Dermatophagoides Farinae and Dermatophagoides Pteronyssinus

Greer Standardized Mite ( Dermatophagoides farinae and/or Dermatophagoides pteronyssinus ) Extracts are allergenic extracts indicated for: skin test diagnosis of mite allergy treatment of patients with mite-induced allergic asthma, rhinitis and conjunctivitis. For immunotherapy, patients must show hypersensitivity to Dermatophagoides farinae ( D. farinae ) or Dermatophagoides pteronyssinus ( D. pteronyssinus ) based on their clinical history, allergen exposure history, and skin test reactivity. Greer Standardized Mite Extracts are allergenic extracts indicated for: Diagnosis of skin test reactivity to dust mite allergen (1) Treatment of mite-induced allergic asthma, rhinitis and conjunctivitis in patients that show hypersensitivity to dust mites based on clinical history, allergen exposure history, and skin test reactivity (1)

For immunotherapy, concentrated extracts are diluted in normal saline, buffered saline, albumin saline or 10% glycerosaline. For intradermal testing extracts may be diluted in normal saline, buffered saline, or albumin saline. Greer Standardized Mite Extract D. farinae and Greer Standardized Mite Extract D. pteronyssinus are supplied as stock concentrates containing 10,000 Allergy Units/mL and Greer Standardized Mite Extract mixture ( D. farinae and D. pteronyssinus ) is supplied as a stock mixture concentrate containing 5,000 Allergy Units/mL of each species for use in percutaneous skin testing. Greer Standardized Mite Extract D. farinae and Greer Standardized Mite Extract D. pteronyssinus are supplied as stock concentrates containing 5,000, 10,000, or 30,000 Allergy Units/mL. Greer Standardized Mite Extract mixture ( D. farinae and D. pteronyssinus ) is supplied as a stock mixture concentrate containing 5,000 and 15,000 Allergy Units/mL of each species for use in intradermal testing and immunotherapy. For percutaneous testing, Greer Standardized Mite Extract stock concentrates containing 10,000 Allergy Units/mL of Dermatophagoides farinae ( D. farinae ), Dermatophagoides pteronyssinus ( D. pteronyssinus ), or both D. farinae and D. pteronyssinus are supplied in 5 mL dropper vials (3) For intradermal testing or immunotherapy, Greer Standardized Mite Extracts stock concentrates containing a total of 5,000, 10,000 or 30,000 Allergy Units/mL of D. farinae , D. pteronyssinus , or a mixture of D. farinae and D. pteronyssinus are supplied in 10, 30 and 50 mL multiple-dose vials (3)

None. None (4)

5.1 Serious Systemic Reactions All concentrates of Greer Standardized Mite Extracts have the ability during skin testing and immunotherapy to elicit serious systemic reactions including anaphylactic shock and death [see Adverse Reactions (6)]. A review of the literature indicates that the incidence of near-fatal reactions to immunotherapy, defined as severe respiratory compromise, hypotension, or both, and requiring emergency treatment with epinephrine, has been estimated as 5.4 events per million injections in a 10-year retrospective survey of allergists. 3 Fatalities from immunotherapy injections have been estimated to occur at a rate of approximately one death per 2.0 to 2.8 million injections in 4-, 10- and 12-year retrospective surveys of allergists. 4-6 Because of the danger of serious reactions, caution is required in testing and treating high risk patients and those with medical conditions that reduce their ability to survive a serious systemic adverse event. High-risk patients are defined as those patients: with labile or steroid-dependent asthma, particularly in those suffering an exacerbation of their symptoms at the time of extract administration; with extreme sensitivity to a particular allergen(s); who are currently using beta blockers; who are receiving an accelerated immunotherapy build-up schedule (e.g., rush immunotherapy); who are being changed from one allergenic extract to another; who are receiving high doses of allergenic extracts. High risk patients have had fatal reactions. In addition, patients not high-risk but on beta blockers have had fatal reactions because beta blockers interfere with beta adrenergics such as epinephrine used in treatment or anaphylaxis. Patients should be kept under observation for a minimum of 30 minutes after receiving allergenic extracts so that any adverse reaction can be observed and properly handled. 2 Medications to treat systemic reactions, as well as emergency equipment should be available for immediate use. Extracts must only be administered by persons who are aware of the risk of systemic reactions, including anaphylaxis; are capable of handling such reactions; and have the necessary drugs and equipment on hand to do so.

5.2 Patients on Beta Blockers Patients receiving beta blockers may be unresponsive to the usual doses of epinephrine used to treat serious systemic reactions, including anaphylaxis. Inhalant allergy immunotherapy should be approached with caution in patients taking beta blockers. The risks of anaphylaxis in these patients should be carefully weighed against the benefits of immunotherapy [see Drug Interactions (7.1)].

5.3 Autoimmune Disease Immunotherapy should be given cautiously to patients with other immunologic diseases and only if the risk from exposure to the allergen is greater than the risk of exacerbating the underlying disorder. 2 All concentrates of Greer Standardized Mite Extracts can cause serious systemic reactions of varying degrees of severity, including anaphylactic shock and death, particularly in patients: With labile or steroid-dependent asthma (5.1) With extreme sensitivity to allergen(s) (5.1) Who are currently using beta blockers (5.2) Who are on an accelerated immunotherapy build-up schedule (5.1) Who are being changed from one allergenic extract to another (5.1) Who are receiving high doses of allergen extracts (5.1)

Systemic reactions consist primarily of allergic symptoms, such as generalized skin erythema, urticaria, pruritus, angioedema, rhinitis, wheezing, laryngeal edema, and hypotension. Additional symptoms that are not usually associated with allergy also may occur, such as nausea, emesis, abdominal cramps, and diarrhea. Serious reactions may cause shock, loss of consciousness, and even death. Based on published studies, 7,8 systemic reactions occur in less than 1% of patients receiving conventional immunotherapy to greater than 36% in some studies of patients receiving rush immunotherapy. Local reactions at the injections site are the most commonly occurring reactions (e.g., erythema, itching, swelling, tenderness, pain). Although most adverse systemic reactions occur within 30 minutes of injection (some within minutes of extract exposure), such reactions also can occur up to six hours after skin tests or immunotherapy [see Dosage and Administration (2.2)]. 9 Systemic reactions may be fatal or near fatal (6) Systemic reactions (e.g. generalized skin erythema, urticaria, pruritus, angioedema, rhinitis, wheezing, laryngeal edema, and hypotension) occur in 4-7% of patients The most common reactions are local reactions at the injection site (e.g., erythema, itching, swelling, tenderness, pain), occuring in 26% to 82% of patients (6) To report SUSPECTED ADVERSE REACTIONS, contact Greer Laboratories, Inc., at 1-855-274-1322 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

7.1 Beta Adrenergic Drugs Patients receiving beta blocker drugs may not be responsive to beta adrenergic drugs used to treat anaphylaxis 10 , and may wish to temporarily postpone treatment day of skin testing. All such decisions should be made in consultation with the physician [see Warnings and Precautions (5.2)].

7.2 Antihistamines 1 Skin testing with allergenic extracts should not be performed within 2-3 days of first-generation H 1 -histamine receptor blockers (e.g., clemastine, diphenhydramine) and within 3 to 10 days of second-generation antihistamines (e.g., loratadine, terfenadine), except for astemizole, which requires an interval of 30-60 days between allergenic extract exposure and use. These products suppress histamine skin test reactions and could mask a positive response.

7.3 Topical Corticosteroids and Topical Anesthetics 1 Topical corticosteroids may suppress skin reactivity and should be discontinued at the skin test site for at least 2-3 weeks before skin testing. Topical local anesthetics may suppress flare responses and should be avoided at skin test sites.

7.4 Tricyclic Antidepressants 1 Tricyclic antidepressants can have potent antihistamine effects and will affect skin testing. Since use of tricyclics may alter skin test results, dosing for both skin testing and immunotherapy should be done with caution. If tricyclic medication has been recently discontinued, allow 7-14 days prior to skin testing to obviate the antihistamine effect. The risk of anaphylaxis in these patients should be carefully weighed against the risks and benefits of stopping tricyclics.

7.5 Other Drugs The suppressive action of other drugs should be considered and emphasizes the need for a histamine positive-control test. Patients who are receiving beta agonists may be unresponsive to the usual doses of epinephrine used to treat serious systemic reactions, including anaphylaxis (7.1) Patients should discontinue medications known to suppress the histamine response prior to skin testing including: antihistamines (7.2), tricyclics (7.4), and topical corticosteroids and topical anesthetics (7.3)

8.1 Pregnancy Pregnancy Category C: Animal reproduction studies have not been conducted with Greer Standardized Mite Extracts. It is also not known whether Greer Standardized Mite Extracts can cause fetal harm when administered to a pregnant woman or whether they can affect reproduction capacity. Standardized Mite Extracts should be given to a pregnant woman only if clearly needed. Studies have not been performed in animals to determine whether extracts affect fertility in males or females, have teratogenic potential, or have other adverse affects on the fetus. Exercise caution in testing or treating pregnant females because a systemic reaction may cause maternal cardiovascular compromise leading to fetal distress with sequelae.

8.3 Nursing Mothers It is not known whether allergenic extracts or their antigens are excreted in human milk. Because many drugs are excreted in human milk, exercise caution when extracts are administered to a nursing woman.

8.4 Pediatric Use No studies have systematically examined differences in response to immunotherapy among child and adult patients. Children appear to tolerate injections of allergenic extracts very well. 2 Very young children (under age 5) can have difficulty cooperating with an immunotherapy program and for this reason, the physician should consider the benefits and risks of immunotherapy and indiviualize treatment in patients under the age of 5 years [see Warnings and Precautions (5)].

8.5 Geriatric Use Clinical studies of Greer Standardized Mite Extract did not include sufficent numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. Other reported clinical experiences has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of concomitant disease or other drug therapy including beta blockers. 2 Pregnancy: No human or animal data. Use only if clearly needed (8.1) Autoimmune Disease: Immunotherapy may exacerbate the autoimmune disease. Use only if clearly needed (5.3) See 17 for PATIENT COUNSELING INFORMATION. Revised: 1/2013