Calcium folinate kabi

Package leaflet: Information for the user

Calcium Folinate Kabi, 10 mg/ml, solution for injection/infusion
Calcii folinas
Please read all of this leaflet carefully before the medicine is administered, because it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If any side effects occur, including any not listed in this leaflet, tell your doctor or nurse. See section 4.

Leaflet contents

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

1. What Calcium Folinate Kabi is and what it is used for

Calcium Folinate Kabi, 10 mg/ml, solution for injection or infusion, contains calcium folinate, which
belongs to a group of medicines: antidotes used in cancer treatment. It is a calcium salt of
folic acid, a vitamin related to folate.
Calcium Folinate Kabi is indicated for use:

• to reduce toxicity and in cases of overdose of certain anticancer medicines, e.g. methotrexate and other folic acid antagonists, known as "calcium folinate rescue therapy";
• in combination with 5-fluorouracil (an anticancer medicine). 5-fluorouracil works better when given together with calcium folinate.

2. Important information before using Calcium Folinate Kabi

When not to use Calcium Folinate Kabi:

• if the patient is allergic to calcium folinate or to any of the other ingredients of this medicine (listed in section 6);
• if the patient has anaemia (insufficient number of red blood cells) caused by vitamin B deficiency, such as:
• pernicious anaemia (the patient's immune system attacks his red blood cells),
• megaloblastic anaemia (red blood cells are larger than normal).

Calcium Folinate Kabi must not be administered simultaneously with certain anticancer medicines in pregnant or breastfeeding women. Your doctor will know which medicines are concerned.
Warnings and precautions
Talk to your doctor or nurse before using Calcium Folinate Kabi.
Calcium Folinate Kabi must be administered only by intramuscular injection, or by intravenous injection or infusion. It must not be administered intrathecally.
Tell your doctor if any of the following apply to the patient:

• the patient is being treated with 5-fluorouracil, especially in elderly patients or those in poor health, because Calcium Folinate Kabi may enhance the harmful effects of 5-fluorouracil. The patient may be more susceptible to infections (due to insufficient number of white blood cells). Mouth ulcers or diarrhoea may occur. Gastrointestinal disorders are also common and may be severe or even life-threatening (see section 4, "Possible side effects"). Your doctor may decide to discontinue treatment with 5-fluorouracil and Calcium Folinate Kabi.
• the patient has epilepsy and is taking antiepileptic medicines (e.g. phenobarbital, phenytoin, primidone or succinic acid derivatives). Because there is a risk of increased frequency of epileptic seizures during treatment with Calcium Folinate Kabi, your doctor may decide to adjust the dose of the antiepileptic medicine.
• the patient has macrocytosis (enlarged red blood cells) caused by anticancer medicines (e.g. hydroxycarbamide, cytarabine, mercaptopurine and thioguanine), because this condition should not be treated with Calcium Folinate Kabi.
• the patient has impaired kidney function, because the dose of Calcium Folinate Kabi may need to be adjusted.

Calcium Folinate Kabi and other medicines
Tell your doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Tell your doctor if the patient is currently taking or has recently taken:

• medicines that block the action of folic acid (folic acid antagonists), such as co-trimoxazole (an antibacterial medicine) or pyrimethamine (used to treat certain infections, e.g. malaria), because Calcium Folinate Kabi may reduce the effectiveness of these medicines.
• antiepileptic medicines, such as phenobarbital, phenytoin, primidone or succinic acid derivatives (e.g. ethosuximide, phensuximide). Calcium Folinate Kabi may reduce the concentration of these medicines in the body, which could increase the frequency of epileptic seizures. Your doctor may order blood tests to monitor the levels of these medicines. Your doctor will also decide whether the dose of antiepileptic medicines needs to be adjusted.
• 5-fluorouracil, because co-administration of calcium folinate with 5-fluorouracil increases its efficacy but also enhances its toxic effects. Your doctor will decide whether the dose of 5-fluorouracil needs to be adjusted.

Pregnancy and breastfeeding
Pregnancy
Calcium folinate may be used during pregnancy or breastfeeding to reduce methotrexate toxicity only if your doctor considers methotrexate treatment necessary. However, methotrexate should generally not be used during pregnancy or breastfeeding.
Breastfeeding
There are insufficient data on the use of calcium folinate and 5-fluorouracil or other anticancer medicines during pregnancy or breastfeeding. However, anticancer medicines should generally not be used during pregnancy or breastfeeding.
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult her doctor or pharmacist before using this medicine.
Driving and using machines
The effect of Calcium Folinate Kabi on the ability to drive and use machines has not been established.
Calcium Folinate Kabi contains sodium
This medicine contains 3.20 mg of sodium (the main component of table salt) in each ml of solution. This corresponds to 0.16% of the maximum recommended daily dietary intake of sodium for adults.

3. How to use Calcium Folinate Kabi

Calcium Folinate Kabi should be administered with anticancer drugs (methotrexate or
5-fluorouracil) only under the strict supervision of an experienced physician.
The physician will decide the dose of the medicine, depending on the patient's health status.
Medical personnel will prepare the medicinal solution for the patient. The medicine is given slowly into a vein (by injection or infusion) or by intramuscular injection. The physician will decide how many injections or infusions the patient should receive and how often the medicine should be administered.
Use of a higher than recommended dose of Calcium Folinate Kabi
There are no reports on the consequences of administering significantly higher doses than recommended of Calcium Folinate Kabi. However, excessively high doses of the medicine may reduce the effectiveness of methotrexate.
If you have any further questions regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You must immediately inform the doctor if the patient develops sudden wheezing,
difficulty breathing, swelling of the eyelids, face or lips, rash or itching
(especially affecting the whole body). These may be symptoms of an allergic reaction to this medicine.
Uncommon adverse reactions (occurring in fewer than 1 in 100 patients):

• fever.

Rare adverse reactions (occurring in fewer than 1 in 1,000 patients):

• sleep problems (after high doses);
• restlessness (inability to remain still after high doses);
• depression (after high doses);
• gastrointestinal disturbances (after high doses), e.g. vomiting, nausea, diarrhoea and dehydration;
• increased frequency of epileptic seizures in patients with epilepsy.

Very rare adverse reactions (occurring in fewer than 1 in 10,000 patients):

• allergic reactions, including severe allergic reactions with difficulty breathing or dizziness and urticaria.

Adverse reactions when Calcium Folinate Kabi is administered together with 5-fluorouracil may
differ. They depend on the dosing schedule (once weekly or once monthly). Elderly patients and those in poor health are more susceptible to adverse reactions. Possible adverse reactions:
Weekly regimen:
Very common adverse reactions (occurring in more than 1 in 10 patients):

• severe diarrhoea and dehydration.

You must immediately inform the doctor if any of the above adverse reactions occur. These may be life-threatening and hospital treatment may be necessary. The doctor will decide whether to discontinue 5-fluorouracil until symptoms resolve.
Monthly regimen:
Very common adverse reactions (occurring in more than 1 in 10 patients):

• vomiting;
• nausea (feeling sick);
• severe oral mucositis, redness and swelling.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
tel.: + 48 22 49 21 301
fax: + 48 22 49 21 309
website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Calcium Folinate Kabi

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the vial and carton after EXP.
The expiry date refers to the last day of the specified month.
Store in a refrigerator (2°C–8°C).
Keep the vial in the outer packaging to protect from light.

Shelf-life after first opening
For single use only. Any unused portion of the solution must be immediately discarded.

Shelf-life after dilution
After dilution with 0.9% sodium chloride solution or 5% glucose solution, calcium folinate solution maintains chemical and physical stability during use, under protection from light.
When diluted with 0.9% sodium chloride solution or 5% glucose solution to a concentration of 1.5 mg/ml, calcium folinate solution maintains chemical and physical stability during use for 24 hours at both 25°C and 2°C–8°C, under protection from light.
When diluted with 0.9% sodium chloride solution to a concentration of 0.2 mg/ml, calcium folinate solution maintains chemical and physical stability during use for 24 hours at 2°C–8°C, under protection from light.

From a microbiological standpoint, the medicine should be used immediately. If not used immediately, the responsibility for storage conditions and duration prior to use lies with the user and should generally not exceed 24 hours at 2°C–8°C, unless dilution was carried out under controlled and validated aseptic conditions.

If discoloration or presence of particulate matter occurs, the solution must be discarded.

Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the package and other information

What Calcium Folinate Kabi contains

• The active substance is folinic acid. Each ml contains 10 mg of folinic acid as calcium folinate.

Each vial of 5 ml, 10 ml, 20 ml, 35 ml, 50 ml, 100 ml contains 50 mg, 100 mg,
200 mg, 350 mg, 500 mg and 1000 mg of folinic acid, respectively, as calcium folinate.

• The other components are: sodium chloride, sodium hydroxide, hydrochloric acid concentrated and water for injections.

What Calcium Folinate Kabi looks like and contents of the pack
This medicine is a solution for injection or infusion. It is a clear, yellowish solution, free from
visible solid particles.
The medicine is available in vials made of amber type I glass containing 5 ml, 10 ml, 20 ml, 35 ml,
50 ml or 100 ml of solution for injection/for infusion, with a chlorobutyl rubber stopper
and an aluminium "flip-off" cap.
Pack sizes:
1, 5 or 10 vials of 5 ml, 10 ml, 20 ml, 35 ml, 50 ml or 100 ml solution.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
FreseniusKabi Deutschland GmbH
Else-Kroener Strasse 1
Bad Homburg v.d.H. 61352
Germany
Manufacturer
Fresenius Kabi Austria GmbH
Hafnerstrasse 36
A-8055 Graz
Austria
For further information, contact the Marketing Authorisation Holder:
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw
Tel.: + 48 22 345 67 89
This medicinal product is authorised for marketing in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Information intended exclusively for medical professionals:

Pharmaceutical incompatibilities
Do not mix Calcium Folinate Kabi with other medicinal products except those mentioned in the section “Method of administration”. Pharmaceutical incompatibilities have been observed between calcium folinate for injection and droperidol, 5-fluorouracil, foscarnet, and methotrexate in injectable forms.

Method of administration
Administer only intramuscularly by injection or intravenously by injection or infusion.
Administration by other routes may result in death. Do not administer intrathecally.

Prior to intravenous infusion, Calcium Folinate Kabi must be diluted with 0.9% sodium chloride solution or 5% glucose solution.

For single use only. Any unused portions of the solution must be discarded.

Before administration, visually inspect the calcium folinate solution. Use only clear solutions without visible particulate matter.

During intravenous infusion, calcium folinate should not be administered at a rate exceeding 160 mg per minute due to its calcium ion content.

Shelf life
Shelf life after first opening
For single use only. Any unused portions of the solution must be immediately discarded.

Shelf life after dilution
After dilution with 0.9% sodium chloride solution or 5% glucose solution, the calcium folinate solution is chemically and physically stable during use when protected from light.

When diluted with 0.9% sodium chloride solution or 5% glucose solution to a concentration of 1.5 mg/ml, the calcium folinate solution is chemically and physically stable during use for 24 hours at both 25°C and 2°C–8°C, when protected from light.

When diluted with 0.9% sodium chloride solution to a concentration of 0.2 mg/ml, the calcium folinate solution is chemically and physically stable during use for 24 hours at 2°C–8°C, when protected from light.

From a microbiological standpoint, the medicinal product should be used immediately. If not used immediately, the user is responsible for the storage duration and conditions prior to use, which should not normally exceed 24 hours at 2°C–8°C, unless dilution was carried out under controlled and validated aseptic conditions.

Disposal
Any unused medicinal product or waste material must be disposed of in accordance with local regulations.