By Naomi Carr
Last updated: 15 April 2024 & medically reviewed by Morgan Blair
It is always important to be aware of the potential drug interactions and adverse effects when starting a new medication. Flexeril (Cyclobenzaprine) can interact with several other medications and substances, which can cause an increased risk of side effects or a decrease in the therapeutic effects of necessary medications.
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What is Flexeril (cyclobenzaprine)
Cyclobenzaprine is a tricyclic amine salt, used as a muscle relaxant. Common brand names for this medication include Flexeril and Amrix.[1]
Flexeril is used to treat acute muscle spasms that occur in the context of musculoskeletal conditions. It acts as a central nervous system (CNS) depressant, causing a relaxing of the muscles. As well as reducing muscle spasms, it can also reduce associated symptoms such as pain, impairments in movement, and restrictions of daily functioning.[2] Cyclobenzaprine, Flexeril, and Amrix are not controlled substances.
Flexeril has no therapeutic benefit in the treatment of spasticity in the context of CNS disease, such as cerebral or spinal cord disease or cerebral palsy. It should only be used for two to three weeks to manage acute symptoms. [2]
Common side effects of cyclobenzaprine (Flexeril) include drowsiness, dizziness, and dry mouth. [1]
How does cyclobenzaprine interact with other drugs?
Various other medications and substances can interact with cyclobenzaprine, causing a risk of adverse effects and a decrease in the therapeutic effect of medications.
Alcohol
Consuming alcohol while taking cyclobenzaprine is likely to increase CNS depressant effects and can cause severe adverse effects, including: [2][3]
Drowsiness
Oversedation
Impaired concentrating and thinking
Dizziness
Slowed heartbeat
Increased risk of overdose
Adderall (amphetamine/dextroamphetamine)
There is no evidence of a dangerous interaction between cyclobenzaprine and Adderall. However, it is advised to consult a medical professional for advice before combining these medications. [3]
Ambien (zolpidem)
Ambien is a CNS depressant, so using this medication in combination with cyclobenzaprine can increase sedating effects, including: [2][3]
Drowsiness
Dizziness
Impaired concentration
Confusion
Aspirin Low Strength (aspirin)
There is no evidence that combining cyclobenzaprine and Aspirin causes an interaction or increased risk of side effects. However, it is always recommended to consult with a doctor prior to commencing a new medication. [3]
Ibuprofen
Combining cyclobenzaprine and Ibuprofen is not known to cause any dangerous interactions or increased risk of side effects. [3] Additionally, studies suggest that the combination of these medications, compared to each alone, offers no additional benefit in terms of pain relief. [4]
Benadryl (diphenhydramine)
Benadryl is a sedating antihistamine. As such, combining Benadryl with cyclobenzaprine can cause an interaction and increase sedating effects. Possible side effects of this interaction can include: [2][3]
Increased drowsiness
Dry mouth
Blurred vision
Intolerance to heat
Urinary retention
Stomach pain
Confusion
Memory impairment
Irregular heartbeat
Celebrex (celecoxib)
There are no known interactions caused by the combination of Celebrex and cyclobenzaprine. However, it is always recommended to consult with a doctor prior to commencing a new medication. [3]
Cymbalta (duloxetine)
Cymbalta is a serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressant. Combining cyclobenzaprine with serotonin-enhancing medications can cause an increased risk of serotonin syndrome, a severe and potentially fatal condition. [5] Symptoms of serotonin syndrome can include: [2][3]
Severe agitation
Hallucinations
Rapid or irregular heartbeat
Severe changes in blood pressure
Increased body temperature
Sweating
Tremors
Muscle pain and stiffness
Nausea
Vomiting
Diarrhea
As such, cyclobenzaprine should not be taken with Cymbalta. If it is medically necessary, the individual should be carefully monitored, especially when commencing treatment or increasing doses.[2]
Lexapro (escitalopram)
Lexapro is a selective serotonin reuptake inhibitor (SSRI) antidepressant. Combining this medication with cyclobenzaprine can increase the risk of serotonin syndrome.[5] This can cause effects including: [2][3]
Severe agitation
Hallucinations
Rapid or irregular heartbeat
Severe changes in blood pressure
Increased body temperature
Sweating
Tremors
Muscle pain and stiffness
Nausea
Vomiting
Diarrhea
As such, Lexapro (escitalopram) should not be used in combination with cyclobenzaprine. If it is deemed necessary for treatment by a medical provider, it should be used with caution and with careful monitoring of symptoms and side effects. [2]
Lyrica (pregabalin)
Combining Lyrica (pregabalin) and cyclobenzaprine can cause an increase in CNS depressant effects, including: [2][3]
Dizziness
Drowsiness
Cognitive impairments including concentration difficulties and confusion
Metoprolol Tartrate (metoprolol)
Combining cyclobenzaprine and Metoprolol Tartrate can cause increased effects on blood pressure. This can cause side effects such as: [3]
Severe drop in blood pressure
Dizziness
Fainting
Headache
Irregular or slowed heart rate
These symptoms are most likely to emerge with new or increased doses and often reduce within a short time. As such, Metoprolol Tartrate can be used in combination with cyclobenzaprine if medically required, with close monitoring. [3]
Nexium (esomeprazole)
There are no known interactions or increased risk of side effects caused by the combination of Nexium and cyclobenzaprine. However, it is advised to consult with a doctor before commencing a new treatment. [3]
Norco (acetaminophen/hydrocodone)
Norco is a narcotic medication and CNS depressant. As such, a combination of Norco and cyclobenzaprine can cause an increased risk of CNS depressant effects that may be severe or even fatal. Side effects of this interaction can include: [2][3]
Drowsiness
Dizziness
Cognitive impairments
Impairments in motor skills and coordination
Oversedation
Breathing difficulties
Reduced heart rate
Loss of consciousness
Coma
Singulair (montelukast)
There are no known interactions or increased risks of side effects caused by the combination of Singulair and cyclobenzaprine. However, it is advised to consult with a doctor before starting a new medication. [3]
Symbicort (budesonide/formoterol)
There is no increased risk of interactions or side effects when combining cyclobenzaprine and Symbicort. However, it is recommended to discuss medications with the prescribing doctor prior to starting a new treatment. [3]
Synthroid (levothyroxine)
Synthroid is not known to interact with cyclobenzaprine. Always discuss medications with a doctor before starting a new treatment. [3]
Tylenol (acetaminophen)
There are no known interactions between Tylenol and cyclobenzaprine. However, it is recommended to consult with a doctor before starting a new medication. [3]
Ventolin HFA (albuterol)
Ventolin HFA is not known to interact with cyclobenzaprine. Always discuss medications with the prescribing doctor before starting a new treatment. [3]
Xanax (alprazolam)
Xanax is a CNS depressant so combining this medication with cyclobenzaprine can cause an increase in sedation, causing effects such as: [2][3]
Drowsiness
Dizziness
Confusion
Impaired coordination
Difficulty with concentration and thinking
Zofran (ondansetron)
Zofran is not known to interact with cyclobenzaprine. However, it is advised to discuss with the prescribing doctor prior to starting a new medication. [3]
Zoloft (sertraline)
Zoloft is a selective serotonin reuptake inhibitor (SSRI) antidepressant. Combining this medication with cyclobenzaprine can increase the risk of serotonin syndrome. [5] This can cause effects including: [2][3]
Severe agitation
Hallucinations
Rapid or irregular heartbeat
Severe changes in blood pressure
Increased body temperature
Sweating
Tremors
Muscle pain and stiffness
Nausea
Vomiting
Diarrhea
Zoloft (sertraline) should not be used in combination with cyclobenzaprine. If it is deemed necessary for treatment by a medical provider, it should be used with caution and with careful monitoring. [2]
Zyrtec (cetirizine)
Zyrtec is a sedating antihistamine so combining this medication with cyclobenzaprine can increase the risk of side effects such as: [2][3]
Drowsiness
Dizziness
Impaired concentration
Impaired coordination
