VELOS 2.5 мг Инъекционный раствор в преднаполненном шприце

Содержание инструкции

1. What VELOS is and what it is used for
2. What you need to know before taking VELOS
3. How to use VELOS
4. Possible side effects
5. How to store VELOS
6. Content of the pack and other information

VELOS 2.5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg, 17.5 mg, 20 mg, 22.5 mg, 25 mg, 27.5 mg and 30 mg
injectable solution in pre-filled syringe
Methotrexate

Read this leaflet carefully before using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

• 1. What VELOS is and what it is used for
• 2. What you need to know before you use VELOS
• 3. How to use VELOS
• 4. Possible side effects
• 5. How to store VELOS
• 6. Contents of the pack and other information

1. What VELOS is and what it is used for

VELOS contains methotrexate as the active ingredient.
Methotrexate is a substance with the following properties:

• interferes with the growth of some cells in the body that reproduce rapidly
• reduces the activity of the immune system (the body's defense mechanism)
• has anti-inflammatory effects.

VELOS is indicated for the treatment of:

• active rheumatoid arthritis in adult patients;
• polyarticular forms of severe active juvenile idiopathic arthritis, with inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs);
• severe, recurrent and disabling psoriasis that does not respond adequately to other forms of therapy such as phototherapy, PUVA and retinoids and severe psoriatic arthritis in adult patients;
• mild to moderate Crohn's disease in adult patients, in cases where adequate treatment with other drugs is not possible.

Rheumatoid arthritis (RA) is a chronic connective tissue disease, characterized
by inflammation of the synovial membranes (joint membranes). These membranes
produce a fluid that acts as a lubricant for many joints. Inflammation causes
thickening of these membranes and swelling of the joints.
Juvenile idiopathic arthritis affects children and adolescents under the age of 16. The forms
polyarticular are those that affect 5 or more joints within the first six months from the onset
of the disease.
Psoriatic arthritis is a type of arthritis with psoriatic lesions of the skin and nails, especially at
the level of the joints of the hands and feet.
Psoriasis is a common chronic skin disease, characterized by red patches covered with scales
dry and thick, silvery in color, difficult to remove.
VELOS has been shown to be able to modify and slow the progression of these diseases.
Crohn's disease is a type of inflammatory bowel disease that can affect any part of the
gastrointestinal tract causing symptoms such as abdominal pain, diarrhea, vomiting or weight loss.

2. What you need to know before taking VELOS

Do not take VELOS

• if you are allergic to methotrexate or any of the other ingredients of this medicine (listed in section 6).
• if you have severe liver or kidney problems or blood diseases.
• if you regularly drink large amounts of alcoholic beverages.
• if you suffer from a serious infection, e.g. tuberculosis, HIV or other immunodeficiency syndromes.
• if you suffer from ulcers in the mouth or gastric or intestinal ulcers.
• if you are pregnant or breastfeeding (see the section “Pregnancy, breastfeeding and fertility”)
• if you are receiving vaccinations with live vaccines at the same time.

Warnings and precautions
Talk to your doctor or pharmacist before using VELOS if:

• you are elderly or generally feel unwell and weak.
• you have problems with liver function.
• you suffer from dehydration (loss of water).

Special precautions for treatment with Velos
Methotrexate temporarily affects the production of sperm and eggs, an effect that is reversible in most
cases. Methotrexate can cause miscarriage and serious birth defects. While using methotrexate and for at least six months after the end of treatment, you should avoid
pregnancy. See also the section “Pregnancy, breastfeeding and fertility”.
Further tests and recommended safety measures
Even if VELOS is administered at a low dose, serious side effects can occur.
To identify them promptly, the doctor must perform checks and laboratory tests.
Before therapy
Before starting treatment, a blood sample must be taken to check that there is
a sufficient number of blood cells and tests must be performed to check the function of the liver
and kidneys, and the amount of serum albumin (a blood protein). The doctor will also ensure
that you do not suffer from tuberculosis (infectious disease associated with small nodules in the affected tissue)
by performing a chest X-ray.
During therapy
At least once a month for the first six months and then at least every three months, the following tests should be performed:

• Examination of the mouth and throat to check for changes in the mucous membranes
• Blood tests
• Liver function check
• Kidney function check
• Check of the respiratory system and, if necessary, pulmonary function tests

Methotrexate can affect the immune system and the results of vaccination. It can also affect the result of immunological tests. Inactive chronic infections can recur (e.g.
herpes zoster [shingles], tuberculosis, hepatitis B or C). During therapy with VELOS, you should not
be vaccinated with live vaccines.
Radiation dermatitis and sunburn can reappear during therapy with methotrexate
(recall reaction). Psoriatic lesions may worsen following concomitant use of
ultraviolet radiation and methotrexate.
Enlarged lymph nodes (lymphoma) may appear and therapy should therefore be discontinued.
Diarrhea can be a toxic effect of VELOS and requires discontinuation of therapy. If you suffer from
diarrhea, tell your doctor.
Encephalopathy (brain disease) and leukoencephalopathy (a particular disease of the white matter
of the brain) have occurred in patients with tumors treated with methotrexate, and it cannot
be ruled out that they may occur during methotrexate therapy in other diseases.

Children
VELOS is not recommended in children under 3 years of age due to the limited experience gained
with this age group.

Other medicines and VELOS
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicine.
The effect of the treatment may be altered if VELOS is administered at the same time as
other drugs such as:

• Medicines harmful to the liver or blood cells, e.g. leflunomide
• Antibiotics (medicines to prevent/fight some infections) such as: tetracyclines, chloramphenicol and broad-spectrum non-absorbable antibiotics, penicillins, glycopeptides, sulfonamides (sulfur-containing medicines that prevent/fight some infections), ciprofloxacin and cephalothin
• Non-steroidal anti-inflammatory drugs or salicylates (medicines against pain and/or inflammation)
• Probenecid (medicine against gout)
• Weak organic acids such as loop diuretics or some medicines used for the treatment of pain and inflammatory diseases (e.g. acetylsalicylic acid, diclofenac and ibuprofen) and pyrazolone derivatives (e.g. metamizole for the treatment of pain)
• Medicines that can have adverse effects on the bone marrow, e.g. trimethoprim-sulfamethoxazole (an antibiotic) and pyrimethamine
• Sulfasalazine (a rheumatic medicine)
• Azathioprine (an immunosuppressant sometimes used in severe rheumatoid arthritis)
• Mercaptopurine (a cytostatic agent)
• Retinoids (medicine against psoriasis and other dermatological diseases)
• Theophylline (medicine against bronchial asthma and other lung diseases)
• Proton pump inhibitors (medicines against stomach disorders)
• Hypoglycemic agents (medicines used to lower blood sugar)

Vitamin complexes containing folic acid may compromise the effect of the treatment and
must be taken only under the control of the doctor.
Vaccinations with live vaccines should be avoided.

VELOS with food, drinks and alcohol
During treatment with VELOS, alcoholic beverages, large amounts of
coffee, caffeinated beverages and black tea should be avoided.

Pregnancy, breastfeeding and fertility
Pregnancy
Do not use VELOS during pregnancy or if you are trying to become pregnant. Methotrexate can
cause birth defects, harm the fetus or cause miscarriage. It is associated with malformations
of the skull, face, heart and blood vessels, brain and limbs. Therefore, it is very important that patients in
pregnancy or planning a pregnancy are not treated with methotrexate.
In women of childbearing potential, every possibility of pregnancy must be excluded by using
adequate measures, for example by performing a pregnancy test before starting
treatment. During the intake of methotrexate and for at least 6 months after the end of treatment
you should avoid pregnancy using reliable contraceptive methods throughout the period
(see also the section “Warnings and precautions”).
If you become pregnant during treatment or suspect you are pregnant, contact your doctor
as soon as possible. You will receive advice on the risk of harmful effects on the baby due to
treatment.
If you wish to become pregnant, you should consult your doctor, who will refer you to a specialist before
the planned start of treatment.

Breastfeeding
Breastfeeding must be discontinued before and during treatment with Velos.

Male fertility
Available evidence does not indicate an increased risk of malformations or miscarriage
if the father takes a dose of methotrexate less than 30 mg/week. However, the risk cannot
be completely excluded. Methotrexate can be genotoxic. This means that the medicine
can cause genetic mutations. Methotrexate can affect sperm production with the possibility of causing birth defects. Therefore, while taking methotrexate and for at least 6 months
after the end of treatment, you should avoid procreation or donating semen.

Driving and operating machinery
Treatment with VELOS can cause adverse reactions affecting the central nervous system, such as
fatigue and dizziness. Therefore, the ability to drive a vehicle and/or operate machinery
may be impaired in some cases. If you feel tired or sleepy, you should not drive or
operate machinery.

VELOS contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is practically “sodium-free”.

3. How to use VELOS

The doctor will decide the dosage, adapting it to the individual patient. Generally, the effects of
treatment are noticeable after 4-8 weeks of treatment.
VELOS is administered by a doctor or under their supervision or by healthcare professionals in the form of an injection once a week only. Decide, together with your doctor, the day of the
week to have the weekly injection. VELOS must be injected subcutaneously (under
the skin).
The doctor will decide the appropriate dosage for children and adolescents with
polyarticular forms of juvenile idiopathic arthritis.

Use in children
VELOS is not recommended in children under 3 years of age due to the limited experience
gained with this age group.

Method of administration and duration of treatment
VELOS is injected once a week!
The duration of treatment is decided by the attending physician. Treatments for rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis vulgaris, psoriatic arthritis and Crohn's disease with VELOS are
long-term treatments.
At the beginning of therapy, VELOS may be administered by medical personnel. In some cases, the
doctor may decide to explain how to personally inject VELOS subcutaneously. In this case, you will receive adequate instructions.
Under no circumstances should you attempt to inject VELOS without first receiving
these instructions.
Handling and disposal must be carried out as with other cytostatic preparations in
compliance with current local regulations. Healthcare professionals who are pregnant should refrain
from handling and/or administering VELOS.
Methotrexate must not come into contact with the surface of the skin or mucous membranes. In case of
contamination, the affected area must be immediately rinsed with plenty of water.

If you use more VELOS than you should
Follow your doctor's dosage recommendations. Do not change the dose on your own initiative.
If you suspect you have used too much VELOS, contact your doctor immediately. They will decide what
treatment is appropriate depending on the severity of the intoxication.

If you forget to use VELOS
Do not take a double dose to make up for forgetting a single dose. Ask your doctor for advice.
Take the dose prescribed by your doctor as soon as possible and then every week.

If you stop using VELOS
Do not stop or suspend treatment with VELOS unless you have discussed it with
your doctor. If you suspect serious side effects, contact your doctor immediately for advice.
If you feel that the effect of VELOS is too strong or too weak, tell your doctor or
pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The frequency and severity of side effects depend on the dosage and frequency of
administration. Because some serious side effects can occur even at a low
dosage, it is important that the doctor performs regular monitoring. The doctor will then

prescribe teststo identify the possible presence of abnormalitiesin the blood (e.g. reduced
number of white blood cells, reduced number of platelets, lymphoma) and changes in the
function of the kidneys and liver.

Immediately inform your doctorif you notice any of the following symptoms, which may indicate
serious side effects, potentially life-threatening, that require urgent specific
treatment:

• persistent dry cough without phlegm, shortness of breath and fever: these may be signs of lung inflammation (pneumonia) [common - may affect up to 1 in 10 people];
• symptoms of liver damage such as yellowing of the skin and the white of the eyes;methotrexate can cause chronic liver damage (liver cirrhosis), formation of liver scar tissue (liver fibrosis), fatty degeneration of the liver [all uncommon - may affect up to 1 in 100 people], liver inflammation (acute hepatitis) [rare - may affect up to 1 in 1,000 people] and liver failure [very rare - may affect up to 1 in 10,000 people]
• allergic symptoms such as skin rashes including red and itchy skin, swelling ofhands, feet, ankles, face, lips, mouth or throat (which may cause difficulty inswallowing or breathing) and feeling of fainting: these may be signs of severe allergic reactions or anaphylactic shock [rare - may affect up to 1 in
• 1,000 people]
• symptoms of kidney damage such as swelling of hands, ankles, feet or changes infrequency of urination or decreased or absence of urine: these may be signs of kidney failure [rare - may affect up to 1 in 1,000 people]
• symptoms of infection, e.g. fever, chills, aches, sore throat: methotrexate can make you more susceptible to infections. Rarely, serious infections [may affect up to 1 in 1,000 people] such as a specific type of pneumonia ( Pneumocystis cariniipneumonia) or blood poisoning ( sepsis) may occur
• severe diarrhea, vomiting with blood and black or tarry stools: these symptoms may be indicative of a serious and rare [may affect up to 1 in
• 1,000 people] complication of the gastrointestinal system caused by methotrexate, e.g. gastrointestinal ulcers
• symptoms associated with blockage (occlusion) of a blood vessel by a detached bloodclot (thromboembolic event) such as weakness on one side of the body (stroke) orpain, swelling, redness and unusual warmth in a leg (deep vein thrombosis): methotrexate can cause thromboembolic events [rare - may affect up to 1 in 1,000 people]
• fever and rapid deterioration of the general condition, or sudden feveraccompanied by sore throat or inflamed mouth, or urinary problems: methotrexate can very rarely [may affect up to 1 in 10,000 people] cause a sharp reduction in the number of white blood cells (agranulocytosis) and severe bone marrow depression
• sudden bleeding, e.g. bleeding gums, blood in the urine,vomiting with blood or bruising: these may be signs of a severe reduction in the number of platelets caused by severe bone marrow depression [very rare - may affect up to 1 in 10,000 people]
• severe skin rash or blisters (may also occur on the mouth, eyes andgenitals): these may be signs of a very rare [may affect up to 1 in 10,000 people] condition called Stevens Johnson syndrome or toxic epidermal necrolysis. Other side effects, listed below, may also occur:

Very common: may affect more than 1 in 10 people

• Inflammation of the mouth, indigestion, nausea, loss of appetite
• Increased liver enzymes

Common: may affect up to 1 in 10 people

• Mouth ulcers, diarrhea
• Skin rash, redness of the skin, itching
• Headache, fatigue, drowsiness
• Reduced formation of blood cells with a decrease in white blood cells and/or red blood cells and/or platelets (leukopenia, anemia, thrombocytopenia)

Uncommon: may affect up to 1 in 100 people

• Sore throat, inflammation of the intestine, vomiting
• Increased sensitivity to light, hair loss, increased number of rheumatic nodules, shingles, inflammation of blood vessels, skin rashes similar to herpes, hives
• Onset of diabetes mellitus
• Dizziness, confusion, depression
• Decreased serum albumin
• Reduction in the number of blood cells and platelets
• Inflammation and ulceration of the urinary bladder or vagina, reduced kidney function, problems with urination
• Joint pain, muscle pain, osteoporosis (reduced bone mass) Rare: may affect up to 1 in 1,000 people
• Increased skin pigmentation, acne, bruising due to bleeding from blood vessels
• Allergic inflammation of blood vessels, fever, red eyes, infection, difficulty healing wounds, reduced number of antibodies in the blood
• Visual disturbances
• Inflammation of the membrane surrounding the heart, fluid accumulation in the membrane surrounding the heart
• Low blood pressure
• Pulmonary fibrosis, shortness of breath and bronchial asthma, fluid accumulation in the membrane lining the lungs
• Electrolyte disturbances.

Very rare: may affect up to 1 in 10,000 people

• Heavy bleeding, toxic megacolon (acute toxic dilation of the intestine)
• Increased pigmentation of the nails, inflammation of the areas around the cuticles, furuncles (deep infection of hair follicles), visible thickening of small blood vessels (capillaries)
• Local damage (formation of sterile abscesses, changes in adipose tissue) at the injection site after intramuscular or subcutaneous administration.
• Visual disturbances, pain, loss of strength or numbness or tingling in arms and legs, changes in taste (metallic taste), convulsions, paralysis, severe headache accompanied by fever
• Retinopathy (eye disorders of non-inflammatory origin)
• Loss of libido, impotence, enlargement of male breast glands (gynecomastia), abnormal sperm formation, menstrual disorders, vaginal bleeding
• Enlargement of lymph nodes (lymphoma)
• lymphoproliferative disorders (excessive growth of white blood cells)

Frequency not known: cannot be estimated from available data:

• Leukoencephalopathy (disease of the white matter of the brain)
• bone damage in the mandible/jaw (secondary to excessive growth of white blood cells)

Subcutaneous administration of methotrexate is locally well tolerated. Only
mild local skin reactions have been observed which have decreased during therapy.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through
the national reporting system at www.agenziafarmaco.gov.it/it/responsabili.
By reporting side effects you can help provide more information on the safety
of this medicine.

5. How to store VELOS

Keep this medicine out of the sight and reach of children.
Store at a temperature below 25  C.
Store the pre-filled syringes in the outer carton to protect the medicine from light.
Do not use this medicine after the expiry date which is reported on the label and on the carton after
EXP. The expiry date refers to the last day of that month.
Single use only. Any remaining solution must be discarded.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Content of the pack and other information

What VELOS contains

• The active ingredient is methotrexate: VELOS 2.5 mg: Each pre-filled syringe of 0.33 ml contains 2.5 mg of methotrexate. VELOS 7.5 mg: Each pre-filled syringe of 0.30 ml contains 7.5 mg of methotrexate. VELOS10 mg: Each pre-filled syringe of 0.40 ml contains 10 mg of methotrexate. VELOS12.5 mg: Each pre-filled syringe of 0.31 ml contains 12.5 mg of methotrexate. VELOS15 mg: Each pre-filled syringe of 0.38 ml contains 15 mg of methotrexate. VELOS17.5 mg: Each pre-filled syringe of 0.44 ml contains 17.5 mg of methotrexate. VELOS20 mg: Each pre-filled syringe of 0.50 ml contains 20 mg of methotrexate. VELOS22.5 mg: Each pre-filled syringe of 0.56 ml contains 22.5 mg of methotrexate. VELOS25 mg: Each pre-filled syringe of 0.63 ml contains 25 mg of methotrexate. VELOS27.5 mg: Each pre-filled syringe of 0.69 ml contains 27.5 mg of methotrexate. VELOS30 mg: Each pre-filled syringe of 0.75 ml contains 30 mg of methotrexate.
• The other components are sodium chloride, sodium hydroxide for pH adjustment, water for injections

Description of the appearance of VELOS and contents of the pack
VELOS syringes contain a clear, yellow-orange solution free from visible particles.

Packs:
VELOS syringes pre-filled with a fixed injection needle, and a rigid protective cap

alcohol-soaked pads> are available in packs of 1 and 4 syringes.

are equipped with a safety system to help prevent injuries due to needle puncture.>
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Difa Cooper S.p.A, 21042, Caronno Pertusella (VA)
Manufacturer
Actavis Italy S.p.A. Via Pasteur 10, Nerviano (MI) 20014 Italy
S.C. Sindan-Pharma S.r.l. 11 Ion Mihalache Blvd, Bucharest – 011171 Romania

This medicinal product is authorised in the Member States of the European Economic Area with the
following denominations:
VELOS

Instructions for use
Read these instructions carefully before starting the injection and always use the injection technique
recommended by your doctor, pharmacist or nurse.
For single use only. Any residual solution must be discarded.
The solution must be clear and free from particles.
If you have any problems or questions, contact your doctor, pharmacist or nurse.

Preparation
Choose a clean, well-lit and flat work surface.
Before starting, gather everything you need:

• 1 pre-filled syringe of VELOS
• 1 pad soaked in disinfectant (alcohol-soaked pad) <(supplied in the pack)> Wash your hands carefully. Before use, check the VELOS syringe for any visible defects (or cracks).

Injection site
The best injection sites are:

• upper thigh,
• abdomen, excluding the area around the navel.

• If you have someone to help you with the injection, the injection can also be given on the back of the arm, just below the shoulder.
• Change the injection site with each injection. This way you can reduce the risk of developing irritation at the injection site.
• Never inject into areas of delicate skin, bruising, redness, hardness, scars or stretch marks. If you suffer from psoriasis, try not to inject directly onto lesions or areas of skin that are raised, thick, red or have scaling skin or lesions.

Injecting the solution

• 1. Remove the pre-filled methotrexate syringe from the pack and read the leaflet carefully. Remove the pre-filled syringe from the pack at room temperature.
• 2. Disinfection

Choose an injection site and disinfect it with a pad soaked in disinfectant

for example using the alcohol-soaked pad included in the pack>.
Allow the disinfectant to dry for at least 60 seconds.

• 3. Remove the plastic protective cap Carefully remove the plastic protective cap by pulling it straight off the syringe. If the cap is very tight, rotate it gently while pulling. Important: Do not touchthe needle of the pre-filled syringe!

• 4. Inserting the needle Using two fingers, pinch up the skin and quickly insert the needle into the skin at a 90-degree angle.

Note: it is normal to have a small air bubble in the syringe. Do not try to remove this air bubble before giving the injection – if you do, you may lose some of the medicine.
< Pre-filled syringes without the needle protection safety system:>
[5. Injection
Insert the needle completely into the skin fold. Inject the liquid subcutaneously by slowly pressing the plunger all the way down into the syringe. Keep a firm hold of the skin fold until the injection is complete.
Carefully withdraw the needle in a vertical direction.

To avoid any injury, put the needle back into the protective cap using one hand and gently press the cap back into place.
< Pre-filled syringes with the needle protection safety system:>
[5. Injection
VELOS pre-filled syringe is equipped with a safety system to help prevent injuries due to needle puncture after use. The following instructions are specific to this safety system and may differ from the instructions for other injection systems.
Insert the needle completely into the skin fold. Inject the liquid subcutaneously by slowly pressing the plunger all the way down into the syringe. Keep a firm hold of the skin fold until the injection is complete.
Carefully withdraw the needle in a vertical direction, keeping your finger on the plunger.

Orienting the needle outwards away from you and others, activate the safety system by firmly pressing the plunger. The protective sleeve will automatically cover the needle and you will hear a “click” confirming the activation of the protection.

• 6. Immediately dispose of the syringe in sharps containers.

Methotrexate must not come into contact with the skin surface or mucous membranes. If contamination occurs, the affected area must be immediately rinsed with plenty of water.
If you or someone near you is injured with the needle, consult a doctor immediately and do not use the pre-filled syringe.

Disposal and other handling
Handling and disposal must be carried out as for other cytotoxic preparations in accordance with local regulations. Healthcare professionals who are pregnant should refrain from handling and/or administering VELOS.