Document: leaflet MAH GENERIC_PL 18719-0001 change

• leaflet MAH GENERIC_PL 00289-0851
• leaflet MAH GENERIC_PL 01502-0094
• leaflet MAH GENERIC_PL 14510-0013
• leaflet MAH GENERIC_PL 18719-0001
• leaflet MAH GENERIC_PL 18727-0041
• leaflet SANDOZ_PL 14510-0013

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Package leaflet: Information for the user

Calcium Folinate 10 mg/ml solution for injection or infusion

Folinic acid

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 nurse.

-    If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet.

See section 4.

What is in this leaflet:

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

2.    What you need to know before you take Calcium Folinate

3.    How to take Calcium Folinate

4.    Possible side effects

5.    How to store Calcium Folinate

6.    Contents of the pack and other information

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

Calcium Folinate 10 mg/ml solution for injection or infusion contains calcium folinate, which is one of a group of medicine called detoxifying agents. It is a calcium salt of folinic acid, which is related to the vitamin folic acid.

Calcium Folinate is used to:

-    reduce the harmful effects and treat overdose of certain types of anti-cancer medicines for instance methotrexate and other folic acid antagonists. This is known as “calcium folinate rescue”.

-    treat cancer in combination with 5-fluorouracil (an anti-cancer medicine). 5-fluorouracil works better when it is given together with Calcium Folinate.

2.    What you need to know before you take Calcium Folinate Do not take Calcium Folinate

-    if you are allergic to Calcium Folinate or any of the other ingredients of this medicine (listed in section 6).

-    if you suffer from anaemia (not enough red blood cells) caused by a lack of vitamin B₁₂, such as:

•    pernicious anaemia (your immune systems fights your red blood cells)

•    megaloblastic anaemia (your red blood cells are larger than normal)

You should not be given Calcium Folinate together with certain anticancer drugs if you are pregnant or breastfeeding (your doctor will know which these are).

Warnings and precautions

Talk to your doctor or nurse before using Calcium Folinate.

Calcium Folinate should only be given by intramuscular injection or intravenous injection or infusion and must not be administered intrathecally.

Please tell your doctor if you have any of the following illnesses or

medical conditions:

-    if you are being treated with 5-fluorouracil, especially if you are elderly or feel unwell, because Calcium Folinate can increase the harmful effects of 5-fluorouracil. This may make you more prone to infections (due to not enough white blood cells). You may also develop a sore mouth or diarrhoea.

Digestive tract problems are also more common and may

be severe or even life-threatening (see section 4, “Possible side effects”).Your doctor may decide stop the treatment with 5-fluorouracil and Calcium Folinate.

-    if you suffer from epilepsy and use anti-epileptic medicines (such as phenobarbital, phenytoin, primidone or succinimides). Because there is a risk that your seizures (fits) may occur more often when you receive Calcium Folinate, your doctor will decide if the dose of your anti-epileptic medicine has to be changed.

-    if you suffer from a macrocytosis (enlarged blood cells) due to treatment with anti-cancer medicines (such as hydroxycarbamide, cytarabine, mecaptopurine, thioguanine), because you should not be treated with Calcium Folinate for this disease.

-    if you have kidney problems, as your doctor might need to change your dose of Calcium Folinate.

Other medicines and Calcium Folinate

Tell your doctor if you are taking or have recently taken any other

medicines.

Please tell your doctor if you are taking or have recently taken any

of the following medicines:

-    medicines which block the action of folic acid (folic acid antagonists) like cotrimoxazole (an antibiotic) or pyrimethamine (to treat special infections like malaria).

Calcium Folinate can reduce the effectiveness of these medicines.

-    medicines to treat epilepsy like phenobarbital, phenytoin, primidone or succinimides (e.g. ethosuximide, phensuximide). Calcium Folinate lowers the concentrations of these drugs

in your body. This can increase the frequency of your seizures (fits). Your doctor will examine your blood to monitor the drug concentrations. Your doctor will also decide if the dose of your anti-epileptic medicine has to be changed.

-    5-fluorouracil:

Calcium Folinate given together with 5-fluorouracil increases not only the efficacy of 5-fluorouracil , but can also increase its poisonousness. Your doctor will decide if your 5-fluorouracil dose has to be changed.

Pregnancy, breast-feeding and fertility Pregnancy

Calcium Folinate can be used to reduce the harmful effects of methotrexate, if your doctor decides that treatment with methotrexate is required for your condition when you are pregnant or breastfeeding. However, methotrexate should not generally be used when you are pregnant or breast-feeding.

Breast-feeding

There are no adequate data for the use of Calcium Folinate and 5-fluorouracil or other anti-cancer drugs in pregnant or breast-feeding women. However, anti-cancer drugs should not generally be used when you are pregnant or 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 taking this medicine.

Driving and using machines

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

Calcium Folinate contains sodium

This medicinal product contains 3.14 mg/ml to 3.20 mg/ml

(0.14 mmol/ml) sodium. To be taken into consideration by patients on

a controlled sodium diet.

3.    How to take Calcium Folinate

The combination of Calcium Folinate with anti-cancer medicines (methotrexate, 5-fluorouracil) should only be given under the supervision of an experienced doctor.

Your doctor will decide about the dose you will receive based on your condition.

The solution of the medicine may be prepared especially for you individually by specialist staff. It is given slowly into a vein (as an injection or infusion) or it may be injected into a muscle. Your doctor will also decide how many injections or infusions you will need and how often they should be given.

If you receive more Calcium Folinate than you should

Reports of patients receiving significantly more Calcium Folinate than recommended dosage have not resulted in any symptoms. However, too much Calcium Folinate can reduce the efficacy of methotrexate.

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.

Tell your doctor straight away if you get any sudden wheeziness, difficulty in breathing, swelling of the eyelids, face or lips, rash or itching (especially affecting your whole body) these could be symptoms of an allergic reaction to this medicine.

Uncommon: may affect up to 1 in 100 people:

-    fever

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

-    trouble sleeping (after high doses)

-    agitation (an inability to keep still, after high doses)

-    depression (after high doses)

-    digestive tract disorders (after high doses) (like vomiting, nausea, diarrhoea and dehydration)

-    increased frequency of seizures (fits) in patients with epilepsy

Very rare: may affect up to 1 in 10,000 people:

-    allergic reactions, including serious allergic reactions with difficulty in breathing or dizziness and hives

The side effects of the combination of Calcium Folinate and 5-fluorouracil may vary. This depends on how often (once a week or once a month) the medicines are given. Elderly or frail patients are more likely to have side effects. Possible side effects include:

Weekly dosing:

Very common: may affect more than 1 in 10 people:

-    severe diarrhoea and dehydration

Tell your doctor immediately if these symptoms occur. They can be life-threatening and may have to be treated in a hospital. Your doctor will decide if your treatment with 5-fluorouracil needs to be stopped until you feel better.

Monthly dosing:

Very common: may affect more than 1 in 10 people:

-    vomiting

-    nausea (feeling sick)

-    severe mouth sores with ulcers, redness and swelling

Reporting of side effects

If you get 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;

UK - Via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. Malta

ADR Reporting The Medicines Authority Post-Licensing Directorate 203 Level 3, Rue D’Argens GZR-1368 Gzira

Website: www. medicinesauthority. gov.mt e-mail: postlicensing.medicinesauthority@gov. mt

The following information is intended for healthcare professionals only:

Incompatibilities

Calcium Folinate must not be mixed with other medicinal products except those mentioned in section “Handling”. Incompatibilities have been reported between injectable forms of Calcium Folinate and injectable forms of droperidol, fluorouracil, foscarnet and methotrexate.

Handling

For intramuscular injection or intravenous injection or infusion.

Fatal if given by other routes. Do not administer Calcium Folinate intrathecally.

For intravenous infusion, Calcium Folinate may be diluted with 0.9% sodium chloride solution or 5% glucose solution.

The medicinal product is for single use only. Any unused solution should be discarded.

The solution for injection should be inspected visually prior to use. Only clear solutions without particles should be used.

In the case of intravenous administration, no more than

160 mg of calcium Folinate should be injected per minute due to the

Calcium content of the solution.

M0xxxxx/00 UK V001

By reporting side effects you can help provide more information on the safety of this medicine.

5.    How to store Calcium Folinate

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

Do not use this medicine after the expiry date which is stated on the vial and carton after EXP The expiry date refers to the last day of that month.

Store in a refrigerator (2°C to 8°C).

Keep the vial in the outer carton in order to protect from light.

After first opening: For Single Dose Use Only. Discard any unused solution immediately after initial use.

After dilution:

When diluted according to directions with 0.9% sodium chloride solution or 5% glucose solution, chemical and physical in-use stability has been demonstrated when protected from light.

Chemical and physical in-use stability after dilution to 1.5 mg/ml with either 0.9% sodium chloride solution or 5% glucose solution was demonstrated for up to 24 hours, at both room temperature (25°C) and 2°C -8°C, when protected from light.

Chemical and physical in-use stability after dilution to 0.2 mg/ml with 0.9% sodium chloride solution was demonstrated for up to 24 hours at 2°C - 8°C, when protected from light.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C -8°C, unless dilution has taken place in controlled and validated aseptic conditions.

If the solution appears discoloured or contains visible particles, it should be discarded.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6.    Contents of the pack and other information What Calcium Folinate contains

- The active substance is Calcium Folinate. Each ml contains 10 mg of folinic acid provided as calcium folinate.

Each 5, 10, 20, 35, 50, 100 ml vial contains 50, 100, 200, 350, 500 and 1000 mg of folinic acid respectively (provided as calcium folinate).

The other ingredients are: Sodium chloride, sodium hydroxide (for pH-adjustment), hydrochloric acid (for pH-adjustment), and water for injections.

What Calcium Folinate looks like and contents of the pack

This medicine is a solution for injection or infusion. It is a clear, yellowish solution. It is filled in amber coloured glass vial, with chlorobutyl rubber stopper and sealed with red, yellow, violet, white, brown and orange aluminium flip-off closure, containing 5 ml, 10 ml, 20 ml, 35 ml, 50 ml or 100 ml solution for injection or infusion.

Package sizes:

The packages contain either 1, 5 or 10 vials of 5 ml, 10 ml, 20 ml, 35 ml, 50 ml or 100 ml, respectively.

This medicinal product is authorised in the Member States of the EEA under the following names:

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Fresenius Kabi Deutschland GmbH Else-Kroener Strasse 1,

Bad Homburg v.d.H. 61352, Germany

Manufacturer

Fresenius Kabi Austria GmbH Hafnerstrasse 36, Graz A-8055 Austria

Shelf life

After first opening: For Single Dose Use Only. Discard any unused solution immediately after initial use.

After dilution:

When diluted according to directions with 0.9% sodium chloride solution or 5% glucose solution, chemical and physical in-use stability has been demonstrated when protected from light.

Chemical and physical in-use stability after dilution to 1.5 mg/ml with either 0.9% sodium chloride solution or 5% glucose solution was demonstrated for up to 24 hours, at both room temperature (25°C) and 2°C -8°C, when protected from light.

Chemical and physical in-use stability after dilution to 0.2 mg/ml with 0.9% sodium chloride solution was demonstrated for up to 24 hours at 2°C - 8°C, when protected from light.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C -8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Disposal:

Any unused product or waste material should be disposed of in accordance with local requirements.