Melphalan Zentiva

Leaflet attached to the packaging: patient information

Melphalan Zentiva, 50 mg, powder and solvent for solution for injection/infusion

for injection/infusion
melfalan

Please read carefully the contents of the leaflet before using the medicine, as it contains important information for the patient.

• Please keep this leaflet, so that you can read it again if necessary.
• In case of any doubts, please consult a doctor, pharmacist, or nurse.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Melphalan Zentiva and what is it used for
• 2. Important information before using Melphalan Zentiva
• 3. How to use Melphalan Zentiva
• 4. Possible side effects
• 5. How to store Melphalan Zentiva
• 6. Contents of the packaging and other information

1. What is Melphalan Zentiva and what is it used for

Melphalan Zentiva contains the active substance melfalan. It belongs to a group of medicines called cytotoxic medicines (also known as chemotherapy). Melfalan is used to treat cancer. Its action is to reduce the number of abnormal cells produced by the body.
Melphalan Zentiva is used to treat:

• multiple myeloma - a type of cancer that arises from cells in the bone marrow, called plasma cells. Plasma cells help fight infections and diseases by producing antibodies.
• advanced ovarian cancer.
• childhood neuroblastoma - a tumor of the nervous system.
• malignant melanoma - a skin cancer.
• soft tissue sarcoma - a tumor of muscle tissue, fat tissue, fibrous tissue, blood vessels, or other supporting tissues of the body.

If there is no improvement or the patient feels worse, they should contact their doctor.

2. Important information before using Melphalan Zentiva

Do not take Melphalan Zentiva if the patient has any of the following conditions. The patient should inform their doctor if:

• the patient is allergic to melfalan or any of the other ingredients of this medicine (listed in section 6).
• the patient is breastfeeding.

Warnings and precautions

Before starting treatment with melfalan, the patient should discuss with their doctor if they have any of the following conditions:

• the patient is currently or has recently undergone radiation therapy or chemotherapy,
• the patient has kidney function disorders.
• the patient plans to be vaccinated or has been vaccinated recently. This is because some vaccines (e.g., against polio, measles, mumps, and rubella) can cause infection if given to a patient being treated with melfalan.
• the patient has or has had a blood clot in the leg (thrombosis), lung (pulmonary embolism), or any other part of the body.
• the patient has a condition that increases the risk of blood clots in the arteries;
• men taking melfalan should not father a child during treatment and for 3 months after its completion.

Melphalan Zentiva and other medicines

The patient should tell their doctor or nurse about all medicines they are taking, including those obtained without a prescription.
In particular, the patient should tell their doctor or nurse if they are taking any of the following medicines:

• other cytotoxic medicines (chemotherapy);
• nalidixic acid (an antibiotic used to treat urinary tract infections);
• cyclosporine (used to prevent transplant rejection or to treat certain skin diseases, such as psoriasis or eczema, or to treat rheumatoid arthritis);
• vaccines containing live organisms (see "Warnings and precautions");
• in children - busulfan (used to treat certain types of cancer).

Pregnancy, breastfeeding, and fertility

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor before using this medicine.
Pregnancy
Melfalan should not be used during pregnancy, as it may cause permanent damage to the fetus. If the patient is already pregnant, it is essential to inform their doctor before receiving melfalan. The doctor will weigh the risks and benefits for the patient and their child associated with melfalan treatment.
During the period when the patient (or their partner) is receiving injections/infusions of the medicine, they should use effective contraception to avoid pregnancy.
Breastfeeding
It is not known whether melfalan passes into human milk. Breastfeeding should not be done while receiving melfalan.
Fertility
Melfalan may affect the ovaries or sperm, leading to infertility (inability to have children). As a result of Melphalan Zentiva treatment in women, amenorrhea (absence of menstruation) may occur, and in men, azoospermia (complete absence of sperm).
Therefore, men are advised to seek advice on sperm storage before starting treatment.

Contraception in men and women

Men taking melfalan should not father a child during treatment and for 3 months after its completion. If the patient wishes to use effective contraception, they should discuss it with their doctor.

Driving and using machines

The effect of this medicine on the ability to drive and use machines has not been studied. It should not be assumed that this medicine will affect the ability to drive and use machines.

Melphalan Zentiva contains sodium

The medicine contains 53.5 mg of sodium (the main component of common salt) per vial. This corresponds to 2.7% of the maximum recommended daily intake of sodium in the diet for adults.

Melphalan Zentiva contains ethanol

The medicine contains 5% ethanol (alcohol), i.e., 0.4 g per vial, which is equivalent to 10 ml of beer or 4 ml of wine per vial.
Harmful to individuals with alcohol dependence.
This should be taken into account in pregnant women, children, and individuals at high risk, such as patients with liver disease or epilepsy.
The alcohol in the medicine may alter the effects of other medicines.
The alcohol in the medicine may impair the ability to drive and use machines.

Melphalan Zentiva contains propylene glycol

The medicine contains 6.2 mg of propylene glycol per vial. The propylene glycol in this medicine may cause symptoms similar to those of alcohol consumption and increase the likelihood of side effects.
The patient should tell their doctor if they are pregnant, have liver or kidney function disorders, or are taking other medicines containing alcohol.
During treatment with this medicine, the doctor may decide to perform additional tests on such patients.

3. How to use Melphalan Zentiva

Melfalan will be administered to the patient by doctors or nurses experienced in administering chemotherapy.
Method of administration:
Melfalan can be administered:

• as an infusion (drip) into a vein,
• into an artery, administering it to a specific part of the body (perfusion).

What dose of Melphalan Zentiva is administered

The doctor will decide what dose of melfalan will be administered to the patient. The dose of melfalan depends on:

• the patient's body weight or body surface area (a measurement that takes into account body weight and height),
• other medicines being taken,
• the patient's disease,
• the patient's age,
• the presence or absence of kidney function disorders.

During treatment with melfalan, the doctor will order regular blood tests. The purpose is to monitor the number of cells in the blood.
Based on the results of these tests, the doctor may change the dose used in the patient.
Risk of blood clots(thromboembolic events)
The doctor will decide whether the patient should receive therapy to prevent blood clots in the veins. This applies to the first 5 months of treatment or if the patient has an increased risk of blood clots in the veins.

Use in children

Melfalan is rarely used in children. Guidelines for dosing in children are not available.

Use in elderly patients

In elderly patients, no special dose adjustment is necessary.

Use in patients with kidney function disorders

If the patient has kidney disease, the doctor will usually administer a lower dose than in other adults.

Receiving a higher than recommended dose of Melphalan Zentiva:

Melfalan will be administered by a doctor, so it is unlikely that the patient will receive too much medicine. If the patient is concerned that they have received too much medicine or have missed a dose, they should tell their doctor or nurse.

Missing a dose of Melphalan Zentiva

Melfalan will be administered by a doctor, so missing a dose is unlikely. If the patient thinks they have missed a dose, they should skip it and receive the next dose at the next scheduled time. They should not take a double dose to make up for the missed dose.

Stopping treatment with Melphalan Zentiva

If the patient thinks they should stop using this medicine, they should first consult their doctor.
In case of any further doubts about using this medicine, the patient should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Severe side effects

If the patient experiences any of the following side effects, they should immediately contact their specialist doctor or go to the hospital:

allergic reaction, whose symptoms may include:

• rash, hives, or itching on the skin;
• swelling of the face, eyelids, or lips;
• sudden wheezing and feeling of tightness in the chest;
• collapse (due to cardiac arrest);
• symptoms like fever or infection (sore throat, mouth ulcers, or problems urinating);
• unexplained bruising, bleeding, or feeling extremely tired, dizzy, or short of breath, as this may indicate a decrease in the production of blood cells of a certain type;
• sudden worsening of the condition (even with normal body temperature);
• muscle pain, stiffness, or weakness, and darker than usual, brown, or red urine during administration of melfalan directly into the arm or leg;

The patient should immediately tell their doctor if they experience symptoms of blood clots in the veins, particularly in the legs. These symptoms include swelling, pain, and redness of the leg. Blood clots can move through the blood vessels to the lungs, causing chest pain and difficulty breathing.
Other side effects include:

Very common side effects (may affect more than 1 in 10 people):

• fever;
• decrease in the number of blood cells and platelets;
• nausea, vomiting, and diarrhea;
• mouth ulcers (at high doses of melfalan);
• hair loss (at high doses of melfalan);
• tingling or feeling of warmth at the injection site;
• muscle disorders, such as atrophy and pain, when melfalan is administered directly into the arm or leg.

Common side effects (may affect up to 1 in 10 people):

• hair loss at normal doses of melfalan;
• high levels of urea in the blood in people with kidney function disorders who are being treated for multiple myeloma;
• muscle disorder that can cause pain, pressure, tingling, burning, or numbness, called compartment syndrome. This can occur when melfalan is administered directly into the arm or leg.

Rare side effects (may affect up to 1 in 1,000 people):

• a disease in which there is a low number of red blood cells, as they are being destroyed prematurely. This can cause feelings of extreme tiredness, shortness of breath, and dizziness, as well as headaches or yellowing of the skin or eyes;
• lung function disorders, which can cause coughing or wheezing and difficulty breathing;
• liver function disorders, which can be seen in blood test results or cause yellowing of the eyes and skin;
• mouth ulcers at normal doses of melfalan;
• skin rashes or itching.

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

• leukemia (blood cancer);
• in women: absence of menstruation (amenorrhea);
• in men: absence of sperm in the semen (azoospermia);
• death of muscle tissue (muscle necrosis);
• breakdown of muscle fibers (rhabdomyolysis);
• formation of a blood clot (thrombosis), in a deep vein, particularly in the legs (deep vein thrombosis) and blockage of one of the pulmonary arteries (pulmonary embolism).

Reporting side effects

If the patient experiences any side effects, including those not listed in the leaflet, they should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, it is possible to gather more information on the safety of the medicine.

5. How to store Melphalan Zentiva

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after:
Expiry date (EXP). The expiry date refers to the last day of the month stated.
There are no special precautions for storage temperature. Store the vial in the outer packaging to protect it from light.
Melfalan will be prepared for use by medical staff. After preparation, it should be used immediately. Any unused product or waste material should be disposed of in accordance with local regulations.

6. Contents of the packaging and other information

What Melphalan Zentiva contains

The active substance of the medicine is melfalan. Each vial contains 50 mg of melfalan.
The other ingredients are:
Vial with powder: povidone K12 and diluted hydrochloric acid.
Vial with solvent: water for injections, sodium citrate, propylene glycol, and 96% ethanol.
Before injection, melfalan is dissolved in the solvent.

What Melphalan Zentiva looks like and contents of the pack

Each pack contains one vial of melfalan and one vial of solvent.
The vial with powder contains 50 mg of the active substance melfalan in powder form, and the vial with solvent contains 10 ml of solvent, in which the powder is reconstituted. After reconstitution, the vial with melfalan powder with 10 ml of solvent produces a solution containing 5 mg/ml of anhydrous melfalan.
Powder: vial made of colorless glass type I, closed with a bromobutyl rubber stopper covered with a fluoropolymer "omniflex 3G", with an aluminum flip-off seal and an orange polypropylene cap with a matte finish. The vials may, but do not have to, be labeled with a shrinkable label.
Pack size: 1 vial containing 50 mg of melfalan.
Solvent: vial made of colorless glass type I, closed with a bromobutyl rubber stopper, with an aluminum flip-off seal and an orange polypropylene cap with a matte finish.
Pack size: 1 vial containing 10 ml.

Marketing authorization holder and manufacturer

Marketing authorization holder

Zentiva, k.s.
U kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic

Importer

SGS Pharma Magyarorszag Kft.
Derkovits Gyula 53
Budapest XIX
1193 Hungary

Tillomed Malta Limited,

Malta Life Sciences Park,
LS2.01.06 Industrial Estate,
San Gwann, SGN 3000, Malta

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

Date of last revision of the leaflet:January 2025
--------------------------------------------------------------------------------------------------------------------------
Information intended for healthcare professionals only:
It is essential to follow the guidelines for handling cytotoxic medicinal products and their disposal:

• 1. Personnel should be instructed in the techniques of reconstituting the medicine.
• 2. Pregnant women should be excluded from working with this medicine.
• 3. During reconstitution of the preparation, personnel should wear appropriate protective clothing, including a face mask, protective glasses, and gloves.
• 4. Any materials used to administer the product or clean up should be disposed of in containers for hazardous waste intended for incineration at high temperatures.

In case of accidental contact of melfalan with the eyes, they should be rinsed immediately with a physiological saline solution for eye washing or a large amount of water, and medical attention should be sought immediately. In case of skin contact, the area should be washed immediately with a large amount of cold water and soap, and medical attention should be sought immediately. Spilled solution should be wiped up immediately with a damp paper towel, which should then be disposed of safely.
Contaminated surfaces should be rinsed with a large amount of water.
Reconstitution
Melphalan Zentiva should be prepared at room temperature (about 25°C) by reconstituting the powder with the supplied solvent.
It is essential to ensure that both the powder and the supplied solvent are at room temperature (about 25°C) before starting reconstitution.
The 10 ml of solvent (the entire amount) should be added quickly, in one step, to the vial containing the powder using a sterile needle and syringe. A 21-gauge or larger needle should be used to puncture the vial stopper during reconstitution. To insert the needle effectively, it should be pushed through the stopper perpendicularly, not too quickly or forcefully, and without rotating it. Immediately after this, the vial should be shaken vigorously (for about 5 minutes) to obtain a clear solution, without visible particles. For proper dissolution of the powder, it is crucial to add the solvent quickly and then shake the vial immediately.
Shaking the preparation leads to the formation of a significant amount of very small air bubbles. These bubbles can persist for 2 to 3 minutes, as the resulting solution is quite viscous. This may make it difficult to assess the clarity of the solution.
Each vial should be reconstituted separately in the same way. The resulting solution contains 5 mg/ml of anhydrous melfalan. Failure to follow the above steps may result in incomplete dissolution of melfalan.
The melfalan solution has limited stability and should be prepared immediately before use.
The reconstituted solution should not be stored in the refrigerator, as this will cause precipitation.
Mixing
10 ml of the above-mentioned reconstituted solution with a concentration of 5 mg/ml of anhydrous melfalan should be transferred to an infusion bag containing 100 ml of 0.9% sodium chloride injection solution. This diluted solution should be mixed thoroughly to obtain a nominal concentration of 0.45 mg/ml of anhydrous melfalan.
In the event of further dilution of the infusion solution, the stability of Melphalan Zentiva decreases, and the degradation process accelerates with increasing temperature.

In the case of administration of Melphalan Zentiva by infusion at room temperature of about 25°C, the maximum time from preparation of the solution to the end of the infusion should not exceed 1.5 hours.

Melphalan Zentiva is incompatible with infusion solutions containing dextrose, and it is recommended to use only 9 mg/ml (0.9%) sodium chloride injection solution.
If the reconstituted or diluted solution shows any visible turbidity or crystals, the medicine should be discarded.
Disposal
Any unused solution after 1.5 hours should be disposed of in accordance with standard guidelines for handling cytotoxic medicinal products and their disposal.
Any unused product or waste material should be disposed of in accordance with local regulations.