FOLINATO 10 mg /Ml Injectable Solution

Contents of the leaflet

1. Introduction
2. What Calcium Folinate Teva is and what it is used for
3. What you need to know before you are given Calcium Folinate Teva
4. How Calcium Folinate Teva is given
5. Possible side effects
6. Storing Calcium Folinate Teva
7. Container Content and Additional Information

Introduction

Package Leaflet: Information for the User

Calcium Folinate Teva 10 mg/ml Solution for Injection 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, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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

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

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

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

Calcium Folinate 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 applied when supervised by a doctor with experience in the use of chemotherapy for cancer.

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

Use

• to decrease the toxicity and effect 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 you are given Calcium Folinate Teva

Do not use Calcium Folinate Teva

• if you are allergic to calcium folinate 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 megaloblastic anaemia due to lack of vitamin B12 (e.g. pernicious anaemia).

Calcium Folinate Teva must not be given to you at the same time as certain cancer medicines if you are pregnant or breast-feeding (your doctor will know which ones).

Warnings and precautions

Calcium Folinate Teva should only be given by injection into a muscle or vein and must not be given by injection into the spine.

Talk to your doctor or pharmacist before you are given Calcium Folinate Teva

• if you get diarrhoea or mucositis during use of Calcium Folinate 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 the treatment. Elderly and debilitated patients are more susceptible to these side effects.
• if you are being treated with methotrexate at the same time; Calcium Folinate Teva must not be given at the same time as methotrexate, because Calcium Folinate Teva is able to counteract the effects of methotrexate completely. Therefore, Calcium Folinate Teva should always be given several hours aftertreatment with methotrexate (see also section 3. “How to use Calcium Folinate Teva”).
• if you have been treated with radiotherapy before, and you receive Calcium Folinate Teva in combination with the medicine 5-fluorouracil; your doctor will reduce the dose of 5-fluorouracil.
• if you receive Calcium Folinate Teva in combination with the medicine 5-fluorouracil and your doctor notices that the amount of calcium in your blood has decreased; your doctor will prescribe extra calcium.
• if you take certain anti-epileptics; epileptic fits may occur more frequently (see also the paragraph “Use of Calcium Folinate Teva with other medicines” and the section “Possible side effects”.
• if you take/receive certain medicines for the treatment of cancer, such as hydroxycarbamide, cytarabine, mercaptopurine and thioguanine. These medicines may produce a blood disorder (macrocytosis) that should not be treated with Calcium Folinate Teva.
• if your kidneys do not work well and you are given Calcium Folinate Teva in combination with methotrexate; your doctor may decide to increase the dose of Calcium Folinate Teva or prescribe that you use it for a longer period.

Talk to your doctor, if any of these circumstances apply to you or have applied in the past.

Using Calcium Folinate Teva with other medicines

Tell your doctor or pharmacist if you are taking/using, have recently taken/used or might take/use any other medicines.

Please note that the names of the medicines mentioned in this section may be known to you by a different name, e.g. the trade name. In this section only the name of the active substance is mentioned and not the trade name. Therefore, check the packaging and the leaflet, what the active substance of the medicine is that you are taking or have taken in the recent past.

Sometimes products (medicines) that are given/taken at the same time may influence the effect of the other and/or the side effect. This is called an interaction. An interaction may occur during concomitant use of the injection solution and:

• 5-fluorouracil (a medicine against certain forms of cancer). The effect and the side effects of 5-fluorouracil are increased. Calcium Folinate Teva and 5-fluorouracil are often given in combination on purpose. However, the unwanted side 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 neutralised. Calcium Folinate Teva and methotrexate are often given in combination on purpose.
• phenobarbital, primidone, phenytoin and succinimides (medicines against epilepsy). The effect of these medicines may be reduced, which may cause epileptic fits.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

The effects of Calcium Folinate Teva on the fetus are not known. Calcium Folinate Teva may only be given during pregnancy when clearly necessary. This will be decided by your doctor.

This advice also applies when Calcium Folinate Teva is given in combination with methotrexate.

Administration of Calcium Folinate Teva in combination with 5-fluorouracil during pregnancy is not allowed due to the harmful effects of 5-fluorouracil.

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

Driving and using machines

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

Calcium Folinate 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 (a major component of cooking/table salt) in each vial. This equals 1.6% of the maximum recommended daily intake of sodium for an adult.

Vials of 20 ml:

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

Vials of 30 ml:

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

Vials of 50 ml:

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

3. How Calcium Folinate Teva is given

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

The dose may vary from patient to patient as the dose will be calculated 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 Calcium Folinate Teva is 15 mg (6-12 mg/m2 of your body surface area) to be given 12-24 hours (at the latest 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

• Bi-monthly regimen: on two consecutive days, every two weeks: 200 mg of Calcium Folinate Teva per square meter of your body surface area by infusion over 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 over a period of 22 hours.
• Weekly regimen: 20 mg of Calcium Folinate Teva per square meter of your body surface area by a single injection, or 200 to 500 mg of Calcium Folinate Teva per square meter of your body surface area by infusion over 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 Calcium Folinate Teva infusion.
• Monthly regimen: once a month for five consecutive days: 20 mg of Calcium Folinate Teva per square meter of your body surface area by a single injection, or 200 to 500 mg of Calcium Folinate Teva per square meter of your body surface area by infusion over 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 adverse effects of trimetrexate, trimetropim, and pyrimethamine:

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

To prevent toxicity caused by trimetrexate, you will receive Calcium Folinate Teva every day during treatment with trimetrexate, and up to 72 hours after the last dose of trimetrexate. Your doctor will give you Calcium Folinate Teva by infusion over 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 during the day. Your doctor may decide to give you another dose.

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

Adverse effects of trimetropim (an antibiotic used to treat certain infections):

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

Adverse effects of pyrimethamine (a medicine used to treat malaria and a disease called toxoplasmosis, caused by a parasite):

If you receive a high dose of pyrimethamine or if you take pyrimethamine for a long time, you will receive 5-50 mg of Calcium Folinate Teva per day at the same time.

If you use more Calcium Folinate Teva than you should

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

If you forget to use Calcium Folinate Teva

When a dose is missed and Calcium Folinate Teva is given in combination with methotrexate, the toxic effects of methotrexate may occur (see Methotrexate Package Leaflet). Contact your doctor if you have any doubts.

If you stop using Calcium Folinate Teva

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

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

See a doctor immediately if younotice any of the following:

• sudden wheezing, difficulty breathing, swelling of the eyelids, face or lips, rash or itching (especially all over the body)
• diarrhoea
• mucositis

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

The following side 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, agitation, depression and gastrointestinal disorders after administration of high doses. In combination with certain anti-epileptics, the frequency of epileptic fits rarely increases (see also the paragraphs “Warnings and precautions” and “Using Calcium Folinate 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, paleness 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 given in combination with the medicine 5-fluorouracil the following side 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 mucous membrane of the intestine and mouth (potentially life-threatening conditions have occurred).
• Reduced 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 the soles of the feet which may cause the skin to peel (hand-foot syndrome)

Frequency not known: cannot be estimated from the available data

• High level of ammonia in the blood.

Reporting of side effects

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

5. Storing Calcium Folinate Teva

Keep out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after “EXP”. The expiry date refers to the last day of the month shown.

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 dispose of medicines no longer required. These measures will help protect the environment.

6. Container Content and Additional Information

Pharmaceutical Form and Content

Calcium Folinate Teva is an injection solution containing calcium folinate equivalent to 10 mg of folinic acid per ml, which corresponds to 50 mg of folinic 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 Calcium Folinate Teva

• The active ingredient 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, and water for injection.

Product Appearance and Container Content

Injectable solution.

Calcium Folinate Teva is a clear, yellow particle-free solution.

Calcium Folinate Teva is packaged in Type I colorless glass vials with chlorobutyl rubber stoppers and aluminum crimping caps.

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

Package size: 1 vial per carton.

Marketing Authorization Holder

TEVA PHARMA S.L.U.

Anabel Segura Street, 11. Albatros Building B, 1st floor

28108 Alcobendas, Madrid

Spain

Manufacturer

PHARMACHEMIE B.V.

Swensweg 5

PO Box 552

2031 GA Haarlem

Netherlands

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

Netherlands: Rescuvolin 10 mg/ml, solution for injection

Spain: Calcium Folinate Teva 10 mg/ml Injectable Solution

United Kingdom

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

Date of the Last Revision of this Leaflet:July 2022

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