Package leaflet: Information for the user

Oxaliplatin 5 mg/ml concentrate for solution for infusion

What is in this leaflet

1.    What Oxaliplatin is and what it is used for

2.    What you need to know before you use Oxaliplatin

3.    How to use Oxaliplatin

4.    Possible side effects

5.    How to store Oxaliplatin

6.    Contents of the pack and other information

1.    What Oxaliplatin is and what it is used for

Oxaliplatin is used to treat metastatic (advanced) cancer of the colon (large bowel) or rectum (back passage), or as additional treatment following surgery to remove a tumour (growth) in the colon.

It is used in combination with other anticancer agents, 5-fluorouracil (5-FU) and folinic acid (FS).

2.    What you need to know before you use Oxaliplatin

Do not use Oxaliplatin

•    if you are allergic to oxaliplatin or any of the other ingredients of this medicine (listed in section 6).

•    if you are breast-feeding

•    if you already have a reduced number of blood cells (white blood cells and/or platelets).

•    if you already have tingling and numbness in the fingers and/or toes, and have difficulty performing delicate tasks, such as buttoning clothes

•    if you have severe kidney problems

Even if you are male, please ensure that you read the section of this leaflet that concerns pregnancy and breast-feeding.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Oxaliplatin

•    if you have ever suffered an allergic reaction to platinum-containing medicines such as carboplatin or cisplatin

•    if you have moderate kidney problems

•    if you have any liver problems

•    if you are pregnant or planning a pregnancy. It is very important that you discuss this with your doctor before you receive any treatment

•    if your blood cell counts are too low after previous oxaliplatin treatment. Your doctor will perform tests to check that you have sufficient blood cells before treatment

•    if you have symptoms of nerve damage such as weakness, numbness, disturbances of feeling or taste after previous oxaliplatin treatment. These effects are often triggered by exposure to cold. If you notice such symptoms tell your doctor, especially if they are troublesome and/or last longer than 7 days. Your doctor will carry out neurological examinations, before and regularly during treatment, especially if you are given other drugs which may cause nerve damage. Symptoms of nerve damage can persist after the end of the treatment

•    if you also receive 5-fluorouracil, because the risk of diarrhoea, vomiting, sore mouth and blood abnormalities is increased

Other medicines and Oxaliplatin

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

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Oxaliplatin should not be used during pregnancy. It is therefore important to tell your doctor if you are pregnant. If you become pregnant during your treatment, you must inform your doctor immediately.

Effective birth control to prevent pregnancy is advised during treatment and after the end of treatment for the following 4 months for women and for 6 months for men.

The following information is intended for healthcare professionals only:

Oxaliplatin 5 mg/ml concentrate for solution for infusionInstructions for use

ANTINEOPLASTIC AGENT Incompatibilities

This medicinal product should not be mixed with other medicinal products except for those mentioned below in section “Dilution for intravenous infusion".

Oxaliplatin can be co-administered with folinic acid (FA) via a Y-line.

Do not mix with alkaline medicinal products or solutions, in particular 5-fluorouracil, folinic acid preparations containing trometamol as an excipient and trometamol salts of other active substances. Alkaline medicinal products or solutions will adversely affect the stability of oxaliplatin (see below in section “Dilution for intravenous infusion").

Do not dilute for infusion with saline or other solutions containing chloride ions (including calcium, potassium or sodium chloride).

Do not mix with other medicinal products in the same infusion bag or infusion line.

Do not use injection equipment containing aluminium.

Storage conditions

Medicinal product as packaged for sale:

Store below 25°C. Do not refrigerate or freeze. Store in the original package in order to protect from light.

Infusion preparation:

After dilution in 5% glucose solution, chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C and for 6 hours at 25°C. From a microbiological point of view, the infusion preparation 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.

Oxaliplatin may have an anti-fertility effect which could be irreversible. Men treated with oxaliplatin are therefore advised not to father a child during and up to 6 months after treatment and to seek advice on conservation of sperm prior to treatment.

Breast-feeding should be discontinued before starting treatment with Oxaliplatin.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

It is unknown whether treatment with Oxaliplatin affects the ability to drive and use machines.

If you feel sleepy and/or dizzy, or have nausea or vomiting, following oxaliplatin infusion do not drive, operate potentially dangerous machinery, or engage in other activities that may be hazardous because of decreased alertness.

Oxaliplatin treatment may transiently affect vision. If you have problems with vision, do not drive, operate potentially dangerous machinery,

or engage in other activities that may be hazardous.

Oxaliplatin contains lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

3.    How to use Oxaliplatin

For adults only.

Oxaliplatin will be prescribed for you by a specialist in cancer treatment.

Oxaliplatin is given by injection into a vein (an intravenous infusion) over a 2 to 6 hour period.

The dose of Oxaliplatin is based on your body surface area (calculated from your height and weight). The dose will also depend on results of blood tests and whether you have previously experienced side effects with Oxaliplatin. The usual dose for adults including the elderly is 85 mg/m2 of body surface area once every 2 weeks at the same time as folinic acid and before the infusion of 5-fluorouracil. The duration of the treatment will be determined by your doctor. Your treatment will last a maximum of 6 months when used after complete resection of your tumour.

The needle must remain in the vein while the drug is being given. If the needle comes out or becomes loose, or the solution is going into the tissue outside the vein (you may feel discomfort or pain) - tell the doctor or nurse immediately.

If you use more Oxaliplatin than you should

As this medicine is given in a hospital, it is unlikely that you will be given too little or too much. However tell your doctor if you have any concerns.

If you forget to use Oxaliplatin

Oxaliplatin needs to be given on a fixed schedule. Be sure to keep all appointments. If you miss a dose, you should discuss this with your doctor. Your doctor will decide when you should be given your next dose of oxaliplatin.

If you stop treatment with Oxaliplatin

Stopping your treatment with oxaliplatin may stop the effect on tumour growth. Do not stop treatment with oxaliplatin unless you have discussed this with your doctor.

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

4.    Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. If you experience any side effect it is important that you inform your doctor before your next treatment.

Immediately inform your doctor if you notice any of the following:

•    Abnormal bruising, bleeding or signs of infection such as a sore throat and high temperature

•    Persistent or severe diarrhoea or vomiting

•    Sore lips or mouth ulcers (stomatitis/mucositis)

•    Unexplained symptoms from the respiratory system such as non-productive cough, breathing difficulties or voice alterations

•    Symptoms of an allergic reaction such as swelling of hands, feet, ankles, face, lips, mouth or throat (which may cause difficulties in swallowing or breathing)

Very common (may affect more than 1 in 10 people):

•    Effects on the nerves (peripheral sensory neuropathy). You may feel a tingling and/or numbness in the fingers, toes, around the mouth or in the throat which may sometimes occur in association with cramps. This side effect is often triggered by exposure

Instructions for handling, use and disposal

As with other potentially toxic compounds, caution should be exercised when handling and preparing oxaliplatin solutions.

Instructions for Handling

The handling of this cytotoxic agent by healthcare personnel requires every precaution to guarantee the protection of the handler and his surroundings.

The preparation of injectable solutions of cytotoxic agents must be carried out by trained specialist personnel with knowledge of the medicines used, in conditions that guarantee the integrity of the medicinal product, the protection of the environment and in particular the protection of the personnel handling the medicines, in accordance with the hospital policy. It requires a preparation area reserved for this purpose. It is forbidden to smoke, eat or drink in this area.

Personnel must be provided with appropriate handling materials, notably long sleeved gowns, protection masks, caps, protective goggles, sterile single-use gloves, protective covers for the work area, containers and collection bags for waste.

Excreta and vomit must be handled with care.

Pregnant women must be warned to avoid handling cytotoxic agents.

Any broken container must be treated with the same precautions and considered as contaminated waste. Contaminated waste should be incinerated in suitably labelled rigid containers. See below section “Disposal"

If oxaliplatin concentrate or solution for infusion should come into contact with skin, wash immediately and thoroughly with water.

If oxaliplatin concentrate or solution for infusion should come into contact with mucous membranes, wash immediately and thoroughly with water.

Read all of this leaflet carefully before you start using this medicine beacuse it contains important information for you.

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

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

•    This medicine has been prescribed for you only. 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, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

to cold e.g. opening a refrigerator or holding a cold drink. You may also have difficulty in performing delicate tasks, such as buttoning clothes. Although in the majority of cases these symptoms disappear completely there is a possibility of continued symptoms of peripheral sensory neuropathy (weakness or numbness because of nerve damage) after the end of the treatment.

•    Some people have experienced a tingling shock-like sensation passing down the arms or trunk when the neck is flexed.

•    Oxaliplatin can sometimes cause an unpleasant sensation in the throat, in particular when swallowing, and give the sensation of shortness of breath. This sensation, if it happens, usually occurs during or within hours of the infusion and may be triggered by exposure to the cold. Although unpleasant, it will not last long and goes away without the need for any treatment. Your doctor may decide to alter your treatment as a result.

•    Signs of infection such as a sore throat and high temperature.

•    Decreased number of white blood cells, which increase the risk of infection.

•    Decreased number of blood platelets, which increase the risk of bleedings and bruising.

•    Decreased number of red blood cells, which may make the skin pale, and cause weakness or breathlessness. Your doctor will take blood to check that you have sufficient blood cells before you start treatment and before each subsequent course.

•    Allergic reaction - skin rash including red itchy skin, swelling of hands, feet, ankles, face, lips, mouth or throat (which may cause difficulties in swallowing or breathing) and can make you feel like fainting.

•    Loss or lack of appetite.

•    High levels of glucose (blood sugar) in your blood, which may cause thirst, dry mouth and frequent urination.

•    Low levels of potassium in your blood, which may cause abnormal heart beat.

•    Low levels of sodium in your blood, which may cause fatigue and confusion, muscular jerking, cramps or coma.

•    Taste alterations.

•    Headache.

•    Nose bleeds.

•    Breathlessness.

•    Cough.

•    Nausea (feeling sick) and vomiting (being sick) - medication to prevent the sickness is usually given before treatment and may be continued after treatment.

•    Diarrhoea, if you suffer from persistent or severe diarrhoea or vomiting contact your doctor immediately for advice.

•    Sore lips or mouth ulcers.

•    Abdominal pain, constipation.

•    Skin disorder.

•    Hair loss.

•    Back pain.

•    Fatigue, weakness and pain.

•    Reaction close to or at the injection site during the infusion (local pain, redness, swelling of skin, hardening of skin, death of skin tissue).

•    Fever.

•    Alteration in blood tests including those relating to abnormalities in liver function.

•    Weight increase.

•    Rigors (tremors).

•    Blood abnormality (deficiency of certain white blood cells) accompanied by increased susceptibility to infections (febrile neutropenia/neutropenic sepsis).

Uncommon (may affect up to 1 in 100 people):

•    Hearing problems.

•    Blockage or swelling of the bowel.

•    Nervousness.

•    Blood test which indicates increased acidity in the blood.

•    Jaw spasms, muscle spasms, involuntary muscle contractions, muscle twitching.

•    Difficulties with co-ordination, balance, and walking.

•    Throat or chest tightness.

•    Eye disorders such as drooping of the upper eye lid, and double vision.

•    Loss or impairment of the voice, roughness of the voice (hoarseness).

•    Abnormal tongue sensation, difficulty speaking.

•    Facial pain and/or eye pain.

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

•    Slurred speech.

•    Deafness.

•    Unexplained symptoms from the respiratory system such as non-productive cough, breathing difficulties or crackles (interstitial lung disease, pulmonary fibrosis).

•    Inflammation of the large bowel which may cause abdominal pain or diarrhoea (colitis).

•    Blood abnormality (lack of platelets) caused by an allergic reaction associated with bruises and abnormal bleeding (immunoallergic thrombocytopenia).

•    Lack of red blood cells caused by too much degradation of blood (haemolytic anaemia).

•    Transient reduction in visual acuity, disturbance of the visual field, inflammation of the optic nerve (optic neuritis).

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

•    Liver disease

•    Kidney inflammation and kidney failure

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via

Yellow Card Scheme,

Website: www.mhra.gov.uk/yellowcard

By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Oxaliplatin

Keep this medicine out of the sight and reach of children.

Store below 25°C. Do not refrigerate or freeze. Store in the original package in order to protect from light.

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

Do not use this medicine if you notice that the solution is not clear and free of particles.

When the infusion has finished, any remaining Oxaliplatin will be disposed of carefully by the doctor or nurse. Oxaliplatin should not come into contact with the eyes or skin. If there is any accidental spillage, tell the doctor or nurse immediately.

Common (may affect up to 1 in 10 people): Runny nose (rhinitis).

Upper respiratory tract infection. Dehydration.

Depression, sleeplessness.

Dizziness.

Swelling of the nerves to the muscles. Rigidity, intolerance of bright light and headache (meningism).

Inflammation of the conjunctiva, abnormal vision.

Abnormal bleeding, blood in the urine/stools. Blood clots, usually in the leg, which can cause pain, swelling or redness.

Blood clots in the lungs, which can cause chest pain and breathing difficulties. Flushing.

Hiccups, chest pain.

Indigestion and heart burn.

Flaking skin, skin rash, increased sweating and nail disorders.

Joint pain and bone pain.

Pain on passing urine and changes in the frequency of urination.

Alteration in blood test which measures the kidney function.

Weight decrease.

Tightness of the chest caused by cramp of the respiratory tract muscles (bronchospasm). Decrease in blood pressure.

Shock (strong blood pressure drop, paleness, restlessness, rapid heart rate, moist skin, decreased consciousness) caused by a sudden vascular dilatation as a result of a severe hypersensitivity reaction to certain substances (anaphylactic shock).

• Swelling of hands, feet, ankles, face, lips, mouth or throat which may cause difficulties in swallowing or breathing (angioedema).

Special precautions for administration

-    DO NOT use injection equipment containing aluminium.

-    DO NOT administer undiluted.

-    Only glucose 5 % (50 mg/ml) infusion solution is to be used as a diluent.

DO NOT dilute for infusion with sodium chloride or chloride containing solutions.

-    DO NOT mix with any other medicinal products in the same infusion bag or administer simultaneously by the same infusion line.

-    DO NOT mix with alkaline medicinal products or solutions, in particular 5 fluorouracil, folinic acid preparations containing trometamol as an excipient and trometamol salts of others active substances. Alkaline medicinal products or solutions will adversely affect the stability of oxaliplatin.

Instruction for use with folinic acid (FA) (as calcium folinate or disodium folinate)

Oxaliplatin 85 mg/m² intravenous infusion in 250 to 500 ml of glucose 5 % (50 mg/ml) solution is given at the same time as folinic acid (FA) intravenous infusion in glucose 5 % solution, over 2 to 6 hours, using a Y-line placed immediately before the site of infusion.

These two medicinal products should not be combined in the same infusion bag. Folinic acid (FA) must not contain trometamol as an excipient and must only be diluted using isotonic glucose 5 % solution, never in alkaline solutions or sodium chloride or chloride containing solutions.

Instruction for use with 5 fluorouracil (5 FU) Oxaliplatin should always be administered before fluoropyrimidines - i.e. 5 fluorouracil (5 FU).

After oxaliplatin administration, flush the line and then administer 5 fluorouracil (5 FU).

For additional information on medicinal products combined with oxaliplatin, see the corresponding manufacturer's summary of product characteristics.

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 protect the environment.

6. Contents of the pack and other information

What Oxaliplatin contains

•    The active substance is oxaliplatin. One millilitre of the concentrate for solution for infusion contains 5 mg oxaliplatin.

•    The other ingredients are lactose monohydrate and water for injection.

What Oxaliplatin looks like and contents of the pack

Oxaliplatin concentrate for solution for infusion is a clear, colourless to pale yellow solution, free from visible particles.

Pack sizes:

1 x 10 ml vial containing 50 mg of oxaliplatin 1 x 20 ml vial containing 100 mg of oxaliplatin

I    x 40 ml vial containing 200 mg of oxaliplatin Not all pack sizes may be marketed.

Marketing Authorisation Holder

Aptil Pharma Limited,

9th Floor, C.P.House, 97-107 Uxbridge Road, Ealing, London W5 5TL

Manufacturer

S.C. Sindan-Pharma S.R.L,

II    Ion Mihalache Blvd, 011171 Bucharest, Romania Or

Actavis Italy S.p.A.

Via Pasteur 10, 20014 Nerviano (Milan), Italy This leaflet was last revised in 05/2014

Dilution for intravenous infusion

Withdraw the required amount of concentrate from the vial(s) and then dilute with 250 ml to 500 ml of a 5% glucose solution to give an oxaliplatin concentration between not less than 0.2 mg/ml and 0.7 mg/ml. The physico-chemical stability of oxaliplatin has been demonstrated for this concentration range.

Administer by intravenous infusion.

After dilution in 5% glucose solution, chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C and for 6 hours at 25°C. From a microbiological point of view, this infusion preparation should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

Inspect visually prior to use. Only clear solutions without particles should be used.

The medicinal product is for single use only. Any unused infusion solution should be discarded.

NEVER use sodium chloride solution or chloride containing solutions for either reconstitution or dilution.

The compatibility of Oxaliplatin solution for infusion has been tested with representative, PVC-based, administrative sets.

Infusion

The administration of oxaliplatin does not require prehydration.

Oxaliplatin diluted in 250 to 500 ml of a 5% glucose solution to give a concentration not less than 0.2 mg/ml must be infused either by peripheral vein or central venous line over 2 to 6 hours. When oxaliplatin is administered with 5-fluorouracil, the oxaliplatin infusion must precede the administration of 5-fluorouracil.

Disposal

Remnants of the medicinal product as well as all materials that have been used for dilution and administration must be destroyed according to standard procedures applicable to cytotoxic agents in accordance with local requirements related to the disposal of hazardous waste.

N. 000000000.0

N. 000000000.0

LOXA5Y-02