TUBERCULINA PPD EVANS 2 UT/0.1 ml INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Tuberculina PPD Evans 2UT/ 0.1ml solution for injection

Tuberculina PPD (purified protein derivative)

Read all of this leaflet carefully before having a skin test because it contains important information for you

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the package leaflet:

1. What is Tuberculina PPD Evans and what is it used for
2. What you need to know before having a skin test with Tuberculina PPD Evans
3. How to have a skin test with Tuberculina PPD Evans
4. Possible side effects
5. Storage of Tuberculina PPD Evans
6. Contents of the pack and further information.

1. What is Tuberculina PPD Evans and what is it used for

This medicine is for diagnostic use only.

The active substance is tuberculina (purified protein derivative from batch RT 23) and is used as an aid in the diagnosis of whether an individual has been infected with the tuberculosis bacterium, using the Mantoux test.

Tuberculina PPD Evans is presented in vials of 1.5 ml containing 30 UT (tuberculin units). Each dose (0.1 ml) contains 2 UT (tuberculin units).

2. What you need to know before having a skin test with Tuberculina PPD Evans

You should not have a test with Tuberculina PPD Evans

• if you are allergic to Tuberculina PPD RT 23 or any of the other ingredients of this medicine (listed in section 6).
• if you know from a previous test that you have been infected with the tuberculosis bacterium, you should not have the tuberculin test as a strong reaction may occur at the injection site.
• if you have experienced a severe local reaction to tuberculin products. A severe local reaction may include blisters and ulceration (sores) at the injection site and skin necrosis (the skin turns black due to cell death) in the center of the tuberculin reaction. The necrosis will usually disappear after a few days.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before having a skin test with Tuberculina PPD Evans.

• If you have been recently vaccinated against tuberculosis (BCG vaccine) or with any other type of vaccine.

Although acute allergic reactions (anaphylactic phenomena) are extremely rare, it is necessary to have adequate facilities available for their management during the skin test.

Subcutaneous or intramuscular injection of tuberculina should be avoided. If this occurs, the local reaction will not occur and general febrile symptoms may appear in highly sensitive individuals.

If acute anaphylactic symptoms (acute allergic reaction) are observed after tuberculina injection, adrenaline (vasoconstrictor medication) will be administered immediately to alleviate the symptoms of the allergic reaction.

Cutaneous preparations with corticosteroids may be applied to alleviate local discomfort if a strong reaction occurs.

Other medicines and Tuberculina PPD Evans

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

An individual's sensitivity to tuberculina may decrease or temporarily disappear due to a series of factors such as:

• being young (children) or elderly,
• malnutrition (states of nutrient deficiency),
• immunosuppression (reduced defenses) due to disease (e.g., cancer) or medication (such as corticosteroids, anti-inflammatory medications),
• viral infections (particularly measles, mononucleosis, chickenpox, and flu).

If you have been vaccinated against measles, mumps, rubella, or with vaccines that contain live viruses, the reaction to tuberculina may be reduced, which may lead to false negatives. You should wait 4 to 6 weeks after vaccination to have the test or have it at the same time as vaccination.

Many HIV-positive patients infected with the tuberculosis bacterium do not react to tuberculina, although they may react or not to other types of skin tests.

In patients with severe tuberculosis (e.g., disseminated tuberculosis), the reaction to tuberculina may be suppressed.

Recent vaccination with BCG (tuberculosis vaccine) or recent infection with other bacteria of the same family as tuberculosis may lead to a false positive in the Mantoux test.

Using Tuberculina PPD Evans with food and drinks

No interactions with food and drinks are known.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before having a skin test.

The use of Tuberculina PPD Evans for the diagnosis of tuberculosis infection (Mantoux test) is considered safe during pregnancy and breastfeeding.

Driving and using machines

Tuberculina PPD Evans has no influence or is insignificant on the ability to drive and use machines.

Tuberculina PPD Evans contains potassium and sodium

This medicine contains less than 39 mg (1 mmol) of potassium per dose (0.1 ml), so it is considered essentially "potassium-free".

This medicine contains less than 23 mg (1 mmol) of sodium per dose (0.1 ml); this is, essentially "sodium-free".

3. How to have a skin test with Tuberculina PPD Evans

This test will be performed by a healthcare professional (doctor or nurse).

The recommended dose is 0.1 ml for children and adults.

A healthcare professional will administer the tuberculina solution by injection into the superficial layer of the skin on the anterior surface of the arm, and a white papule (elevated area of the skin) with a diameter of 8-10 mm will appear in the skin area, which will disappear after about 10 minutes. Later, the area where the injection was given may become red and, after a few hours, an induration (discrete elevation of the skin with a nodule) may appear in the center. Do not rub or scratch. Do not apply band-aids or adhesive tape to the area.

After 48-72 hours, your doctor will examine the skin reaction and indicate the test result. After about 72 hours, the size of the induration is expected to decrease.

These skin reactions are normal and characteristic of the test being performed.

If you use more Tuberculina PPD Evans than you should:

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20, indicating the medicine and the amount ingested.

4. Possible side effects

Like all medicines, Tuberculina PPD Evans can cause side effects, although not everybody gets them.

The side effects of Tuberculina PPD Evans are classified by frequency and are as follows:

Common(may affect up to 1 in 10 people):

? Pain

? Irritation

? Discomfort at the injection site (immediately after injection).

Uncommon(may affect up to 1 in 100 people):

? Headache

? Fever

? Enlargement of the regional lymph node.

Rare(may affect up to 1 in 1,000 people):

? Acute allergic reactions (anaphylactic reactions)

? Blister formation (vesiculation)

? Urticaria

? Skin necrosis (blackening of the area due to cell death).

Frequency not known(cannot be estimated from the available data)

? Ulcers at the injection site

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Tuberculina PPD Evans

Keep this medicine out of the sight and reach of children.

Do not use Tuberculina PPD Evans after the expiry date stated on the carton after EXP. The expiry date is the last day of the month indicated.

Store in a refrigerator (between 2°C - 8°C). Keep in the original packaging to protect from light.

From a microbiological point of view, the product should be used immediately. If, after the first extraction, the remaining medicine is not used immediately, the time and conditions of storage during use are the responsibility of the user and should not normally exceed 24 hours at 2°C - 8°C.

It is not recommended to use it after 24 hours of the first extraction.

Medicines should not be disposed of via wastewater or household waste. Place the cartons and any remaining medicines in the SIGRE point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the cartons and any remaining medicines. This will help protect the environment.

6. Container contents and additional information

Composition of Tuberculina PPD Evans

The active ingredient is tuberculina PPD (purified protein derivative of batch RT 23). Each 0.1 ml dose contains 2 TU (tuberculin units) = 0.04 micrograms of tuberculina PPD.

Each 1.5 ml vial of solution contains 30 TU (tuberculin units) = 0.6 micrograms of tuberculina PPD.

The other components are: disodium hydrogen phosphate dihydrate, sodium chloride, potassium dihydrogen phosphate, potassium hydroxyquinoline sulfate, polysorbate 80, and water for injectable preparations.

Appearance of the product and container contents

Tuberculina PPD Evans injectable solution is a clear, colorless to pale yellow solution, free of particles.

Transparent glass vials type 1 with chlorobutyl rubber stoppers: each vial contains 1.5 ml of Tuberculina PPD Evans solution.

Each container contains 1 or 10 vials.

Only some package sizes may be marketed.

Marketing authorization holder and manufacturer

AJ Vaccines A/S

Artillerivej 5

DK-2300 Copenhagen S

Denmark

Phone: +45 7229 7000

Email: info@ajvaccines.com

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

MEDICARE PHARMA, S.L.

Pº de la Castellana, 177 3ºB

28046 Madrid

Spain

Phone: 91 339.54.89

Date of last revision of this leaflet: 06/2019

This information is intended only for healthcare professionals:

Guidelines for correct administration:

1. To perform the test, short-bevel needles (25 or 26 gauges) and sterile 1 ml syringes, graduated in tenths, disposable and for single use, will be used.
2. The rubber stopper of the vial must be cleaned with a cotton swab soaked in alcohol, insert the needle gently through the stopper, invert the vial, withdraw 0.1 ml, eliminating air bubbles.
3. Clean the skin of the forearm with alcohol beforehand and let it dry. No dermatological product with local anesthesia should be used on the skin area where the tuberculin injection will be applied.

The administration route will be intradermal in the middle third of the forearm, on its anterior face. Administration near the wrist or elbow joint may decrease the reaction.

1. The skin should be slightly stretched and the tip of the needle (keeping it almost parallel to the skin surface, with the bevel upwards) inserted into the superficial layer of the dermis, according to the longitudinal axis of the forearm. The needle should be visible through the epidermis during insertion.
2. Inject 0.1 ml slowly, measured with the greatest possible precision. If the injection is done correctly, a papule of 8-10 mm in diameter will be produced, which will remain for about 10 minutes. If the papule does not appear, it means that the solution has been injected too deeply (subcutaneously) or too superficially, so that a significant part of the dose will come out of the injection site, and the test should be repeated on the other arm. If the same arm is used, the injection site should be at least 4 cm away from the first injection site.
3. Each vial contains 1.5 ml, sufficient for several doses, each of 0.1 ml. If the test is performed on several people at the same time, a 1 ml needle and syringe should be used for each person.

The injection may produce an induration surrounding the erythema area a few hours after the injection.

Reading and evaluation of the reaction:

The reaction should be evaluated 48-72 hours after the injection. After approximately 72 hours, it is expected that the size of the induration will decrease.

The reading is based on the presence or absence of induration.

A positive reaction to Tuberculina is defined as a flat, uneven, slightly raised induration with a diameter of at least 5 millimeters, surrounded by a more or less defined reddened area. Only the induration should be assessed.The diameter of the induration, in millimeters, is measured transversely to the longitudinal axis of the forearm with a transparent and flexible plastic ruler.

Any induration, produced in non-vaccinated individuals, equal to or greater than 5 mm, is considered positive, while in the population vaccinated with BCG in less than 10 years, the induration must be greater than or equal to 15 mm to be considered positive (there is no method to distinguish between the reaction to tuberculin caused by BCG vaccination and that caused by mycobacterial infections).

According to current criteria, the test will be estimated as positive based on the risk of tuberculosis within the individual's population. The criteria for the size of the induration to consider the reaction to tuberculin as positive are indicated below.

Induration greater than or equal to 5 mm:

? HIV-positive patients.

? Individuals with recent cases of tuberculosis (less than two years).

? Radiological evidence of old tuberculosis.

? Patients with solid organ transplants and other patients with immunosuppression (receiving more than 15 mg/day of prednisone for more than a month)

Induration greater than or equal to 10 mm:

? Residents or employees of the following institutions: prisons, nursing homes, hospitals, and other healthcare centers, detoxification centers for drug addicts, and shelters for homeless people.

? Individuals with pathology considered to be at risk, such as: silicosis, diabetes, chronic renal failure, hematological neoplasms, gastrectomized or with intestinal bypass, intestinal malabsorption syndrome, prolonged steroid treatment, low weight (considered as 10% or less of ideal weight), cancer (e.g., head or neck cancer and lung cancer).

? History of drug use (e.g., cocaine, alcohol).

? Parenteral drug users seronegative for HIV.

? Immigrants (arrived less than five years ago) from countries with high prevalence

? Children under 4 years old or children or adolescents exposed to high-risk adults

Induration greater than or equal to 15 mm:

? Individuals without risk factors for tuberculosis

Repetition of the tuberculin test:

If it is likely that the Mantoux test will be repeated, for example, in healthcare workers potentially exposed to tuberculosis infection, a two-stage method is recommended. Individuals with an initial weak or absent tuberculin skin test should undergo a second tuberculin skin test 2 to 4 weeks after the first test. The result of the second test will be considered the valid result

Booster effect:

In most people who have not been vaccinated with BCG, sensitivity to tuberculin is maintained throughout life. However, in some individuals, this sensitivity may be decreased or disappear over time (see section 4.5).

In individuals vaccinated with BCG, sensitivity to tuberculin decreases after a few years. If tuberculin is administered to individuals vaccinated with BCG or to individuals infected with M. tuberculosiswhose sensitivity to tuberculin is decreased, the reaction to the first test may be minor or even absent. If the test is repeated after 7-10 days, the response may be enhanced. This is interpreted as a booster effect, reinforcement of the weakened immune response to tuberculin (not absent), and should not be interpreted as a tuberculin conversion. The result of the second test will be considered valid.

Repeated tuberculin skin tests do not induce a positive reaction in individuals who do not have prior cellular immunity to the antigens of tuberculin PPD.RT 23.

Tuberculin conversion:

Tuberculin does not sensitize even if performed more than once. Therefore, if it is positive in someone who previously had a negative test, it means that there has been a tuberculin conversion due to tuberculous infection.

Recent tuberculin conversion is considered to be the change, in less than two years, from negative to positive or an increase in the diameter of the induration by 6 mm or more in relation to the first test and an induration of more than 10 mm in the second test. This means the recent acquisition of tuberculous infection if the booster effect has been previously ruled out.

Causes of false results:

False negatives, the causes may be due to viral (measles, mumps, chickenpox, HIV), bacterial (typhoid fever, brucellosis, typhus, leprosy), or fungal (South American blastomycosis) infections, vaccination with live viruses (measles, mumps, polio, chickenpox), metabolic disorders (chronic renal failure, diabetes), decreased protein states (severe protein elimination, afibrinogenemia), diseases affecting lymphoid organs (Hodgkin's disease, lymphoma, chronic leukemia, sarcoidosis), drugs (corticosteroids and other immunosuppressive agents), age (neonates, elderly patients with decreased sensitivity), stress (surgery, burns, mental illness), incorrect use of tuberculin (incorrect storage, incorrect dilution, chemical denaturation of tuberculin, contamination), errors in administration (administration of a small amount of antigen, subcutaneous administration, delay in performing the test once the injection is prepared, performing the test very close to other tests on the skin) or errors in reading the test.

The Mantoux test may be negative for disseminated tuberculosis.

False positives, the causes may be due to infections with atypical mycobacteria, previous BCG vaccination, errors in technique, errors in preparation, or incorrect conservation of the product.

In elderly individuals, the response may appear late at 72 hours, but this does not invalidate its reading.