Urticaria DR.A.Asilian

Mechanism of Allergy TH1 TH2 Infections Allergy

Mechanism of Allergy II Peanut antigen TH2 B cell Plasma cell

Mechanism of Allergy III Plasma Cell IgE

Mechanism of Allergy IV Mast Cell IgE

Mechanism of Allergy V Mast Cell

Mechanism of Allergy VI Peanut antigen Exploding Mast Cell Histamine

Mechanism of Allergy VII Urticaria

Urticaria Affects 20% of population Occurs across the age spectrum1 Sometimes possible to identify a trigger such as food, drug, insect sting or infection More than 2/3 of cases are self-limiting

Characteristics Pruritic (most severely at night) Erythematous Often exhibit central pallor Blanches Oval, round or irregular shape or plaques Plaques “move” to different locations over minutes to hours Last less than 24 hours Leave no residual marks (other than those created by scratching)

Urticaria Urticaria is characterized by wheals (itchy hives) and lesions that look like burns from stinging nettle.

Hives or angioedema In some patients, only hives occur – in others, only angioedema. Angioedema is swelling of the skin and mucous membranes.

Hives and angioedema Most patients experience both hives and angioedema.

Men and women Both sexes are affected - women twice as often as men.

Young and elderly Urticaria occurs most commonly in young adults. But, children and the elderly can also suffer from urticaria.

Classification Acute versus Chronic Urticaria Acute episodes < 6 weeks more likely to have an identifiable trigger Chronic episodes last > 6 weeks less likely to have an identifiable trigger

Treatment of Urticaria H1 antihistamines First generation: diphenhydramine, chlorpheniramine, hydroxyzine Second generation: cetirizine, loratadine, fexofenadine

Treatment of Urticaria (cont) First generation antihistamines: more sedating, require more frequent dosing Second generation antihistamines: higher dosing than standard dosing to obtain positive effects Can be sedating at higher dosages

Treatment of Urticaria (cont) Pregnant women or those breastfeeding may use loratidine or cetirizine

Treatment of Urticaria (cont) Consider use of H2 blocker as well although data is not particularly supportive ranitidine, nizatidine, famotidine and cimetidine (note cimetidine can increase drug levels in other medications taken concurrently)

Neotadin

Neotadin (Desloratadine) Active & Potent metabolite of Loratadin New Second generation H1 receptor antagonist

CLINICAL PHARMACOLOGY

Mechanism of Action A long-acting tricyclic histamine antagonist with selective H1-receptor histamine antagonist activity A study in guinea pigs showed that desloratadine did not readily cross the blood brain barrier.

Pharmacodynamics Exhibits an antihistaminic effect by 1 hour This effect persists for as long as 24 hours. Effects on QTc : No clinically relevant adverse events were reported

PHARMACOKINETICS Tmax : 3 hr Half-life : 27 hr Absorption : Tmax : 3 hr Neither food nor grapefruit juice had an effect on the bioavailability (Cmax and AUC) of desloratadine Distribution : 82% - 87% bind to plasma protein Elimination : Half-life : 27 hr equally distributed in urine and feces as metabolic products

Seasonal Allergic Rhinitis: Perennial Allergic Rhinitis: INDICATIONS AND USAGE: Seasonal Allergic Rhinitis: relief of nasal and non-nasal symptoms in patients 2 years of age and older Perennial Allergic Rhinitis: relief of nasal and non-nasal symptoms in patients 6 months of age and older Chronic Idiopathic Urticaria: symptomatic relief of pruritus, reduction in the number of hives, and size of hives in patients 6 months of age and older

Adults and Adolescents 12 Years of Age and Over: DOSAGE Adults and Adolescents 12 Years of Age and Over: • Neotadin Tablets - one 5 mg tablet once daily or • Neotadin Oral Solution - 2 teaspoonfuls (5 mg in 10 mL) once daily Children 6 to 11 Years of Age: • Neotadin Oral Solution - 1 teaspoonful (2.5 mg in 5 mL) once daily Children 12 Months to 5 Years of Age: • Neotadin Oral Solution - 1/2 teaspoonful (1.25 mg in 2.5 mL) once daily Children 6 to 11 Months of Age: • Neotadin Oral Solution - 2 mL (1 mg) once daily

Neotadin Oral Solution - 0.5 mg/1 mL DOSAGE FORMS AND ADMINISTRATION Neotadin Tablets - 5 mg Neotadin Oral Solution - 0.5 mg/1 mL Take tablet immediately after opening the blister may be taken without regard to meals, with or without water

Contraindication Hypersensitivity

WARNINGS AND PRECAUTIONS Hypersensitivity reactions including rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis have been reported. In such cases, stop Neotadin at once and consider alternative treatments.

ADVERSE REACTIONS Pharyngitis, dry mouth, myalgia, fatigue, The most common adverse reactions (reported in ≥2% of adult and adolescent patients with allergic rhinitis and greater than placebo) were: Pharyngitis, dry mouth, myalgia, fatigue, somnolence, Dysmenorrhea With Chronic Idiopathic Urticaria: Headache, nausea, fatigue, dizziness, pharyngitis, dyspepsia , myalgia

USE IN SPECIFIC POPULATIONS* Renal impairment: dosage adjustment is recommended Hepatic impairment: dosage adjustment is recommended A starting dose of one 5-mg tablet every other day Pregnancy: category C Desloratadine was not teratogenic in animals Desloratadin passes into breast milk Geriatric : dose selection for an elderly patient should be cautious *Dosing recommendation for children with liver or renal impairment cannot be made due to lack of data.

NO DRUG INTERACTIONS

Important notes: FDA approved >6 months old No CNS suppression (selective H1 antagonist) Limited penetration of BBB(no anticholinergic effects) Active & potent metabolite of Loratadine 2nd generation Antihistamines : the first choice in guidelines for AR & CIU Once daily (Half-life=27 Hours) Absorption is unaffected by food Not metabolized by CytP450 Excellent compliance

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