Aplisol should not be administered to persons who previously experienced a severe reaction (e.g., vesiculation, ulceration, or necrosis) because of the severity of reactions that may occur at the test site (see
Not all infected persons will have a delayed hypersensitivity reaction to a tuberculin test. A number of factors have been reported to cause a decreased ability to respond to the tuberculin test, such as the presence of infections, viral infections (measles, mumps, chickenpox, HIV), live virus vaccinations (measles, mumps, rubella and other live vaccines), bacterial infections (typhoid fever, brucellosis, typhus, leprosy, pertussis, overwhelming tuberculosis, tuberculous pleurisy), fungal infections (South American blastomycosis), drugs (corticosteroids and other immunosuppressive agents), metabolic derangements (chronic renal failure), low protein states (severe protein depletion, afibrinogenemia), age (newborns, elderly patients with waned sensitivity), stress (surgery, burns, mental illness, graft-versus-host reactions), diseases affecting lymphoid organs (Hodgkin's disease, lymphoma, chronic leukemia, sarcoidosis), and malignancy.7,8,9
Any condition that impairs or attenuates cell mediated immunity potentially can cause a false negative reaction, including aging.10,11
Tuberculin skin test results are less reliable in HIV-infected individuals as CD4 counts decline (see
Avoid injecting tuberculin subcutaneously. If this occurs, no local reaction develops, but a general febrile reaction and/or acute inflammation around old tuberculous lesions may occur in highly sensitive individuals.
The predictive value of the tuberculin skin test depends on the prevalence of infection with M. tuberculosis and the relative prevalence of cross-reactions with nontuberculous mycobacteria.9,12
A separate, sterile, single-use disposable syringe and needle should be used for each individual patient to prevent possible transmission of serum hepatitis virus and other infectious agents from one person to another. Special care should be taken to ensure that the product is injected intradermally and not into a blood vessel.
Before administration of Aplisol, a review of the patient's history with respect to possible immediate-type hypersensitivity to the product, determination of previous use of Aplisol and the presence of any contraindication to the test should be made (see
As with any biological product, epinephrine should be immediately available in case an anaphylactoid or acute hypersensitivity reaction occurs.
Failure to store and handle Aplisol as recommended may result in a loss of potency and inaccurate test results.8,13
Reactivity to the test may be depressed or suppressed for as long as 5–6 weeks in individuals following immunization with certain live viral vaccines, viral infections or discontinuation of corticosteroids or immunosuppressive agents.8,9
Information to Patients
Patients should be instructed to report adverse events such as vesiculation, ulceration or necrosis which may occur at the test site in highly sensitive individuals. Patients should be informed that pain, pruritus and discomfort may occur at injection site.
Patients should be informed of the need to return to their physician or health care provider for the reading of the test and of the need to keep and maintain a personal immunization record.
In patients who are receiving corticosteroids or immunosuppressive agents, reactivity to the test may be depressed or suppressed. This reduced reactivity may be present for as long as 5–6 weeks after discontinuation of therapy (see
PRECAUTIONS – General).9
The reactivity to PPD may be temporarily depressed by certain live virus vaccines (measles, mumps, rubella, oral polio, yellow fever, and varicella). Therefore, if a tuberculin test is to be performed, it should be administered either before the live vaccine or given simultaneously, but at a separate site than the live vaccine, or testing should be postponed for 4–6 weeks.9
Carcinogenesis, Mutagenesis, Impairment of Fertility
No long term studies have been conducted in animals or in humans to evaluate carcinogenic or mutagenic potential or effects on fertility with Aplisol.
Pregnancy Category C
Animal reproduction studies have not been conducted with Aplisol. It is also not known whether Aplisol can cause fetal harm when administered to a pregnant woman or can affect the reproduction capacity. Aplisol should be given to a pregnant woman only if clearly needed. However, the risk of unrecognized tuberculosis and the postpartum contact between a mother with active disease and an infant leaves the infant in grave danger of tuberculosis and complications such as tuberculous meningitis. Although there have not been any reported adverse effects upon the fetus recognized as being due to tuberculosis skin testing, the prescribing physician will want to consider if the potential benefits outweigh the possible risks for performing the tuberculin test on a pregnant woman or a woman of childbearing age, particularly in certain high risk populations.
Tuberculin skin testing is considered valid and safe throughout pregnancy.3
Once acquired, tuberculin sensitivity tends to persist, although it often wanes with time and advancing age. In geriatric patients or in patients receiving a tuberculin skin test for the first time, the reaction may develop more slowly and may not be maximal until after 72 hours.6,7 (see
CLINICAL PHARMACOLOGY). Not all infected persons will have a delayed hypersensitivity reaction to a tuberculin test. A number of factors have been reported to cause a decreased ability to respond to the tuberculin test, such as elderly patients with waned sensitivity.7 Any condition that impairs or attenuates cell mediated immunity potentially can cause a false negative reaction, including aging10,11 (see
WARNINGS). An induration of >10 mm is classified as positive in all persons who do not meet any of the criteria listed under an induration of >5 mm, but who belong to one or more of the following groups at high risk for TB, including residents and employees of high risk congregate settings, such as nursing homes and other long-term facilities for the elderly.
The negative tuberculin skin test should never be used to exclude the possibility of active tuberculosis among person for whom the diagnosis is being considered (symptoms compatible with tuberculosis) (see
DOSAGE AND ADMINISTRATION-Interpretation of Tuberculin Reaction).
Because their immune systems are immature, many neonates and infants <6 weeks of age, who are infected with M. tuberculosis, may not have a delayed hypersensitivity reaction to a tuberculin test (see
WARNINGS). Older infants and children develop tuberculin sensitivity 3-6 weeks, and up to 3 months, after initial infection.5,20 Infants and children who have been exposed to persons with active tuberculosis should be considered positive when reaction to the tuberculin skin test measures ≥ 5 mm. Those children younger than 4 years of age who are exposed to persons at increased risk to acquire tuberculosis are considered positive when reaction measures ≥10 mm. Children with minimal risk exposure to tuberculosis would be considered positive when reaction measures ≥15 mm. 5,20 Other criteria for positive tuberculin reactions that are applicable to both pediatric and adult patients are provided in
DOSAGE AND ADMINISTRATION, Interpretation of Tuberculin Reaction.