Sumatriptan and Cyclobenzaprine (Flexeril) Interaction
Caution is advised when taking sumatriptan with cyclobenzaprine (Flexeril) due to the potential risk of serotonin syndrome, a rare but potentially serious adverse reaction.
Risk Assessment
Cyclobenzaprine has structural similarity to tricyclic antidepressants and has been reported to have serotonergic properties:
- Multiple case reports document serotonin syndrome when cyclobenzaprine is combined with other serotonergic medications 1, 2
- Cyclobenzaprine blocks serotonin and norepinephrine transporters and binds to multiple serotonin receptors 2
- A specific case report documents serotonin syndrome in a patient taking Lexapro (escitalopram) and Flexeril (cyclobenzaprine) 3
Sumatriptan is a serotonin 5-HT1B/1D receptor agonist used for migraine treatment:
- The Mayo Clinic Proceedings consensus statement recommends holding triptans on the day of surgery due to theoretical concerns about drug-drug interactions with serotonergic medications 4
- Triptans have been associated with a low risk of serotonin syndrome when combined with SSRIs or SNRIs 4
Clinical Considerations
Signs and Symptoms of Serotonin Syndrome to Monitor For:
- Mental status changes (agitation, confusion)
- Neuromuscular abnormalities (tremors, clonus, hyperreflexia, muscle rigidity)
- Autonomic hyperactivity (hypertension, tachycardia, diaphoresis, vomiting, diarrhea)
- Advanced symptoms include fever, seizures, arrhythmias, and unconsciousness 4
Conflicting Evidence
Some research suggests the combination may be safer than previously thought:
- A 1995 study reported no significant side effects in patients taking sumatriptan with various antidepressants across 103 migraine episodes 5
- A 1998 review found that most patients tolerate sumatriptan with SSRIs without incident 6
However, more recent evidence and case reports highlight the potential risks of combining serotonergic medications 3, 1, 2.
Recommendations
Avoid concurrent use if possible, especially if you are taking other serotonergic medications (SSRIs, SNRIs, MAOIs, etc.)
If both medications are deemed necessary:
- Use the lowest effective doses
- Space the administration times (take several hours apart)
- Be vigilant for early signs of serotonin syndrome
- Seek immediate medical attention if symptoms develop
Alternative options to consider:
- For muscle spasm: non-serotonergic muscle relaxants (methocarbamol)
- For migraine: NSAIDs or acetaminophen for milder headaches
Special Precautions
- Absolute contraindication: Do not combine with MAOIs (monoamine oxidase inhibitors) 4
- Use extreme caution if you are already taking other serotonergic medications
- Patients with liver or kidney disease should use extra caution due to potential altered drug metabolism
Remember that this information represents general guidance. Your specific medical history and other medications may influence the safety of this combination.