Prospect: Patient Information

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

Read this prospect carefully before starting to use this medication, as 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 ofMetoxaleno G. L. Pharmais metoxaleno, a medication that is activated by UV radiation.

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

Metoxaleno G. L. Pharmais used to alleviate skin symptoms ofcutaneous T-cell lymphoma in advanced stage(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.

Do not use Metoxaleno G. L. Pharma:

• if you are allergic to methoxsalen, related substances (psoralens) or any of the other ingredients of this medication (listed in section 6)
• if you have skin cancer (for example 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 any contraceptive measures
• if you have had a corneal transplant
• if you are pregnant or breastfeeding

Do not use photopheresis:

• 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 a splenectomy
• if you have a bleeding disorder
• if you have a high white blood cell count (more than 25,000 per mm3)

Warnings and precautions

Consult your doctor before starting to useMethoxsalen G. L. Pharma.

• If you normally take medications 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 must be as low as possible. Therefore, your doctor will instruct you to fast before each treatment.
• During treatment withMethoxsalen 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 control your liver values.

Important notes to prevent skin and eye damage

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

During treatment withMethoxsalen G. L. Pharmaand the 24 hours following, you must wear special sunglasses (that prevent the passage of UVA rays) to prevent light from damaging your eyes.

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 (under 18 years)

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

Use of Methoxsalen G. L. Pharma with other medications

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

Phenytoin (a medication used to treat seizures) may lead to faster elimination ofMethoxsalen G. L. Pharmafrom the body and therefore reduce the effectiveness of photopheresis treatment.

The effect ofMethoxsalen G. L. Pharmais influenced by substances that also destroy cells or increase sensitivity to light. These include:

• other medications used to treat skin diseases (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 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 salicylanilide derivatives).
• colorants (for example, methylene blue/toluidine, rosaniline, methyl orange)
• medications containing caffeine.

Use of Methoxsalen G. L. Pharma with beverages and alcohol

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

You should avoid alcohol during treatment withMethoxsalen G. L. Pharmabecause the effects of ethanol (alcohol) inMethoxsalen G. L. Pharmamay increase with other medications taken at the same time.

Pregnancy and lactation

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

Methoxsalen G. L. Pharmashould not be used during pregnancy and lactation.

If you are sexually active and of childbearing age, you should use appropriate contraceptive methods during treatment withMethoxsalen G. L. Pharma, as the active ingredient methoxsalen may cause damage to the fetus conceived during treatment withMethoxsalen G. L. Pharma.

Driving and operating machinery

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

You should not drive or operate machinery immediately after treatment.

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

This medication contains 10.4% ethanol (alcohol), which corresponds to10.4 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 prescribing it will monitor you to detect any possible interactions with other medications. Special caution is required in patients with liver disorders, alcoholism, epilepsy, brain injury or cerebral disease.

Methoxsalen G. L. Pharma contains sodium

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

This medication is always administered by a specialist doctor who is completely familiar with the handling of Metoxaleno G. L. Pharma. Your doctor will decide how many treatment sessions you need.

Administration Method

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 are mixed with an individually calculated dose of Metoxaleno G. L. Pharma, exposed to UV light, and then returned to your body.

During the administration of the treatment and the 24 hours following, you must wear protective eyewear (which prevents the passage of UVA rays) at all times to avoid damaging your eyes, causing cataract formation.

Treatment Duration

During the first 3 months, it is recommended to treat patients 2 consecutive days every 2 to 4 weeks. Subsequently, 2-day treatment cycles usually take place once every 3 to 4 weeks. At the time of the best response to treatment, the intervals will gradually be extended to 4 to 8 weeks, and treatment will 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 be continued for 2 years or more.

If you do not respond to treatment with photopheresis alone, your doctor may recommend an additional medication (e.g., interferon and/or bexaroteno).

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

The procedure takes a total of 3 to 4 hours, from the time your doctor places the needle to the time all components of your blood have been returned.

Patients with liver or renal insufficiency

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

After treatment

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

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

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

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 may 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)

• Eye changes resulting from 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 (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.

Keep this medication out of sight and reach of children.

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

Composition of Metoxaleno G. L. Pharma

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

Appearance of the product and contents of the packaging

Transparent and colorless solution.

The solution has a pH value of 5.0 to 7.0.

Amber glass ampoules of 5 ml.

Package sizes: packages of 5, 25, 50 ampoules and a multiple package of 5 boxes with 25 ampoules each.

It is possible that not all package sizes will be marketed.

Holder of the marketing authorization and responsible 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 authorized in the EEA member states with the following names:

Austria: Oxsoralen 20 µg/ml-Solution for modification of a blood fraction

Germany: Methoxsalen G.L. Pharma 20 µg/ml Solution for modification of a blood fraction

Italy: Metoxsalene G.L. Pharma 20 µg/ml solution for modification of a blood fraction

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

Last review date of this leaflet: July 2017

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