Diflunisal and Orphenadrine, aspirin, and caffeine interaction

Diflunisal and Orphenadrine, aspirin, and caffeine: 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 Diflunisal label · effective 2026-08-04

Major

Diflunisal tablets should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.

Contraindicationsnames Orphenadrine, aspirin, and caffeineView label on DailyMed
Major

This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS, Preexisting Asthma ).

Warningsnames Orphenadrine, aspirin, and caffeineView label on DailyMed
Major

The concomitant use of diflunisal tablets and other NSAIDs is not recommended due to the increased possibility of gastrointestinal toxicity, with little or no increase in efficacy.

Drug interactionsby drug classView label on DailyMed
Moderate

There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use.

Warningsnames Orphenadrine, aspirin, and caffeineView label on DailyMed
Moderate

The concurrent use of aspirin and an NSAID, such as diflunisal, increases the risk of serious gastrointestinal (GI) events (see WARNINGS ).

Warningsnames Orphenadrine, aspirin, and caffeineView label on DailyMed

From the Orphenadrine, aspirin, and caffeine (Norgesic) label · effective 2026-01-08

Major

Pregnancy Embryo-Fetal Toxicity Inform pregnant women to avoid use of aspirin and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus.

Precautionsby drug classView label on DailyMed
Moderate

Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive.

Warningsby 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.