TUBERSOL

INDICATIONS AND USAGE TUBERSOL Tuberculin Purified Protein Derivative (Mantoux), is indicated to aid diagnosis of tuberculosis infection (TB) in persons at increased risk of developing active disease. The Centers for Disease Control and Prevention (CDC) have published guidelines regarding populations that would benefit from tuberculin skin testing (TST). Current recommendations can be accessed at: http://www.cdc.gov/tb/publications/factsheets/testing.htm. Previous BCG vaccination is not a contraindication to tuberculin testing. The skin-test results of BCG vaccinated persons can be used to support or exclude the diagnosis of TB infection. However, an FDA-approved interferon gamma release assay is preferred over tuberculin skin test for persons 5 years of age and older who were previously vaccinated with BCG. (8)

DOSAGE AND ADMINISTRATION Dosage Five (5) tuberculin units (TU) per test dose of 0.1 mL is the standard strength used for intradermal (Mantoux) testing. Method of Administration TUBERSOL is indicated for intradermal injection only. Do not inject intravenously, intramuscularly, or subcutaneously . If subcutaneous injection occurs, the test cannot be interpreted. Inspect for extraneous particulate matter and/or discoloration before use. If these conditions exist, do not administer the product. Use a separate syringe and needle for each injection. (12) The following procedure is recommended for performing the Mantoux test: The preferred site of the test is the volar aspect of the forearm. Avoid areas on the skin that are red or swollen. Avoid visible veins. Clean the skin site with a suitable germicide and allow the site to dry prior to injection of the antigen. Administer the test dose (0.1 mL) of TUBERSOL with a 1 mL syringe calibrated in tenths and fitted with a short, one-quarter to one-half inch, 26 or 27 gauge needle. Wipe the stopper of the vial with a suitable germicide and allow to dry before needle insertion. Then insert the needle gently through the stopper and draw 0.1 mL of TUBERSOL into the syringe. Avoid injection of excess air with removal of each dose so as not to over pressurize the vial and possibly cause seepage at the puncture site. Insert the point of the needle into the most superficial layers of the skin with the needle bevel pointing upward and administer the dose by slow intradermal injection . If the intradermal injection is performed properly, a definite pale bleb will rise at the needle point, about 10 mm ( 3 / 8 ") in diameter. This bleb will disperse within minutes. Do not dress the site. A drop of blood may appear at the administration site following injection. Blot the site lightly to remove the blood but avoid squeezing out the injected tuberculin test fluid. In the event of an improperly performed injection (i.e., no bleb formed), repeat the test immediately at another site, at least 2 inches from the first site and circle the second injection site as an indication that this is the site to be read. Inform the patient of the need to return for the reading of the test by a trained health professional. Self-reading may be inaccurate and is strongly discouraged. Interpretation of the Test The skin test should be read by a trained health professional 48 to 72 hours after administration of TUBERSOL. Skin test sensitivity is indicated by induration only; redness should not be measured. Measure the diameter of induration transversely to the long axis of the forearm and record the measurement in millimeters (including 0 mm). (7) The tip of a ballpoint pen, gently pushed at a 45° angle toward the site of injection, will stop at the edge of induration. Also record presence and size (if present) of necrosis and edema, although these are not used in the interpretation of the test. Positive Reactions Tuberculin reactivity may indicate latent infection, prior infection and/or disease with M. tuberculosis and does not necessarily indicate the presence of active tuberculous disease. Persons showing positive tuberculin reactions should be considered positive by current public health guidelines and referred for further medical evaluation. (7)(9) The repeated testing of uninfected persons does not sensitize them to TUBERSOL. (6)(7)(9) The significance of induration measurements in diagnosing latent TB infection must be considered in terms of the patient's history and the risk of developing active TB disease as indicated in Table 1. (9) Table 1: Criteria for tuberculin positivity, by risk group Reaction ≥5 mm of Induration Reaction ≥10 mm of Induration Reaction ≥15 mm of Induration HIV-positive persons Recent contacts of tuberculosis (TB) case patients Fibrotic changes on chest radiograph consistent with prior TB Patients with organ transplants and other immunosuppressed patients (receiving the equivalent of ≥15 mg/…

WARNINGS Hypersensitivity Allergic reactions may occur following the use of TUBERSOL even in persons with no prior history of hypersensitivity to the product components. (10) Epinephrine injection (1:1,000) and other appropriate agents used for the control of immediate allergic reactions must be immediately available. Syncope Syncope (fainting) can occur in association with administration of injectable medicines, including TUBERSOL. Procedures should be in place to avoid falling injury and to restore cerebral perfusion following syncope.

CONTRAINDICATIONS Allergy to any component of TUBERSOL or an anaphylactic or other allergic reaction to a previous test of tuberculin PPD is a contraindication to the use of TUBERSOL. (See DESCRIPTION and HOW SUPPLIED .) TUBERSOL should not be administered to: Persons who have had a severe reaction (e.g., necrosis, blistering, anaphylactic shock, or ulcerations) to a previous TST, Persons with documented active tuberculosis or a clear history of treatment for TB infection or disease, (9) Persons with extensive burns or eczema.

Drug Interactions Reactivity to the test may be depressed or suppressed in persons who are receiving corticosteroids or immunosuppressive agents. (7) Reactivity to TUBERSOL may be temporarily depressed by certain live virus vaccines (measles, mumps, rubella, oral polio, yellow fever, and varicella). If a parenteral live attenuated virus vaccine has been administered recently, tuberculin testing should be delayed for >1 month after vaccination. (7)(11) (See Interpretation of the Test .) When tuberculin screening is required at the same time as a measles-containing vaccine or other parenteral live attenuated virus vaccine, simultaneous administration of TUBERSOL and the vaccine at separate sites is the preferred option.

Pregnancy Animal reproduction studies have not been conducted with TUBERSOL. It is also not known whether TUBERSOL can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. TUBERSOL should be given to a pregnant woman only if clearly needed.

Nursing Mothers It is not known whether TUBERSOL is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when TUBERSOL is administered to a nursing woman.

ADVERSE REACTIONS Induration at the TUBERSOL injection site is the expected reaction for a positive skin test. (See Interpretation of the Test .) The information pertaining to adverse events has been compiled from historical clinical studies and post-marketing experience with TUBERSOL. General disorders and administration site conditions Injection site pain, injection site pruritus and injection site discomfort. Injection site erythema or injection site rash (without induration) occurring within 12 hours of testing. These reactions do not indicate TB infection. Injection site hemorrhage and injection site hematoma up to three days after the administration of the test. Injection site vesicles, injection site ulcer or injection site necrosis in highly sensitive persons. Injection site scar as a result of strongly positive reactions. Pyrexia Immune system disorders Hypersensitivity, including anaphylaxis/anaphylactic reactions, angioedema, urticaria Respiratory, thoracic, and mediastinal disorders Stridor, dyspnea Skin and subcutaneous tissue disorders Rash, generalized rash Nervous system disorders Presyncope, syncope (including syncope associated with tonic-clonic movements and other seizure-like activity) sometimes resulting in transient loss of consciousness with injury Reporting of Adverse Events To report SUSPECTED ADVERSE REACTIONS, contact the Pharmacovigilance Department, Sanofi Vaccines US Inc., Discovery Drive, Swiftwater, PA 18370 or call 1-800-822-2463 (1-800-VACCINE) or Food and Drug Administration (FDA) MEDWATCH Program at 1-800-332-1088 and www.fda.gov/medwatch.