CARMUSTINA 100 mg Roztwór Do Infuzji

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1. Carmustina Waymade 100 mg powder and solvent for concentrate for infusion solution
   1. What is Carmustina Waymade and what is it used for
   2. What you need to know before using Carmustina Waymade
   3. How to use Carmustina Waymade
   4. Possible side effects
   5. How to store Carmustina Waymade
   6. Content of the pack and other information

Carmustina Waymade 100 mg powder and solvent for concentrate for infusion solution

Generic medicine

Read this leaflet carefully before using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What is Carmustina Waymade and what is it used for

Carmustina Waymade is a medicine that contains carmustine as the active ingredient. Carmustine
belongs to a group of anticancer drugs known as nitrosoureas, which work by slowing down the
growth of cancer cells.
Carmustina Waymade is effective in the following malignant tumors as a single agent or in combination
with other antineoplastic agents and/or other therapeutic measures (radiotherapy, surgery):

• brain tumors (glioblastoma, brainstem gliomas, medulloblastoma, astrocytoma and ependymoma), brain metastases;
• secondary therapy in non-Hodgkin lymphomas and Hodgkin's disease;
• as conditioning treatment prior to autologous hematopoietic progenitor cell transplantation (HPTC) in malignant hematological diseases (Hodgkin's disease / non-Hodgkin lymphoma).
• Multiple myeloma (a malignant tumor that develops from the bone marrow) - in combination with glucocorticoids such as prednisone.

2. What you need to know before using Carmustina Waymade

Do not use Carmustina Waymade:

• if you are allergic to carmustine or any of the other ingredients of this medicine (listed in section 6);
• if you suffer from inhibition of blood cell formation in the bone marrow and the number of platelets, white blood cells (leukocytes) or red blood cells (erythrocytes) is therefore reduced, following chemotherapy or for other reasons;
• if you suffer from severe kidney dysfunction;
• in children and adolescents;
• during pregnancy or breastfeeding.

Warnings and precautions
Consult your doctor, pharmacist or nurse before taking Carmustina Waymade.
The main undesirable effect of this medicine is delayed myelosuppression, which can
manifest with fatigue, bleeding of the skin and mucous membranes as well as with infections and fever
due to changes in the blood. Therefore, after each dose, the doctor will monitor the blood count
weekly for at least 6 weeks. At the recommended dosages, treatment cycles with
Carmustina Waymade would not occur with a frequency of less than 6 weeks. The dosage will be
confirmed with the blood count.
Liver, lung and kidney function will be checked before treatment and kept under
regular observation during treatment.
Since the use of Carmustina Waymade can cause lung damage, a chest X-ray will be performed and lung
function tests will be carried out before starting treatment (see also section “Possible side effects”).
High-dose treatment with Carmustina Waymade (up to 600 mg/m²) is administered
only in combination with subsequent stem cell transplantation. Such a high dose may
increase the frequency or severity of toxicity to the lungs, kidneys, liver, heart and
gastrointestinal tract, as well as infections and electrolyte imbalances (low levels of potassium, magnesium and
phosphate in the blood).
Stomach pain (neutropenic enterocolitis) may occur as an adverse event related to therapy
following treatment with chemotherapeutic agents.
The doctor will inform you about the possibility of lung damage and allergic reactions, as well as their
symptoms. If such symptoms occur, contact your doctor immediately (see section 4).

Children and adolescents
Carmustina Waymade must not be used in children and adolescents under the age of 18 years.

Other medicines and Carmustina Waymade
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines, including those available without a prescription, such as:

• phenytoin, used for epilepsy;
• dexamethasone, used as an immunosuppressant and anti-inflammatory agent;
• cimetidine, used for stomach problems such as indigestion;
• digoxin, used for heart rhythm abnormalities (arrhythmia);
• melphalan, an anti-cancer drug.

Carmustina Waymade and alcohol
The amount of alcohol contained in this medicine can alter the effect of other medicines.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding with
breast milk, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy and fertility
Carmustina Waymade must not be used during pregnancy because it can cause harm to the
fetus. Therefore, this medicine is generally not administered to pregnant women. If
used during pregnancy, the patient should be aware of the potential risks to the fetus. It is
recommended that women of childbearing potential use effective contraceptive methods to avoid becoming
pregnant during and for at least 6 months after the treatment period with this medicine.
Male patients should use adequate contraceptive methods during treatment with
Carmustina Waymade and for at least 6 months after the end of treatment to avoid pregnancy of the
partner.
Breastfeeding
You must not breastfeed during the period of taking the medicine and for up to 7 days
after treatment. The risk to newborns/infants cannot be excluded.

Driving and operating machinery
Carmustina Waymade does not alter or negligibly alters the ability to drive vehicles or operate
machinery. You should consult your doctor before driving vehicles or using tools or machinery because
the amount of alcohol contained in this medicine may impair the ability to drive vehicles or
operate machinery.

Carmustina Waymade contains anhydrous ethanol (alcohol)
This medicine contains 2.4 g of alcohol (ethanol) in a vial, corresponding to 7.68 g at the maximum dose (320 mg). The amount of alcohol in the maximum dose (200 mg / m² in patients weighing 70
kg) of this medicine corresponds to the amount contained in 192 ml of beer or 76.8 ml of wine.
Since this medicine is usually administered slowly over 6 hours, the effects
of alcohol may be reduced.
The amount of alcohol in this medicine can impair the ability to drive vehicles or operate
machinery. This is because alcohol can alter the ability to judge and how quickly you react
to stimuli.
If you have epilepsy or liver problems, talk to your doctor or pharmacist before taking
this medicine.
The alcohol in this medicine can alter the effects of other medicines. Talk to your doctor or pharmacist
if you are taking other medicines.
If you are pregnant, talk to your doctor or pharmacist before taking
this medicine.
If you have an alcohol dependence, talk to your doctor or pharmacist before taking this
medicine.

3. How to use Carmustina Waymade

Carmustina Waymade will always be administered by a healthcare professional experienced
in the use of anticancer medicines.
This medicine is intended for intravenous infusion.

Adults
The dosage depends on the medical condition, body size and response to treatment. It is
generally administered at least every 6 weeks. The recommended dose of Carmustina
Waymade as a single agent in patients not previously treated is between 150 and 200
mg/m intravenously every 6 weeks. It can be administered as a single dose or divided into
daily infusions of 75-100 mg/m over two consecutive days. The dosage also varies depending on
the possible use of Carmustina Waymade in combination with other anticancer drugs.
The doses will be adjusted based on the response to treatment.
The recommended dose of Carmustina Waymade administered in combination with other
chemotherapeutic agents before hematopoietic stem cell transplantation is 300 - 600 mg/m
intravenously.
The blood count will be monitored frequently to avoid bone marrow toxicity and the dose will be
adjusted if necessary.

Route of administration
After reconstitution and dilution, Carmustina Waymade is administered intravenously
via infusion for a period of 1-2 hours protected from light. The duration of the infusion must not be
less than one hour to avoid burning and pain at the injection site. The injection site is
monitored during administration.
The duration of treatment is established by the doctor and may vary for each patient.

If you use more Carmustina Waymade than you should
Since a doctor or nurse will administer this medicine to you, it is unlikely that you will be given an incorrect dose. Inform the doctor or nurse if you have doubts regarding
the amount of medicine administered to you.
If you have any doubts about the use of this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

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

Tell your doctor or nurse immediately if you notice any of the following:
sudden wheezing, difficulty breathing, swelling of the eyelids, face or lips, skin rash or itching (especially all over the body) and feeling faint. These may be signs of a serious allergic reaction.

Carmustina Waymade may cause the following side effects:
very common(may affect more than 1 in 10 people):

• delayed myelosuppression (decrease in blood cells in the bone marrow) which can increase the likelihood of contracting infections if the number of white blood cells (leukocytes) decreases;
• ataxia (lack of voluntary coordination of muscle movements);
• dizziness;
• headache;
• temporary redness of the eyes, blurred vision due to retinal bleeding;
• hypotension (low blood pressure);
• phlebitis (inflammation of the veins) associated with pain, swelling, redness, tenderness;
• respiratory disorders (lung problems) with breathing difficulties. This medicine can cause severe (even fatal) lung damage that can manifest years after treatment. See your doctor immediately if you notice any of the following symptoms: shortness of breath, persistent cough, chest pain, persistent weakness/fatigue;
• severe nausea and vomiting;
• if used on the skin, skin inflammation (dermatitis);
• accidental contact with the skin can cause transient hyperpigmentation (darkening of an area of skin or nails);

common(may affect up to 1 in 10 people)

• acute leukemia and bone marrow dysplasia (abnormal development of the bone marrow). Symptoms may include bleeding gums, bone pain, fever, frequent infections, frequent or severe nosebleeds, lumps caused by swollen lymph nodes in the neck and surrounding area, armpits, abdomen or groin, pale skin, shortness of breath, weakness, fatigue or general decrease in energy;
• anemia (decrease in the amount of red blood cells in the blood);
• encephalopathies (brain disorder). Symptoms may include muscle weakness in a specific area, poor ability to make decisions or concentrate, involuntary contraction, tremor, difficulty speaking or swallowing, seizures;
• anorexia;
• constipation;
• diarrhea;
• inflammation of the mouth and lips;
• reversible hepatic toxicity in high-dose therapy, which can cause an increase in liver enzymes and bilirubin (shown by blood tests);
• alopecia (hair loss);
• skin redness;
• reactions at the injection site;

rare(may affect up to 1 in 1,000)

• veno-occlusive disease (progressive obstruction of the veins) in which very small veins of the liver (microscopic in size) become blocked. Symptoms may include: accumulation of fluid in the abdomen, enlargement of the spleen, severe bleeding from the esophagus, yellowing of the skin and whites of the eyes;
• respiratory problems caused by interstitial fibrosis (with lower doses);
• kidney problems;
• gynecomastia (development of breasts in men);

Not known(frequency cannot be estimated from available data)

• muscle pain;
• seizures (fits) including status epilepticus;
• tissue damage due to leakage at the injection site;
• infertility;
• carmustine has been shown to have a negative effect on fetal development;
• electrolyte disturbances (and electrolyte imbalances (low levels of potassium, magnesium and phosphate in the blood)).

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet. You can also report side effects directly through the national reporting system at https://www.aifa.gov.it/content/segnalazioni-
reazioni-avverse. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Carmustina Waymade

This medicine will be stored by the doctor or qualified healthcare professional.
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 label and the package after
“EXP.”. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C). Do not freeze.
Store both vials (active and solvent) in the outer packaging to protect the
medicine from light.
After reconstitution and dilution
After reconstitution, Carmustina Waymade is stable for 24 hours under refrigeration conditions (2°C

• 8°C), stored in a glass container and protected from light. The reconstituted solution is further diluted with 500 ml of sodium chloride 9 mg/ml (0.9%) solution or 500 ml of dextrose 50 mg/ml (5%) solution in a glass or polypropylene container. It must be stored at room temperature, protected from light and used within 4 hours. These solutions are also stable for 24 hours under refrigeration conditions (2°C - 8°C) and for an additional 6 hours at room temperature and protected from light. From a microbiological point of view, unless the opening/reconstitution/dilution method excludes the risk of microbial contamination, the product must be used immediately. If not used immediately, the storage times and conditions in use are the responsibility of the user.

Do not dispose of any medicine in the drain or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Content of the pack and other information

What Carmustina Waymade contains
The active ingredient is carmustine.
Each vial of powder for concentrate for solution for infusion contains 100 mg of
carmustine. Following reconstitution and dilution, 1 ml of solution contains 3.3 mg of carmustine.

• Excipients:
• powder: no excipients;
• solvent: anhydrous ethanol.

Description of the appearance of Carmustina Waymade and contents of the pack
A pack of Carmustina Waymade is a powder and solvent for concentrate for solution for
infusion and contains a vial with 100 mg of Carmustina powder and a vial of 3 ml of
solvent, Anhydrous Ethanol.
The powder is lyophilized in flakes or a matted mass of pale yellow color supplied in a vial of
amber glass.
The solvent is a clear, colorless liquid supplied in a transparent glass vial.
Lyophilized flakes or matted mass of pale yellow color for reconstitution.
Appearance of the solution: The reconstituted solution is a transparent solution, from colorless to
slightly yellowish.
Powder: amber type I glass vial (30 ml) with a grey bromobutyl rubber stopper of
20 mm with an opaque blue flip-off seal.
Solvent: type I glass vial (5 ml) with a grey chlorobutyl rubber stopper of 13 mm and
sealed with an opaque blue flip-off seal.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Waymade B.V.
Herikerbergweg 88,
1101CM Amsterdam,
Netherlands

Manufacturer
Drehm Pharma GmbH
Hietzinger Hauptstraβe 37/2,
Wien, 1130, Austria

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The following information is intended exclusively for healthcare professionals:

A brief description of preparation and/or handling, incompatibilities, dosage of the medicinal
product, overdose or control measures and laboratory investigations is provided

based on the current summary of product characteristics.
Carmustina Waymade powder for concentrate for solution for infusion does not contain preservatives and
is not a multi-dose vial. Reconstitution and further dilutions should be carried out under aseptic
conditions.
Following the storage instructions on the product, deterioration of the intact vial can be avoided until
the expiry date indicated on the pack.
The lyophilized product does not contain preservatives and is for single use. The lyophilized product
may appear as flakes or a matted mass. The presence of an oily film may indicate melting of the
medicinal product. In such cases, it should not be used due to the risk of temperature excursions
above 30°C.
The medicinal product should no longer be used. If you are not sure about adequate cooling of the
product, you should immediately check each vial in the pack. To perform this check, expose the vial to
intense light.
Reconstitution and dilution of the powder for concentrate for solution for infusion:
Dissolve the 100 mg of Carmustina Waymade powder for concentrate for solution for infusion with
3 ml of the sterile refrigerated anhydrous ethanol solvent provided in the pack. Carmustine must be
completely dissolved in anhydrous ethanol before adding sterile water for injections. Then
add in aseptic conditions 27 ml of sterile water for injections to the alcoholic solution. The
30 ml mother liquor must be mixed thoroughly. Reconstitution, performed as
recommended, results in a transparent solution, from colorless to slightly yellowish.
Before use, check the reconstituted vials for crystal formation. If
crystals are observed, they can be redissolved by warming the vial to room temperature with shaking.
After reconstitution, Carmustina Waymade is stable for 24 hours in
refrigeration conditions (2°C - 8°C), stored in a glass container and protected from light.
The reconstituted solution must be further diluted with 500 ml of sodium chloride 9 mg/ml (0.9%) or
500 ml of dextrose 50 mg/ml (5%) solution. The reconstituted and diluted solution (i.e. the ready-to-use
solution) must be mixed for at least 10 seconds before
administration. The ready-to-use solution must be stored at room temperature in a
glass or polypropylene container, protected from light and used within 4 hours. These solutions are
also stable for 24 hours in refrigeration conditions (2°C - 8°C) and for another 6 hours at room
temperature protected from light.
The pH and osmolarity of the ready-to-use infusion solutions:
The pH of the ready-to-use infusion solutions is between 4.0 and 6.8.
Route of administration
The reconstituted and diluted solution (i.e. the ready-to-use solution) must be administered by
intravenous route and must be administered via a drip for an administration period of one to
two hours. The administration of the infusion must be carried out using an infusion set or
PVC-free PE containers. During the administration of the medicinal product, the container must be
exclusively made of glass or polypropylene. Ensure that the polypropylene containers used
are free of PVC and DEHP. Carmustine has a low melting point (30.5°C - 32.0°C or 86.9°F -
89.6°F). Exposure of this drug to this temperature or higher will cause
liquefaction of the drug and will appear as an oily film on the vials. This is a sign of
decomposition and the vials must be discarded.
Infusion of Carmustina Waymade in shorter time intervals may cause intense pain and
burning at the injection site. The injection site must be monitored during
administration.
Guidelines for the handling and safe disposal of antineoplastic agents must be followed.
Dosage and laboratory investigations

Initial doses
The recommended dose of Carmustina Waymade as a single agent in previously untreated patients is
between 150 and 200 mg/m intravenously every 6 weeks. It can be
administered as a single dose or divided into daily infusions of 75-100 mg/m for two consecutive days.
When Carmustina Waymade is used in combination with other myelosuppressive medicinal products or in
patients with depletion of the bone marrow reserve, the doses must be adjusted to the patient's
hematological profile as indicated below.

Monitoring and subsequent doses
A new cycle of Carmustina Waymade must not be administered until the circulating blood elements have
returned to acceptable levels (platelets above 100,000/mm , leukocytes
above 4,000/mm ), which usually occurs within six weeks. Blood values must be
monitored frequently and repeated cycles must not be administered before six
weeks due to late hematological toxicity.
Subsequent doses to the initial dose must be adjusted based on the patient's hematological response to the
previous dose, both in monotherapy and in combination therapy with other myelosuppressive medicinal
products. The table below is provided as a guide for dosage adjustment:

In cases where the nadir after the initial dose does not fall into the same row for leukocytes and platelets (e.g.
leukocytes >4,000 and platelets <25,000), the value with the lowest percentage of
the previous dose must be used (e.g. with platelets <25,000, a maximum of 50% of the
previous dose must be administered).
There are no limits to the duration of carmustine therapy. If the
tumor remains incurable or serious or intolerable adverse reactions occur, carmustine therapy must be discontinued.

Conditioning treatment prior to HSCT
Carmustine is administered intravenously in combination with other chemotherapeutic agents in patients with
malignant hematological diseases prior to HSCT at a dosage of 300 - 600 mg/m .
Special populations

Paediatric population
For safety reasons, carmustine should not be used in subjects under the age of 18 years.

Elderly
In general, the choice of dose for an elderly patient should be cautious, usually starting
from the lower part of the dosage range, considering the increased frequency of decreased
hepatic, renal or cardiac function and taking into account any concomitant diseases or therapies with other
medicinal products. Because elderly patients are more likely to have reduced renal function, caution should be
exercised in choosing the dosage and monitoring glomerular filtration rate and therefore reducing the dose
accordingly.

Renal impairment
For patients with renal impairment, the dose of Carmustina Waymade must be reduced if there is
a reduction in glomerular filtration rate.
Compatibility/Incompatibility with containers
The intravenous solution is unstable in polyvinyl chloride containers. Do not use PVC containers. The Carmustina solution can only be administered from glass or
polypropylene containers. Ensure that the polypropylene containers used are free of PVC and DEHP.