Acute Urticaria Medication

Updated: Sep 18, 2023
  • Author: Henry K Wong, MD, PhD; Chief Editor: Michael A Kaliner, MD  more...
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Medication Summary

Use of antihistamines is the mainstay of therapy. In acute cases, a short course of steroids can be very effective. Long-term treatment with steroids should be avoided, if possible, but may be necessary in severe cases. A number of other classes of medicines have been found to be effective, mostly on an experimental basis. If urticaria does not respond to antihistamine treatment (with the possible addition of a short course of steroids), then referral to a specialist is indicated. [70, 2, 52, 71, 72]


H1 Antagonists (first-generation antihistamines)

Class Summary

Primary agents used for urticaria. [17] The older, first-generation H1 antagonists (eg, diphenhydramine, hydroxyzine) are effective in reducing the lesions and pruritus but can produce adverse effects, such as drowsiness and anticholinergic effects. [49]  These are no longer first-line treatments, but can be helpful when sedation is needed.

The first-generation agents can be useful if administered at bedtime because the sedative effects can help with sleep; however, the patient must be warned that the sedation and cognitive effects may continue until the next day. Any patient who is taking a medication that has potential sedative effects should be cautioned about driving and operating heavy machinery. Commonly used first-generation agents include diphenhydramine, hydroxyzine, doxepin, chlorpheniramine, and cyproheptadine.

Diphenhydramine (Benadryl, Diphen, Banophen, Genahist)

Diphenhydramine is a common first-generation agent that is available without a prescription in the United States and can be used to control pruritus. It acts by competitive inhibition of histamine at the H1 receptor, which mediates the wheal-and-flare reactions.


Cyproheptadine is a first-generation agent and historically has been a drug of choice for prophylaxis of primary acquired cold-induced urticaria.

Chlorpheniramine (Chlor-Trimeton, Aller-Chlor, Ed-Chlortan)

Chlorpheniramine is a first-generation agent and is one of the safest antihistamines to use during pregnancy.

Hydroxyzine (Vistaril)

Hydroxyzine is used for control of pruritus. It is an effective first-generation agent but frequently produces sedation, particularly with higher doses. Historically, it has been considered a drug of choice for cholinergic urticaria. SC and IV are not recommended administration routes. Hydroxyzine also may suppress histamine activity in the subcortical region of the CNS.


H1 Antagonists (second-generation antihistamines)

Class Summary

The newer second-generation antihistamines are nonsedating in most patients, with very few adverse effects reported. These agents are preferred for acute and chronic urticaria, with first-generation agents reserved for efractory cases. Commonly used H1 antagonists currently available in the United States are cetirizine, levocetirizine, desloratadine, loratadine, and fexofenadine.

Loratadine (Claritin, Alavert)

Loratadine selectively inhibits peripheral histamine H1 receptors. It is tolerated very well, with a rate of sedation that is not significantly different from that of placebo. The once-daily dosing makes it convenient.

Fexofenadine (Allegra)

Fexofenadine is a second-generation agent that is effective in urticaria. It is tolerated very well, with a rate of sedation that is not significantly different from that of placebo. Fexofenadine competes with histamine for H1 receptors on the GI tract, blood vessels, and respiratory tract, reducing hypersensitivity reactions.

Desloratadine (Clarinex)

Desloratadine is a long-acting tricyclic histamine antagonist selective for H1 receptors. It is a major metabolite of loratadine, which, after ingestion, is metabolized extensively to active metabolite 3-hydroxydesloratadine.

Levocetirizine (Xyzal)

Levocetirizine is a histamine1-receptor antagonist and an active enantiomer of cetirizine. Peak plasma levels are reached within 1 hour, and the half-life is about 8 hours. It is available as a 5-mg breakable (scored) tab and is indicated for uncomplicated skin manifestations of chronic idiopathic urticaria

Cetirizine (Zyrtec)

Cetirizine is a second-generation agent that is frequently used in urticaria. It acts by competitive inhibition of histamine at the H1 receptor. Once-daily dosing makes it convenient, and sedation occurs in approximately 10% of patients. Dosing qhs may be useful if sedation is a problem. Although the standard dose is 5-10 mg qd, some specialists increase this to 10 mg bid for chronic urticaria that is not responding to the usual FDA-approved maximum dose.


H2 antagonists (antihistamines)

Class Summary

These are reversible, competitive blockers of histamine at H2 receptors, particularly those in gastric parietal cells. The H2 antagonists are highly selective, do not affect H1 receptors, and are not anticholinergic agents. They block the vasodilation mediated by the H2 receptors in blood vessels, possibly leading to less edema formation in urticaria.

When used as single agents for urticaria, they are not effective. However, the combination of an H1 antagonist with an H2 antagonist is more effective than an H1 antagonist alone. [51, 52] Any of the H2 blockers can be used. Two of the most commonly used agents are ranitidine and cimetidine.

Famotidine (Pepcid)

Famotidine is an H2 antagonist that, when combined with an H1 type, may be useful in treating allergic reactions that do not respond to H1 antagonists alone.

Cimetidine (Tagamet)

Cimetidine is an H2 antagonist that, when combined with an H1 antagonist, may be useful in treating itching and flushing in urticaria and contact dermatitis that do not respond to H1 antagonists alone. Use in addition to H1 antihistamines.

Ranitidine (Zantac)

Ranitidine is an H2 antagonist that, when combined with an H1 type, may be useful in treating urticaria when urticaria is not responsive to H1 antagonists alone.



Class Summary

In instances of acute or chronic urticaria in which antihistamines may fail, even at high doses, or adverse effects may be problematic, mediators other than histamine may be involved. In such situations, corticosteroids may be administered. The current recommendation is to avoid prednisone when possible. If not, then consider the possibility of another disease process (eg, malignancy, mastocytosis, [73] vasculitis). Corticosteroids may also be used in urticarial vasculitis, which usually does not respond to antihistamines.

In refractory cases, a short course of an oral corticosteroid (administered daily for 5-7 d, with or without a taper) or a single dose of a long-acting injectable steroid is not usually associated with long-term sequelae and can be helpful when used for an acute episode of urticaria nonresponsive to antihistamines. [30]

Because of adverse effects of chronic or recurrent use of systemic corticosteroids, the long-term use of these agents should be avoided, when possible. If urticaria is severe and cannot be safely controlled with other medications, low-dose therapy and/or alternate day therapy can be considered.

A large number of preparations are available. Representative examples are prednisolone, methylprednisolone, and prednisone.

Prednisolone (Millipred, Orapred, Pediapred)

Prednisone is a commonly used oral agent that must be metabolized to the active metabolite prednisolone for effect. Conversion may be impaired in liver disease. It is useful in cases that have not responded to traditional antihistamine. For extensive, symptomatic urticaria, a burst of prednisone over 4 days can lead to marked improvement and control of symptoms. Prednisone decreases inflammation by suppressing migration of polymorphonuclear leukocytes and by reversing increased capillary permeability.

Methylprednisolone (Medrol, Depo-Medrol, Solu-Medrol)

Methylprednisolone is used for the treatment of severe urticaria reactions. It reverses increased capillary permeability.

Prednisone (Deltasone, Rayos)

Prednisolone is available in both tablet and liquid forms. It reduces capillary permeability.


Sympathomimetic Agents

Class Summary

These agents cause vasoconstriction and reduction in vascular dilation, which contributes to urticaria formation.

Epinephrine (Adrenalin, Epi-Pen)

Epinephrine is DOC for the treatment of severe or generalized urticaria as part of an anaphylactic reaction. The alpha-agonist effects of this medication increase peripheral vascular resistance and reverse peripheral vasodilatation, vascular permeability, and systemic hypotension. Conversely, the beta-agonist effects of epinephrine produce bronchodilatation, cause positive inotropic and chronotropic cardiac activity, and result in an increased production of intracellular cAMP. Any patient who has had a potentially life-threatening allergic reaction should have injectable epinephrine available for use at all times (eg, portable Epi-Pen). Intramuscular administration of epinephrine is preferred over subcutaneous.


Leukotriene Receptor Antagonist

Class Summary

In recent years, leukotriene receptor antagonists (eg, montelukast) have been added to antihistamines to control urticaria. These can be used as third-line agents as there is only weak evidence to support their use in acute urticaria.

Montelukast (Singulair)

Montelukast is a potent and selective antagonist of leukotriene D4 (LTD4) at the cysteinyl leukotriene receptor, CysLT1. It prevents or reverses some of the pathologic features associated with the inflammatory process mediated by leukotrienes C4, D4, and E4. It is available as a tablet, chewable tablet, or PO granules. Granules may be administered directly in the mouth or dissolved in 1 tsp of cold or room-temperature baby formula, breast milk, or food (stable with applesauce, carrots, rice, or ice cream).

Zafirlukast (Accolate)

Zafirlukast inhibits the effects by leukotriene receptors, whose activity has been associated with airway edema, smooth muscle contraction, and cellular activity associated with the symptoms.


Tricyclic Antidepressants

Class Summary

These agents are a complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects, and block the active reuptake of norepinephrine and serotonin. Some TCAs (eg, doxepin) have antihistamine effects, blocking both the H1 and H2 receptors and have been used in the treatment of allergic reactions, especially urticaria.


Doxepin inhibits histamine and acetylcholine activity and has proven to be useful in the treatment of allergic dermatologic disorders. It has both H1 antagonist activity and H2 antagonist activity that is far more potent than traditional antihistamines. It also has antidepressant properties attributed to blocking MAO.


Monoclonal Antibodies, Anti-asthmatics

Class Summary

Agents in this class are recombinant DNA-derived humanized immunoglobulin G monoclonal antibodies that bind selectively to human immunoglobulin E on the surface of mast cells and basophils. The drug reduces mediator release, which promotes an allergic response.

Omalizumab (Xolair)

Omalizumab, a recombinant humanized monoclonal antibody against immunoglobulin E (IgE), has been successfully used in patients with physical urticaria, including symptomatic dermographism. Patients should undergo a full allergy evaluation prior to starting omalizumab, if needed, because it interferes with prick skin test and in vitro serum specific IgE assay results.