FOLINIC ACID CALCIUM KALCEKS 10 MG/ML INJECTABLE SOLUTION AND PERFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Calcium Folinate Kalceks 10mg/ml Solution for Injection and Infusion EFG

folinic acid

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 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.

Contents of the pack

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

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

Calcium Folinate Kalceks 10 mg/ml Solution for Injection and Infusion contains the active substance folinic acid, as calcium folinate hydrate (hereinafter referred to as calcium folinate). Calcium folinate is the calcium salt of folinic acid. This belongs to a group of medicines called 'antidotes'.

This medicine is used to:

• reduce the harmful effects and treat overdose of certain cancer medicines, such as methotrexate and other folinic acid antagonists in adults and children. This process is known as "calcium folinate rescue";
• treat cancer in combination with fluorouracil (a cancer medicine). Fluorouracil works better when given with calcium folinate.

2. What you need to know before you are given Calcium Folinate Kalceks

Do not useCalcium Folinate Kalceks

• if you are allergic to calcium folinate or any of the other ingredients of this medicine (listed in section 6);
• if you have a type of anemia (low red blood cell count) caused by a lack of vitamin B12.

If you are not sure if any of the above applies to you, consult your doctor or nurse before you are given this medicine.

If you are pregnant or breastfeeding, you should not receive Calcium Folinate Kalceks with certain cancer medicines (your doctor will know which ones).

This medicine must not be injected into the spine (by intrathecal route).

Warnings and precautions

Tell your doctor or nurse before you are given this medicine if:

• you have kidney problems (you may need to take a higher dose or need this medicine for a longer period);
• you have epilepsy.

Use of calcium folinate with fluorouracil

You must not receive this medicine with fluorouracil if you have noticed that your medicine causes stomach and intestine problems.

If you are to receive calcium folinate with fluorouracil at the same time, consult your doctor or nurse before you are given this medicine if:

• you have received radiotherapy;
• you have stomach or intestine problems;
• you have inflammation inside your mouth;
• you are elderly;
• you feel very weak.

Your doctor will monitor your liver and/or kidney function and will do regular blood tests to check this.

Other medicines and Calcium Folinate Kalceks

Tell your doctor or nurse if you are using, have recently used or might use any other medicines.

This is especially important if you are using any of the following medicines, as special care may be needed:

• medicines known as folinic acid antagonists, such as cotrimoxazole (an antibiotic) or pyrimethamine (used to treat malaria). Calcium folinate may reduce or completely counteract the effect of these medicines;
• fluorouracil(a cancer medicine). Calcium folinate increases the effectiveness and also the side effects of fluorouracil;
• medicines for treating epilepsy(phenobarbital, phenytoin, primidone or succinimides, for example, ethosuximide). Calcium folinate may decrease the effect of these medicines. Your doctor may check the levels of these medicines in your blood and change your dose to avoid an increase in seizures (epileptic fits).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before you are given this medicine.

Calcium folinate is not harmful if used alone during pregnancy.

You must not receive Calcium Folinate Kalceks with fluorouracil during pregnancy or breastfeeding, as it may harm your baby.

Calcium folinate will only be given with methotrexate during pregnancy or breastfeeding if your doctor thinks it is necessary.

Driving and using machines

There is no evidence that calcium folinate affects your ability to drive or use machines.

Calcium Folinate Kalceks contains sodium

This medicine contains 3.15 mg of sodium (a major component of cooking/table salt) in each ml of solution. This is equivalent to 0.16% of the maximum recommended daily intake of sodium for an adult.

3. How to use Calcium Folinate Kalceks

This medicine can be given as an injection or infusion (drip) into a vein or as an injection into a muscle. If given by infusion, it must first be diluted.

Your doctor will decide the correct dose of this medicine for you and how often you should receive it. The decision will depend on the health problem being treated, your body surface area and any other treatment you may be receiving.

If you receive more Calcium Folinate Kalceks than you should

This medicine will be given to you in a hospital under the supervision of a doctor. It is unlikely that you will be given too much or too little of this medicine. However, tell your doctor or nurse if you have any questions.

If you have any further questions on the use of this product, ask your doctor 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 immediatelyif you experience:

• a sudden rash with itching (urticaria), swelling of hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), and feeling like you are going to faint. These can be signs of a very rare and serious allergic reaction (may affect up to 1 in 10,000 people). You may need urgent medical attention
• red patches on the body, target-like or circular patches on the trunk, often with blisters in the center, peeling of the skin, ulcers in the mouth, throat, nose, genitals and eyes. These severe skin reactions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis) (frequency cannot be estimated from the available data)

Uncommon(may affect up to 1 in 100 people)

• fever

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

• insomnia
• agitation and depression (after high doses)
• increased seizures (fits) in patients with epilepsy
• gastrointestinal disorders (after high doses)

Only with combination treatment with fluorouracil

If you receive calcium folinate in combination with fluorouracil, you are more likely to experience the following side effects:

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

• bone marrow failure (even life-threatening)
• inflammation of the lining of the intestine and mouth (potentially life-threatening diseases have occurred)
• nausea, vomiting and diarrhea (with monthly doses)
• severe diarrhea and dehydration (with weekly doses)

Common(may affect up to 1 in 10 people)

• redness and swelling of the palms of the hands or soles of the feet, which can cause skin peeling (palmar-plantar erythrodysesthesia or 'hand-foot syndrome')

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

• high levels of ammonia in the blood

Tell your doctor if you experience diarrhea or mouth ulcers, as your doctor may consider reducing the dose of fluorouracil until the symptoms have completely disappeared.

As diarrhea can be a sign of stomach and intestine toxicity, if you have these symptoms, you will be closely monitored until the symptoms have completely disappeared. These symptoms can be the start of a rapid deterioration leading to death.

Your doctor may do tests to check if you have low calcium levels in your blood.

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Calcium Folinate Kalceks

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 vial and carton after EXP. The expiry date refers to the last day of the month shown.

Store in a refrigerator (2°C - 8°C).

Store the vial in the outer carton in order to protect from light.

Once the vial is opened: the product should be used immediately.

Shelf-life after dilution

The chemical and physical in-use stability has been demonstrated for 4 days at 25°C (protected from light) and for 2 to 8°C after dilution with sodium chloride 0.9% injection solution (9 mg/ml).

From a microbiological point of view, the diluted solution should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless dilution has been made in controlled and validated aseptic conditions.

The chemical and physical in-use stability has been demonstrated for 24 hours at 2 to 8°C after dilution with glucose 5% injection solution (50 mg/ml).

From a microbiological point of view, unless the method of opening/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 the user.

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

6. Contents of the pack and other information

Composition of Calcium Folinate Kalceks

• The active substance is folinic acid, as calcium folinate hydrate.

Each ml of solution contains calcium folinate hydrate, equivalent to 10 mg of folinic acid.

Each vial with 5 ml of solution contains calcium folinate hydrate, equivalent to 50 mg of folinic acid.

Each vial with 10 ml of solution contains calcium folinate hydrate, equivalent to 100 mg of folinic acid.

Each vial with 20 ml of solution contains calcium folinate hydrate, equivalent to 200 mg of folinic acid.

Each vial with 30 ml of solution contains calcium folinate hydrate, equivalent to 300 mg of folinic acid.

Each vial with 50 ml of solution contains calcium folinate hydrate, equivalent to 500 mg of folinic acid.

Each vial with 100 ml of solution contains calcium folinate hydrate, equivalent to 1,000 mg of folinic acid.

Each 1 mg of folinic acid is equivalent to 1.08 mg of calcium folinate.

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

Appearance and packaging

Clear, colorless or yellowish solution, without visible particles.

5 ml, 10 ml, 20 ml, 30 ml, 50 ml or 100 ml of solution in transparent glass vials, closed with bromobutyl rubber stoppers and sealed with flip-off aluminum caps. The vials are packaged in cardboard boxes.

Presentation:

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 authorization holder and manufacturer

AS KALCEKS

Krustpils iela 71E,

Riga, LV-1057,

Latvia

Tel.: +371 67083320

E-mail: [email protected]

You can obtain further information on this medicine from the local representative of the marketing authorization holder

EVER Pharma Therapeutics Spain SL

C/ Toledo 170

28005 Madrid

Spain

This medicine is authorized in the Member States of the European Economic Area 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 ???????????/?????????? ???????

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 škidums injekcijam/infuzijam

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 solución inyectable y para perfusión EFG

Date of last revision of this leaflet November 2023

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

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This information is intended only for healthcare professionals:

Incompatibilities

This medicine must not be mixed with other medicines except for those mentioned in the "Instructions for use, disposal and other handling" section below.

Incompatibilities have been reported between injectable forms of calcium folinate and injectable forms of droperidol, fluorouracil, foscarnet and methotrexate.

Droperidol

• Droperidol 1.25 mg/0.5 ml with calcium folinate 5 mg/0.5 ml, immediate precipitation after direct mixing in a syringe for 5 minutes at 25°C followed by 8 minutes of centrifugation.
• Droperidol 2.5 mg/0.5 ml with calcium folinate 10 mg/0.5 ml, immediate precipitation when the medicines are injected sequentially into a Y-shaped equipment without flushing the Y-shaped equipment between injections.

Fluorouracil

Calcium folinate must not be mixed in the same infusion as fluorouracil because a precipitate may form. 50 mg/ml of fluorouracil with 20 mg/ml of calcium folinate, with or without glucose 5% injection solution (50 mg/ml), have been shown to be incompatible when mixed in different amounts and stored at 4°C, 23°C or 32°C in polyvinyl chloride containers.

Foscarnet

A yellowish turbid solution has been observed when mixing 24 mg/ml of foscarnet with 20 mg/ml of calcium folinate.

Instructions for use, disposal and other handling

For single use only.

The solution should be used immediately after opening the vial. Discard any remaining contents after use.

The solution must be inspected visually before use. Do not use if it shows signs of deterioration (e.g. particles). It should only be used if the solution is clear and particle-free.

Dilution for intravenous infusion

To administer the dose to a specific patient, aseptically withdraw the appropriate amount of Calcium Folinate Kalceks 10 mg/ml Solution for Injection and Infusion from the vial and then dilute with one of the compatible solutions listed below.

For storage conditions and shelf-life after dilution, see section 5.

For intravenous infusion, it can be diluted with:

• sodium chloride 0.9% injection solution (9 mg/ml);
• glucose 5% injection solution (50 mg/ml).

Disposal of unused medicine and all materials that have come into contact with it should be done in accordance with local regulations.