Codeine and Cyclobenzaprine Interaction

Drug interaction information between Codeine and Cyclobenzaprine.

Codeine and Cyclobenzaprine have a documented minor interaction in FDA labeling.

FDA drug labeling documents a minor-severity interaction between Codeine and Cyclobenzaprine. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.

Drug A

Codeine

Opioid Analgesic

Drug B

Cyclobenzaprine

Muscle Relaxant

How They Interact

Taking these two drugs together can raise serotonin levels in your brain to an unsafe level. This increases the risk of a serious reaction called serotonin syndrome.

FDA Label Information

Examples of these drugs include, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), and monoamine oxidase (MAO) inhibitors (used to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) (see PRECAUTIONS; Information for Patients/Caregivers ).

Frequently Asked Questions

What SPL severity band is on file for Codeine + Cyclobenzaprine?

Compiled FDA labeling labels this pair minor. That is a source-record field, not an individual medication-combination decision.

Which drug in this pair has the larger labeled-interaction portfolio?

Codeine has 27 labeled pairs on file vs Cyclobenzaprine's 17. In the minor band specifically: Codeine has 27 (also Bupropion, Fluoxetine, Trazodone, Tramadol); Cyclobenzaprine has 14 (also Acetaminophen/Oxycodone, Buprenorphine, Buprenorphine/Naloxone, Buprenorphine).

What mechanism field is on file for Codeine and Cyclobenzaprine?

Taking these two drugs together can raise serotonin levels in your brain to an unsafe level. This increases the risk of a serious reaction called serotonin syndrome.

Codeine's labeled portfolio outnumbers Cyclobenzaprine

SPL source-record counts only. This page's band is minor · classes on file: Codeine (Opioid Analgesic); Cyclobenzaprine (Muscle Relaxant).

Codeine

0 major · 0 moderate · 27 minor · 27 total

Cyclobenzaprine

0 major · 3 moderate · 14 minor · 17 total

Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. This registry does not provide individual medication-combination directions.