Norgesic Drug Interactions: What to Avoid and What to Tell Your Doctor

Because Norgesic contains three active ingredients — orphenadrine (a muscle relaxant with anticholinergic effects), aspirin (an NSAID), and caffeine (a CNS stimulant) — it has the potential to interact with a broad range of medications and substances. This guide covers the most important interactions to be aware of when taking Norgesic.

Important: Always tell your doctor and pharmacist about every medication, supplement, and herbal product you take before starting Norgesic. This list is not exhaustive.

Major Interactions: Do Not Combine Without Medical Guidance

Anticoagulants (warfarin, heparin, enoxaparin, dabigatran): The aspirin in Norgesic has antiplatelet effects and can increase bleeding risk significantly when combined with blood thinners. If you're on warfarin or another anticoagulant, this combination requires very careful monitoring — most providers will avoid it entirely.

Ketorolac (Toradol): The prescribing information lists ketorolac as a contraindicated combination. Both aspirin and ketorolac are NSAIDs, and combining them dramatically increases the risk of serious GI bleeding and peptic ulceration.

Defibrotide: Aspirin plus defibrotide significantly increases bleeding risk. Do not combine.

Abrocitinib: Aspirin-containing products should generally not be combined with abrocitinib in certain dosing scenarios without provider guidance.

Moderate Interactions: Use With Caution — Tell Your Doctor

Other NSAIDs (ibuprofen, naproxen, diclofenac, celecoxib): Combining Norgesic with other NSAIDs significantly increases the risk of GI irritation, ulcers, and bleeding. Many OTC pain relievers (Advil, Motrin, Aleve) are NSAIDs — read labels carefully. Do not take additional NSAIDs while on Norgesic without consulting your doctor.

CNS depressants (opioid pain medications, benzodiazepines, sleep aids, barbiturates): Orphenadrine adds to the sedating effects of these medications. Combining Norgesic with opioids (like oxycodone, hydrocodone) or benzodiazepines (like alprazolam, diazepam) can cause dangerous sedation, respiratory depression, or unconsciousness.

Antidepressants (amitriptyline, trazodone, SSRIs): Tricyclic antidepressants have overlapping anticholinergic effects with orphenadrine. SSRIs combined with aspirin significantly increase the risk of GI bleeding. The clinical package insert specifically warns about confusion, anxiety, and tremors with concomitant propoxyphene and orphenadrine.

Antihistamines (diphenhydramine, promethazine): Many antihistamines have anticholinergic properties that overlap with orphenadrine, potentially causing additive dry mouth, urinary retention, confusion, and drowsiness.

Corticosteroids (prednisone, dexamethasone): Combining aspirin with corticosteroids increases the risk of GI ulcers and bleeding. Avoid combining unless specifically directed by your doctor.

Anticonvulsants (phenobarbital, primidone): May increase CNS depressant effects. Monitor for excessive sedation.

Substances to Avoid While Taking Norgesic

Alcohol: Increases both the sedating effects of orphenadrine and the risk of GI bleeding from aspirin. Daily alcohol use while on Norgesic is particularly dangerous. Avoid alcohol entirely while taking this medication.

Tobacco: Smoking increases the risk of aspirin-related GI bleeding. Avoid tobacco during treatment.

OTC Products to Watch Out For

Many over-the-counter medications contain hidden aspirin or other NSAIDs. While taking Norgesic, read labels carefully before taking:

Cold, flu, and cough medications (many contain aspirin or ibuprofen)

Antacids and digestive aids (some contain salicylates)

Combination pain relievers (Excedrin contains aspirin and caffeine — very similar to components of Norgesic)

Sleep aids containing diphenhydramine (antihistamine with overlapping anticholinergic effects)

What to Tell Your Doctor Before Starting Norgesic

At your appointment, disclose all of the following:

All prescription medications, including blood thinners, heart medications, antidepressants, and seizure medications

All OTC medications and supplements, including aspirin, ibuprofen, naproxen, and vitamins

Herbal supplements (ginkgo biloba and fish oil both increase bleeding risk when combined with aspirin)

Alcohol use history

History of peptic ulcer, GI bleeding, glaucoma, enlarged prostate, or kidney disease

For a broader overview of side effects, see our article on Norgesic side effects.