Prospecto: Information for the User

Tuberculina PPD Evans 2UT/ 0.1ml injectable solution

Tuberculina PPD (purified protein derivative)

Read this prospectus carefully before undergoing a skin test because it contains important information for you

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only to you, and you should not give it to others who have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they do not appear in this prospectus. See section4.

This medication is solely for diagnostic use.

The active ingredient is tuberculina (purified protein derivative from lot RT 23) and is used as an aid to diagnose, through the Mantoux test, whether an individual has been infected by the tuberculosis bacteria.

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

Do not perform a test with Tuberculina PPD Evans

• if you are allergic to Tuberculina PPD RT 23 or any of the other components of this medication (listed in section6).
• if you know from a previous test that you have been infected with the tuberculosis bacteria, the test should not be performed 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 (wounds) at the injection site and necrosis of the skin (skin turns black due to cell death) at the center of the tuberculin reaction. Necrosis usually disappears within a few days.

Warnings and precautions

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

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

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

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

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

Corticosteroid preparations may be applied to the skin to alleviate local discomfort if a strong reaction occurs.

Other medications and Tuberculina PPD Evans

Inform your doctor or pharmacist if you are using, have recently used, or may need to use any other medication.

The sensitivity of an individual to tuberculin may decrease or disappear temporarily due to a series of factors such as:

• being young (children) or elderly,
• malnutrition (states of nutrient deficiency),
• immunosuppression (decreased defenses) due to disease (e.g. cancer) or medications (such as corticosteroids, medications that reduce inflammation),
• infections caused by viruses (particularly measles, mononucleosis, chickenpox, and influenza).

If you have been vaccinated against measles, mumps, rubella, or with vaccines containing live viruses, the reaction to tuberculin may be reduced, leading to false negatives. You should wait 4to 6weeks after vaccination to undergo the test or have it done at the same time as the vaccination.

Many HIV-positive patients and those infected with the tuberculosis bacteriado not react to tuberculin, although they may react or not react to other types of skin tests.

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

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

Use of Tuberculina PPD Evans RT23 2 U.T. with food and beverages

No interactions with food and beverages are known.

Pregnancy, lactation, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant or plan to become pregnant, consult your doctor or pharmacist before undergoing a skin test.

The test for diagnosing infection with the tuberculosis bacteria (Mantoux test) with Tuberculina PPD Evans is considered safe during pregnancy and lactation.

Driving and operating machinery

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

Tuberculina PPD Evans contains potassium and sodium

This medication contains less than 39mg (1mmol) of potassium per dose (0.1ml), making it essentially “potassium-free”.

This medication contains less than 23mg (1mmol) of sodium per dose (0.1ml); it is essentially “sodium-free”.

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 tuberculin solution through an injection in the superficial layer of the skin on the anterior surface of the arm, and a papule (elevated area on the skin) will appear, which is a white area 8-10 mm in diameter on the skin, which will disappear within 10 minutes. Subsequently, the area where the injection was administered will become red, and within a few hours, an induration (discrete elevation of the skin with a nodule) may appear in the middle. Do not rub or scratch. Do not place bandages or adhesive tape on the area.

After 48-72 hours, your doctor will examine the skin reaction and inform you of the test results. Approximately 72 hours after the test, it is expected that the size of the induration will decrease.

These skin reactions are normal and part 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 Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

Like all medications, Tuberculina PPD Evans may cause adverse effects, although not everyone will experience them.

The adverse effects of Tuberculina PPD Evansare classified by frequency and are as follows:

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

?Pain

?Irritation

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

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

?Headache

?Fever

?Enlargement of regional lymph nodes.

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

?Acute allergic reactions (anaphylactic reactions)

?Formation of blisters (vesiculation)

?Urticaria

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

Unknown frequency(cannot be estimated from available data)

?Ulcers at the injection site

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through theSpanish System for Pharmacovigilance of Medicinesfor Human Use:www.notificaRAM.es.By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

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

Do not use Tuberculina PPD Evans after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

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

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

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

Medications should not be disposed of through drains or trash. Dispose of the packaging and medications you no longer need at the SIGRE point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. In this way, you will help protect the environment.

Composition of Tuberculina PPD Evans

?The active principle is tuberculina PPD (purified protein derivative from lot RT 23). Each dose of 0.1ml contains 2UT (tuberculin units) = 0.04micrograms of tuberculina PPD.

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

?The other components are: dihydrogen phosphate of disodium dihydrate, sodium chloride, potassium dihydrogen phosphate, potassium hydroxylquinoline sulfate, polisorbate 80 and water for injectable preparations.

Aspect of the product and content of the package

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

Transparent glass vials type1 with chlorobutyl rubber stoppers: each vial contains 1.5ml of tuberculina PPD Evans solution.

Each package contains 1or 10vials.

Only some package sizes may be commercially available.

Holder of the marketing authorization and responsible for manufacturing

AJ Vaccines A/S

Artillerivej 5

DK-2300 Copenhagen S

Denmark

Phone: +45 7229 7000

Email: [email protected]

You can request more information about this medication by contacting 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

Last review date of this leaflet: 06/2019

This information is intended only for doctors or healthcare professionals:

Guidelines for correct administration:

1.To perform the test, use short-beveled needles (25or 26gauges) and sterile 1ml syringes, graduated in tenths, disposable and for single use.

2.Clean the rubber stopper of the vial with an alcohol-soaked cotton swab, insert the needle gently through the stopper, invert the vial, extract 0.1ml, eliminating air bubbles.

3.Clean the skin of the forearm with alcohol and let it dry. Do not use any dermatological products with local anesthesia in the area of the skin where the tuberculina injection will be administered.

4.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 reduce the reaction.

5.Extend the skin slightly and insert the needle tip (keeping it almost parallel to the skin surface, with the bevel up) into the superficial layer of the dermis, along the longitudinal axis of the forearm. The needle should be visible through the epidermis during insertion.

6.Inject slowly 0.1ml, measured with the greatest possible precision. If the injection is well done, a papule of 8-10mm in diameter will appear, lasting about 10minutes. 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 escape from the injection site, so the test should be repeated on the other arm. If the same arm is used, the injection site should be separated from the first injection site at least 4cm.

7.Each vial contains 1.5ml, sufficient for several doses, each of 0.1ml. If the test is performed on several people at the same time, a separate needle and syringe should be used for each person.

The injection may cause induration around the area of the erythema a few hours after the injection.

Reading and evaluation of the reaction:

The reaction should be evaluated 48-72hours after the injection. After about 72hours, 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, irregular, slightly elevated induration with a diameter of at least 5mm, surrounded by a reddened area, more or less defined.Only the induration should be evaluated.The diameter of the induration, in millimeters, is measured transversely to the longitudinal axis of the forearm with a transparent, flexible plastic ruler.

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

According to current criteria, the test will be considered positive based on the risk of tuberculosis within the population of the individual to be evaluated. The following criteria for the size of the induration are indicated to consider the reaction to tuberculina as positive.

Induration equal to or greater than 5mm:

?Individuals with HIV.

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

?Radiological evidence of old tuberculosis.

?Patients with solid organ transplant and other immunosuppressed patients (receiving equivalent to more than15mg/day of prednisone for more than a month)

Induration equal to or greater than 10mm:

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

?People with risk pathology such as: silicosis, diabetes, chronic renal insufficiency, 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 and neck and lung cancer).

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

?Parenteral drug users who are HIV-negative.

?Immigrants (arrived in the last five years) from countries with high prevalence

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

Induration equal to or greater than 15mm:

?People without risk factors for tuberculosis

Repeating the tuberculina 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 a weak or absent initial tuberculina skin test should undergo a second tuberculina skin test 2-4weeks after the first test. The result of the second test will be considered as the valid result

Booster effect:

In most people who have not been vaccinated with BCG, sensitivity to tuberculina is maintained throughout life. However, in some people, this sensitivity may be decreased or disappear over time (see section4.5).

In people vaccinated with BCG, sensitivity to tuberculina decreases over time. If tuberculina is administered to people vaccinated with BCG or to people infected withM.tuberculosiswhose sensitivity to tuberculina is decreased, the reaction to the first test may be weaker or even absent. If the test is repeated 7-10days later, the response may be enhanced. This is interpreted as a booster effect, reinforcement of the weakened immune response to tuberculina (not absent), and should not be interpreted as a tuberculina conversion. The result of the second test will be considered valid.

Repeated tuberculina skin tests do not induce a positive reaction in individuals who do not have prior cellular immunity against tuberculina PPD.RT 23 antigens.

Tuberculina conversion:

Tuberculina does not sensitize, even if it is administered more than once. Therefore, if it is positive in someone who previously had a negative test, it means that there has been a recent tuberculina conversion due to tuberculosis infection.

Tuberculina conversion or recent change is defined as the passage, in less than two years, from negative to positive or an increase in the diameter of the induration of 6mm or more compared to the first test and an induration of more than 10mm in the second test. This means recent acquisition of tuberculosis infection if previously ruled out the booster effect.

Causes of false results:

False negatives, the causes may be due to viral infections (measles, mumps, varicella, HIV), bacterial infections (typhoid fever, brucelosis, typhus, leprosy, ), fungal infections (South American blastomycosis), vaccination with live viruses (measles, mumps, polio, varicella), metabolic disorders (chronic renal insufficiency, diabetes), protein disorders (severe protein elimination, afibrinogenemia), diseases affecting lymphoid organs (Hodgkin's disease, lymphoma, chronic leukemia, sarcoidosis), drugs (corticosteroids and other immunosuppressants), age (neonates, elderly patients with decreased sensitivity), stress (surgery, burns, mental illness), incorrect use of tuberculina (incorrect storage, incorrect dilution, chemical denaturation of tuberculina, 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 too 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, incorrect conservation of the product.

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