Prospect: Patient Information

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

Read this prospect carefully before starting to use this medication, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

The active ingredient of this medication is metoxaleno, a medication that is activated by ultraviolet radiation.

Metoxaleno adheres to white blood cells or leucocytes outside the body and is activated by ultraviolet light (long-wave ultraviolet light).Subsequently, the leucocytes are returned to the body. This process is called photoapheresis. As a result of this process, diseased white blood cells can be destroyed, preventing them from attacking the body from within. This will interrupt the body's immune system defense mechanism to stop the symptoms of the disease.

This medication is used to alleviate skin symptoms of the advanced phase of 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.

No use Metoxaleno Macopharma

• If you are allergic to metoxaleno, related substances (psoralenos) or any of the other components of this medication (listed in section 6),
• If you have skin cancer (for example, melanoma or basal cell carcinoma);
• If you have 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 crystalline lens removed from your eye,
• If you are pregnant or breastfeeding.

Do not perform a photoapheresis procedure:

• If your body cannot tolerate the temporary loss of blood caused by the treatment, for example, due to heart disease or severe anemia;
• If you have had your spleen removed,
• If you have a blood clotting 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 medication:

• If you are taking medications to lower blood pressure, you should wait until the end of the photoapheresis treatment before taking them.
• To ensure the photoapheresis procedure can be performed effectively, the concentration of triglycerides (a certain type of fat) in your blood should be as low as possible. Therefore, your doctor will instruct you to fast before each treatment.
• During treatment with this medication, sexually active men and women of childbearing age should use an appropriate contraceptive method.
• If you have liver problems, your doctor may require monitoring of your liver values.

Important notes to prevent skin and eye damage

This medication will make your skin more sensitive to sunlight and artificial light similar to sunlight. Since the amount of medication used in the photoapheresis treatment is very low, it is unlikely that this adverse effect will occur. However, to minimize the risk of adverse effects, especially on the eyes and skin, you should not expose yourself to sunlight during the first 24 hours after the photoapheresis treatment.

During treatment with this medication and for 24 hours afterwards, 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 sunlight exposure for a longer period.

Children and adolescents

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

Other medications and Metoxaleno Macopharma

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

The phenytoin (a medication used to treat seizures) may cause a faster elimination of this medication from your body and therefore reduce the effectiveness of the photoapheresis treatment.

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

• Other medications used to treat skin conditions (for example, anthralin, coal tar, griseofulvin, retinoids).
• Various antibiotics (for example, tetracyclines, fluoroquinolones) and chemotherapeutic agents (for example, nalidixic acid, sulfonamides).
• Medications used to treat diabetes (sulfonylureas, particularly tolbutamide)
• Diuretics ("water-removing tablets", for example, thiazides, furosemide).
• Medications with calming and/or sedative effects (phenothiazines).
• Certain medications that affect blood clotting (oral anticoagulants derived from coumarin, halogenated salicylanilides).
• Dyes (for example, methylene blue/toluidine, Bengal rose, methyl orange)
• Medications containing caffeine.

Use of Metoxaleno Macopharma with beverages and alcohol

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

You should avoid alcohol during treatment with metoxaleno as the effects of ethanol (alcohol) contained in this medication may be increased by other medications taken at the same time.

Pregnancy and lactation

This medication should not be used during pregnancy and lactation

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

If you are sexually active and of childbearing age, you should use an appropriate contraceptive method during treatment with this medication, as the active ingredient, metoxaleno, may harm the conceived child during treatment with this medication. In men and women, contraceptive measures should be continued for 3 months and 6 months, respectively, after completing the last cycle of photoapheresis treatment.

Driving and operating machinery

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

You should not drive or operate machinery immediately after treatment.

Metoxaleno Macopharma contains ethanol and sodium

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

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

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

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

Administration form

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

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

A specially trained professional in the administration of photopheresis will use a needle to extract 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 will be mixed with an individually calculated dose of this medication, exposed to ultraviolet light, and then returned to your body.

You must wear special sunglasses at all times during the administration of your treatment and for the 24 hours following, as they block UVA rays to prevent eye damage, which may cause cataract formation.

Treatment duration

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

Once the best therapeutic response is achieved, the intervals will gradually increase to 4 to 8 weeks, and from there, 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 an additional medication (e.g., interferon, bexarotene, or both).

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

The procedure takes a total of 3 to 4 hours, from when the doctor places the needle to when all blood components are returned.

Patients with liver or renal function impairment

If you have liver or kidney problems, your doctor will likely check your blood count regularly. This medication has not been clinically tested in patients with renal or hepatic function impairment.

After treatment

After receiving treatment, you should avoid direct sunlight for at least 24 hours, as it is possible to cause skin damage, such as sunburns or, in the long term, premature skin aging. If you need to go outside, cover your skin, use a high-protection sunscreen, and wear special sunglasses (see above).

If you use more Metoxaleno Macopharma than you should

A overdose is unlikely. However, if you have been administered an overdose, you should remain in a dark room for 24 hours or more.

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

Like all medications, this medication may produce adverse effects, although not all people will experience them.

The following adverse effects have been reported:

Frequent(may affect up to 1 in 10 people)

• Infections.
• Low blood pressure, dizziness.
• Nausea, vomiting.
• Complications in venous access after repeated venipuncture.

Unknown Frequency(cannot be estimated from available data)

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

Reporting Adverse Effects:

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

Store in the original packaging to protect it from light. This medication must be used immediately after opening.

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date that appears on the box. The expiration date is the last day of the month indicated.

Do not use this medication if you observe visible particles.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Methoxsalen Macopharma Composition

• The active ingredient is methoxsalen. A 5 ml ampoule contains 100 micrograms (μg) of methoxsalen. 1 ml of solution contains 20 micrograms of methoxsalen.
• The other components are: sodium chloride, ethanol at 96%, water for injectable preparations.

Methoxsalen Macopharma Appearance and Packaging Contents

Clear and colorless solution, free of visible particles.

The solution has a pH value of 5.0 to 7.0.

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

Packaging sizes: 50 ampoules

Marketing Authorization Holder

Maco Pharma

Rue Lorthiois

59420 Mouvaux

France

Responsible for Manufacturing

G.L. Pharma Gmbh

Schlossplatz 1

8502 Lannach

Austria

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

Maco Spania S.L.

Avenida de la Vega, 1

28108 Alcobendas,

Madrid - Spain

This medicinal product is authorized in the Member States of the EEA with the following names:

Austria:Methoxsalen Macopharma 20 micrograms/mL, Solution for modification of a blood fraction

Belgium: Methoxsalen Macopharma 20 Mikrogramm/mL Lösung zur Modifikation einer Blutfraktion (German)/Methoxsalen Macopharma 20 microgrammes/mL solution pour la préparation ex vivo de fractions sanguines (French)/Methoxsalen Macopharma 20 micrograms/ml oplossing voor het modificeren van een bloedfractie (Dutch)

Czech Republic: Methoxsalen Maco Pharma

Slovenia: Metoksalen Maco Pharma, 20 mikrogramov/ml raztopina za modificiranje krvnih frakcij

Spain: Metoxaleno Macopharma 20 microgramos/mL solution for modification of blood fractions

France: METHOXSALEN MACOPHARMA 20 microgrammes/mL, solution for modification of the blood fraction

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

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

Last review date of this leaflet: September 2021

Further detailed information about this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/.