DOSAGE AND ADMINISTRATION It is imperative that the physician determine the initial dose of the product by skin testing. Patients being switched from a Standardized Mite extract to a new Standardized Mite extract (both labeled in AU/mL) should be skin tested with both extracts to determine the relative potency of the extracts and the dosage adjusted accordingly. For safe and effective use of allergen extracts, sterile solutions, vials, syringes, etc. should be used and aseptic precautions observed in making dilution's. The usual precautions to be observed in administering extracts are necessary. A sterile tuberculin syringe graduated in 0.1 mL units to measure each dose for the prescribed dilution should be used. Recommended dosage and range:(Diagnostic) The concentration of Standardized Mite extract for Scratch or Prick-puncture testing is 10,000 AU/mL, glycerinated, supplied in 5 mL dropper vials. Skin tests are graded in terms of the wheal and erythema response noted at 10 to 20 minutes. Wheal and erythema size may be recorded by actual measurement or the extent of both responses. Prick-puncture tests on Mite allergic subjects: 10 puncture tests (bifurcated needle) on mite allergic subjects yielded the following: # Person Mean sum of wheal Range Mean sum of Erythema Range (mm) D. farinae 10 17.4 mm 12-21 mm 78.8 mm 63-97 mm D. pteronyssinus 10 18.0 mm 10-37 mm 68.7 mm 46-114 mm Intradermal tests (using 0.05 mL) on 10 puncture positive patients AU/mL to elicit 50 mm sum of dia. of erythema reaction (10) # Persons Mean Range (AU/mL) D. farinae 10 0.029 AU/mL 0.077-0.005 AU/mL D. pteronyssinus 10 0.024 AU/mL 0.78-0.0004 AU/mL Patients with a negative scratch or prick-puncture test: Patients who do not react to a valid scratch or prick- puncture test should be tested intradermally with a 0.02 to 0.05 mL of a 50 AU/mL extract solution. If this test is negative, a second intradermal test may be performed using a 100 AU/mL extract dilution. The negative puncture test control must be diluted appropriately for ID use. It is supplied in 5 mL and 10 mL vials of 50% glycerin (v/v). To prepare a 50 AU/mL dilution from 10,000 AU/mL vial: Take 5.0mL of 10,000AU/mL + 5.0 mL of diluent = Vial A @5,000 AU/mL. Take 1.0 of Vial A + 9.0 mL diluent = Vial B @ 500 AU/mL. Take 1.0 of Vial B + 9.0 mL diluent = Vial C @ 50 AU/mL. Patients tested only by the intradermal method: Patients being suspected of being highly allergic should be tested with 0.02 to 0.05 mL of a 0.1 AU/mL dilution.(3) A negative test should be followed by repeat tests using progressively stronger concentrations until the maximal recommended strength of 100 AU/mL is reached. The negative puncture test control must be diluted appropriately for intradermal use. It is supplied in 5 mL and 10 mL vials of 50% glycerin (v/v). Recommended dosage and range: (Therapeutic) Dosage of allergenic extracts is a highly individualized matter 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 0.1 mL of 0.01 to 0.1 AU/mL. Patients with lesser sensitivity may be started at 1.0 to 10.0 AU/mL. 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 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%) for the subsequent dose. Maximum dosage has not been established however, the upper limits of l mL of 10,000 AU/mL may be painful due to glycerin content. The dosage of allergenic extract does not vary significantly with the allergic disease under treatment. After therapeutic injections patients should always be observed for at least 30 minutes. If adverse reactions appear, the next therapeutic injection of extract should be reduced to the dose which does not elicit a reaction and subsequent doses increased slowly. If local reactions occur, reduce subsequent injections to a dose which did not elicit this reaction. Preparation Instructions: To prepare dilution for intradermal and therapeutic use, one starts with 10,000 AU/mL concentrate and makes a 1:10 dilution by adding 1.0 mL of the concentrate to 9.0 mL of sterile diluent. Subsequent dilution's are made in similar manner. TEN-FOLD DILUTION SERIES Dilution Extract Diluent mL AU/mL 0 Concentrate 0 10,000 1 1 mL concentrate 9 1,000 2 1 mL dilution #1 9 100 3 1 mL dilution #2 9 10 4 1 mL dilution #3 9 1 5 1 mL dilution #4 9 0.1 6 1 mL dilution #5 9 0.01 Intervals between doses: The optimal interval between doses of allergenic extract has not been definitely established. However, as it is customary practiced, injections are given 1,2, or 3 times per week until the maintenance dose of extract is reached. At this time, the injection interval may be increased to 2 weeks, then 3 weeks and finally to 4 weeks. If the patient does not return for 6-8 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 1,2, or 3 dilution's 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 a fresh extract the initial dose should be reduced 3/4 so that 25% of previous dose is administered.(14) Duration of Treatment: The usual duration of treatment has not been established. A period of two or three years of injection therapy constitutes an average minimum course of treatment. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.