CANDIN
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candida albicans injection
Physicians Total Care, Inc.
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Candida albicans Skin Test Antigen for Cellular Hypersensitivity (CANDIN® ) is a clear, colorless, sterile solution with a pH of 8.0 - 8.5. The
antigen should be administered intradermally according to the directions included under DOSAGE AND ADMINISTRATION of this package insert.
CAN DIN ® is made from the culture filtrate and cells of two strains of Candida albicans. The fungi are propagated in a chemically defined medium consisting of inorganic salts, biotin and sucrose. Lyophilized source material is extracted with a solution of 0.25% NaCl, 0.125% NaHCO3 and 50% v/v glycerol. The concentrated extract is diluted with a solution of 0.5% NaCl, 0.25% NaHCO3 , 0.03% Albumin (Human) USP, 8 ppm polysorbate 80 and 0.4% phenol.
The potency of CANDIN® is measured by DTH skin tests in humans. The procedure involves concurrent (side-by-side) testing of production lots with
an Internal Reference (IR), using sen sitive adults who have been previously screened and qualified to serve as test subjects. The induration response at 48 hours elicited by 0.1 mL of a production lot is measured and compared to the response elicited by 0.1 mL of the IR. The test is satisfactory if the potency of the production lot does not differ more than ± 20% from the potency of the IR, when analyzed by the paired t-test (two-tailed) at a p value of 0.05.
The potency of the IR is monitored by DTH skin testing. Persons included in the potency assay are qualified as test subjects by receiving four skin tests with the IR from which a mean induration response (mm) is calculated. Current skin tests with the IR must show that the potency of the IR has not changed more than ± 20% from the mean qualifying response in the same test subjects, when analyzed by the paired t-test (two-tailed) at a p value of 0.05. The required induration response at 48 hours to the IR is 15 mm ± 20%.
Skin Test Strength
The skin-test strength of CANDIN® has been determined from dose-response studies in healthy adults (see CLINICAL PHARMACOLOGY). The product is intended to elicit an induration response $5 mm in immunologically competent persons with cellular hypersensitivity to the antigen (see DOSAGE AND ADMINISTRATION).
Cellular or delayed-type hypersensitivity (DTH) can be assessed by intracutaneous testing with bacterial, viral and fungal antigens to which most
healthy persons are sensitized. A positive skin test denotes prior antigenic exposure, T-cell competency and an intact inflammatory response (1,2). The reaction usually peaks 48 hours after antigen is introduced into the skin and is manifest as induration at the test site.
Recall antigens may be usefu l in evaluating delayed-type hypersensitivity by eliciting positive induration reactions 48 to 72 hours after intracutaneous administration. Except for mumps skin test antigen, most commonly used recall antigens were developed for other purposes, and the size of the reaction elicited may not be directly related to cellular immunity because of variability in antigen source and dose and skin test administration and measurement techniques. Useful antigens are those which elicit a reaction size $ 5 mm in more than 50% of normal individuals. The combination of results from skin testing with more than one antigen should result in detection of DTH in at least 95% of normal subjects (2).
The inflammatory response associated with the DTH reaction is characterized by an infiltration of lymphocytes and macrophages at the site of
antigen deposition. Specific cell types that appear to play a major role in the DTH response include CD4 + and CD8 + T lymphocytes which leave the recirculating lymphocyte pool in response to exogenous antigen (3). Both CD4 + and CD8 + lymphocytes have been recovered from DTH reactions elicited by Candida antigen (4).
In the literature, the incidence of DTH reactions to unstandardized Candida antigens has been reported to vary from 52 - 89%, depending upon the
strength of the antigen and the mm induration required for a positive test (5,6,7,8,9).
Published studies have reported that antigens of Candida albicans are useful in the assessment of diminished cellular immunity in persons infected with human immunodeficiency virus (10,11). Responses to DTH antigens have been reported to have prognostic value in patients with cancer (5).
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| Age range (years) | Number reactions > 5 mm at 48 hours | Response overall |
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Study 1 (a)
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Male | 16 | 25 - 83 | 14 |
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Female | 2 | 61 - 69 | 2 | 78% |
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Study 2
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Male | 20 | 23 - 63 | 13 |
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Femaile | 15 | 28 - 62 | 8 | 60% |
(a) Control group in Table 2.
Response to CANDIN® in Healthy Adults (Table 1): In one group of 18 subjects, 14 (78%) of the individuals reacted to CANDIN® with an induration response of $ 5 mm at 48 hours. In a second study of 35 subjects, 21 (60%) had induration reactions $ 5 mm at 48 hours. In this study, 65% of males tested positive compared to 53% of females; the mean induration in responding males was 12.8 mm and in responding females was 13.0 mm. When subjects in these studies w ere tested with two reagents, CANDIN® and Mumps Skin Test Antigen, 92% were positive to at least one antigen, a higher response rate than to either antigen used alone (15).
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Group
| Classification*
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| Zidovudine Use | Range
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| Induration (mm) | N >5 (mm) | %
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AIDS | A3,B3,C | 32 | 14 | 4 - 483 | 145 | 3.35 (a) | 9 | 28 (b) |
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HIV POS. | A1,A2, B1,B2 | 28 | 13 | 201-1065 | 455 | 5.67 | 15 | 54 |
CONTROL | --- | 18 | 0 | 554-1876 | 869 | 8.03 | 14 | 78 |
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| Age Range | Number reactions > 5 mm at 48 hours | Response
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Study 1
| 18 | 52 - 75 | 5 | 28% |
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Study 2
| 20 | 47 - 81 | 0 | 0% |
CANDIN® is indicated for use as a recall antigen for detecting DTH by intracutaneous (intradermal) testing. The product may be useful in evaluating
the cellular immune response in patients suspected of having reduced cellular hypersensitivity. Because some persons with normal cellular immunity are not hypersensitive to Candida, a response rate less than 100% to the antigen is to be expected in normal individuals. Therefore, the concurrent use of other licensed DTH skin test antigens is recommended. The product should not be used to diagnose or treat Type 1 allergy to Candida albicans.
CANDIN® should not be used after a previous unacceptable adverse reaction to this antigen or to a similar product, i.e., extreme hypersensitivity/allergy
As has been observed with other, unstandardized, antigens used for DTH skin testing (14), it is possible that some patients may have exquisite immediate hypersensitivity to CANDIN®. In persons with bleeding tendency, bruising and non-specific induration may occur due to the trauma of the skin test.
General: Physicians using this product must have available the facilities and medications necessary to treat all potential local and systemic side effects that can occur from the injection of an antigenic substance. Epinephrine (1:1,000) must be immediately available. The patient, or parent or guardian, should be questioned about previous reactions to this product or a similar product.
The antigen must be injected intradermally as superficially as possible, causing a distinct, sharply defined bleb at the skin test site. An unreliable
reaction may result if the product is injected subcutaneously. It must not be given intravenously; care should be taken to avoid injection into a blood vessel.
A separate sterile syringe and needle should be used for each patient to prevent transmission of infectious agents. Needles should be disposed of
properly and should not be recapped. Delayed or cellular hypersensitivity reactions can be diminished or completely suppressed if the person has received corticosteroids (see DRUG INTERACTIONS).
Patient Information: Local reactions to CANDIN® can include redness, swelling, pruritus, excoriation and discoloration of the skin. These
reactions usually subside within hours or d ays after administration of the skin test. In some patients, skin discoloration may persist for several weeks. Progression of the DTH reaction to vesiculation, necrosis and ulceration are possible. Patients should be informed that all foreign antigens have the remote possibility of causing Type I anaphylactic reactions that may require the administration of epinephrine and other drugs or emergency procedures and may be life threatening in some cases. Patients should report any serious adverse reactions to their health care provider.
Drug Interactions: Pharmacologic doses of corticosteroids may variably suppress the DTH skin test response after two weeks of therapy. The
mechanism of suppression is believed to involve a decrease in monocytes and lymphocytes, particularly T-cells. The skin test response usually returns to the pretreatment level within several weeks after steroid therapy is discontinued (1).
Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals have not been conducted with CANDIN® to determine its potential for carcinogenicity, mutag enicity or impairment of fertility.
Pregnancy Category C: Animal reproduction studies have not been conducted with CANDIN®. It is also not known whether CANDIN® can cause
fetal harm when administered to a pregnant woman or can affect reproduction capacity. CANDIN® should be given to pregnant women only if clearly needed.
Nursing Mothers: It is not known whether CANDIN® is excreted in human milk. Because drugs may be excreted in human milk, caution should be
exercised when this product is administered to a nursing woman.
Pediatric Use: The safety and effectiveness of intradermally administered CANDIN® have not been established in children.
Geriatric Use: Candin7 has not been adequately studied in geriatric patients. However, the DTH response to CANDIN® may be diminished in geriatric patients, since the aging process is known to alter cell-mediated immunity (1).
Local reactions to CANDIN® have included swelling, pruritus and vesiculation. Reactions involving necrosis and ulceration have not been
observed, but such reactions are theoretically possible and might occur in persons with exquisite cellular hypersensitivity to the antigen. Local
reactions may be treated with a cold compress and topical steroids. Severe local reactions may require additional measures as appropriate.
In a published study (13) of 479 HIV positive adults tested with CANDIN® , adverse local reactions were observed in six subjects as follows: pruritus (three), swelling at the test site (one), vesiculation (one) and vesiculation with weeping edema (one). Pruritus and swelling cleared within 48 hours; vesiculation with edema req uired approximately 1 week to resolve (15).
In two studies involving 171 persons discussed under CLINICAL PHARMACOLOGY in Tables 1, 2, 3, and text, one adverse reaction was
observed. This reaction consisted of induration 22 x 55 mm at 48 hours which resolved within 1 week (15).
Testing of CANDIN® for consistency of potency is performed in healthy human subjects who are known to be skin-test positive to the antigen. In 58 subjects tested to-date, there have been no cases of Type 1 allergy manifested as either generalized or adverse local reactions. One subject had induration with a central vesicle which subsided within a few days (15).
Severe local reactions, including rash, vesiculation, bullae, dermal exfoliation and cellulitis, have been reported to MedWatch for unstandardized
allergenic extracts of Candida albicans used for anergy testing (17).
Systemic reactions to CANDIN® have not been observed. However, all foreign antigens have the remote possibility of causing Type 1 anaphylaxis (14) and even death w hen injected intradermally. Systemic reactions usually occur within 30 minutes after the injection o f antigen and may include the following symptoms: sneezing, coughing, itching, shortness of breath, abdominal cramps, vomiting, diarrhea, tachycardia, hypotension and respiratory failure in severe cases. Systemic allergic reactions including anaphylaxis must be immediately treated with Epinephrine HCL 1:1,000. Additional measures may be required, depending upon the severity of the reaction.
Immediate Hypersensitivity reactions to CANDIN® occur in some individuals. These reactions are characterized by the presence of an
edematous hive surrounded by a zone of erythema. They occur approximately 15 - 20 minutes after the intradermal injection of the antigen.
The size of the immediate reaction varies depending upon the sensitivity of the individual. Immediate hypersensitivity reactions were observed in the control and HIV-infected (AIDS and HIV positive) subjects reported in Table 2 as follows: HIV-infected subjects (20% with erythema of 10 - 21 mm in diameter; 13% with erythema of 5 - 9 mm). Control subjects (22% with erythema of 10 - 15 mm; 5% with erythema of 8.5 mm). Cancer subjects (Group 1, Table 3), 17% with erythema of 10 - 24 mm and 11% with erythema of 6 - 9 mm.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container used and it should be discarded.
CANDIN® should be administered intradermally on the volar surface of the forearm or on the outer aspect of the upper arm. The test dose is 0.1 mL. The skin should be cleansed with 70% alcohol before applying the skin test. The intradermal injection must be given as superficially as possible causing a distinct, sharply defined bleb. An unreliable reaction may result if the product is injected subcutaneously. A positive DTH reaction to CANDIN® consists of induration $ 5 mm.
The time required for the induration response to reach maximum intensity varies with the individual. The reaction usually begins within 24 hours and
peaks between 24 and 48 hours. The skin test should be read at 48 hours by visually inspecting the test site and palpating the indurated area. Measurements should be made across two diameters as shown in the figure below. The mean of the longest and midpoint orthogonal diameters of the indurated area should be reported as the DTH response. For example, a reaction that is 10 mm (longest diameter) by 8 mm (midpoint orthogonal diameter) has a sum of 18 mm and a mean of 9 mm. The DTH response is therefore 9 mm.
Area of induration (shaded area) Longest diameter (a) 10 mm
Orthogonal diameter (b) 8 mm
10 mm + 8 mm = 18 mm (Sum of Induration)
18 mm = 9 mm (Mean of Induration)
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CANDIN® is supplied in a 1 mL multidose vial containing ten 0.1 mL doses NDC 54868-5559-0.
STORAGE
Store between 2 - 8°C. Do not freeze..
CANDIN
candida albicans injection |
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Marketing Information | |||
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
BLA | BLA102211 | 03/23/2006 | 06/30/2011 |
Labeler - Physicians Total Care, Inc. (194123980) |
Establishment | |||
Name | Address | ID/FEI | Operations |
Physicians Total Care, Inc. | 194123980 | relabel |
Revised: 03/2012 Physicians Total Care, Inc.