OBJECT DRUGS

NSAIDs:

• Diclofenac (Voltaren, etc.)
• Diflunisal (Dolobid)
• Etodolac (Lodine)
• Fenoprofen (Nalfon)
• Flurbiprofen (Ansaid, etc.)
• Ibuprofen (Motrin, etc.)
• Indomethacin (Indocin, etc.)
• Ketoprofen (Orudis)
• Ketorolac (Toradol, etc.)
• Meclofenamate
• Mefenamic acid
• Meloxicam (Mobic)
• Nabumetone (Relafen)
• Naproxen (Aleve, etc.)
• Oxaprozin (Daypro)
• Piroxicam (Feldene)
• Sulindac (Clinoril)
• Tolmetin (Tolectin)

PRECIPITANT DRUGS

SSRI and SNRI:

• Citalopram (Celexa)
• Clomipramine (Anafranil)
• Desvenlafaxine (Pristiq, etc.)
• Duloxetine (Cymbalta)
• Escitalopram (Lexapro)
• Fluoxetine (Prozac, etc.)
• Fluvoxamine (Luvox, etc.)
• Imipramine (Tofranil, etc.)
• Levomilnacipran (Fetzima)
• Milnacipran (Savella)
• Nefazodone
• Paroxetine (Paxil, etc.)
• Sertraline (Zoloft)
• Venlafaxine (Effexor)
• Vilazodone (Viibryd)
• Vortioxetine (Brintellix)

Comment:

Some studies suggest that the concurrent use of NSAIDs or aspirin with serotonin reuptake inhibitors (SSRI) or serotonin-norepinephrine uptake inhibitors (SNRI) increases the risk of gastrointestinal (GI) bleeding compared to either drug used alone. Some evidence suggests that even low-dose aspirin may increase GI bleeding when combined with SSRIs or SNRIs. However, the vast majority of patients on concurrent therapy with an NSAID or aspirin and an SSRI will not develop GI bleeding. Since GI bleeding can be fatal, however, anything that increases the risk should be avoided if possible. The putative mechanism is inhibition of serotonin uptake by platelets added to gastric toxicity and antiplatelet effect caused by the NSAIDs. The risk of GI bleeding appears to be related to the potency of the serotonin reuptake inhibition, a finding that lends additional support to the existence of an interaction.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• NSAIDs: If the NSAID is being used as an analgesic, consider using acetaminophen instead. COX-2 inhibitors do not affect platelets, and may offer a lower risk of GI bleeding when combined with a SSRI.
• Antidepressant: If appropriate for the patient, consider using agents with low serotonin reuptake inhibition such as desipramine (Norpramin), maprotiline (Ludiomil), nortriptyline (Aventyl), trimipramine (Surmontil) or moderate serotonin reuptake inhibitors such as amitriptyline (Elavil) or imipramine (Tofranil).
• Monitor: Patients and health professionals should be alert for evidence of gastrointestinal bleeding if these combinations are used.