Can You Take Ibuprofen with Flexeril (Cyclobenzaprine)?
Yes, you can safely take ibuprofen together with cyclobenzaprine (Flexeril), as there is no dangerous drug interaction between these medications. 1, 2
Evidence for Safety of Combination Therapy
Multiple randomized controlled trials have directly studied the combination of cyclobenzaprine with ibuprofen and found no safety concerns or dangerous interactions 1, 2
A community-based trial of 867 patients compared cyclobenzaprine 5 mg three times daily alone versus in combination with ibuprofen 400 mg or 800 mg three times daily, finding all three regimens were well tolerated with no significant differences in adverse events between groups 1
An emergency department study of 102 patients with acute myofascial strain compared cyclobenzaprine 10 mg plus ibuprofen 800 mg versus ibuprofen alone, confirming the combination was safe to use together 2
Important Caveat About Efficacy
The combination does not provide better pain relief than ibuprofen alone, despite being safe to take together:
The emergency department trial found no statistically significant difference in pain scores between the combination group and ibuprofen alone over 48 hours (P = 0.962), though the combination group experienced significantly more central nervous system side effects like drowsiness and dizziness 2
The community-based trial similarly found no superiority of combination therapy over cyclobenzaprine alone for patient global impression of change after 7 days (P = 0.41) 1
The American College of Physicians guidelines note that ibuprofen plus cyclobenzaprine showed no statistically significant pain reduction compared to placebo in the acute phase (less than 2 hours), while ibuprofen alone did reduce pain by approximately 1 cm on a 10-cm scale 3
Special Consideration for Aspirin Users
If you are taking low-dose aspirin for heart protection, avoid ibuprofen or take it at specific times to prevent interference with aspirin's cardioprotective effects:
The American College of Cardiology/American Heart Association strongly recommends that patients taking low-dose aspirin (≤325 mg per day) for cardioprotection should use a nonselective NSAID other than ibuprofen, because ibuprofen blocks aspirin's access to its binding site and reduces its protective effects 4
If ibuprofen must be used with aspirin, take ibuprofen at least 30 minutes after immediate-release aspirin or at least 8 hours before aspirin to minimize this interaction 4
This interaction between ibuprofen and aspirin has been associated with increased cardiovascular mortality 4
Common Side Effects to Expect
Cyclobenzaprine commonly causes drowsiness, dry mouth, dizziness, fatigue, and sedation—these are dose-related and occur in 42-54% of patients 5, 1, 2
When combined with ibuprofen, central nervous system side effects (drowsiness, dizziness, sedation) occur more frequently: 42% at 24 hours and 39% at 48 hours versus 18% and 13% with ibuprofen alone 2
Ibuprofen can cause gastrointestinal discomfort, dyspepsia, and carries a risk of GI bleeding, particularly in older adults or those with prior ulcer history 4
Duration of Use
Use cyclobenzaprine only for short-term treatment (2 weeks or less), as all clinical trials were limited to this duration and there is insufficient evidence for chronic use 6, 3
If you have been taking cyclobenzaprine for a prolonged period, taper gradually over 2-3 weeks when discontinuing to prevent withdrawal symptoms (malaise, nausea, headache) 6, 7