Drug interactions of both cyclobenzaprine (Flexeril) and ibuprofen are valid options for muscle pain management, but would it be wise to combine them?

Before mixing over-the-counter (OTC) painkillers with skeletal muscle relaxants, you need to evaluate whether this combination yields better results with fewer side effects than a single drug.


As it happens, the cyclobenzaprine-ibuprofen mix is, more often than not, a fruitless combination.In this post, we’ll go over why you might want to avoid mixing the two drugs. Then, we’ll see what alternatives are there to consider.

Co-Prescribing Cyclobenzaprine With Ibuprofen

Generally speaking, a co-prescription of cyclobenzaprine and ibuprofen is common in medical condition cases of neck and acute low back pain interventions. That’s because the former is a relaxant that eases muscle spasms, sprains, and pain, and the latter is a non-steroidal anti-inflammatory drug (NSAID) that works as a general analgesic.

Plus, there are no reports of major interactions between them.

Of course, we can’t say there’s a 100% safe drug (or combination therapy) out there. However, the gist here is that these two are considered generally safe to be taken together.

So, it’s not unheard of for an orthopedic doctor to co-prescribe both drugs in an attempt to give the patient short-term pain relief. However, the combination doesn’t always work as planned.

Downsides of Using Cyclobenzaprine and Ibuprofen Together

Just because the cyclobenzaprine-ibuprofen combination isn’t dangerous doesn’t mean that it should be the first step in treating neck and back pain.

A couple of drawbacks keep physicians from prescribing the two drugs together.

It’s Often a Fruitless Combination

Although it would be nice to have a painkilling co-prescription that gives the patient better results than single-drug therapies, research proves that isn’t always the case with cyclobenzaprine and ibuprofen.

For one, a randomized trial proved that cyclobenzaprine alone calms neck and back spasms just as well as a cyclobenzaprine-ibuprofen combination.

Interestingly, those results were based on a low muscle relaxant dose (5 mg) three times daily with 400–800 mg of the NSAID, also three times per day.


That’s not to say that ibuprofen is the weak link in this situation.

In fact, a Cambridge University Press trial proved there’s no point in adding cyclobenzaprine to ibuprofen, either. That’s not all. A review by NEJM Journal Watch confirms the same results; the NSAID works fine without the added help.

So, it’s less about which drug is more potent and more about the fact that mixing them is just not rewarding enough in many cases.

That said, it’s always possible that your treating physician will have a different perspective on the matter. So, don’t be shocked if they ask you to take ibuprofen and cyclobenzaprine. Every patient is a unique case, after all!

It Can Magnify Side Effects

Not only is the combination not very fruitful, but it can also come with some unpleasant effects.

Although ibuprofen acts peripherally to reduce inflammation, it also acts inside the brain to provide pain relief.

As you might have suspected, cyclobenzaprine’s muscle-relaxing effects start in the central nervous system (CNS).

So, you can only expect some side effects on the central nervous system, like drowsiness. However, the combination makes these side effects even more common somehow.

Don’t just take our word for it; one randomized, double-blind clinical trial found that 42% of patients taking cyclobenzaprine with ibuprofen reported CNS side effects within 24 hours.

That’s a huge gap when you consider that this percentage was only 18% in patients on ibuprofen alone!

Alternatives to the Co-Prescription

There are some alternative combinations to try rather than the cyclobenzaprine-ibuprofen mix.

Just remember to talk to your physician or seek medical advice from a healthcare provider before you stop the current prescription and move on to a different treatment plan.

Physical Therapy

Cyclobenzaprine With Physical Therapy

It’s pretty much common practice to recommend rest and physical therapy for patients on cyclobenzaprine. This should help control the pain without the need for NSAIDs, but it’s not clear how much it helps (in percentages).

However, physical therapy can also help reduce the risk of tolerance to cyclobenzaprine. After all, the muscle relaxant is supposed to be taken short-term only.

All in all, you’ll want to stop cyclobenzaprine in 2–3 weeks and rely on physical therapy sessions to control the pain in the long term.

Ibuprofen With Caffeine

A cup of coffee, on its own, won’t do you much good if you’re looking for painkilling effects.

However, caffeine’s power shines when it’s taken with other drugs since it’s known to boost the painkilling action of other analgesics. That includes ibuprofen.

Plus, in this case, you can use lower doses of the NSAID—which is always good—without compromising the net analgesic effect.

The main drawback here is that large amounts of caffeine can do a number on your stomach, but you probably already know that if you’re an avid coffee drinker.

Considering that ibuprofen and all NSAIDs eat away at the stomach lining and form ulcers, you might be adding insult to injury if you overdo the doses.


Drugs to Avoid With Cyclobenzaprine or Ibuprofen

Although there are no serious interactions between cyclobenzaprine and ibuprofen, that doesn’t mean that the same applies to any co-prescription that has one of the two drugs.

If you’re on cyclobenzaprine, you’ll want to avoid the following medications or take them with caution:

  • Cetirizine
  • Diphenhydramine
  • Hydrocodone
  • Duloxetine

Meanwhile, any of the following drugs can be considered risky for patients using ibuprofen:

  • Aspirin
  • Drugs with gingko biloba
  • Escitalopram
  • Duloxetine

Note that while both cyclobenzaprine and ibuprofen interact with duloxetine, it’s for a different reason in each case.

With the muscle relaxant, duloxetine can lead to what healthcare professionals refer to as “serotonin syndrome.”

That’s not the same concern people have about mixing ibuprofen and duloxetine. Instead, we’d be more worried about the bleeding risk.

Final Thoughts

Many patients won’t benefit from adding cyclobenzaprine to their ibuprofen prescription (or vice versa). Additionally, the combination can increase the patient’s odds of showing CNS adverse effects.

Overall, we’d recommend that you avoid mixing OTC analgesics and muscle relaxants without discussing the potential benefits and risks with your physician first.


  • Can you take cyclobenzaprine and ibuprofen together?

Published on: 2023-03-06
Updated on: 2024-06-21