Melfalan Tarbis 50 mg powder and solvent for solution for injection and for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Melphalan Tarbis 50 mg powder and solvent for solution for injection and for infusion EFG

Read the entire 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, pharmacist or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Melfalan Tarbis is and what it is used for

This medicine contains the active substance called melphalan, which belongs to a group of medicines known as cytotoxic agents (also called chemotherapy). It works by reducing the number of abnormal cells produced by the body. This medicine is used for the treatment of cancer.

This medicine is used for:

• Localized malignant melanoma of the limbs (malignant growths locally present in the arms or legs)
• Localized soft tissue sarcoma of the limbs (local neoplasms of the soft tissues of the arms or legs)
• Multiple myeloma: a type of cancer that arises from bone marrow cells called plasma cells. Plasma cells help fight infections and diseases by producing antibodies.
• Advanced neuroblastoma (a cancer affecting the nervous system) in children
• Advanced ovarian carcinoma (ovarian cancer)

You should consult a doctor if your condition worsens or does not improve.

2. What you need to know before using Melfalan Tarbis

Do not use Melfalan Tarbis:

• if you are allergic to melphalan or to any of the other ingredients of this medicine (listed in section 6),
• if you are breastfeeding.

Warnings and precautions

Talk to your doctor or nurse before using this medicine if:

• you have recently received radiation or chemotherapy, or are currently receiving radiation or chemotherapy;
• you have kidney problems;
• you need to be vaccinated. Because melphalan suppresses the body's immune responses, there is an increased susceptibility to infections. Therefore, vaccination with live vaccines is not recommended;
• you have or have had a blood clot in your leg (thrombosis), lung (pulmonary embolism), or another part of your body;
• you have a condition that increases your risk of developing a blood clot in the arteries.

Melphalan may increase the risk of developing other types of cancer (e.g., secondary solid tumors) in a small number of patients, particularly when used in combination with lenalidomide, thalidomide, and prednisone. Your doctor must carefully evaluate the benefits and risks before prescribing melphalan.

Thromboembolic events

There is an increased risk of deep vein thrombosis (formation of a blood clot called a thrombus within a deep vein, predominantly in the legs), and pulmonary embolism (a blockage in the main artery of the lung or one of its branches caused by a blood clot that has broken loose and traveled to the lung) when melphalan is used in combination with other medicines that may affect the function of your immune system (such as lenalidomide/thalidomide) and other agents that may enhance the benefits of melphalan treatment (such as prednisone/dexamethasone).

Your doctor will decide which measures should be taken after a careful assessment of your underlying risk factors (such as smoking, high blood pressure, high lipid levels in the blood, history of thrombosis).

If you are unsure whether any of the above situations apply to you, consult your doctor or pharmacist before receiving treatment with melphalan.

Other medicines and Melfalan Tarbis

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

In particular, inform your doctor or nurse if you are using medicines such as:

• vaccines containing live organisms (see Warnings and precautions)
• nalidixic acid (an antibiotic used to treat urinary tract infections)
• cyclosporine (used to prevent organ or tissue transplant rejection or to treat certain skin diseases such as eczema and psoriasis, or to treat rheumatoid arthritis)
• busulfan (another chemotherapeutic drug used to treat certain types of cancer) in children.

Pregnancy, breastfeeding, and fertility

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

Menstruation may be absent in female patients, and there is a risk of reduced fertility in male patients. In men, complete absence of sperm may occur. Therefore, men are advised to seek counseling regarding sperm preservation before treatment with melphalan.

Melphalan may have adverse effects on sperm, eggs, and/or the baby if you or your partner use this infusion solution. Because pregnancy is not desired during treatment with melphalan, it is recommended that both male and female patients use an adequate method of contraception (contraception). This applies during treatment and for up to three months after discontinuation.

It is not known whether this medicine is excreted in breast milk. Women taking melphalan must not breastfeed.

Driving and use of machines

No studies on the effects on the ability to drive and use machines have been performed in patients taking this medicine. This medicine is not expected to affect the ability to drive or use machines.

Melfalan Tarbis contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per vial; this is essentially “sodium-free.”

Melfalan Tarbis contains ethanol

This medicine contains 410 mg of alcohol (ethanol) in each solvent vial, equivalent to 0.52 ml. The amount of ethanol in the solvent vial is equivalent to 10 ml of beer or 4 ml of wine.

The small amount of alcohol contained in this medicine does not produce any noticeable effect.

Melfalan Tarbis contains propylene glycol

This medicine contains 6.24 g of propylene glycol per 10 ml of solvent, equivalent to 6.0 ml per vial.

If you are pregnant or breastfeeding, do not take this medicine unless recommended by your doctor. Your doctor may perform additional monitoring while you are taking this medicine.

If you have hepatic or renal impairment, do not take this medicine unless recommended by your doctor. Your doctor may perform additional monitoring while you are taking this medicine.

3. How to use Melphalan Tarbis

This medicine should only be prescribed by a specialist doctor experienced in cancer treatment.

This medicine is a cytotoxic agent that must be used under the supervision of physicians experienced in the administration of such agents.

This medicine may be administered:

• as an intravenous infusion
• as an infusion into a specific part of the body through an artery.

Your doctor will decide the dose of this medicine to be administered. The dose of this medicine will depend on:

• your body weight or body surface area (a specific measure that takes into account your weight and height),
• other medicines you are taking,
• the disease being treated,
• your age,
• whether you have kidney problems.

During treatment with this medicine, your doctor will carry out regular blood tests. These are performed to count the number of cells in your blood. Occasionally, your doctor may adjust your dose based on the results of these tests.

Your doctor will decide whether you should receive preventive treatment for blood clots in the veins. This applies during the first 5 months of treatment, or if you have an increased risk of developing a blood clot in the veins.

Use in children

Melphalan is rarely used in children. Dosing guidelines for children are not available.

Use in elderly patients

There are no specific dose adjustments required for elderly patients.

Use in patients with renal impairment

If you have kidney problems, your doctor will usually give you a lower dose than that given to other adults.

If you receive more Melphalan Tarbis than you need

Your doctor will administer the dose of melphalan, so it is unlikely that you will receive an excessive dose. If you think you have been given too much, or if a dose has been missed, inform your doctor or nurse.

If you forget to use Melphalan Tarbis

Do not use a double dose to make up for missed doses, but continue with your regular dosing schedule. You should also consult your doctor.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

If you experience any of the following effects, contact your specialist doctor immediately or go immediately to hospital:

• Allergic reaction, signs may include:
  • skin rash, lumps on the skin or hives
  • swelling of the face, eyelids or lips
  • wheezing and sudden tightness in the chest
  • collapse (due to cardiac arrest)
• signs of fever or infection (sore throat, mouth ulcers or urinary problems)
• unexpected bruising or bleeding, or feeling extremely tired, dizzy or short of breath, as this could mean that too few blood cells of a particular type are being produced
• sudden feeling of illness (even with normal temperature)
• muscle pain, stiffness or weakness and urine darker than usual, or brown or red in colour – when this medicine is administered directly into an arm or leg.
• Inform your doctor immediately if you have symptoms of blood clots in the veins, especially in the legs. Symptoms include swelling, pain and redness of the leg. Blood clots can travel through blood vessels to the lungs, causing chest pain and difficulty breathing.

Very common: may affect more than 1 in 10 people

• Fever
• a condition in which the bone marrow stops producing certain types of blood cells (bone marrow suppression)
• nausea, vomiting and diarrhoea
• mouth ulcers – at high doses
• hair loss – at high doses
• a tingling or warm sensation at the site where melfalan was injected
• muscle problems, such as loss of muscle tissue due to disuse (muscle atrophy), increase in connective tissue in the muscle (muscle fibrosis), muscle pain, when melfalan is administered directly into an arm or leg.

Common: may affect up to 1 in 10 people

• hair loss – with usual doses of this medicine
• elevated levels of a chemical called urea in the blood – in people with kidney problems receiving treatment for myeloma
• a muscle problem that may cause pain, tightness, tingling, burning or numbness, called compartment syndrome. This may occur when this medicine is administered directly into an arm or leg

Rare: may affect up to 1 in 1,000 people

• anaemia due to excessive breakdown of blood (haemolytic anaemia)
• lung problems that may cause cough or wheezing, and difficulty breathing
• jaundice (yellowing of the whites of the eyes and skin)
• mouth ulcers – with usual doses of this medicine
• skin rashes or itching

The following adverse effects may also occur with Melfalán Tarbis:

• leukaemia (blood cancer)
• in women: cessation of menstruation (amenorrhoea)
• in men: absence of spermatozoa in semen (azoospermia)
• death of muscle tissue (muscle necrosis)
• rupture of muscle fibres (rhabdomyolysis)
• formation of a blood clot, known as thrombus, in a deep vein, especially in the legs (deep vein thrombosis) and blockage of a pulmonary artery (pulmonary embolism).
• secondary primary malignant neoplasm

Reporting of adverse effects

If you experience any kind of adverse effect, consult your doctor, pharmacist or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Melphalan Tarbis

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

Do not store above 30°C. Do not refrigerate.

Keep the vial in the outer packaging to protect from light.

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

6. Contents of the pack and other information

Composition of Melfalan Tarbis

The active substance is melphalan hydrochloride.

Each vial contains melphalan hydrochloride equivalent to 50 mg of melphalan.

The other components are povidone and hydrochloric acid (to adjust pH).

This medicine must be dissolved in 10 ml of solvent before injection. The solvent contains water for injections, anhydrous sodium citrate, propylene glycol (E-1520), and ethanol (96 percent).

Appearance of the product and contents of the container

Each pack contains one vial of powder and one vial of solvent. The powder vial contains 50 mg of the active substance melphalan in powder form, and the solvent vial contains 10 ml of solvent for reconstitution (dissolving) of the powder. The powder is a lyophilized powder or a white to off-white cake, and the solvent is a transparent, colourless liquid/solution. After reconstitution with 10 ml of solvent, the resulting solution contains 5 mg/ml of melphalan.

Marketing Authorization Holder

Tarbis Farma S.L.

Gran Vía Carlos III, 94

08028 Barcelona

Spain

Manufacturer

Amarox Pharma B.V.

Rouboslaan 32

Voorschoten, 2252TR

The Netherlands

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park

Paola, PLA 3000

Malta

This medicinal product is authorised in the European Economic Area member states under the following names:

The Netherlands: Melfalan Amarox 50 mg powder and solvent for solution for injection/infusion
Germany: Melphalan Amarox 50 mg powder and solvent for the preparation of an injection/infusion solution
Spain: Melfalán Tarbis 50 mg powder and solvent for injectable solution and for perfusion EFG

Date of the most recent review of this summary: July/2021

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

Information intended exclusively for healthcare professionals:

Precautions

Melfalan is a cytotoxic agent with significant activity and must be used under the supervision of physicians experienced in the use of such agents. Care must be taken during handling and preparation. The use of gloves and other protective clothing is recommended to avoid skin contact.

Safe handling of melphalan

Handling of melphalan formulations must comply with guidelines for handling cytotoxic drugs.

Preparation

This medicine should be prepared at room temperature (approximately 25 °C), by reconstituting the lyophilized powder with the provided solvent.

Reconstitution:

It is important that both the lyophilized powder and the provided solvent are at room temperature before starting reconstitution. Warming the solvent in the hand may facilitate reconstitution. Rapidly add 10 ml of the solvent as a single volume to the vial containing the lyophilized powder, and immediately shake vigorously (for approximately 1 minute) until a clear solution without visible particles is obtained. Each vial should be reconstituted individually in this manner. The resulting solution contains the equivalent of 5 mg per ml of anhydrous melphalan and has a pH of approximately 6.0 to 7.0.

The reconstituted solution must not be refrigerated, as this will cause precipitation.

Mixing

Immediately withdraw the reconstituted solution with a concentration of 5 mg/mL of anhydrous melphalan from the reconstituted vial and, using a new 10 mL syringe, add it to an intravenous infusion bag containing 0.9% sodium chloride solution. Mix thoroughly by gentle manual rotation to obtain a nominal concentration of 0.45 mg/mL of anhydrous melphalan.

After reconstitution and dilution, chemical and physical stability has been demonstrated for 1 hour and 15 minutes at 25 °C. Therefore, the total time from reconstitution and dilution to completion of the infusion must not exceed 1 hour and 15 minutes.

From a microbiological standpoint, the product should be used immediately after reconstitution. If not used immediately, the times for use and storage conditions prior to use are the responsibility of the user. The reconstituted solution must not be refrigerated, as this will cause precipitation.

Melphalan is not compatible with infusion solutions containing dextrose, and it is recommended to use exclusively 0.9 % p/v sodium chloride solution for intravenous infusion.