Short Ragweed

INDICATIONS Studies have shown that properly performed an interpreted skin tests with ragweed pollen extract are useful in the diagnosis of allergy to ragweed pollen 7, 8, 20, 21 . Immunotherapy with the appropriate dosage of short ragweed pollen extract is effective in reducing symptoms of hay fever and asthma resulting from exposure to short ragweed pollen (9, 10, 11), and it is believed to be effective with extract of giant ragweed, although carefully controlled studies are unavailable. However, clinical observations and known cross reactivity between short and giant ragweed pollens have led to the practice of using a mixture of the two species for skin testing and treatment 22, 23, 24, 25, 26, 27 . This form of treatment is recommended for patients who cannot avoid exposure to pollen and who do not obtain satisfactory relief of symptoms from other medications, such as antihistamines. Immunologic changes resulting from treatment with short ragweed pollen extract are believed to include: The induction of specific anti-ragweed IgG antibodies commonly referred to as "blocking antibodies" 12, 13 . A decrease in the elevation of ragweed specific IgE during and immediately following the ragweed pollen season 14 . A reduction of circulating anti-ragweed IgE after long-term immunotherapy 15 . A decrease in skin reactivity to the extract 16 and a decrease in leukocyte sensitivity to histamine release 17 after long-term immunotherapy.

DOSAGE AND ADMINISTRATION DIAGNOSIS. If the extract supplied in this package is concentrated product (w/v 1:20), it should not be used for intradermal testing. Concentrated extract may be used for scratch or prick testing providing the patient is not exposed to high levels of ragweed pollen and experiencing pronounced symptoms of hay fever or asthma at the time of testing. Extract for intradermal testing must be diluted to a strength of 0.25 units of antigen E per ml 7 . Skin tests should not be performed if the patient has taken antihistamine within 24 hours prior to testing. PROCEDURES Scratch Test: 1 drop of extract concentrate applied to a small scratch or scarification of the volar surface of the forearm or the flat aspect of the back. Prick Test : 1 drop of extract concentrate applied to the unbroken skin of the forearm or the back followed by pricking the skin under the drop. Intradermal Test : 0.05 ml of extract containing 0.25 antigen E units per ml given intradermally on the volar surface of the forearm or outer aspect of the upper arm. This test should not be performed unless the patient is negative to a properly administered and interpreted scratch or prick test. A final intradermal test using 0.05 ml of extract containing 2.5 antigen E units per ml may be used to rule out skin sensitivity to ragweed allergen. INTERPRETATION OF RESULTS 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 5 mm wheal 2+ Erythema with 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 5 mm wheal created by the I.D. injection of 0.05 ml of extract. Positive tests are scored as follows: 1+ Erythema with 10-20 mm with a 5-10 mm wheal 2+ Erythema with 20-30 mm with a 5-10 mm wheal 3+ Erythema with 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 Concentrated ragweed extract must be diluted before administration to new patients. As a rule, extract containing 0.01 to 0.05 units of antigen E per ml are safe to initiate immunotherapy. An intradermal skin test with the intended starting dose may be done as an additional precaution in evaluating the patient's sensitivity. Injections should be given subcutaneously in the outer aspect of the upper arm. Care must be taken to avoid injecting the extract into a blood vessel, because of the potential hazard of anaphylaxis. Concentrated extract is usually administered once every two to four weeks at a maximum dose of 0.2 ml. A mild burning sensation immediately following the injection of concentrated extract is due to the glycerol in the extract. It should not be interpreted as an adverse allergic response. A suggested dosage schedule is shown in the Table below. Patients who have received allergenic extract for maintenance therapy should not be given the same dose from a fresh vial of extract. The antigen E content of ragweed pollen extract varies from lot to lot. Although the potency of fresh extract can be compared with that of previously administered product and adjusted accordingly, it is advisable to reduce the dosage of fresh extract to one-half the amount give from a previous lot. The antigen E content of ragweed pollen extract diminishes during storage and use in the physician's office, and, therefore, may be less than that specified on the vial label. In addition, ragweed pollen extract contains other components which may contribute to the overall allergenicity of the product 18 . SUGGESTED DOSAGE SCHEDULE FOR RAGWEED EXTRACT BASED ON ANTIGEN E CONCENTRATION (units per ml ) Concentrated extracts (w/v 1:20) of short ragweed pollen usually contain between 100 and 300 units antigen E per ml. Mixed short-giant ragweed pollen extracts contain approximately one-ha…

WARNINGS Physicians who elect to administer ragweed pollen extract should be familiar with the clinical use of allergenic extracts and have the necessary emergency equipment and medication available to treat systemic allergic reactions. The injection of ragweed pollen extract may cause severe local and/ or systemic anaphylactic reactions in some individuals. To minimize this potential hazard, the relative sensitivity of the patient must be assessed from the allergic history and from clinical observations. Patients should be informed of this risk prior to skin testing and immunotherapy (see adverse reactions). The dosage must be reduced when starting a patient on fresh standardized (Antigen E) extract or when transferring a patient from non-standardized 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 antigen E content of old and new extract must be compared and adjusted by dosage reduction and/or dilution before new extract is administered. The amount of new extract given from the old vial, assuming both extracts contain comparable amounts of antigen E. Any evidence of a local or generalized reaction requires a reduction in dosage during the initial stages of hyposensitization as well as during maintenance therapy.

CONTRAINDICATIONS There are no absolute contraindications to the use of ragweed pollen extract in the diagnosis and treatment of ragweed allergy. When used in accordance with accepted principles of skin testing and immunotherapy, the extract is considered safe and effective. Relative contraindications include (1) extreme sensitivity to the extract as demonstrated by previous anaphylaxis following skin testing or subcutaneous injection, (2) recent myocardial infarction, and (3) pregnancy (see Precautions #4). The benefit to risk ration must be evaluated in each of the above situations. Ragweed pollen extract should not be administered to persons who are not sensitive to ragweed pollen

ADVERSE REACTIONS LOCAL REACTIONS. The occurrence of a hive 5 to 15 minutes after injection 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. 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 dosage should be reduced three levels, e.g., from 0.4 cc to 0.5 cc or the equivalent, and held at that level for two or three treatments. A second reaction at or near the dose which caused the first local response indicates that a maximum tolerated amount of extract has been reached and no further increases in dosage should be attempted. Maintenance therapy should be continued thereafter at the highest possible non-reacting dose. SYSTEMIC REACTIONS. Systemic (generalized) reactions may range from a mild exaggeration of the patient's allergic symptoms to hives, anaphylactic shock, or even death from anaphylaxis. Systemic reactions may occur when a previous local reaction has not been heeded, or when the extract is accidentally injected intravenously. The reaction usually occurs 5 to 20 minutes after injection. 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 tracheostomy and for cardiac arrest with cardiopulmonary resuscitation and other appropriate measures.