Leaflet: information for the user

Folinic Acid Teva 10 mg/ml injectable solution EFG

Folinic Acid

Read 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, consult your doctor or pharmacist.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What Folinic Acid Teva is and what it is used for

2. What you need to know before you are given Folinic Acid Teva

3. How to administer Folinic Acid Teva

4. Possible side effects

5. Storage of Folinic Acid Teva

6. Contents of the pack and additional information

Calcium Folinate Teva is an antidote. Antidotes prevent damage caused by other substances.

Calcium Folinate Teva is administered by injection or infusion by your doctor.

Calcium Folinate Teva is used to help prevent adverse effects of treatment or overdose with the medication methotrexate when used in high doses. Calcium Folinate Teva is administered a few hours after methotrexate, to allow methotrexate to take effect first.

Calcium Folinate Teva is also used in combination with the medication 5-fluorouracil for the treatment of certain forms of colon cancer (metastatic colorectal carcinoma). This treatment should only be applied when supervised by a doctor experienced in the use of chemotherapy for cancer.

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

Use

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

Do not use Folinato cálcico Teva

- if you are allergic to folic acid or 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 anaemia due to a lack of vitamin B12 (for example, pernicious anaemia).

Do not be given Folinato cálcico Teva with certain cancer medicines if you are pregnant or breastfeeding (your doctor will know which ones).

Warnings and precautions

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

Consult your doctor or pharmacist before you are given Folinato cálcico Teva

• if diarrhoea or mucositis occurs during the use of Folinato cálcico Teva in combination with the medicine 5-fluorouracil (see also “Possible side effects”). Your doctor may decide to reduce the dose of 5-fluorouracil or stop treatment. Elderly and debilitated patients are more susceptible to these adverse effects.
• if you are being treated simultaneously with methotrexate; Folinato cálcico Teva should not be administered with methotrexate, because Folinato cálcico Teva is able to counteract the effects of methotrexate completely. Therefore, Folinato cálcico Teva must always be administered several hoursafterthe treatment with methotrexate (see also section 3. “How to use Folinato cálcico Teva”).
• if you have been treated with radiation therapy before, and receive Folinato cálcico Teva in combination with the medicine 5-fluorouracil; your doctor will reduce the dose of 5-fluorouracil.
• if you receive Folinato cálcico Teva in combination with the medicine 5-fluorouracil and your doctor notes that the amount of calcium in your blood has decreased; your doctor will prescribe extra calcium.
• if you take certain antiepileptic medicines; seizures may occur more frequently (see also the paragraph “Use of Folinato cálcico Teva with other medicines” and the section “Possible side effects”.
• if you take/receive certain cancer medicines, such as hydroxycarbamide, cytarabine, mercaptopurine and thioguanine. These medicines may cause a blood disorder (macrocytosis) that should not be treated with Folinato cálcico Teva.
• if your kidneys do not function well and you are given Folinato cálcico Teva in combination with methotrexate; your doctor may decide to increase the dose of Folinato cálcico Teva or prescribe that you use it for a longer period.

Consult your doctor, if any of these circumstances occur or have occurred in the past.

Use of Folinato cálcico Teva with other medicines

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

Please note that the names of the medicines mentioned in this section may be known by a different name, for example, the brand name. In this section only the active ingredient is mentioned and not the brand name. Therefore, check the packaging and the leaflet, which is the active ingredient of the medicine you are taking or have taken in the recent past.

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

- 5-fluorouracil (a medicine against certain types of cancer). The effect and adverse effects of 5-fluorouracil are increased. Folinato cálcico Teva and 5-fluorouracil are often administered in combination intentionally. However, also the unwanted adverse effects are increased.

- antagonists of folic acid such as cotrimoxazole (an antibiotic), pyrimethamine (a treatment for malaria) or methotrexate. The effect of the antagonist of folic acid may either be reduced or be completely neutralized. Folinato cálcico Teva and methotrexate are often administered in combination intentionally.

- phenobarbital, primidone, phenytoin and succinimides (medicines against epilepsy). The effect of these medicines may be reduced, which may cause epileptic seizures.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, consult your doctor or pharmacist before using this medicine.

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

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

The 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 it is clearly necessary. This will be decided by your doctor. In combination with 5-fluorouracil, the administration of Folinato cálcico Teva during breastfeeding is not recommended due to the harmful effects of 5-fluorouracil.

Driving and operating machines

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

Folinato cálcico Teva contains sodium

Vials of 5 ml:

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

Vials of 10 ml:

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

Vials of 20 ml:

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

Vials of 30 ml:

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

Vials of 50 ml:

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

Teva Calcium Folinate will only be administered by a doctor or nurse under the supervision of a doctor experienced in the use of chemotherapy. Teva Calcium Folinate can be administered by injection or infusion into a vein or as an injection into a muscle.

The dosage may vary from patient to patient since the dose will be calculated based on your body surface area (based on your height and weight). Your doctor will decide what dose is best for you.

The recommended dose is

After a cycle of methotrexate at moderate to high doses:

Adults, elderly patients, and children:

As a rule, the first dose of Teva Calcium Folinate is 15 mg (6-12 mg/ per square meter of your body surface area) to be administered 12-24 hours (at most, 24 hours) after the start of the methotrexate infusion. During a period of 72 hours, the same dose is repeated every 6 hours. After administration of a few injections or infusions, it is possible to switch to tablets.

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

Adults and elderly patients

• Bimonthly regimen: on two consecutive days, every two weeks: 200 mg of Teva Calcium Folinate per square meter of your body surface area by infusion for a period of two hours, followed by an injection of 400 mg of 5-fluorouracil per square meter of your body surface area and 600 mg of 5-fluorouracil per square meter of body surface area by infusion for a period of 22 hours.
• Weekly regimen: 20 mg of Teva Calcium Folinate per square meter of your body surface area by a single injection, or 200 to 500 mg of Teva Calcium Folinate per square meter of your body surface area by infusion for a period of two hours plus 500 mg of 5-fluorouracil per square meter of your body surface area by intravenous injection in the middle or at the end of the Teva Calcium Folinate infusion.
• Monthly regimen: once a month for five consecutive days: 20 mg of Teva Calcium Folinate per square meter of your body surface area by a single injection, or 200 to 500 mg of Teva Calcium Folinate per square meter of your body surface area by infusion for a period of two hours, immediately followed by 425 or 370 mg of 5-fluorouracil per square meter of body surface area by a single injection.

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

Toxic effects of trimetrexate (a medication used to treat certain forms of pneumonia, especially in patients with AIDS):

To prevent the toxicity caused by trimetrexate, you will receive Teva Calcium Folinate every day during the treatment with trimetrexate, and up to 72 hours after the last dose of trimetrexate. Your doctor will administer Teva Calcium Folinate by infusion for 5-10 minutes in a dose of 20 mg per square meter of your body surface area. This will be repeated every 6 hours, resulting in a total daily dose of 80 mg per square meter of your body surface area. Tablets are an alternative to infusion. Four times a day, you will receive a dose of 20 mg per square meter of your body surface area, equally divided throughout the day. Your doctor may decide to administer another dose.

In case of trimetrexate overdose, your doctor will administer Teva Calcium Folinate after interrupting trimetrexate. Teva Calcium Folinate will be administered into a vein every 6 hours for 3 days, in a dose of 40 mg per square meter of your body surface area.

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

After interrupting treatment with trimethoprim, you will receive 3-10 mg of Teva Calcium Folinate per day. Your doctor will decide on the duration of this treatment.

Toxic effects of pyrimethamine (a medication used to treat malaria and for a disease called toxoplasmosis, caused by a parasite):

If you receive a high dose of pyrimethamine or if pyrimethamine is taken for a long period of time, you will receive 5-50 mg of Teva Calcium Folinate per day simultaneously.

If you use more Teva Calcium Folinate than you should

If you are given more Teva Calcium Folinate than recommended, your doctor will treat you appropriately. If you suspect a severe overdose, consult your doctor or pharmacist immediately. In case of a high dose, the effects described in the "possible adverse effects" section may occur. If you are given Teva Calcium Folinate in combination with methotrexate, too much Teva Calcium Folinate may decrease the effect of methotrexate.

If you forgot to use Teva Calcium Folinate

When you forget a dose and Teva Calcium Folinate is administered in combination with methotrexate, toxic effects of methotrexate (see Methotrexate Prospect) may occur. Consult your doctor if you have doubts.

If you interrupt Teva Calcium Folinate

When Teva Calcium Folinate is administered in combination with methotrexate and treatment is interrupted abruptly, adverse effects of methotrexate that were previously counteracted by Teva Calcium Folinate may appear. Therefore, it is not recommended to interrupt Teva Calcium Folinate abruptly.

If you have any other questions about the use of this medication, ask your doctor or pharmacist

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

Consult your doctor immediately ifyou notice any of the following symptoms:

• abrupt palpitations, difficulty breathing, swelling of the eyelids, face, or lips, rash, or itching (especially all over the body)
• diarrhea
• mucositis

The reactions mentioned above can be serious side effects. Your doctor may decide to stop treatment.

The following side effects have been reported:

Rare: may affect up to 1 in 100 people

fever

Uncommon: may affect up to 1 in 1,000 people

insomnia, agitation, depression, and gastrointestinal disturbances after high-dose administration. In combination with certain antiepileptic drugs, the frequency of seizures rarely increases (see also the 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, feeling of fear, chills, itching, pallor, or flushing, sweating, infrequent shortness of breath, rapid heartbeat, and shock (anaphylactic or anaphylactoid reaction), intense itching skin rash (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 5-fluorouracil drug, the following side effects may occur:

Very common: may affect more than 1 in 10 people

• diarrhea (possibly severe and leading to dehydration), vomiting, and nausea
• inflammation of the intestinal and oral mucosa (potentially life-threatening conditions)
• 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 that may cause skin peeling (hand-foot syndrome)

Unknown frequency: cannot be estimated from available data

• elevated blood ammonia levels.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, 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 the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep out of sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging after “CAD”. The expiration date is the last day of the month indicated.

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

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

Pharmaceutical form and content

Teva Calcium Folinic is a solution for injection and contains calcium folinate corresponding to 10 mg of folic acid per ml, which is equivalent to 50 mg of folic acid for the 5 ml vial, 100 mg for the 10 ml vial, 200 mg for the 20 ml vial, 300 mg for the 30 ml vial, and 500 mg for the 50 ml vial.

Composition of Teva Calcium Folinic

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

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

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

Appearance of the product and contents of the container

Injectable solution.

Teva Calcium Folinic is a transparent, yellow, particle-free solution.

Teva Calcium Folinic is packaged in Type I colorless glass vials with chlorobutyl rubber stoppers, with aluminum crimping capsules.

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

Package 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

Responsible for manufacturing

PHARMACHEMIE B.V.Swensweg 5

PO Box 552

2031 GAHaarlem

Netherlands

This medicine is authorized in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Netherlands:Rescuvolin 10 mg/ml, solution for injection

Spain:Folinato Cálcico Teva 10 mg/ml Injectable Solution

United Kingdom

(Northern Ireland):Calcium Folinate 10 mg/ml solution for injection

Last review date of this leaflet:July 2022

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