Calcium folinate Teva 10 mg/ml solution for injection EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Folinato cálcico Teva 10 mg/ml injection solution EFG

Calcium folinate

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Folinato cálcico Teva is and what it is used for
2. What you need to know before being administered Folinato cálcico Teva
3. How Folinato cálcico Teva is administered
4. Possible adverse effects
5. How to store Folinato cálcico Teva
6. Contents of the pack and other information

1. What Folinato cálcico Teva is and what it is used for

Folinato cálcico Teva is an antidote. Antidotes prevent damage caused by other substances.

Folinato cálcico Teva is administered by injection or infusion by your doctor.

Folinato cálcico Teva is used to help prevent adverse effects of treatment or overdose with the medicine methotrexate when used in high doses. Folinato cálcico Teva is given several hours after methotrexate, allowing methotrexate to exert its effect first.

Folinato cálcico Teva is also used in combination with the medicine 5-fluorouracil for the treatment of certain forms of colon cancer (metastatic colorectal carcinoma). This treatment should only be administered under the supervision of a physician experienced in the use of cancer chemotherapy.

Finally, Folinato cálcico Teva is also used to prevent or treat folate deficiency, only when it is impossible to administer folic acid tablets.

Uses

• to reduce the toxicity and effects of certain medicines (such as methotrexate) in children and adults.
• in combination with the medicine 5-fluorouracil, for the treatment of certain forms of cancer.

2. What you need to know before Folinato cálcico Teva is administered to you

Do not use Folinato cálcico Teva

• if you are allergic to folinic acid calcium salt or to any of the other ingredients of this medicine (listed in section 6). An allergic reaction may include rash, itching, difficulty breathing, or swelling of the face, lips, throat, or tongue.
• if you have anemia due to vitamin B12 deficiency (e.g. pernicious anemia).

Folinato cálcico Teva must not be administered together with certain anticancer medicines if you are pregnant or breastfeeding (your doctor will know which ones).

Warnings and precautions

Folinato cálcico Teva must only be administered by intramuscular or intravenous injection and must not be administered by intrathecal route.

Consult your doctor or pharmacist before Folinato cálcico Teva is administered to you

• if you develop diarrhoea or mucositis during treatment with Folinato cálcico Teva in combination with 5-fluorouracil (see also “Possible side effects”). Your doctor may decide to reduce the dose of 5-fluorouracil or discontinue treatment. Elderly and debilitated patients are more susceptible to these adverse effects.
• if you are simultaneously being treated with methotrexate; Folinato cálcico Teva must not be administered together with methotrexate, because Folinato cálcico Teva is capable of completely counteracting the effects of methotrexate. Therefore, Folinato cálcico Teva must always be administered several hours after methotrexate treatment (see also section 3. “How to use Folinato cálcico Teva”).
• if you have previously received radiotherapy and are receiving Folinato cálcico Teva in combination with 5-fluorouracil; your doctor will reduce the dose of 5-fluorouracil.
• if you receive Folinato cálcico Teva in combination with 5-fluorouracil and your doctor observes that the calcium level in your blood has decreased; your doctor will prescribe additional calcium.
• if you are taking certain antiepileptic medicines; epileptic seizures may occur more frequently (see also the paragraph “Use of Folinato cálcico Teva with other medicines” and section “Possible side effects”).
• if you are taking/receiving certain medicines for the treatment of cancer, such as hydroxycarbamide, cytarabine, mercaptopurine, and thioguanine. These medicines may cause a blood disorder (macrocytosis) which must not be treated with Folinato cálcico Teva.
• if your kidneys do not function properly and you are administered Folinato cálcico Teva in combination with methotrexate; your doctor may decide to increase the dose of Folinato cálcico Teva or prescribe a longer duration of treatment.

Please consult your doctor if any of these situations apply to you or have applied to you in the past.

Use of Folinato cálcico Teva with other medicines

Inform your doctor or pharmacist if you are taking/using, have recently taken/used, or might need to take/use any other medicine.

Please note that the names of the medicines mentioned in this section may be known to you by a different name, e.g. the brand name. This section only mentions the name of the active substance and not the brand name. Therefore, check the packaging and the leaflet to find out which active substance is contained in the medicine you are taking or have taken recently.

Sometimes products (medicines) administered/taken concomitantly can influence the effect of each other and/or the adverse effect. This is called an interaction. An interaction may occur during concomitant use of the injectable solution and:

• 5-fluorouracil (a medicine for certain forms of cancer). The effect and adverse effects of 5-fluorouracil are increased. Folinato cálcico Teva and 5-fluorouracil are often administered together intentionally. However, unwanted adverse effects are also increased.
• folic acid antagonists such as cotrimoxazole (an antibiotic), pyrimethamine (a treatment for malaria), or methotrexate. The effect of the folic acid antagonist may be reduced or completely neutralized. Folinato cálcico Teva and methotrexate are frequently administered together intentionally.
• phenobarbital, primidone, phenytoin, and succinimides (medicines for epilepsy). The effect of these medicines may be reduced, which may lead to epileptic seizures.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

The effects of Folinato cálcico Teva on the foetus are unknown. Folinato cálcico Teva may only be administered during pregnancy when clearly necessary. This will be decided by your doctor.

This advice also applies when Folinato cálcico Teva is administered in combination with methotrexate.

Administration of Folinato cálcico Teva in combination with 5-fluorouracil during pregnancy is not permitted due to the harmful effects of 5-fluorouracil.

It is not known whether Folinato cálcico Teva is excreted in breast milk. Folinato cálcico Teva should only be administered to breastfeeding mothers when clearly necessary. This will be decided by your doctor. In combination with 5-fluorouracil, administration of Folinato cálcico Teva during breastfeeding is not recommended due to the harmful effects of 5-fluorouracil.

Driving and using machines

There is no evidence that Folinato cálcico Teva has an effect on the ability to drive or use machines.

Folinato cálcico Teva contains sodium

5 ml vials:

This medicine contains less than 1 mmol of sodium (23 mg) per vial; i.e., essentially “sodium-free”.

10 ml vials:

This medicine contains 32.2 mg of sodium (main component of table/cooking salt) in each vial. This corresponds to 1.6% of the maximum daily sodium intake recommended for an adult.

20 ml vials:

This medicine contains 64.4 mg of sodium (main component of table/cooking salt) in each vial. This corresponds to 3.2% of the maximum daily sodium intake recommended for an adult.

30 ml vials:

This medicine contains 96.6 mg of sodium (main component of table/cooking salt) in each vial. This corresponds to 4.8% of the maximum daily sodium intake recommended for an adult.

50 ml vials:

This medicine contains 161 mg of sodium (main component of table/cooking salt) in each vial. This corresponds to 8.1% of the maximum daily sodium intake recommended for an adult.

3. How Folinato cálcico Teva is administered

Folinato cálcico Teva will only be administered by a physician or nurse under the supervision of a physician experienced in the use of chemotherapy. Folinato cálcico Teva can be given by intravenous injection or infusion, or as an intramuscular injection.

The dosage may vary from patient to patient, as the dose is calculated based on your body surface area (which is determined by your height and weight). Your doctor will decide which dose is best for you.

The recommended doses are:

After moderate to high-dose methotrexate therapy:

Adults, elderly patients, and children:

As a rule, the first dose of Folinato cálcico Teva is 15 mg (6–12 mg per square meter of your body surface area) to be administered 12–24 hours (maximum 24 hours) after the start of methotrexate infusion. This same dose is repeated every 6 hours for a period of 72 hours. After a few injections or infusions, it may be possible to switch to oral tablets.

In combination with 5-fluorouracil for the treatment of certain forms of colorectal cancer (metastatic colorectal carcinoma):

Adults and elderly patients:

• Biweekly regimen: On two consecutive days, every two weeks: 200 mg of Folinato cálcico Teva per square meter of body surface area administered by infusion over two hours, followed by 400 mg of 5-fluorouracil per square meter of body surface area as an intravenous injection, and 600 mg of 5-fluorouracil per square meter of body surface area by infusion over 22 hours.
• Weekly regimen: 20 mg of Folinato cálcico Teva per square meter of body surface area as a single injection, or 200 to 500 mg of Folinato cálcico Teva per square meter of body surface area by infusion over two hours, followed by 500 mg of 5-fluorouracil per square meter of body surface area administered as an intravenous injection during or at the end of the Folinato cálcico Teva infusion.
• Monthly regimen: Once a month for five consecutive days: 20 mg of Folinato cálcico Teva per square meter of body surface area as a single injection, or 200 to 500 mg of Folinato cálcico Teva per square meter of body surface area by infusion over two hours, immediately followed by 425 or 370 mg of 5-fluorouracil per square meter of body surface area as a single injection.

To counteract the harmful effects of trimetrexate, trimethoprim, and pyrimethamine:

• Harmful effects of trimetrexate (a drug used to treat certain forms of pneumonia, especially in patients with AIDS):

  To prevent trimetrexate-induced toxicity, you will receive Folinato cálcico Teva daily during trimetrexate treatment and for up to 72 hours after the last dose of trimetrexate. Your doctor will administer Folinato cálcico Teva by infusion over 5–10 minutes at a dose of 20 mg per square meter of body surface area. This will be repeated every 6 hours, resulting in a total daily dose of 80 mg per square meter of body surface area. Tablets are an alternative to infusion. You will receive a dose of 20 mg per square meter of body surface area four times a day, divided evenly throughout the day. Your doctor may decide to administer an additional dose.

  In case of trimetrexate overdose, your doctor will administer Folinato cálcico Teva after discontinuing trimetrexate. Folinato cálcico Teva will be given intravenously every 6 hours for 3 days at a dose of 40 mg per square meter of body surface area.

• Harmful effects of trimethoprim (an antibiotic used to treat certain infections):

  After discontinuation of trimethoprim treatment, you will receive 3–10 mg of Folinato cálcico Teva per day. Your doctor will determine the duration of this treatment.

• Harmful effects of pyrimethamine (a drug used to treat malaria and a parasitic disease called toxoplasmosis):

  If you receive a high dose of pyrimethamine or take pyrimethamine over a prolonged period, you will receive 5–50 mg of Folinato cálcico Teva per day simultaneously.

If you use more Folinato cálcico Teva than you should

If you are given more Folinato cálcico Teva than recommended, your doctor will treat you appropriately. If you suspect a serious overdose, consult your doctor or pharmacist immediately. With a high dose, side effects described in section “Possible side effects” may occur. If Folinato cálcico Teva is administered in combination with methotrexate, excessive Folinato cálcico Teva may reduce the effect of methotrexate.

If you forget to use Folinato cálcico Teva

When a dose is missed and Folinato cálcico Teva is being used in combination with methotrexate, methotrexate toxic effects may occur (see methotrexate package leaflet). Consult your doctor if you have any doubts.

If you stop Folinato cálcico Teva

When Folinato cálcico Teva is administered in combination with methotrexate and treatment is abruptly discontinued, adverse effects of methotrexate that were previously counteracted by Folinato cálcico Teva may reappear. Therefore, abrupt discontinuation of Folinato cálcico Teva is not recommended.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Contact your doctor immediately if you notice any of the following symptoms:

• sudden ringing in the ears, difficulty breathing, swelling of the eyelids, face or lips, rash or itching (especially affecting the whole body)
• diarrhoea
• mucositis

The reactions listed above may be serious adverse effects. Your doctor may decide to discontinue treatment.

The following adverse effects have been reported:

Uncommon: may affect up to 1 in 100 people
Fever

Rare: may affect up to 1 in 1,000 people
Insomnia, restlessness, depression and gastrointestinal disorders after administration of high doses. When used in combination with certain antiepileptic medicines, the frequency of seizures may rarely increase (see also sections “Warnings and precautions” and “Use of Folinato cálcico Teva with other medicines” in section 2).

Very rare: may affect up to 1 in 10,000 people
Severe allergic reactions, including sudden feeling of illness, sense of fear, chills, itching, pallor or redness, sweating, shortness of breath, rapid heartbeat and shock (anaphylactic or anaphylactoid reaction), skin rash with intense itching (urticaria), and swelling of hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty swallowing or breathing).

When administered in combination with the medicine 5-fluorouracil, the following adverse effects may occur:

Very common: may affect more than 1 in 10 people

• Diarrhoea (possibly severe and leading to dehydration), vomiting and nausea
• Inflammation of the mucosa of the intestine and mouth (potentially life-threatening conditions have occurred)
• Reduction in the number of blood cells (including life-threatening conditions)

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 lead to peeling of the skin (hand-foot syndrome)

Frequency not known: cannot be estimated from available data

• Elevated blood ammonia levels

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Calcium Folinate Teva

Keep out of sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging after "EXP". The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2°C–8°C) in the original packaging.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of unused medicines and their containers. This will help protect the environment.

6. Contents of the pack and other information

Pharmaceutical form and contents

Folinato cálcico Teva is an injection solution and contains calcium folinate equivalent to 10 mg of folinic acid per ml, corresponding to 50 mg of folinic acid in the 5 ml vial, 100 mg in the 10 ml vial, 200 mg in the 20 ml vial, 300 mg in the 30 ml vial, and 500 mg in the 50 ml vial.

Composition of Folinato cálcico Teva

• The active substance is calcium folinate, equivalent to 50 mg (5 ml), 100 mg (10 ml), 200 mg (20 ml), 300 mg (30 ml), and 500 mg (50 ml) of folinic acid, respectively.

Each ml of injectable solution contains 10.8 mg of calcium folinate, equivalent to 10.0 mg of folinic acid.

• The other components are sodium chloride, sodium hydroxide, hydrochloric acid, water for injection.

Appearance of the product and contents of the container

Injectable solution.

Folinato cálcico Teva is a yellow, transparent, particle-free solution.

Folinato cálcico Teva is packaged in colorless Type I glass vials with chlorobutyl rubber stoppers and aluminum crimp caps.

The vials contain 5 ml, 10 ml, 20 ml, or 30 ml of solution for injection.

Pack size: 1 vial per carton.

Marketing Authorization Holder

TEVA PHARMA S.L.U.
C/ Anabel Segura, 11. Edificio Albatros B, 1st floor
28108 Alcobendas, Madrid
Spain

Manufacturer

PHARMACHEMIE B.V.
Swensweg 5
P.O. Box 552
2031 GA Haarlem
The Netherlands

This medicinal product is authorized in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Netherlands: Rescuvolin 10 mg/ml, solution for injection
Spain: Folinato Cálcico Teva 10 mg/ml Solucion Inyectable
United Kingdom (Northern Ireland): Calcium Folinate 10 mg/ml solution for injection

Date of the most recent review of this leaflet: July 2022

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/