Fluoxetine and Hydrocodone and ibuprofen interaction

Fluoxetine and Hydrocodone and ibuprofen: 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 Hydrocodone and ibuprofen (Hydrocodone Bitartrate and Ibuprofen) label · effective 2025-12-23

Major

S er otonin Syndrome Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs.

Precautionsby drug classView label on DailyMed
Moderate

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status.

Warningsby drug classView label on DailyMed
Moderate

Co-morbid conditions such as coagulation disorders, concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk.

Warningsby drug classView label on DailyMed
Moderate

Serotonergic Drugs The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system…

Drug interactionsby drug classView label on DailyMed
Moderate

Monitor patients with concomitant use of hydrocodone bitartrate and ibuprofen tablets with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), SSRIs, and SNRIs for signs of bleeding (see WARNINGS: Hematologic Toxicity ).

Drug interactionsby drug classView label on DailyMed

From the Fluoxetine (Prozac) label · effective 2026-01-08

Moderate

Use with NSAIDs, aspirin, warfarin, or other drugs that affect coagulation may potentiate the risk of gastrointestinal or other bleeding ( 5.7 )

Warnings and precautionsby drug classView label on DailyMed
Moderate

Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anti-coagulants may add to this risk.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Patients should be cautioned about the increased risk of bleeding associated with the concomitant use of fluoxetine and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation [see Drug Interactions ( 7.4 )] .

Warnings and precautionsby drug classView label on DailyMed
Moderate

Serotonergic Drugs: ( 2.9 , 2.10 , 4.1 , 5.2 ) Drugs that Interfere with Hemostasis (e.g. NSAIDs, Aspirin, Warfarin): May potentiate the risk of bleeding ( 7.4 )

Drug interactionsby drug classView label on DailyMed
Moderate

Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding.

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.