Metex pen

Package leaflet: Information for the user

Metex PEN, 7.5 mg, solution for injection in a pre-filled pen
Metex PEN, 10 mg, solution for injection in a pre-filled pen
Metex PEN, 12.5 mg, solution for injection in a pre-filled pen
Metex PEN, 15 mg, solution for injection in a pre-filled pen
Metex PEN, 17.5 mg, solution for injection in a pre-filled pen
Metex PEN, 20 mg, solution for injection in a pre-filled pen
Metex PEN, 22.5 mg, solution for injection in a pre-filled pen
Metex PEN, 25 mg, solution for injection in a pre-filled pen
Metex PEN, 27.5 mg, solution for injection in a pre-filled pen
Metex PEN, 30 mg, solution for injection in a pre-filled pen
Methotrexatum
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. 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, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Metex PEN is and what it is used for
2. Important information before using Metex PEN
3. How to use Metex PEN
4. Possible side effects
5. How to store Metex PEN
6. Contents of the pack and other information

1. What Metex PEN is and what it is used for

Indications for Metex PEN

• Active rheumatoid arthritis in adult patients, and polyarticular forms of severe, active juvenile idiopathic arthritis in patients aged 3 years and older, when response to non-steroidal anti-inflammatory drugs (NSAIDs) is inadequate,
• Moderate to severe psoriasis in adult patients, and severe psoriatic arthritis in adults,
• Crohn's disease of mild to moderate severity in adult patients when treatment with other appropriate medications is not possible.

Rheumatoid arthritis (RA) is a chronic disease classified as a collagenosis, characterized by inflammation of the synovial membranes lining the joints. These membranes produce fluid that acts as lubricant for many joints. Inflammation causes thickening of the membranes and joint swelling.
Juvenile arthritis occurs in children and adolescents under 16 years of age. The polyarticular form is defined by involvement of five or more joints within the first six months of the disease.
Psoriasis is a common chronic skin disease characterized by red patches covered with thick, dry, silvery, tightly adherent scales.
Psoriatic arthritis refers to joint inflammation, particularly in the fingers and toes, associated with psoriatic skin and nail changes.
Metex PEN modifies and slows the progression of the disease.
Crohn's disease is a type of inflammatory bowel disease that may affect any segment of the gastrointestinal tract, causing symptoms such as abdominal pain, diarrhoea, vomiting, or weight loss.

2. Information before using Metex PEN

When not to use Metex PEN

• if the patient is allergic to methotrexate or any of the other ingredients of this medicine (listed in section 6);
• if the patient has liver disease, severe kidney disease, or blood disorders;
• if the patient regularly consumes large amounts of alcohol;
• if the patient has severe infections, such as tuberculosis, HIV infection, or other immunodeficiency syndromes;
• if the patient has mucosal ulcers in the mouth, gastric or intestinal ulcers;
• if the patient is pregnant or breastfeeding (see section "Pregnancy, breastfeeding and fertility");
• if the patient is simultaneously receiving a vaccine containing live microorganisms.

Warnings and precautions
Before starting treatment with Metex PEN, discuss with your doctor or pharmacist:

• if the patient is elderly, debilitated, or in poor general health;
• if the patient has impaired liver function;
• if the patient has dehydration (lack of water in the body);
• if the patient has diabetes and is using insulin.

Special precautions for the use of Metex PEN
Methotrexate temporarily impairs the production of sperm and egg cells; in most cases, this effect is reversible. Methotrexate may cause miscarriage and severe congenital malformations. Women should avoid becoming pregnant during methotrexate treatment and for at least 6 months after treatment ends. Men should avoid impregnating their partner during methotrexate treatment and for at least 3 months after treatment ends. See also section "Pregnancy, breastfeeding and fertility".

Recommended monitoring tests and precautions
Severe adverse effects may occur even after administration of low doses of methotrexate. To detect them early, the doctor must perform regular check-ups and laboratory tests.

Before starting treatment
Prior to initiating therapy, a blood test will be performed to check whether the patient has an adequate number of blood cells. Blood tests will also be carried out to assess liver function and to determine whether the patient has hepatitis. Additionally, serum albumin (a blood protein) levels, kidney function, and signs of hepatitis (liver infection) will be evaluated. The doctor may also decide to perform further liver tests, which may include imaging studies of the liver or taking a small tissue sample from the liver for more detailed assessment. Furthermore, the doctor may check for tuberculosis and may perform a chest X-ray or lung function tests.

During treatment
The doctor may perform the following tests:

• examination of the mouth and throat for mucosal changes such as inflammation or ulceration;
• blood tests / blood cell counts and measurement of methotrexate serum concentration;
• blood tests to monitor liver function;
• imaging tests to monitor liver status;
• taking a small tissue sample from the liver for more detailed assessment;
• blood tests to monitor kidney function;
• respiratory system check-up and, if necessary, lung function tests.

It is very important that the patient attends these scheduled examinations.
If any of these test results show abnormalities, the doctor will adjust the treatment accordingly.

Elderly patients
Elderly patients receiving methotrexate should remain under close medical supervision to detect possible adverse effects as early as possible. Age-related impairments in liver and kidney function and low levels of folic acid in the body of elderly individuals require relatively low dosing of methotrexate.

Other precautions
Cases of acute pulmonary hemorrhage have been reported in patients with underlying rheumatologic disease during methotrexate treatment. If the patient develops hemoptysis (coughing up blood), immediate medical attention is required.

Methotrexate may affect the immune system, vaccine efficacy, and results of immunological tests. It may lead to reactivation of latent chronic diseases (e.g. shingles, tuberculosis, hepatitis B or C virus). During treatment with Metex PEN, do not use vaccines containing live microorganisms.

Methotrexate may increase skin sensitivity to sunlight. Avoid intense sun exposure and do not use sunbeds or tanning lamps without consulting a doctor. To protect the skin from intense sunlight, wear appropriate clothing or use a high-protection sunscreen.

During methotrexate treatment, radiation-induced skin inflammation and sunburn ("recall reaction") may be triggered. UV radiation exposure during methotrexate treatment may worsen psoriatic lesions.

Lymph node enlargement (lymphadenopathy) may occur. In such a case, treatment should be discontinued.

Diarrhea may be a sign of toxic effects of Metex PEN and requires discontinuation of treatment. If the patient develops diarrhea, inform the doctor immediately.

In cancer patients receiving methotrexate treatment, certain brain function disorders (encephalopathy/leukoencephalopathy) have been reported. The occurrence of such adverse effects cannot be ruled out when methotrexate is used to treat other diseases.

If the patient, their partner, or caregiver notices new onset or worsening of neurological symptoms, including general muscle weakness, visual disturbances, changes in thinking, memory, and orientation leading to disorientation and personality changes, immediate medical attention is required, as these may be symptoms of a very rare but severe brain infection called progressive multifocal leukoencephalopathy (PML).

Metex PEN and other medicines
Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines the patient plans to take in the future. This includes all medications, including those to be taken in the future.

Concomitant administration of certain medicines may affect the action of Metex PEN:

• antibiotics, e.g.: tetracyclines, chloramphenicol, non-absorbable broad-spectrum antibiotics, penicillins, glycopeptides, sulfonamides, ciprofloxacin, and cephalothin (medicines used to prevent and treat certain infections);
• non-steroidal anti-inflammatory drugs or salicylates (analgesic and/or anti-inflammatory medicines, e.g. acetylsalicylic acid, diclofenac, ibuprofen, or pyrazole);
• metamizole (synonyms: novaminsulfone and dipyrone) (a potent analgesic and/or antipyretic);
• probenecid (used in the treatment of gout);
• weak organic acids such as loop diuretics (diuretic medicines);
• medicines that may adversely affect bone marrow function, e.g. trimethoprim-sulfamethoxazole (a bactericidal agent) or pyrimethamine;
• other medicines used in the treatment of rheumatoid arthritis, e.g. leflunomide, sulfasalazine, and azathioprine;
• cyclosporine (an immunosuppressive agent);
• mercaptopurine (a cytostatic medicine);
• retinoids (medicines for psoriasis and other skin diseases);
• theophylline (a medicine for bronchial asthma and other lung diseases);
• certain medicines used for stomach disorders, e.g. omeprazole and pantoprazole;
• hypoglycemic agents (reducing glucose ["sugar"] concentration in blood).

Vitamin products containing folic acid should be used only if prescribed by a doctor, as they may reduce the effectiveness of methotrexate.
Avoid vaccines containing live microorganisms.

Metex PEN with food, drink, and alcohol
During treatment with Metex PEN, avoid alcohol consumption as well as large amounts of coffee, caffeine-containing beverages, and black tea.

Pregnancy, breastfeeding and fertility

Pregnancy
Do not use Metex PEN if the patient is pregnant or trying to become pregnant. Methotrexate may cause congenital malformations, harm the unborn child, or cause miscarriage. This is associated with developmental abnormalities of the skull, face, heart and blood vessels, brain, and limbs. Therefore, it is extremely important that women who are pregnant or planning pregnancy do not take methotrexate. If the patient is of childbearing age, pregnancy must be definitively ruled out before starting treatment by appropriate measures, such as a pregnancy test.

The patient should avoid becoming pregnant during methotrexate treatment and for at least 6 months after its completion, using reliable contraception methods throughout this period (see also section "Warnings and precautions").

If the patient becomes pregnant during treatment or suspects she may be pregnant, she should consult her doctor as soon as possible. The patient should seek advice regarding the potential harmful effects of treatment on the child.

If the patient plans to become pregnant, she should consult her treating physician, who may refer her to a specialist for preconception counseling.

Breastfeeding
Breastfeeding must be discontinued before starting and during treatment with Metex PEN.

Male fertility
Available evidence does not indicate an increased risk of developmental abnormalities or miscarriages following paternal exposure to methotrexate at doses below 30 mg/week. However, a risk cannot be completely excluded. Methotrexate may be genotoxic, meaning it may cause genetic mutations. Methotrexate may affect sperm and cause congenital malformations. Therefore, the patient should avoid impregnating his partner and must not be a sperm donor during methotrexate treatment and for at least 3 months after its completion.

Driving and operating machinery
During treatment with Metex PEN, adverse effects on the central nervous system may occur, such as fatigue and dizziness. Therefore, the ability to drive motor vehicles and/or operate machinery may be impaired in some cases. If feeling drowsy or fatigued, do not drive or operate machinery.

Metex PEN contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, meaning the medicine is considered "sodium-free".

3. How to use Metex PEN

Important warning regarding dosing of Metex PEN (methotrexate):
In the treatment of rheumatoid arthritis, juvenile idiopathic arthritis,
psoriasis, psoriatic arthritis, and Crohn's disease, Metex PEN must be used only once a week.
Taking more Metex PEN (methotrexate) than prescribed may result in death. Please read section 3 of this leaflet carefully. If you have any questions, consult your doctor or pharmacist before taking the medicine.
This medicine should always be used exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
The doctor decides on the dosage, which is individually adjusted to the patient.
Therapeutic effects are usually observed only after 4 to 8 weeks of treatment.
Metex PEN is administered as a subcutaneous injection by, or under the supervision of, a doctor or qualified healthcare professional only once a week. The patient should agree with the doctor on a specific day of the week for the injection.

Use in children and adolescents
The doctor determines the appropriate dose for children and adolescents with polyarticular course juvenile idiopathic arthritis.
Metex PEN is not recommended for use in children under 3 years of age due to insufficient experience in this age group.

Method and timing of administration
Metex PEN is injected once a week!
The duration of treatment is determined by the treating physician. Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, and Crohn's disease with Metex PEN is long-term therapy.
At the beginning of treatment, Metex PEN may be administered by healthcare personnel. However, the doctor may decide that the patient is able to perform self-injection of Metex PEN. The patient will be properly trained accordingly. Never attempt self-injection of the medicine without prior training.
Instructions on how to correctly use Metex PEN are provided in the "Instructions for Use" section at the end of this leaflet.
Remember to use the entire contents of the pre-filled syringe.
Preparation of the medicine for use and disposal of the pre-filled auto-injector must comply with local requirements. Pregnant healthcare personnel must not prepare or (and) administer the medicinal product Metex PEN.
Methotrexate must not come into contact with the skin or mucous membranes. In case of contact, the affected area should be immediately rinsed thoroughly with plenty of water.

Overdose of Metex PEN
If a patient has taken more than the recommended dose of Metex PEN, seek medical advice immediately.

Missed dose of Metex PEN
Do not use a double dose to make up for a missed dose.

Stopping Metex PEN treatment
If treatment with Metex PEN is interrupted, inform your doctor immediately.
If you feel that the effect of Metex PEN is too strong or too weak, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The frequency and severity of adverse reactions depend on the dose size and frequency of
administration. Since serious adverse reactions may occur even after administration of small
doses, regular medical examinations are necessary. Therefore, the doctor should perform examinations to rule out abnormalities in blood parameters (e.g. low white blood cell count, platelets, lymphoma) and changes in the liver and kidneys.
You should inform the doctor immediately if any of the following symptoms occur in the patient, as they may indicate serious, potentially life-threatening adverse reactions requiring urgent treatment:

• persistent dry cough without sputum, shortness of breath, and fever; these may be symptoms of lung inflammation [common]
• coughing up blood (haemoptysis); this may be a sign of bleeding from the lungs [frequency not known]
• signs of liver damage, such as yellowing of the skin and whites of the eyes; methotrexate may cause chronic liver damage (liver cirrhosis), scarring of liver tissue (liver fibrosis), fatty degeneration of the liver (fatty liver), [all uncommon], liver inflammation (acute hepatitis) [rare], and liver failure [very rare]
• allergic symptoms such as skin rash, including itchy redness of the skin, swelling of the hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing), and the patient may feel faint; these may be symptoms of severe allergic reactions or anaphylactic shock [rare]
• symptoms of kidney damage such as swelling of the hands, ankles, or feet, or changes in the frequency of urination, reduced urine volume (oliguria), or absence of urine (anuria); these may be symptoms of kidney failure [rare]
• signs of infection, such as fever, chills, pain, sore throat; methotrexate may increase susceptibility to infections. Severe infections may occur, such as a specific type of pneumonia (Pneumocystis jirovecii pneumonia) and blood poisoning (sepsis) [rare]
• symptoms such as weakness on one side of the body (stroke) or pain, swelling, redness, and unusual warmth in one leg (deep vein thrombosis); this may occur if a dislodged blood clot blocks a blood vessel (thromboembolic event) [rare]
• symptoms such as fever and severe worsening of general health or sudden fever accompanied by sore throat or mouth pain or disturbances in urination; methotrexate may cause acute reduction in the number of certain white blood cells (agranulocytosis) and severe bone marrow suppression [very rare]
• unexpected bleeding, e.g. bleeding gums, blood in urine, in vomit, or appearance of petechiae (small red or purple spots on the skin due to bleeding); these may be symptoms of significant reduction in platelet count due to severe bone marrow suppression [very rare]
• symptoms such as severe headache accompanied by fever, neck stiffness, nausea, vomiting, disorientation, and light sensitivity; these may indicate meningitis (acute aseptic meningitis) [very rare]
• in cancer patients receiving methotrexate treatment, certain brain function disorders (encephalopathy/leukoencephalopathy) have been reported. Occurrence of such adverse reactions cannot be excluded when methotrexate is used to treat other diseases. Symptoms of these brain function disorders include altered mental state, movement disorders (ataxia), visual and memory disturbances [frequency not known]
• severe skin rash or blisters on the skin (which may also occur in the mouth, eyes, and genital organs); these may be symptoms of Stevens-Johnson syndrome or toxic epidermal necrolysis (Lyell's syndrome) [very rare]

Other adverse reactions that may occur are listed below:
Very common: may occur in more than 1 in 10 patients

• inflammation of the mucous membrane of the mouth, indigestion, nausea, decreased appetite, abdominal pain,
• abnormal liver function tests (AST, ALT, bilirubin, alkaline phosphatase).

Common: may occur in 1 in 10 patients

• mouth ulcers, diarrhoea,
• rash, skin redness, itching,
• headache, fatigue, drowsiness,
• reduced production of blood cells leading to decreased number of white and/or red blood cells and/or platelets.

Uncommon: may occur in 1 in 100 patients

• sore throat,
• enteritis, vomiting, pancreatitis, black or tarry stools, gastrointestinal bleeding and ulcers,
• sunburn-like reactions due to increased skin sensitivity to sunlight, hair loss, increase in number of rheumatoid nodules, skin ulceration, shingles, vasculitis, herpes-like rash, urticaria,
• onset of diabetes,
• dizziness, confusion, depression,
• decreased serum albumin concentration,
• decreased number of all blood cells and platelets,
• inflammation and ulceration of the bladder or vagina, impaired kidney function, disturbances in urination,
• joint pain, muscle pain, decreased bone mass.

Rare: may occur in 1 in 1,000 patients

• gingivitis,
• increased skin pigmentation, acne, blue spots on the skin due to bleeding from blood vessels (purpura, petechiae), allergic vasculitis,
• decreased concentration of antibodies in the blood,
• infection (including latent chronic infection), eye redness (conjunctivitis),
• mood changes (mood swings),
• visual disturbances,
• inflammation of the sac surrounding the heart (pericarditis), fluid accumulation in the pericardium, impaired heart filling due to fluid in the pericardial sac,
• low blood pressure,
• formation of scar tissue in the lungs (pulmonary fibrosis), shortness of breath and bronchial asthma, fluid accumulation in the pleural cavity,
• stress fractures,
• electrolyte disturbances,
• fever, impaired wound healing.

Very rare: may occur in 1 in 10,000 patients

• acute toxic dilation of the large intestine (toxic megacolon),
• increased nail pigmentation, inflammation of the nail cuticle (acute paronychia), deep infection of hair follicles (furunculosis), visible enlargement of small blood vessels,
• pain, loss of muscle strength, or numbness or tingling sensation, reduced response to stimuli, taste disturbances (metallic taste), seizures, meningeal reaction,
• blurred vision, non-inflammatory eye disease (retinopathy),
• decreased libido, impotence, gynaecomastia in men, disturbances in sperm production (oligospermia), menstrual disorders, vaginal discharge,
• enlarged lymph nodes (lymphadenopathy),
• lymphoproliferative disorders (overproduction of white blood cells).

Frequency not known: frequency cannot be determined from available data

• elevated number of certain white blood cells,
• nosebleeds,
• proteinuria,
• feeling of fatigue,
• jaw bone damage (due to overproduction of white blood cells),
• tissue damage at the injection site,
• redness and peeling of the skin,
• swelling.

Subcutaneously administered doses of methotrexate are locally well tolerated. Only mild local
skin reactions (such as burning sensation, erythema, swelling, discoloration, itching, intense
itching, pain) have been observed, which tend to diminish during treatment.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, you should inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, PL-02-222 Warsaw, tel.: +48 22 49-21-301, fax: +48 22 49-21-309,
website: ://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Metex PEN

Keep the medicine out of the sight and reach of children.
Do not store above 25°C. Do not freeze.
Store the prefilled automatic injection pens in the outer carton to protect from light.
Do not use this medicine after the expiry date stated on the carton and on the injector under "Expiry date". The expiry date refers to the last day of the stated month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Contents of the pack and other information

What Metex PEN contains

• The active substance is methotrexate. One pre-filled semi-automatic injector with a solution volume of 0.15 ml contains 7.5 mg of methotrexate. One pre-filled semi-automatic injector with a solution volume of 0.2 ml contains 10 mg of methotrexate. One pre-filled semi-automatic injector with a solution volume of 0.25 ml contains 12.5 mg of methotrexate. One pre-filled semi-automatic injector with a solution volume of 0.3 ml contains 15 mg of methotrexate. One pre-filled semi-automatic injector with a solution volume of 0.35 ml contains 17.5 mg of methotrexate. One pre-filled semi-automatic injector with a solution volume of 0.4 ml contains 20 mg of methotrexate. One pre-filled semi-automatic injector with a solution volume of 0.45 ml contains 22.5 mg of methotrexate. One pre-filled semi-automatic injector with a solution volume of 0.5 ml contains 25 mg of methotrexate.

One pre-filled semi-automatic injector with a solution volume of 0.55 ml contains 27.5 mg
of methotrexate.
One pre-filled semi-automatic injector with a solution volume of 0.6 ml contains 30 mg
of methotrexate.

• The other ingredients are sodium chloride, hydrochloric acid and sodium hydroxide (for pH adjustment), and water for injections.

What Metex PEN looks like and contents of the pack
Metex PEN is a solution for injection in a pre-filled injector.
The solution is clear and yellowish-brown in colour.

Metex PEN pre-filled semi-automatic injector is a three-step automatic injector with a yellow cap and a yellow injection button.

Metex PEN pre-filled semi-automatic injector is a two-step automatic injector with a transparent protective cap and a blue needle shield.
The following pack sizes are available:
Metex PEN is available in packs containing 1, 2, 4, 5, 6, 10, 11, 12, 14, 15 or 24 pre-filled semi-automatic injectors.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
medac
Gesellschaft für klinische Spezialpräparate mbH
Theaterstr. 6
22880 Wedel
Germany
Telephone: +49 4103 8006-0
Fax: +49 4103 8006-100

This medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:
Austria, Czech Republic, Finland, Greece, Spain, Netherlands, Slovakia, Slovenia, Hungary, United Kingdom (Northern Ireland):
Metoject PEN
Iceland, Sweden:
Metojectpen
Germany:
metex PEN
Estonia, Lithuania, Latvia, Norway:
Metex
Poland, Portugal:
Metex PEN
Denmark:
Metex Pen
Belgium:
Metoject

Instructions for use
Recommendations

• Before administering the medicine, carefully read the instructions below.
• Always use the injection technique recommended by your doctor, pharmacist or nurse.

Additional information
The method of preparing the medicine for use and the disposal of the medicine and the pre-filled semi-automatic injector must comply with local regulations. Healthcare professionals who are pregnant should not prepare or (and) administer the medicinal product Metex PEN.
Methotrexate must not come into contact with the skin or mucous membranes. In case of contact, the affected area must be immediately rinsed thoroughly with plenty of water.

Components of the Metex PEN injector:

Injection button
Area for holding the injector
Transparent control zone
Cap

a) With cap before injection
b) After removing the cap before injection
c) After completing the injection

What to do before administering the injection

1. Wash hands thoroughly.
2. Remove the set from the packaging.
3. Check the Metex PEN injector before use:

If the Metex PEN injector appears damaged,

do not use it. Use another injector and contact your doctor, pharmacist or nurse.
If a small air bubble is visible in the transparent control zone, this does not affect the dose and does not pose a risk to the patient.
If the patient is unable to properly see or check the injector before injection, ask another person for help.

4. Place the Metex PEN injector on a clean, flat surface (e.g. on a table).

Where to administer the injection
The most suitable injection sites

include:

• the upper thigh,
• the abdomen, excluding the area around the navel.
  • If another person administers the injection to the patient, it may also be given in the upper, posterior part of the upper arm, just below the shoulder.
  • Always select a different injection site each time. This will help reduce the likelihood of injection site reactions.
  • Never inject the medicine into painful areas, areas with bleeding, redness, hardened skin, scars or stretch marks. If the patient has psoriasis, do not inject the medicine directly into raised, thickened, red or flaky skin areas or lesions.

How to prepare the injection

5. Select the injection site and clean

the selected injection site and the surrounding skin area.

• Do not remove the cap before preparing for

injection.

6. Hold the injector in one hand at the designated holding area, with the cap pointing upwards. With the other hand, gently remove the cap with a straight motion (do not bend or twist the cap). A small needle shield inside the cap should automatically slide off with the cap. If the needle shield does not slide off, use another injector and contact your doctor, pharmacist or nurse.

• If the patient has difficulty removing the cap, ask another person for help.

Warning: After removing the cap, administer the injection immediately.

7. Create a skin fold by gently pinching the skin at the

selected injection site.

• Hold the skin fold until the injector is withdrawn from the skin after the injection.

8. Place the exposed, transparent end

of the Metex PEN injector perpendicularly onto the skin fold.

9. Without pressing the button, firmly press the Metex PEN injector against the skin to unlock the button.

• If the patient cannot firmly press the Metex PEN injector in place, ask another person for help.

How to administer the injection:

10. While firmly holding the Metex PEN injector

pressed against the skin, press the button with your thumb.

11. A clicking sound will be heard, indicating the start of the injection. Keep holding the injector pressed against the skin until the full dose of medicine has been injected. This may take up to 5 seconds.

Warning:
To avoid incomplete injection, do not remove the Metex PEN injector from the skin before the injection is complete.
If the injection does not start, release the button, ensure the Metex PEN injector is firmly pressed against the skin, and press the button firmly again.
If you have difficulty hearing the click, count 5 seconds from the moment you press the button, then lift the injector away from the injection site.

12. Remove the Metex PEN injector from the injection

site by pulling it straight out (perpendicular to the skin).

13. The protective shield automatically returns to cover the needle. The shield then locks into place, covering the needle.
14. If there is slight bleeding, apply a plaster or dressing.

Before disposing of the Metex PEN injector, visually check whether any liquid remains at the bottom of the transparent control zone. If liquid remains in the injector, this indicates that an incomplete dose was administered, and you should contact your doctor.

Warning
To avoid needlestick injuries, never insert fingers into the opening of the protective needle shield.
Do not destroy the injector.

Whom to contact if needed

• For any problems or questions, contact your doctor, pharmacist or nurse.
• In case of a needlestick injury to the patient or another person, seek immediate medical advice and dispose of the Metex PEN injector.

INSTRUCTIONS FOR USE

This Instructions for Use contains information on how to inject using the Metex PEN prefilled autoinjector
Metex PEN prefilled autoinjector.

Before using the prefilled semi-automatic injector for subcutaneous injection,
read this entire Instructions for Use. Read this Instructions for Use
each time a new prescription is received and keep this Instructions for Use for reference
as needed after use.

After receiving a new medicine or a new dosage of medicine, always check whether it is consistent
with the doctor's recommendations. Before using the injector, a healthcare professional should show the patient or caregiver how to properly use the injector.
The user should not use the injector until instructed by a healthcare professional on how to use the injector.
If there are any questions, contact a healthcare professional.

Important information to read before administering an injection using the prefilled semi-automatic injector for Metex PEN
The injection using the prefilled semi-automatic injector for Metex PEN must be administered once weekly, always on the same day of the week.
Pregnant women must not administer or prepare the medication.

• Store the injector in a safe place, out of sight and out of reach of children.
• If the medication comes into contact with the skin, immediately rinse the affected area thoroughly with plenty of water.

Do NOT remove the protective cap until immediately before administering the injection.
Do NOT share your injector with anyone else.
Do NOT use the injector if:

• it has fallen onto a hard surface or appears damaged;
• the clear yellow solution has changed color, become cloudy, or contains solid particles;
• it has been frozen or stored at temperatures above 25°C;
• the expiration date has passed. If in doubt, consult a healthcare professional.

How to store the prefilled semi-automatic Metex PEN injector

• Store below 25°C.
• Transport and store the injector in its original outer packaging to protect it from light.
• Store the injector in a safe place, out of sight and out of reach of children.

Do NOT freeze.
Do NOT store above 25°C.
Metex PEN prefilled semi-automatic injector (Fig. A)
The Metex PEN prefilled semi-automatic injector is a two-step, automatic fixed-dose injector for single use. It is available in 10 different doses ranging from 7.5 mg to 30 mg.
Before use After use

Protective cap Blue needle shield
(transparent) (locks in place after injection, needle inside)
Viewing window

(yellow medication inside) Protective cap
(needle shield
Plunger
(position depends on prescribed dose) inside)
Blue plunger rod

(indicates complete
injection)
Medication label
7.5 mg 15 mg 30 mg
(for verifying dose
(sample doses)
and expiration date)
Color-coded area
(unique for each dose)
Fig. A
Materials needed for administering the injection (Fig. B)
On the day of your weekly injection, find a comfortable place, ensure it is well-lit, and prepare a clean, flat surface, such as a table, where you can place the materials needed for administering the injection.
Required item:

• Metex PEN prefilled semi-automatic injector.

Ensure that the following additional materials, which are not included in the packaging, are available for administration of the injection:

• A calendar to track the weekly injection day;
• Skin cleansing agent, e.g., alcohol swab, or if unavailable, soap and water;
• Cotton swab or gauze pad for wiping the injection site;
• A waste container compliant with local regulations.

Metex PEN calendar indicating the weekly injection day Auto-injector Skin cleansing agent Cotton swab or gauze Waste container
Fig. B
Preparing for the injection

1. Wash hands and remove the syringe
from the packaging (Fig. C)

• Wash hands with soap and water.
• Carefully remove the syringe from the packaging.

Do not remove the protective cap until
the patient is ready for injection.

Fig. C
2. Check the injector before use

(Fig. D)

Check carefully the name and dose on the
injector and make sure it is the correct
medicine. If the user cannot see well enough,
ask someone for help.
ask someone for help.

• Check the expiry date on the injector label.
• Do not use the injector if the Fig. D expiry date has passed.
• Check the medicine through the viewing window by turning the injector upside down or gently shaking it. The medicine in the injector should be clear and yellow.
  • Do not inject if the solution is cloudy, has changed colour, or contains solid particles.
  • It is normal to see one or more small air bubbles. Do not attempt to remove them.
  • A scale may be visible in the viewing window; this does not require attention.
• Check that the injector is not damaged and that the cap is properly attached. Do not use the injector if it appears damaged or if the cap has been removed or is not securely attached.

If the expiry date of the injector has passed,
or if it appears damaged or does not look as
expected, do not use it and contact a healthcare
professional.
Before proceeding with the next steps,
carefully place the injector on a clean,
flat surface, such as a table.
3. Choose the injection site (Fig. E)

• The patient may self-inject in:
  • the upper thigh,
  • the lower abdomen, except for the area within 5 cm of the navel.
• If the injection is administered by a caregiver, the back of the upper arm may also be used.
• Use a different injection site than the one used for the previous injection.

When choosing the injection site:
do not inject into other parts of the body;
do not inject into bruised, tender, flaky, red, or hardened skin;
do not inject into moles, scars, or stretch marks;
do not inject through clothing.

Site
Site
for
for
caregiver
caregiver
only
only
Fig. E
4. Clean the injection site (Fig. F)

• Clean the injection site with an alcohol swab; if unavailable, use water and soap.
• Wait until the skin is dry. Do not fan or do not blow on the cleaned area. Do not touch the injection site again until the injection is completed. Fig. F

Administering the dose
5. Remove the cap (Fig. G)

The protective cap should only be removed
when the patient is ready to administer
the injection.
Do not attempt to reattach the cap
onto the injector after removal.

• Hold the injector with the cap pointing upward and remove the cap with a firm motion. Fig. G Do not bend or do not twist the cap while removing it.
• Immediately discard the cap.
• Small droplets of medicine may appear. This is normal.
• Administer the injection immediately after removing the cap.

Do not touch the blue needle shield with fingers.
Touching the blue needle shield may
accidentally activate the injection
and cause injury.

6. Position the injector (Fig. H)

• Place the open blue needle shield flat on the skin at a 90-degree angle, with the viewing window facing toward you so it remains visible.
• It may be more comfortable to pinch a skin fold by gently squeezing the area around the injection site between the thumb and other fingers before injecting, but this is not required for this injector. Fig. H

7. Start the injection (Fig. I)

• To start the injection, press the injector firmly all the way down. This will retract the blue needle shield into the injector and the injection will begin automatically.
• The first audible click indicates the start of the injection. The blue plunger rod will move downward.
• Keep holding the injector pressed firmly against the skin until the entire Fig. I dose is delivered. Once the injection has started, do not change the position of the injector.

8. Hold the injector in place to complete
the injection (Fig. J)

• Continue to hold the injector firmly pressed against the skin. 5 seconds
• The injection is complete when:
  • a second click is heard shortly after the first;
  • or: the blue plunger rod has stopped moving and fills the viewing window;
  • or: 5 seconds have passed. Fig. J

Do not remove the injector from the injection site
until at least
5 seconds have passed.

9. Completing the injection (Fig. K)

• Remove the injector straight upwards from the injection site.
• The blue needle shield automatically returns into place around the needle and locks.
• Check the viewing window to ensure no yellow medicine residue remains. If yellow medicine is still visible in the window, the full dose may not have been delivered. In such a case, or if you have any other Fig. K doubts, contact a healthcare professional.

Do not touch the blue needle shield after
the injection, as this may cause injury.
After the injection

10. Cover the injection site (Fig. L)

• A small drop of blood may appear at the injection site. This is normal. If necessary, press a cotton swab or gauze lightly against the site.
• If needed, cover the injection site with a small plaster or bandage.

Do not rub the injection site.
Fig. L

11. Disposing of the injector (Fig. M)
Each injector may only be used once.
Do not reattach the cap to the injector.
Store the used injector and protective cap
out of sight and out of reach of children.
Fig. M

• The cap and injector must be disposed of immediately after use. The method of disposal of the pre-filled semi-automatic injector must comply with local regulations.

• Discard used materials into a household waste container. The cardboard box can be disposed of in paper recycling.

Pre-filled semi-automatic injectors
containing Metex PEN that have passed
their expiry date, are no longer needed,
or are no longer suitable for use must be
disposed of safely.