Description of Tuberculin PPD RT 23

1 NAME OF THE MEDICINAL PRODUCT 

Tuberculin PPD RT 23 SSI

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

2 T.U./0.1 mL:
One single dose of 0.1 mL contains 0.04 micrograms of Tuberculin PPD RT 23.

10 T.U./0.1 mL:
One single dose of 0.1 mL contains 0.2 micrograms of Tuberculin PPD RT 23.

3 PHARMACEUTICAL FORM

Solution for injection.
Clear, colourless to pale yellow solution.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Tuberculin PPD RT 23 is used for Mantoux tuberculin skin testing to help diagnose if a person has ever been infected with Mycobacterium tuberculosis. Some countries also recommend Mantoux tuberculin skin testing in conjunction with BCG vaccination, either to ensure that only tuberculinnegative individuals are vaccinated or as a post-vaccination test.

This medicinal product is for diagnostic use only.

4.2 Posology and method of administration

Dosage and strength:
The dosage is always 0.1 mL regardless of the strength used.
The route of administration is strictly intradermal injection.
The strength 2 T.U./0.1 mL is recommended.
If low tuberculin reactivity is expected 10 T.U./0.1 mL may be used.

Administration:

• 0.1 mL is administered with a 1 mL graduated syringe fitted with a short bevel needle (gauge 25 or 26).

• The injection should be given strictly intradermally in the middle third of the forearm.
   Administration near the wrist or the elbow joint may weaken the reaction.

• The skin is slightly stretched, and the needle is held almost parallel with the skin surface with bevel upwards. The tip of the needle is inserted into the superficial layer of the dermis.

• The needle should be visible through the epidermis during insertion. The 0.1 mL is slowly injected and a small blanched papule of 8 – 10 mm in diameter appears. This papule will disappear after approximately ten minutes.

• If a papule does not appear the injection has been given too deep, and the skin test should be repeated on the other arm or on the same arm, separated at least 4 cm from the first injection site.

National recommendations regarding the application of the skin test may be taken into consideration.

Evaluating the reaction:
A skin test reaction is seen as a flat, uneven, slightly raised induration surrounded by an area of redness. The induration should be evaluated 48-72 hours after the injection. Hereafter the induration will decrease.

Only the induration is assessed.
The diameter of the induration is measured in millimetres transversely to the long axis of the forearm with a transparent, flexible plastic ruler.
Recommendations for interpreting the Mantoux tuberculin skin test are shown in table 1.
Alternative interpretations, depending on national recommendations, individual and epidemiological factors, may be applied.

Diameter of induration in milimetres
Negative 0-5 mm	Positive 6-14 mm	Strongly positive 15+ mm

Table 1: Normal interpretation of the skin test result

Interpretation:
A positive reaction indicates an immune response due to one or more of the following reasons:

• Infection with Mycobacterium tuberculosis complex, including M. tuberculosis, M. bovis, M. africanum, M. microtii, or M. tuberculosis subsp. caprae.

• Infection with non-tuberculous mycobacteria.

• Previous BCG vaccination (BCG vaccinated persons normally become tuberculin positive after 4 – 8 weeks).

Reactions larger than 15 mm are unlikely to be due to previous BCG vaccination or exposure to environmental mycobacteria.

Waning of tuberculin sensitivity:
In most individuals tuberculin sensitivity caused by infection with M. tuberculosis or related mycobacteria normally persists throughout life.
However, in some individuals this sensitivity may decrease or disappear over time.
In BCG vaccinated individuals the tuberculin sensitivity most often wanes within a few years.

Booster effect:
If tuberculin is administered to individuals whose tuberculin sensitivity has waned, the reaction to the skin test will be weak or absent. Retesting with tuberculin weeks or months later may result in an accentuation of the response, i.e. a booster effect.
Repeated tuberculin skin testing will not induce a positive reaction in individuals who have no previous cellular immunity against the antigens in tuberculin PPD.

Repeated tuberculin skin testing:
If it is anticipated to repeat the tuberculin skin test e.g. in health care workers potentially exposed to tuberculosis infection, a two-step method is recommended. In this method, the individual who has a weak or an absent initial Mantoux tuberculin skin test should receive a second tuberculin skin test 2 - 4 weeks after the first test.
Skin test conversion in such individuals is defined as a reaction to the second test of more than 10 mm and an increase of at least 6 mm compared to the first test.
Individuals showing skin test conversion after the second test should be considered to be previously infected with Mycobacteria or may have been BCG vaccinated, whereas individuals with a negative reaction to the second test should be considered uninfected.
It is important to emphasize that the predictive value of the skin test result and the expected risk of tuberculosis should be considered on an individual basis.

4.3 Contraindications

Tuberculin PPD RT 23 SSI should not be administered to:

• Patients known to be hypersensitive (Type I) to the active substance or any of the excipients. This can cause vesiculation and skin necrosis in the centre of a widespread tuberculin reaction. The necrosis will generally disappear after a few days.

• Patients who previously have experienced a severe local reaction to Tuberculin products.
 

4.4 Special warnings and precautions for use

 
Although anaphylaxis is rare, facilities for its management should always be available during Mantoux tuberculin skin test.

Avoid subcutaneous or intramuscular injection of Tuberculin PPD RT 23 SSI. If this occurs, a papule will not develop and the Mantoux tuberculin skin test should be repeated on the other arm or if the same arm is used the injection site should be separated at least 4 cm from the first injection site.

4.5 Interaction with other medicinal products and other forms of interaction

A variety of host-related factors such as age, nutrition, renal failure, diabetes, immunosuppression by medicinal products (e.g. corticosteroids) or disease, e.g. cancer, HIV infection and sarcoidosis, can cause false negative tuberculin reactions. Viral infections (particularly measles, mumps, mononucleosis, varicella and influenza) can lower the tuberculin reactivity for a few months.
After vaccinations with vaccines containing live virus (e.g. vaccines against measles, mumps and rubella) a reduced reactivity may be observed. This decreased reactivity may result in false negative reactions. Therefore, if Mantoux tuberculin skin testing cannot be done at the same time as measles, mumps and rubella immunisation, the test should be postponed for 4 – 6 weeks.
Tuberculin PPD RT 23 SSI can be safely administered simultaneously with all live and inactivated vaccines.
Many patients co-infected with HIV and M. tuberculosis have anergy for tuberculin with or without anergy to other skin test antigens. In patients with severe tuberculosis (e.g. miliary tuberculosis) tuberculin reactivity may be suppressed.
Previous BCG vaccination or recent infection with environmental non-tuberculous mycobacteria can result in cross-sensitization and a false-positive reaction to a Mantoux tuberculin skin test.

4.6 Pregnancy and lactation

Animal reproduction studies have not been performed with Tuberculin PPD RT 23 SSI.
Mantoux tuberculin skin test with Tuberculin PPD RT 23 SSI is considered safe during pregnancy and lactation.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.
Tuberculin PPD RT 23 SSI should not affect the ability to drive and use machines.

4.8 Undesirable effects

The most common side-effects after administration of Tuberculin PPD RT 23 SSI are pain, itching and irritation at the injection site.

Blood and lymphatic system disorders
Uncommon (> 1/1,000 to <1/100)	Enlargement of regional lymph nodes
Skin and subcutaneous tissue disorders
Rare (>1/10,000 to <1/1,000)	Vesiculation Skin necrosis Urticaria
General disorders and administration site conditions
Common (> 1/100 to 1/10)	Pain at the injection site Itching at the injection site Irritation at the injection site
Uncommon (> 1/1,000 to <1/100)	Fever
Immune system disorders
Very rare (<1/10,000)	Hypersensitivity, including anaphylactic reactions
Nervous system disorders
Uncommon (>1/1,000 to <1/100)	Headache

4.9 Overdose

Undesirable effects in relation to overdosage are not expected.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group, ATC code: V04CF01

6 Pharmaceutical particulars

6.1 List of excipients

Disodium phosphate dehydrate
Potassium dihydrogen phosphate
Sodium chloride
Potassium hydroxychinoline sulphate
Water for injections
Polysorbate 80

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products.

6.3 Special precautions for storage

Store in a refrigerator (2ºC – 8ºC).

Store in the original package in order to protect from light.

6.4 Nature and contents of container

Type I glass vials, Ph. Eur.
Stoppers of chlorobutyl rubber, Ph. Eur.
The stoppers do not contain latex.
Vials containing 1.5 mL or 5 mL in pack sizes of 1 or 10.
 

6.5 Special precautions for disposal and other handling

Any unused product or waste material should be disposed of in accordance with local requirements.

Tuberculin PPD RT 23 SSI does not contain any live material.