CARMUSTINE HIKMA 100 mg POWDER AND SOLVENT FOR CONCENTRATE FOR PERFUSION SOLUTION - Generic

Introduction

Package Leaflet: Information for the Patient

Carmustine Hikma 100 mg powder and solvent for concentrate for solution for infusion EFG

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, pharmacist, or nurse.
• 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 pack

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

1. What is Carmustine Hikma and what is it used for

Carmustine belongs to a group of anticancer medicines, known as nitrosoureas, which work by slowing down the growth of cancer cells.

Carmustine is indicated as adjuvant treatment in monotherapy or in established combination therapy with other authorized antineoplastic agents in the following malignant neoplasias:

• Brain tumors: glioblastoma, brainstem gliomas, medulloblastoma, astrocytoma, ependymoma, and brain metastases.
• Second-line treatment in Non-Hodgkin's Lymphoma and Hodgkin's Disease.
• Tumors of the gastrointestinal tract or digestive system
• Malignant melanoma (skin cancer) in combination with other antineoplastic agents
• As conditioning treatment prior to autologous hematopoietic progenitor cell transplantation (HPCT) in malignant hematological disorders (Hodgkin's lymphoma / non-Hodgkin's lymphoma).

2. What you need to know before you use Carmustine Hikma

Do not use Carmustine Hikma

• if you are allergic to carmustine or any of the other ingredients of this medicine (listed in section 6).
• if you have bone marrow suppression and therefore have a reduced number of platelets, white blood cells (leukocytes), or red blood cells (erythrocytes), either as a result of chemotherapy or for other reasons.
• if you have severe kidney failure.
• in children or adolescents
• if you are breastfeeding.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with carmustine.

Since the main side effect of this medicine is delayed bone marrow suppression, which can manifest as fatigue, bleeding from the skin and mucous membranes, as well as infections and fever due to changes in the blood. Therefore, your doctor will check your blood counts every week for at least 6 weeks after each dose. Following the recommended dosage, carmustine cycles will not be administered more frequently than every 6 weeks. The dosage will be confirmed with the blood count.

Before treatment, your liver, lung, and kidney function will be evaluated and monitored periodically during treatment.

Since the use of carmustine can cause lung damage, a chest X-ray and lung function tests will be performed before starting treatment (see also the section "Possible side effects").

Treatment with high doses of carmustine (up to 600 mg/m2) is only performed in combination with subsequent hematopoietic cell transplantation. These high doses may increase the frequency or severity of pulmonary, renal, hepatic, cardiac, and gastrointestinal toxicities, as well as infections and changes in electrolyte balance (low levels of potassium, magnesium, and phosphate in the blood).

Stomach pain (neutropenic enterocolitis) may occur as an adverse reaction related to therapy after treatment with chemotherapeutic agents. Your doctor will inform you about the possibility of lung damage and allergic reactions and their symptoms. If these symptoms appear, you should contact your doctor immediately (see section 4).

Children and adolescents

Carmustine should not be used in children and adolescents under 18 years of age.

Other medicines and Carmustine Hikma

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

• Phenytoin, used in epilepsy.
• Dexamethasone, used as an anti-inflammatory and immunosuppressant.
• Cimetidine, used for stomach problems such as indigestion.
• Digoxin, used if you have an abnormal heart rhythm.
• Melphalan, an anticancer medicine.

Carmustine Hikma with alcohol

The amount of alcohol present in this medicine may alter the effects of other medicines.

Pregnancy, breastfeeding, and fertility

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.

Pregnancy and fertility

Carmustine has a potential mutagenic effect and may harm the embryo/fetus.

Carmustine should not be used during pregnancy. If treatment is absolutely necessary (vital indication) in a pregnant woman, medical advice should be given on the risk of harmful effects on the fetus associated with treatment. Women of childbearing age are recommended to use an effective contraceptive method to avoid pregnancy during treatment with this medicine and for at least 6 months after treatment.

Male patients should use an effective contraceptive method during treatment with carmustine and for at least 6 months after treatment to avoid pregnancy of their partner.

Breastfeeding

Do not breastfeed while using this medicine and for 7 days after finishing treatment. The risk to newborns/infants cannot be excluded.

Driving and using machines

The effect of this medicine on the ability to drive and use machines is unknown. The amount of alcohol in this medicine may reduce your ability to drive or use machines.

Special populations

Carmustine is contraindicated in children and adolescents under 18 years of age (see section 4.3).

Carmustine Hikma contains ethanol (alcohol)

This medicine contains 0.57% ethanol (alcohol) by volume, or up to 7.68 g per dose. This is equivalent to 11.32 ml of beer or 4.72 ml of wine per dose. These amounts are derived from a calculated example of 320 mg of carmustine (200 mg/m2 of BSA for 1.6 m2) dissolved in 9.6 ml (anhydrous sterile ethanol) and a final infusion volume of 1696 ml.

If you have a history of alcoholism, talk to your doctor or pharmacist before taking this medicine.

If you are pregnant or breastfeeding, talk to your doctor or pharmacist before taking this medicine. If you have epilepsy or liver problems, talk to your doctor or pharmacist before taking this medicine. The amount of alcohol in this medicine may alter the effect of other medicines. Talk to your doctor or pharmacist if you are taking other medicines. The amount of alcohol in this medicine may affect your ability to drive or use machines because it can alter your judgment and reaction time.

3. How to use Carmustine Hikma

Carmustine will always be administered by a healthcare professional with experience in the use of anticancer medicines.

Adults

The dosage depends on the disease, body size, and response to treatment. It is usually administered at least every 6 weeks. The recommended dose of carmustine in monotherapy in previously untreated patients is 150 to 200 mg/m2 by intravenous infusion every 6 weeks. This amount can be administered in a single dose or divided into daily infusions of 75 to 100 mg/m2 over two consecutive days. The dosage will also depend on whether carmustine is administered with other anticancer medicines.

The doses will be adjusted according to your response to treatment.

The recommended dose of carmustine administered in combination with other chemotherapeutic agents before autologous hematopoietic progenitor cell transplantation is 300-600 mg/m2 by intravenous infusion.

Blood counts will be monitored frequently to avoid bone marrow toxicity and the dose will be adjusted if necessary.

Method of administration

After reconstitution and dilution, carmustine is administered into a vein by drip (intravenously) over a period of one to two hours, protected from light. The duration of the infusion should not be less than one hour to avoid burning and pain at the injection site. The injection site will be monitored during administration.

The duration of treatment will be determined by your doctor and may vary for each patient.

If you use more Carmustine Hikma than you should

Since it will be a doctor or nurse who administers this medicine to you, it is unlikely that you will receive an incorrect dose. Tell your doctor or nurse if you have any doubts about the amount of medicine you have received.

If you have any further questions on 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 pharmacist if any of the following side effects get serious or if you notice any side effects not listed in this leaflet.

Tell your doctor or nurse immediately if you experience any of the following side effects:

Sudden wheezing, difficulty breathing, swelling of the eyelids, face, or lips, rash, or itching (especially if it affects the whole body) and feeling faint. These may be signs of a severe allergic reaction.

Carmustine can cause the following side effects:

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

• Delayed bone marrow suppression (decrease in blood cells) that can increase the risk of infections if white blood cells decrease;
• Ataxia (lack of voluntary muscle coordination).
• Dizziness.
• Headache.
• Transient eye redness, blurred vision, retinal hemorrhage.
• Hypotension (low blood pressure) in high-dose treatments.
• Phlebitis (inflammation of the veins) associated with pain, swelling, redness, sensitivity.
  • Respiratory diseases (related to the lungs) with respiratory problems

• This medicine can cause severe lung damage (possibly fatal). Lung damage can occur years after treatment. Tell your doctor immediately if you experience any of the following symptoms: difficulty breathing, persistent cough, chest pain, persistent weakness/fatigue.
• Severe nausea and vomiting; starts 2-4 hours after administration and lasts 4-6 hours.
• When used on the skin, skin inflammation (dermatitis).
• Accidental contact with the skin can cause transient hyperpigmentation (darkening of a skin area or nails).

Common (may affect up to 1 in 10 people)

• Acute leukemia and bone marrow dysplasias (abnormal development of the bone marrow) after prolonged use. The following symptoms may occur: gum bleeding, bone pain, fever, frequent infections, frequent or severe nosebleeds, swelling of lymph nodes in and around the neck, armpits, abdomen, or groin, pallor, difficulty breathing, weakness, fatigue, or general decrease in energy.
• Anemia (decrease in red blood cells).
• Encephalopathy (brain disorder) in high-dose treatments. Symptoms may include muscle weakness in one area, decreased ability to make decisions or concentrate, involuntary contractions, tremors, difficulty speaking or swallowing, seizures.
• Loss of appetite (anorexia).
• Constipation.
• Diarrhea.
• Inflammation of the mouth and lips.
• Reversible liver toxicity with high-dose treatment, delayed up to 60 days after administration. This can cause an increase in liver enzymes and bilirubin (detected by blood tests).
• Alopecia (hair loss).
• Redness of the skin.
• Reactions at the injection site.

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

• Veno-occlusive disease (progressive blockage of small veins) in high-dose treatments, in which very small (microscopic) veins in the liver are blocked. This can include symptoms of: fluid accumulation in the abdomen, enlargement of the spleen, severe bleeding from the esophagus, yellowing of the skin and the whites of the eyes.
• Respiratory problems caused by interstitial fibrosis (with lower doses).
• Kidney problems.
• Gynecomastia (breast growth in males).

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

• Muscle pain.
• Seizures (crises), including status epilepticus.
• Tissue damage due to leakage at the injection site.
• Infertility.
• Carmustine has been shown to have a negative effect on embryonic/fetal development.
• Any sign of infection.
• Changes in electrolyte balance (low levels of potassium, magnesium, and phosphate in the blood).

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Monitoring System for Human Use: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Carmustine Hikma

This medicine will be stored by your doctor or healthcare professional.

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

After opening, this medicine should be used immediately.

Do not use this medicine after the expiry date which is stated on the label of the vial or carton after EXP. The expiry date is the last day of the month shown.

Carmustine Hikma has a shelf life of 2 years if stored in suitable conditions.

.

Store and transport refrigerated (2°C-8°C).

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

The solution should be administered within 4 hours after reconstitution and dilution of the product. The solution should be protected from light until the end of administration.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Composition ofCarmustineHikma

The active ingredient is carmustine.

Each vial of powder for concentrate for solution for infusion contains 100 mg of carmustine. After reconstitution, each ml of solution contains 3.3 mg of carmustine.

The other components are: anhydrous ethanol.

Each vial of solvent for solution for infusion contains 3 ml of anhydrous ethanol.

Appearanceof the productand container content

Carmustine Hikma is a powder and solvent for concentrate for solution for infusion.

The powder is a pale yellow granulate or a frozen mass, packaged in an amber-colored vial.

The solvent is a clear, colorless liquid supplied in a clear glass vial.

A container contains 1 vial of 100 mg of powder for concentrate for solution for infusion and 1 vial with 3 ml of solvent for solution for infusion.

Marketing Authorization Holder and Manufacturer

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó n.º 8, 8A e 8B, Fervença

2705-906 Terrugem SNT

Portugal

Further information on this medicinal product can be obtained from the local representative of the Marketing Authorization Holder:

Hikma España, S.L.U.

Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2

28108 - Alcobendas, Madrid

Spain

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

Germany: Carmustin Hikma 100 mg Pulver und Lösungsmittel für ein Konzentrat zur Herstellung einer Infusionslösung

Austria: Carmustin Hikma 100 mg Pulver und Lösungsmittel für ein Konzentrat zur Herstellung einer Infusionslösung

Spain: Carmustina Hikma 100 mg polvo y disolvente para concentrado para solución para perfusión EFG

France: CARMUSTINE HIKMA 100 mg, poudre et solvant pour solution à diluer pour perfusion

Italy: CARMUSTINA HIKMA

Netherlands: Carmustine Hikma 100 mg, poeder en oplosmiddel voor concentraat voor oplossing voor infusie

Portugal: Carmustina Hikma

Date of last revision of this leaflet: November 2023

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).

This information is intended solely for healthcare professionals:

This information is a brief description of the preparation and/or handling, incompatibilities, dosage, overdose, or laboratory monitoring measures based on the current technical data sheet.

The carmustine powder concentrate for solution for infusion does not contain preservatives and is not designed as a multiple-dose vial. Reconstitution and subsequent dilutions should be performed under aseptic conditions.

The pH and osmolality of the ready-to-use carmustine infusion solution diluted with 0.9% sodium chloride injection solution are 4.0~6.8 and 380 mOsm/kg, respectively. The pH and osmolality of the ready-to-use carmustine infusion solution diluted with 5% glucose injection solution are 4.0 ~ 6.8 and 360 mOsm/kg, respectively.

.

The freeze-dried product does not contain preservatives and is intended for single use. The lyophilized product may appear as a fine powder; however, handling may cause it to appear as a heavier and more granular lyophilized product due to the mechanical instability of the freeze-dried mass. The presence of an oily film may be an indication of drug melting. Storage of Carmustin Hikma at temperatures above 27 °C will cause the substance to liquefy, as Carmustine has a low melting point. The appearance of an oily film at the bottom of the vial is a sign of carmustine degradation. These vials should not be used. Do not use the product if it has liquefied. When in doubt about whether the product has been properly refrigerated, each vial in the box should be inspected immediately. For verification, hold the vial up to intense light. Reconstitution and dilution of the powder for concentrate for solution for infusion

Dissolve carmustine (100 mg of powder) with 3 ml of the sterile, refrigerated ethanol solvent supplied in the primary packaging (amber vial). Carmustine must be completely dissolved in ethanol before adding sterile water for injectable preparations.

Then, add 27 ml of sterile water for injectable preparations to the ethanol solution in an aseptic manner. The reconstituted 30 ml solution should be mixed well. Reconstitution, following the recommendations, results in a clear, colorless, or pale yellow solution.

The reconstituted 30 ml solution should be diluted immediately by adding the 30 ml of the reconstituted solution to 500 ml of 5% glucose injection solution or to 500 ml of 0.9% sodium chloride injection solution in glass containers. The 530 ml of diluted solution (i.e., the ready-to-use solution) should be mixed for at least 10 seconds before administration. The ready-to-use solution should be administered within 1 to 2 hours, and administration should be completed within 4 hours after reconstitution of the product.

Infusion administration should be performed using a PVC-free PE infusion set.

During administration of the medicinal product, the container should be made of suitable glass. Additionally, the ready-to-use solution should be protected from light (e.g., by wrapping the ready-to-use solution container with aluminum foil) and should be stored, preferably, at temperatures below 20 °C, as carmustine degrades more rapidly at higher temperatures.

Infusion of carmustine in less than one hour may produce intense pain and burning at the injection site (see section 4.2 of the technical data sheet).

Proper handling and disposal procedures for antineoplastics should be followed.

Cytostatic drugs should be handled with special care. Accidental contact should be avoided at all costs. This includes taking adequate precautions (such as wearing gloves) and washing hands with water and soap after handling the product.

Disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.