BICARLOG 300 MG POWDER AND SOLVENT FOR CONCENTRATE FOR SOLUTION FOR INFUSION - patient leaflet, side effects, dosage

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Package leaflet: Information for the user Bicarlog 50 mg powder and solvent for concentrate for solution for infusion Bicarlog 300 mg powder and solvent for concentrate for solution for infusion carmustine

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 or pharmacist or nurse.

• – If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

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• 1. What Bicarlog is and what it is used for

• 2. What you need to know before Bicarlog is given to you

• 3. How to use Bicarlog

• 4. Possible side effects

• 5. How to store Bicarlog

• 6. Contents of the pack and other information

1. What Bicarlog is and what it is used for

Bicarlog is a medicine which contains carmustine. Carmustine belongs to a group of anticancer medicines known as nitrosourea that act by slowing the growth of cancer cells.

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Bicarlog is indicated, in combination with other chemotherapy medicinal products with or without total body irradiation (TBI), as conditioning treatment prior to autologous haematopoietic progenitor cell transplantation (HPCT) in Lymphomas. (Hodgkin’s disease and Non-Hodgkin’s lym­phoma).

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। 2. What you need to know before

। Bicarlog is given to you

Do not use Bicarlog:

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

• – if you suffer from suppression of blood cell formation in the bone marrow and the number of your platelets, white blood cells (leucocytes), or red blood cells (erythrocytes) is therefore reduced, either as a result of chemotherapy or other causes.

• – if you suffer from higher-grade kidney dysfunction.

• – in children and adolescents

• – if you are breast-feeding.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Bicarlog.

The major side effect of this medicine is delayed bone marrow suppression, which may show as tiredness, bleeding from the skin and mucous membranes as well as infections and fever due to changes in the blood. Therefore your doctor will monitor blood counts weekly for at least 6 weeks after a dose. The dosage will be confirmed with the blood count.

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Before treatment, your liver, lung and kidney function will be tested and observed regularly during treatment.

Since the use of Bicarlog can lead to lung damage, an X-ray of the chest region and lung function tests will be conducted before treatment is started (please also see the section “Possible side effects”).

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High-dose treatment with Bicarlog (up to 600 mg/m2) is only performed in combination with subsequent stem cell transplantation. Such a higher dose can increase frequency or severity of lung, kidney, liver, heart, and gastrointestinal toxicities as well as infections and disturbances in the electrolyte balance (low blood levels of potassium, magnesium, phosphate).

Stomach pain (neutropenic enterocolitis) can occur as therapy-related adverse event upon treatment with chemotherapeutic agents.

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Your doctor will talk to you about the possibility of lung damage and allergic reactions and their symptoms. If such symptoms occur, you should contact your doctor immediately (see section 4).

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Children and adolescents

Bicarlog must not be used in children and adolescents aged less than 18 years.

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Other medicines and Bicarlog

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

• – Phenytoin, used in epilepsy

• – Dexamethasone, used as an anti-inflammatory and immunosuppres­sive agent

• – Cimetidine, used for stomach problems like indigestion – Digoxin, used if you have abnormal heart rhythm i

• – Melphalan, an anticancer medicine

Bicarlog with alcohol

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

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy and fertility

Bicarlog should not be used during pregnancy because it may harm your unborn baby. Therefore this medicine should not normally be administered to pregnant women. If used during pregnancy, the patient must be aware of the potential risk to the unborn baby. Women of childbearing potential are advised to use effective contraception to avoid becoming pregnant whilst being treated with this medicine and for at least 6 months after treatment.

Male patients should use adequate contraceptive measures while on treatment with Bicarlog and for at least 6 months after treatment to prevent their partners becoming pregnant.

Breast-feeding

You must not breast-feed while taking this medicine and up to 7 days after treatment. A risk to the newborn/infant cannot be excluded.

Driving and using machines

Bicarlog has no or negligible influence on the ability to drive and use machines. You must check with your doctor before driving or operating any tools or machines because the amount of alcohol in this medicine may impair your ability to drive or use machines.

Bicarlog contains ethanol (alcohol)

This medicine contains 2.4 g of alcohol (ethanol) per vial for 50 mg strength and 7.1 g of alcohol (ethanol) per vial for 300 mg strength which is equivalent to 25.92 g per maximal dose (10 vol %). The amount in maximal dose (600 mg/m2 in 70 kg patient) of this medicine is equivalent to 648 ml beer or 259 ml wine.

The amount of alcohol in this medicine can affect your ability to drive or use machines. This is because it may affect your judgement and how fast you react.

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 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 are addicted to alcohol, talk to your doctor or pharmacist before taking this medicine.

3. how to use bicarlog.

Bicarlog will always be given to you by a healthcare professional with experience in the use of anticancer medicines.

Adults

Dosage is based on your medical condition, body size and response to treatment. The recommended dose of Bicarlog given in combination with other chemotherapeutic agents before haematopoietic progenitor cell transplantation is 300 – 600 mg/m2 intravenously.

Your blood count will be monitored frequently to avoid toxicity in your bone marrow and the dose adjusted if necessary.

Route of administration

Following reconstitution and dilution Bicarlog is given into a vein by a drip (intravenously) over a one- to two-hour period protected from light. The duration of infusion should not be less than one hour to avoid burning and pain at the injected area. The injected area will be monitored during the administration.

The duration of the treatment is determined by the doctor and may vary for each patient.

If you use more Bicarlog than you should

As a doctor or nurse will be giving you this medicine, it is unlikely that you will receive an incorrect dose. Tell your doctor or nurse if you have any concern about the amount of medicine that you received.

If you have any further questions on the use of this medicine, ask your doctor or 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:

Any sudden wheeziness, difficulty in breathing, swelling of the eyelids, face or lips, rash or itching (especially affecting your whole body), and feeling you are going to faint. These may be signs of a severe allergic reaction.

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The following information is intended for healthcare professionals only:

This information is a short description of preparation and/or handling, incompatibilities, posology of the medicine, overdose or monitoring measures and laboratory investigations based on the current SmPC.

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The carmustine powder for concentrate for solution for infusion contains no preservative and is not intended as a multiple dose vial. Reconstitution and further dilutions should be carried out under aseptic conditions.

By following the recommended storage conditions it is possible to avoid any decomposition of the unopened vial until the date of expiry mentioned on the packaging.

The dry frozen product does not contain any preservatives and is suitable only for one use. The lyophilisate can appear as a fine powder, however handling can cause it to appear as a heavier and lumpier lyophilisate than as a powdery lyophilisate due to the mechanical instability of the freeze drying cake. The presence of an oily film can be an indication of melting of the medicinal product. Such products are not accepted for use due to the risk of temperature excursions to more than 30°C. This medicinal product should not be used any further. When you are not clear about the fact whether the product is adequately cooled, then you should immediately inspect each vial in the carton. For verification, hold the vial in bright light.

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Reconstitution and dilution of Bicarlog 50 mg powder for concentrate for solution for infusion

Dissolve carmustine (50 mg powder) with 1.5 ml supplied sterile refrigerated ethanol solvent in the primary packaging (brown glass vial). Carmustine must be completely dissolved in ethanol before sterile water for injections is added. Then aseptically add 13.5 ml of sterile water for injection to the alcohol solution. The 15 ml stock solution needs to be mixed thoroughly.

One ml of the reconstituted stock solution contains

3.3 mg carmustine in 10% ethanol. Reconstitution, as recommended, results in a clear, colourless to yellowish stock solution, which should be further diluted immediately to either 250 ml sodium chloride 9 mg/ml (0.9%) solution for injection or 5% glucose solution for injection to get final concentration of 0.2 mg/ml. The 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 over 1–2 hours.

Reconstitution and dilution of Bicarlog 300 mg powder for concentrate for solution for infusion

Dissolve carmustine (300 mg powder) with 9 ml of supplied sterile refrigerated ethanol solvent in the primary packaging (brown glass vial). Carmustine must be completely dissolved in ethanol before sterile water for injections is added. Then aseptically add 81 ml of sterile water for injection to the alcohol solution. The 90 ml stock solution needs to be mixed thoroughly.

One ml of the reconstituted stock solution contains

3.3 mg carmustine in 10% ethanol. Reconstitution, as recommended, results in a clear, colourless to yellowish stock solution, which should be further diluted immediately to either 1500 ml sodium chloride 9 mg/ml (0.9%) solution for injection or 5% glucose solution for injection to get final concentration of 0.2 mg/ml. The diluted solution (i.e. the ready-to-use solution) should be

	Artwork No.	–		Colours Used
	Customer	Accord	■	Pantone Black
	Description	Carmustine Inj.
	Market	UK
	Language	English
	Size	170 × 550 mm (FF 50×30mm) (PIL)
	Min. Font Size	8 pt.
	Version No.	6 (Page 2 of 2)
	Date	24.11.21 (Carmustine Inj. (ACC-UK) PIL)

Bicarlog may cause the following side effects:

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

• – Delayed myelosuppression (decrease in blood cells in bone marrow) which can increase the chance of infections if white blood cells are decreased

• – Ataxia (lack of voluntary coordination of muscle movements);

• – Dizziness;

• – Headache;

• – Transient redness in the eye, blurred vision due to retinal bleeding;

• – Hypotension (fall in blood pressure);

• – Phlebitis (inflammation of the veins) associated with pain, swelling, redness, tenderness;

• – Respiratory disorders (lung related disorders) with breathing problems;

This medicine may cause severe (possibly fatal) lung damage. Lung damage may occur years after treatment. Tell your doctor immediately if you experience any of the following symptoms: shortness of breath, persistent cough, chest pain, persistent weakness/tiredness.

• – Severe nausea and vomiting

• – When used on the skin, inflammation of the skin (dermatitis);

• – Accidental contact with skin 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 development of the bone marrow).Symptoms may include bleeding from the gums, bone pain, fever, frequent infections, frequent or severe nosebleed, lumps caused by swollen lymph nodes in and around the neck, underarm, abdomen or groin, pale skin, shortness of breath, weakness, fatigue or a general decrease in energy;

Anaemia (decrease in the amount of red blood cells in the blood);

Encephalopathy (disorder of brain). Symptoms may include muscle weakness in one area, poor decision-making or concentration, involuntary twitching, trembling, difficulty speaking or swallowing, seizures; Anorexia;

• – Constipation;

• – Diarrhoea;

• – Inflammation of the mouth and lips;

• – Reversible liver toxicity in high-dose therapy. This can result in increased liver enzymes and bilirubin (detected by blood tests);

• – Alopecia (loss of hair);

• – Flushing of the skin;

• – Reactions on the injection site

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

• – Veno-occlusive disease (progressive blockage of the veins) where very small (microscopic) veins in the liver are blocked. Symptoms may include: fluid accumulation in the abdomen, enlargement of spleen, severe bleeding of the oesophagus, yellow-colouring of skin and whites of the eyes;

• – Breathing problems caused by interstitial fibrosis (with lower doses);

• – Kidney problems;

• – Gynecomastia (breast growth in males)

From a microbiological point of view, unless the method of opening, reconstitution and dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of user.

The solution should be protected from light until the end of administration.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist or doctor how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Bicarlog contains

The active substance is carmustine.

Bicarlog 50 mg

One 20 ml vial of powder for concentrate for solution for infusion contains 50 mg carmustine. One 5 ml vial of solvent contains 3 ml of ethanol anhydrous.

Once the solution is reconstituted with the solvent provided and further diluted with sterile water, one ml of solution will contain 3.3 mg of carmustine.

Bicarlog 300 mg

One 100 ml vial of powder for concentrate for solution for infusion contains 300 mg carmustine. One 10 ml vial of solvent contains 9 ml of ethanol anhydrous.

Once the solution is reconstituted with the solvent provided and further diluted with sterile water, one ml of solution will contain 3.3 mg of carmustine.

Other excipients:

• – Powder: No excipients.

• – Solvent: Ethanol anhydrous.

What Bicarlog looks like and contents of the pack

Bicarlog is a powder and solvent for concentrate for solution for infusion.

The powder is pale yellow dry flakes or dry congealed mass is in a type I amber glass vial sealed with rubber stopper and aluminium seal having polypropylene cap.

The solvent is a clear colourless liquid in a type I clear glass vial sealed with rubber stopper and aluminium seal having polypropylene cap.

Pack sizes: Pack contains 1 vial of 50 mg powder and 1 vial of 3 ml solvent

Pack contains 10 vials of 50 mg powder and 10 vials of 3 ml solvent

Pack contains 1 vial of 300 mg powder and 1 vial of 9 ml solvent

Pack contains 10 vials of 300 mg powder and 10 vials of 9 ml solvent

Not all pack sizes may be marketed.

Not known (frequency cannot be estimated from the available data)

• – Muscular pain;

• – Seizures (fits) including status epilepticus;

• – Tissue damage due to leakage in injection area;

• – Infertility;

• – Carmustine has been shown to adversely affect the development of unborn babies

• – Electrolyte abnormalities (and disturbances in the electrolyte balance (low blood levels of potassium, magnesium, phosphate))

5. how to store bicarlog

This medicine will be stored by your doctor or health care 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 carton after EXP. The expiry date refers to the last day of that month.

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

Keep the vials in the outer carton in order to protect from light.

After reconstitution (reconstituted stock solution) Chemical and physical in-use stability of reconstituted stock solution has been demonstrated for 24 hours at 2 to 8°C.

After dilution (solution after dilution for infusion) Chemical and physical in-use stability of solution after dilution for infusion in sodium chloride solution for injection or 5% glucose solution for injection at final concentration of 0.2 mg/ml and stored in a glass or polypropylene container has been demonstrated for 6 hours at 20 to 25°C, protected from light. These solutions will also remain stable for 24 hours in cold storage (2 to 8 °C) and a further 4 hours at 20 to 25 °C, protected from light.

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mixed for at least 10 seconds before administration. The Ready-to-Use solution should be administered over 1–2 hours.

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The pH and osmolality of diluted ready-to-use solutions for infusion are

pH: 3.2 to 7.0 diluted in normal saline or 5% glucose solution for injection.

Osmolality: 340 to 400 mOsmol/l (diluted in glucose 50 mg/ml [5%] solution for injection or sodium chloride 9 mg/ml [0.9%] solution for injection).

Method of administration

The reconstituted and diluted solution (i.e. ready-to-use solution) must be given intravenously and should be administered by intravenous drip over a one- to two-hour period. Administration of the infusion should be performed using a PVC free PE infusion set. During administration of the medicinal product, the glass or polypropylene container shall be used. Further, the ready-to-use solution needs to be protected from light (e.g. using alu-foil wrapped around the container of the ready-to-use solution) and preferably kept at temperatures below 20–25°C as Carmustine degrades faster at higher temperatures.

Infusion of Bicarlog over shorter periods of time may produce intense pain and burning at the site of injection. The injected area should be monitored during the administration.

Guidelines for the safe handling and disposal of antineoplastic agents must be observed. chemotherapeutic medicinal products prior to autologous HPCT at a dose of 300 mg/m2 to 600 mg/m2 intravenously.

Special populations

Paediatric population

Bicarlog is contraindicated in children and adolescents aged <18 years.

Elderly

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dose range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and take into consideration concomitant disease or therapy with other medicinal products. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and the glomerular filtration rate should be monitored and the dose reduced according to this.

Renal impairment

For patients with renal impairment the dose of Bicarlog should be reduced if the glomerular filtration rate is reduced.

Compatibility/In­compatibility with containers

The intravenous solution is unstable in polyvinyl chloride containers. All plastic coming into contact with the carmustine solution for infusion (e.g. infusion set etc.) should be PVC free polyethylene plastic, otherwise glass ware should be used.

Posology and laboratory investigations

Bicarlog is administered in combination with other

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