OTC NSAID and ASA GI Bleeding Analysis of Spontaneous

							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




      Center for Drug Evaluation and Research
           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




                                  2
     NSAID OTC Indications

• Temporary relief pain
  – headache
  – muscular aches
  – the minor pain of arthritis
  – toothache
  – backache
  – common cold
  – menstrual cramps
• Fever
                                  3
      ASA OTC Indication

• Temporary relief pain




                           4
      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
                                                5
  AERS case selection, cont

279 cases included in series
   NSAIDs-197
     Ibuprofen
     Ketoprofen
     Naproxen
   Aspirin-82



                               6
              Reporters

•   Healthcare practitioner-125
•   Consumer-63
•   Attorney-3
•   Unknown-3




                                  7
        Demographics

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


                            8
       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


                                        9
          Location of bleed

•   Stomach; n=63
•   Duodenum; n=35
•   Unspecified upper GI; n=15
•   Esophagus; n=13
•   Rectum/colon/small intestine;
    n=9



                                    10
     Median time to onset

• NSAIDs-7 days
• ASA-30 days
  (wide range)




                            11
                 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
                                         12
           Risk factors

• 70% (195/279) at least 1 RF
• 40% (112/279) had > 1 RF
• 29% (81/279) no RF




                                13
      Risk factors, cont’

• Concomitant meds (~50%)
  –NSAID (inc COX-2)
  –Aspirin
• Age > 65 (~40%)
• GI history (~18%)
• ETOH (~12%)
• Tobacco use (~5%)


                            14
      Risk factors, cont’

• Dose exceeding OTC labeling
  –NSAID-13.7% (27/197)
  –ASA-1.2% (1/82)




                                15
            Outcome

• Hospitalization-76% (212/279)
• Death-4.7% (13/279)




                                  16
         Conclusions

• GI bleeding occurs with OTC use
  of NSAIDs & ASA
• Most patients recovered after
  hospitalization




                                17
       Conclusions, cont’

• Most patients had risk factors for
  GI bleeding
  –Concomitant medications
  –Advanced age
  –GI history




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