Candin

Candin information, interactions and side effects, Candida albicans Skin Test Antigen for Cellular Hypersensitivity (CANDIN® (candida albicans) ) 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.

CANDIN® (candida albicans) 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 sals, 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® (candida albicans) 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 sensitive 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 IRfrom 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® (candida albicans) 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).

INDICATIONS

CANDIN® (candida albicans) 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.

DOSAGE AND ADMINISTRATION

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If particles or discoloration are observed, the product should not be used and it should be discarded.

CANDIN® (candida albicans) 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® (candida albicans) 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.

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HOW SUPPLIED

CANDIN® (candida albicans) is supplied in a 1 mL multidose vial containing ten 0.1 mL doses.

Storage

Store between 2 – 8°C. Do not freeze.

SIDE EFFECTS

Local reactions to CANDIN® (candida albicans) 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® (candida albicans) , 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 required approximately 1 wee k 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® (candida albicans) 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 da ys (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® (candida albicans) have not been observed. However, all foreign antigens have the remote possibility of causing Type 1 anaphylaxis (14) and even death when 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® (candida albicans) 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.

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).

REFERENCES

1. Middleton, E. Jr., Ree d, C.E., Ellis, F.E., Adkinson, N.F., Jr., Yunginger, J.W., Busse, W.W., Allergy Principles and Practice, 4th Ed., Vol II, pp 963-982, Mosby, St. Louis, 1993.

13. Huebner, R.E., Schein, M.F., Hall, C.A., Barnes, S.A., Delayed-type hypersensitivity anergy in human immunodeficiency virus-infected persons screened for infection with Mycobacterium tuberculosis. Clin. Infect. Dis., 19: 26-32, 1994.

14. Klotz, S.D., Sweeney, M .J., Diens t, S., Klotz, L.R., Moeller, R.K., Rosenberg, S., Systemic anaphylaxis immediately following delayed hypersensitivity skin tests. Ann. Allergy, 49: 142-144, 1982.

15. Data on file, Allermed Laboratories, Inc.

17. Data on file, MedWatch, The FDA Medical Products Reporting Program, Rockville MD 20852.

WARNINGS

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® (candida albicans) . In persons with bleeding tendency, bruising and non-specific induration may occur due to the trauma of the skin test.

PRECAUTIONS

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).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been conducted with CANDIN® (candida albicans) to determine its potential for carcinogenicity, mutagenicity or impairment of fertility.

Pregnancy Category C

Animal reproduction studies have not been conducted with CANDIN® (candida albicans) . It is also not known whether CANDIN® (candida albicans) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. CANDIN® (candida albicans) should be given to pregnant women only if clearly needed.

Nursing Mothers

It is not known whether CANDIN® (candida albicans) 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® (candida albicans) have not been established in children.

Geriatric Use

Candin (candida albicans) 7 has not been adequately studied in geriatric patients. However, the DTH response to CANDIN® (candida albicans) may be diminished in geriatric patients, since the aging process is known to alter cell-mediated immunity (1).

REFERENCES

1. Middleton, E. Jr., Ree d, C.E., Ellis, F.E., Adkinson, N.F., Jr., Yunginger, J.W., Busse, W.W., Allergy Principles and Practice, 4th Ed., Vol II, pp 963-982, Mosby, St. Louis, 1993.

14. Klotz, S.D., Sweeney, M .J., Diens t, S., Klotz, L.R., Moeller, R.K., Rosenberg, S., Systemic anaphylaxis immediately following delayed hypersensitivity skin tests. Ann. Allergy, 49: 142-144, 1982.

CONTRAINDICATIONS

CANDIN® (candida albicans) should not be used after a previous unacceptable adverse reaction to this antigen or to a similar product, i.e , extreme hypersensitivity/allergy.

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