Calcium folinate Kalceks

Package Leaflet: Information for the User

Calcium Folinate Kalceks, 10 mg/mL, Solution for Injection/Infusion

Folinic Acid

Read All of This Leaflet Carefully Before Using This Medicine.

• 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. See Section 4.

Contents of the Pack

• 1. What is Calcium Folinate Kalceks and What is It Used For
• 2. Before You Use 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 is Calcium Folinate Kalceks and What is It Used For

Calcium Folinate Kalceks, 10 mg/mL, Solution for Injection/Infusion contains the active substance calcium folinate, which is the calcium salt of folinic acid (also known as leucovorin). Folinic acid is an antidote used to treat or prevent low blood cell counts caused by certain chemotherapy drugs, such as methotrexate. This medicine is used to:

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

2. Before You Use Calcium Folinate Kalceks

Do Not Use Calcium Folinate Kalceks:

• if you are allergic to folinic acid or any of the other ingredients of this medicine (listed in section 6);
• if you have a certain type of anemia (low red blood cell count) caused by a lack of vitamin B12. If you are unsure whether any of the above conditions apply to you, consult your doctor or nurse before using this medicine.

Calcium Folinate Kalceks should not be used with certain chemotherapy drugs (known to your doctor) in pregnant or breastfeeding women. This medicine must not be administered directly into the spine (intrathecally).

Warnings and Precautions

Before Using Calcium Folinate Kalceks, Tell Your Doctor or Nurse If:

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

Using Folinic Acid with Fluorouracil Do not use this medicine with fluorouracil if it causes stomach or intestinal problems. If you need to use folinic acid and fluorouracil together, talk to your doctor or nurse before using this medicine if:

• you have had radiation therapy;
• you have stomach or intestinal problems;
• you have mouth sores;
• you are elderly;
• you feel very weak.

Your Doctor Will Monitor Your Liver and Kidney Function and Perform Regular Blood Tests to Check This.

Calcium Folinate Kalceks and Other Medicines

Tell Your Doctor or Nurse About All Medicines You Are Taking or Have Recently Taken, as Well as Any Medicines You Plan to Take. This is Especially Important for the Following Medicines:

• medicines known as folate antagonists, such as trimethoprim/sulfamethoxazole (an antibiotic) or pyrimethamine (used to treat malaria). Folinic acid may reduce or completely counteract the effects of these medicines;
• fluorouracil(a chemotherapy drug). Folinic acid increases the effectiveness and side effects of fluorouracil;
• medicines used to treat epilepsy(phenobarbital, phenytoin, primidone, or succinimides, such as ethosuximide). Folinic acid may reduce the effects of these medicines. Your doctor may check the levels of these medicines in your blood and adjust the dose to prevent increased seizures.

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 Using This Medicine. Calcium Folinate Kalceks does not cause harmful effects when used alone during pregnancy. However, do not use Calcium Folinate Kalceks with fluorouracil during pregnancy or breastfeeding, as it may harm the baby. Calcium Folinate Kalceks will only be used with methotrexate during pregnancy or breastfeeding if your doctor considers it necessary.

Driving and Using Machines

There is No Evidence That Folinic Acid 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 Common Salt) per mL of Solution. This is Equivalent to 0.16% of the Maximum Recommended Daily Intake of Sodium for Adults.

3. How to Use Calcium Folinate Kalceks

This Medicine Can Be Given by Injection or Infusion (Drip) into a Vein, or by Intramuscular Injection. If the Medicine is to Be Given by Infusion, It Must Be Diluted First. Your Doctor Will Decide the Dose and Frequency of Administration Based on Your Medical Condition, Body Surface Area, and Other Treatments You Are Receiving.

Overdose of Calcium Folinate Kalceks

This Medicine Will Be Administered in a Hospital Under the Supervision of a Doctor. It is Unlikely That You Will Receive Too Much or Too Little of This Medicine. However, If You Have Any Concerns, Talk to Your Doctor or Nurse. If You Have Any Further Questions About Using This Medicine, Ask Your Doctor or Nurse.

4. Possible Side Effects

Like All Medicines, Calcium Folinate Kalceks Can Cause Side Effects, Although Not Everybody Gets Them. Seek Medical Attention Immediatelyif You Experience:

• sudden itchy rash (hives), swelling of hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing) and feeling of fainting. These may be symptoms of a very rare but serious allergic reaction (affecting up to 1 in 10,000 people). You may need urgent medical attention;
• red, flat, target-like, or circular patches on the trunk, often with blisters in the center, peeling of the skin, mouth sores, throat, nose, genitals, and eyes. These serious skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis) (frequency cannot be estimated from the available data).

Uncommon(affecting less than 1 in 100 people)

• fever.

Rare(affecting less than 1 in 1,000 people)

• insomnia;
• excitement and depression (after high doses);
• increased frequency of seizures (fits) in patients with epilepsy;
• gastrointestinal disorders (after high doses).

Combination Therapy with Fluorouracil Only

Using Folinic Acid with Fluorouracil Increases the Risk of the Following Side Effects:

Very Common(affecting more than 1 in 10 people)

• bone marrow suppression (including life-threatening cases);
• mouth and intestinal ulcers (including life-threatening cases);
• nausea, vomiting, and diarrhea (with monthly dosing);
• severe diarrhea and dehydration (with weekly dosing).

Common(affecting less than 1 in 10 people)

• redness and swelling of the palms of the hands or soles of the feet, which may cause skin peeling (hand-foot syndrome).

Frequency Not Known(cannot be estimated from the available data)

• increased blood ammonia levels.

Tell Your Doctor if You Experience Diarrhea or Mouth Ulcers, as Your Doctor May Want to Reduce the Dose of Fluorouracil Until the Symptoms Have Completely Resolved. Since Diarrhea Can Be a Sign of Toxicity to the Stomach and Intestines, If You Experience These Symptoms, You Will Be Closely Monitored Until the Symptoms Have Completely Resolved. These Symptoms Can Be the Beginning of a Rapid Decline in Your Condition, Leading to Death. Your Doctor May Perform Tests to Check for Low Calcium Levels in Your Blood.

Reporting Side Effects

If You Experience Any Side Effects, Including Those Not Listed in This Leaflet, Tell Your Doctor or Nurse. You Can Also Report Side Effects Directly to the National Medicines Agency. By Reporting Side Effects, You Can Help Provide More Information on the Safety of This Medicine.

5. How to Store Calcium Folinate Kalceks

Keep This Medicine Out of the Sight and Reach of Children. Do Not Use This Medicine After the Expiry Date Stated on the Label and Carton After "EXP". The Expiry Date Refers to the Last Day of the Month. EXP - Expiry Date. Lot - Batch Number. Store in a Refrigerator (2°C-8°C). Keep the Vial in the Outer Carton to Protect It from Light. After Opening the Vial: Use Immediately. Shelf-Life After Dilution The Chemical and Physical Stability Has Been Demonstrated for 4 Days at 25°C (Protected from Light) and for 4 Days at 2-8°C After Dilution with Sodium Chloride 9 mg/mL (0.9%) Solution for Injection. From a Microbiological Point of View, the Diluted Product Should Be Used Immediately. If Not Used Immediately, the Storage Times and Conditions Are the Responsibility of the User. The Storage Time Should Not Exceed 24 Hours at 2-8°C, Unless Dilution Has Taken Place in Controlled and Validated Aseptic Conditions. The Chemical and Physical Stability Has Been Demonstrated for 24 Hours at 2-8°C After Dilution with Glucose 50 mg/mL (5%) Solution for Injection. From a Microbiological Point of View, If the Method of Opening/Reconstitution Does Not Preclude the Risk of Microbial Contamination, the Product Should Be Used Immediately. If Not Used Immediately, the 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. This 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.

Each mL of Solution Contains Calcium Folinate Equivalent to 10 mg of Folinic Acid. Each 5 mL Vial Contains Calcium Folinate Equivalent to 50 mg of Folinic Acid. Each 10 mL Vial Contains Calcium Folinate Equivalent to 100 mg of Folinic Acid. Each 20 mL Vial Contains Calcium Folinate Equivalent to 200 mg of Folinic Acid. Each 30 mL Vial Contains Calcium Folinate Equivalent to 300 mg of Folinic Acid. Each 50 mL Vial Contains Calcium Folinate Equivalent to 500 mg of Folinic Acid. Each 100 mL Vial Contains Calcium Folinate Equivalent to 1000 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), and Water for Injections.

What Calcium Folinate Kalceks Looks Like and Contents of the Pack

A Clear, Colorless or Yellowish Solution, Free from Visible Particles. 5 mL, 10 mL, 20 mL, 30 mL, 50 mL, or 100 mL Solution in Vials Made of Colorless Glass, Closed with Bromobutyl Rubber Stoppers, and Aluminum Flip-Off Seals. The Vials Are Packaged 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 Authorization Holder and Manufacturer

AS KALCEKS Krustpils iela 71E LV-1057 Rīga Latvia Tel.: +371 67083320 E-mail: kalceks@kalceks.lv

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 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

Date of Last Revision of the Leaflet:

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Information Intended for Healthcare Professionals Only:

Incompatibilities

This Medicinal Product Must Not Be Mixed with Other Medicinal Products, Except for Those Mentioned in the "Instructions for Use, Handling, and Disposal" Section Below. Incompatibilities Have Been Reported Between Calcium Folinate and Droperidol, Fluorouracil, Foskarnet, 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 Was Observed When the Medicines Were Injected Sequentially into a Y-Connector Without Flushing the System Between Injections.

FluorouracilCalcium Folinate Must Not Be Mixed with Fluorouracil in the Same Infusion, Due to the Risk of Precipitation. Incompatibility Has Been Demonstrated Between Fluorouracil 50 mg/mL and Calcium Folinate 20 mg/mL with or Without Glucose 50 mg/mL (5%) Solution for Injection, Mixed in Various Proportions and Stored in Polyvinyl Chloride Containers at 4°C, 23°C, or 32°C.

FoskarnetFoskarnet 24 mg/mL Mixed with Calcium Folinate 20 mg/mL Produces a Turbid Yellow Solution.

Instructions for Use, Handling, and Disposal

For Single Use Only. Use Immediately After Opening the Vial. Discard Any Remaining Contents After Use. Inspect the Solution Before Use. Do Not Use If You Notice Any Visible Signs of Deterioration (e.g., Particulate Matter). Only Use Clear Solutions Free from Particulate Matter. Dilution for Intravenous Infusion To Administer the Desired Dose, Withdraw the Required Amount of Calcium Folinate Kalceks from the Vial, Using Aseptic Technique, and Dilute It with One of the Compatible Solutions Listed Below. Storage Conditions and Shelf-Life After Dilution, See Section 5. For Intravenous Infusion, the Medicinal Product Can Be Diluted With:

• Sodium Chloride 9 mg/mL (0.9%) Solution for Injection;
• Glucose 50 mg/mL (5%) Solution for Injection.

Any Unused Product or Waste Material Should Be Disposed of in Accordance with Local Requirements.