Cyclobenzaprine and Flibanserin interaction

Cyclobenzaprine and Flibanserin: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Cyclobenzaprine (TONMYA) label · effective 2026-08-14

Major

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…

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Major

If serotonin syndrome symptoms occur with the use of other serotonergic drugs, immediately discontinue TONMYA.

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Major

Other serotonergic Drugs: Serotonin syndrome has been reported ( 5.2 , 7 )

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Moderate

If concomitant treatment with TONMYA and other serotonergic drugs is clinically warranted, careful observation is advised, particularly during treatment initiation or dosage increases.

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Moderate

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) ].

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From the Flibanserin (ADDYI) label · effective 2025-12-22

Moderate

Exacerbated by other CNS depressants, and in settings where flibanserin concentrations are increased.

Warnings and precautionsby drug classView label on DailyMed
Moderate

The risk of CNS depression is increased if ADDYI is taken during waking hours, or if ADDYI is taken with alcohol or other CNS depressants, or with medications that increase flibanserin concentrations, such as CYP3A4 inhibitors [see Contraindications (4), Warnings and Precautions (5.1, 5.2), Adverse Reactions (6.1) , and Drug Interactions (7) ].

Warnings and precautionsby drug classView label on DailyMed
Moderate

Other CNS Depressants Examples Diphenhydramine, opioids, hypnotics, benzodiazepines Clinical Implications The concomitant use of ADDYI with CNS depressants may increase the risk of CNS depression (e.g., somnolence) compared to the use of ADDYI alone.

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Minor

Preventing or Managing DI Discuss the concomitant use of other CNS depressants with the patient when prescribing ADDYI.

Drug interactionsby drug classView label on DailyMed

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Not 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.