Jonathan Wilkin, M.D. Director, Division of Dermatologic and Dental Drug Products, FDA URTICARIA: Overview and OTC Considerations April 22, 2002

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10 HEURISTIC SUBDIVISIONS 1.Acute urticaria - less than 6 weeks; history implicates cause in approx. 50%; difficult to study in clinical trials; good prognosis. 2.Chronic urticaria - greater than 6 weeks; workup indicated; easier to study; often persistent. 3.Chronic idiopathic urticaria - subset of chronic urticaria in which workup fails to pinpoint cause; diagnosis by exclusion; not homogeneous.

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12 OBSERVATIONS 1.Urticaria is not a single disease, but a REACTION PATTERN mediated by HISTAMINE release in the superficial skin. 2.Acute urticaria and chronic urticaria are not single diseases, but are useful heuristic distinctions directing clinical decisions. 3.Most types of urticaria will respond to an antihistamine found safe and effective in patients with Chronic Idiopathic Urticaria.

13 Urticaria Requiring a Physician  Possibly related to peanut or latex allergy  Persisting beyond six weeks  Which leaves bruising or skin tone changes  With blistering or other rash

14 Urticaria Requiring a Physician (cont’d)  Associated with fever, joint pain, malaise, systemic features  Poorly responsive to oral antihistamines  Associated with swelling of lips, tongue, throat  Which doesn’t itch

15 CIU vs “Hives” as OTC Indication 1.“Urticarial lesions are generally easy to recognize since they typically occur in visible locations and are associated with intense itching.” 2.“… it is likely that acute hive sufferers are already using (sic: sedating) OTC antihistamines.” 3.The “hive” and the associated itching of almost all urticaria are mediated by histamine. 4.Perhaps with proper labeling, “hives” may be the preferable OTC indication.

16 “…(Loratadine’s) effectiveness, combined with its selectivity, safety, and tolerability, distinguishes it from other members of its class and makes it an excellent choice for the treatment of most urticarias.” E.W. Monroe Clin Ther 19: , 1997

17 Chronic Urticaria and Angioedema  Angioedema and urticaria in 40%  Urticaria alone in 40%  Angioedema alone in 20%

18 Angioedema  Same pathologic process as urticaria but additionally involves subdermal vessels.  Often IgE-mediated, complement-mediated, or due to direct mast cell-releasing agents.  Hereditary angioedema

19 Anaphylaxis  A severe allergic reaction  Full-blown syndrome includes: urticaria, angioedema, hypotension, bronchospasm  Inciting agents: parenteral antibiotics, IV contrast materials, insect stings, certain foods  (Anaphylactoid reaction - clinically similar, but not involving IgE)