Prospect: information for the user

Folinic acid calcium Kalceks 10mg/ml injectable and perfusion solution EFG

Folic acid

Read this prospect thoroughly before starting to use this medication, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or nurse.
• If you experience adverse effects, consult your doctor or nurse, even if they are not listed in this prospect. See section4.

1.What is Folinic acid calcium Kalceks and for what it is used

2.What you need to know before Folinic acid calcium Kalceks is administered to you

3.How to use Folinic acid calcium Kalceks

4.Possible adverse effects

5.Storage of Folinic acid calcium Kalceks

6.Contents of the package and additional information

Calcium Folinate Kalceks 10mg/ml injectable solution and for perfusioncontains the active ingredient folic acid, in the form of calcium folinate hydrate (hereinafter, referred to as calcium folinate). Calcium folinate is the calcium salt of folic acid. This belongs to a group of medications called ‘detoxifiers’.

This medication is used for:

• reducing the harmful effects and treating overdoses of certain cancer medications, such as methotrexate and other folate antagonists in adults and children. This process is known as “calcium folinate rescue”;
• treating cancer in combination with fluorouracil (a cancer medication). Fluorouracil works better when administered with calcium folinate.

No useFolinic acid Kalceks

• if you are allergic to folic acid or any of the other components of this medication (listed in section6);
• if you have a type of anemia (insufficient red blood cells) caused by a lack of vitamin B12.

Consult your doctor or nurse if you are unsure if any of the above situations apply to you, before this medication is administered.

If you are pregnant or breastfeeding, do not receiveFolinic acid Kalcekswith some cancer medications (your doctor will know which ones).

This medication should not be injected into the spinal column (intrathecally).

Warnings and precautions

Consult your doctor or nurse before this medication is administered if:

• you have kidney problems (you may need a higher dose or longer treatment);
• you have epilepsy.

Use of folic acid with fluorouracil

Do not receive this medication with fluorouracil if you have noticed that your medication causes stomach and intestinal problems.

Before receiving folic acid with fluorouracil at the same time, consult your doctor or nurse if:

• you have received radiation therapy;
• you have stomach or intestinal disorders;
• you have inflammation in the mouth;
• you are elderly;
• you feel very weak.

Your doctor will monitor your liver and/or kidney function and perform periodic blood tests to check on it.

Other medications and Folinic acid Kalceks

Inform your doctor or nurse if you are using, have used recently, or may need to use any other medication.

This is especially important if you are using any of the following medications, as special care is required:

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

Pregnancy and lactation

If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant,consultyour doctor before this medication is administered.

Folic acid does not produce harmful effects if used as the only medication during pregnancy.

Do not receiveFolinic acid Kalcekswith fluorouracil during pregnancy or lactation, as it may harm the baby.

You will only be givenFolinic acidwith methotrexate during pregnancy or lactation if your doctor considers it necessary.

Driving and operating machines

There is no evidence that folic acid affects the ability to drive or operate machines.

Folinic acid Kalceks contains sodium

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

This medication may be administered as an injection or infusion (drip) into a vein or as a muscle injection. If administered by infusion, it must be diluted first.

Your doctor will decide on the correct dose of this medication for you and how often you should receive it. The decision will depend on the health issue 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 medication will be administered to you in a hospital under the supervision of a doctor. It is unlikely that you will receive too much or too little of the medication. However, if you have any questions, speak with your doctor or nurse.

If you have any other questions about the use of this medication, consult your doctor or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Consult your doctor or nurseimmediatelyif you experience:

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

Rare(may affect up to 1 in 100 people)

• fever

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

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

Only with combined 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)

• myelosuppression (even with a risk of death)
• inflammation of the intestinal lining and mouth (potentially fatal 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 may cause skin peeling (erythema multiforme or 'hand-foot' syndrome)

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

• high blood ammonia concentration

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

Since diarrhea can be a sign of stomach and intestinal toxicity, if you experience these symptoms, you will be closely monitored until the symptoms have completely disappeared. These symptoms may be the beginning of a rapid deterioration leading to death.

Your doctor may perform tests to check if there is a low calcium concentration in the blood.

Reporting of side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the vial and on the box after EXP. The expiration date is the last day of the month indicated.

Store in the refrigerator (between 2°C and 8°C).

Store the vial in the outer packaging to protect it from light.

Once the vial is opened:The product must be used immediately.

Period of validity after dilution

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

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

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

From a microbiological point of view, unless the opening/dilution method prevents the risk of microbial contamination, the medication must be used immediately. If not used immediately, storage times and conditions in use are the responsibility of the user.

Medicines should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Folinic acid Kalceks

• The active principle is folic acid, as calcium folinate.

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

Each vial with 5ml of solution containscalcium folinate, equivalent to50mg of folic acid.

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

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

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

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

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

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

• The other components are sodium chloride, sodium hydroxide (for pH adjustment), and water for injection.

Appearance of the product and contents of the package

Clear, colorless or yellowish solution, without visible particles.

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

Presentations:

1, 5 or 10vials of 5ml

1 or 10vials of 10ml

1 or 10vials of 20ml

1 or 10vials of 30ml

1 or 10vials of 50ml

1 or 10vials of 100ml

Only some sizes of packaging may be commercially available.

Marketing authorization holder and responsible manufacturer

AS KALCEKS

Krustpils iela 71E,

Riga, LV‑1057,

Latvia

Tel.: +37167083320

E‑mail:[email protected]

Further information on this medicinal product can be obtained from the local representative of the marketing authorization holder

EVER Pharma Therapeutics Spain SL

C/ Toledo 170

28005 Madrid

Spain

This medicinal product is authorized in the Member States of the European Economic Area with the following names:

Finland, Czech Republic, Denmark,Estonia,Norway, Poland, SwedenCalcium folinate Kalceks

Austria, GermanyFolinsäure Kalceks 10mg/ml Injektions-/Infusionslösung

BelgiumFolinic acid Kalceks 10mg/ml solution injectable/pour perfusion

Folinic acid Kalceks 10mg/ml oplossing voor injectie/infusie

Folinic acid Kalceks 10mg/ml Injektions-/Infusionslösung

BulgariaFolinic acid Kalceks 10mg/ml???????????/?????????????????

CroatiaFolinatna kiselina Kalceks 10mg/ml otopina za injekciju/infuziju

FranceFOLINATE DE CALCIUM KALCEKS 10mg/mL, solution injectable/pour perfusion

HungaryCalcium folinate Kalceks 10mg/ml oldatos injekció vagy infúzió

IrelandFolinic acid (as calcium folinate) 10mg/ml solution for injection/infusion

LatviaCalcium folinateKalceks 10mg/ml škidums injekcijam/infuzijam

LithuaniaFolinic acid Kalceks 10mg/ml injekcinis ar infuzinis tirpalas

NetherlandsFolinezuurKalceks 10mg/ml oplossing voor injectie/infusie

SpainFolinato cálcico Kalceks 10mg/ml solución inyectable y para perfusión EFG

Last revision date of this leaflet November 2023

The detailed information on this medicinal product is availableon the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

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This information is intended solely for healthcare professionals:

Incompatibilities

This medicinal product should not be mixed with others, except those mentioned in the "Instructions for use, disposal and other manipulations" section below.

Compatibility issues have been reported between injectable forms of calcium folinate and injectable forms of droperidol, 5‑fluorouracil, foscarnet and methotrexate.

Droperidol

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

Fluorouracil

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

Foscarnet

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

Instructions for use, disposal and other manipulations

For single use only.

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

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

Dilution for intravenous infusion

To administer the dose for a particular patient, aseptically extract the required amount of Folinic acid Kalceks 10mg/ml injectable solution from the vial and, subsequently, dilute it with any of the compatible solutions mentioned below.

For the storage conditions and shelf life after dilution, see section5.

To administer intravenously, it can be diluted with:

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

The disposal of unused medicinal product and all materials that have been in contact with it should be carried out in accordance with local regulations.