Xilaz 50 mg/10 ml/100 mg/20 ml/200 mg/40 ml Solution

The active ingredient of XILAZ is oxaliplatin. XILAZ is an antineoplastic or anticancer medicine that contains oxaliplatin, which is a medicine which has platinum in its chemical structure. It is used to treat cancer of the large bowel (colon and rectum). XILAZ is used in combination with other anticancer medicines called 5-fluorouracil (5-FU) and folinic acid. XILAZ has to be dissolved and made into a solution before it can be injected into a vein.

XILAZ should not be administered to you:

• if you are allergic to oxaliplatin or any of the other ingredients of this medicine (listed in section 6).
• if you are breastfeeding.
• if you already have a reduced number of blood cells.
• if you already have tingling and numbness in the fingers and/or toes, and have difficulty performing delicate tasks, such as buttoning clothes (a sign of peripheral nerve damage).
• if you have severe kidney problems.

Warnings and precautions

XILAZ may only be administered to you under the supervision of a doctor, who specialised in oncology and has the facilities for regular monitoring, during and after therapy. Special care with XILAZ should be taken:

• If you have ever suffered an allergic reaction to platinum-containing medicines such as carboplatin, cisplatin. Allergic reactions can occur during any oxaliplatin infusion.
• If you have a kidney disease or kidney problems. You may need additional monitoring and a different dose.
• If you have any liver problems or abnormal liver function test results during your treatment.
• If you have or had heart disorders such as an abnormal electrical signal called prolongation of the QT interval, an irregular heartbeat, or a family history of heart problems.

If any of the following applies to you at any time, tell your healthcare provider immediately. Your healthcare provider may need to treat you for these events. Your healthcare provider may need to reduce the dose of XILAZ, or delay or stop your treatment with XILAZ:

• If you have an unpleasant sensation in the throat, in particular when swallowing, and have a sensation of shortness of breath, during the treatment.
• If you have nerve problems in your hands or feet, such as numbness or tingling, or decreased sensations in your hands or feet.
• If you have headache, altered mental functioning, seizures and abnormal vision from blurriness to vision loss. It may influence your ability to drive and use machines (see Driving and using machinery) and your doctor may decide to do additional brain imaging tests.
• If you feel or are sick – nausea (feel sick) or vomiting (being sick).
• If you have severe diarrhoea.

You will not be expected to give yourself XILAZ. XILAZ will be administered to you under the direction of a doctor specialised in oncology (cancer treatment). XILAZ is intended only for adults and is for single use only.

How much to receive:

• Your doctor will work out your dose of XILAZ. This depends on your height and weight (body surface area).
• The usual dose is 85 mg/m2 of body surface area. You will receive XILAZ by intravenous infusion (infusion into a vein) over a 2 to 6-hour period.
• The dose you receive will also depend on results of blood tests and whether you have previously experienced side effects with XILAZ.

Method and route of administration

• XILAZ will be prescribed for you by a specialist in cancer treatment.
• You will be treated by a healthcare professional, who will have made up the required dose of XILAZ.
• XILAZ is given by slow injection into one of your veins (an intravenous infusion) over a 2 to 6-hour period.
• XILAZ will be given to you at the same time as folinic acid and before the infusion of 5-fluorouracil.
• To prevent the onset of nausea and vomiting, your doctor may prescribe an additional treatment.

Frequency of administration

You should usually receive your infusion once every 2 weeks.

Duration of treatment

The duration of the treatment will be determined by your doctor. Your treatment will last a maximum of 6 months when used after complete removal of your tumour.

While you are being given XILAZ and between each treatment cycle. Things you must do:

• The needle must remain in the vein while the medicine 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.
• Avoid cold foods and drinks and cover skin prior to exposure to cold during or within 48 hours following being given XILAZ, since neurological effects may be brought on or worsened by exposure to cold.

XILAZ can have side effects. Not all side effects reported for XILAZ are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking XILAZ, please consult your healthcare provider for advice.

If any of the following happens, stop taking XILAZ and tell your doctor immediately or go to the casualty department at your nearest hospital:

• Swelling of your hands, feet, ankles, face, lips, mouth or throat, which may cause difficulty in swallowing or breathing.
• Skin rash or itching.
• Fainting.
• Yellowing of your skin and eyes (also called jaundice).

These are all very serious side effects. If you have them, you may have had a serious reaction to XILAZ. You may need urgent medical attention or hospitalisation.

Tell your doctor immediately if you notice any of the following:

Frequent side effects:

• XILAZ can affect the nerves (peripheral 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. These effects are often triggered by exposure 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 resolve themselves completely there is a possibility of persistent symptoms of peripheral sensory neuropathy 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 (movement of lowering your chin down to your chest).
• XILAZ 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.
• XILAZ may cause diarrhoea, mild nausea (feeling sick) and vomiting (being sick); however, medication to prevent the sickness is usually given to you by your doctor before treatment and maybe continued after treatment.
• XILAZ causes temporary reduction in the number of blood cells. The reduction of red cells may cause anaemia (a reduction of red cells), abnormal bleeding or bruising (due to a reduction in platelets). The reduction in white blood cells may make you prone to infections. Your doctor will take blood to check that you have sufficient blood cells before you start treatment and before each subsequent course.
• Sensation of discomfort close to or at the injection site during the infusion, fever, rigors (tremors), mild or severe tiredness, body pain, weight changes, loss or lack of appetite, taste disorders, constipation, headache, back pain, swelling of the nerves to your muscles, neck stiffness, abnormal tongue sensation possibly altering speech, stomatitis/mucositis (sore lips or mouth ulcers).
• Stomach pain, abnormal bleeding including nose bleeds, coughing, difficulty in breathing, allergic reactions, skin rash which may be red and itchy, mild hair loss (alopecia), alteration in blood tests including those relating to abnormalities in liver function, infection due to a reduction in white blood cells, serious infection of the blood in addition to a reduction in white blood cells (neutropenic sepsis), which may be fatal, reduction in white blood cells accompanied by fever >38.3 °C or a prolonged fever >38 °C for more than one hour (febrile neutropenia), indigestion and heart burn, hiccups, flushing, dizziness, increased sweating and nail disorders, flaking skin, chest pain, lung disorders and runny nose, joint pain and bone pain, pain on passing urine and changes in kidney function, changes of frequency of urination, dehydration, blood in the urine/stools, swelling of the veins, clots in the lung, high blood pressure, depression and insomnia (inability to fall asleep), conjunctivitis (eye infection) and visual problems, decreased levels of calcium in the blood.

These are all serious side effects. You may need urgent medical attention.

Your doctor, nurse or pharmacist is responsible for storing XILAZ. STORE ALL MEDICINES OUT OF REACH OF CHILDREN. Store at or below 25 °C. Do not freeze. Keep the vial in the outer carton in order to protect from light. Protect from moisture. Do not store in a bathroom. Do not use after the expiry date stated on the label.

Infusion preparation: If not used immediately, XILAZ should be stored at or between 2 °C to 8 °C for not longer than 24 hours. For single use only, any unused solution should be discarded. When the infusion has finished, XILAZ will be disposed of carefully by the doctor or nurse. Return all unused medicine to your pharmacist. Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets).