cyclobenzaprine/Cyclobenzaprine Hydrochloride Oral Cap ER: 15mg, 30mg
    Cyclobenzaprine/Cyclobenzaprine Hydrochloride/Fexmid/Flexeril Oral Tab: 5mg, 7.5mg, 10mg
    EnovaRX Topical Pwd F/Recon: 1.2g, 2.4g

    DOSAGE & INDICATIONS

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

    Initially, 5 mg PO 3 times daily. If needed, may increase to 7.5 mg or 10 mg PO 3 times daily based on therapeutic response. Use this drug in the elderly only if clearly needed; less frequent dosing should be considered in the geriatric adult. Max: 30 mg/day PO. Treatment duration beyond 2 to 3 weeks is not recommended.

    Adolescents 15 years and older

    Initially, 5 mg PO 3 times daily. If needed, may increase to 7.5 mg or 10 mg PO 3 times daily based on therapeutic response. Use this drug in the elderly only if clearly needed. Max: 30 mg/day PO. Treatment duration beyond 2 to 3 weeks is not recommended.

    Oral dosage (extended-release capsules)
    Adults

    15 mg PO once daily is the initial and usual dose. Some patients may require 30 mg PO once daily. Limit the duration of treatment to 2 to 3 weeks.

    Geriatric Adults

    Do not use in geriatric patients. Not recommended due to substantial increases in plasma concentrations and half-life observed in the elderly.

    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

    MAXIMUM DOSAGE

    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.

    DOSING CONSIDERATIONS

    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.

    ADMINISTRATION

    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.

    STORAGE

    Active - Cyclobenzaprine:
    - Prior to compounding, store at room temperature (between 59 to 86 degrees F)
    - Product should be used within 60 days after reconstitution
    Amrix:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    EnovaRX:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    - Store in a cool, dry place
    Fexmid:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Flexeril:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Tricyclic antidepressant hypersensitivity

    Cyclobenzaprine is structurally related to tricyclic antidepressants (e.g., amitriptyline). The potential for cross-sensitivity between tricyclic antidepressants and cyclobenzaprine has not been established; however, caution should be used when changing from one of these chemically-related agents to another. Alternative therapy to cyclobenzaprine should be considered in patients with tricyclic antidepressant hypersensitivity, particularly if the reaction was severe or life-threatening.

    Hyperthyroidism

    Because of a potential risk of cardiac events, the manufacturer contraindicates the use of cyclobenzaprine in patients with hyperthyroidism.

    Depression, MAOI therapy

    Because of it's chemical similarity to tricyclic antidepressants (TCAs), use cyclobenzaprine with caution in patients being treated for psychological or psychotic illnesses (e.g., depression or schizophrenia). Cyclobenzaprine is not an effective treatment for depression, and it is unclear if cyclobenzaprine, like the TCAs, can transform depression into mania or hypomania in predisposed individuals (e.g., some patients with bipolar disorder). Cyclobenzaprine is contraindicated for use within 14 days of MAOI therapy. Concomitant use of these drugs has resulted in hyperpyretic crisis seizures and death. Cases of serotonin syndrome have developed when cyclobenzaprine was combined with other serotonergic drugs, such as MAOIs, TCAs, selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tramadol, bupropion, meperidine, and verapamil. If concurrent use of these drugs are required, carefully monitor the patient for signs and symptoms of serotonin syndrome. If such a reaction occurs, immediately discontinue cyclobenzaprine and any other serotonergic drug.

    Seizure disorder, seizures

    Use cyclobenzaprine with caution in patients with a seizure disorder. Tricyclic drugs can lower the seizure threshold. If seizures occur during therapy with cyclobenzaprine, discontinue the drug.

    Coadministration with other CNS depressants, driving or operating machinery, ethanol ingestion

    Cyclobenzaprine can induce significant sedation, particularly during the initiation of treatment. Caution patients about driving or operating machinery or performing other hazardous tasks until it is reasonably certain that cyclobenzaprine will not adversely affect their ability to engage in such activities. Advise patients that cyclobenzaprine effects may be additive to impairment from ethanol ingestion. Coadministration with other CNS depressants may also result in additive sedation and impairment.

    Acute myocardial infarction, AV block, bradycardia, bundle-branch block, cardiac arrhythmias, cardiac disease, coronary artery disease, diabetes mellitus, females, heart failure, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, long QT syndrome, malnutrition, myocardial infarction, QT prolongation, thyroid disease

    Cyclobenzaprine, like the tricyclic antidepressants, should not be given to patients who are in the acute recovery phase following acute myocardial infarction; this could cause re-infarction or sudden death. Do not administer cyclobenzaprine to patients with QT prolongation or familial histories of long QT syndrome or in those patients with cardiac conduction defects (e.g., cardiac arrhythmias, AV block, bundle-branch block, or congestive heart failure). Further, use cyclobenzaprine with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, elderly patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic dysfunction, or may also be at increased risk for QT prolongation. Although the risk of cardiovascular adverse events is higher after acute overdose, patients with cardiovascular disease should be closely monitored. Many adverse cardiovascular effects are associated with the use of tricyclic-related drugs.

    Closed-angle glaucoma, contact lenses, ileus, prostatic hypertrophy, urinary retention

    Cyclobenzaprine exhibits anticholinergic activity, which may cause gastrointestinal, urinary, ocular, and other side effects. This drug should not be used in patients with paralytic ileus. Patients with increased intraocular pressure, closed-angle glaucoma, prostatic hypertrophy, or urinary retention should receive cyclobenzaprine with caution. The anticholinergic effects of cyclobenzaprine may make the eyes dry, which may cause discomfort for wearers of contact lenses. The use of lubricating drops may be necessary.

    Hepatic disease

    Like other tricyclic drugs, cyclobenzaprine may rarely cause liver dysfunction. Cyclobenzaprine should be used with caution in patients with hepatic disease. Cyclobenzaprine is extensive metabolized by the liver to glucuronides. Peak plasma concentrations and AUC of cyclobenzaprine are nearly doubled in patients with hepatic impairment (15 of 16 patients studied had mild hepatic impairment). Cyclobenzaprine is not recommended for patients with moderate to severe hepatic impairment due to insufficient data. In patients with mild hepatic impairment, initiate therapy with 5 mg doses and titrate cautiously; less frequent dosing may be needed.

    Cerebral palsy, children, infants, neonates

    Cyclobenzaprine has not been found effective in the treatment of spasticity associated with cerebral or spinal cord disease, or in children with cerebral palsy. Safety and efficacy of immediate-release cyclobenzaprine in neonates, infants, children, and adolescents under the age of 15 years have not been established, while use of extended-release cyclobenzaprine has not been established in any pediatric patients.

    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]

    Breast-feeding

    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]

    Radiographic contrast administration

    Cyclobenzaprine lowers the seizure threshold. Because of a potential increased risk of seizures, cyclobenzaprine should not be used during intrathecal radiographic contrast administration. Cyclobenzaprine therapy should be discontinued 48 hours before and not restarted until at least 24 hours after myelography.

    Sunlight (UV) exposure

    Patients may be more prone to sunburn during therapy with cyclobenzaprine. Suitable precautions should be taken prior to sunlight (UV) exposure, such as using sunscreens and protective clothing.

    Anticholinergic medications, geriatric

    Cyclobenzaprine should be used in geriatric adults only if clearly needed. If needed, initiate cyclobenzaprine therapy with low doses and titrate cautiously and consider less frequent dose intervals. Anticholinergic effects of cyclobenzaprine are the most frequently encountered adverse drug effects and cause the greatest morbidity in the elderly. The anticholinergic effects of cyclobenzaprine may be additive with other anticholinergic medications, particularly in the older adult. Elderly patients are at higher risk for adverse CNS (e.g. hallucinations, confusion) and cardiac events due to cyclobenzaprine, potentially leading to falls or other sequelae. Because of reduced clearance and a 40% or larger increase in cyclobenzaprine exposure, the use of cyclobenzaprine extended-release capsules in the elderly patients is not recommended. The plasma concentrations of cyclobenzaprine are elevated 1.7-fold in older adults relative to younger adults. According to the Beers Criteria, skeletal muscle relaxants including cyclobenzaprine are considered potentially inappropriate medications (PIMs) in geriatric patients; avoid use because most muscle relaxants are poorly tolerated by older adults. Some muscle relaxants can cause anticholinergic effects, sedation and are associated with an increased risk of fractures. Also, there is questionable effectiveness of the dosages tolerated by older adults. Avoid drugs with strong anticholinergic properties, such as cyclobenzaprine, in geriatric patients with the following conditions due to the potential for symptom exacerbation or adverse effects: dementia/cognitive impairment (adverse CNS effects), delirium/high risk of delirium (new-onset or worsening delirium), or lower urinary tract symptoms/benign prostatic hyperplasia in men (urinary retention or hesitancy). The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of medications in residents of long-term care facilities; most muscle relaxants are poorly tolerated by older adults due to anticholinergic side effects, sedation, and/or weakness. Cyclobenzaprine has significant anticholinergic properties. Periodic use (e.g., once every 3 months) for no more than 7 days may be appropriate when other interventions or alternative medications are not effective or indicated. Chronic use in individuals with complications due to selected conditions may be indicated, although close monitoring is warranted. Abrupt discontinuation of some muscle relaxants after chronic use may cause adverse effects.

    Abrupt discontinuation

    Abrupt discontinuation of cyclobenzaprine treatment after prolonged administration rarely may produce discontinuation symptoms such as nausea, headache, and malaise. Such symptoms are not indicative of addiction.

    ADVERSE REACTIONS

    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

    DRUG INTERACTIONS

    Acetaminophen; Butalbital: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary.
    Acetaminophen; Butalbital; Caffeine: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Major) Concomitant use of codeine with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary.
    Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of dihydrocodeine with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    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; Phenyltoloxamine: (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 a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Cyclobenzaprine and sedating antihistamines such as doxylamine 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; 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; 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) Cyclobenzaprine and sedating antihistamines such as diphenhydramine 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; Hydrocodone: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Acetaminophen; Oxycodone: (Major) Concomitant use of oxycodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Acetaminophen; Pentazocine: (Moderate) Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity. Coadministration of pentazocine with skeletal muscle relaxants may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation.
    Acetaminophen; Propoxyphene: (Moderate) Cyclobenzaprine may cause additive CNS depression, if used concomitantly with other CNS depressants. such as opiate agonists. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness.
    Acetaminophen; Tramadol: (Major) Concomitant use of tramadol with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Additionally, concurrent use of tramadol and cyclobenzaprine increases the possibility of developing serotonin syndrome and enhances the risk of seizures in patients taking tramadol. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. Closely monitor the patient for signs and symptoms of serotonin syndrome. Immediately discontinue concurrent use if serotonin syndrome occurs. Educate patients about the risks and symptoms of respiratory depression and sedation.
    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.
    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.
    Ambenonium Chloride: (Moderate) The therapeutic benefits of ambenonium may be diminished when co-administered with the antimuscarinics. Drugs known to exhibit anticholinergic properties that could potentially interfere with the cholinesterase inhibitor activity include cyclobenzaprine.
    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: (Major) The concurrent use of cyclobenzaprine with tricyclic antidepressants should be avoided whenever possible due to the potential for adverse effects resulting from similar pharmacology and chemical structures; consider alternative agents for skeletal muscle relaxation. Additive anticholinergic, cardiovascular, and serotonergic activity may occur. The administration of cyclobenzaprine with drugs that increase serotonin concentrations, such as tricyclic antidepressants, may cause serotonin syndrome. Postmarketing cases of serotonin syndrome have been reported during combined use of cyclobenzaprine and other drugs, such as the TCAs,
    Amitriptyline; Chlordiazepoxide: (Major) The concurrent use of cyclobenzaprine with tricyclic antidepressants should be avoided whenever possible due to the potential for adverse effects resulting from similar pharmacology and chemical structures; consider alternative agents for skeletal muscle relaxation. Additive anticholinergic, cardiovascular, and serotonergic activity may occur. The administration of cyclobenzaprine with drugs that increase serotonin concentrations, such as tricyclic antidepressants, may cause serotonin syndrome. Postmarketing cases of serotonin syndrome have been reported during combined use of cyclobenzaprine and other drugs, such as the TCAs, (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.
    Amobarbital: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary.
    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.
    Anticholinergics: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    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) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Concomitant use of codeine with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Major) Concomitant use of dihydrocodeine with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    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 a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Aspirin, ASA; Oxycodone: (Major) Concomitant use of oxycodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Atracurium: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants can result in additive CNS depression. Also, dantrolene may potentiate neuromuscular block.
    Atropine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Atropine; Difenoxin: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Atropine; Diphenoxylate: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Atropine; Edrophonium: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary. (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Azelastine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including skeletal muscle relaxants.
    Azelastine; Fluticasone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including skeletal muscle relaxants.
    Bacitracin: (Minor) Use skeletal muscle relaxants cautiously in patients receiving systemic bacitracin. If bacitracin is administered parenterally during surgery, there may be increased skeletal muscle relaxation, and postoperative use may reinstate neuromuscular blockade.
    Barbiturates: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary. (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Belladonna; Opium: (Major) Concomitant use of opium with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    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.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Benztropine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Bismuth Subsalicylate: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of cyclobenzaprine may produce additive effects.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of cyclobenzaprine may produce additive 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; Carbetapentane; 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. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Brompheniramine; Dextromethorphan; Guaifenesin: (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; Guaifenesin; Hydrocodone: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (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; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (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.
    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: (Major) Concurrent use of cyclobenzaprine with bupropion increases the possibility of developing 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 both drugs. Additionally, 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 bupropion, anticholinergic side effects can be additive. Particular attention should be paid to GI problems because of the possible development of paralytic ileus.
    Bupropion; Naltrexone: (Major) Concurrent use of cyclobenzaprine with bupropion increases the possibility of developing 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 both drugs. Additionally, 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 bupropion, anticholinergic side effects can be additive. Particular attention should be paid to GI problems because of the possible development of paralytic ileus.
    Buspirone: (Moderate) Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Dosage adjustments of either or both medications may be necessary.
    Butabarbital: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary.
    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.
    Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and cyclobenzaprine. CNS depressants can potentiate the effects of cannabidiol.
    Carbetapentane; 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. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbetapentane; 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. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Cyclobenzaprine and sedating antihistamines such as diphenhydramine 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. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbetapentane; Guaifenesin: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbetapentane; Pseudoephedrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbetapentane; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    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.
    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.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (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.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (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.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (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.
    Carbinoxamine; Phenylephrine: (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.
    Carbinoxamine; Pseudoephedrine: (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.
    Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with skeletal muscle relaxants should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with skeletal muscle relaxants should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    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.
    Chloral Hydrate: (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.
    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.
    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. (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    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 a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (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; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of dihydrocodeine with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (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; Pseudoephedrine: (Major) Concomitant use of dihydrocodeine with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (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; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (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 a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (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; Phenylephrine: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (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; Pseudoephedrine: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (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) Cyclobenzaprine is structurally related to the tricyclic antidepressants and Clonidine's antihypertensive effect can be reduced by TCAs. Caution is warranted when combining cyclobenzaprine with clonidine.
    Cisatracurium: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants can result in additive CNS depression. Also, dantrolene may potentiate neuromuscular block.
    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: (Major) The concurrent use of cyclobenzaprine with tricyclic antidepressants should be avoided whenever possible due to the potential for adverse effects resulting from similar pharmacology and chemical structures; consider alternative agents for skeletal muscle relaxation. Additive anticholinergic, cardiovascular, and serotonergic activity may occur. The administration of cyclobenzaprine with drugs that increase serotonin concentrations, such as tricyclic antidepressants, may cause serotonin syndrome. Postmarketing cases of serotonin syndrome have been reported during combined use of cyclobenzaprine and other drugs, such as the TCAs,
    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.
    Clonidine: (Moderate) Cyclobenzaprine is structurally related to the tricyclic antidepressants and Clonidine's antihypertensive effect can be reduced by TCAs. Caution is warranted when combining cyclobenzaprine with clonidine.
    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.
    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 a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Codeine; Guaifenesin: (Major) Concomitant use of codeine with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of codeine with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (Moderate) Cyclobenzaprine and promethazine, a phenothiazine with sedating antihistaminic activity, 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.
    Codeine; Promethazine: (Major) Concomitant use of codeine with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (Moderate) Cyclobenzaprine and promethazine, a phenothiazine with sedating antihistaminic activity, 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.
    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.
    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.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Systemic exposure and the maximum serum concentration (Cmax) of cyclobenzaprine were decreased when a single 5 mg dose was administered concurrently with ombitasvir; paritaprevir; ritonavir. If these drugs are given together, monitor for reduced cyclobenzaprine efficacy; consider increasing the cyclobenzaprine dose if clinically needed.
    Desipramine: (Major) The concurrent use of cyclobenzaprine with tricyclic antidepressants should be avoided whenever possible due to the potential for adverse effects resulting from similar pharmacology and chemical structures; consider alternative agents for skeletal muscle relaxation. Additive anticholinergic, cardiovascular, and serotonergic activity may occur. The administration of cyclobenzaprine with drugs that increase serotonin concentrations, such as tricyclic antidepressants, may cause serotonin syndrome. Postmarketing cases of serotonin syndrome have been reported during combined use of cyclobenzaprine and other drugs, such as the TCAs,
    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; Diphenhydramine; Phenylephrine: (Moderate) Cyclobenzaprine and sedating antihistamines such as diphenhydramine 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.
    Dextromethorphan; Promethazine: (Moderate) Cyclobenzaprine and promethazine, a phenothiazine with sedating antihistaminic activity, 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.
    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.
    Dicyclomine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of dihydrocodeine with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Dimenhydrinate: (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 sedating H1-blockers, 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. Dosage adjustments of either or both drugs may be necessary.
    Diphenhydramine: (Moderate) Cyclobenzaprine and sedating antihistamines such as diphenhydramine 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.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (Moderate) Cyclobenzaprine and sedating antihistamines such as diphenhydramine 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.
    Diphenhydramine; Ibuprofen: (Moderate) Cyclobenzaprine and sedating antihistamines such as diphenhydramine 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.
    Diphenhydramine; Naproxen: (Moderate) Cyclobenzaprine and sedating antihistamines such as diphenhydramine 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.
    Diphenhydramine; Phenylephrine: (Moderate) Cyclobenzaprine and sedating antihistamines such as diphenhydramine 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.
    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.
    Doxacurium: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants can result in additive CNS depression. Also, dantrolene may potentiate neuromuscular block.
    Doxepin: (Major) The concurrent use of cyclobenzaprine with tricyclic antidepressants should be avoided whenever possible due to the potential for adverse effects resulting from similar pharmacology and chemical structures; consider alternative agents for skeletal muscle relaxation. Additive anticholinergic, cardiovascular, and serotonergic activity may occur. The administration of cyclobenzaprine with drugs that increase serotonin concentrations, such as tricyclic antidepressants, may cause serotonin syndrome. Postmarketing cases of serotonin syndrome have been reported during combined use of cyclobenzaprine and other drugs, such as the TCAs,
    Doxylamine: (Moderate) Cyclobenzaprine and sedating antihistamines such as doxylamine 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.
    Doxylamine; Pyridoxine: (Moderate) Cyclobenzaprine and sedating antihistamines such as doxylamine 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.
    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.
    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.
    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: (Moderate) Cyclobenzaprine may cause additive CNS depression, if used concomitantly with other CNS depressants, such as ethanol.
    Etomidate: (Moderate) General anesthetics, such as etomidate, potentiate the effects of other CNS depressants, including skeletal muscle relaxants like cyclobenzaprine.
    Fentanyl: (Major) Concomitant use of fentanyl 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.
    Flavoxate: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    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.
    Fluoxetine; Olanzapine: (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.
    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.
    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.
    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) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Glycopyrrolate; Formoterol: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    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 a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Homatropine; Hydrocodone: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Hydrocodone: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Hydrocodone; Ibuprofen: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Hydrocodone; Phenylephrine: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Hydrocodone; Potassium Guaiacolsulfonate: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Hydrocodone; Pseudoephedrine: (Major) Concomitant use of hydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients taking a skeletal muscle relaxant. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Hydromorphone: (Major) Concomitant use of hydromorphone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Hydroxyzine: (Moderate) Cyclobenzaprine and sedating antihistamines such as hydroxyzine 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.
    Hyoscyamine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Ibuprofen; Oxycodone: (Major) Concomitant use of oxycodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Imipramine: (Major) The concurrent use of cyclobenzaprine with tricyclic antidepressants should be avoided whenever possible due to the potential for adverse effects resulting from similar pharmacology and chemical structures; consider alternative agents for skeletal muscle relaxation. Additive anticholinergic, cardiovascular, and serotonergic activity may occur. The administration of cyclobenzaprine with drugs that increase serotonin concentrations, such as tricyclic antidepressants, may cause serotonin syndrome. Postmarketing cases of serotonin syndrome have been reported during combined use of cyclobenzaprine and other drugs, such as the TCAs,
    Indacaterol; Glycopyrrolate: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    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.
    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: (Severe) 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.
    Kava Kava, Piper methysticum: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants, such as kava kava can result in additive CNS depression. Persons taking other CNS-active medications such as, skeletal muscle relaxants, should discuss the use of herbal supplements with their health care professional prior to consuming kava kava. Patients should not abruptly stop taking their prescribed medications.
    Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with skeletal muscle relaxants should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Levorphanol: (Major) Concomitant use of levorphanol with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant 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 dose of levorphanol by approximately 50% or more. Educate patients about the risks and symptoms of respiratory depression and sedation.
    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.
    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.
    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.
    Mepenzolate: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Meperidine: (Major) Concomitant use of meperidine with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Meperidine; Promethazine: (Major) Concomitant use of meperidine with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. (Moderate) Cyclobenzaprine and promethazine, a phenothiazine with sedating antihistaminic activity, 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.
    Mephobarbital: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary.
    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) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Methohexital: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary.
    Methscopolamine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    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.
    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.
    Mivacurium: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants can result in additive CNS depression. Also, dantrolene may potentiate neuromuscular block.
    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: (Severe) 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. 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. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. 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.
    Morphine; Naltrexone: (Major) Concomitant use of morphine 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. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. 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.
    Nabilone: (Moderate) Concomitant use of nabilone with other CNS depressants like skeletal muscle relaxants can potentiate the effects of nabilone on respiratory depression, sedation and dizziness, which can impair the ability to undertake tasks requiring mental alertness.
    Nalbuphine: (Moderate) Concomitant use of nalbuphine with other CNS depressants, such as skeletal muscle relaxants, can potentiate the effects of nalbuphine on respiratory depression, CNS depression, and sedation.
    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.
    Neuromuscular blockers: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants can result in additive CNS depression. Also, dantrolene may potentiate neuromuscular block.
    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: (Major) The concurrent use of cyclobenzaprine with tricyclic antidepressants should be avoided whenever possible due to the potential for adverse effects resulting from similar pharmacology and chemical structures; consider alternative agents for skeletal muscle relaxation. Additive anticholinergic, cardiovascular, and serotonergic activity may occur. The administration of cyclobenzaprine with drugs that increase serotonin concentrations, such as tricyclic antidepressants, may cause serotonin syndrome. Postmarketing cases of serotonin syndrome have been reported during combined use of cyclobenzaprine and other drugs, such as the TCAs,
    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.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Systemic exposure and the maximum serum concentration (Cmax) of cyclobenzaprine were decreased when a single 5 mg dose was administered concurrently with ombitasvir; paritaprevir; ritonavir. If these drugs are given together, monitor for reduced cyclobenzaprine efficacy; consider increasing the cyclobenzaprine dose if clinically needed.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Systemic exposure and the maximum serum concentration (Cmax) of cyclobenzaprine were decreased when a single 5 mg dose was administered concurrently with ombitasvir; paritaprevir; ritonavir. If these drugs are given together, monitor for reduced cyclobenzaprine efficacy; consider increasing the cyclobenzaprine dose if clinically needed.
    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.
    Oxybutynin: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Oxycodone: (Major) Concomitant use of oxycodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    Oxymorphone: (Major) Concomitant use of oxymorphone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant 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 1/3 to 1/2. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Pancuronium: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants can result in additive CNS depression. Also, dantrolene may potentiate neuromuscular block.
    Paroxetine: (Moderate) Cyclobenzaprine and paroxetine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS effects causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary. There is the possibility of serotonin syndrome with this combination. 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 all serotonergic medications and implement appropriate medical treatment.
    Pentazocine: (Moderate) Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity. Coadministration of pentazocine with skeletal muscle relaxants may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation.
    Pentazocine; Naloxone: (Moderate) Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity. Coadministration of pentazocine with skeletal muscle relaxants may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation.
    Pentobarbital: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary.
    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: (Major) The concurrent use of cyclobenzaprine with tricyclic antidepressants should be avoided whenever possible due to the potential for adverse effects resulting from similar pharmacology and chemical structures; consider alternative agents for skeletal muscle relaxation. Additive anticholinergic, cardiovascular, and serotonergic activity may occur. The administration of cyclobenzaprine with drugs that increase serotonin concentrations, such as tricyclic antidepressants, may cause serotonin syndrome. Postmarketing cases of serotonin syndrome have been reported during combined use of cyclobenzaprine and other drugs, such as the TCAs, (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.
    Phenelzine: (Severe) 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) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary.
    Phenylephrine; Promethazine: (Moderate) Cyclobenzaprine and promethazine, a phenothiazine with sedating antihistaminic activity, 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.
    Primidone: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary.
    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) Cyclobenzaprine and promethazine, a phenothiazine with sedating antihistaminic activity, 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.
    Propantheline: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Propoxyphene: (Moderate) Cyclobenzaprine may cause additive CNS depression, if used concomitantly with other CNS depressants. such as opiate agonists. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness.
    Protriptyline: (Major) The concurrent use of cyclobenzaprine with tricyclic antidepressants should be avoided whenever possible due to the potential for adverse effects resulting from similar pharmacology and chemical structures; consider alternative agents for skeletal muscle relaxation. Additive anticholinergic, cardiovascular, and serotonergic activity may occur. The administration of cyclobenzaprine with drugs that increase serotonin concentrations, such as tricyclic antidepressants, may cause serotonin syndrome. Postmarketing cases of serotonin syndrome have been reported during combined use of cyclobenzaprine and other drugs, such as the TCAs,
    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.
    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.
    Rapacuronium: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants can result in additive CNS depression. Also, dantrolene may potentiate neuromuscular block.
    Rasagiline: (Severe) 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.
    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.
    Rocuronium: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants can result in additive CNS depression. Also, dantrolene may potentiate neuromuscular block.
    Safinamide: (Severe) 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) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Secobarbital: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary.
    Selegiline: (Severe) 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.
    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.
    Succinylcholine: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants can result in additive CNS depression. Also, dantrolene may potentiate neuromuscular block.
    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.
    Tacrine: (Moderate) The therapeutic benefits of tacrine may be diminished when coadministered with drugs known to exhibit anticholinergic properties, such as cyclobenzaprine.
    Tapentadol: (Major) Concomitant use of tapentadol with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant 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.
    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.
    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.
    Thiopental: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with skeletal muscle relaxants. Caution should be exercised during concomitant use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary.
    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.
    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 a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Additionally, concurrent use of tramadol and cyclobenzaprine increases the possibility of developing serotonin syndrome and enhances the risk of seizures in patients taking tramadol. Limit the use of opioid pain medications with a skeletal muscle relaxant 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. Closely monitor the patient for signs and symptoms of serotonin syndrome. Immediately discontinue concurrent use if serotonin syndrome occurs. Educate patients about the risks and symptoms of respiratory depression and sedation.
    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: (Severe) 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 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.
    Tricyclic antidepressants: (Major) The concurrent use of cyclobenzaprine with tricyclic antidepressants should be avoided whenever possible due to the potential for adverse effects resulting from similar pharmacology and chemical structures; consider alternative agents for skeletal muscle relaxation. Additive anticholinergic, cardiovascular, and serotonergic activity may occur. The administration of cyclobenzaprine with drugs that increase serotonin concentrations, such as tricyclic antidepressants, may cause serotonin syndrome. Postmarketing cases of serotonin syndrome have been reported during combined use of cyclobenzaprine and other drugs, such as the TCAs,
    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) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Monitor for effects such as constipation and urinary retention. Additive drowsiness may also occur, depending on the interacting agent.
    Trimipramine: (Major) The concurrent use of cyclobenzaprine with tricyclic antidepressants should be avoided whenever possible due to the potential for adverse effects resulting from similar pharmacology and chemical structures; consider alternative agents for skeletal muscle relaxation. Additive anticholinergic, cardiovascular, and serotonergic activity may occur. The administration of cyclobenzaprine with drugs that increase serotonin concentrations, such as tricyclic antidepressants, may cause serotonin syndrome. Postmarketing cases of serotonin syndrome have been reported during combined use of cyclobenzaprine and other drugs, such as the TCAs,
    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.
    Tubocurarine: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants can result in additive CNS depression. Also, dantrolene may potentiate neuromuscular block.
    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.
    Vecuronium: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants can result in additive CNS depression. Also, dantrolene may potentiate neuromuscular block.
    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.

    PREGNANCY AND LACTATION

    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]

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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.