Product Monograph - Negative Skin Test Control - Glycerin
RECENT MAJOR LABEL CHANGES
| All Sections and Subsections updated to Plain Language Labeling Format | 10/2024 |
|---|
TABLE OF CONTENTS
Sections or subsections that are not applicable at the time of authorization are not listed.
RECENT MAJOR LABEL CHANGES ........................................................................................................................... 2
TABLE OF CONTENTS .............................................................................................................................................. 2
PART I: HEALTH PROFESSIONAL INFORMATION ..................................................................................................... 4
- 1.
INDICATIONS ............................................................................................................................................ 4
1.1. Pediatrics ........................................................................................................................................... 4
1.2. Geriatrics ........................................................................................................................................... 4
- 2. CONTRAINDICATIONS .............................................................................................................................. 4
- 3. SERIOUS WARNINGS AND PRECAUTIONS BOX ......................................................................................... 4
- 4.
DOSAGE AND ADMINISTRATION .............................................................................................................. 5
4.1. Dosing Considerations ...................................................................................................................... 5
4.2. Recommended Dose and Dosage Adjustment .................................................................................. 5
4.3. Reconstitution ................................................................................................................................... 5
4.4. Administration .................................................................................................................................. 6
- 5. OVERDOSAGE........................................................................................................................................... 7
- 6. DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING .............................................................. 7
- 7.
WARNINGS AND PRECAUTIONS ............................................................................................................. 10
7.1. Special Populations ......................................................................................................................... 11
7.1.1. Pregnant Women ............................................................................................................................ 11
7.1.2. Breast Feeding ................................................................................................................................ 11
7.1.3. Pediatrics ......................................................................................................................................... 11
7.1.4. Geriatrics ......................................................................................................................................... 11
- 8.
ADVERSE REACTIONS ............................................................................................................................. 11
8.1. Adverse Reaction Overview ............................................................................................................ 11
8.5. Post-Market Adverse Reactions ...................................................................................................... 12
- 9.
DRUG INTERACTIONS ............................................................................................................................. 12
9.1. Serious Drug Interactions ................................................................................................................ 12
9.2. Drug Interactions Overview ............................................................................................................ 12
9.4. Drug-Drug Interactions ................................................................................................................... 12
9.5. Drug-Food Interactions ................................................................................................................... 14
9.6. Drug-Herb Interactions ................................................................................................................... 14
9.7. Drug-Laboratory Test Interactions .................................................................................................. 14
- 10.
CLINICAL PHARMACOLOGY .................................................................................................................... 14
10.1. Mechanism of Action ...................................................................................................................... 14
- 11. STORAGE, STABILITY AND DISPOSAL ...................................................................................................... 14
- 12. SPECIAL HANDLING INSTRUCTIONS ........................................................................................................ 15
PART II: SCIENTIFIC INFORMATION ..................................................................................................................... 15
- 13. PHARMACEUTICAL INFORMATION ......................................................................................................... 15
- 14. CLINICAL TRIALS ..................................................................................................................................... 15
- 15. MICROBIOLOGY ..................................................................................................................................... 15
- 16. NON-CLINICAL TOXICOLOGY .................................................................................................................. 15
PATIENT MEDICATION INFORMATION ................................................................................................................. 16
PART I: HEALTH PROFESSIONAL INFORMATION
1. INDICATIONS
ALLERGENIC EXTRACT – POLLENS and ALLERGENIC EXTRACT – NON-POLLENS Scratch, Prick, Puncture (Percutaneous) Diagnostic Testing labeled in 50 % Glycerin are indicated for:
- Diagnosis of allergic conditions.
In addition to a carefully taken history, the use of glycerin-containing extracts in scratch, prick or puncture testing is an accepted method in the diagnosis of allergic conditions. Extracts of all allergens do not produce equivalent results in scratch, prick or puncture tests. The intensity of the skin reactions produced will be determined by two factors: the degree of sensitivity of the patient, and the nature of the allergenic extract applied.
Scratch, prick or puncture tests are not as sensitive as the intradermal test, but are safer and cause less discomfort. They may, therefore, be the method of choice when a large number of tests are needed, or when testing the pediatric patient. In some cases, where the relatively insensitive scratch, prick or puncture tests are negative or do not confirm the allergic history, follow-up intradermal tests may be positive. However, ANTIGENS PRODUCING LARGE 3 to 4+ SCRATCH, PRICK OR PUNCTURE TESTS SHOULD NOT BE TESTED INTRADERMALLY.
Certain diagnostics carry labelling which states Allergenic Extract for Diagnostic Use Only. Data to support the therapeutic use of products labelled with this statement have not been established.
1.1. Pediatrics
Allergenic extracts for diagnostic use have been given safely in infants and young children (see Section 7.1.3 Pediatrics).
1.2. Geriatrics
Geriatrics: Evidence from clinical studies and experience suggests that use in the geriatric population is associated with differences in safety or effectiveness (see Section 7.1.4 Geriatrics).
2. CONTRAINDICATIONS
- There are no known absolute contraindications to allergy skin testing. Patients with cardiovascular diseases or pulmonary may be at higher risk for severe adverse reactions (see Section 3 SERIOUS WARNINGS AND PRECAUTIONS BOX, Section 7 WARNINGS AND PRECAUTIONS, Section 9 DRUG INTERACTIONS).
- SERIOUS WARNINGS AND PRECAUTIONS BOX
Serious Warnings and Precautions
- The product is intended for use only by physicians who are experienced in the use of allergenic extracts, or for use under the guidance of an allergist.
- Allergenic extracts may potentially elicit a severe life-threatening systemic reaction (anaphylaxis), which can result in death. Therefore, emergency measures and personnel trained in their use must be available immediately in the event of such a reaction. Patients should be instructed to recognize adverse reaction symptoms and cautioned to contact the physician’s office if symptoms occur.
- 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 (see Section 9 DRUG INTERACTIONS).
- This product should never be injected intravenously.
Refer also to the Section 2 CONTRAINDICATIONS, Section 4 DOSAGE AND ADMINISTRATION, Section 5 OVERDOSAGE, Section 7 WARNINGS AND PRECAUTIONS, and Section 8 ADVERSE REACTIONS for further discussion.
4. DOSAGE AND ADMINISTRATION
4.1. Dosing Considerations
For individuals suspected to be at greater risk for anaphylaxis (for example, as indicated by a history of allergen-induced anaphylaxis), initiate percutaneous testing with a sequence of serial 10-fold dilutions of undiluted allergenic extract spaced 15-20 minutes apart (see Section 4.2 RECOMMENDED DOSE AND DOSAGE ADMINISTRATION).
There is a potential for systemic reactions to occur, but it must be remembered that allergenic extracts are highly potent in sensitive individuals and OVERDOSE could result in anaphylactic symptoms. Therefore, it is imperative that physicians administering allergenic extracts understand and be prepared for the treatment of severe reactions.
4.2. Recommended Dose and Dosage Adjustment
The dose is the same in patients of all age groups. Unless an individual is suspected to be at greater risk for anaphylaxis (see Section 4.1 DOSING CONSIDERATIONS), the initial starting dose is 1 drop (approximately 0.05 mL) of undiluted allergenic extract. The dose amount may be less when using self-loading skin test devices.
4.3. Reconstitution
See Section 4.2 RECOMMENDED DOSE AND DOSAGE ADJUSTMENT and Section 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
Table – Reconstitution
| Product | Vial Size | Volume of Diluent to be Added to Vial | Approximate Available Volume | Concentration |
| AP Dog Hair-Dander | 5 mL (Diagnostic) | N/A – Concentrate Used | 5 mL | 1:100 w/v |
AP Cattle Hair and Dander / AP Horse Hair and Dander | 5 mL (Diagnostic) | N/A – Concentrate Used | 5 mL | 1:50 w/v |
| Non-AP Epidermals/Inhalants | 5 mL (Diagnostic) | N/A – Concentrate Used | 5 mL | 1:10 w/v |
| UF Dog Hair and Dander | 5 mL (Diagnostic) | N/A – Concentrate Used | 5 mL | 1:650 w/v |
| Grass Pollen | 5 mL (Diagnostic) | N/A – Concentrate Used | 5 mL | 1:20 w/v |
| Insects | 5 mL (Diagnostic) | N/A – Concentrate Used | 5 mL | 1:10 w/v |
| Molds | 5 mL (Diagnostic) | N/A – Concentrate Used | 5 mL | 1:10 w/v or 1:1,000 w/v |
| Tree Pollen | 5 mL (Diagnostic) | N/A – Concentrate Used | 5 mL | 1:20 w/v or 1:50 w/v |
| Ragweed | 5 mL (Diagnostic) | N/A – Concentrate Used | 5 mL | 100 Amb a 1 UA/mL or 200 Amb a 1 UA/mL |
| Weed Pollen | 5 mL (Diagnostic) | N/A – Concentrate Used | 5 mL | 1:20 w/v |
4.4. Administration
All skin tests should be validated by appropriate positive control tests (e.g., histamine) and negative control tests [e.g., Glycerin, Sterile Albumin Saline with Phenol (0.4%), or Buffered Saline with Phenol (0.4%)]. The negative control test should be the same material used as a diluting fluid in the tested extracts. Diluting fluid is used in the same way as an active test extract.
Test sites should be examined at 15 and 20 minutes immediate reactions to allergens typically peak at 15 minutes. To prevent excessive absorption, wipe off antigens producing large reactions as soon as the wheal appears. Record the size of the reaction. Delayed reactions rarely occur from tests, so it may be helpful to examine the test sites in 24 hours.
Use of Self-Loading Devices. The criteria for interpretation of positive and negative results of percutaneous allergen tests (wheal diameter) are specific to the device used.
Use of Scarifiers and Spacing. Make scarifications at least 2.5 cm apart. Use more space between pollen tests to prevent smearing into adjacent sites. Hold the scarifier between the thumb and index finger, press the sharp edge of the instrument against the skin and twirl instrument rapidly. The scratch should disrupt only the outer layers of epidermis, but should not produce immediate oozing of blood. The amount of pressure needed to produce a satisfactory scratch will vary between patients according to the thickness or fragility of their skin. Experience will indicate the proper amount of pressure to exert in making the scratch. If the scarifier is kept sharp and the scratch made quickly, discomfort to the patient is minimized.
Use of Prick Test Needles. The skin is cleaned and single drops of each extract applied to the properly identified test sites. A small, sterile disposable needle, such as a 1/2-inch 26-gauge needle (with the bevel up), a bifurcated vaccinating needle, or a Prick Lancetter™ is inserted through the drop superficially into the skin, the skin lifted slightly and the needle withdrawn. No bleeding should be produced. After about 1 minute the extract may be wiped away.
Most Satisfactory Sites for Testing
Prior to testing, clean the skin area to be tested with ether or alcohol and allow to dry. Use a sterile instrument for each patient. The back or the volar surface of the arms are the most satisfactory sites for testing. Skin of the posterior thighs or abdomen may be used if necessary. Avoid very hairy areas where possible, since the reactions will be smaller and more difficult to interpret. The most satisfactory areas of the back are from the posterior axillary fold to 2.5 cm from the spinal column, and from the top of the scapula to the lower rib margins. The best areas of the arms are the volar surfaces from the axilla to 2.5 or 5 cm above the wrist skipping the antecubital space.
Use of Antigen Mixes
The use of mixed or unrelated antigens for skin testing is not recommended since in the case of a positive reaction it does not indicate which antigens are responsible, and in the case of a negative reaction it fails to indicate whether the individual antigens at full concentration would give a positive reaction.
The extracts for scratch, prick or puncture testing are supplied in dropper vials and should be kept in a rack or box in rows of 10 vials corresponding to the rows of tests to be applied to the skin.
Reading Skin Test Reactions
Testing is performed to identify patients that exhibit an allergic response at the site of administration. False positive/negative reactions may occur. A positive reaction consists of an urticarial wheal with surrounding erythema (resembling somewhat a mosquito bite reaction) larger than the control site. The smallest reaction considered positive is erythema with a central papule at least 3-5 mm in diameter. In some instances when there is no reaction at the control site, erythema may be considered an indication of sensitivity. In general, the size of wheal and erythema response correlates directly with the patient’s sensitivity to that allergen. If using self-loading devices, refer to the manufacturer's directions for use.
Interpretation of test results is variable depending on the test method and device employed. Manufacturers of commercially available skin test devices often recommend a specific grading system. When available, follow the manufacturer’s recommended grading system.
The sum of a skin response is the sum of the longest diameter and the mid-point orthogonal diameter.
Ragweed Pollen: (Short Ragweed or Giant and Short Ragweed Mixture) Amb a 1: Short Ragweed extract in 50 % glycerin containing 200 Units of Amb a 1/mL or Giant and Short Ragweed Mix in 50 % glycerin containing 100 Units of Amb a 1/mL, are usually used for scratch, prick or puncture testing.
Refer to the following table to determine the skin test sensitivity grade. The corresponding ƩE (sum of the longest diameter and the mid-point orthogonal diameters of erythema) is also presented.
| Grade | Erythema mm | Papule or Wheal mm | Corresponding mm Ʃ |
|---|---|---|---|
| 0 | <5 | <5 | <10 |
| ± | 5-10 | 5-10 | 10-20 |
| 1+ | 11-20 | 5-10 | 20-40 |
| 2+ | 21-30 | 5-10 | 40-60 |
| 3+ | 31-40 | 10-15a | 60-80 |
| 4+ | >40 | >15b | >80 |
| a. or with pseudopods. | |||
| b. or with many pseudopods. | |||
A positive skin reaction to any allergen must be interpreted in light of the patient’s history of symptoms, time of the year, known exposures, and eating habits.
THE SKIN TESTS ARE IN NO WAY A SUBSTITUTE FOR A CAREFUL ALLERGIC HISTORY. RATHER THEY SERVE AS ADDITIONAL INFORMATION TO AID IN IDENTIFYING CAUSATIVE ALLERGENS IN PATIENTS WITH ALLERGIC DISORDERS.
5. OVERDOSAGE
See Section 4 DOSAGE AND ADMINISTRATION and Section 8 ADVERSE REACTIONS.
For management of a suspected drug overdose, contact your regional poison control center.
6. DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING
In 5 mL dropper bottles of extract at 1:10 w/v, except pollens at 1:20 w/v; Short Ragweed at 200 Amb a 1 Units/mL; Giant and Short Ragweed Mixture at 100 Amb a 1 Units/mL; and AP™ Cattle Hair and Dander plus Horse Hair and Dander extracts at 1:50 w/v; AP™ Dog Hair and Dander at 1:100 w/v; and UF Dog 1:650 w/v; Negative Skin Test Control at 50% Glycerin v/v.
Weight per volume (w/v). For regular extracts this describes the extraction ratio, i.e., the amount of crude allergen added to the extracting fluid. A 1:10 extract, therefore indicates that the solution contains the extracted material from one gram of raw material added to each 10 mL of extracting fluid. The amount and composition of extracted materials will vary with the type of antigen, the extracting fluid, duration of extraction, pH, temperature, and other variables.
AP™ (acetone precipitated) extracts, if present, are prepared by reconstituting dry, allergenically active concentrates produced by precipitation process from extracts of raw materials. For those AP™ extracts labelled on a weight per volume (w/v) basis, the strength designation indicates the dry weight of finished (acetone) precipitate per volume of reconstituting fluid. For example, 1:50 (w/v) means that each gram of dry precipitate obtained from the original extract is reconstituted in 50 mL of solution.
Amb a 1 (UA/mL). Amb a 1 is considered the most important allergen in Ragweed Pollen and is measured by agar gel immune-diffusion against a reference standard established by the CBER. The concentration of Amb a 1 is expressed as units of Amb a 1 per mL of extract.
Table #1 – ALLERGENIC EXTRACT – NON-POLLENS Dosage Forms, Strengths, Composition and Packaging
| Route of Administration | Dosage Form / Strength / Composition | Non-medicinal Ingredients |
Percutaneous (scratch, prick/puncture) | Solution/ Refer to Product List Table | 50 % Glycerin (v/v) 0.5 % Sodium chloride (w/v) 0.275 % Sodium bicarbonate (w/v) |
Table #2 – ALLERGENIC EXTRACT – POLLENS Dosage Forms, Strengths, Composition and Packaging
| Route of Administration | Dosage Form / Strength / Composition | Non-medicinal Ingredients |
Percutaneous (scratch, prick/puncture) | Solution/ Refer to Product List Table | Variable % Glycerin or Phenol 0.5 % Sodium chloride (w/v) 0.275 % Sodium bicarbonate (w/v) |
Table #3 – NEGATIVE SKIN TEST CONTROL – GLYCERIN Dosage Forms, Strengths, Composition and Packaging
| Route of Administration | Dosage Form / Strength / Composition | Non-medicinal Ingredients |
Percutaneous (scratch, prick/puncture) | Liquid/No Active Pharmaceutical Ingredient | 50 % Glycerin (v/v) 0.5 % Sodium chloride (w/v) 0.275 % Sodium bicarbonate (w/v) In Water for Injection |
Table – Product List
ALLERGENIC EXTRACT - POLLENS ANTIGEN | CONC. | ALLERGENIC EXTRACT - POLLENS ANTIGEN (CONT.) | CONC. | |||
|---|---|---|---|---|---|---|
| TREE | ACACIA, GOLDEN | 1:20 w/v | WEED | CARELESS WEED | 1:20 w/v | |
| ALDER, RED | CARELESS/PIGWEED (CR) | |||||
| ASH, WHITE | COCKLEBUR, COMMON | |||||
| BEECH, AMERICAN | DOCK/SORREL MIX (DS) | |||||
| BIRCH MIX (PRW) | DOG FENNEL, EASTERN | |||||
| BOTTLEBRUSH TREE | GOLDENROD | |||||
| BOXELDER/MAPLE MIX (BHR) | KOCHIA | |||||
| CEDAR, MOUNTAIN | LAMBS QUARTERS | |||||
| CEDAR, RED | MARSHELDER/POVERTY MIX | |||||
| COTTONWOOD, COMMON | (BPT) | |||||
| CYPRESS, ARIZONA | NETTLE | |||||
| ELM, AMERICAN | PIGWEED, ROUGH REDOOT | |||||
| ELM, CHINESE | PLANTAIN, ENGLISH | |||||
| GUM, SWEET | RAGWEED, GIANT | |||||
| HACKBERRY | RAGWEED, WESTERN | |||||
| HICKORY, SHAGBARK | RUSSIAN THISTLE | |||||
| MAPLE, HARD/SUGAR | SAGEBRUSH, MUGWORT | |||||
| MELALEUCA | SCALE, WING | |||||
| MESQUITE TREE | SHEEP SORREL | |||||
| MULBERRY MIX (RW) | WEED MIX 2630 | |||||
| OAK MIX (RVW) | RAGWEED, MIX (GS) | 100 Amb a 1 UA/mL | ||||
| OAK, RED | RAGWEED, SHORT | 200 Amb a 1 UA/mL | ||||
| OLIVE TREE | ALLERGENIC EXTRACT NON-POLLENS ANTIGEN | CONC. | ||||
| PALM, QUEEN | ||||||
| PECAN TREE | EPIDERMAL | DOG HAIR & DANDER | 1:10 w/v | |||
| PINE MIX (LY) | FEATHER MIX | |||||
| PRIVET, COMMON | GUINEA PIG HAIR & DANDER | |||||
| SYCAMORE, AMERICAN | A.P. CATTLE HAIR & DANDER | 1:50 w/v | ||||
| TREE MIX #5 | A.P. HORSE HAIR & DANDER | |||||
| TREE MIX #11 | A.P. DOG HAIR & DANDER | 1:100 w/v | ||||
| WALNUT, BLACK | U.F. DOG HAIR & DANDER | 1:650 w/v | ||||
| WILLOW, BLACK | INSECT | COCKROACH, AMERICAN | 1:10 w/v | |||
| CYPRESS, BALD | 1:50 w/v | COCKROACH, GERMAN | ||||
| GRASS | BAHIA GRASS | 1:20 w/v | COCKROACH MIX | |||
| BROME, SMOOTH | FIRE ANT, RED | |||||
| CORN, COMMON | MOLD | ALTERNARIA TENUIS | 1:10 w/v | |||
| CULTIVATED | ASPERGILLUS FUMIGATUS | |||||
| JOHNSON GRASS | CEPHALOSPORIUM ACREMORIUM | |||||
| OATS, COMMON | ||||||
| CULTIVATED | EPICACCUM NIGRUM | |||||
| FUSARIUM VASINFECTUM | ||||||
HELMINTHOSPORIUM INTERSEMINATUM | ||||||
| MUCOR RACEMOSUS | ||||||
| PENICILLIUM NOTATUM | ||||||
| PHOMA HERBARUM | ||||||
| PULLULARIA PULLULANS | ||||||
| CANDIDA ALBICANS | ||||||
| CANDIDA ALBICANS | 1:1,000 w/v | |||||
7. WARNINGS AND PRECAUTIONS
General
Please see Section 3 SERIOUS WARNINGS AND PRECAUTIONS BOX.
Always have injectable epinephrine and a tourniquet available when tests are being made. Emergency resuscitation measures and personnel trained in their use should be available immediately in the event of a serious systemic or anaphylactic reaction not responsive to the above measures. See Section 8 ADVERSE REACTIONS.
Generally, 50-60 scratch, prick or puncture tests can be applied safely at one sitting. Patients whose history suggests severe sensitivity should have only 5-10 tests applied at a time and these tests applied to the volar surface of one arm. These tests should not all be of the same type of antigen; that is, all grass pollens, all weed pollens, all danders, etc. One or two tests from several classes of antigens should be applied at a time.
As soon as a large wheal begins to develop, wipe the antigen from it with a damp cotton sponge. After 30 minutes wipe off all the antigens with a damp cotton sponge, followed by a dry cotton sponge. Be careful not to wipe antigen from a positive reaction into an adjacent scratch site.
Carcinogenesis and Mutagenesis
Long-term studies in animals have not been conducted with allergenic extracts to determine their potential for carcinogenicity or mutagenicity. See Section 16 NON-CLINICAL TOXICOLOGY.
Cardiovascular
Patients with cardiovascular diseases or pulmonary diseases such as symptomatic asthma, and/or who are receiving cardiovascular drugs such as beta blockers, may be at higher risk for severe adverse reactions (see Section 3 SERIOUS WARNINGS AND PRECAUTIONS BOX, Section 9 DRUG INTERACTIONS). These patients may also be more refractory to the normal anaphylaxis treatment regimen.
Reproductive Health: Female and Male Potential
Fertility
Long-term studies in animals have not been conducted with allergenic extracts to determine their potential for impairment of fertility. See Section 7.1.1 Pregnant Women.
Respiratory
The presence of asthmatic signs and symptoms appear to be an indicator for severe reactions following allergy testing or 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 diagnostic testing or an allergy injection.
Sensitivity/Resistance
Excessively large local reactions or systemic reactions are more likely to occur if the patient is skin tested shortly after exposure to large amounts of antigen to which they are sensitive. Use caution when skin testing patients during a season when pollen is present or after exposure to inhalant allergens that produce symptoms. See Section 8 ADVERSE REACTIONS.
Skin
Allergenic extracts for percutaneous testing, used according to Section 4 DOSAGE AND ADMINISTRATION, produce erythema or erythema and wheal reactions in patients with significant IgE-mediated sensitivity to the relevant allergen. This allergic inflammatory response, although not completely understood, is thought to begin with reaction of antigen with IgE on the surface of basophils or mast cells, which initiates a series of biochemical events resulting in the production of histamine and other mediators. These, in turn, produce the immediate-type “wheal and flare” skin reaction. See Section 8.1 Adverse Reaction Overview.
If a severe local reaction occurs during scratch, prick or puncture testing, WIPE OFF test antigen. Large, persistent local reactions or minor exacerbations of the patient’s allergic symptoms may be treated by local cold applications and/or the use of oral antihistamines, but they should be considered a warning of possible severe systemic reactions.
7.1. Special Populations
7.1.1. Pregnant Women
Use in Pregnancy
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.
On the basis of histamine’s known ability to contract the uterine muscle, allergenic extracts should be used cautiously in pregnant women.
7.1.2. Breast Feeding
There are no current studies on the secretion of the allergenic extract components in human milk, or effect on the nursing infant. Because many drugs are excreted in human milk, caution should be exercised when allergenic extracts are administered to a nursing woman.
7.1.3. Pediatrics
The dose is the same in patients of all age groups.
Wheal sizes in response to allergen skin testing can be smaller in infants than in adults. The skin response to histamine parallels that for allergens; therefore, appropriate positive control skin tests should always be performed.
7.1.4. Geriatrics
The dose is the same in patients of all age groups. Skin test wheal size decreases with age, therefore, appropriate positive skin test controls should always be performed.
8. ADVERSE REACTIONS
8.1. Adverse Reaction Overview
Information to be Provided to the Patient
Patients should be instructed in the recognition of adverse reactions to diagnostic testing. Patients should be made to understand the importance of a 30-minute observation period, and be warned to return to the office promptly if symptoms occur after leaving.
Systemic Reactions
See Section 3 SERIOUS WARNINGS AND PRECAUTIONS BOX.
Frequency data for adverse reactions resulting from allergenic extract administration for testing and treatment show that risk is low.
It cannot be overemphasized that, under certain unpredictable combinations of circumstances, anaphylactic shock is a possibility. Other possible systemic reaction symptoms include fainting, pallor, bradycardia, hypotension, angioedema, cough, wheezing, conjunctivitis, rhinitis and urticaria.
If a systemic or anaphylactic reaction does occur, WIPE OFF test antigen, and apply epinephrine.
Emergency resuscitation measures and personnel trained in their use should be available immediately in the event of a serious systemic or anaphylactic reaction not responsive to the above measures. Patients should have an emergency anaphylaxis kit containing epinephrine available and be instructed in its use for emergency treatment of possible systemic reactions occurring at times after the patient has departed from treatment premises.
8.5. Post-Market Adverse Reactions
The most frequently reported serious and expected reactions is anaphylaxis.
9. DRUG INTERACTIONS
9.1. Serious Drug Interactions
Serious Drug Interactions
- Patients on beta blockers. See Section 9.4 Drug-Drug Interactions.
9.2. Drug Interactions Overview
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.
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. Topical steroids should be discontinued at the skin test site for at least 2-3 weeks before skin testing.
Tricyclic antidepressants such as doxepin should be withheld for at least 7 days before skin testing. Topical local anesthetics may suppress the flare responses and should be avoided in skin test sites.
9.4. Drug-Drug Interactions
The drugs listed in this table are based on either drug interaction case reports or studies, or potential interactions due to the expected magnitude and seriousness of the interaction (i.e., those identified as contraindicated).
Table #4 - Established or Potential Drug-Drug Interactions
| [Proper/Common name] | *Source of Evidence | Effect | Clinical comment |
| [Proper/Common name] | *Source of Evidence | Effect | Clinical comment |
| [Proper/Common name] | *Source of Evidence | Effect | Clinical comment |
Beta Blocking Agents (ex. Acebutolol, Atenolol, Bisoprolol, Carvedilol, Labetalol, Metoprolol, Nadolol, Nebivolol, Oxprenolol, Pindolol, Sotalol, Propranolol, Timolol) | C | Increased reactivity on skin test | Beta-blockers may attenuate the response to epinephrine in the treatment of anaphylactic reactions. Noncardioselective beta-blockers, in particular, can antagonize the bronchodilating effects of epinephrine by blocking beta-2 adrenergic receptors in smooth muscles of the bronchial tree. Consider alternative medication or withholding medication for 24 hours prior to skin test or an immunotherapy injection; consult prescribing physician on risks of switching or withholding medication. |
| C | Blocks cardio-stimulatory effects of epinephrine | ||
Beta2 Agonists (ex. Oral terbutaline and parenteral ephedrine) | T | Possible suppression of skin test response to allergen | Do not withhold if prescribed for asthma or other respiratory conditions. |
First/Second Generation Antihistamines (ex. Chlorpheniramine, Dexchlorpheniramine, Diphenhydramine, Promethazine, Azelastine nasal, Fexofenadine, Levocabastine) | C | Suppression of wheal & flare response to skin test | First- and second-generation antihistamines should be discontinued 2 to 3 days before skin tests with notable exceptions being cetirizine, hydroxyzine, clemastine, loratadine, and cyproheptadine which may suppress skin test responses for up to 11 days. |
Long acting antihistamines (ex. Cetirizine, Fexofenadine, Desloratadine, Hydroxyzine, Astemizole) | C | Suppression of wheal & flare response to skin test | Discontinue for at least 2 weeks prior to skin testing. |
Histamine2 Antagonists (ex. Ranitidine) | C | Mild suppression of skin test responses | Discontinue for 24 hours prior to skin testing. |
Prostaglandin D2 Inhibitors (ex. Indomethacin) | C | Increases wheal response on skin test | Withhold on day of skin testing. |
Tricyclic antidepressants (ex. Amitriptyline, Amoxapine, Desipramine, Doxepin, Imipramine, Maprotiline, Nortriptyline, Protriptyline, Trimipramine) | C | Suppression of wheal & flare response to skin test | Withhold for at least 7 days before skin testing. Consult with prescribing physician to determine whether the risk of severe depression in patients who discontinue their medication outweighs the benefits that could be obtained from skin testing. |
Benzodiazepines (ex. Clonazepam, Diazepam, Lorazepam, Midazolam, Alprazolam) | C, T | Suppression of wheal & flare response to skin test | Withhold for at least 7 days before skin testing. Consult with prescribing physician to determine whether the risk discontinuing medication outweighs the benefits that could be obtained from skin testing. |
Dopamine (ex. Pramipexole, Ropinirole, Rotigorine, Apomorphine, Bromocriptine, Amantadine, Fenoldopam, Piribedil, Aripiprazole, Brexpiprazole, Cabergoline, Cariprazine) (ex. Pramipexole, Ropinirole, Rotigorine, Apomorphine, Bromocriptine, Amantadine, Fenoldopam, Piribedil, Aripiprazold, Brexpiprazole, Cabergoline, Cariprazine) | C | Suppression of skin test response | Withhold on day of skin testing. |
Topical local anesthetics (ex. Lidocaine, Mepivacaine, Ropivacaine, Bupivacaine, Chloroprocaine, Etidocaine, Tetracaine, Benzocaine, Prilocaine, Procaine, Proparacaine, Cocaine, Dibucaine, Lidoderm, Tetracaine) | C | May suppress the flare (i.e. erythema) response to skin test | Avoid skin testing at sites of topical administration; or withhold on day of test. |
Oral corticosteroids (ex. Dexamethasone, Prednisolone, Betamethasone, Decadron, Beclomethasone Methylprednisolone, Medrol, Kenalog) | C | Suppression of skin test response | Avoid skin testing at sites where medication was applied for greater than 3 weeks. |
| T | Reduced efficacy of allergy immunotherapy | There is a theoretical risk of reduced immune response to allergy immunotherapy in patients requiring systemic corticosteroid treatment | |
Topical steroids (ex. Hydrocortisone, Betamethasone, Mometasone, Clobetasol, Fluocinonide, Diflorasone) | C | Suppression of skin test response | Avoid skin testing at sites where medication was applied for greater than 3 weeks. |
Omalizumab (Xolair) | C, T | Suppression of wheal & flare response to skin test | Discontinue for 5 half-lives (~100 days) prior to skin testing |
In Vitro Immunoglobulin (IVIG) | T | Possible suppression of skin test response | Discontinue for 5 half-lives (4-6 months) prior to skin testing |
Immunomodulating Biologics (ex. Tecfidera, Abetacept, Enbrel, Humira) | T | Reduced efficacy of allergy immunotherapy | There is a theoretical risk of reduced immune response to allergy immunotherapy in patients treated with biologics for other immune disorders. |
| * Legend: C = Case Study; CT = Clinical Trial; T = Theoretical | |||
9.5. Drug-Food Interactions
Interactions with food have not been established.
9.6. Drug-Herb Interactions
Interactions with herbal products have not been established.
9.7. Drug-Laboratory Test Interactions
Interactions with laboratory tests have not been established.
10. CLINICAL PHARMACOLOGY
10.1. Mechanism of Action
Allergenic extracts for scratch, prick or puncture testing, used according to the DOSAGE AND ADMINISTRATION section, produce erythema or erythema and wheal reactions in patients with significant IgE-mediated sensitivity to the relevant allergen. This allergic inflammatory response, although not completely understood, is thought to begin with reaction of antigen with IgE on the surface of basophils or mast cells, which initiates a series of biochemical events resulting in the production of histamine and other mediators. These, in turn, produce the immediate-type “wheal and flare” skin reaction.10.2 Pharmacodynamics
11. STORAGE, STABILITY AND DISPOSAL
The expiration date of the diagnostic extracts is listed on the container label. The extract should be stored at 2-8 °C and kept at this temperature range during office use.
12. SPECIAL HANDLING INSTRUCTIONS
A number of factors beyond our control could reduce the efficacy of this product or even result in an ill effect following its use. These include storage and handling of the product after it leaves our hands, diagnosis, dosage, method of administration, and biological differences in individual patients. Because of these factors, it is important that this product be stored properly, and that the directions be followed carefully during use.
For disposal of allergenic extracts, consider the use of a licensed disposal company or dispose of product in accordance with local, provincial, and federal regulations.
PART II: SCIENTIFIC INFORMATION
13. PHARMACEUTICAL INFORMATION
Drug Substance
Proper name: ALLERGENIC EXTRACT- POLLENS and ALLERGENIC EXTRACT- NON-POLLENS.
Various Proteins extracted from biological source materials:
- Chicken, Duck and Goose: Feathers
- Variable Bovine Type: Hair/Dander
- Mixed Breed Canine Type: Hair/Dander
- Variable Equine: Hair/Dander
Guinea Pig: Hair/Dander
- Whole Body Insects: Fire Ant and Cockroach
- Various Grasses
- Various Molds
- Various Trees
- Various Weeds
Pharmaceutical standard: Sterile extracts for scratch, prick or puncture (percutaneous) testing are supplied in dropper vials containing, in addition to the extract allergens and antigens, 50 % (v/v) glycerin as preservative, 0.5 % sodium chloride and 0.275 % sodium bicarbonate. The extracts may be labelled in terms of:
- 1. Weight to Volume (w/v)
- 2. Amb a 1 Units/mL
Product Characteristics: Appearance is clear to slightly opalescent. Parenteral Drug Products should be inspected visually for particulate matter and discoloration, prior to administration, whenever solution and container permit.
14. CLINICAL TRIALS
No clinical trials were sponsored by Jubilant HollisterStier LLC for the ALLERGENIC EXTRACT – POLLENS or ALLERGENIC EXTRACT – NON-POLLENS when the products were approved in 1997.
15. MICROBIOLOGY
No microbiological information is required for this drug product.
16. NON-CLINICAL TOXICOLOGY
General Toxicology: No long-term animal studies have been performed to evaluate carcinogenic or mutagenic potential or whether ALLERGENIC EXTRACT – POLLENS and ALLERGENIC EXTRACT – NON-POLLENS affects fertility in males or females.
Carcinogenicity: No long-term animal studies have been performed to evaluate carcinogenic potential on ALLERGENIC EXTRACT – POLLENS and ALLERGENIC EXTRACT – NON-POLLENS.