Paclitaxel 6 mg/ml concentrate for solution for infusion

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, or pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Paclitaxel Injection is and what it is used for
2. What you need to know before you use Paclitaxel Injection
3. How to take Paclitaxel Injection
4. Possible side effects
5. How to store Paclitaxel Injection
6. Contents of the pack and other information

• as first therapy (after initial surgery in combination with the platinum-containing medicine cisplatin).
• after standard platinum-containing medicines have been tried but did not work.

• as first therapy for advanced disease or disease which has spread to other parts of the body (metastatic disease). Paclitaxel Injection is either combined with an anthracycline (e.g. doxorubicin) or with a medicine called trastuzumab (for patients for whom anthracycline is not suitable and whose cancer cells have a protein on their surface called HER 2, see package leaflet of trastuzumab).
• after initial surgery following treatment with anthracycline and cyclophosphamide (AC) as an additional treatment.
• as a second-line treatment for patients who have not responded to standard treatments using anthracyclines, or for whom such treatment should not be used.

• in combination with cisplatin, when surgery and/or radiation therapy aren’t suitable.

• where another treatment (i.e. liposomal anthracyclines) has been tried but did not work.

• if you are allergic (hypersensitive) to paclitaxel or any of the other ingredients of this medicine listed in section 6 especially polyoxyethylated 35 castor oil (macrogolglycerol ricinoleate 35);
• if you are breast-feeding;
• if you have too few white blood cells count (baseline neutrophil counts < 1.5 x 10⁹/l - your doctor will advise you on this) in your blood. Your doctor will take blood samples to check this.
• if you have a serious and uncontrolled infection and Paclitaxel Injection is used to treat Kaposi’s sarcoma.

If any of these apply to you, talk to your doctor before starting treatment with Paclitaxel Injection.

Paclitaxel Injection is not recommended for use in children (under 18 years).

Talk to your doctor or pharmacist or nurse before using Paclitaxel Injection. Take special care with Paclitaxel Injection

To minimize allergic reactions, you will be given other medicines before you receive Paclitaxel Injection.

• If you experience severe allergic reactions (for example difficulty breathing, shortness of breath, chest tightness, drop in blood pressure, dizziness, light headedness, skin reactions such as rash or swelling).
• If you have fever, severe chills, sore throat or mouth ulcers (signs of bone marrow suppression).
• If you have numbness, tingling, pricking sensations, sensitivity to touch, or weakness of the arms and legs (signs of peripheral neuropathy); a dose reduction of Paclitaxel Injection may be necessary.
• If you have severe liver problems; in that case the use of Paclitaxel Injection is not recommended.
• If you have heart conduction problems.
• If you develop severe or persistent diarrhoea, with fever and stomach pain, during or shortly after the treatment with Paclitaxel Injection. Your colon could be inflamed (pseudomembranous colitis).
• If you had previous radiation to your chest (because it may increase the risk of lung inflammation).
• If you have a sore or red mouth (signs of mucositis) and are treated for Kaposi’s Sarcoma. You may need a lower dose.

Tell your doctor immediately if any of these apply to you.

Paclitaxel Injection should always be administered into veins. Administration of Paclitaxel Injection in the arteries can cause inflammation of the arteries, and you can suffer from pain, swelling, redness and heat.

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

Speak to your doctor when taking paclitaxel at the same time as any of the following:

• medicines for treating infections (i.e. antibiotics such erythromycin, rifampicin, etc.; ask your doctor, nurse or pharmacist if you are unsure whether the medicine you are taking is an antibiotic), and including medicines for treating fungal infections (e.g. ketoconazole)
• medicines used to help you stabilize your mood also sometimes referred to as anti-depressants (e.g. fluoxetine)
• medicines used to treat seizures (epilepsy) (e.g. carbamazepine, phenytoin)
• medicines used to help you lower blood lipid levels (e.g. gemfibrozil)
• medicine used for heartburn or stomach ulcers (e.g. cimetidine)
• medicines used to treat HIV and AIDS (e.g. ritonavir, saquinavir, indinavir, nelfinavir, efavirenz, nevirapine)
• a medicine called clopidogrel used to prevent blood clots.

Paclitaxel Injection is unaffected by food and drink.

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. Paclitaxel concentrate for solution for infusion must not be given if you are pregnant unless clearly advised. This medicine may cause birth defects, therefore, you must not become pregnant during treatment with paclitaxel and you and/or your partner must use an effective method of contraception whilst you are receiving treatment with paclitaxel and for six months after treatment has finished. If pregnancy occurs during treatment, or within the six months after treatment has finished, inform your doctor immediately.

Male patients treated with paclitaxel are advised not to father a child during and up to six months after treatment.

If you are breast-feeding, tell your doctor. It is not known if paclitaxel passes into breast milk. Because of the possibility of harm to the infant stop breast-feeding if you are taking Paclitaxel Injection. Do not restart breast-feeding unless your doctor has allowed you to.

Fertility

Paclitaxel may have an anti-fertility effect which could be irreversible. Male patients are therefore advised to seek advice on conservation of sperm prior to treatment.

Paclitaxel Injection may cause side effects such as tiredness (very common) and dizziness (common) that may affect your ability to drive and use machinery. If you experience these symptoms, do not drive or operate machinery until they have fully resolved. If you are given other medicines as part of your treatment, you should ask your doctor for advice on driving and using machines.

This medicine contains alcohol. Therefore it may be unwise to drive immediately after a course of treatment.

Paclitaxel Injection contains castor oil (about 50% polyethoxylated 35 caster oil) that may cause severe allergic reactions. If you are allergic to castor oil, talk to your doctor before you receive Paclitaxel Injection.

Paclitaxel Injection contains alcohol (49.7%v/v ethanol) – each millilitre of Paclitaxel Injection includes 0.392 g of alcohol. A Paclitaxel Injection dose of 300 mg/50 ml contains 20 g of alcohol, equivalent to 429 ml beer or 179 ml wine.

Harmful for those suffering from alcoholism. To be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease or epilepsy.

The amount of alcohol in this medicinal product may alter the effects of other medicines.

There is no known antidote for Paclitaxel Injection overdose. You will receive treatment of your symptoms.

If you think a dose has been missed let your doctor or nurse know.

A double of the dose should not be given if a dose has been forgotten.

Your doctor will decide when to stop treatment with paclitaxel.

• If you have fever, severe chills, sore throat or mouth ulcers (signs of bone marrow suppression).
• If you have numbness or weakness of the arms and legs (signs of peripheral neuropathy).
• If you develop severe or persistent diarrhoea, with fever and stomach pain.

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

• Minor allergic reactions such as flushing, rash, itching
• Infections: mainly upper respiratory infection, urinary tract infection
• Shortness of breath
• Sore throat or mouth ulcers, sore and red mouth, diarrhoea, feeling or being sick (nausea, vomiting)
• Loss of hair. When it happens, hair loss is pronounced (over 50%) in the majority of patients.
• Pain in the muscles, cramps, pain in the joints
• Fever, severe chills, headache, dizziness, tiredness, looking pale, bleeding, bruising more easily than normal
• Numbness, tingling or weakness in arms and legs (all symptoms of peripheral neuropathy)
• Tests may show: reduction of blood platelet count, white or red blood cells count, low blood pressure

Common (may affect up to 1 in 10 people):

• Temporary mild nail change and skin changes, reactions at injection sites (localised swelling, pain, and redness of the skin)
• Tests may show: slower heart rate, severe elevation in liver enzymes (alkaline phosphatase and AST - SGOT)

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

• Shock due to infections (known as 'septic shock')
• Palpitations, cardiac dysfunction (AV block), rapid beating of the heart, heart attack, respiratory distress
• Fatigue, sweating, fainting (syncope), significant allergic reactions, thrombophlebitis (inflammation of a vein caused by a blood clot), swelling of the face, lips, mouth, tongue or throat
• Back pain, chest pain, pain around hands and feet, chills, abdominal (tummy) pain
• Tests may show: severe elevation of bilirubin (jaundice), high blood pressure, and blood clot.

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

• Shortage of white blood cells with fever and increased risk of infection (febrile neutropenia)
• Affection of nerves with feeling of weakness in muscles of arms and legs (motor neuropathy)
• Shortness of breath, pulmonary embolism, lung fibrosis, interstitial pneumonia, dyspnoea, pleural effusion
• Bowel obstruction, bowel perforation, inflammation of colon (ischaemic colitis), inflammation of the pancreas (pancreatitis)
• Pruritus, rash, skin redness (erythema)
• Blood poisoning (sepsis), peritonitis
• Pyrexia, dehydration, asthenia, oedema, malaise
• Serious and potentially fatal hypersensitivity reactions (anaphylactic reactions)
• Tests may show: increase in blood creatinine indicating renal function impairment
• Heart failure

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

• Irregular rapid heart rhythm (atrial fibrillation, supraventricular tachycardia)
• Sudden disorder in blood forming cells (acute myeloid leukaemia, myelodysplastic syndrome)
• Optic nerve and/or visual disturbances (scintillating scotomata)
• Hearing loss or reduction (ototoxicity), ringing in the ears (tinnitus), vertigo
• Cough
• Blood clot in a blood vessel of abdomen and bowel (mesenteric thrombosis), inflammation of colon sometimes with persistent severe diarrhoea (pseudomembranous colitis, neutropenic colitis),
dropsy (ascites), oesophagitis, constipation.
• Serious hypersensitivity reactions including fever, skin redness, pain in joints and/or inflammation of the eye (Stevens-Johnson syndrome), local peeling of the skin (epidermal necrolysis),
redness with irregular red (exudative) spots (erythema multiforme), inflammation of the skin with blisters and peeling (exfoliative dermatitis), urticaria, loose nails (patients on therapy should wear sun protection on hands and feet).
• Loss of appetite (anorexia).
• Serious and potentially fatal hypersensitivity reactions with shock (anaphylactic shock).
• Disturbed liver function (hepatic necrosis, hepatic encephalopathy (both with reported cases of fatal outcome))
• Confusional state.

Not known (the frequency cannot be determined based on the available data):

• Hardending/thickening of the skin (sclerodema)
• Tumour lysis syndrome
• Macular oedema, photopsia, vitreous floaters
• Phlebitis
• Systemic lupus erythematosus
• Disseminated intravascular coagulation, or "DIC," has been reported. This concerns a serious condition that makes people bleed too easily, get blood clots too easily, or both.

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

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

This medicinal product does not require any special temperature storage conditions. Store in the original package in order to protect from light.

From a microbiological point of view, once opened the product may be stored for a maximum of 28 days at 25°C. Other in-use storage times and conditions are the responsibility of the user.

From a microbiological point of view, the diluted product should be used immediately. If not used immediately, store in a refrigerator (2 to 8°C) for no more than 24 hours, unless dilution has taken place in controlled and validated aseptic conditions. For more details on the stability after dilution, see the section for health-care professionals.

Do not use if you notice a cloudy solution or an insoluble precipitate.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer used. These measures will help to protect the environment.

• The active substance is Paclitaxel.
• Each ml of concentrate for solution for infusion contains 6 mg of paclitaxel.
• Each vial contains 5, 16.7 and 50 ml (equivalent to 30, 100 and 300 mg of paclitaxel respectively).
• The other ingredients are polyoxyl 35 castor oil (macrogolglycerol ricinoleate 35) and ethanol.

Paclitaxel Injection is a clear colourless to slightly yellow viscous solution.

It is available in vials containing 5 ml, 16.7 ml and 50 ml of concentrate for solution for infusion.

Not all pack sizes may be marketed.