Package leaflet: Information for the user ISOVORIN® Solution for Injection 10 mg/ml

calcium levofolinate

Read all of this leaflet carefully before you start taking 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 or pharmacist.

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

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

What is in this leaflet:

1.    What ISOVORIN Solution is and what it is used for

2.    What you need to know before you use ISOVORIN Solution

3.    How to use ISOVORIN Solution

4.    Possible side effects

5.    How to store ISOVORIN Solution

6.    Contents of the pack and other information

1.    WHAT ISOVORIN SOLUTION IS AND WHAT IT IS USED FOR

ISOVORIN Solution for Injection 10 mg/ml may be used in combination with other medicines to treat cancer. In particular it may be used to reduce the harmful effects of an anti-cancer drug called methotrexate.

ISOVORIN Solution can be used to increase the effect of another drug, 5-fluorouracil (5FU) in treating some types of cancer such as cancer of the colon or rectum.

2.    WHAT YOU NEED TO KNOW BEFORE YOU USE ISOVORIN SOLUTION Do not use ISOVORIN Solution if:

•    You are allergic to levofolinate or any of the other ingredients of this medicine (listed in section 6).

•    You have a blood disease called anaemia caused by too little Vitamin B₁₂

•    You are pregnant, think you might be pregnant or are breast- feeding.

Warnings and precautions

Talk to your doctor or pharmacist before using Isovorin Solution if:

•    you have anaemia (megaloblastic or pernicious) caused by vitamin B12 deficiency.

•    you have blood problems caused by anti-cancer medicines.

•    you are elderly or debilitated and being treated with 5-Fluorouracil.

•    you are suffering from diarrhoea or stomach upset and receiving treatment along with 5-Flurouracil.

•    you have undergone preliminary radiotherapy.

•    you take an accidental overdose with methotrexate.

•    you have taken an excessive dose of this as the activity of methotrexate may be impaired especially in anti tumour therapy.

•    you are resistant to methotrexate or folinic acid

Other medicines and Isovorin Solution

Tell your doctor or pharmacist if you are taking, have recently taken or might take other medicines. In particular, you should tell your doctor if you are using:

-    medicines for the treatment of epilepsy (e.g. phenobarbital, phenytoin, primidone or succinimides) as your medicine may reduce their effects

-    anti folate drugs (e.g cotrimoxazole, pyrimethamine).

Pregnancy and breast-feeding

Do not use ISOVORIN Solution if you are pregnant, think you might be pregnant or are breast- feeding. Levofolinate may be excreted in breast milk. If you are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.

3.    HOW TO USE ISOVORIN SOLUTION

Your doctor will give you ISOVORIN Solution by injecting it into one of your veins or muscle.

ISOVORIN Solution should not be injected into your spine When used to reduce the harmful effects of methotrexate, your treatment will usually start about 24 hours after your methotrexate treatment starts. The usual dose of ISOVORIN Solution is 7.5 mg every 6 hours for 10 doses. However, the doctor may decide to change this, depending on your condition and the dose of methotrexate you have already received. During your treatment your doctor may also wish to give you other fluids and to take blood samples from you.

When used in combination with other drugs such as 5FU, the higher dose of 175 mg in 17.5 ml of ISOVORIN Solution will be given to you.

If you use more ISOVORIN Solution than you should

As this medicine will be given to you whilst you are in hospital it is unlikey that you will be given too little or too much however if you have any concerns then tell you doctor.

If you miss a dose of ISOVORIN Solution

If you think you have not been given a dose of ISOVORIN Solution, tell your doctor immediately.

If you think that you have missed a dose or have been given too much medicine, tell your doctor/nurse immediately.

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

4.    POSSIBLE SIDE EFFECTS

Like all medicines, ISOVORIN Solution can cause side effects, although not everybody gets them.

If any of the following happen, tell your doctor immediately or go to the casualty department at your nearest hospital:

•    Severe allergic reactions such as breathing difficulties, swelling of the lips, face, neck and throat, and low blood pressure

•    Very severe skin reactions with reddening, blistering, severe inflammation and skin loss

•    Severe diarrhoea

•    Excessive bruising, shortness of breath, tiredness or repeated infections.

Side effects may occur with different frequencies, which are defined as follows:

•    Very common: affects more than 1 user in 10

•    Common: affects 1 to 10 users in 100

•    Uncommon: affects 1 to 10 users in 1,000

•    Rare: affects 1 to 10 users in 10,000

•    Very rare: affects less than 1 user to 10,000

•    Not known: frequency cannot be estimated from available data.

The side effects listed below are those that have been seen with the use of ISOVORIN Solution.

•    Rare: Fits; fainting.

•    Not known: Mild allergic reactions, such as skin rash and itching; fever.

The side effects listed below are those that have also been seen when ISOVORIN Solution has been used in combination with 5FU.

•    Very common: Feeling or being sick; diarrhoea.

•    Not known: Elevated levels of ammonia in the blood; pain, swelling, tingling or redness of the hands and feet; inflammation of the lining of the gut (causing diarrhoea); inflammation of the mouth and lips.

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 ISOVORIN SOLUTION

Keep out of the sight and reach of children.

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

ISOVORIN Solution for Injection 10 mg/ml should be kept in a refrigerator (2-8°C) in the original container. Protect from light.

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 to protect the environment.

6.    CONTENTS OF THE PACK AND OTHER INFORMATION What ISOVORIN Solution contains

•    The active substance is calcium levofolinate.

•    The other ingredients are Sodium Chloride, Water for Injection,

Hydrochloric acid and Sodium Hydroxide.

What ISOVORIN Solution looks like and contents of the pack

The name of this medicine is ISOVORIN Solution for Injection 10 mg/ml. It is supplied in small amber glass bottles (called vials). Each vial contains 25 mg, 50 mg or 175 mg of the active ingredient calcium levofolinate in 2.5 ml, 5 ml and 17.5 ml respectively.

ISOVORIN Solution for Injection 10mg/ml is supplied in cartons containg one vial.

Marketing Authorisation Holder and Manufacturer

The marketing authorisation holder is: Pfizer Limited, Ramsgate Road,

Sandwich, Kent, CT13 9NJ, United Kingdom

The manufacturer of this medicine is: Wyeth Lederle S.p.A, Via Franco Gorgone, Zona Industriale, Catania, Italy

The information in this leaflet applies only to ISOVORIN Solution. If you would like more information about ISOVORIN Solution for Injection 10 mg/ml, have any questions, or you are not sure about anything, you should ask your doctor.

This leaflet was last revised in MM/YYYY

Ref: IO 4_0 UK

8930046 RB2.indd 3 15/04/13 13.52