Pollens - Weeds and Garden Plants, Short Ragweed, Ambrosia artemisiifolia .05 g/mL Injection, Solution, 5 mL — NDC 65044-2297-1 (Billing 65044-2297-01)

WARNINGS See WARNINGS box at the beginning of this package insert. See also PRECAUTIONS . Allergenic extracts must be temporarily withheld from patients or the dose adjusted downward if any of the following conditions exist: (1) severe symptoms of rhinitis and/or asthma; (2) infection or flu accompanied by fever; (3) any evidence of an excessively large local or generalized reaction during the initial stages of immunotherapy or during maintenance therapy, and/or (4) exposure to excessive amounts of clinically relevant allergen prior to a scheduled injection.

Do not administer immunotherapy during a period of symptoms due to exposure. Since the individual components of the extract are those to which the patient is allergic, and to which s/he will be exposed, typical allergic symptoms may follow shortly after the injection, particularly when the antigen load from exposure plus the injected antigen exceeds the patient's antigen tolerance. THE CONCENTRATE MUST NOT BE INJECTED AT ANY TIME UNLESS TOLERANCE HAS BEEN ESTABLISHED.

DILUTE CONCENTRATED EXTRACTS WITH STERILE DILUENT FOR INTRADERMAL TESTING AND IMMUNOTHERAPY. INJECTIONS MUST NEVER BE GIVEN INTRAVENOUSLY. Subcutaneous injection is recommended.

Intracutaneous or intramuscular injection may produce large local reactions or be excessively painful. AFTER INSERTING NEEDLE SUBCUTANEOUSLY, BUT BEFORE INJECTING, ALWAYS WITHDRAW THE PLUNGER SLIGHTLY. IF BLOOD APPEARS IN THE SYRINGE, CHANGE NEEDLE AND GIVE THE INJECTION IN ANOTHER SITE.

IF CHANGING TO A DIFFERENT LOT OF EXTRACT: All extracts lose potency over time, and a fresh extract could have an effective potency that is substantially greater than that of the old extract. Even though it is the same formula and concentration, the first dose from the new vial should not exceed 50% of the previous dose. IF THE EXTRACT PREVIOUSLY USED WAS FROM ANOTHER MANUFACTURER: Since manufacturing processes and sources of raw materials differ among manufacturers, the interchangeability of extracts from different manufacturers cannot be insured.

The starting dose of the extract therefore should be greatly decreased even though the extract is the same formula and dilution. In general, a dose reduction of 50% of the previous product dose should be adequate, but each situation must be evaluated separately considering the patient's history of sensitivity, tolerance of previous injections, and other factors. If the patient tolerates a 50% decrease, the next dose could be raised to the previous dose amount.

If the decrease is greater than 50%, the next dose would need to be determined by the allergist, depending on the situation. Dose intervals should not exceed one week when rebuilding dose. See DOSAGE AND ADMINISTRATION .

IF A PROLONGED PERIOD OF TIME HAS ELAPSED SINCE THE LAST INJECTION: Patients may lose tolerance for allergen injections during prolonged periods between doses. The duration of tolerance is an individual characteristic and varies from patient to patient. In general, the longer the lapse in the injection schedule, the greater dose reduction required.

If the interval since last dose is over four weeks, perform skin tests to determine starting dose. See DOSAGE AND ADMINISTRATION . IF THE PREVIOUS EXTRACT WAS OUTDATED: The dating period for allergenic extracts indicates the time that they can be expected to remain potent under refrigerated storage conditions (2° - 8°C).

During the storage of extracts, even under ideal conditions, some loss of potency occurs. For this reason, extracts should not be used beyond their expiration date. If a patient has been receiving injections of an outdated extract, s/he may experience excessive local or systemic reactions when changed to a new and possibly more potent extract.

In general, the longer the material has been outdated, the greater the dose reduction necessary for the fresh extract. IF CHANGING FROM ALUM-ADSORBED TO AQUEOUS OR GLYCERINATED EXTRACTS: When the patient previously has been receiving… [Excerpted — this section continues on DailyMed.]

ADVERSE REACTIONS Physicians administering allergenic extract testing or treatment materials should be experienced in the treatment of severe systemic reactions. See WARNINGS box at the beginning of this package insert. 1.

Local Reactions Some erythema, swelling, or pruritus at the site of injection are common, the extent varying with the patient. Such reactions should not be considered significant unless they persist for at least 24 hours. Local reactions (erythema or swelling) which exceed 4-5 cm in diameter are not only uncomfortable, but also indicate the possibility of a systemic reaction if dosage is increased.

In such cases the dosage should be reduced to the last level not causing the reaction and maintained at this level for two or three treatments before cautiously increasing again. Large, persistent local reactions may be treated by local cold, wet dressings and/or the use of oral antihistamines. They should be considered a warning of possible severe systemic reactions and the need for temporarily reduced dosages.

A mild burning immediately after the injection is to be expected; this usually subsides in 10 to 20 seconds. 2. Systemic Reactions With careful attention to dosage and administration, systemic reactions occur infrequently, but it cannot be overemphasized that in sensitive individuals any injection could result in anaphylactic shock.

Therefore, it is imperative that physicians administering allergenic extracts understand and be prepared for the treatment of severe reactions. Most severe systemic reactions will begin within a 30 minute time period, but systemic reactions may occur at any time after skin tests or immunotherapy. Symptoms may range from mild to life-threatening (due to anaphylaxis) as described below.

Other possible systemic reaction symptoms which may occur in varying degrees of severity are laryngeal edema, fainting, pallor, bradycardia, hypotension, angioedema, cough, wheezing, conjunctivitis, rhinitis, and urticaria. Adverse reaction frequency data for allergenic extract administration for testing and treatment show that risk is low. 1, 41 If a systemic or anaphylactic reaction does occur, apply a tourniquet above the site of injection and inject 1:1000 epinephrine-hydrochloride intramuscularly into the opposite arm.

Loosen the tourniquet at least every 10 minutes. Do not obstruct arterial blood flow with the tourniquet. EPINEPHRINE DOSAGE ADULT: 0.3 to 0.5 mL should be injected.

Repeat in 5 to 10 minutes if necessary. PEDIATRIC : The usual initial dose is 0.01 mg (mL) per kg body weight or 0.3 mg (mL) per square meter of body surface area. Suggested dosage for infants to 2 years of age is 0.05 mL to 0.1 mL; for children 2 to 6 years, 0.15 mL; and children 6 to 12 years, 0.2 mL.

Single pediatric doses should not exceed 0.3 mg (mL). Doses may be repeated as frequently as every 20 minutes, depending on the severity of the condition and the response of the patient. After administration of epinephrine, profound shock or vasomotor collapse should be treated with intravenous fluids, and possibly vasoactive drugs.

Airway patiency should be insured. Oxygen should be given by mask. Intravenous antihistamine, inhaled bronchodilators, theophylline, and/or adrenal corticosteroids may be used if necessary after adequate epinephrine and circulatory support have been given.

Emergency resuscitation measures and personnel trained in their use must be available immediately in the event of a serious systemic or anaphylactic reaction not responsive to the above measures [ Ref. J. Allergy and Clinical Immunology 77(2): p.

271-273, 1986]. Rarely are all of the above measures necessary; the tourniquet and epinephrine usually produce prompt responses. However, the physician should be prepared in advance for all contingencies.

Promptness in beginning emergency treatment measures is of utmost importance. Severe systemic reactions mandate a decrease of at least 50% in the next dose, followed by cautious increases. Re… [Excerpted — this section continues on DailyMed.]

3. Drug Interactions Patients with cardiovascular diseases and/or pulmonary diseases such as symptomatic unstable, steroid-dependent asthma, and/or those who are receiving cardiovascular drugs such as beta blockers, may be at higher risk for severe adverse reactions. These patients may also be more refractory to the normal allergy treatment regimen.

Patients should be treated only if the benefit of treatment outweighs the risks. 1 Patients on beta blockers may be more reactive to allergens given for testing or treatment and may be unresponsive to the usual doses of epinephrine used to treat allergic reactions. 2 (See WARNINGS .) Certain medications may lessen the skin test wheal and erythema responses elicited by allergens and histamine for varying time periods.

Conventional antihistamines should be discontinued at least 5 days before skin testing. Long acting antihistamines should be discontinued for at least 3 weeks prior to skin testing. 32 Topical steroids should be discontinued at the skin test site for at least 2-3 weeks before skin testing.

32, 33 Tricyclic antidepressants such as Doxepin should be withheld for at least 7 days before skin testing. 34 Topical local anesthetics may suppress flare responses and should be avoided in skin test sites. 35 When using other drugs in patients receiving allergenic extracts, always consult the product labeling of the other drugs to determine any possible interaction with use of allergenic extracts.

PRECAUTIONS 1. General The presence of asthmatic signs and symptoms appear to be an indicator for severe reactions following allergy injections. An assessment of airway obstruction either by measurement of peak flow or an alternate procedure may provide a useful indicator as to the advisability of administering an allergy injection.

1, 28, 29, 30, 31 Concentrated extracts must not be injected unless tolerance has been established. Concentrated extracts must be diluted prior to use. See DOSAGE AND ADMINISTRATION for detailed instructions on the dilution of allergenic extracts.

Any evidence of a local or generalized reaction requires a reduction in dosage during the initial stages of immunotherapy, as well as during maintenance therapy. Allergenic extracts diluted with sterile Albumin Saline with Phenol (0.4%) may be more potent than extracts diluted with diluents which do not contain stabilizers. When changing from non-stabilized to stabilized diluent, consider weaker initial dilutions for both intradermal testing and immunotherapy.

Dilutions for both intradermal testing and immunotherapy. Sterile solutions, vials, syringes, etc., should be used and aseptic precautions observed in making dilutions. To avoid cross-contamination, do not use the same needle to withdraw materials from vials of more than one extract, or extract followed by diluent.

A sterile tuberculin syringe graduated in 0.01 mL units and with a needle at least 5/8" long should be used to measure each dose from the appropriate dilution. Aseptic techniques should always be employed when injections of allergenic extracts are being administered. A separate sterile syringe should be used for each patient to prevent transmission of hepatitis and other infectious agents from one person to another.

Patient reactions to previous injections should be reviewed before each new injection, so that dosage can be adjusted accordingly. See ADVERSE REACTIONS and WARNINGS . Rarely, a patient is encountered who develops systemic reactions to minute doses of allergen and does not demonstrate increasing tolerance to injections after several months of treatment.

If systemic reactions or excessive local responses occur persistently at very small doses, efforts at immunotherapy should be stopped. PATIENTS SHOULD BE OBSERVED IN THE OFFICE FOR AT LEAST 30 MINUTES AFTER SKIN TESTING AND EACH TREATMENT INJECTION. Most severe reactions will occur within this time period, and rapid treatment measures should be instituted.

See ADVERSE REACTIONS for these treatment measures. 2. Information for Patients Patients should be instructed in the recognition of adverse reactions to immunotherapy, and in particular, to the symptoms of shock.

(See WARNINGS box at the beginning of this package insert.) Patients should be made to understand the importance of a 30 minute observation period following skin testing or therapeutic injections, and be cautioned to return to the office promptly if symptoms occur after leaving. Patients should be instructed to report any symptoms of exposure to the allergen, so the physician can adjust the dosage appropriately. 3.

Drug Interactions Patients with cardiovascular diseases and/or pulmonary diseases such as symptomatic unstable, steroid-dependent asthma, and/or those who are receiving cardiovascular drugs such as beta blockers, may be at higher risk for severe adverse reactions. These patients may also be more refractory to the normal allergy treatment regimen. Patients should be treated only if the benefit of treatment outweighs the risks.

1 Patients on beta blockers may be more reactive to allergens given for testing or treatment and may be unresponsive to the usual doses of epinephrine used to treat allergic reactions. 2 (See WARNINGS .) Certain medications may lessen the skin test wheal and erythema responses elicited by allergens and histamine for varying time periods. Conventional antihistamines should be discontinued at least 5 days before skin testing.

Long actin… [Excerpted — this section continues on DailyMed.]