METOXALENO MACOPHARMA 20 micrograms/ml SOLUTION FOR MODIFICATION OF BLOOD FRACTIONS

Introduction

Package Leaflet: Information for the Patient

Metoxaleno Macopharma 20 micrograms/ml solution for modification of blood fractions

Read all of this leaflet carefully before you start using this medicine 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 or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist, even if you have read it in this leaflet. See section 4.

Contents of the pack:

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

1. What is Metoxaleno Macopharma and what is it used for

The active substance of this medicine is metoxalene, a medicine that is activated by ultraviolet radiation.

Metoxalene binds to white blood cells or leukocytes outside the body and is activated by ultraviolet light (long-wave ultraviolet light). Then, the leukocytes are returned to the body. This process is called photopheresis. As a result of this process, diseased white blood cells can be destroyed, preventing them from attacking your body from the inside. This will interrupt the defense mechanism of the body's immune system to stop the symptoms of the disease.

This medicine is used to relieve skin symptoms of advanced cutaneous T-cell lymphoma (a tumor that occurs in the skin and is caused by specific white blood cells, known as T lymphocytes) when other treatments have not been effective.

2. What you need to know before you use Metoxaleno Macopharma

Do not use Metoxaleno Macopharma

• if you are allergic to metoxalene, related substances (psoralens) or any of the other components of this medicine (included in section 6),
• if you have skin cancer (e.g. melanoma or basal cell carcinoma);
• if you suffer from a disease related to increased sensitivity to light (photosensitivity), such as porphyria, systemic lupus erythematosus or albinism,
• if you are sexually active and of childbearing age and have not taken any contraceptive measures,
• if you have had your lens removed from your eye,
• if you are pregnant or breastfeeding.

A photopheresis procedure should not be performed:

• if your body cannot tolerate the temporary blood loss caused by treatment, for example, due to heart disease or severe anemia;
• if you have had your spleen removed,
• if you have a blood coagulation disorder,
• if you have a high number of white blood cells (more than 25,000/mm3).

Warnings and precautions

Consult your doctor before receiving treatment with this medicine:

• If you regularly take medications to lower blood pressure, you should wait until the end of photopheresis treatment before taking them.
• For photopheresis to be performed effectively, the concentration of triglycerides (a certain fatty component) in your blood should be as low as possible. Therefore, your doctor will instruct you to fast before each treatment.
• During treatment with this medicine, sexually active men and women of childbearing age should use an adequate contraceptive method.
• If you have liver problems, your doctor may require monitoring of your blood counts.

Important notes to prevent skin and eye damage

This medicine will make your skin more sensitive to sunlight and artificial light similar to sunlight. Since the amount of medicine used in photopheresis treatment is very low, it is unlikely that this side effect will occur. However, to minimize the risk of side effects, especially in the eyes and skin, you should not expose yourself to sunlight for at least 24 hours after photopheresis treatment.

During treatment with this medicine and for 24 hours thereafter, you should wear special sunglasses that block UVA rays to protect your eyes from damage.

Inform your doctor if you have liver function problems, as you may need to continue these precautions against sun exposure for a longer period.

Children and adolescents

This medicine is not indicated for use in children and adolescents (under 18 years), as there is not enough experience in this age group.

Other medicines and Metoxaleno Macopharma

Inform your doctor if you are taking, have recently taken, or may need to take any other medicine.

Phenytoin (a medicine used to treat seizures) may cause faster elimination of this medicine from the body and thus decrease the effectiveness of photopheresis treatment.

The effect of this medicine is affected by substances that can also destroy cells or increase sensitivity to light. These include:

• other medicines used to treat skin diseases (e.g. anthralin, coal tar, griseofulvin, retinoids).
• various antibiotics (e.g. tetracyclines, fluoroquinolones) and chemotherapeutic agents (e.g. nalidixic acid, sulfonamides).
• medicines used to treat diabetes (sulfonylureas, particularly tolbutamide)
• diuretics ("water pills", e.g. thiazides, furosemide).
• medicines with a calming and/or sedative effect (phenothiazines).
• certain medicines that affect blood coagulation (oral anticoagulants derived from coumarin, halogenated salicylanilide derivatives).
• dyes (e.g. methyl blue/toluidine, rose bengal, methyl orange)
• medicines that contain caffeine.

Use of Metoxaleno Macopharma with beverages and alcohol

You should avoid drinking coffee or tea during treatment with this medicine. The substances they contain (caffeine, theophylline) can prolong the duration of light sensitivity.

You should avoid alcohol during treatment with metoxalene because the effects of ethanol (alcohol) it contains may be increased with other medicines taken at the same time.

Pregnancy and breastfeeding

This medicine should not be used during pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

If you are sexually active and of childbearing age, you should use adequate contraceptive methods during treatment with this medicine, as the active substance, metoxalene, can harm the unborn child during treatment with this medicine. In males and females, contraceptive measures should be continued for 3 months and 6 months, respectively, after the last cycle of photopheresis treatment.

Driving and using machines

Warning: this medicine may affect your reaction ability and ability to drive.

Do not drive or use machines immediately after treatment.

Metoxaleno Macopharma contains ethanol and sodium

This medicine contains 10.4% ethanol (alcohol), which corresponds to 10.4 mg/ampoule.

This medicine contains small amounts of ethanol (alcohol), less than 100 mg per milliliter. In extracorporeal therapy, it can be expected that the general effects on your body will be limited. However, the doctor who prescribes it will monitor you for possible interactions with other medicines. Special caution is required in patients with liver disorders, alcoholism, epilepsy, brain injury, or brain disease.

This medicine contains less than 23 mg (1 mmol) of sodium per milliliter; it is essentially "sodium-free".

3. How to use Metoxaleno Macopharma

This medicine is always administered by a specialist doctor who is perfectly familiar with the handling of this medicine. Your doctor will decide how many treatment sessions you need.

Method of administration

Extracorporeal use (i.e. outside the patient's body).

The contents of the ampoule are never injected directly into the patient.

A professional specially trained in the administration of photopheresis will use a needle to draw a small amount of blood from one of your veins. This blood is separated into red blood cells, white blood cells, and plasma. The red blood cells and most of the plasma are returned to the bloodstream during the procedure. The white blood cells and the remaining plasma are mixed with a individually calculated dose of this medicine for you, exposed to ultraviolet light radiation, and then returned to your body.

During the administration of your treatment and for 24 hours thereafter, you should wear special sunglasses that block UVA rays to protect your eyes from damage, as they can cause cataract formation.

Duration of treatment

During the first 3 months, it is recommended to treat patients on 2 consecutive days every 2 to 4 weeks. After that, 2-day treatment cycles usually take place every 3 to 4 weeks.

Once the best therapeutic response is achieved, the intervals will be gradually extended to 4 or 8 weeks, and from then on, treatment should continue every 8 weeks.

Photopheresis should be performed for at least 6 months.

If you respond well to treatment or if your disease does not worsen, photopheresis should continue for 2 years or more.

If you do not respond to photopheresis treatment alone, your doctor may recommend another additional medicine (e.g. interferon, bexarotene, or both).

This is a general guide. Your doctor may adapt the treatment cycle based on individual symptoms and response.

The procedure lasts from 3 to 4 hours in total, from when the doctor places the needle until all blood components are returned.

Patients with impaired liver or kidney function

If you have liver or kidney problems, your doctor will probably check your blood count regularly. This medicine has not been clinically tested in patients with impaired liver or kidney function.

After treatment

After receiving treatment, you should avoid direct sunlight for at least 24 hours, as skin damage, such as sunburn or premature aging of the skin, may occur. If you need to go outside, cover your skin, use a sunscreen with a high protection factor, and wear special sunglasses (see above).

If you use more Metoxaleno Macopharma than you should

Overdose is unlikely. However, if you have been given an overdose, you should stay in a dark room for 24 hours or more.

If you have any other questions about the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following side effects have been reported:

Common(may affect up to 1 in 10 people)

• infections.
• low blood pressure, dizziness.
• nausea, vomiting.
• complications in venous access after repeated venipunctures.

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

• eye changes due to light exposure (phototoxic reactions), such as cataract formation and inflammation of the middle layer of the eye (choroid) with subsequent inflammation of the retina (chorioretinitis);
• skin changes due to light exposure (phototoxic reactions) such as itching or redness of the skin;
• fever (mild fever may occur between 2 and 12 hours after treatment).

Reporting of side effects:

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

5. Storage of Metoxaleno Macopharma

Keep in the original packaging to protect it from light. This medicine should be used immediately after opening.

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

Do not use this medicine after the expiry date stated on the carton. The expiry date is the last day of the month indicated.

Do not use this medicine if you notice the presence of visible particles.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Metoxaleno Macopharma

• The active substance is metoxalene. One 5 ml ampoule contains 100 micrograms (μg) of metoxalene. 1 ml of solution contains 20 micrograms of metoxalene.
• The other ingredients are: sodium chloride, ethanol 96%, water for injectable preparations.

Appearance of Metoxaleno Macopharma and contents of the pack

Clear and colorless solution, free of visible particles.

The solution has a pH of 5.0 to 7.0.

Metoxalene is presented in 5 ml amber glass ampoules, in a PVC blister/tray, covered or not with a transparent film, placed in a carton.

Package sizes: 50 ampoules

Marketing authorisation holder

Maco Pharma

Rue Lorthiois

59420 Mouvaux

France

Manufacturer

G.L. Pharma GmbH

Schlossplatz 1

8502 Lannach

Austria

You can request more information about this medicine by contacting the local representative of the marketing authorisation holder:

Maco Spania S.L.

Avenida de la Vega, 1

28108 Alcobendas,

Madrid - Spain

This medicine is authorised in the Member States of the EEA under the following names:

Austria: Methoxsalen Macopharma 20 micrograms/ml solution for modification of blood fractions

Belgium: Methoxsalen Macopharma 20 micrograms/ml solution for modification of blood fractions (German)/Methoxsalen Macopharma 20 micrograms/ml solution for the preparation of blood fractions (French)/Methoxsalen Macopharma 20 micrograms/ml solution for modification of blood fractions (Dutch)

Czech Republic: Methoxsalen Maco Pharma

Slovenia: Metoksalen Maco Pharma, 20 micrograms/ml solution for modification of blood fractions

Spain: Metoxaleno Macopharma 20 micrograms/ml solution for modification of blood fractions

France: METHOXSALEN MACOPHARMA 20 micrograms/ml solution for modification of blood fractions

Germany, Denmark, Hungary, Italy, Poland, Sweden: Methoxsalen Macopharma

United Kingdom: Methoxsalen Macopharma 20 micrograms/ml solution for blood fraction modification

Date of last revision of this leaflet: September 2021

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.