House Dust Mite, Dermatophagoides Farinae

INDICATIONS AND USAGE 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).

DOSAGE AND ADMINISTRATION Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The product should be discarded if discoloration or particles are observed. DIAGNOSTIC USE: Percutaneous Tests : The skin test concentration of 10,000 AU/mL in dropper vials is used for scratch or prick-puncture testing. Puncture tests performed with D. farinae extract on 5 persons sensitive to mite showed a mean diameter wheal of 8.8 mm ± 1.8 mm and mean diameter erythema of 39.2 mm ± 5.3 mm. Puncture tests with D. pteronyssinus extract on 10 persons sensitive to mite showed a mean diameter wheal of 7.8 mm ± 4.1 mm and mean erythema of 33.7 mm ± 12.0 mm. Intradermal Tests : Extract for intradermal testing should be prepared by diluting the 10,000 AU/mL stock concentrate in bulk vials with sterile saline with or without human serum albumin. Intradermal skin tests (0.05 mL) in persons highly sensitive to mite showed the following results: Table 1 AU/mL to elicit 50 mm sum of diameter erythema reaction Allergen No. of Persons Mean Range D. farinae 5 0.0040 0.0013-0.0124 D. pteronyssinus 10 0.0031 0.0001-0.1416 Intradermal tests should only be performed after a scratch or prick-puncture test has been administered with a negative result. Patients who do not react to a valid scratch or prick-puncture test should be tested intradermally with 0.02 to 0.05 mL of a 10 AU/mL (1:1,000 v/v of the 10,000 AU/mL concentrate). If this test is negative, a second intradermal test may be performed using a 100 AU/mL (1:100 v/v dilution of 10,000 AU/mL concentrate). Skin tests are graded in terms of the wheal and erythema response noted at 15 to 20 minutes. Wheal and erythema size may be recorded by actual measurement of the extent of both responses. THERAPEUTIC USE: The dosage of mite extract administered by subcutaneous injection is highly individualized and varies according to the degree of sensitivity of the patient, his clinical response and tolerance to the extract administered during the early phases of an injection regimen. In patients who appear to be highly sensitive by history and skin test, the initial dose of the extract should be 0.05 mL of a 0.1 AU/mL dilution or as established by skin test titration. The amount of allergenic extract is increased at each injection by not more than 50% - 100% of the previous amount, and the next increment is governed by the response to the last injection. Large local reactions which persist for longer than 24 hours are generally considered an indication for repeating the previous dose or reducing the dose. Any evidence of systemic reaction is an indication for a significant reduction (at least 50%) in the subsequent dose. The upper limits of dosage have not been established; however, doses larger than 0.2 mL of the concentrate may be painful due to the glycerin content of the extract. The optimal interval between doses of mite extract has not been definitely established. However, as is customarily practiced, injections are given one or two times per week until the maintenance dose of extract is reached. At this time, the injection interval may be increased to 2 weeks, then to 3 weeks and finally to 4 weeks. If the patient does not return for 6 to 8 weeks after the last injection, the dose should be reduced to 25% of the last dose. If longer than 8 weeks, a dose reduction of one, two or three dilutions may be made depending on a consideration of the components and the patient's sensitivity The dosage and the interval between injections may need to be modified according to the clinical response of the patient. When switching patients to fresh extract, the initial dose should be reduced to one-quarter (25%) of the previous dose. The usual duration of treatment has not been established. A period of three to five years of injection therapy constitutes an average course of treatment. Children and older age patients appear to tolerate injections of allergenic extract well, and no special recommendations need to be made for these groups. PREPARING DILUTIONS To prepare dilutions for intradermal skin tests and therapeutic use as shown in the table below, make a series of ten-fold dilutions starting with the 5,000 AU/mL or 10,000 AU/mL as follows: add 1.0 mL of the concentrate to 9.0 mL of sterile diluent to make the 1:10 dilution; add 1.0 mL of the 1:10 dilution to 9.0 mL of sterile diluent to make the 1:100 dilution. Continue making dilutions as shown in the table below until the highest desired dilution is reached. The number of allergy units per mL in each dilution is shown in the table below. Table 2 Volume per volume dilutions of 5,000 AU/mL and 10,000 AU/mL concentrates to provide a ten-fold dilution series. Vial No. w/v Dilution of Concentrate 5,000 AU/mL Concentrate AU/mL 10,000 AU/mL Concentrate AU/mL 1 1:100,000 0.05 0.1 2 1:10,000 0.5 1 3 1:1,000 5 10 4 1:100 50 100 5 1:10 500 1,000 6 No Dilution 5,000 10,000

ADVERSE REACTIONS 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.