Folinic acid Hikma 10 mg/ml solution for injection and infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Folinato Cálcico Hikma 10 mg/ml solution for injection and infusion EFG

Folinic acid

Read the entire 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, pharmacist, or nurse.

• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, since it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

1. What Folinato Cálcico Hikma is and what it is used for
2. What you need to know before using Folinato Cálcico Hikma
3. How to use Folinato Cálcico Hikma
4. Possible side effects
5. How to store Folinato Cálcico Hikma
6. Contents of the pack and other information

1. What Folinato Cálcico Hikma is and what it is used for

Folinato Cálcico Hikma contains calcium folinate, which belongs to a group of medicines called detoxifying agents. It is the calcium salt of folinic acid, which is related to folic acid vitamin.

Folinato Cálcico Hikma is used to:

• reduce harmful effects and to treat overdose of certain anticancer medicines, such as methotrexate and other folic acid antagonists. This process is known as "calcium folinate rescue".
• treat cancer in combination with 5-fluorouracil (an anticancer medicine). 5-fluorouracil works better when administered together with Folinato Cálcico Hikma.

2. What you need to know before starting to use Folinato Cálcico Hikma

Folinato Cálcico Hikma must not be administered intrathecally (into the spinal column).

Do not use Folinato Cálcico Hikma:

• if you are allergic to calcium folinate or any of the other ingredients of this medicine (listed in section 6).
• if you have a type of anaemia caused by low vitamin B12 levels.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to use Folinato Cálcico Hikma.

If you are receiving treatment with calcium folinate and fluorouracil at the same time, take special care if:

• you have undergone radiotherapy.
• you have stomach or intestinal problems.

Special care is also required if you are over 65 years of age and are to receive treatment with calcium folinate and fluorouracil simultaneously.

Use of Folinato Cálcico Hikma with other medicines

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines.

Special care is required if you are taking/using other medicines, as they may interact with Folinato Cálcico Hikma, for example:

• folic acid antagonists (see section 1) – the effectiveness of these medicines may be reduced by calcium folinate;
• fluorouracil (a cancer medicine) – the effectiveness and side effects of this medicine may be increased by calcium folinate;
• medicines used to treat epilepsy (phenobarbital, phenytoin, primidone, or succinimides) – the effectiveness of these medicines may be reduced by calcium folinate. Your doctor may monitor blood levels of these medicines and adjust the dose to prevent increased seizures (epilepsy).

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.

It is unlikely that your doctor will ask you to take/use a folic acid antagonist or fluorouracil during pregnancy or breastfeeding. However, if you have taken/used a folic acid antagonist while pregnant or breastfeeding, this medicine (calcium folinate) may be used to reduce side effects.

Folinato Cálcico Hikma contains sodium

This medicine contains less than 23 mg (1 mmol) of sodium per vial and is therefore considered essentially “sodium-free”.

3. How to use Folinato Cálcico Hikma

This medicine may be administered by injection (using a syringe) into the muscle. Alternatively, it may also be given by injection or infusion (drip) into a vein. If administered by infusion, Folinato Cálcico Hikma must first be diluted.

Your doctor will decide the correct dose of Folinato Cálcico Hikma for you and how often you should receive it. This decision will depend on the medical condition being treated.

If you use more Folinato Cálcico Hikma than you should

This medicine is administered in a hospital setting under the supervision of a doctor.

It is unlikely that you will be given too much or too little, but speak to your doctor or nurse if you have any questions.

4. Possible side effects

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

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

• severe allergic reaction – you may experience sudden itchy rash (urticaria), swelling of hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), and you may feel weak. This is a serious side effect. Medical attention may be required.

Uncommon: may affect up to 1 in 100 people

• fever.

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

• increased number of seizures (epilepsy) in patients with epilepsy.
• depression.
• agitation.
• gastrointestinal disorders.
• difficulty sleeping (insomnia).

Combination therapy with 5-fluorouracil:

If you are receiving calcium folinate in combination with a cancer medicine containing fluoropyrimidines, you are more likely to experience the following side effects from the other medicine:

Very common: may affect more than 1 in 10 people

• nausea.
• vomiting.
• severe diarrhoea.
• dehydration which may be due to diarrhoea.
• inflammation of the intestinal and oral mucosa (life-threatening conditions have occurred).
• reduction in blood cell counts (including life-threatening conditions).

Common: may affect up to 1 in 10 people

• redness and swelling of the palms of the hands and soles of the feet, which may lead to skin peeling (hand-foot syndrome).

Frequency not known: cannot be estimated from the available data

• high levels of ammonia in the blood.

Reporting of side effects

If you experience any side effect, talk to your doctor or pharmacist, including any possible side effects 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 side effects, you can help provide more information on the safety of this medicine.

5. Storage of Calcium Folinate Hikma

Store in a refrigerator (2°C – 8°C).

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 packaging following EXP. The expiry date is the last day of the month indicated.

Keep vials in the outer packaging to protect from light.

Unopened vials: 36 months (3 years).

After first opening: 28 days at room temperature or at 2–8°C.

After dilution: chemical and physical stability during use after dilution to concentrations between 0.5 mg/mL and 4 mg/mL in 0.9% sodium chloride or 5% glucose has been demonstrated for 28 days, both at room temperature and at 2–8°C.

From a microbiological point of view, the product should be used immediately.

If not used immediately, the in-use storage times and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at temperatures of 2 to 8°C, unless the dilution was carried out under controlled and validated aseptic conditions.

6. Package Contents and Additional Information

Composition of Folinato Cálcico Hikma

• The active substance is calcium folinate. Each ml contains 10 mg of folinic acid in the form of calcium folinate.
• Each 5, 10, 30 and 50 ml of solution contains 50, 100, 300 and 500 mg of folinic acid, respectively (in the form of calcium folinate).
• The other components are sodium chloride, hydrochloric acid, sodium hydroxide and water for injection.

Appearance of the product and contents of the container

Folinato Cálcico Hikma is a clear, pale yellow solution supplied in glass containers called vials.

It is available in packs containing:

1 or 5 vials of 10 ml with 5 ml of calcium folinate

1 or 5 vials of 10 ml with 10 ml of calcium folinate

1 or 5 vials of 50 ml with 30 ml of calcium folinate

1 or 5 vials of 50 ml with 50 ml of calcium folinate

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Hikma Farmacêutica (Portugal) S.A.

Estrada do Rio da Mó, nº8, 8A and 8B, Fervença

2705-906 Terrugem SNT

Portugal

Manufacturer

Hikma Italia S.p.A

Viale Certosa, 10

27100 - Pavia

Italy

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Hikma España, S.L.U.

Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2

28108 - Alcobendas, Madrid

Spain

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Germany: Calciumfolinat Hikma 10 mg/ml Injektions-/Infusionslösung

Spain: Folinato Cálcico Hikma 10 mg/ml Solución inyectable y para perfusión EFG

France: Folinate de Calcium Hikma 10 mg/ml solution injectable/pour perfusion

Portugal: Folinato de Cálcio Hikma 10mg/ml solução injetável ou para perfusão

United Kingdom: Calcium Folinate 10 mg/ml Solution for injection/infusion

Date of the most recent review of this summary: February 2024

This information is intended for healthcare professionals only:

In addition to the information included in section 3, practical information on the preparation/handling of this product is provided below.

Incompatibilities

Incompatibilities have been observed between injectable forms of calcium folinate and injectable forms of droperidol, fluorouracil, foscarnet and methotrexate.

Droperidol

Droperidol 1.25 mg/0.5 ml with calcium folinate 5 mg/0.5 ml: immediate precipitation observed after direct mixing in a syringe, held for 5 minutes at 25°C followed by 8 minutes of centrifugation.

Droperidol 2.5 mg/0.5 ml with calcium folinate 10 mg/0.5 ml: immediate precipitation observed when the drugs are injected sequentially into a Y-set without flushing one arm of the set between injections.

Fluorouracil

Calcium folinate must not be mixed in the same infusion with 5-fluorouracil, as a precipitate may form. Mixtures of 50 mg/ml fluorouracil with 20 mg/ml calcium folinate, with or without 5% dextrose in water, have been shown to be incompatible when mixed in various proportions and stored at 4°C, 23°C, or 32°C in polyvinyl chloride containers.

Foscarnet

24 mg/ml foscarnet with 20 mg/ml calcium folinate: formation of a cloudy yellow solution has been reported.

Special precautions for disposal and other handling

Folinato Cálcico Hikma is intended for single use only. Disposal of unused medication and of all materials that have come into contact with it must be carried out in accordance with local regulations.

Prior to administration, calcium folinate should be inspected visually. The solution for injection or infusion should be clear and yellowish. If the solution appears cloudy or particulate matter is observed, the solution must be discarded.