Bermuda Grass, Standardized: Package Insert and Label Information

BERMUDA GRASS, STANDARDIZED- cynodon dactylon pollen solution
KENTUCKY BLUEGRASS (JUNE) STANDARDIZED- poa pratensis pollen injection, solution
KENTUCKY BLUEGRASS (JUNE) STANDARDIZED- poa pratensis pollen solution
MEADOW FESCUE GRASS, STANDARDIZED- festuca pratensis pollen injection, solution
MEADOW FESCUE GRASS, STANDARDIZED- festuca pratensis pollen solution
ORCHARD GRASS, STANDARDIZED- dactylis glomerata pollen injection, solution
ORCHARD GRASS, STANDARDIZED- dactylis glomerata pollen solution
REDTOP GRASS, STANDARDIZED- agrostis gigantea pollen injection, solution
REDTOP GRASS, STANDARDIZED- agrostis gigantea pollen solution
RYE GRASS, PERENNIAL STANDARDIZED- lolium perenne pollen injection, solution
RYE GRASS, PERENNIAL STANDARDIZED- lolium perenne pollen solution
SWEET VERNAL GRASS, STANDARDIZED- anthoxanthum odoratum pollen injection, solution
SWEET VERNAL GRASS, STANDARDIZED- anthoxanthum odoratum pollen solution
TIMOTHY, STANDARDIZED- phleum pratense pollen injection, solution
TIMOTHY, STANDARDIZED- phleum pratense pollen solution
BERMUDA GRASS, STANDARDIZED- cynodon dactylon pollen injection, solution
STANDARDIZED PERENNIAL RYE GRASS POLLEN- lolium perenne pollen injection, solution
ALK-Abello, Inc.

DESCRIPTION

Standardized allergenic extract of grass pollens from Timothy (Phleum pratense), Orchard (Dactylis glomerata), June (Poa pratensis), Red Top (Agrostis alba),Sweet Vernal (Anthoxanthum odoratum), Meadow Fescue (Festuca elatior), Perennial Rye (Lolium perenne), Bermuda Grass (Cynodon dactylon), in the accompanying vial are sterile, and contain glycerin 50% v/v and phenol 0.4% (preservative). Inert ingredients may include sodium chloride for isotonicity and sodium bicarbonate buffer.

Glycerinated pollen extracts, for subcutaneous injection for immunotherapy and/or percutaneous or intracutaneous testing (see Dosage and Administration section), are prepared from defatted dried pollen extracted in glycerinated Coca’s Fluid, filtered aseptically, and dispensed into multiple dose vials. These are subsequently tested for sterility, safety, and potency.

For ease in use and for lot-to-lot consistency, the potency is expressed in Bioequivalent Allergy Units (BAUs) per milliliter. A value of 10,000 BAU/mL is assigned to the CBER reference standard that can be diluted 1:0.5 million to produce intradermal ƩE (sum of Erythema) of 50 mm in highly puncture reactive subjects¹. A value of 100,000 BAU/mL is assigned to the CBER reference standard that can be diluted 1:5 million to produce intradermal ƩE (sum of Erythema) of 50 mm in highly puncture reactive subjects. The relative potency of each lot of standardized extract has been compared to the official CBER reference standard by an acceptable assay such as ELISA Inhibition.² When the potency is equivalent by ELISA Inhibition to the reference, the product is assigned 10,000 BAU/mL or 100,000 BAU/mL. Standardized grass pollen extracts, except for Bermuda, have potency designations of either 10,000 BAU/mL or 100,000 BAU/mL. Bermuda grass pollen extract is only available with a 10,000 BAU/mL potency designation.

In the ELISA Inhibition assay, a competitive binding assay, the wells of microtiter plates are coated using a characterized allergenic extract. Allergic sera is added to each well. The binding of IgE specific for the coating allergen is inhibited by concentrations of a test sample of an extract of the same allergen. The amount of IgE bound to the solid phase allergen (and subsequently the degree of inhibition) is determined using enzyme-labeled anti-human IgE antibodies and the appropriate substrate. The potency relative to a reference is determined using a parallel line bioassay method.

CLINICAL PHARMACOLOGY

Diagnostically (for skin testing) the allergen combines with IgE antibodies fixed to mast cells in the skin.³ This complexing causes an increase in cellular permeability and degranulation of the mast cells releasing chemical mediators. These mediators (such as histamine) are responsible for a local inflammatory response of wheal and erythema typical of a positive skin test reaction and also, the symptoms commonly associated with allergic disease. The more mediator released, the larger the reaction (wheal and erythema).

Treatment consists of the subcutaneous injection of gradually increasing doses of the allergens to which the patient is allergic. It has been demonstrated that this method of treatment induces an increased tolerance to the allergens responsible for the symptoms on subsequent exposure. Although the exact relationships between allergen, skin-sensitizing antibody (IgE) and the blocking antibody (IgG) have not been precisely established, clinically confirmed immunological studies have adduced evidence of the efficacy of hyposensitization therapy.

Numerous controlled studies have demonstrated the clinical efficacy of immunotherapy with cat, dust mites and some pollen, including grass pollen extracts.⁴ Nevertheless, responses are variable, and in a few studies patients reported no appreciable benefit.

Puncture test data with 10,000 BAU/mL Grass Pollen Extract CBER reference preparations, in 15 grass allergic patients yielded the following sizes of wheal and erythema (Ʃ = sum of longest diameter and orthogonal cross diameter). ⁵

A. Puncture bifurcated needle data with 10,000 BAU/mL CBER Reference Grass Pollen Extract.

Reference	FDA		P Ʃ Erythema (mm)		P Ʃ Wheal (mm)
Pollen	Lot #	N	Mean	Range	Mean	Range
Bermuda	E4-Ber	15	90.3	43-123	15.7	7-31
June	E3-Jkb	15	77.3	47-107	15.9	6-28
Meadow Fescue	E4-MF	15	81.1	57-115	11.9	7-22
Orchard	E4-Or	15	84.3	57-111	14.1	9-19
Perennial Rye	E10-Rye	15	92.3	73-135	17.5	6-36
Red Top	E4-Rt	15	77.1	42-98	14.1	8-19
Sweet Vernal	E4-SV	15	81.2	28-123	15.7	8-30
Timothy	E6-Ti	15	88.3	51-109	16.9	8-40

The intradermal dose (BAU₅₀ ) of the CBER (FDA) Grass Pollen Extract Reference Preparation required producing a 50 mm Sum of Erythema was calculated based on titration in sensitive individuals.

B. Intradermal Dose of CBER Reference Grass Pollen Extracts for 50mm Sum of Erythema Diameter (BAU₅₀ )⁵.

Reference	FDA	BAU 50 /mL
Pollen	Lot #	Mean	Range
Bermuda	E4-Ber	0.02	0.4-0.0003
June	E3-Jkb	0.02	0.1-0.004
Meadow Fescue	E4-MF	0.02	0.9-0.002
Orchard	E4-Or	0.02	1.9-0.002
Perennial Rye	E10-Rye	0.02	0.7-0.002
Red Top	E4-Rt	0.02	0.8-0.004
Sweet Vernal	E4-SV	0.02	1.0-0.002
Timothy	E6-Ti	0.02	0.6-0.002

Bermuda Grass, Standardized Indications and Usage

Indicated use of allergenic extracts is for the diagnosis and treatment (hyposensitization therapy) of patients who experience allergic symptoms due to exposure to grass pollen and who exhibit type I skin sensitivity when tested to those specific allergens.

Hyposensitization (injection) therapy is a treatment for patients exhibiting allergic reactions to seasonal pollens, dust mites, molds, animal danders, and various other inhalants in situations where the offending allergen cannot be avoided.

For previously untreated patients, prior to the initiation of therapy, clinical sensitivity to the standardized grass pollen extract should be established by careful evaluation of the patient’s history confirmed by diagnostic skin testing. Hyposensitization should not be prescribed for sensitivities to allergens which can easily be avoided.

10,000 BAU/mL extracts are indicated for percutaneous testing. If negative, the 100,000 BAU/mL dose may be used. Availability of 10,000 and 100,000 BAU/mL dosages facilitate safe switching. Patients who tolerate dilutions prepared from the 10,000 BAU/mL dosage and require a higher dose may be treated with dilutions prepared from the 100,000 BAU/mL dosage.

100,000 BAU/mL concentrations may be especially useful when patients are hyposensitized to numerous allergens. Mixing of allergenic extracts dilutes the potency of each constituent. Using higher concentrations such as 100,000 BAU/mL allows for dilution with other extracts without sacrificing immunizing properties. CAUTION: The final potency of each individual component in a patient mixture should never exceed 10,000 BAU/mL. See also, DOSAGE AND ADMINISTRATION section for discussion of mixture labeling.

CONTRAINDICATIONS

A patient should not be immunized with preparations of allergens to which the patient has not demonstrated symptoms, IgE antibodies, positive skin tests, or properly controlled challenge testing. In most cases, immunotherapy is not indicated for those allergens that can be eliminated or minimized by environmental control.

Patients on beta-blockers are not candidates for immunotherapy, as they can be non-responsive to beta-agonists that may be required to reverse a systemic reaction (also see WARNINGS and ADVERSE REACTIONS). In the presence of active symptoms such as rhinitis, wheezing, dyspnea, etc., the indications of immunotherapy must be weighed carefully against the risk of temporarily aggravating the symptoms by the injection itself.

Also, there is some evidence, although inconclusive, that routine immunizations may exacerbate autoimmune diseases. ^6,7,8 Hyposensitization should be given cautiously to patients with this predisposition. Patients with severe cardiorespiratory symptoms are at an additional risk during a systemic reaction. The physician must weigh risk to benefit in these cases.