Chronic Urticaria Medication

Antihistamines ^{[25, 26]}

The mainstay of pharmacotherapy for chronic urticaria is low-sedation anti-H1 antihistamines, which have a low incidence of adverse effects. Quality of life appears to be improved more by daily therapy than therapy administered on an "as needed" basis.^[27] Low-sedating antihistamines such as loratadine, cetirizine, levocetirizine, and fexofenadine decrease the intensity of hives and pruritus in patients with mild, chronic urticaria and are considered first-line therapy. Crossover studies comparing the suppression of skin papule and erythema formation induced by intradermal histamine injection following a single antihistamine dose suggest the following order of inhibitory effect: (1) levocetirizine, (2) cetirizine, (3) terfenadine, (4) fexofenadine, and (5) loratadine.

Skin concentration—not plasma concentration—correlates to drug potency in inhibiting wheal and erythema formation response to intradermal histamine injection. Sedation and impairment of performance are concerns when using sedating antihistamines, yet these adverse effects may diminish after 1-2 weeks of therapy.

Pregnancy

Cetirizine and loratadine are category B; nevertheless, a first-generation antihistamine, such as chlorpheniramine, may be considered the drug of choice because the cumulative experience of use of this agent in pregnant women is greater.

Kidney or liver impairment

For cetirizine, 60% is eliminated via the kidneys. For levocetirizine, the figure is 85%. Most H1 or H2 antihistamines undergo presystemic metabolism in the liver via cytochrome P-450. A reduction in dose of low-sedating antihistamines is advised in patients with liver or renal failure.

Children

Cetirizine and fexofenadine are approved by the US Food and Drug Administration for chronic urticaria in children aged 6 months and older. Desloratadine is approved for chronic urticaria in children aged 1 year and older. Loratadine is approved for chronic urticaria in children aged 2 years and older. Levocetirizine is approved for chronic urticaria in children aged 6 years and older. Hydroxyzine has been used to alleviate pruritus in children with atopic dermatitis and is an appropriate second-line agent in children with chronic urticaria refractory to low-sedating antihistamines.

Antileukotrienes ^{[28, 29]}

Leukotriene antagonists have been shown to be superior to placebo in the treatment of patients with chronic urticaria but are considered less effective than nonsedating antihistamines; however, the agents can be combined. Montelukast at 10 mg/d may be particularly helpful for patients experiencing flare-ups due to aspirin or other nonsteroidal anti-inflammatory drugs. Montelukast is approved for perennial allergic rhinitis in children aged 6 months and older.

Cyclosporine

Cyclosporine at 4-6 mg/kg/d has been shown in randomized double-blind studies to be effective for chronic urticaria. Cyclosporine therapy should be limited to 3 months or less for chronic urticaria. A sustained remission is observed in approximately one third of patients treated with his medication.

Systemic corticosteroids

Systemic corticosteroids are usually effective when antihistamines are not adequate. In the rare situation when systemic corticosteroid treatment is needed to treat chronic urticaria, a low dose daily or alternate-day dosing of corticosteroids is advised, and the dose should be titrated to the lowest effective level. Patients receiving long-term corticosteroid therapy should be routinely monitored for bone density changes and adverse ocular effects.

Levothyroxine

Some patients with chronic urticaria and antithyroid antibodies have been shown to benefit from levothyroxine treatment, perhaps by suppression of thyroid activity and, possibly, the autoimmune process. The goal of treatment is to maximally suppress thyrotropin without rendering the patient clinically hyperthyroid. The urticaria may respond within 2 weeks of initiation of adequate treatment. Some patients may maintain a sustained remission after 3-6 months of treatment, at which point the levothyroxine can be tapered and then discontinued.

Class Summary

Compete with histamine at tissue receptor level, preventing it from carrying out its mediator functions in urticaria.

Diphenhydramine (Benadryl)

For symptomatic relief of symptoms caused by release of histamine in allergic reactions.

Hydroxyzine (Atarax, Vistaril)

Antagonizes H1 receptors in periphery. May suppress histamine activity in subcortical region of CNS. Available in 10-, 25-, and 50-mg tab or cap and 100-mg cap. Susp is 25 mg/5 mL and syr is 10 mg/5 mL (tsp)

For patients who have difficulty swallowing, a 25-mg/5-mL oral susp is available.

Doxepin (Sinequan, Zonalon)

Inhibits histamine and acetylcholine activity.

Class Summary

Modify the immune response to diverse stimuli.

Prednisone (Deltasone, Orasone, Meticorten, Sterapred)

Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.

Colchicine

Decreases leukocyte motility and phagocytosis in inflammatory responses.

Class Summary

May reduce inflammation.

Dapsone (Avlosulfon)

Mechanism of action is similar to that of sulfonamides, in which competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth. Effects in inflammatory reactions unknown.

Class Summary

Also known as less-sedating antihistamines, these drugs produce less sedation than traditional H1 blockers because they are less lipid soluble and only cross the blood-brain barrier in small amounts. Also have longer half-lives, allowing for less-frequent dosing.

Cetirizine (Zyrtec)

Forms complex with histamine for H1-receptor sites in blood vessels, GI tract, and respiratory tract.

Available as 5- or 10-mg tab and as 1-mg/mL syr; each teaspoonful (5 mL) contains 5 mg.

Fexofenadine (Allegra)

Competes with histamine for H1 receptors in GI tract, blood vessels, and respiratory tract, reducing hypersensitivity reactions. Does not sedate. Available as 30-, 60-, or 180-mg tab. Allegra ODT tab formulated for disintegration in mouth immediately following administration. Each orally disintegrating tab contains 30 mg fexofenadine hydrochloride. Allegra oral susp contains 6 mg fexofenadine hydrochloride per mL or 30 mg/5 mL.

Loratadine (Claritin)

Selectively inhibits peripheral histamine H1 receptors. Available in 10-mg tab or 10-mg RediTabs; syr is 5 mg/5 mL (tsp).

Desloratadine (Clarinex)

Long-acting tricyclic histamine antagonist selective for H1 receptor. Relieves nasal congestion and systemic effects of seasonal allergy. Is a major metabolite of loratadine, which, after ingestion, is metabolized extensively to active metabolite 3-hydroxydesloratadine. Available as 5-mg tab; syr is 0.5 mg/mL (2.5 mg/5 mL; tsp); RediTab (desloratadine orally disintegrating tab) is 2.5 mg and 5 mg.