FOLINATE CALCIUM HIKMA 10 mg/ml INJECTABLE SOLUTION AND PERFUSION SOLUTION

2. What you need to know before you use Calcium Folinate Hikma

Calcium Folinate Hikma must not be administered intrathecally (in the spine).

Do not use Calcium Folinate 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 anemia caused by having very low vitamin B12.

Warnings and Precautions

Consult your doctor, pharmacist, or nurse before starting treatment with Calcium Folinate Hikma.

If you are receiving treatment with calcium folinate and fluorouracil at the same time, be particularly careful if:

• you have had radiotherapy
• you have stomach or intestine problems

Special care is also needed if you are over 65 years old and are going to receive treatment with calcium folinate and fluorouracil at the same time.

Using Calcium Folinate Hikma with other medicines

Tell your doctor if you are using, have recently used, or might use any other medicines.

Special care is needed if you are taking/using other medicines as they may interact with Calcium Folinate Hikma, for example:

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

Pregnancy and Breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice 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.

Calcium Folinate Hikma contains sodium

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

3. How to use Calcium Folinate Hikma

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

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

If you use more Calcium Folinate Hikma than you should

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

It is unlikely that you will be given too much or too little, but talk 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 feel a 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. You may need medical attention.

Uncommon: may affect up to 1 in 100 people

• fever

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

• an increase in seizures (epilepsy) in patients with epilepsy
• depression
• agitation
• gastrointestinal disorders
• difficulty sleeping (insomnia)

Combination therapy with 5-fluorouracil:

If you receive calcium folinate in combination with a cancer medicine that contains fluoropyrimidines, you are more likely to have the following side effects of the other medicine:

Very common: may affect more than 1 in 10 people

• nausea
• vomiting
• severe diarrhea
• dehydration that may be due to diarrhea
• inflammation of the intestinal and oral mucosa (life-threatening situations have occurred)
• reduction in the number of blood cells (including life-threatening situations)

Common: may affect up to 1 in 10 people

• redness and swelling of the palms of the hands and soles of the feet, which can cause 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 effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use 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

Keep in the 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 which is stated on the label and carton after EXP. The expiry date is the last day of the month stated.

Store the vials in the outer packaging to protect them from light.

Unopened vials: 18 months.

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

After dilution: the chemical and physical stability during use after dilution between 0.5 mg/ml and 4 mg/ml in 0.9% sodium chloride or 5% glucose has been demonstrated for 28 days at both room temperature and 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 are the responsibility of the user and normally should not be longer than 24 hours at 2 to 8°C, unless the dilution has been carried out in a controlled and validated aseptic environment.

6. Contents of the pack and other information

Composition of Calcium Folinate Hikma

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

Appearance and packaging of the product

Calcium Folinate Hikma is a clear, pale yellow solution, which comes 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 Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Hikma Farmacêutica (Portugal) S.A.

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

2705-906 Terrugem SNT

Portugal

Manufacturer

Hikma Italia S.p.A

Viale Certosa, 10

27100 - Pavia

Italy

You can ask for more information about this medicine from the local representative of the Marketing Authorisation Holder:

Hikma España, S.L.U.

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

28108 - Alcobendas, Madrid

Spain

This medicine is authorised 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

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

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

Date of last revision of this leaflet: February 2024

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This information is intended only for healthcare professionals:

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

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 after direct mixing in a syringe 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 when the medicines are injected sequentially into a Y-piece without flushing one arm of the equipment between injections.

Fluorouracil

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

Foscarnet

24 mg/ml of Foscarnet with 20 mg/ml of calcium folinate: the formation of a yellowish turbid solution has been reported.

Special precautions for disposal and other handling

Calcium Folinate Hikma is intended for single use. Disposal of unused medicine and all materials that have come into contact with it should be done in accordance with local regulations.

Before administration, calcium folinate should be visually inspected. The solution for injection or infusion should be clear and pale yellow in color. If it is cloudy in appearance or particles are observed, the solution should be discarded.