"The U.S. Food and Drug Administration is alerting hospitals, health care professionals, and patients of a voluntary recall of all non-expired drug products produced and distributed for sterile use by Abrams Royal Compounding Pharmacy in Dallas, T"...
Tuberculin Purified Protein Derivative (Mantoux) - TUBERSOL (tuberculin purified protein) ® is indicated as an aid in the detection of infection with M. tuberculosis.
For the intradermal (Mantoux) tuberculin test, the dose is 5 U.S.units (TU) per test dose of 0.1 mL.
PPD tuberculin may be used as an aid in the diagnosis of tuberculosis infection in persons with a history of BCG vaccination.
HIV-infected individuals should receive tuberculin skin testing as recommended.13,18
DOSAGE AND ADMINISTRATION
Parenteral biological products should be inspected visually for extraneous particulate matter and/or discoloration before administration. If these conditions exist, the product should not be administered.
In addition, it is essential that the physician or nurse record the test results in millimeters of induration, including 0, in the permanent medical record of each patient. This permanent medical record should contain the name of the product, date given, dose, manufacturer and lot number. Reporting results only as negative or positive is not satisfactory.
The Test: The Mantoux test is performed by injecting intradermally, with a syringe and needle, 0.1 mL of TUBERSOL®. For the intradermal (Mantoux) tuberculin test, the dose is 5 US units (TU) per test dose of 0.1 mL.
The result is read 48 to 72 hours after administration. Only palpable induration is considered in interpreting the test.
Two-step testing should be performed on the initial testing if tuberculin testing will subsequently be conducted at regular intervals, for instance among health-care workers.9 If the first test showed either or no reaction or a small reaction, the second test should be performed one to four weeks later. Both tests should be read and recorded at 48 to 72 hours.9 Patients with a second tuberculin test (booster) response of 10 mm or more should be considered to have experienced past or old infection.14
Persons who do not boost when given repeat tests at one week, but whose tuberculin reactions change to positive after one year, should be considered to have newly acquired tuberculosis infection and managed accordingly.15
Method of Administration: The following procedure is recommended for performing the Mantoux test:
- The preferred site of the test is the flexor (volar) surface of the forearm.
- The skin site is first cleansed with a suitable germicide and should be dry prior to injection of the antigen.
- The recommended test dose (0.1 mL) of Tuberculin PPD is administered with a 1 mL syringe calibrated in tenths and fitted with a short, one-quarter to one-half inch, 26 or 27 gauge needle.
- The rubber cap of the vial should be wiped with a suitable germicide and should be dry prior to needle insertion. The needle is then inserted gently through the cap and 0.1 mL of Tuberculin PPD is drawn into the syringe. Care should be taken to avoid injection of excess air with removal of each dose so as to not overpressurize the vial thus causing possible seepage at the site of puncture.
- The point of the needle is inserted into the epidermal (most superficial) layers of the skin with the needle bevel pointing upward. 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. No dressing is required.
In the event of an improperly performed injection (i.e. no bleb formed), the test should be repeated immediately at another site.
Interpretation of the Test: The test should be read 48 to 72 hours after administration of TUBERSOL (tuberculin purified protein) ®. Sensitivity is indicated by induration only and any erythema is disregarded. Distinctly palpable induration should be measured in millimeters (mm) transversely to the long axis of the forearm and recorded in mm.14
Sensitivity to tuberculin, may be the result of a previous infection with mycobacteria. This infection, likely due to M. tuberculosis, may have occurred years ago or may be of recent origin.
According to the most recent recommondations, reactions should be interpreted as follows:13,29
1. An induration of ≥ 5 mm is classified as positive in:
- persons who have human immunodeficiency virus (HIV) infection or risk factors for HIV infection but unknown HIV status;
- persons who have had recent close contact* with persons who have active tuberculosis (TB);
- persons who have fibrotic chest radiographs (consistent with healed TB).
2. An induration of ≥ 10 mm is classified as positive in all persons who do not meet any of the criteria above but who have other risk factors for TB, including:
- injecting-drug users known to be HIV seronegative;
- persons who have other medical conditions that reportedly increase the risk for progressing from latent TB infection to active TB (e.g., silicosis; gastrectomy or jejuno-ileal bypass; being ≥ 10% below ideal body weight; chronic renal failure with renal dialysis; diabetes mellitus; high-dose corticosteroid or other immunosuppressive therapy; some hematologic disorders, including malignancies such as leukemias and lymphomas; and other malignancies);
- children < 4 years of age.
- persons born in countries in Asia, Africa, the Caribbean, and Latin America that have high prevalence of TB;
- persons from medically underserved, low-income populations;
- residents of long-term-care facilities (e.g., correctional institutions and nursing homes);
- persons from high-risk populations in their communities, as determined by local public health authorities.
3. An induration of ≥ 15 mm is classified as positive in persons who do not meet any of the above criteria.
4.Recent converters are defined on the basis of both size of induration and age of the person being tested:
- ≥ 10 mm increase within a 2-year period is classified as a recent conversion for persons < 35 years of age;
- ≥ 15 mm increase within a 2-year period is classified as a recent conversion for persons ≥ 35 years of age.
5. PPD skin-test results in health-care workers (HCWs)
- In general, the recommendations in section 1, 2, and 3 above should be followed when interpreting skin test results in HCWs.
However, the prevalence of TB in the facility should be considered when choosing the appropriate cut-point for defining a positive PPD reaction. In facilities where there is essentially no risk for exposure to M. tuberculosis (i.e., minimal- or very low-risk facilities), an induration ≥ 15 mm may be a suitable cut-point for HCWs who have no other risk factors. In facilities where TB patients receive care, the cut-point for HCWs with no other risk factors may be ≥ 10 mm.
- A recent conversion in an HCW should be defined generally as a ≥ 10 mm increase in size of induration within a 2-year period. For HCWs who work in facilities where exposure to TB is very unlikely (e.g., minimal-risk facilities), an increase of ≥ 15 mm within a 2-year period may be more appropriate for defining a recent conversion because of the lower positive-predictive value of the test in such groups.
*Recent close contact implies either household or social contact or unprotected occupational exposure similar in intensity and duration to household contact.29
The possibility should be considered that the skin test sensitivity may also be due to a previous contact with atypical mycobacteria or previous BCG vaccination.13,16
BCG vaccination may produce a PPD reaction that cannot be distinguished reliably from a reaction caused by infection with M. tuberculosis. For a person who was vaccinated with BCG, the probability that a PPD reaction results from infection with M. tuberculosis increases a) as the size of the reaction increases, b) when the person is a contact of a person with TB, c) when the person's country of origin has a high prevalence of TB, and d) as the length of time between vaccination and PPD testing increases. For example, a PPD test reaction of ≥ 10 mm probably can be attributed to M. tuberculosis infection in an adult who was vaccinated with BCG as a child and who is from a country with high prevalence of TB.29
Induration of less than 15 mm in normal, healthy persons, is considered negative.An individual who does not show a positive reaction to 5 TU on the first test, but is suspected of being TB positive, may be retested with 5 TU.
Any individual who does not show a positive reaction to an initial injection of 5 TU, or a second test with 5 TU may be considered as tuberculin negative.
An individual who is considered to be at a high risk for contacting tuberculosis, should have an annual PPD skin test.30
False-negative tuberculin skin-test reactions have many potential causes.19,31 Non-responsiveness to delayed-type hypersensitivity-inducing antigens like tuberculin is common among persons having impaired immunity (e.g., HIV-infected persons). Delayed-type hypersensitivity can also be assessed with skin-test antigens such as tetanus toxoid, mumps, and Candida. Most healthy persons in the population are sensitized to these antigens. Anergy testing is usually not part of routine screening for TB infection.32
All HIV-infected persons should be tuberculin tested.19,33,34 Those who are tuberculin-positive (greater than or equal to 5 mm) should be evaluated for TB disease and placed on appropriate curative or preventive therapy. Preventive therapy should be administered to tuberculin-positive, HIV-infected persons, regardless of age. If they are at high risk for TB, persons failing to react to tuberculin may be evaluated for anergy,35 although the lack of standardization of anergy testing practices should be considered.13
Booster Effect: Infection of an individual with tubercle bacilli or other mycobacteria results in a delayed hypersensitivity response to tuberculin which is demonstrated by the skin test. The delayed hypersensitivity response may gradually wane over a period of years. If a person receives a tuberculin test at this time (after several years) the response may be a reaction that is not significant. The stimulus of the test may boost or increase the size of the reaction to a second test, sometimes causing an apparent conversion or development of sensitivity.14
Tuberculin reactivity may indicate prior infection and/or disease with M. tuberculosis and does not necessarily indicate the presence of active tuberculous disease. Individuals showing a tuberculin reaction should be further evaluated with other diagnostic procedures.
Those individuals giving a positive tuberculin reaction may or may not show evidence of tuberculosis disease. Chest x-ray examination and microbiological examination of the sputum in these cases are recommended as a means of determining the presence or absence of pulmonary tuberculosis.
Vial - 5 TU 1 mL - NDC# 49281-752-21
Vial - 5 TU 5 mL - NDC# 49281-752-22
TUBERSOL (tuberculin purified protein) ® solutions do not require further dilution.
Store at 2º to 8ºC (35º to 46ºF).6,21 DO NOT FREEZE. Discard product if exposed to freezing. Tuberculin solutions can be adversely affected by exposure to light. The product should be stored in the dark except when doses are actually being withdrawn from the vial.22
A VIAL OF TUBERCULIN PPD WHICH HAS BEEN ENTERED AND IN USE FOR 30 DAYS SHOULD BE DISCARDED BECAUSE OXIDATION AND DEGRADATION MAY HAVE REDUCED THE POTENCY.23
Do not use after expiration date.
6. U.S.Code of Federal Regulations, Title 21, Part 650, Subpart B - tuberculin.
9. Canadian Lung Association. Canadian Tuberculosis Standards. 5th edition. 2000.
13. Screening for tuberculosis and tuberculosis infection in high-risk populations. Recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR 1995;44,RR-11.
14. American Thoracic Society: Diagnostic standards and classification of tuberculosis in adults and children. Am J Respir Crit Care Med 2000;161:1376-1395.
15. Thompson N, et al.The booster phenomenon in serial tuberculin testing. Am Rev Respir Dis 1979;119:587-597.
16. The tuberculin skin test.Clin Infect Dis 1993;17:968-975.
18. Current trends update:acquired immunodeficiency syndrome - United States, 1981-1988.MMWR 1989;38(14):245-247.
19. CDC Core Curriculum on Tuberculosis, Third Edition, 1994.
21. Landi S, et al.Stability of dilute solution of tuberculin purified protein derivative at extreme temperatures. J Biol Stand 1981;9:195-199.
22. Landi S, et al.Effect of light on tuberculin purified protein derivative solutions. Am Rev Respir Dis 1975; 111:52-61.
23. Landi S, et al.Effect of oxidation on the stability of tuberculin purified protein derivative (PPD) In: International Symposium on Tuberculins and BCG Vaccine. Basel: International Association of Biological Standardization, 1983.Dev Biol Stand 1986; 58:545-552.
29. Supplement 2: Diagnosis and treatment of latent TB infection and active TB. MMWR 1994;43 RR-13:59-64.
30. Prevention and control of tuberculosis in correctional facilities. MMWR 1996;45, RR-8.
31. Diagnositic standards and classification of tuberculosis. Am Rev Respir Dis 1990;142:725-35.
32. Anergy skin testing and preventive therapy for HIV-infected persons:revised recommendations. MMWR 1997;46,RR-15.
33. USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus:a summary. MMWR 1995;44,RR-8.
34. Tuberculosis and human immunodeficiency virus infection:recommendations of the Advisory Committee for the Elimination of Tuberculosis (ACET). MMWR 1989;38:236-238,243-250.
35. Purified protein derivative (PPD) tuberculin anergy and HIV infection: guidelines for anergy testing and management of anergic persons at risk of tuberculosis. MMWR 1991;40,RR-5:27-33.
Manufactured by: Aventis Pasteur Limited, Toronto, Ontario, Canada. Distributed by: Aventis Pasteur Inc. Swiftwater PA 18370 USA. FDA Rev date: n/a
Last reviewed on RxList: 1/30/2009
This monograph has been modified to include the generic and brand name in many instances.
Additional Tubersol Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.