METOXALENE G.L. PHARMA 20 micrograms/ml SOLUTION FOR MODIFICATION OF BLOOD FRACTIONS

Introduction

Package Leaflet: Information for the Patient

Methoxsalen 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, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the package leaflet:

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

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

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

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

Methoxsalen G. L. Pharma 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 Methoxsalen G. L. Pharma

Do not use Methoxsalen 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 yet taken any 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 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 per mm3).

Warnings and precautions

Talk to your doctor before you start using Methoxsalen G. L. Pharma.

• If you normally take medicines that lower high blood pressure, you should wait until the end of the photopheresis treatment before taking them again.
• To ensure that the photopheresis procedure can be carried out effectively, the level of triglycerides (a certain 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 Methoxsalen 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 damage to skin and eyes

Methoxsalen G. L. Pharma will make your skin more sensitive to sunlight and artificial light similar to sunlight. Since the amount of medicine used in the treatment with photopheresis 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 photopheresis treatment.

During treatment with Methoxsalen G. L. Pharma and for 24 hours thereafter, you should wear special sunglasses (that prevent the passage of UVA rays) to prevent light from damaging your eyes.

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

Children and adolescents (under 18 years)

Methoxsalen G. L. Pharma should not be used in children and adolescents as there is not enough experience available for this age group.

Using Methoxsalen G. L. Pharma with other medicines

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

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

The effect of Methoxsalen G. L. Pharma is influenced 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, in particular 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, Bengal rose, methyl orange)
• medicines that contain caffeine.

Using Methoxsalen G. L. Pharma with drinks and alcohol

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

You should avoid alcohol during treatment with Methoxsalen G. L. Pharma because the effects of ethanol (alcohol) contained in Methoxsalen G. L. Pharma may increase with other medicines taken at the same time.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Methoxsalen G. L. Pharma should not be used during pregnancy and breastfeeding.

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

Driving and using machines

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

You should not drive or use machines immediately after treatment.

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

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

Methoxsalen G. L. Pharma 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 to you 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.

Methoxsalen G. L. Pharma contains sodium

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

3. How to use Methoxsalen G. L. Pharma

This medicine is always administered by a specialist doctor who is completely familiar with the handling 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 the administration of photopheresis 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 Methoxsalen G. L. Pharma for you, exposed to UV light radiation, and then returned to your body.

During the administration of the treatment and for 24 hours thereafter, you should wear special sunglasses (that prevent the passage of UVA rays) at all times to prevent light from damaging your eyes and causing cataracts.

Duration of treatment

During the first 3 months, it is recommended to treat patients 2 days in a row every 2 to 4 weeks. Subsequently, 2-day treatment cycles usually take place every 3 to 4 weeks. At the time of the best response to treatment, the intervals will be slowly extended to 4 to 8 weeks and treatment will continue 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 more.

If you do not respond to photopheresis treatment alone, your doctor may recommend another additional medicine (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 from three to four hours in total, from the moment your doctor inserts the needle to the moment all components of your blood have been returned to you.

Patients with liver or kidney impairment

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

After treatment

After receiving the treatment, you should avoid direct sunlight for at least 24 hours because it could damage your skin by causing sunburn or premature aging of the skin in the long term. If you need to go outside, you should cover your skin, use a product with a high sun protection factor, and wear special sunglasses (see above).

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

Overdose is unlikely. However, if you are given an overdose, you will have to stay in a dark room for 24 hours or more as part of your treatment.

If you have any further questions on 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 venous puncture.

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

• eye changes 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 side effects:

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report side effects directly to the Spanish Medicines and Health Products Agency (AEMPS) via the website: https://www.notificaram.es. By reporting side 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 which is stated on the carton after EXP. The expiry date is the last day of the month stated.

6. Contents of the pack and other information

Composition of Methoxsalen 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 ingredients are: sodium chloride, ethanol 96%, water for injections.

Appearance and packaging of the product

Clear and colorless solution.

The solution has a pH of 5.0 to 7.0.

Ambber glass ampoules of 5 ml.

Package sizes: packs of 5, 25, 50 ampoules and a multipack of 5 packs with 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 medicine is authorised in the Member States of the EEA 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 last revision of this leaflet: July 2017

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