Coccidioides Immitis Spherule-Derived Skin Test Antigen

Description

11 DESCRIPTION Spherusol ® is a sterile aqueous solution of extracts of C. immitis spherules. The multi-dose vial contains 0.9% sodium chloride and 0.014% sodium borate with 0.4% phenol as a preservative. Residual thimerosal from the manufacturing process is present at a concentration of ≤0.0001% (<0.05 mcg mercury/0.1 mL dose). Each 0.1 mL dose contains 1.27 mcg of spherule-derived antigen. The potency of each lot of Spherusol ® is determined in sensitized guinea pigs.

What Is Coccidioides Immitis Spherule-Derived Skin Test Antigen Used For?

1 INDICATIONS AND USAGE Spherusol ® is a skin test antigen indicated for the detection of delayed-type hypersensitivity to Coccidioides immitis in individuals with a history of pulmonary coccidioidomycosis. Spherusol ® is approved for use in individuals 18-64 years of age. The use of Spherusol ® to detect delayed-type hypersensitivity responses in a general population with unknown exposure to C. immitis has not been evaluated. Persons with acute or disseminated coccidioidomycosis may not develop a delayed-type hypersensitivity response to Spherusol ® . Persons with immunodeficiency and a history of coccidioidomycosis may not develop a delayed-type hypersensitivity response to Spherusol ® . Spherusol ® is a skin test antigen indicated for the detection of delayed-type hypersensitivity to Coccidioides immitis in individuals with a history of pulmonary coccidioidomycosis. Spherusol ® is approved for use in individuals 18-64 years of age. The use of Spherusol ® to detect delayed-type hypersensitivity responses in a general population with unknown exposure to C. immitis has not been evaluated. Persons with acute or disseminated coccidioidomycosis may not develop a delayed-type hypersensitivity response to Spherusol ® . Persons with immunodeficiency and a history of coccidioidomycosis may not develop a delayed-type hypersensitivity response to Spherusol ® .( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION A single 0.1 mL intradermal injection. Induration at injection site to be evaluated 48 hours after administration. ( 2.1 , 2.3 ) 2.1 Preparation for Administration Spherusol ® is a clear, colorless sterile solution for intradermal administration. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If any of these conditions exists, the skin test antigen should not be administered. 2.2 Administration: Spherusol ® is administered as a 0.1 mL dose by intradermal injection to the volar surface of the forearm using a tuberculin syringe (0.5 or 1.0 mL) and a ½ inch 26-27 gauge needle. The needle should be inserted bevel side up in the skin at a 15-20 degree angle. Intradermal injection of 0.1 mL Spherusol ® will result in a bleb 5-10 mm in diameter at the injection site. 2.3 Skin Test Assessment The injection site should be assessed for induration at 48 hours (±4 hours) following administration. The response to the skin test should be measured by taking the mean of the orthogonal diameters of the area of induration. A mean induration of ≥ 5 mm is considered a positive delayed-type hypersensitivity response to Spherusol ® . Repeat administration of Spherusol ® has not been evaluated.

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The most commonly reported local adverse reactions were itching and swelling (>75%) and pain (>15%) within 7 days of administration.( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Nielsen Biosciences, Inc. at (855) 855-1212 or Food and Drug Administration (FDA) at 1-800-332-1088 or www.vaers.hhs.gov . ( 6.3 ) 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a skin test antigen cannot be directly compared to rates in the clinical trials of another skin test antigen, and may not reflect the rates observed in practice. As with any skin test antigen, there is the possibility that broad use of Spherusol ® could reveal adverse reactions not observed in clinical trials. In a double-blinded placebo-controlled clinical trial conducted in areas of the U.S. endemic for C. immitis (Bakersfield, CA and Tucson, AZ), 54 adults (23-64 years of age) with a history of pulmonary coccidioidomycosis of at least 45 days duration, diagnosed by clinical findings, radiography and serological and/or mycological evidence of the disease, received a single dose of Spherusol ® concomitantly with two licensed skin test extracts (Candin ® and Trichophyton) and two controls (product diluent [thimerosal ≤0.0001%] and saline). Each intradermal injection of 0.1 mL of reagent was given at pre-determined sites on the right and left forearms. Solicited local adverse reactions and systemic adverse events occurring within 7 days after injection were recorded by study subjects via diary card. These events were also recorded on case report forms (CRFs) by study personnel during clinical visits 48 hours and 7 days following injections. Diary cards and CRFs did not record solicited local reactions by specific site. Local adverse reactions and systemic adverse events that occurred within 7 days were monitored until resolution. Reports of unsolicited adverse events and serious adverse events that occurred within 7 days after administration were collected on the diary cards or reported at study visits. Table 1 lists the percentage of subjects reporting solicited local reactions (at any site) and solicited systemic adverse events within 7 days following the administration of Spherusol ® , Candin ® , Trichophyton, diluent control and placebo control. Table 1. Frequency of Solicited Local Reactions and Systemic Adverse Events within 7 days of Administration of Spherusol ® , Candin ® , Trichophyton, Diluent Control and Saline Control in Subjects with a History of Pulmonary Coccidioidomycosis (N=53) Symptom Frequency (%) Local ∗ Any Mild Moderate Severe Itching 85 36 47 2 Swelling 79 36 41 2 Pain 17 13 4 0 Necrosis/Ulceration 4 2 0 2 Systemic Increased heart rate 4 2 2 0 Weakness 6 2 4 0 Faintness 0 0 0 0 Dizziness 2 2 0 0 Nausea/cramps 2 2 0 0 Flu-like symptoms 7 2 6 0 Difficulty breathing/shortness of breath 0 0 0 0 Any = Percentage of subjects experiencing adverse event of any intensity; Mild = Barely noticeable, not bothersome; Moderate = Distinctly noticeable discomfort; Severe = Needs medical attention. ∗ Local reactions occurring at any injection site Of subjects with severe reactions, one subject required treatment with oral corticosteroids for ulceration and swelling. Based on investigator's determination the reaction was at the site of Trichophyton injection. All severe reactions resolved without sequelae. During the 7 days following administration two subjects reported unsolicited adverse events: one subject reported joint pain, fatigue, cough, sensitivity at a test site (test site not specified), and one subject with erythema immediately after administration (test site not specified). The intensities of these unsolicited adverse events were not recorded. No serious adverse events or deaths were reported during the clinical study. 6.2 To report SUSPECTED ADVERSE REACTIONS, contact Nielsen BioSciences, Inc. at (855) 855-1212 or...

Drug Interactions

7 DRUG INTERACTIONS Corticosteroids and immunosuppressive agents may suppress the response to the skin test.( 7.1 ) 7.1 Corticosteroids and Immunosuppressives Corticosteroids and Immunosuppressive agents may suppress the response to the skin test. Pharmacologic doses of corticosteroids may suppress the response to skin test antigens after two weeks of therapy. The mechanism of suppression is thought to involve a decrease in monocytes and lymphocytes, particularly T-cells. The normal DTH response usually returns to pre-treatment levels within several weeks after steroid therapy is discontinued. (5) The use of Spherusol ® has not been evaluated during or following the use of corticosteroids or immunosuppressive agents. 7.2 Antifungal Medications It is not known if concurrent treatment with antifungal medications interferes with delayed-type hypersensitivity responses to Spherusol ® in patients with a history of pulmonary coccidioidomycosis.

Contraindications

4 CONTRAINDICATIONS A severe allergic reaction (e.g., anaphylaxis) to Spherusol ® , or any component of Spherusol ® or other coccidioidin products is a contraindication to administration. Severe allergic reaction (e.g., anaphylaxis) to Spherusol ® , or any component of Spherusol ® or other coccidioidin products. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy The safety and effectiveness of Spherusol ® in pregnant women have not been established. Pregnancy Category C Animal reproduction studies have not been conducted with Spherusol ® . It is also not known whether Spherusol ® can cause fetal harm when administered to a pregnant woman or affect reproduction capacity. Spherusol ® should be given to a pregnant woman only if clearly needed.

8.3 Nursing Mothers The safety and effectiveness of Spherusol ® in nursing women have not been established. It is not known whether Spherusol ® is excreted in human milk. However, because the potential exists for Spherusol ® to be excreted in human milk, caution should be exercised when administering Spherusol ® to a nursing woman.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Spherusol ® is available in 1 mL multidose vial. NDC# 59584-140-01: multi-dose vial. Store refrigerated at 2° to 8°C (35° to 46°F). Do not freeze. Discard if frozen. Do not use after expiration date.