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Calcium Folinate 10mg/Ml Solution For Injection Bp

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PACKAGE LEAFLET: INFORMATION FOR THE USER CALCIUM FOLINATE 10 MG/ML INJECTION BP SOLUTION FOR INJECTION OR INFUSION

Calcium folinate

The name of your medicine is Calcium Folinate 10 mg/ml Injection BP, which will be called Calcium folinate

throughout this leaflet.

Read all of this leaflet carefully before you start taking this medicine.

-    Keep this leaflet. You may need to read it again.

-    If you have any further questions, ask your doctor or pharmacist.

-    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

-    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

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

2.    Before you are given Calcium folinate

3.    How you are given Calcium folinate

4.    Possible side effects

5.    How to store Calcium folinate

6.    Further information

1.    WHAT CALCIUM FOLINATE IS AND WHAT IT IS USED FOR

Calcium folinate is a solution containing the active ingredient Calcium folinate, which is one of a group of medicines called detoxifying agents.

Calcium folinate is used to reduce the side effects of certain anticancer drugs or if too much has been given in adults and children. Calcium folinate works by acting against drugs that work against folic acid such as methotrexate. This is called “Calcium Folinate Rescue”.

Calcium folinate may also be used in combination with 5-fluorouracil (another anticancer drug).

2.    BEFORE YOU ARE GIVEN CALCIUM FOLINATE You should not be given Calcium folinate if you:

-    are allergic (hypersensitive) to calcium folinate or any of the other ingredients of Calcium folinate (see list of ingredients in Section 6). An allergic reaction may include rash, itching, difficulty breathing or swelling of the face, lips, throat or tongue.

-    have anaemia

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).

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

Take special care with Calcium folinate and tell your doctor if you have any of the following conditions:

-    epilepsy

-    a kidney disorder

Tell your doctor if you develop any of the following conditions during treatment:

-    diarrhoea

-    inflammation of the mouth

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription, e.g.:

-    treatments for epilepsy

-    5-fluorouracil (an anticancer drug)

-    co-trimoxazole (an antibiotic)

-    pyrimethamine (a treatment for malaria)

Pregnancy and breast-feeding

You should not be given Calcium folinate together with 5-fluorouracil while pregnant or breast-feeding as it might harm the baby.

You will only be given Calcium folinate together with methotrexate when pregnant or breast-feeding if your doctor thinks it is necessary.

Driving and using machines

There is no evidence that Calcium folinate affects driving or using machines.

3.    HOW YOU ARE GIVEN CALCIUM FOLINATE

Calcium folinate 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 may be given by injection or infusion into a vein, or as an injection into a muscle.

Adults, children and the elderly

The dose depends on your body surface area, the type of anticancer treatment used, and any other treatment you may be receiving.

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

4.    POSSIBLE SIDE EFFECTS

Like all medicines, Calcium folinate can cause side effects, although not everybody gets them.

All medicines can cause allergic reactions, although serious allergic reactions are very rare. 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).

The following side effects have been reported:

Uncommon (between 1 in 1000 and 1 in 100)

•    fever

Rare (between 1 in 1000 and 1 in 10,000)

•    difficulty sleeping (insomnia)

•    agitation

•    depression

•    digestive tract disorders (like vomiting, nausea, diarrhoea and dehydration)

•    increased attacks in patients with epilepsy.

Very rare (less than 1 in 10000)

•    allergic reactions, including severe allergic attacks and nettle rash.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5.    HOW TO STORE CALCIUM FOLINATE

Your doctor or pharmacist knows how to store Calcium folinate.

Calcium folinate should be kept out of the reach and sight of children.

Store at 2-8°C. Store in the original container to protect from light.

Do not use Calcium folinate after the expiry date which is stated on the label and the carton after EXP. The expiry date refers to the last day of that month.

The following information is intended for medical and healthcare professionals only:

Instructions for use/handling For single use only.

For intravenous infusion, calcium folinate may be diluted with 0.9% sodium chloride solution or 5% glucose solution before use (see storage and shelf-life).

Prior to administration, calcium folinate should be inspected visually. The solution for injection or infusion should be a clear yellowish solution. If cloudy in appearance or particles are observed, the solution should be discarded. Calcium folinate solution for injection or infusion is intended for single use only. Any unused portion of the solution should be disposed of in accordance with the local requirements.

Incompatibilities

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

Droperidol

1.    Droperidol 1.25 mg/0.5 ml with calcium folinate 5 mg/0.5 ml; immediate precipitation was observed after direct admixture in a syringe for 5 minutes at 25°C followed by 8 minutes of centrifugation.

2.    Droperidol 2.5 mg/0.5 ml with calcium folinate 10 mg/0.5 ml; immediate precipitation was observed when the drugs were injected sequentially into a Y-connector without flushing the Y-side arm between injections.

Fluorouracil

Calcium folinate must not be mixed in the same infusion as 5-fluorouracil because a precipitate may form. Fluorouracil 50 mg/ml with calcium folinate 20 mg/ml, with or without dextrose 5% in water, has 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

The formation of a cloudy yellow solution has been reported when Foscarnet 24 mg/ml is mixed with with calcium folinate 20 mg/ml.

Administration

For intravenous and intramuscular use only. Fatal if given by other routes.

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.

Calcium Folinate Rescue in methotrexate therapy:

Refer to the applied intermediate- or high-dose methotrexate protocol for posology and method of administration of calcium folinate. The methotrexate protocol will dictate the dosage regimen of Calcium Folinate Rescue because it depends heavily on the posology and method of the intermediate- or high-dose methotrexate administration. The following guidelines may serve as an illustration of regimens used in adults, elderly and children:

Calcium Folinate Rescue is necessary when methotrexate is given at doses exceeding 500 mg/m2 body surface and has to be considered with doses of 100 mg - 500 mg/m2 body surface. Calcium Folinate Rescue should be performed by parenteral administration in patients with malabsorption syndromes or other gastrointestinal disorders where enteral absorption is not assured. Dosages above 25-50 mg should be given parenterally due to saturable enteral absorption of calcium folinate.

Dosage and duration of use of Calcium folinate primarily depend on the type and dosage of methotrexate therapy, the occurrence of toxicity symptoms, and the individual excretion capacity for methotrexate. As a rule, the first dose of Calcium folinate is 15 mg (6-12 mg/m2) to be given 12-24 hours (24 hours at the latest) after the beginning of the methotrexate infusion. The same dose is given every 6 hours throughout a period of 72 hours. After several parenteral doses treatment can be switched over to the oral form.

In addition to calcium folinate administration, measures to ensure the rapid excretion of methotrexate (maintenance of high urine output and alkalinisation of urine) are integral parts of the Calcium Folinate Rescue treatment. Renal function should be monitored by measuring serum creatinine levels daily.

The residual methotrexate-level, in the blood, should be measured, forty-eight hours after the start of the methotrexate-infusion. If the residual methotrexate-level is > 0.5 pmol/l, then the dosage of calcium folinate dosages should be adapted according to the following table:

Residual methotrexate level in the blood 48 hours after the start of the methotrexate administration:

Additional Calcium folinate to be administered every 6 hours for 48 hours or until levels of methotrexate are lower than 0.05 [jmol/l:

> 0.5 [jmol/l

15 mg/m2

> 1.0 [jmol/l

100 mg/m2

> 2.0 [jmol/l

200 mg/m2

In combination with 5-fluorouracil in cytotoxic therapy:

Different regimens and different dosages are used, however, no optimal dosage or regimen have been determined.

The following regimens have been used in adults and the elderly in the treatment of advanced or metastatic colorectal cancer and are given as examples. There are no data on the use of calcium folinate in combination with 5-fluorouracil in children:

Bimonthly regimen: Calcium folinate 200 mg/m2 by intravenous infusion over two hours, followed by an intravenous bolus of 400 mg/m2 of 5-Fluorouracil and a 22-hour intravenous infusion of 5-Fluorouracil (600 mg/m2) for 2 consecutive days, every 2 weeks on days 1 and 2.

Weekly regimen: Calcium folinate 20 mg/m2 by intravenous bolus injection or 200 to 500 mg/m2 intravenous infusion over a period of 2 hours, plus 500 mg/m2 5-fluorouracil as an intravenous bolus injection in the middle, or at the end, of the calcium folinate infusion.

Monthly regimen: Calcium folinate 20 mg/m2 by bolus i.v. injection or 200 to 500 mg/m2 as i.v. infusion over a period of 2 hours immediately followed by 425 or 370 mg/m2 5-fluorouracil as an intravenous bolus injection over five consecutive days.

For the use of calcium folinate in combination with 5-fluorouracil, modification of the 5-fluorouacil dosage and the treatment-free interval may be necessary depending on patient condition, clinical response and dose limiting toxicity as stated in the product information of 5-fluorouracil. A reduction of calcium folinate dosage is not required.

The number of repeat cycles used is at the discretion of the clinician.

Antidote to the folic acid antagonists trimetrexate, trimethoprim, and pyrimethamine:

Trimetrexate toxicity:

•    Prevention: Calcium folinate should be administered every day during treatment with trimetrexate and for 72 hours after the last dose of trimetrexate. Calcium folinate can be administered either intravenously at a dose of 20 mg/m2 for 5 to 10 minutes every 6 hours (total daily dose of 80 mg/m2), or orally with four doses of 20 mg/m2 administered at equal time intervals. Daily doses of calcium or calcium folinate should be adjusted depending on the haematological toxicity of trimetrexate.

•    Over dosage (possibly occurring with trimetrexate doses above 90 mg/m2 without concomitant administration of calcium folinate): Calcium folinate should be administered intravenously at a dose of 40 mg/m2 every 6 hours for 3 days, following cessation of treatment with trimetrexate.

Trimethoprim toxicity:

•    Following cessation of treatment with trimethoprim, calcium folinate should be administered intravenously at a dose of 3-10 mg/day calcium folinate until recovery of a normal blood count.

Pyrimethamine toxicity:

In cases of high dose pyrimethamine or prolonged treatment with low doses, calcium folinate 5 to 50 mg/day should be simultaneously administered, based on the results of the peripheral blood counts.

11782838-Reg

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6. FURTHER INFORMATION What Calcium folinate contain:

The active substance is Calcium folinate 10 mg/ml.

The other ingredients are: sodium chloride and water for injection What Calcium folinate looks like and contents of the pack

Amber glass vials packed in a carton.

Vials are closed with a rubber stopper with an aluminium cap.

1 vial containing 100 mg/10 ml of Calcium folinate.

1 vial containing 200 mg/20 ml of Calcium folinate.

1 vial containing 300 mg/30 ml of Calcium folinate.

1 vial containing 350 mg/35 ml of Calcium folinate.

1 vial containing 800 mg/80 ml of Calcium folinate.

Also amber glass ampoules packed in a carton.

5 ampoules each containing 30 mg/3 ml of Calcium folinate.

5 ampoules each containing 50 mg/5 ml of Calcium folinate.

5 ampoules each containing 100 mg/10 ml of Calcium folinate.

Not all pack sizes may be marketed

Marketing Authorisation Holder and Manufacturer

EBEWE Pharma Ges.m.b.H. Nfg. KG

MondseestraBe 11

4866 Unterach

Austria

This leaflet was last revised in

06/2013

Storage and shelf-life

Unopened - 24 months.

The chemical and physical in-use stability of the solution diluted with Sodium Chloride 0.9 % or Glucose 5 % for intravenous infusion has been demonstrated for 24 hours at a temperature not exceeding 25°C.

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 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Special precautions for storage Store at 2-8°C (in a refrigerator).

Store in original container to protect from light.

A copy of the full SPC can be requested from the Marketing Authorisation Holder.

d0ycklh5.indd 3 04.07.2013 12:59:20