STANDARDIZED CAT HAIR

Standardized Cat Hair Extract is a clear, light yellow to amber solution of the allergens of cat hair, extracted in buffered saline containing sodium chloride, sodium bicarbonate and 50% glycerol by volume. Phenol at 0.4% w/v is added as a preservative. Source material for the extract is obtained from the hair of the domestic cat The importance of surface allergens in cat allergy has been shown in several investigations (1,2,3). Standardization The potency of Standardized Cat Hair Extract is based on the amount of Fel d 1 allergen in the extract. Extract containing 5-9.9 units per mL is assigned a potency of 5,000 Bioequivalent Allergy Units (BAU/mL). Extract containing 10-19.9 Fel d 1 units is assigned a potency of 10,000 BAU/mL. BAU/mL values are based on quantitative skin testing. The primary allergen of Standardized Cat Hair Extract is Fel d 1 . Standardized Cat Pelt Extract contains Fel d 1 , as well as non-Fel d 1 allergens. The latter are believed lobe components of cat serum, such as albumin. Pelt extracts have a higher protein content than hair extracts, and the isoelectric focusing (IEF) pattern of the pelt extract reveals protein bands that are not present in cat hair extracts. The IEF pattern of cat hair extracts shows primarily Fel d 1 allergen without serum components. The importance of Fel d1 as a means of standardizing the potency of cat extract is based on the following observations: 1. The intensity of skin reactions to cat extract correlates with the Fel d 1 content of the extract in most cat sensitive patients(1). 2. The absorption of cat extract with monospecific antisera to Fel d 1 causes a reduction in the allergenic activity of cat extract (1). 3. The precipitin arc of Fel d 1 in cat extract binds most of the IgE antibody in sera obtained from cat allergic individuals (2).

Studies have shown that skin tests with cat extract are useful in the diagnosis of cat allergy. As a rule, persons with cat allergy have positive skin reactions when tested with cat extract, and non-allergic individuals rarely react (7, 8, 9). However, the relationship between a positive skin test and the appearance of clinical symptoms after exposure to a cat is not absolute, i.e., some skin-test positive persons do not experience allergic symptoms after exposure (10). Failure to experience symptoms may be dose related, since it is known that cats vary significantly in the amount of Fel d1 they produce (11). The efficacy of cat extract immunotherapy in the treatment of bronchial asthma has been shown in two studies (12, 13) A reduction in bronchial sensitivity was observed in five patients with cat allergy, whereas no reduction was observed in placebo treated, cat-allergic patients.

Diagnosis: Concentrated extract (10,000 BAU/mL) may be used for scratch or prick-puncture testing. Puncture tests performed with a bifurcated needle in ten cat allergic persons showed a mean wheal diameter of 6.6 mm (S.D. 1.3) with a mean sum of erythema of 57.3 mm (S.D. 10.4). Intradermal tests with serial three-fold dilution of the 10,000 BAU/mL showed the following results: Serial 3-Fold Dilutions of 10,000 BAU/mL Extract Subject 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X The mean three-fold dilution eliciting a response of 50 mm sum of erythema diameters was 11.120 (S.D. 2,38). The number of BAU/mL required to elicit this response was 0.05 (range 0.0003 to 9.24 BAU/mL). This concentration is approximately a 1:200,000 v/v dilution of the 10,000 BAU/mL extract. Extract for intradermal testing should be used as follows: Patients with a positive scratch or prick test to Standardized Cat Hair Extract. It is not advisable to perform an intradermal skin test in these patients. Patients with a negative scratch or prick test to Standardized Cat Hair Extract. Patients who do not react to a scratch or prick test with the 10,000 BAU/mL concentrate maybe tested intradermally with 0.05 mL of a 1:2,000 v/v dilution of the concentrate (5 BAU/mL). If the test is negative, a second test should be performed with 0.05 mL of a 1:200 v/v dilution of concentrate (50 BAU/mL). Patients tested only by the intradermal method with Standardized Cat Hair Extract. Patients suspected of being highly allergic to cats should be tested with 0.05 mL of a 1:200,000 v/v dilution (0.05 BAU/mL) of the concentrate. A negative test should be followed by repeat tests using 10 fold stronger concentrations until the maximum dose of 0.05 mL of a 1:200 v/v dilution (50 BAU/mL) is reached. Interpretation Of Skin Tests: The interpretation of skin tests should be based on the size of the erythema and wheal response to the allergen compared to a negative saline control. A suggested method of scoring skin tests is shown below. Measurements refer to the longest (single), diameter of erythema and wheal response. Scratch and Prick Test A negative test shows only a slight red area at the site of scarification or prick penetration. Positive tests are scored as follows: 1 + Erythema with a 5 mm wheal 2 + Erythema with a 5 -10 mm wheal 3 + Erythema with a 10 - 15 mm wheal 4 + Erythema with a wheal 15 mm (or larger) with pseudopodia Intradermal Test A negative test shows no change in the appearance and size of the 5mm wheal created by the 1.D. injection of 0.05 mL of extract. Positive tests are scored as follows: 1 + Erythema 10 - 20 mm with a 5 -10 mm wheal 2 + Erythema 20 - 30 mm with a 5 -10 mm wheal 3 + Erythema 30 - 40 mm with a 10 - 15 mm wheal 4 + Erythema greater than 40 mm with a 15 mm wheal (or larger) with pseudopodia Immunotherapy Allergenic extract should be administered subcutaneously in the outer aspect of the upper arm using a sterile tuberculin syringe and needle. The skin should be cleaned with 70% alcohol and aseptic technique should be observed in removing the extract from the vial. Care must be taken to avoid injecting the extract into a blood vessel because of the potential hazard of anaphylaxis. Standardized Cat Hair Extract must be diluted before administration to new patients. As a precaution against overdose, a skin test with the intended starting dose should be done to help evaluate the patient's sensitivity to the product. If the skin response is larger than 5/15 mm (edema/erythema), the extract should be diluted before it is given subcutaneously. The doses shown in the Dosage Schedule may be followed unless the patient's skin test response and allergic history indicate that more dilute extract should be used. Little is known about the required accumulated dosage of Fel d 1 (and other allergens that may be present in cat extract) that is needed to relieve symptoms. However, studies with other allergenic substances have shown that high dose immunotherapy is most efficacious in the treatment of allergic rhinitis and asthma. The amount of cat extract that is tolerated during immunotherapy depends upon the sensitivity of the patient. In one study in which patients with cat asthma were treated for a period of one year, the accumulated dose of Fel d 1 varied from 3.6 to 115.8 (median 46.2) units (13). A burning sensation immediately following the injection of extract from the concentrate is due to the glycerol in the extract. It should not be interpreted as an adverse allergic response. Patients who have received allergenic extract for maintenance therapy SHOULD NOT be given the same dose from a fresh vial of extract. IT IS ADVISABLE TO REDUCE THE DOSAGE OF FRESH EXTRACT TO ONE-FOURTH THE AMOUNT GIVEN FROM A PREVIOUS LOT. Dosage Schedule for Standardized Cat Hair Extract (The safety and efficacy of this schedule has not been determined by well-controlled clinical trials.) [BAU = Bioequivalent Allergy Units per mL] Vial #1 0.05 BAU Vial #2 0.5 BAU Vial #3 5 BAU Vial #4 50 BAU Vial #5 500 BAU Vial #6 5,000 BAU frequency twice weekly No. mL mL mL mL mL mL 1 0.05 0.05 0.05 0.05 0.05 0.05 2 0.1 0.1 0.1 0.1 0.1 0.1 3 0.2 0.2 0.2 0.2 0.2 0.2 4 0.3 0.3 0.3 0.3 0.3 0.3 5 0.4 0.4 0.4 0.4 0.4 0.4 v/v dilutions of concentrate containing 10,000 BAU per mL required to make the above concentrations. BAU per mL v/v Dilution of Concentrate 0.05 1:200,000 0.5 1:20,000 5.0 1:2,000 50.0 1:200 500.0 1:20 5,000.0 1:2

Standardized Cat Hair Extract should not be used for immunotherapy in persons who do not have cat related allergic symptoms and a positive skin test to the extract.

Local Reactions From Skin Testing Large local reactions may result from skin tests with Standardized Cat Hair Extract. To help prevent this, a patient should be skin tested initially by the prick or scratch method. If a positive response is NOT observed, an intradermal skin test may be performed with a more dilute solution of the extract. Oral antihistamines and topical corticosteroids may be administered to relieve itching and swelling resulting from large skin test reactions. Local Reactions From Subcutaneous Injections The occurrence of a hive 5 to 15 minutes after the subcutaneous injection of extract is usually due to leakage of extract into the skin along the needle tract. Firm pressure (not rubbing) at the site of injection immediately after withdrawal of the needle will usually prevent this reaction. It does not require a reduction in dosage. However, a strong local reaction with erythema and edema which persists at the injection site for several hours indicates that too much extract has been given. Failure to note this response may result in a serious generalized reaction. Treatment should be altered as follows: Additional injections should not be given until all evidence of the reaction has disappeared. The next injection administered should be 50% of the last nonreacting dose or less, depending upon the size and severity of the local reaction. Subsequent injections should be continued at the reduced dosage unless the physician responsible for treatment believes that it is safe to increase the dose, and that possible clinical improvement would result from the administration of a larger dose of extract. Systemic Reactions Systemic reactions may range from a mild exacerbation of the patient's allergic symptoms to hives, anaphylactic shock, or even death from anaphylaxis. The reaction usually occurs 5 to 20 minutes after injection. As a rule, the more quickly a reaction develops, the more serious it is likely to become. Symptoms may include sneezing, coughing, itching, shortness of breath, abdominal cramps, vomiting, diarrhea, tachycardia, hypotension and respiratory failure in severe cases. The reaction is usually stopped by the subcutaneous injection of Epinephrine HCL 1:1,000 (See Overdosage below). The oral administration of antihistamines and the placement of a tourniquet proximal to the injection site are helpful adjuncts. In the event that additional measures are required, it may be necessary to treat the patient for BRONCHOSPASM with intravenous aminophylline, intravenous fluids and corticosteroids; for HYPOTENSION with vasopressors, volume repletion, isoproterenol and corticosteroids; for LARYNGEAL OBSTRUCTION with oxygen and tracheotomy and for CARDIAC ARREST with cardiopulmonary resuscitation and other appropriate measures.

STORAGE AND HANDLING Extract should be stored at 2°C to 8°C since higher temperatures may adversely affect stability. Do not freeze.