eMedicine Specialties > Allergy and Immunology > Allergy Pathogenesis
Hypersensitivity Reactions, Immediate: Treatment & Medication
Updated: Jun 16, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Treatment may vary depending on the type of allergic reaction. Some general observations are made below, but refer to articles on the specific topics for more details about treatment (eg, Anaphylaxis; Rhinitis, Allergic; Allergic and Environmental Asthma; Urticaria).
- Anaphylaxis
- Assessment of the reaction is described as follows:
- Withdraw the offending agent if applicable (eg, stop drug infusion).
- Check the airway and secure if needed. Patients with respiratory compromise may need to be intubated. If laryngeal edema causes oral intubation to be difficult, a tracheostomy must be performed.
- Assess the level of consciousness and vital signs.
- Treatment is as follows:
- Administer epinephrine immediately (see Medication).
- Start intravenous fluids; these should be administered rapidly and as blood pressure and overall fluid status warrant.
- Consider other vasopressors (eg, dopamine) if hypotension does not respond to the above measures. Norepinephrine may be used if dopamine is not effective. Importantly, isoproterenol should not be used because it is a peripheral vasodilator. Patients with beta-adrenergic blockade may be particularly difficult to treat. They have both chronotropic and inotropic cardiac suppression and may not respond to the above treatments. Glucagon has positive inotropic and chronotropic effects and is the drug of choice in these cases. Atropine can also be used but will only be effective in treating bradycardia.
- H1- and H2-receptor blockers can be helpful in alleviating hypotension, pruritus, urticaria, rhinorrhea, and other symptoms. Cimetidine, when combined with any of several H1 antihistamines, has been demonstrated to block histamine-induced hypotension. Other H2 blockers have not been studied in this context.
- Use albuterol nebulizers if needed.
- Administer a corticosteroid, which is believed to help prevent or control the late-phase reaction.
- Transfer the patient to the hospital for further observation and care.
- Late phase reactions can occur 4-6 hours after the initial reaction and can be as severe as or worse than the original reaction. In some cases, late phase reactions can occur up to 36 hours later. Education of the patient and observation is, therefore, important.
- Prevention is as follows:
- Avoid the triggering allergen as much as possible.
- Patients should be given a prescription for at least 2 autoinjectable epinephrine doses (eg, 2 EpiPens or 1 Twinject) and instructed in their proper use. Importantly, patients must carry them at all times.
- Patients can also be instructed to carry both an H1 and an H2 antihistamine with them.
- Patients must wear a Medic Alert type of bracelet to alert emergency responders to the possibility of anaphylaxis.
- Patients should be taught what measures to take in case of a future anaphylactic reaction, ie, immediately administer epinephrine and take the antihistamine, call emergency services (eg, 911), or go to the nearest emergency department (even if feeling better after the epinephrine).
- Assessment of the reaction is described as follows:
- Allergic rhinitis
- Avoid the offending allergen, if possible.
- H1-receptor blockers are helpful for controlling itchiness, rhinorrhea, and lacrimation but most have little effect on nasal congestion.
- Administer an intranasal glucocorticosteroid to control nasal symptoms, including nasal congestion.
- These need to be used regularly to be effective, and patients may need to use them for a week or more before maximum effect is seen.
- Other topical nasal agents include azelastine (an H1-receptor blocker) and cromolyn (a mast cell stabilizer).
- Nasal azelastine has the advantage of treating both allergic and nonallergic vasomotor rhinitis and also treating congestion. Topical nasal decongestants can provide immediate relief of nasal congestion and can be used temporarily. Patients should be cautioned not to use them for more than a few days, however, as they can cause rebound congestion (aka, rhinitis medicamentosa).
- Topical decongestants, mast cell stabilizers, or antihistamines can be used for ocular symptoms; artificial tears might be helpful in mild cases, and this product can be refrigerated for an extra cooling effect. Cold compresses can also be used.
- Again, use of topical decongestants should be limited to a few days, as longer use can result in rebound vasodilation.
- Antigen-injection immunotherapy is very effective in treating inhalant allergies and can be considered in patients whose symptoms do not respond well to medications or in patients who cannot avoid the allergen in question (eg, cat owner allergic to cats). The mechanism of action of immunotherapy is not yet fully elucidated. Immunotherapy causes antigen-specific immunoglobulin G to be formed and lowers antigen-specific IgE over time. Some authorities theorize that immunotherapy results in an increase in the TH1-to-TH2 cell ratio. Regulatory T cells may also play an important role.
- Asthma
- Avoid the offending allergen, if possible.
- A key factor in controlling allergic asthma is controlling allergic rhinitis symptoms.
- Therapy depends on the severity of disease.
- Patients should have an albuterol metered-dose inhaler (MDI) (or nebulizers for young children) to use as needed.
- Long-acting beta-agonists and inhaled glucocorticosteroids should be added if appropriate. In general, these medications are used if symptoms occur more than twice weekly or if spirometry findings are abnormal in the absence of symptoms.
- Leukotriene inhibitors can also be added.
- Systemic corticosteroid bursts may need to be used for exacerbations of severe cases.
- Patients with allergic asthma may respond well to specific allergen immunotherapy.
- In patients refractory to the usual medications and who have antigen-specific IgE to environmental aeroallergens (positive skin test or RAST result), therapy with omalizumab (Xolair), a humanized monoclonal antibody that prevents binding of IgE to high-affinity IgE receptors on mast cells and basophils, may result in improvement.6,7
- Urticaria/angioedema
- Avoid the offending allergen if known.
- An H1-receptor blocker should be added. If symptoms are not controlled with this alone, an H2-receptor blocker, leukotriene inhibitor, or oral glucocorticosteroid can be added. Most patients require higher than the usual doses; employing twice daily H1 and H2 antihistamines for successful control is not uncommon.
- Atopic dermatitis
- Avoid the offending allergen if possible, and properly hydrate and care for the skin.
- Topical glucocorticosteroids and topical immunomodulators (eg, tacrolimus) can be used.
Consultations
- Consultation with a pulmonologist and/or critical care medicine specialist may be necessary for protracted anaphylactic shock or severe asthma exacerbations.
- Consult an allergist or immunologist for the following conditions:
- Allergic rhinitis not easily controlled with medications
- Nonallergic, vasomotor rhinitis
- Asthma: Of patients with asthma, at least 50% of adults have allergies as factors causing or contributing to their asthmatic inflammation. More than 90% of children with asthma are allergic.
- Chronic urticaria or angioedema (>6 wk)
- History of anaphylaxis from insect bite or sting
- History of anaphylaxis with unknown cause
- Possible drug desensitization (if known allergy to drug for which no good alternatives are available)
- Atopic dermatitis
- Sinusitis before proceeding to surgery
- Persistent or bothersome conjunctivitis
- Eosinophilic esophagitis or gastritis
- Suspicion of congenital or acquired immune abnormalities
- Diagnosis and treatment of acquired immunoglobulin deficiencies
Diet
- Patients should avoid foods to which they are allergic.
- Certain food proteins can cross-react with other proteins (eg, latex with avocado, banana, kiwi, chestnut, pineapple, passion fruit, apricot, and grape; ragweed with watermelon, cantaloupe, and honeydew melon).
- Patients must be counseled about these possible cross-reactivities and should avoid the food if it causes symptoms.
Medication
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
First-line choice 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.
Predosed autoinjectable epinephrine is now available in 2 forms: EpiPen and Twinject. Two doses of each are available (0.3 mg for EpiPen or Twinject 0.3 and 0.15 mg for EpiPen Jr. or Twinject 0.15). One Twinject pen actually has 2 doses of epinephrine available, which can be administered separately, and also has directions printed on a wraparound label on the pen that can be referred to at the time of use. EpiPen Duopacks contain 2 pens and, therefore, 2 doses. Twinject Two-packs contain 2 pens for a total of 4 doses.
Epinephrine (Adrenalin, Bronitin, EpiPen, Twinject)
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).
Adult
IM: 0.25-0.50 mL of a 1:1000 solution for moderate symptoms; repeat prn; anterior lateral thigh is preferred site for severe anaphylaxis;
Self-injection (IM): Preloaded autoinjector (EpiPen or Twinject)
IV: 0.5-1 mL of 1:10000 solution for severe symptoms; repeat prn; continuous infusion at 0.1-1 mcg/kg/min may be required for anaphylactic shock
ET: 1 mL of 1:10,000 solution in 10 mL NS; repeat prn
Pediatric
IM: 0.01 mg/kg of 1:1000 solution; repeat q5min prn; not to exceed 0.3-0.5 mg; anterior lateral thigh is preferred site for severe anaphylaxis
Self-injection (IM): Preloaded autoinjector (EpiPen Jr or Twinject 0.15)
IV: 0.01 mg/kg of 1:10000 solution; repeat prn
ET: 0.01 mg/kg of a 1:1000 solution in 5 mL NS; repeat prn
Beta-blockers decrease effectiveness; may decrease effectiveness of diabetic medications; MAOIs, methyldopa, methylphenidate, TCAs, thyroxine, and sodium bicarbonate can potentiate effects of all sympathomimetics
Documented hypersensitivity; relative (not absolute) contraindications include severe CAD, hypertension, narrow-angle glaucoma, and presence of life-threatening arrhythmias
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Consult PDR for all possible adverse effects; caution should be used in patients with known severe CAD, advanced age, prostatic hypertrophy, hypertension, cardiovascular disease, diabetes mellitus, hyperthyroidism, and cerebrovascular insufficiency; rapid IV infusions may cause death from cerebrovascular hemorrhage or cardiac arrhythmias
Bronchodilators
Inhaled bronchodilators are beta-agonists that come in short- and long-acting forms. Short-acting bronchodilators are used to treat acute bronchospasm. Can also be used prophylactically. For example, a patient with a history of asthma exacerbation in the presence of cats can use a short-acting bronchodilator before exposure to cats. Long-acting bronchodilators (eg, salmeterol) can be used twice daily and to help maintain bronchodilation over 12 h.
Pirbuterol is now available and is both a short- and long-acting form. Onset of action is approximately 15 min, but effects last up to 12 h. Of note, when long-acting beta agonists are used alone, concern exists of increased mortality. These medications should be combined with an inhaled corticosteroid and should be reserved for patients with more frequent or moderate to severe symptoms or lung function. Finally, 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.
Previously, MDIs were made using chlorofluorocarbons (CFCs) as the propellant. However, the use of CFCs is being 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. Once all previously manufactured CFC MDIs have been distributed, only HFA forms will be available. Importantly, note that, while a spacer should be used with traditional MDIs, spacers may not be necessary for certain HFA inhalers.
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.
Adult
1.25-5 mg in 2-5 mL of sterile 0.9% NS solution via nebulization
2-4 puffs via MDI q4-6h prn; not to exceed 12 puffs/d
Pediatric
PO
<2 years: Not established
2-5 years: 0.1-0.2 mg/kg/dose divided tid; not to exceed 12 mg/d
5-12 years: 2 mg/dose divided tid or qid; not to exceed 24 mg/d
>12 years: Administer as in adults
MDI
<12 years: 1-2 puffs qid with tube spacer
>12 years: Administer as in adults
Nebulizer
<5 years: 1.25-2.5 mg in 1-2.5 mL q4-6h; to make solution, dilute 0.25-0.5 mL (1.25-2.5 mg) of 0.5% inhalation solution in 1-2.5 mL of NS
>5 years: Administer as in adults
Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilation; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents
Documented hypersensitivity; relative contraindications include severe CAD, hypertension, narrow-angle glaucoma, and presence of life-threatening arrhythmias
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Anecdotally, has been used during pregnancy for approximately 40 y and detrimental effects have not been reported; consult PDR for all possible adverse effects; caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders
Fluticasone and Salmeterol (Advair)
Fluticasone inhibits bronchoconstriction mechanisms, produces direct smooth muscle relaxation, may decrease number and activity of inflammatory cells, in turn decreasing airway hyper-responsiveness. Also has vasoconstrictive activity.
Salmeterol relaxes the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, and can relieve bronchospasms. Effect may also facilitate expectoration.
Adverse effects are more likely to occur when administered at high or more frequent doses than recommended.
Adult
1 inhalation bid; not to exceed 500 mcg fluticasone/50 mcg salmeterol
Pediatric
<4 years: Not established
4 to 12 years: 1 inhalation bid; not to exceed 100 mcg fluticasone/50 mcg salmeterol
>12 years: Administer as in adults
Coadministration of fluticasone with CYP450 3A4 isoenzyme inhibitors (eg, amprenavir, atazanavir, darunavir, delavirdine, fosamprenavir, indinavir, ketoconazole, nelfinavir, ritonavir, tipranavir) decreases fluticasone elimination and increases plasma fluticasone levels, case reports of iatrogenic Cushingoid symptoms have been reported
Concomitant use of salmeterol with beta-blockers may decrease bronchodilating and vasodilating effects of beta agonists; concurrent administration of salmeterol with methyldopa may increase pressor response; coadministration of salmeterol with oxytocic drugs may result in severe hypotension; ECG changes and hypokalemia resulting from diuretics may worsen when coadministered with salmeterol
Documented hypersensitivity; bronchospasm, status asthmaticus, other types of acute episodes of asthma, angina, tachycardia, and cardiac arrhythmias associated with tachycardia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Coughing, upper respiratory tract infection, and bronchitis may occur with fluticasone; not indicated to treat acute asthmatic symptoms; black box FDA warning describes that chronic use of salmeterol may result in increased asthma morbidity and mortality, use only as additional therapy for patients not adequately controlled on other asthma-controller medications (eg, low- to medium-dose inhaled corticosteroids) or patients whose disease severity clearly warrants initiation of treatment with 2 maintenance therapies, including salmeterol
Corticosteroids
Immunosuppressing agents and, thus, can decrease inflammation. Have particular efficacy in skin eruptions and bronchospasm. Role in anaphylactic shock is limited, although believed to help prevent delayed type of anaphylaxis.
Several different formulations are available; only one is listed. Others include methylprednisolone, dexamethasone, prednisolone (often used in children), and hydrocortisone. 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.
Inhaled corticosteroids are another form of corticosteroids and are key in controlling inflammation of bronchial airways and nasal mucosa. Similarly, topical corticosteroids are useful in treating atopic dermatitis.
Prednisone (Deltasone, Orasone, Meticorten)
Believed to ameliorate delayed effects of anaphylactic reactions and may limit biphasic anaphylaxis. Doses below are general guidelines for usage; dosing is highly individualized.
Adult
5-60 mg/d PO qd or divided bid/qid; length and dose of therapy varies with severity of the condition being treated; doses must be tapered for patients on steroids for more than 14 days
Pediatric
1-2 mg/kg PO qd or divided bid/qid; length and dose of therapy varies with severity of the condition being treated; doses must be tapered for patients on steroids for more than 14 days
Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective-tissue infections, and fungal or tubercular infections; GI disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation after long-term use (4-6 wk) can result in adrenal insufficiency/crisis; although relatively safe for short-term usage, long-term use can result in undesirable adverse effects, including osteoporosis, cataracts, and weight gain; patients who are on long-term steroids should be placed on a bisphosphonate and calcium/vitamin D supplementation for osteoporosis prevention; consult PDR for all possible adverse effects; may worsen diabetes mellitus, congestive heart failure, infections, peptic ulcer disease, volume status, myasthenia gravis, and psychoses; hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications
Histamine1-receptor antagonists (antihistamines)
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 and nonsedating second-generation H1 antihistamines are available. Typically, sedating antihistamines have more adverse anticholinergic effects. Sedating antihistamines include diphenhydramine, hydroxyzine, cyproheptadine, chlorpheniramine, and brompheniramine. Nonsedating antihistamines include cetirizine (cause drowsiness in 15% people), fexofenadine, loratadine, and desloratadine. Desloratadine and fexofenadine may also help decrease nasal congestion. Liquid forms are more rapidly absorbed orally and should be used for immediate treatment of an allergic reaction if intravenous access is not available.
Diphenhydramine (Benadryl, Dihydrex injection, Belix)
Most widely available antihistamine (available OTC). Sedating antihistamines may be necessary to control more severe allergic reactions because they are very potent. Dosing interval of diphenhydramine is 4-6 h. Nonsedating antihistamines are all now available in a 24-h formulation but can only be administered PO.
Adult
12.5-50 mg PO/IV/IM q4-6h; not to exceed 400 mg qd
Pediatric
<6 years: 5 mg/kg/d PO/IV; not to exceed 300 mg qd
6-12 years: 12.5-25 mg PO q6-8h; not to exceed 300 mg qd
>12 years: Administer as in adults
Potentiates effect of CNS depressants; because of alcohol content, do not administer syrup dosage form to patients taking medications that can cause disulfiramlike reactions
Documented hypersensitivity; MAOIs
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Warn patients to not drive or operate heavy machinery; administer with caution to elderly patients, patients with a seizure history, and children; can have additive adverse anticholinergic effects and can cause somnolence; may exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, or urinary tract obstruction; xerostomia may occur; consult PDR for all possible adverse effects
Azelastine (Astelin)
An 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).
Adult
2 puffs/nostril (137 mcg/puff) bid
Pediatric
<5 years: Not established
5-12 years: 1 puff/nostril (137 mcg/puff) bid
>12 years: Administer as in adults
Increases CNS toxicity of CNS depressant medications
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hepatic or renal dysfunction; doses higher than 10 mg/d may cause drowsiness
Cetirizine (Zyrtec)
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 if sedation is a problem.
Adult
5-10 mg PO qd
Pediatric
Oral syrup:
<6 months: Not established
6-12 months: 2.5 mg PO qd
12-24 months: 2.5 mg PO qd-bid
2-5 years: 2.5-5 mg PO qd
>5 years: 5-10 mg PO qd
Chewable tablet:
<2 years: Not established
2-5 years: For children taking cetirizine syrup 5 mg PO qd, may take chewable tablet at same dose (do not substitute 5 mg chewable tablets for children taking oral syrup 2.5 mg/d)
>5 years and adults: 5-10 mg PO qd
Increases CNS toxicity of depressants
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in hepatic or renal dysfunction; doses higher than 10 mg/d may cause drowsiness
Histamine2- antagonists
Can be administered in addition to H1-receptor blockers for additional control of urticaria and angioedema. Examples include ranitidine, famotidine, and cimetidine. Cimetidine has been studied more extensively for this indication than other members of this class.
Ranitidine (Zantac)
Multiple formulations are available. Cimetidine was first to be widely used but tends to have more drug interactions than other H2-receptor blockers. If no response to H1-receptor antagonist alone, coadministration with an H2-receptor antagonist can help relieve symptoms of itching and flushing in anaphylaxis, pruritus, and urticaria. Cimetidine plus an H1 blocker blocks cardiovascular effects of histamine.
Adult
150 mg PO bid; not to exceed 600 mg/d; alternatively, 50 mg/dose IV/IM q6-8h
Pediatric
<12 years: Not established
>12 years: 1.25-1.5 mg/kg/dose PO q12h; not to exceed 300 mg/d; alternatively, 0.75-1.5 mg/kg/dose IV/IM q6-8h; not to exceed 400 mg/d
May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin
Documented hypersensitivity
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment; consult PDR for all possible adverse effects
Leukotriene inhibitors
Leukotrienes are synthesized by degranulated mast cells and basophils and likely contribute significantly to symptoms of allergic reactions. Three leukotriene inhibitors are now available in the United States. Montelukast and zafirlukast act as leukotriene-receptor blockers, whereas zileuton acts to inhibit production of leukotrienes. Disadvantages of the latter medication are its qid dosing and the need to monitor liver enzymes.
Montelukast (Singulair)
Leukotriene inhibitors can be a helpful addition to asthma and allergic rhinitis not well controlled with H1-receptor blockers and inhaled corticosteroids.
Adult
10 mg PO qd
Pediatric
<2 years: Not established
2-5 years: 4 mg PO qpm
6-14 years: 5 mg PO qpm
>14 years: Administer as in adults
Phenobarbital and rifampin reduce effects
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Not indicated to reverse acute asthma attacks; not for use as monotherapy in management of exercise-induced bronchospasm; consult PDR for all possible adverse effects
Neuropsychiatric events have been reported, and following further FDA evaluation, the prescribing information has been updated to include case reports during postmarketing surveillance that include agitation, aggression, anxiousness, dream abnormalities, hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking and behavior (including suicide), and tremor
Immunomodulators
Tacrolimus is a calcineurin inhibitor initially used in oral form as an immunosuppressant for transplantation patients. It has since been developed in topical form (Protopic) and can be used to treat atopic dermatitis that does not respond well to topical corticosteroids. A similar topical agent, pimecrolimus (Elidel), became available in the past few years and is indicated for mild atopic dermatitis. 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.8 To date, studies have not shown significant systemic absorption, systemic immunosuppression, or increased risk of malignancy with the topical formulations. Trials are currently underway to assess possible benefit of inhaled tacrolimus for asthma.
Tacrolimus (Protopic)
Reduces itching and inflammation by suppressing release of cytokines from T cells. Can be used in patients as young as 2 y. More expensive than topical corticosteroids.
Adult
Apply 0.03% ointment or 0.1% ointment to affected areas bid
Pediatric
<2 years: Not established
>2 years: Administer as in adults
None reported
Documented hypersensitivity to tacrolimus or components of ointment
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
May cause burning sensation during first few days of application; skin can become photosensitive, and patients should be cautioned about exposure to direct or artificial sunlight and to use sunscreen; safety and efficacy in infected atopic dermatitis is not known; application under occlusion, which may promote systemic exposure, has not been evaluated (do not use with occlusive dressings); absorption following topical applications is minimal (relative to systemic administration), but tacrolimus is excreted in human milk, and thus, a decision should be made whether to discontinue nursing or to discontinue drug, taking into account importance of drug to mother (potential for serious adverse reactions in nursing infants should also be a concern); consult PDR for listing of all adverse effects
Monoclonal antibodies
Omalizumab (Xolair) is a monoclonal anti-IgE antibody indicated for refractory asthma. Has been shown to greatly improve severity of asthma in patients and can be used to help patients dependent on oral steroids to be weaned from steroids. Omalizumab has also been shown to decrease allergic response to peanuts in patients with severe peanut allergy. This could be helpful in preventing anaphylaxis from accidental peanut exposure in patients who normally would not tolerate even the slightest exposure to peanut allergen, but it only has FDA approval for asthma at this time. Patients should undergo a full allergy evaluation prior to starting omalizumab, if needed, because it interferes with prick skin test and RAST results.
Omalizumab (Xolair)
Binds to IgE and thereby prevents IgE from binding to mast cells and basophils.
Adult
Dependent on serum IgE level and body weight
Serum IgE 30-100
30-90 kg: 150 mg SC monthly
90-150 kg: 300 mg SC monthly
Serum IgE levels 101-200
30-90 kg: 300 mg SC monthly
90-150 kg: 225 mg twice monthly
Serum IgE 201-300
30-60 kg: 300 mg monthly
61-90 kg: 225 mg twice monthly
91-150 kg: 300 mg q2wk
Serum IgE levels 301-400
30-70 kg: 225 mg twice monthly
71-90 kg: 300 mg q2wk
Serum IgE 401-500
30-70 kg: 300 mg q2wk
70-90 kg: 375 mg twice monthly
Serum IgE 501-600
30-60 kg: 300 mg q2wk
61-70 kg: 375 mg q2wk
Serum IgE 601-700
30-60 kg: 375 mg q2wk
Manufacturer did not seek approval for dosing with IgE >700 or for IgE 601-700 for people weighing >60 kg because high resultant doses would be cost prohibitive
Pediatric
>12 years: Administer as in adults
No formal drug interaction studies have been performed
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Not indicated to reverse acute asthma attacks; systemic or inhaled corticosteroids should not be abruptly discontinued with initiation of omalizumab; serum IgE levels increase after initiation of therapy because of omalizumab-IgE complex formation and may remain high up to 1 y after discontinuation; therefore, serum IgE levels should not be routinely checked; patients may have false-negative skin prick test and RAST results
More on Hypersensitivity Reactions, Immediate |
| Overview: Hypersensitivity Reactions, Immediate |
| Differential Diagnoses & Workup: Hypersensitivity Reactions, Immediate |
 Treatment & Medication: Hypersensitivity Reactions, Immediate |
| Follow-up: Hypersensitivity Reactions, Immediate |
| Multimedia: Hypersensitivity Reactions, Immediate |
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Further Reading
Keywords
type I hypersensitivity reactions, allergic reactions, IgE-mediated reactions, immunoglobulin E-mediated reactions, atopy, immunopathology, immediate hypersensitivity reactions, cytotoxic hypersensitivity reactions, delayed hypersensitivity reactions, anaphylaxis, allergic asthma, urticaria, angioedema, allergic rhinitis, drug reaction, atopic dermatitis, inactivation antibody reactions, activation antibody reactions, cytotoxic antibody reactions, cytolytic antibody reactions, immune-complex reactions, T-cell cytotoxic reactions, granulomatous reactions
