NSAID drug interactions

Question 1

Warfarin

Answer 1

• Nonselective NSAIDs inhibit platelet aggregation; especially ASA with irreversible effect; can increase bleeding
• All NSAIDs can cause GI bleeding
• May get protein binding displacement
• Increased INR/PT and GI bleeding may also be seen with COX-2 selective NSAIDs (inhibition of warfarin metabolism?)
• If NSAID needed, use celecoxib or nonacetylated salicylate

Question 2

Direct oral anticoagulants

Answer 2

Increased bleeding risk since coagulation pathway and platelet aggregation both affected by combination

Question 3

Probenecid

Answer 3

• Decreases excretion of NSAIDs; especially affects drugs with glucuronide metabolites e.g. diflunisal, indomethacin, ketoprofen, naproxen
• Probenecid’s effect inhibited by aspirin and other salicylates

Question 4

Hypoglycemics

Answer 4

• Protein binding displacement

* Salicylate can decrease glucose in pts on glipizide and other hypoglycemics

Question 5

Methotrexate

Answer 5

• Excretion of methotrexate may be inhibited by e.g. salicylate, fenoprofen, naproxen, tolmetin, ibuprofen; low dose aspirin probably okay
• General concern with decreased renal function by NSAIDs since MTX is excreted primarily by kidneys

Question 6

Antihypertensives

Answer 6

• May blunt antihypertensive effects of beta blockers, ACE inhibitors, thiazides; negligible effects with calcium channel blockers; Beta blockers affected > vasodilators > diuretics
• NSAIDs only increased BP in hypertensive pts
- Effects of NSAIDs on mean arterial pressure (MAP): indomethacin, naproxen, piroxicam, diclofenac
- Negligible effects with ASA, ibuprofen, sulindac

Question 7

Lithium

Answer 7

• Shares excretion pathway with NSAIDs

* Lithium clearance decreased with indomethacin, diclofenac, piroxicam

Question 8

Diuretics

Answer 8

• NSAIDs decrease Na excretion with loop diuretics by preventing PG-induced increase in renal plasma flow
• Less effect on diuresis with thiazides
• Monitor for increased K with potassium-sparing diuretics

Question 9

Aspirin

Answer 9

• Ibuprofen may decrease cardioprotective effects of low-dose ASA
• Competitive binding to COX-1
• Ibuprofen effect greatest at 2 h after dose, continues to 6 h
• Aspirin decreases GI benefits of celecoxib