Metoxaleno G.L. Pharma 20 micrograms/ml solution for modification of blood components

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the patient

Metoxalene G. L. Pharma 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 as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor or pharmacist, even if it is a side effect not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What Metoxaleno G. L. Pharma is and what it is used for

The active substance of Metoxaleno G. L. Pharma is methoxsalen, a medicine that is activated by UV radiation.

Methoxsalen binds to your leukocytes outside the body and is activated by ultraviolet light (long-wave UV light). The leukocytes are then returned to your body. This process is called photopheresis. As a result of this process, diseased leukocytes may be destroyed.

Metoxaleno G. L. Pharma is used to relieve cutaneous symptoms of advanced-stage cutaneous T-cell lymphoma (a tumor occurring in the skin caused by specific leukocytes known as T-lymphocytes) when other treatments have not been effective.

2. What you need to know before starting to use Metoxalen G. L. Pharma

Do not use Metoxalen G. L. Pharma:

• if you are allergic to methoxsalen, related substances (psoralens), or any of the other components of this medicine (listed in section 6)
• if you have skin cancer (e.g. melanoma or basal cell carcinoma)
• if you have a disease associated with 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 contraceptive measures
• if you have had your lens removed
• if you are pregnant or breastfeeding

Photopheresis procedure must not be used:

• 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 coagulation disorder.
• if you have a high number of white blood cells (more than 25,000 per mm³).

Warnings and precautions

Talk to your doctor before starting to use Metoxalen G. L. Pharma.

• If you normally take medications to lower high blood pressure, you should wait until the end of the photopheresis treatment before resuming them.
• To ensure that the photopheresis procedure can be carried out effectively, the level of triglycerides (a specific component of fat) in the blood should be as low as possible. Therefore, your doctor will instruct you to fast before each treatment.
• During treatment with Metoxalen G. L. Pharma, sexually active men and women of childbearing age must use an appropriate contraceptive method.
• If you have liver problems, your doctor may take measures to monitor your liver values.

Important notes to prevent skin and eye damage

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

During treatment with Metoxalen G. L. Pharma and for 24 hours afterwards, you must wear special sunglasses (blocking UVA rays) to prevent light from damaging your eyes.

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

Children and adolescents (under 18 years of age)

Metoxalen G. L. Pharma must not be used in children and adolescents, as there is insufficient experience available for this age group.

Use of Metoxalen G. L. Pharma with other medicines

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

Phenytoin (a medicine used to treat seizures) may lead to faster elimination of Metoxalen G. L. Pharma from the body and thus reduce the effectiveness of photopheresis treatment.

The effect of Metoxalen G. L. Pharma is influenced by substances that may also destroy cells or increase light sensitivity. 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 tablets", e.g. thiazides, furosemide).
• medicines with calming and/or sedative effects (phenothiazines).
• certain medicines affecting blood coagulation (oral anticoagulants derived from coumarin, halogenated salicylanilide derivatives).
• dyes (e.g. methylene blue/toluidine blue, rose bengal, methyl orange).
• medicines containing caffeine.

Use of Metoxalen G. L. Pharma with food and alcohol

You should avoid drinking coffee or tea during treatment with Metoxalen G. L. Pharma. Substances present in these beverages (caffeine, theophylline) may prolong the duration of light sensitivity.

You should avoid alcohol during treatment with Metoxalen G. L. Pharma because the effects of ethanol (alcohol) contained in Metoxalen G. L. Pharma may be increased when taken together with other medicines.

Pregnancy and breastfeeding

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

Metoxalen G. L. Pharma must not be used during pregnancy and breastfeeding.

If you are sexually active and of childbearing age, you must use appropriate contraceptive methods during treatment with Metoxalen G. L. Pharma, because the active substance methoxsalen may cause harm to children conceived during treatment with Metoxalen G. L. Pharma.

Driving and use of machines

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

You must not drive or operate machinery immediately after treatment.

Metoxalen G. L. Pharma contains ethanol 96% (alcohol)

This medicine contains 10.4% ethanol (alcohol); this small amount corresponds to 10.4 mg/vial.

Metoxalen G. L. Pharma contains small amounts of ethanol (alcohol), less than 100 mg per milliliter. In extracorporeal therapy, systemic effects on the body are expected to be limited. However, your prescribing doctor 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.

Metoxalen G. L. Pharma contains sodium

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

3. How to use Methoxsalen G. L. Pharma

This medicine is always administered by a specialist doctor who is fully familiar with the management of Methoxsalen G. L. Pharma. 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 specially trained professional in 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 an individually calculated dose of Methoxsalen G. L. Pharma, exposed to UV light radiation, and then returned to your body.

During treatment administration and for 24 hours afterwards, you must wear sunglasses (which block UVA rays) at all times to prevent light from damaging your eyes and causing cataracts.

Duration of treatment

During the first 3 months, patients are recommended to be treated on two consecutive days every 2 to 4 weeks. Subsequently, the two-day treatment cycles usually occur once every 3 to 4 weeks. At the time of optimal response to treatment, intervals may be gradually extended to every 4 to 8 weeks, and treatment continued every 8 weeks thereafter.

Photopheresis should be performed for at least 6 months.

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

If you do not respond to photopheresis alone, your doctor may recommend adding another medication (e.g., interferon and/or bexarotene).

This is a general guideline. Your doctor may adapt the treatment cycle according to individual symptoms and response.

The procedure lasts a total of three to four hours, from the moment your doctor inserts the needle until all components of your blood have been returned to you.

Patients with hepatic or renal impairment

If you have liver or kidney problems, your doctor will likely monitor your blood cell counts regularly; Methoxsalen G. L. Pharma has not been clinically tested in patients with renal or hepatic impairment.

After treatment

After receiving treatment, you must avoid direct sunlight for at least 24 hours, as it could damage your skin, causing sunburn or long-term premature skin aging. If you need to go outdoors, you must cover your skin, use a high-protection sunscreen product, and wear special sunglasses (see above).

If you use more Methoxsalen G. L. Pharma than you should

An overdose is unlikely. However, if an overdose is administered, you will need to remain in a darkened room for 24 hours or longer as part of your treatment.

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

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone experiences 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 at the vein access site following repeated venous access (venipuncture).

Frequency not known (cannot be estimated from available data)

• changes in the eye as a result of 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).
• skin changes due to light exposure (phototoxic reactions), such as itching or redness.
• fever (mild fever may occur between 2 and 12 hours after treatment).

Reporting of 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 leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Methoxsalen G. L. Pharma

Keep in the original packaging to protect from light.

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

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

6. Contents of the pack and other information

Composition of Metoxaleno G. L. Pharma

• The active substance is methoxsalen. One 5 ml ampoule contains 100 micrograms (μg) of methoxsalen. One ml of solution contains 20 micrograms of methoxsalen.
• The other components are: sodium chloride, ethanol 96%, water for injections.

Appearance of the product and contents of the pack

Clear, colourless solution.

The solution has a pH value of 5.0 to 7.0.

Amber glass ampoules of 5 ml.

Pack sizes: packs of 5, 25, 50 ampoules and multiple pack of 5 boxes containing 25 ampoules each.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

G.L. Pharma GmbH,

Schlossplatz 1, 8502

Lannach, Austria

Local Representative

Waas-Anita, S.A.

C/ General Prim, 13

28035 Madrid

Spain

This medicinal product is authorised in EEA Member States under the following names:

Austria: Oxsoralen 20 µg/ml-Lösung zur Modifikation einer Blutfraktion

Germany: Methoxsalen G.L. Pharma 20 µg/ml Lösung zur Modifikation einer Blutfraktion

Italy: Metoxsalene G.L. Pharma 20 µg/ml soluzione per la modifica di frazione ematica

United Kingdom: Methoxsalen G.L. Pharma 20 µg/ml solution for blood fraction modification

Date of the most recent review of this leaflet: July 2017

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.