House Dust Mite, Dermatophagoides Pteronyssinus

Standardized mite extract is indicated for use in the diagnosis of patients with a history of allergy to mites or house dust and for the treatment of patients with a history of mite allergy who have established sensitivity to mites by diagnostic skin testing. The use of mite extract for the above purposes should be made only by physicians with special familiarity and knowledge of allergy as described in a standard allergy textbook (10).

Injections of mite extract should not be administered in the presence of diseases characterized by a bleeding diathesis. Immunotherapy should not be started in patients until a specific diagnosis of Type I allergy to mite is made by a physician based on skin testing with this product. Other contraindications include: EXTREME SENSITIVITY TO MITE: Determined from previous anaphylaxis following skin testing, immunotherapy, or natural exposure. AUTOIMMUNE DISEASE: Individuals with autoimmune disease maybe at risk, due to the possibility of routine immunizations exacerbating symptoms of the underlying disease. MYOCARDIAL INFARCTION: Patients who have experienced a recent myocardial infarction may not be able to tolerate immunotherapy. The benefit-to-risk ratio must be carefully evaluated. CHILDREN WITH NEPHROTIC SYNDROME: Children with nephrotic syndrome require careful consideration and probably should not receive immunotherapy due to a variety of seemingly unrelated events that may cause an exacerbation of nephrotic disease.

Concentrated extract must be diluted with sterile diluent prior to first use on a patient for treatment or intradermal testing. All concentrates of allergenic extract are manufactured to assure high potency and therefore have the ability to cause serious local and systemic reactions, including death in sensitive patients (11). Patients should be informed of this risk and precautions should be discussed prior to initiating immunotherapy (see PRECAUTIONS below). Allergenic extract should be temporarily withheld from patients or the dose adjusted downward if any of the following conditions exist: 1) severe symptoms of rhinitis and/or asthma; 2) infection or flu accompanied by fever; 3) exposure to excessive amounts of clinically relevant allergen prior to a scheduled injection. The dosage must be reduced when starting a patient on fresh standardized mite extract or when transferring a patient from non-standardized or modified extract to standardized extract, even though the labeled strength of the old and new vials may be the same. This is necessary due to a loss of extract potency during storage in the physician's office. The mite allergen content of old and new extract may be compared and adjusted by dosage reduction and/or dilution before the new extract is administered. The amount of new extract given should not exceed 25% of the last dose given from the old vial, assuming both extracts contain comparable amounts of mite allergen. Any evidence of a local or generalized reaction requires a reduction in dosage during the initial stages of immunotherapy, as well as during maintenance therapy. Beta-blocking drugs may make patients refractory to the usual dose of epinephrine, in the event epinephrine is required to treat an adverse allergic reaction.

GENERAL: This product should not be injected intravenously. The risk of severe allergic reactions can be minimized by taking a careful history and by the use of scratch or prick-puncture testing prior to intradermal testing. If the scratch or prick-puncture test is negative, an intradermal test with a one hundred-fold dilution of the concentration used for scratch or prick tests usually is safe. If there is a history of unusual sensitivity or if the scratch or prick-puncture test is not performed first, a more dilute solution such as 1:10,000 v/v of the concentrate should be used initially for intradermal testing. Systemic allergic reactions may occur as a result of immunotherapy. The risk can be minimized by adherence to a careful injection schedule, which starts with a low concentration of extract and is increased slowly. The physician must be prepared to treat anaphylaxis should it occur and have the necessary drugs and equipment on hand to do so. Extracts should not be administered by the patient or other individuals who are not prepared to treat anaphylaxis should it occur. A separate sterile tuberculin syringe graduated in 0.01 mL should be used for each injection. Antihistamines and hydroxyzine can significantly inhibit the immediate skin test reaction (see DRUG INTERACTION). INFORMATION FOR PATIENTS: Because most serious reactions following the administration of allergenic extracts occur within 20 minutes of the injection, the patient should remain under observation for this period of time. The size of the local reaction should be recorded, because increasingly large local reactions may precede a subsequent systemic reaction with increasing dosage. The patient should be instructed to report any unusual reactions to the attention of the physician. In particular, this includes swelling and/or tenderness at the injection site or reactions such as rhinorrhea, sneezing, coughing, wheezing, shortness of breath, nausea, dizziness or faintness. Caution should be exercised in testing or treating pregnant females because a systemic reaction might conceivably cause uterine muscle contractions leading to abortion. CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY: Long term studies in animals have not been conducted with allergenic extracts to determine their potential for carcinogenicity, mutagenicity or impairment of fertility. PREGNANCY CATEGORY C: Animal reproduction studies have not been conducted with mite extract. It is also not known whether mite extract can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Mite extract should be given to a pregnant woman only if clearly needed. NURSING MOTHERS: It is not known whether allergenic extracts are excreted in human milk. Because many drugs are excreted in human milk caution should be exercised when allergenic extracts are administered to a nursing woman. PEDIATRIC USE: Although standardized mite extract has not been studied in children, unstandardized extract of D. farinae has been administered by the prick test to asthmatic children ages 1 to 16 without any reported adverse response (6). Extract of D. pteronyssinus has been given subcutaneously for hyposensitization to children ages 5 to 14 with adverse reactions being limited to local discomfort, redness and swelling for one or two days (7). DRUG INTERACTION: Antihistamines and hydroxyzine can inhibit the immediate skin test reaction. Patients being treated with delayed absorption antihistamine tablets should be free of such medication for 48 hours before testing. Non-sedating antihistamines, such as terfinadine and astemizole, may variably suppress the skin response for longer periods of time. Epinephrine injection inhibits the immediate skin test reaction for several hours. Beta-blocking drugs may make patients refractory to the usual dose of epinephrine, in the event epinephrine is required to treat an adverse allergic reaction.

Adverse systemic reactions usually occur within minutes and consist primarily of allergic symptoms such as generalized skin erythema, urticaria, pruritus, angioedema, rhinitis, wheezing, laryngeal edema and hypotension. Less commonly, nausea, emesis, abdominal cramps, diarrhea and uterine contractions may occur. Severe reactions may cause shock and loss of consciousness. Fatalities have occurred rarely (11). Systemic reactions occur with varying frequency in different clinics. To some extent, the reaction rate is related to the type and dose of administered extract and to the degree of sensitivity of the patient. Despite all precautions, occasional reactions are unavoidable. Reports from regulatory authorities in Sweden to the Center for Biologics Evaluation and Research (CBER) indicated that several deaths have been associated with the use of mite extracts. CBER was subsequently informed that these deaths may have been related to use by physicians or other health professionals untrained in the administration of potent allergens, rather than a product defect. It should be noted that anaphylaxis and deaths following the injection of mite and other extracts also have been reported by the British Committee on Safety in Medicine in the British Medical Journal, 293:943, 1986. Local reactions consisting of erythema, itching, swelling, tenderness and sometimes pain may occur at the injection site. These reactions may appear within a few minutes to hours and persist for several days. Local cold applications and oral antihistamines may be effective treatment. For marked and prolonged local reactions, steroids may be helpful. The treatment of systemic allergic reactions is somewhat dependent upon the symptom complex. Epinephrine hydrochloride 1:1,000 aqueous, in an adult dose of 0.3 – 0.5 mL (or 0.01 mL per kg. for children) administeredsubcutaneously in the opposite arm is the immediate treatment of choice. A tourniquet should be placed above the site of the extract injection if the injection was done on the extremities. Antihistamines may offer relief of recurrent urticaria, associated skin reactions and gastrointestinal symptoms. Persistent wheezing may necessitate intravenous aminophylline treatment. For profound shock and hypotension, intravenous fluids, vasopressors and oxygen also may be needed. Maintenance of an open airway is critical if upper airway obstruction is present. Corticosteroids may provide benefit if symptoms are prolonged or recurrent.