Hydrocodone and ibuprofen and Orphenadrine, aspirin, and caffeine interaction

Hydrocodone and ibuprofen 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 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

From the Hydrocodone and ibuprofen (Hydrocodone Bitartrate and Ibuprofen) label · effective 2025-12-23

Major

History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs.

Contraindicationsnames Orphenadrine, aspirin, and caffeineView label on DailyMed
Major

Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients (see WARNINGS: Anaphylactic Reactions, Exacerbation of Asthma Related to Aspirin Sensitivity ).

Contraindicationsnames Orphenadrine, aspirin, and caffeineView label on DailyMed
Major

Exacerbation of Asthma Related to Aspirin Sensitivity A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs.

Warningsnames Orphenadrine, aspirin, and caffeineView label on DailyMed
Major

Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, hydrocodone bitartrate and ibuprofen tablets are contraindicated in patients with this form of aspirin sensitivity (see CONTRAINDICATIONS).

Warningsnames Orphenadrine, aspirin, and caffeineView label on DailyMed
Major

…LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P4503A4 INTERACTION; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; and SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF HYDROCODONE BITARTRATE AND IBUPROFEN TABLETS Addiction,…

Boxed warningby 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.