Calcium folinate sandoz

Package leaflet: Information for the patient

Calcium folinate Sandoz, 10 mg/ml, solution for injection/infusion
Acidum folinicum
Read the entire leaflet carefully before 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, please ask your doctor, pharmacist, or nurse.
 If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse.
See section 4.
Table of contents:

1. What Calcium folinate Sandoz is and what it is used for
2. Important information before using Calcium folinate Sandoz
3. How to use Calcium folinate Sandoz
4. Possible side effects
5. How to store Calcium folinate Sandoz
6. Contents of the pack and other information

1. What Calcium folinate Sandoz is and what it is used for

Calcium folinate Sandoz solution contains the active substance calcium folinate, which belongs to a group of medicines known as antidotes.
Calcium folinate Sandoz is used to reduce the side effects of certain anticancer medicines or in cases of their overdose in adults and children. It counteracts the toxic effects of folic acid antagonists such as methotrexate (this is known as the "calcium folinate rescue").
Calcium folinate Sandoz may also be used in combination with 5-fluorouracil (another anticancer medicine).
Calcium folinate Sandoz is also used to reduce side effects of other medicines (a group of medicines called folic acid antagonists). Examples of medicines in this group include:

• trimetrexate (an antibiotic and anticancer medicine),
• trimethoprim (an antibiotic),
• pyrimethamine (a medicine often used in the treatment of malaria).

It may also be used in the treatment of overdose of these medicines.

2. Information before using Calcium folinate Sandoz

When not to use Calcium folinate Sandoz
 if the patient is allergic to calcium folinate or any of the other ingredients of this medicine
(listed in section 6);
 if the patient has a reduced number of red blood cells (anaemia).
Calcium folinate Sandoz must not be used together with certain (known to the physician) anticancer medicines in pregnant or breastfeeding women.
Calcium folinate Sandoz should be administered only by intramuscular or intravenous injection. It must not be administered directly into the spinal canal or brain (intrathecally).

Warnings and precautions
Before using Calcium folinate Sandoz, discuss with the doctor if the patient has:

• epilepsy,
• impaired kidney function.

Inform the doctor if the following occur during treatment:

• diarrhoea,
• inflammation of the mouth.

Calcium folinate Sandoz and other medicines
Tell the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Examples include:

• antiepileptic medicines,
• 5-fluorouracil (an anticancer medicine),
• co-trimoxazole (an antibiotic),
• pyrimethamine (an antimalarial medicine).

Pregnancy, breastfeeding and fertility
Calcium folinate Sandoz must not be used together with 5-fluorouracil in pregnant or breastfeeding women, as it may harm the child.
Pregnant or breastfeeding women may receive Calcium folinate Sandoz together with methotrexate only if the doctor considers it necessary.

Driving and using machines
There is no evidence that Calcium folinate Sandoz affects the ability to drive or operate machinery.

Calcium folinate Sandoz contains sodium
This medicine contains 3.3 mg (0.14 mmol) of sodium per ml.
Doses less than 7 ml (70 mg):
The medicine contains less than 1 mmol (23 mg) of sodium, meaning the medicine is considered "sodium-free".
For maximum single doses of 500 mg/m², i.e. 850 mg (for average body surface area of 1.7 m²):
This medicine contains 280.5 mg of sodium (main component of table salt) in each maximum single dose of 85 ml. This corresponds to 14% of the maximum recommended daily dietary intake of sodium for adults.

3. How to use Calcium folinate Sandoz

Calcium folinate Sandoz is administered by a doctor or by a nurse under the supervision of a doctor experienced in the use of chemotherapy. The medicine may be given as an intravenous injection or infusion, or as an intramuscular injection.
The dose depends on the patient's body surface area, the type of anticancer treatment, and other concomitant medicines or therapies.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them.
You should contact a doctor immediately

• if the patient experiences a severe allergic reaction with symptoms such as sudden itchy rash (urticaria), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing) and a feeling of fainting. This is a serious side effect. Immediate medical attention is required.

This is a very rare side effect (may occur in fewer than 1 in 10,000 people).
Other side effects
The following side effects have been reported:
Uncommon (may occur in fewer than 1 in 100 people)

• fever

Rare (may occur in fewer than 1 in 1,000 people)

• difficulty sleeping (insomnia)
• restlessness
• depression
• gastrointestinal disturbances
• increased frequency of seizures in patients with epilepsy

If the patient is receiving Calcium folinate Sandoz together with an anticancer medicine containing fluoropyrimidine, there is an increased likelihood of experiencing the following side effects associated with that anticancer medicine:
Very common (may affect more than 1 in 10 people)

• nausea
• vomiting
• severe diarrhoea
• dehydration (which may be caused by diarrhoea)
• inflammation of the mucous membranes of the intestine and mouth (including life-threatening cases)
• decreased blood cell counts (including life-threatening conditions)

Common (may occur in fewer than 1 in 10 people)

• redness and swelling of the palms of the hands or soles of the feet, which may lead to skin peeling (hand-foot syndrome, also known as palmar-plantar erythrodysesthesia)

Side effects with unknown frequency (frequency cannot be estimated from the available data)

• increased blood ammonia levels

Reporting of side effects
If any side effects occur, including any not listed in this leaflet, inform a doctor, pharmacist or nurse. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw
tel.: +48 22 49 21 301/fax: +48 22 49 21 309/website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorisation holder.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Calcium folinate Sandoz

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 the outer carton following EXP. The expiry date refers to the last day of the stated month.
Store in a refrigerator (2°C - 8°C).
The batch number on the packaging is indicated by "Lot".
Information on storage and the duration of use of Calcium folinate Sandoz after dilution for infusion is provided in the section for healthcare professionals at the end of this leaflet.
Do not use the medicine if the solution is cloudy or contains visible particles.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Calcium folinate Sandoz contains

• The active substance is calcium folinate. Each ml of injection/infusion solution contains 10 mg of folinic acid in the form of calcium folinate.
• The other ingredients are: sodium chloride, water for injections, sodium hydroxide, hydrochloric acid (diluted).

What Calcium folinate Sandoz looks like and contents of the pack
Calcium folinate Sandoz is a clear, yellowish solution.
The amber glass vials are packed in cardboard cartons.
The vials are closed with bromobutyl rubber stoppers and aluminium seals.
Pack sizes available:
1, 5, 10 vials of 3 ml
1, 5, 10 vials of 5 ml
1 vial of 10 ml
1 vial of 20 ml
1 vial of 35 ml
1 vial of 50 ml
1 vial of 100 ml
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:
Marketing Authorisation Holder
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl, Austria

Manufacturers
EBEWE Pharma Ges.m.b.H. Nfg.KG
Mondseestraße 11
4866 Unterach am Attersee, Austria
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl, Austria
Salutas Pharma GmbH
Otto-von-Guericke-Allee 1,
Barleben, Sachsen-Anhalt, 39179
Germany

For further information, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw
tel. 22 209 70 00

___________________________________________________________________________

Information intended exclusively for medical professionals

Instructions for preparation and administration of the medicinal product
For intravenous infusion, Calcium folinate Sandoz may be diluted with 0.9% sodium chloride solution or 5% glucose solution (see storage and shelf life).
Before administration, the product should be visually inspected. The injection or infusion solution should be clear and yellowish in appearance. If turbidity or particulate matter is observed, the solution must be discarded.

Incompatibilities
There are data indicating incompatibilities between calcium folinate for injection and droperidol, fluorouracil, foscarnet, and methotrexate for injection.

Droperidol

1. Droperidol 1.25 mg/0.5 ml mixed with calcium folinate 5 mg/0.5 ml: immediate precipitation was observed when mixed directly in a syringe for 5 minutes at 25 **°**C, followed by centrifugation for 8 minutes.
2. Droperidol 2.5 mg/0.5 ml mixed with calcium folinate 10 mg/0.5 ml: immediate precipitation occurred when the drugs were injected sequentially into an infusion line (Y-connector) without flushing the line between administrations.

Fluorouracil
Calcium folinate should not generally be mixed with 5-fluorouracil in the same infusion due to the risk of precipitate formation. Incompatibility has been demonstrated between 5-fluorouracil solutions at 50 mg/ml and calcium folinate at 20 mg/ml, mixed in various proportions with or without 5% aqueous glucose solution and stored in polyvinyl chloride containers at 4 **°**C, 23 **°**C, or 32 **°**C.
However, it has been shown that mixtures of calcium folinate (10 mg/ml) and fluorouracil (50 mg/ml) in a 1:1 ratio remain compatible and stable for 48 hours at temperatures up to 32°C when protected from light.

Foscarnet
Foscarnet 24 mg/ml mixed with calcium folinate 20 mg/ml forms a cloudy yellow solution.

Route of administration
Calcium folinate must be administered only by intramuscular or intravenous injection.
It must not be administered intrathecally.
Fatalities have been reported following intrathecal administration of calcium folinate after intrathecal overdose of methotrexate.

Intravenous administration: calcium folinate should not be administered at a rate exceeding 160 mg per minute due to the calcium content of the solution.

Storage
Store in a refrigerator (2°C – 8°C).

Shelf life
Unopened vial
2 years

After dilution for infusion
Chemical and physical stability has been demonstrated for 28 days at 2°C – 8°C after dilution with 0.9% sodium chloride solution to concentrations of 0.2 mg/ml and 4.0 mg/ml.
Chemical and physical stability has been demonstrated for 4 days at 2°C – 8°C after dilution with 5% glucose solution to a concentration of 0.2 mg/ml, and for 28 days at 2°C – 8°C after dilution to a concentration of 4.0 mg/ml.

From a microbiological standpoint, the product should be used immediately. If not used immediately, the responsibility for storage conditions and duration prior to administration lies with the user. Under normal circumstances, the storage period should not exceed 24 hours at 2°C – 8°C, unless dilution has been carried out under controlled and validated aseptic conditions.