Calcium folinate kalceks

Package leaflet: Information for the user

Calcium folinate Kalceks, 10 mg/mL, solution for injection / infusion
Acidum folinicum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any questions, please consult your doctor or nurse.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, tell your doctor or nurse. See section 4.

Table of contents

1. What Calcium folinate Kalceks is and what it is used for
2. Important information before using Calcium folinate Kalceks
3. How to use Calcium folinate Kalceks
4. Possible side effects
5. How to store Calcium folinate Kalceks
6. Contents of the pack and other information

1. What Calcium folinate Kalceks is and what it is used for

Calcium folinate Kalceks, 10 mg/mL, solution for injection / infusion contains the active substance
folic acid in the form of calcium folinate hydrate (referred to hereinafter as calcium folinate).
Calcium folinate is the calcium salt of folinic acid, belonging to a group of medicines known as "antidotes".
This medicine is used for:

• reducing harmful effects and treating overdose of certain antineoplastic agents, such as methotrexate and other folic acid antagonists in adults and children. This procedure is known as "calcium folinate rescue therapy";
• treatment of tumours in combination with fluorouracil (an antineoplastic agent). Fluorouracil works better when administered together with calcium folinate.

2. Important information before using Calcium folinate Kalceks

When not to use Calcium folinate Kalceks:

• 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 a type of anaemia (insufficient number of red blood cells) caused by vitamin B deficiency. If in doubt whether any of the above conditions apply to the patient, discuss this with a doctor or nurse before administering this medicine.

Calcium folinate Kalceks must not be used together with certain (known to the physician) anticancer medicines in pregnant or breastfeeding women.
This medicine must not be administered directly into the spine (intrathecally).
Warnings and precautions
Before starting treatment with Calcium folinate Kalceks, discuss with a doctor or nurse if:

• the patient has any kidney disease (it may be necessary to increase the dose or administer this medicine for a longer period);
• the patient has epilepsy.

Use of calcium folinate with fluorouracil
Do not use this medicine together with fluorouracil if the patient experiences gastrointestinal problems due to the medicine.
When concomitant use of calcium folinate and fluorouracil is necessary, discuss this with a doctor or nurse if:

• the patient has previously undergone radiotherapy;
• the patient has gastrointestinal disorders;
• the patient has inflammation inside the mouth;
• the patient is elderly;
• the patient feels very unwell.

The doctor will monitor liver and (or) kidney function and will perform regular blood tests to check this.
Calcium folinate Kalceks and other medicines
Inform the doctor or nurse about all medicines currently taken or recently taken, as well as any medicines the patient plans to take.
Due to the need for special caution, this is particularly important when using any of the following medicines:

• medicines known as folic acid antagonists, such as co-trimoxazole (an antibiotic) or pyrimethamine (used to treat malaria). Calcium folinate may reduce or completely counteract the effect of these medicines;
• fluorouracil (an anticancer medicine). Calcium folinate increases both the efficacy and the adverse effects of fluorouracil;
• medicines used to treat epilepsy (phenobarbital, phenytoin, primidone or succinimides such as ethosuximide). Calcium folinate may reduce the effectiveness of these medicines. The doctor may check blood levels of these medicines and adjust the dose to prevent worsening of seizures (convulsions).

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor before using this medicine.
Calcium folinate Kalceks does not cause harmful effects when used as the sole medicine during pregnancy.
Calcium folinate Kalceks must not be administered together with fluorouracil during pregnancy or breastfeeding, as this may harm the child.
Calcium folinate Kalceks may be administered together with methotrexate during pregnancy or breastfeeding only if the doctor considers it necessary.
Driving and operating machinery
There is no evidence that calcium folinate affects the ability to drive or operate machinery.
Calcium folinate Kalceks contains sodium
This medicine contains 3.15 mg of sodium (the main component of table salt) in each mL of solution. This corresponds to 0.16% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to use Calcium folinate Kalceks

This medicine may be given as an injection or infusion (in a drip) into a vein, or as an intramuscular injection. If the medicine is to be given as an infusion, it must first be diluted.
The doctor will decide the dose and how often the medicine is given to the patient. This will depend on the condition being treated, the patient's body surface area, and any other treatments the patient is receiving.
Use of a higher than recommended dose of Calcium folinate Kalceks
This medicine will be administered in a hospital under the supervision of a doctor. It is unlikely that it will be given in too high or too low a dose. However, if you have any doubts, discuss this with your doctor or nurse.
If you have any further questions about the use of this medicine, consult your doctor or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Immediate medical attention from a doctor or nurse is required if the patient experiences:

• sudden itchy rash (urticaria), swelling of hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing) and a feeling of fainting. These may be symptoms of a very rare severe allergic reaction (may affect up to 1 in 10,000 people). Urgent medical help may be needed;
• red, flat, target-like or circular skin lesions on the trunk, often with blisters in the center, peeling skin, and ulceration of the mouth, throat, nose, genital organs and eyes. These serious skin reactions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis) (frequency cannot be determined from available data).

Uncommon (may affect fewer than 1 in 100 people)

• fever.

Rare (may affect fewer than 1 in 1,000 people)

• insomnia;
• agitation and depression (after administration of high doses);
• increased frequency of seizures in patients with epilepsy;
• gastrointestinal disturbances (after administration of high doses).

Combination therapy with fluorouracil only
The use of calcium folinate in combination with fluorouracil increases the likelihood of the following adverse reactions:
Very common (may affect more than 1 in 10 people)

• bone marrow dysfunction (including life-threatening cases);
• inflammation of the mucous membranes of the intestine and oral cavity (including life-threatening cases);
• nausea, vomiting and diarrhoea (with monthly dosing);
• severe diarrhoea and dehydration (with weekly dosing).

Common (may affect fewer than 1 in 10 people)

• redness and swelling of the palms or soles of the feet, which may lead to skin peeling (so-called hand-foot syndrome).

Frequency unknown (frequency cannot be determined from available data)

• increased blood ammonia levels.

Patients should inform their doctor if they experience diarrhoea or inflammation of the oral mucosa, as the doctor may wish to reduce the dose of fluorouracil until symptoms have completely resolved.
Since diarrhoea may be a sign of toxic effects on the stomach and intestines, patients experiencing these symptoms will be closely monitored until symptoms have completely resolved.
These symptoms may be the beginning of a rapid deterioration in health leading to death.
The doctor may perform tests to check for low blood calcium levels.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, patients should inform their doctor or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
PL-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 Kalceks

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial and outer carton following
"EXP". The expiry date refers to the last day of the stated month.
EXP – expiry date.
Lot – batch number.
Store in a refrigerator (2°C–8°C).
Keep the vial in the outer packaging to protect from light.
After opening the vial: the product should be used immediately.

Shelf life after dilution
Chemical and physical stability has been demonstrated for 4 days at 25°C (protected from light) and at temperatures from 2 to 8°C after dilution with sodium chloride solution for injection 9 mg/mL (0.9%).
From a microbiological standpoint, the diluted medicinal product should be used immediately.
If not used immediately, the user is responsible for the storage duration and conditions prior to use. Storage should not exceed 24 hours at 2 to 8°C, unless dilution has taken place under controlled and validated aseptic conditions.

Chemical and physical stability has been demonstrated for 24 hours at 2 to 8°C after dilution with glucose solution for injection 50 mg/mL (5%).
From a microbiological standpoint, if the method of opening/dilution does not exclude the risk of microbiological contamination, the product should be used immediately. If not used immediately, the user is responsible for the storage duration and conditions.

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

6. Contents of the pack and other information

What Calcium folinate Kalceks contains

• The active substance is folinic acid in the form of calcium folinate monohydrate.

Each mL of solution contains calcium folinate monohydrate equivalent to 10 mg of
folinic acid.
Each 5 mL vial contains calcium folinate monohydrate equivalent to 50 mg of
folinic acid.
Each 10 mL vial contains calcium folinate monohydrate equivalent to 100 mg of folinic acid.
Each 20 mL vial contains calcium folinate monohydrate equivalent to 200 mg of
folinic acid.
Each 30 mL vial contains calcium folinate monohydrate equivalent to 300 mg of
folinic acid.
Each 50 mL vial contains calcium folinate monohydrate equivalent to 500 mg of
folinic acid.
Each 100 mL vial contains calcium folinate monohydrate equivalent to 1000 mg of
folinic acid.
Each 1 mg of folinic acid corresponds to 1.08 mg of calcium folinate.

• The other ingredients are: sodium chloride, sodium hydroxide (for pH adjustment) and water for injections.

What Calcium folinate Kalceks looks like and contents of the pack
A clear, colourless or slightly yellow solution, free from visible particles.
5 mL, 10 mL, 20 mL, 30 mL, 50 mL or 100 mL of solution in vials made of colourless glass,
closed with bromobutyl rubber stoppers and aluminium flip-off seals. The vials are packed in
cardboard boxes.
Pack sizes:
1, 5 or 10 vials of 5 mL
1 or 10 vials of 10 mL
1 or 10 vials of 20 mL
1 or 10 vials of 30 mL
1 or 10 vials of 50 mL
1 or 10 vials of 100 mL
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Importer
AS KALCEKS
Krustpils iela 71E
LV-1057 Rīga
Latvia
Tel.: +371 67083320
E-mail: [email protected]

This medicinal product is authorised in the European Economic Area countries under the following names:
Finland, Czech Republic, Denmark, Estonia, Norway, Poland, Sweden: Calcium folinate Kalceks
Austria, Germany: Folinsäure Kalceks 10 mg/ml Injektions-/Infusionslösung
Belgium: Folinic acid Kalceks 10 mg/ml solution injectable/pour perfusion
Folinic acid Kalceks 10 mg/ml oplossing voor injectie/infusie
Folinic acid Kalceks 10 mg/ml Injektions-/Infusionslösung
Bulgaria: Folinic acid Kalceks 10 mg/ml инжекционен/инфузионен разтвор
Croatia: Folinatna kiselina Kalceks 10 mg/ml otopina za injekciju/infuziju
France: FOLINATE DE CALCIUM KALCEKS 10 mg/mL, solution injectable/pour perfusion
Hungary: Calcium folinate Kalceks 10 mg/ml oldatos injekció vagy infúzió
Ireland: Folinic acid (as calcium folinate) 10 mg/ml solution for injection/infusion
Latvia: Calcium folinate Kalceks 10 mg/ml šķīdums injekcijām/infūzijām
Lithuania: Folinic acid Kalceks 10 mg/ml injekcinis ar infuzinis tirpalas
Netherlands: Folinezuur Kalceks 10 mg/ml oplossing voor injectie/infusie
Spain: Folinato cálcico Kalceks 10 mg/ml soluciόn inyectable y para perfusiόn EFG

Information intended exclusively for healthcare professionals:

Pharmaceutical incompatibilities
This medicinal product must not be mixed with other medicinal products, except as mentioned in the section "Instructions for use, disposal and other handling" below.
Incompatibilities have been reported between calcium folinate injection solution and droperidol, 5-fluorouracil, foscarnet and methotrexate for injection.

Droperidol

• Droperidol 1.25 mg / 0.5 mL with calcium folinate 5 mg / 0.5 mL: precipitation was observed immediately after direct mixing in a syringe for 5 minutes at 25°C, followed by centrifugation for 8 minutes.
• Droperidol 2.5 mg / 0.5 mL with calcium folinate 10 mg / 0.5 mL: immediate precipitation occurred when the drugs were injected sequentially into an infusion line (Y-connector) without flushing between injections.

Fluorouracil
Calcium folinate must not be mixed with 5-fluorouracil in the same infusion due to the risk of precipitate formation. Incompatibility has been demonstrated between 5-fluorouracil solutions at 50 mg/mL and calcium folinate at 20 mg/mL mixed with or without glucose injection solution 50 mg/mL (5%) in various proportions, stored in polyvinyl chloride containers at 4°C, 23°C or 32°C.

Foscarnet
Foscarnet 24 mg/mL mixed with calcium folinate 20 mg/mL forms a turbid yellow solution.

Instructions for use, disposal and other handling
For single use only.
Use immediately after opening the vial. Discard any remaining contents after use.
The solution should be inspected visually prior to use. Do not use if there are any visible signs of deterioration (e.g., particulate matter). Only clear, particle-free solutions should be administered.

Dilution for intravenous infusion administration
To administer a dose appropriate for the individual patient, aseptically withdraw the required volume of Calcium folinate Kalceks 10 mg/mL solution for injection/infusion from the vial and dilute it with one of the compatible diluents listed below.
For storage conditions and stability after dilution, see section 5.

For intravenous infusion, the medicinal product may be diluted with:

• Sodium chloride 9 mg/mL (0.9%) solution for injection
• Glucose 50 mg/mL (5%) solution for injection

Any unused portions or waste material should be disposed of in accordance with local regulations.