1. OTC NSAID and ASA GI Bleeding Analysis of Spontaneous Reports Nonprescription Drugs Advisory Committee Meeting Joyce P. Weaver, Pharm.D. Office of Drug Safety September 20, 2002 Nonprescription Drugs Advisory Committee Meeting Joyce P. Weaver, Pharm.D. Office of Drug Safety September 20, 2002 Center for Drug Evaluation and Research

2. 2 Objective To describe cases reported to the FDA’s Adverse Event Reporting System (AERS) of GI bleeding in individuals who ingested an OTC NSAID or ASA

3. 3 NSAID OTC Indications Temporary relief pain –headache –muscular aches –the minor pain of arthritis –toothache –backache –common cold –menstrual cramps Fever Temporary relief pain –headache –muscular aches –the minor pain of arthritis –toothache –backache –common cold –menstrual cramps Fever

4. 4 ASA OTC Indication Temporary relief pain

5. 5 AERS case selection AERS* searched for cases rec 1/1/1998 - 12/31/2001 Cases screened for “OTCness” –NSAIDs-use of OTC product, or OTC use in narrative –ASA-analgesic indication * AERS is an FDA database of spontaneously reported adverse drug events AERS* searched for cases rec 1/1/1998 - 12/31/2001 Cases screened for “OTCness” –NSAIDs-use of OTC product, or OTC use in narrative –ASA-analgesic indication * AERS is an FDA database of spontaneously reported adverse drug events

6. 6 AERS case selection, cont 279 cases included in series  NSAIDs-197  Ibuprofen  Ketoprofen  Naproxen  Aspirin-82 279 cases included in series  NSAIDs-197  Ibuprofen  Ketoprofen  Naproxen  Aspirin-82

7. 7 ReportersReporters Healthcare practitioner-125 Consumer-63 Attorney-3 Unknown-3 Healthcare practitioner-125 Consumer-63 Attorney-3 Unknown-3

8. 8 DemographicsDemographics Age –Mean 59.3 yrs (range 1-99) Gender –Male-49.5% (138/279) –Female-42.7% (119/279) –Unknown-7.9% (22/279) Age –Mean 59.3 yrs (range 1-99) Gender –Male-49.5% (138/279) –Female-42.7% (119/279) –Unknown-7.9% (22/279)

9. 9 Indications for use Pain, “aches and pains”; n=70 Arthritis; n=49 Headache; n=35 Back, neck, or shoulder pain; n=25 Hip, knee, ankle, foot, joint; n=18 Fever; n=11 Pain, “aches and pains”; n=70 Arthritis; n=49 Headache; n=35 Back, neck, or shoulder pain; n=25 Hip, knee, ankle, foot, joint; n=18 Fever; n=11

10. 10 Location of bleed Stomach; n=63 Duodenum; n=35 Unspecified upper GI; n=15 Esophagus; n=13 Rectum/colon/small intestine; n=9 Stomach; n=63 Duodenum; n=35 Unspecified upper GI; n=15 Esophagus; n=13 Rectum/colon/small intestine; n=9

11. 11 Median time to onset NSAIDs-7 days ASA-30 days (wide range) NSAIDs-7 days ASA-30 days (wide range)

12. 12 Risk factors Previous GI bleed/ulcer, H. pylori Other medical hx Social hx –ETOH, tobacco Concomitant meds –NSAID, ASA, anticoagulant, corticosteroid Dose > labeled OTC dose Advanced age Wolfe et al. NEJM 1999; 340: 1888-99 Previous GI bleed/ulcer, H. pylori Other medical hx Social hx –ETOH, tobacco Concomitant meds –NSAID, ASA, anticoagulant, corticosteroid Dose > labeled OTC dose Advanced age Wolfe et al. NEJM 1999; 340: 1888-99

13. 13 Risk factors 70% (195/279) at least 1 RF 40% (112/279) had > 1 RF 29% (81/279) no RF 70% (195/279) at least 1 RF 40% (112/279) had > 1 RF 29% (81/279) no RF

14. 14 Risk factors, cont’ Concomitant meds (~50%) –NSAID (inc COX-2) –Aspirin Age > 65 (~40%) GI history (~18%) ETOH (~12%) Tobacco use (~5%) Concomitant meds (~50%) –NSAID (inc COX-2) –Aspirin Age > 65 (~40%) GI history (~18%) ETOH (~12%) Tobacco use (~5%)

15. 15 Risk factors, cont’ Dose exceeding OTC labeling –NSAID-13.7% (27/197) –ASA-1.2% (1/82) Dose exceeding OTC labeling –NSAID-13.7% (27/197) –ASA-1.2% (1/82)

16. 16 OutcomeOutcome Hospitalization-76% (212/279) Death-4.7% (13/279) Hospitalization-76% (212/279) Death-4.7% (13/279)

17. 17 ConclusionsConclusions GI bleeding occurs with OTC use of NSAIDs & ASA Most patients recovered after hospitalization GI bleeding occurs with OTC use of NSAIDs & ASA Most patients recovered after hospitalization

18. 18 Conclusions, cont’ Most patients had risk factors for GI bleeding –Concomitant medications –Advanced age –GI history Most patients had risk factors for GI bleeding –Concomitant medications –Advanced age –GI history

19. 19