Carmustine Teva 100 mg powder and solvent for concentrate for infusion solution EFG
Spain
Table of Contents
Package leaflet: Information for the user
Introduction
Package leaflet: information for the patient
Carmustine Teva 100 mg powder and solvent for concentrate for solution 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, consult your doctor or nurse.
- If you experience any adverse reactions, consult your doctor or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.
Contents of this leaflet
- What Carmustine Teva is and what it is used for
- What you need to know before using Carmustine Teva
- How to use Carmustine Teva
- Possible side effects
- How to store Carmustine Teva
- Contents of the pack and other information
1. What Carmustine Teva is and what it is used for
Carmustine is a medicine containing carmustine. Carmustine belongs to a group of anticancer medicines known as nitrosoureas, which work by slowing the growth of cancer cells.
Carmustine is indicated in the following malignant neoplasms as monotherapy or in combination with other antineoplastic agents and/or other therapeutic measures (radiotherapy, surgery):
- brain tumors (glioblastoma, brainstem gliomas, meduloblastoma, astrocytoma, ependymoma), brain metastases
- multiple myeloma (in combination with glucocorticoids such as prednisolone)
- second-line treatment in Hodgkin's disease and non-Hodgkin's lymphoma
- as conditioning treatment prior to autologous hematopoietic progenitor cell transplantation (HPCT) in malignant hematological diseases (Hodgkin's disease/non-Hodgkin's lymphoma)
- advanced gastrointestinal tract tumors after failure of other anticancer drugs.
2. What you need to know before using Carmustine Teva
Do not use Carmustine Teva
- if you are allergic to carmustine, to other nitrosourea drugs, or to any of the other ingredients of this medicine (listed in section 6);
- if you have bone marrow suppression resulting in low levels of platelets, white blood cells (leukocytes), or red blood cells (erythrocytes), whether due to chemotherapy or other causes;
- if you have severe renal impairment;
- if you are breastfeeding;
- in children and adolescents;
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before starting treatment with Carmustine.
The main adverse effect of this medicine is delayed bone marrow suppression, which may present as fatigue, skin and mucosal bleeding, infections, and fever due to blood abnormalities. Therefore, your doctor will monitor your blood counts weekly for at least 6 weeks after each dose. Following the recommended dosage, carmustine cycles will not be administered more frequently than every 6 weeks. Dosage will be confirmed based on blood counts.
Before treatment, liver, lung, and kidney function will be assessed and monitored periodically during treatment.
Because carmustine use may cause lung injury, a chest X-ray and pulmonary function tests will be performed before starting treatment (see also section "Possible side effects").
High-dose carmustine treatment (up to 600 mg/m²) is only performed in combination with subsequent stem cell transplantation. Such high doses may increase the frequency or severity of pulmonary, renal, hepatic, cardiac, and gastrointestinal toxicities, as well as infections and electrolyte imbalances (low blood levels of potassium, magnesium, and phosphate).
Abdominal pain (neutropenic enterocolitis) may occur as a therapy-related adverse event following treatment with chemotherapeutic agents.
Your doctor will inform you about the possibility of developing lung injury and allergic reactions, and their symptoms. If these symptoms occur, you must contact your doctor immediately (see section 4).
Children and adolescents
Carmustine must not be used in children and adolescents under 18 years of age.
Other medicines and Carmustine Teva
Inform your doctor if you are taking, have recently taken, or might need to 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.
Use of Carmustine Teva with alcohol
The amount of alcohol contained 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 become pregnant, consult your doctor or pharmacist before using this medicine.
Pregnancy and fertility
Carmustine must not be used during pregnancy because it may harm the fetus.
Therefore, this medicine should normally not be given to pregnant women. If used during pregnancy, the patient must be aware of the potential risk to the fetus. Women of childbearing potential should use effective contraceptive methods to avoid becoming pregnant during treatment with this medicine and for at least 6 months after completion of treatment.
Male patients must use adequate contraceptive methods during treatment with carmustine and for at least 6 months after completion of treatment to prevent their partners from becoming pregnant.
Breastfeeding
You must not breastfeed while receiving this medicine and for 7 days after treatment. Risk to newborns/infants cannot be excluded.
Driving and using machines
The influence of carmustine on the ability to drive and use machines is none or negligible. However, you should consult your doctor before driving or operating tools or machinery, as the amount of alcohol contained in this medicine may affect your ability to drive or operate machinery.
Carmustine Teva contains ethanol (alcohol)
This medicine contains 2.37 g of ethanol (alcohol) per vial, equivalent to 25.6 g per maximum dose (1080 mg). The amount in the maximum dose (600 mg/m² in a 70 kg patient) of this medicine is equivalent to 648 ml of beer or 259 ml of wine.
The amount of alcohol in this medicine may affect your ability to drive or operate machinery, as it may impair your judgment and reaction speed.
If you have epilepsy or liver problems, consult your doctor or pharmacist before taking this medicine.
The amount of alcohol in this medicine may alter the effects of other medicines. Consult your doctor or pharmacist if you are taking other medicines.
If you are pregnant, consult your doctor or pharmacist before taking this medicine.
If you have alcohol addiction, consult your doctor or pharmacist before taking this medicine.
3. How to use Carmustine Teva
Carmustine will always be administered by a healthcare professional experienced 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 as monotherapy in previously untreated patients is 150 to 200 mg/m² administered intravenously every 6 weeks. This amount may be given as a single dose or divided into daily infusions of 75 to 100 mg/m² on two consecutive days. The dosage regimen may also depend on whether carmustine is administered together with other anticancer medicines.
Doses will be adjusted according to your response to treatment.
The recommended dose of carmustine administered in combination with other chemotherapeutic agents prior to hematopoietic progenitor cell transplantation is 300 to 600 mg/m² intravenously.
Blood counts will be monitored frequently to avoid bone marrow toxicity, and the dose will be adjusted if necessary.
Route of administration
For intravenous use.
After reconstitution with sterile anhydrous alcohol (3 ml vial) and water for injections (27 ml), and subsequent dilution with 500 ml of sodium chloride 9 mg/ml (0.9%) solution for injection or glucose 50 mg/ml (5%) solution for injection, carmustine is administered intravenously by infusion over a period of one to two hours, protected from light. The infusion duration 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 the physician and may vary for each patient.
If you use more Carmustine Teva than you should
Since the medicine will be administered by a doctor or nurse, it is unlikely that you will receive an incorrect dose. Inform your doctor or nurse if you have any doubts regarding the amount of medicine you have received.
If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.
4. Possible adverse effects
Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Tell your doctor or nurse immediately if you experience any of the following adverse 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 serious allergic reaction.
Carmustine may cause the following adverse effects:
Very common (may affect more than 1 in 10 people)
- Delayed myelosuppression (reduction in blood cells in the bone marrow), which may increase the risk of infections if white blood cells are reduced
- Reduction in platelets in the blood, which may increase the risk of bleeding or bruising
- Ataxia (lack of voluntary coordination of muscle movements)
- Dizziness
- Headaches
- Eye problems, transient redness of the eyes, blurred vision due to retinal haemorrhage
- Hypotension (low blood pressure)
- Phlebitis (inflammation of the veins) associated with pain, swelling, redness, sensitivity
- Respiratory disorders (lung-related) with breathing difficulties
This medicine may cause severe (possibly fatal) lung damage. Lung damage may appear years after treatment. Inform your doctor immediately if you experience any of the following symptoms: difficulty breathing, persistent cough, chest pain, persistent weakness/tiredness
- Severe nausea and vomiting
- When used on the skin, skin inflammation (dermatitis)
- Accidental skin contact may cause transient hyperpigmentation (darkening of an area of skin or nails)
Common (may affect up to 1 in 10 people)
- Acute leukaemias and bone marrow dysplasias (abnormal bone marrow development)
Some of the symptoms include bleeding gums, bone pain, fever, frequent infections, frequent or severe nosebleeds, lumps caused by swelling of lymph nodes in and around the neck, armpits, abdomen or groin, paleness, difficulty breathing, weakness, fatigue, or general loss of energy.
- Anaemia (reduction in the number of red blood cells in the blood)
- Encephalopathy (brain disorder). This may include symptoms such as muscle weakness in one area, reduced ability to make decisions or concentrate, involuntary contractions, tremors, difficulty speaking or swallowing, seizures
- Anorexia
- Constipation
- Diarrhoea
- Inflammation of the mouth and lips
- Reversible hepatic toxicity with high-dose treatment. This may cause an increase in liver enzymes and bilirubin (detected by blood tests)
- Alopecia (hair loss)
- Skin flushing
- Reactions at the injection site
Rare (may affect up to 1 in 1,000 people)
- Veno-occlusive disease (progressive blockage of veins) at high doses, in which very small (microscopic) veins in the liver become blocked. Symptoms may include: fluid accumulation in the abdomen, enlarged spleen, severe bleeding from the oesophagus, yellowing of the skin and whites of the eyes.
- Respiratory problems caused by interstitial fibrosis (with lower doses)
- Kidney problems
- Gynaecomastia (breast enlargement in males)
Frequency not known (cannot be estimated from available data)
- Any sign of infection (opportunistic infections, including fatal outcomes)
- Muscle pain
- Chest pain
- Rapid heartbeat (tachycardia)
- Seizures (fits), including status epilepticus
- Tissue damage due to leakage at the injection site
- Infertility
- Carmustine has been shown to have harmful effects on fetal development.
- Electrolyte abnormalities (and disturbances in electrolyte balance (low blood levels of potassium, magnesium and phosphate))
Reporting of adverse effects
If you experience any type of adverse effect, consult your doctor or nurse, even if they are possible adverse effects not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.
5. Storage of Carmustine Teva
This medicine will be stored by your doctor or healthcare professional.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and the carton after “EXP”. The expiry date refers to the last day of the month indicated.
Unopened vials containing dry powder:
Store and transport refrigerated (between 2°C and 8°C).
Keep in the original packaging to protect from light.
After reconstitution and dilution:
The solution must be administered within 4 hours after reconstitution and dilution at room temperature, or within 2 hours if the prepared solution has been refrigerated (2 - 8°C) for up to 18 hours. The solution must be protected from light until administration is complete.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.
6. Contents of the pack and other information
Composition of Carmustine Teva
The active substance is: carmustine
Each vial of powder for concentrate for solution for infusion contains 100 mg of carmustine. After reconstitution with 3 ml of anhydrous ethanol and 27 ml of water for injections, one ml of solution contains 3.3 mg of carmustine.
Excipients:
Powder: No excipients
Solvent: Anhydrous ethanol
Appearance of the product and contents of the pack
Carmustine is a powder and solvent for concentrate for solution for infusion.
Powder: yellowish powder for reconstitution in a 30 ml type I amber glass vial closed with a grey type I bromobutyl rubber stopper coated with a metallic aluminum flip-off cap with a colored polypropylene disc.
Solvent: clear type I glass vial (4 ml) closed with a grey coated butyl rubber stopper of type I and sealed with a metallic aluminum cap with a colored polypropylene disc.
Each pack contains one vial with 100 mg of powder (carmustine) and one vial with 3 ml of sterile solvent (anhydrous ethanol).
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Teva B.V.
Swensweg 5
2031GA Haarlem
The Netherlands
Manufacturer:
S.C. Sindan Pharma, S.R.L.
11 Ion Mihalache Ave., the 1st district
Bucharest, 011171,
Romania
For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:
Teva Pharma, S.L.U
C/ Anabel Segura, 11, Edificio Albatros B, 1st floor,
Alcobendas, 28108, Madrid (Spain)
Date of the most recent review of this leaflet: February 2022
Other sources of information
Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS): http://www.aemps.gob.es
This information is intended exclusively for healthcare professionals:
This information is a brief description of the preparation and/or handling, incompatibilities, dosage, overdose, or monitoring measures and complementary laboratory tests based on the current summary of product characteristics.
The powder for concentrate for solution for infusion of Carmustine Teva contains no preservatives and is not intended for multi-dose use. Reconstitution and subsequent dilutions must be carried out under aseptic conditions.
If the recommended storage conditions are followed, degradation of the unopened vial can be avoided until the expiry date indicated on the packaging.
The lyophilized product contains no preservatives and is suitable for single use only. The lyophilized powder may appear as a fine powder, but handling may cause it to appear as a heavier, clumped lyophilisate rather than a powdered form due to the mechanical instability of the lyophilized suspension powder. The presence of an oily film may indicate melting of the medicinal product. These products are not suitable for use due to the risk of temperature deviations above 30 °C.
This medicinal product should no longer be used. When there is any doubt about whether the product has been properly refrigerated, each vial in the pack should be inspected immediately. For verification, hold the vial up to a bright light.
Reconstitution and dilution of the powder for concentrate for solution for infusion
Dissolve the 100 mg of carmustine powder for concentrate for solution for infusion with 3 ml of sterile refrigerated solvent (anhydrous ethanol) supplied in the primary packaging (amber glass vial). Carmustine must be completely dissolved in ethanol before adding sterile water for injections.
Then, aseptically add 27 ml of sterile water for injections to the alcoholic solution. The resulting 30 ml stock solution must be thoroughly mixed. Reconstitution, following the recommendations, yields a clear, colorless or pale yellow, particle-free stock solution, which must be immediately diluted in 500 ml of 9 mg/ml (0.9%) sodium chloride injection solution or 50 mg/ml (5%) glucose injection solution in polypropylene containers. The diluted solution (i.e., the ready-to-use solution) must be mixed for at least 10 seconds before administration.
Prior to administration, the infusion solution should be inspected for precipitates. If precipitates are observed, they may be redissolved by gently warming the vial to room temperature with gentle agitation.
Carmustine has a low melting point (approximately 30.5–32.0 °C). Exposure of this medicinal product to this temperature or higher will cause the product to liquefy and appear as an oily film at the bottom of the vials. This is a sign of degradation, and the vials must be discarded.
The pH and osmolarity of the ready-to-use infusion solutions are:
pH: 4.0 to 6.8
The osmolarity of ready-to-use infusion solutions (when diluted in 50 mg/ml (5%) glucose injection solution or 9 mg/ml (0.9%) sodium chloride injection solution) ranges from 360 to 390 mOsm/l.
Method of administration
The ready-to-use solution must be administered intravenously as an intravenous infusion over a period of one to two hours.
Administration must be completed within 4 hours after reconstitution/dilution of the medicinal product at room temperature, or within 2 hours if the ready-to-use solution has been refrigerated (2–8°C) for up to 18 hours.
The infusion must be administered using a PE (polyethylene) infusion set free of PVC. Additionally, ready-to-use solutions must be protected from light (e.g., by wrapping the solution container in aluminum foil) and preferably stored at temperatures below 20–22 °C, as carmustine degrades more rapidly at higher temperatures.
Shorter infusion periods of Carmustine Teva may cause intense pain and burning at the injection site. The injection site should be monitored during administration.
Standard guidelines for the safe handling and disposal of antineoplastic agents must be followed.
Dosage and complementary laboratory tests
Initial doses
The recommended dose of Carmustine Teva as monotherapy in previously untreated patients is 150 to 200 mg/m² administered intravenously every 6 weeks. This dose may be given as a single dose or divided into daily infusions of 75 to 100 mg/m² on two consecutive days.
When Carmustine Teva is used in combination with other myelosuppressive agents or in patients with depleted bone marrow reserve, doses should be adjusted according to the patient's hematological profile, as shown below.
Monitoring and subsequent doses
A new cycle of Carmustine Teva must not be administered until circulating blood elements have recovered to acceptable levels (platelets above 100,000/mm³, white blood cells above 4,000/mm³), which generally occurs after six weeks. Blood counts should be monitored frequently, and repeated cycles must not be administered before six weeks due to delayed hematological toxicity.
Subsequent doses after the initial dose should be adjusted according to the patient's hematological response to the previous dose, both in monotherapy and in combination with other myelosuppressive agents. The following scheme is suggested as a guide for dose adjustment:
Nadir after previous dose | Percentage of previous dose to administer | ||
Leukocytes/mm3 | Platelets/mm3 | ||
> 4,000 | >100,000 | 100% | |
3,000 – 3,999 | 75,000 – 99,999 | 100% | |
2,000 – 2,999 | 25,000 – 74,999 | 70% | |
<2,000 | <25,000 | 50% |
In cases where the nadir of leukocytes and platelets after the initial dose does not fall within the same row (e.g., leukocytes > 4,000 and platelets < 25,000), the value corresponding to the lower percentage of the previous dose should be used (e.g., if the platelet count is < 25,000, a maximum of 50% of the previous dose should be administered).
There are no limits regarding the duration of carmustine treatment. If the tumor remains incurable or if severe or intolerable adverse reactions occur, carmustine treatment should be discontinued.
Conditioning treatment prior to HPCT
Carmustine is administered in combination with other chemotherapeutic agents in patients with malignant hematological diseases prior to HPCT at a dose of 300–600 mg/m² intravenously.
Special populations
Paediatric population
Carmustine is contraindicated in children and adolescents under 18 years of age.
Elderly patients
In general, dose selection for elderly patients should be cautious, usually starting at the lower end of the dosing range, reflecting the higher frequency of impaired hepatic, renal, or cardiac function, concomitant diseases, or concomitant medication use. Since elderly patients are more likely to have decreased renal function, care should be taken when selecting the dose, glomerular filtration should be monitored, and the dose adjusted accordingly.
Renal impairment
In patients with renal impairment, the dose of Carmustine Teva should be reduced if glomerular filtration rate is decreased.
Compatibility/incompatibility with containers
The intravenous solution is unstable in polyvinyl chloride (PVC) containers. Carmustine solution may only be administered from glass vials or polypropylene containers. All plastics coming into contact with the carmustine infusion solution (e.g., infusion sets, etc.) must be made of polyethylene without PVC.