METOXALENO S.A.L.F. 20 micrograms/ml SOLUTION FOR MODIFICATION OF BLOOD FRACTIONS

Introduction

Package Leaflet: Information for the User

Metoxaleno S.A.L.F. 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, pharmacist, or nurse.

• If you experience side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the package leaflet

1. What is Metoxaleno S.A.L.F. and what is it used for
2. What you need to know before you start using Metoxaleno S.A.L.F.
3. How to use Metoxaleno S.A.L.F.
4. Possible side effects
5. Storage of Metoxaleno S.A.L.F.
6. Contents of the pack and further information

1. What is Metoxaleno S.A.L.F. and what is it used for

The active substance of Metoxaleno S.A.L.F. is metoxaleno, a medicine that is activated by ultraviolet radiation.

Metoxaleno binds to white blood cells or leukocytes outside the body and is activated by ultraviolet light (long-wave ultraviolet light). The leukocytes are then returned to the body. This process is called photoapheresis. As a result of this process, diseased white blood cells can be destroyed.

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 start using Metoxaleno S.A.L.F.

Do not use Metoxaleno S.A.L.F.

• if you are allergic to metoxaleno or any of the other components of this medicine (listed in section 6);
• if you have skin cancer (e.g., melanoma, basal cell carcinoma, or squamous cell carcinoma);
• if you suffer from a disease related to increased sensitivity to light, 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.

Photoapheresis should not be performed:

• if your body cannot tolerate the temporary blood loss 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 coagulation disorder;
• if you have a high number of white blood cells (more than 25,000/mm3).

Warnings and precautions

Consult your doctor, pharmacist, or nurse before you start using this medicine.

Only specially trained personnel can administer this medicine in institutions that have the necessary equipment for this treatment. Therapy should be performed under the constant supervision of a doctor with the appropriate training.

During treatment with metoxaleno, sexually active men and women of childbearing age must use an adequate contraceptive method.

This medicine may cause a decrease in blood pressure. If you regularly take medications to lower blood pressure, you should wait until the end of the photoapheresis treatment before taking them.

In order for the photoapheresis procedure to be carried out 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.

If you have liver problems, your doctor may require monitoring of your liver values.

Important notes to prevent damage to the skin and eyes:

This medicine will make your skin more sensitive to sunlight and artificial light similar to sunlight. Since the amount of medicine used in the photoapheresis 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 during the first 24 hours after photoapheresis treatment.

During treatment with metoxaleno and for 24 hours thereafter, you must 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

Metoxaleno is not indicated for use in children and adolescents, as there is not enough experience in this age group.

Other medicines and Metoxaleno S.A.L.F.

Tell your doctor, pharmacist, or nurse if you are using, have recently used, or might use any other medicine.

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

The effect of metoxaleno 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 sedating 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 S.A.L.F. with beverages and alcohol

You should avoid drinking coffee or tea during treatment with metoxaleno. The substances they contain (caffeine, theophylline) may prolong the duration of light sensitivity. You should avoid alcohol during treatment with metoxaleno because the effects of ethanol (alcohol) it contains may be increased with other medicines taken at the same time.

Pregnancy and breastfeeding

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

This medicine should not be used during pregnancy and breastfeeding.

If you are sexually active and of childbearing age, you should use adequate contraceptive methods during treatment with this medicine, as the active substance, metoxaleno, may harm the unborn child during treatment with metoxaleno.

Driving and using machines

This medicine may affect your reaction and ability to drive. You should not drive or use machines immediately after treatment.

Metoxaleno S.A.L.F. contains ethanol and sodium

This medicine contains up to 162 mg of ethanol (alcohol) per treatment volume of 240 ml (4.1 ml of metoxaleno). The amount in volume of this medicine is equivalent to 4 ml of beer or 1.6 ml of wine. The amount of alcohol in this medicine is unlikely to have effects in adults and adolescents and is likely to have no appreciable effects in children. It may have some effects in smaller children, such as a feeling of sleepiness. The alcohol in this medicine may alter the effects of other medicines. Consult your doctor or pharmacist if you are taking other medicines. If you are pregnant or breastfeeding, consult your doctor or pharmacist before taking this medicine. If you are addicted to alcohol, consult your doctor or pharmacist before taking this medicine.

This medicine contains less than 1 mmol of sodium (23 mg) per milliliter; this is essentially "sodium-free." This medicine contains 17.2 mg of sodium per ampoule (5 ml), equivalent to 0.86% of the maximum recommended daily intake of 2 g of sodium for an adult.

3. How to use Metoxaleno S.A.L.F.

Follow exactly the instructions for administration of this medicine given by your doctor, pharmacist, or nurse. If you are unsure, ask your doctor, pharmacist, or nurse.

Method of administration

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

The contents of the ampoule should never be injected directly into the patient. A specially trained professional in the administration of photoapheresis will use a needle to withdraw 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, exposed to ultraviolet radiation, and then returned to your body.

During administration of your treatment and for 24 hours thereafter, you must wear special sunglasses that block UVA rays at all times to avoid eye 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. Afterward, 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 to 8 weeks, and from then on, treatment should continue every 8 weeks. Photoapheresis should be performed for at least 6 months. If you respond well to treatment or if your disease does not worsen, photoapheresis should continue for 2 years or more.

This is a general guideline. 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.

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.

This medicine should not be injected directly into the patient.

Patients with hepatic or renal impairment

If you have liver or kidney problems, your doctor will likely check your blood count regularly.

This medicine has not been clinically tested in patients with renal or hepatic function impairment.

If you are given more Metoxaleno S.A.L.F. 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 further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

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, edema
• Nausea, vomiting
• Complications in venous access after repeated accesses to the veins (venipuncture).

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

• Changes in the eye due to light exposure (phototoxic reactions), such as cataract formation and inflammation of the middle layer of the eye (choroiditis), with subsequent inflammation of the retina (chorioretinitis).
• Depression, dizziness, headache, insomnia, malaise, nervousness, vertigo.
• Changes in the skin 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, consult your doctor, pharmacist, or nurse. Even if it is a possible side effect not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Metoxaleno S.A.L.F.

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

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

Store in the original packaging to protect from light.

This medicine does not require any special storage temperature.

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 further information

Composition of Metoxaleno S.A.L.F.

• The active substance is metoxaleno. One 5 ml ampoule contains 100 micrograms (μg) of metoxaleno. 1 ml of solution contains 20 micrograms of metoxaleno.
• The other components (excipients) are: propylene glycol, sodium chloride, sodium acetate trihydrate, ethanol 96%, glacial acetic acid, and water for injectable preparations.

Appearance and packaging of the product

Clear and colorless solution.

Ampoules of amber glass of 5 ml.

Package sizes: packs of 5 ampoules.

Marketing authorization holder and manufacturer

S.A.L.F. S.p.A. Pharmacological Laboratory

Via Marconi, 2

24069 Cenate Sotto (BG)

Italy

This medicine is authorized in the Member States of the European Economic Area under the following names:

Date of last revision of this leaflet: 06/2023

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/)