Clozapine and Cyclobenzaprine interaction
Clozapine and Cyclobenzaprine: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Clozapine (Clozaril) label · effective 2025-06-06
When possible, avoid concomitant use, with other anticholinergic medications because the risk for anticholinergic toxicity or severe gastrointestinal adverse reactions is increased [see Warnings and Precautions ( 5.7 ), Drug Interactions ( 7.1 )].
Anticholinergic Drugs Concomitant treatment with clozapine and other drugs with anticholinergic activity (e.g., benztropine, cyclobenzaprine, diphenhydramine) can increase the risk for anticholinergic toxicity and severe gastrointestinal adverse reactions related to hypomotility.
• Anticholinergic Toxicity : When possible, avoid use with other anticholinergic drugs and use with caution in patients with a current diagnosis or prior history of constipation, urinary retention, clinically significant prostatic hypertrophy, or other conditions in which anticholinergic effects can lead to significant adverse reactions.
Use with caution in patients with a current diagnosis or prior history of constipation, urinary retention, clinically significant prostatic hypertrophy, or other conditions in which anticholinergic effects can lead to significant adverse reactions.
From the Cyclobenzaprine (TONMYA) label · effective 2026-08-14
Based on its structural similarity to TCAs, concomitant use of TONMYA with: MAO inhibitors may be life-threatening [see Contraindications (4) ] , Alcohol, barbiturates, and other CNS depressants may increase the risk of adverse reactions associated with these drugs, Tramadol may increase the seizure risk, Guanethidine or other similar acting drugs may block the…
CNS Depression and Risk of Operating a Motor Vehicle or Hazardous Machinery TONMYA monotherapy may cause CNS depression and concomitant use of TONMYA with alcohol, barbiturates, or other CNS depressants may increase the risk of CNS depression [see Drug Interactions (7) ].
CNS Depressants: CNS depressant effects of alcohol, barbiturates, and other CNS depressants may be enhanced ( 5.5 , 7 )
Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.
Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.