Medication Summary
Medical therapy varies somewhat depending on which type of allergic reaction is being treated. Some of the drugs and their categories are listed here, but refer to the articles on the specific allergic reaction for more detail.
Vasopressors
Class Summary
Epinephrine is the first medication that should be used to reverse effects of systemic vasodilation and increased vasopermeability observed with anaphylaxis. Although not the first choice for bronchoconstriction, epinephrine can also relieve some symptoms of bronchospasm and rhinitis. In the past, protocols called for subcutaneous or intravenous administration of epinephrine. However, studies have shown that intramuscular epinephrine leads to higher plasma levels than subcutaneous delivery. Intramuscular administration is now preferred over subcutaneous administration. [45, 46]
Predosed autoinjectable epinephrine is available in many forms, which include EpiPen, Auvi-Q, and other epinephrine auto-injectors. Three doses of each are available (0.3 mg for EpiPen, Auvi-Q, and Epinephrine auto-injector; 0.15 mg for EpiPen Jr., Auvi-Q, or Epinephrine auto-injector; 0.1 mg for Auvi-Q). EpiPen, Auvi-Q, and other epinephrine auto-injectors all come in two-packs (i.e., 2 auto-injectors). Auvi-Q comes with a trainer and is only available in the English and Spanish language.
Epinephrine (Adrenalin, EpiPen, Auvi-Q, Symjepi)
Should be administered immediately for anaphylaxis/anaphylactic shock. Multiple preparations allow for delivery SC, IM, IV, or ET. Doses can be repeated q5min prn to maintain blood pressure (and as heart rate allows).
Bronchodilators
Class Summary
Inhaled bronchodilators are beta-agonists that come in short- and long-acting forms.
Short-acting bronchodilators (i.e., albuterol, levalbuterol) are used to treat acute bronchospasm. Can also be used prophylactically before activity if needed. Levalbuterol is the R-enantiomer of albuterol and is available in nebulizer and metered dose inhaler (MDI) forms. Advantage of levalbuterol is that it is less likely to cause paradoxical bronchospasm than racemic albuterol.
Long-acting bronchodilators (e.g., salmeterol, formoterol) can be used twice daily in conjunction with inhaled glucocorticoids and to help maintain bronchodilation over 12 hours. Long acting beta-agonists are not recommended as monotherapy. [47] The FDA had issued a “black box warning” on medications containing long-acting beta-agonists due to concern for increased risk of asthma but this “black box warning” has been removed as treatment with an inhaled corticosteroid plus a long acting beta-agonist has been found to be safe and efficacious in the treatment of asthma. [48]
Formoterol have both short- and long-acting activity. Onset of action is approximately 15 min, but effects last up to 12 hours. Again, this medication should be combined with an inhaled corticosteroid and it now is being recommended for maintenance as well as rescue for asthma treatment.
Previously, MDIs were made using chlorofluorocarbons (CFCs) as the propellant. However, the use of CFCs has been phased out because of environmental concerns. For this reason, companies are now making MDIs with hydrofluoroalkane-134a (HFA), which is not damaging to the ozone layer. CFC inhalers are no longer available in the United States. The MDI formulations should be used with spacer or spacer and mask for administration.
Albuterol (ProAir HFA, Ventolin HFA, Proventil HFA)
Sympathomimetic that stimulates beta-2 receptors, leading to bronchodilation. Used for bronchospasm refractory to epinephrine with anaphylaxis. First-line choice for acute bronchospasm associated with asthma.
Salmeterol/fluticasone inhaled (Advair Diskus, Advair HFA, AirDuo RespiClick, Wixela Inhub)
Salmeterol: Selective LABA; stimulates intracellular adenyl cyclase resulting in increased cAMP levels causing bronchial smooth muscle relaxation; also inhibits release of mediators of immediate hypersensitivity from cells, especially from mast cells.
Fluticasone: Trifluorinated corticosteroid with potent anti-inflammatory activity; inhibits multiple cell types (e.g., mast cells, eosinophils, basophils, lymphocytes, macrophages, neutrophils) and mediator production or secretion (e.g., histamine, eicosanoids, leukotrienes, cytokines) involved in the asthmatic response.
Formoterol and budesonide (Symbicort)
Formoterol: Long-acting selective beta2-adrenergic agonist with rapid onset of action; acts locally as bronchodilator; stimulates intracellular adenyl cyclase, which results in increased cyclic adenosine monophosphate levels, causing relaxation of bronchial smooth muscle and inhibition of release of mast cell mediators.
Budesonide: Anti-inflammatory corticosteroid; has potent glucocorticoid activity and weak mineralocorticoid activity.
Formoterol and mometasone (Dulera)
Mometasone: Glucocorticoid; elicits local anti-inflammatory effects on respiratory tract with minimal systemic absorption.
Formoterol: Long-acting selective beta2-adrenergic agonist with rapid onset of action; acts locally as bronchodilator; stimulates intracellular adenyl cyclase, which results in increased cyclic adenosine monophosphate levels, causing relaxation of bronchial smooth muscle and inhibition of release of mast cell mediators.
Levalbuterol (Xopenex)
Used for treatment or prevention of bronchospasm. A selective beta2-agonist agent. Albuterol is a racemic mixture, while levalbuterol contains only the active R- enantiomer of albuterol. The S-enantiomer does not bind to beta2-receptors, but may be responsible for some adverse effects of racemic albuterol, including bronchial hyperreactivity and reduced pulmonary function during prolonged use.
Corticosteroids
Class Summary
Immunosuppressing agents, such as corticosteroids, can decrease inflammation. They are particularly efficacious in the treatment of skin eruptions and the underlying inflammation in asthma. Additionally, the role of corticosteroids in anaphylactic shock is limited, although believed to help prevent delayed type or biphasic of anaphylaxis.
Several different formulations are available. Depending on type of corticosteroid, oral, intravenous, and topical forms may be available. In more severe cases of anaphylaxis and asthma, intravenous forms of corticosteroids can be used initially. These can later be switched to oral forms as doses are tapered. Oral steroids are typically used to treat asthma exacerbations where prednisone, prednisolone and dexamethasone are common forms used. Dosing and duration vary greatly.
Inhaled corticosteroids are another form of corticosteroids and are key in controlling inflammation of bronchial airways and nasal mucosa in such cases in persistent asthma and allergic rhinitis. Similarly, topical corticosteroids are useful in treating atopic dermatitis.
Prednisone (Rayos)
Believed to ameliorate delayed effects of anaphylactic reactions and may limit biphasic anaphylaxis. Doses below are general guidelines for usage; dosing is highly individualized.
Dosing for asthma exacerbation is 2 mg/kg/day up to 60 mg daily for 5 days.
Methylprednisolone (Medrol, Solu-Medrol, Depo-Medrol)
Potent glucocorticoid with minimal-to-no mineralocorticoid activity.
Modulates carbohydrate, protein, and lipid metabolism and maintenance of fluid and electrolyte homeostasis.
Controls or prevents inflammation by controlling rate of protein synthesis, suppressing migration of polymorphonuclear leukocytes (PMNs) and fibroblasts, reversing capillary permeability, and stabilizing lysosomes at cellular level.
Dexamethasone (Decadron)
Believed to ameliorate delayed effects of anaphylactic reactions and may limit biphasic anaphylaxis.
Dosing for asthma exacerbation is 0.6 mg/kg/day up to 16 mg daily for 2 days.
Prednisolone (Orapred ODT, Millipred, Pediapred)
Glucocorticosteroid; elicits mild mineralocorticoid activity and moderate anti-inflammatory effects; controls or prevents inflammation by controlling rate of protein synthesis, suppressing migration of polymorphonuclear leukocytes (PMNs) and fibroblasts, reversing capillary permeability, and stabilizing lysosomes at cellular level.
Dosing for asthma exacerbation is 2 mg/kg/day up to 60 mg daily for 5 days.
Hydrocortisone (Cortef, Solu-Cortef)
Glucocorticoid; elicits mild mineralocorticoid activity and moderate anti-inflammatory effects; controls or prevents inflammation by controlling rate of protein synthesis, suppressing migration of polymorphonuclear leukocytes (PMNs) and fibroblasts, and reversing capillary permeability.
Histamine 1 receptor antagonists (antihistamines)
Class Summary
Type 1 histamine-receptor blockers act to block action of histamine on H1 receptor after its release from mast cells and basophils. Most effective when used prophylactically. Sedating first-generation and nonsedating second-generation formulations are available. Typically, sedating antihistamines have more adverse anticholinergic effects. Sedating antihistamines include diphenhydramine, hydroxyzine, cyproheptadine, chlorpheniramine, and brompheniramine. The use of sedating antihistamines are discouraged because the nonsedating antihistamines, such as cetirizine and fexofenadine, are highly efficacious with reduced central nervous system side effects. Other nonsedating antihistamines include loratadine (not as efficacious as cetirizine or fexofenadine), levocetirizine, and desloratadine. Intranasal antihistamines azelastine and olopatadine can directly help with nasal congestion.
Oral antihistamines are indicated for allergic rhinoconjunctivitis, urticaria and/or certain types of angioedema, and an adjuvant for anaphylaxis. Second generation oral antihistamines can be dosed up to 4 times the recommended dosage for the treatment of recalcitrant chronic urticaria.
Intranasal antihistamines are indicated for seasonal allergic rhinitis (olopatadine and azelastine), perennial allergic rhinitis (azelastine) and vasomotor rhinitis (azelastine).
Fexofenadine (Allegra)
Selectively inhibits histamine H1 receptor sites in blood vessels, GI tract, and respiratory tract, which in turn inhibits physiologic effects that histamine normally induces at H1 receptor sites. Once-daily dosing is convenient.
Cetirizine (Zyrtec, Quzyttir)
Selectively inhibits histamine H1 receptor sites in blood vessels, GI tract, and respiratory tract, which in turn inhibits physiologic effects that histamine normally induces at H1 receptor sites. Once-daily dosing is convenient. Bedtime dosing may be useful as sedation occurs in 10-15% of persons using cetirizine.
Levocetirizine (Xyzal)
Selectively inhibits histamine H1 receptor sites in blood vessels, GI tract, and respiratory tract, which in turn inhibits physiologic effects that histamine normally induces at H1 receptor sites.
Desloratadine (Clarinex)
Long-acting antihistamine (H1 receptor antagonist). Selectively inhibits receptor sites in blood vessels, GI tract, and respiratory tract, which in turn inhibits physiologic effects that histamine normally induces at H1 receptor sites.
Loratadine (Claritin, Alavert)
Long-acting antihistamine (H1 receptor antagonist). Selectively inhibits receptor sites in blood vessels, GI tract, and respiratory tract, which in turn inhibits physiologic effects that histamine normally induces at H1 receptor sites.
Azelastine (Astepro)
Effective antihistamine delivered via the intranasal route. Mechanism is similar to oral antihistamines. Systemic absorption occurs and may cause sedation, headache, and nasal burning. Forms complex with histamine for H1-receptor sites in blood vessels, GI tract, and respiratory tract.
Use prn or qd. Use alone or in combination with other medications. Unlike oral antihistamines, has some effect on nasal congestion. Helpful for vasomotor rhinitis. Some patients experience a bitter taste. Systemic absorption may occur, resulting in sedation (reported in approximately 11% of patients).
Olopatadine intranasal (Patanase)
Effective antihistamine delivered via the intranasal route. Mechanism is similar to oral antihistamines. Systemic absorption occurs and may cause sedation, headache, and nasal burning. Forms complex with histamine for H1-receptor sites in blood vessels, GI tract, and respiratory tract.
Administer once daily or as necessary. Use alone or in combination with other medications. Unlike oral antihistamines, has some effect on nasal congestion. Helpful for vasomotor rhinitis. Some patients experience a bitter taste. Systemic absorption may occur, resulting in sedation (reported in approximately 11% of patients).
Histamine 2 receptor antagonists (H2 antagonists)
Class Summary
Examples include ranitidine, famotidine, and cimetidine. Even though cimetidine has been studied more extensively than ranitidine and famotidine for allergic problems; ranitidine and famotidine should be used given the significant drug interactions of cimetidine with other medications.
Ranitidine (Zantac)
On 4/1/2020, the FDA requested all manufacturers withdraw all prescription and over-the-counter ranitidine drugs from the market immediately. This request was due to the presence of a contaminant in ranitidine called NMDA (N-Nitrosodimethylamine).
Used in the treatment of chronic idiopathic urticaria: If no response to H1-receptor antagonists alone, coadministration with an H2-receptor antagonist can help relieve symptoms
Also used as an adjuvant in anaphylaxis therapy.
Famotidine (Pepcid, Heartburn Relief Max)
H2 receptor antagonist. used in the treatment of chronic idiopathic urticaria: If no response to H1-receptor antagonists alone, coadministration with an H2-receptor antagonist can help relieve symptoms.
Also used as an adjuvant in anaphylaxis therapy.
Leukotriene inhibitors
Class Summary
Leukotrienes are synthesized by degranulated mast cells and basophils and contribute to symptoms of asthma (smooth muscle contraction, airway edema) and allergic rhinitis.
Montelukast (Singulair)
A selective and competitive inhibitor of the cysteinyl leukotriene receptor. Cysteinyl leukotrienes and leukotriene receptor binding has been associated with inflammatory process that contributes to the symptoms and signs of asthma.
FDA approved for asthma, allergic rhinitis (perennial and seasonal), and exercise-induced bronchoconstriction (administered 2 hr before activity). Used off-label for chronic urticaria.
The prescribing information includes a black box warning for neuropsychiatric side effects including suicidal ideations.
Zafirlukast (Accolate)
Inhibits bronchoconstriction as competitive receptor antagonist of leukotrienes D4 & E4; receptor occupation and cysteinyl leukotriene production have been associated with the pathophysiology of asthma.
Immunomodulators
Class Summary
Topical tacrolimus and pimecolimus are calcineurin inhibitors that can be used to treat atopic dermatitis that does not respond well to topical corticosteroids. Systemic calcineurin inhibitors have been shown to cause immunosuppression and certain malignancies such as lymphoma. In January 2006, the FDA issued a black box warning for topical tacrolimus and pimecrolimus for these reasons. [43] To date, studies have not shown significant systemic absorption, systemic immunosuppression, or increased risk of malignancy with the topical formulations.
Tacrolimus ointment (Protopic)
Reduces itching and inflammation by suppressing release of cytokines from T cells. Suppresses cellular immunity (inhibits T-lymphocyte activation), by binding to an intracellular protein, FKBP-12 and complexes with calcineurin-dependent proteins to inhibit calcineurin phosphatase activity. FDA approved for the treatment of moderate-to-severe atopic dermatitis
Pimecrolimus (Elidel)
Calcineurin inhibitor; inhibits T-cell activation; also shown to inhibit release of inflammatory mediators from mast cells. Inhibits T-cell activation by binding with high affinity to macrophilin-12 (FKBP-12) and inhibiting the calcium-dependent phosphatase, calcineurin. As a consequence, it inhibits T cell activation by blocking the transcription of inflammatory cytokines.
Monoclonal Antibodies
Class Summary
Monoclonal antibodies can greatly improve severity of allergic reactions and prevent anaphylaxis.
Omalizumab (Xolair)
Binds free IgE thereby preventing IgE from binding to the high-affinity IgE receptor on mast cells and basophils. Also decreases free total IgE to down-regulate expression of the high-affinity IgE receptor. FDA approved for patients with moderate-to-severe persistent asthma with sensitization to a perennial aeroallergen and uncontrolled on inhaled corticosteroid therapy.
Also shown to decrease allergic response to peanuts in patients with severe peanut allergy, which could be helpful in preventing anaphylaxis from accidental peanut exposure.
Patients should undergo a full allergy evaluation prior to starting therapy, if needed, because it interferes with prick skin test and in vitro serum specific IgE assay results.
Mepolizumab (Nucala)
Monoclonal antibody that binds and inhibits the bioactivity of IL-5, the cytokine responsible for growth and differentiation, activation, recruitment, and survival of eosinophils. FDA approved as add-on maintenance therapy for patients with severe eosinophilic asthma.
Dupilumab (Dupixent)
Monoclonal antibody that binds to IL-4R alpha subunit (shared by IL-4 and IL-13) to inhibit IL-4 and IL-13 cytokine-induced inflammatory responses. FDA approved as add-on maintenance therapy in patients with moderate-to-severe asthma in patients with an eosinophilic phenotype or with oral corticosteroid-dependent asthma.
Also approved for moderate-to-severe atopic dermatitis in patients whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. It may be used with or without topical corticosteroids
Approved also as add-on maintenance treatment in patients with inadequately controlled chronic rhinosinusitis with nasal polyposis.
Benralizumab (Fasenra)
Monoclonal antibody that directly binds to the alpha-subunit of the human interleukin-5 receptor to reduce the production and survival of basophils and eosinophils through antibody-dependent cell-mediated cytotoxicity.
FDA approved as add-on maintenance therapy of severe asthma in patients with an eosinophilic phenotype.
Reslizumab (Cinqair)
Monoclonal antibody that binds free interleukin-5 (IL-5) to reduce the production and survival of eosinophils, a cell type involved in inflammatory responses.
FDA-approved as add-on maintenance therapy for severe asthma with an eosinophilic phenotype.
5-Lipoxygenase Inhibitors
Class Summary
These agents inhibit leukotriene formation.
Zileuton (Zyflo, Zyflo CR)
Inhibitor of 5-lipoxygenase, which inhibits formation of leukotrienes (LTB4, LTC4, LTD4, & LTE4). Inhibition of leukotriene formation reduces eosinophil and neutrophil migration, neutrophil and monocyte aggregation, capillary permeability, and smooth muscle contraction.
FDA-approved as add-on maintenance therapy in asthma patients.
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Immediate hypersensitivity reactions. Sensitization phase of an immunoglobulin E–mediated allergic reaction.
Tables
Age |
Step 1 |
Step 2 |
Step 3 |
Step 4 |
Step 5 |
Step 6 |
0-4 years |
SABA PRN |
Low-dose ICS |
Medium-dose ICS |
Medium-dose ICS plus LABA or montelukast |
High-dose ICS plus LABA or montelukast |
High-dose ICS plus LABA or montelukast and oral corticosteroids |
5-11 years |
SABA PRN |
Low-dose ICS |
Low-dose ICS plus LABA or LTRA or theophylline |
Medium-dose ICS plus LABA |
High-dose ICS plus LABA |
High-dose ICS plus LABA plus oral corticosteroids |
12 years or older |
SABA PRN |
Low-dose ICS |
Low-dose ICS plus LABA or medium-dose ICS |
Medium-dose ICS plus LABA |
High-dose ICS plus LABA |
High-dose ICS plus LABA plus oral corticosteroids |
