PRECAUTIONS SECTION

GENERAL PRECAUTIONS

Pregnancy Category C: There are no adequate and well controlled studies in pregnant women. Allergenic extracts should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pediatric Use: Doses of allergenic extracts for children are generally the same as those for adults. The maximum volume of extract tolerated without undue pain and swelling may be less for smaller individuals and therefore the maximum dose and treatment schedule must be individualized.

Animal reproduction studies have not been conducted with allergenic extracts. It is also not known whether allergenic extracts can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Allergenic extracts should be given to a pregnant woman only if clearly needed. 15

Refrigerate at 2-8 degrees C.

Sterile solutions, vials, syringes, etc. should be used. Aseptic technique should be observed when making dilutions, skin testing, and extracts for treatment. The usual precautions in administering allergenic extracts are necessary.

A separate autoclave sterilized or disposable syringe and needle should be used for each individual patient to prevent transmission of serum hepatitis, A.I.D.S. and other infectious agents from one person to another.

The initial dilution of allergen extract, starting dose, and progression of dosage must be carefully determined on the basis of the patient's history and results of skin tests. Patients with a history of severe sensitivity and markedly positive skin tests to high dilutions of the allergen extract should be started with low doses of highly diluted extract. Pregnancy or a history of prior reactions to allergen immunotherapy dictates the need to start with small quantities of antigen.

If the first injection of the initial dilution of extract is tolerated without significant local reaction, increasing doses by 5-20% increments of that dilution may be administered. The rate of increase in dosage in the early stages of treatment with highly diluted extracts is usually more rapid than the rate of increase possible with more concentrated extracts. This schedule is intended only as a guide and must be modified according to the reactivity of the individual patient. Needless to say, the physician must proceed cautiously in the treatment of the highly sensitive patient who develops large local or systemic reactions.

Some patients may tolerate larger doses, but it is rarely necessary to give maintenance doses larger than 2,000 AU/ml of the standardized extract or 0.5 ml of 1:100 w/v of the unstandardized extract. Because dilute extracts tend to lose activity on storage, the first dose from a more concentrated vial, should be the same or less than the previous dose.1,2,3,4,16

Immunotherapy must be given under the supervision of a physician. Before an injection is given the patient should be asked about any reaction following the previous injection to help determine the next dose. Target maintenance dose should be determined by the physician’s experience and patient response to skin testing and treatment.

Dosages progressively increase thereafter according to the tolerance of the patient at intervals of one to seven days until, (1) the patient achieves relief of symptoms, (2) induration at the site of injection is no larger than 50 mm in 36 to 48 hours, (3) a maintenance dose short of aggravating existing symptoms, systemic symptoms, or anaphylaxis. The dose should be escalated until the patient is receiving a final maintenance dose containing 2.7 to 22 u/ml or more of ragweed AgE (using Short Ragweed as example) or demonstrates untoward reactions that indicate the dose to be excessive. This maintenance dose may be continued at regular intervals perennially or achieved each year by a new, but shortened course of treatment. It may be necessary to adjust the progression of dosage downward to avoid local and constitutional reactions.

Immunotherapy of patients highly sensitive to ragweed pollen (using Short Ragweed as an example) receiving a dose of 2.7 to 46.8 units of ragweed AgE (1,000-2,000 or more AU/ml of standardized ragweed extract) was significantly more effective than placebo for (1) relieving symptoms of ragweed hay fever, (2) producing increase in serum levels of anti-ragweed IgG, (3) decrease in seasonal rises in levels of anti-ragweed IgE, (4) decrease in leukocyte histamine release from exposure to ragweed pollen extract in some patients, and (5) increase in IgG and IgA antibodies in nasal secretions. 17

In addition to these changes in humoral antibody production, immunotherapy also effects some cellular changes. Basophils from treated subjects release less histamine in vitro and are less sensitive to the allergen (that is, higher concentrations of allergens are required to induce histamine release) than are basophils from non-treated patients. Lymphocytes from treated patients exhibit decreased proliferative response and decreased production of lymphokine in the presence of the specific allergen. A state of tolerance may be induced in the IgE producing B lymphocytes, there may be impairment in T-lymphocyte helper function, or immunotherapy may generate suppressor cells. Antigen specific suppressor cells, probably bearing histamine receptors, are generated during immunotherapy for allergy and may be partly responsible for the efficacy of this therapy. 14

Loss of potency of aqueous pollen extracts has been recognized as a problem since shortly after the introduction of modern methods of immunotherapy. This loss of potency occurs more rapidly in saline extracts without added preservatives at high temperature and at greater extract dilutions. At concentrations of 1:100 all dilutions containing glycerin, human serum albumin, maintained extract potency within 1 logarithm (log) dilution of the original strength for 12 months; glycerin was significantly superior to all other extracts at 1, 3, and 12 months; and the deleterious effect of phenol was minimal. The deleterious effect of phenol was more marked at the higher dilutions. It was concluded that there may be marked loss of potency of dilute pollen extracts stored for periods of only two weeks under conditions which may be encountered in normal clinical practice. 12

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