Paclitaxel 6 Mg/Ml Concentrate For Solution For Infusion
PACKAGE LEAFLET: INFORMATION FOR THE USER
PACLITAXEL 6 mg/ ml
CONCENTRATE FOR SOLUTION FOR INFUSION (Paclitaxel)
Read all of this leaflet carefully before you start using 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 Paclitaxel is and what it is used for
2. Before you use Paclitaxel
3. How to use Paclitaxel
4. Possible side effects
5. How to store Paclitaxel
6. Further information
1. WHAT PACLITAXEL IS AND WHAT IT IS USED FOR
The name of your medicine is Paclitaxel 6 mg/ ml concentrate for solution for infusion. Paclitaxel is available as vials containing 30 mg, 100 mg, or 300 mg paclitaxel in a 6 mg/ml solution which has to be diluted before being given to you.
Paclitaxel is used to treat:
Ovarian cancer: either as initial therapy in combination with the platinum-containing medicine, cisplatin, or as a second-line treatment when other platinum-containing treatments have not worked. Breast cancer: As initial therapy either in combination with a medicine belonging to the group known as anthracyclines (i.e. doxorubicin, epirubicin, daunorubicin) for patients that are suitable, or with a medicine called trastuzumab. As adjuvant therapy following treatment with anthracycline and cyclophosphamide (AC). On its own in patients who have not responded to standard treatments using anthracyclines, or for whom such treatment should not be used.
Non-small cell lung cancer: in combination with cisplatin, in patients who are not candidates for potentially curative surgery and/or radiotherapy.
AIDs-related Kaposi’s sarcoma: where other treatments i.e. liposomal anthracyclines have not worked.
Do not use PACLITAXEL
if you have shown signs of hypersensitivity (severe) allergy to paclitaxel or any other ingredients on previous occasions
if you are pregnant or breastfeeding
if the number of white blood cells (neutrophils) is too low. This is measured by a doctor or nurse.
in patients with Kaposi's sarcoma, this product should not be used if you have a serious uncontrolled infection.
if you are unsure about anything, ask your doctor or pharmacist.
Take special care with PACLITAXEL
- if you have heart disease or liver problems
- when diarrhoea occurs during or shortly after the treatment with paclitaxel (pseudomenbranous colitis)
- if you have Kaposi's sarcoma and severe inflammation of the mucous membrane (membranes lining the passages of the body that open to the outside) occurs
- if you have had nerve problems in your hands or in feet, such as numbness, tingling or burning (peripheral neuropathy)
- if you have blood problems, such as changes in the number of some cells
- if paclitaxel is given to you in combination with radiotherapy of the lung.
It is important to tell the doctor about any of your medical conditions, whether they are included in the
above lists or not. Please tell your doctor if you are taking, or have recently taken, any other medicines,
including ones that are not prescribed for you.
Using other medicines
- please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription
- when used in combination, paclitaxel should be given before cisplatin
- paclitaxel should be given 24 hours after doxorubicin
- special care should be observed if you are taking medicines which influence the metabolism of paclitaxel such as: erythromycin, fluoxetine, gemfibrozil, rifampicin, carbamazepine, phenytoin, phenobarbital, efavirenz, and nevirapine and for HIV patients receiving protease inhibitors
(ritonavir, nelfinavir) as concomitant therapy
if you go into hospital, let the medical staff know you are taking paclitaxel.
Pregnancy and breast-feeding Pregnancy
Do not use paclitaxel if you think you are pregnant or you are trying to become pregnant. Paclitaxel can damage the unborn baby.
Pregnancy must be avoided and both partners should use reliable contraception during treatment with paclitaxel and for at least 6 month after treatment. Tell your doctor immediately if you do become pregnant.
Breast-feeding
Paclitaxel should not be used when you are breast-feeding. You should stop breast feeding while you are being treated with paclitaxel. Do not restart breast feeding until your doctor tells you it is safe to do so.
Ask your doctor or pharmacist for advice before taking any medicine
Driving and using machines
There is no reason why you cannot continue driving between courses of paclitaxel but you should remember that this medicine contains some alcohol and it may be unwise to drive or use machines immediately after a course of treatment. As in all cases, you should not drive or use machines if you feel dizzy or light-headed.
Important Information about PACLITAXEL
This medicinal product contains polyoxyl castor oil which may cause severe allergic reactions.
It also contains 49.7% vol ethanol (alcohol), i.e. up to 21 g (19.5 g ) per average dose, equivalent to 740 ml (687 ml) of a 3.5% vol beer, 190 ml (176.4) of a 14% vol wine per dose. This may be harmful to patients suffering from alcoholism.
It should also be taken into account when considering using this medicine in children and high risk groups such as those with liver disease or epilepsy. The alcohol in this medicine may also affect the way other medicines work.
3. HOW TO USE PACLITAXEL
If you are prescribed Paclitaxel, it will be given to you by doctors or nurses experienced in giving chemotherapy.
Paclitaxel will normally be given to you by a doctor or a nurse through a drip (infusion) into a vein. Your doctor will decide what dose to give and the number of days treatment you will receive depending upon your condition. The dose you receive will be based on your body surface area and the result of blood tests carried out before treatment. The usual dose is 175mg/m2, body surface area, given over 3 hours followed by the cisplatin for ovarian and lung cancer. You will also receive cisplatin after paclitaxel if you are being treated for lung cancer. For breast cancer recommended dose is 175mg/m2 administered over 3 hours following therapy with anthracycline and cyclophosphamide. When used in combination with doxorubicin paclitaxel will be administered 24 hours after doxorubicin at a dose of 220 mg/m2. The timing of paclitaxel administration after trastuzumab will depend on how you react to this medicine.
Your dose will be carefully calculated by the doctors, so overdose is unlikely. However, if too much is given this is likely to make the usual side effects worse, particularly blood disorders, numbness/tingling especially of the arms, hands, legs or feet and stomach upsets including vomiting and diarrhoea.
4. POSSIBLE SIDE EFFECTS
Like all medicines, paclitaxel can cause side effects, although not everybody gets them.
The following side effects may occur after treatment with Paclitaxel concentrate for solution for infusion.
The most frequent side effects are hair loss and decreased blood cell count. Your hair grows back and your blood cell count returns to normal after you have finished your paclitaxel treatment.
If any of the following happen, tell the doctor immediately
• any abnormal bruising, bleeding, or signs of infections such as a sore throat and high temperature
• severe allergic reaction - you may experience a sudden itchy rash (hives), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), and you may feel you are going to faint
• breathlessness and dry cough due to damage to the lung
• reaction at the injection site, e.g. local swelling, pain, redness.
Other known side effects are
Very common (affects more than 1 out of 10 people):
• an effect on the bone marrow, which can cause decreased numbers of some blood cells. This may cause anaemia. It can also lead to infections, mainly urinary tract and upper respiratory tract infections with reported cases of fatal outcome pain, redness or swelling at the injection site
• decreased number of blood platelets and bleeding
• milder allergic (hypersensitivity) reactions, such as flushing and rash
• nerve problems affecting the hands and or feet (peripheral neuropathy), which can cause tingling feelings in the skin, numbness and/or pain
• low blood pressure
• feeling sick (nausea), being sick (vomiting) and diarrhoea
• hair loss
• muscle or joint pain
• inflammation of areas such as the lining of the mouth.
Common (affects more than l out of 100 people):
• slow heart beat (pulse)
• mild changes in nail and skin which soon disappear
• painful swelling and inflammation where the injection is given which may cause tissue hardening (occasionally cellulitis, thickening and scarring of the skin (skin fibrosis), death of skin cells(skin necrosis))
• changes in blood tests that check how the liver is working.
Uncommon (affects less than l out of 100 people):
• a state of shock resulting from blood poisoning
• serious allergic (hypersensitivity) reactions with e.g. decreased or increased blood pressure, swelling of the face, difficulty in breathing, skin rash, chills back pain, chest pain, fast heart beat, abdominal pain, pain in arms and legs, sweating
• serious heart problems like heart muscle degeneration (cardiomyopathy), serious changes in your heart's rhythm even with fainting heart attack
• increased blood pressure
• blood clot (thrombosis), inflammation of a vein in connection with blood clots.
• yellowing of the skin (jaundice).
Rare (affects less than 1 out of 1,000 people):
• pneumonia
• reduced number of a type of white blood cell with fever (febrile neutropenia)
• serious allergic (anaphylactic) reaction. Effects on the nerves, which can cause muscle weakness in the arms and legs
• difficulty in breathing, fluid on the lungs, inflammation of the lungs and other lung problems (lung fibrosis, pulmonary embolism), markedly impaired pulmonary function (respiratory failure)
• itching, rash and reddened skin
• weakness, high temperature (fever), dehydration, oedema, feeling ill
• blood poisoning
• blockage of the intestines, penetration of the wall of the small intestine or large bowel, inflammation of the lining of the belly (peritoneum), inflammation of the intestine caused by inadequate blood supply, inflammation of the pancreas
• increased level of the substance creatinine in the blood.
Very rare (occurs with less than l out of 10,000 of the users):
• acute leukaemia (a type of blood cancer), myelodysplastic syndrome (a diverse collection of blood cell disorders)
• life threatening allergic reaction (anaphylactic shock)
• loss of appetite, shock due to decreased blood pressure, cough
• effects on the nervous system which can cause paralysis of the intestines (gut) and a decrease in blood pressure when standing up or sitting up from a lying down position
• fits (epileptic seizures), cramps, confusion, dizziness, alteration in brain function or structure, headache, loss of the ability to coordinate muscular movement
• problems with eyesight and visual disturbances, usually in patients given larger doses
• reduction or loss of hearing, ringing in the ears (tinnitus), vertigo
• abnormal heart rhythm (atrial fibrillation, supraventricular tachycardia).
• a blood clot in the mesenteric artery, pseudomembranous colitis (an infection
of the colon caused by specific bacteria), inflammation of the oesophagus constipation, collection of fluid in the abdomen (belly).
• severe inflammation of the large bowel presenting with fever, watery or bloody diarrhoea, and crampy abdominal pain (neutropenic colitis)
• death of liver cells (necrosis of the liver), confusion and other effects (hepatic encephalopathy) caused by changes in the way the liver works (both with reported causes of fatal outcome)
• hives (urticaria) scaling and shedding of the skin usually accompanied by redness
• severe inflammatory eruption of the skin and mucous membranes (severity ranging
from erythema multiform to Stevens-Johnson syndrome to the most serious toxic epidermal necrolysis (TEN)).
• disintegration of nails. Hands and feet should be protected against sunshine during the treatment time.
If any of the side effects gets serious, or if you notice any side effects not mentioned in this leaflet, please tell your doctor or pharmacist.
5. HOW TO STORE PACLITAXEL
Keep out of the reach and sight of children.
This medicine should not be used after the expiry date which is stated on the vial label and carton after “EXP”. The expiry date refers to the last day of that month.
Your medication should not be stored above 25°C. The vials should be kept in the original package in order to protect from light.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
6. FURTHER INFORMATION
What PACLITAXEL Concentrate for solution for infusion contains
The active substance is paclitaxel.
The other ingredients are citric acid anhydrous, ethanol and polyoxyl castor oil.
Each ml contains 6 mg of the active ingredient paclitaxel.
Remember: This medicine is for you. Only a doctor can prescribe it for you. Never give it to someone else. It may harm them even if their symptoms are the same as yours.
What PACLITAXEL Concentrate for solution for infusion looks like and contents of the pack
Paclitaxel 6 mg/ ml concentrate for solution for infusion is a clear colourless viscous solution and is packed into type 1 flint glass vials.
Pack Sizes:
1 x 5 ml vial (30mg/5ml)
1 x 20 ml vial (l00mg/16.7ml)
1 x 50 ml vial (300mg/50ml)
The vials are packaged individually in a carton. Boxes containing 10 cartons are also available. Not all presentations may be marketed.
Marketing Authorisation Holder:
Cipla (EU) Limited, Hillbrow House, Hillbrow Road, Esher, Surrey, KT10 9NW Manufacturer:
Cipla (EU) Limited, 4th Floor, 1 Kingdom Street, London, W2 6BY, United Kingdom This leaflet was last revised in August 2014
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INFORMATION FOR HEALTH PROFESSIONALS
Below is a summary of information to assist in the administration of PACLITAXEL. You should be experienced in the handling and use of cytotoxic agents and be familiar with the SPC for PACLITAXEL.
Reference should be made to guidelines on the safe handling of antineoplastic agents.
Handling: as with all antineoplastic agents, caution should be exercised when handling Paclitaxel Concentrate for solution for infusion. Dilution should be carried out under aseptic conditions by trained personnel in a designated area. Adequate protective gloves should be worn. Precautions should be taken to avoid contact with the skin and mucous membranes. In the event of contact with the skin, the area should be washed with soap and water. Following topical exposure, tingling, burning and redness have been observed. In the event of contact with the mucous membranes, these should be flushed thoroughly with water. Upon inhalation, dyspnoea, chest pain, burning throat and nausea have been reported.
If unopened vials are refrigerated, a precipitate may form that redissolves with little or no agitation upon reaching room temperature. Product quality is not affected. If the solution remains cloudy or if an insoluble precipitate is noted, the vial should be discarded.
Following multiple needle entries and product withdrawals, the vials maintain microbial, chemical and physical stability for up to 28 days at 25°C. Other in-use storage times and conditions are the responsibility of the user.
The Chemo Dispensing Pin device or similar devices with spikes should not be used since they can cause the vial stopper to collapse, resulting in loss of sterile integrity.
Preparation, storage and administration should be carried out in non-PVC containing equipment.
Preparation for IV administration: prior to infusion, Paclitaxel must be diluted using aseptic techniques in 0.9% Sodium Chloride Injection, or 5% Dextrose Injection, or 5% Dextrose and 0.9% Sodium Chloride Injection, or 5% Dextrose in Ringer's Injection, to a final concentration of 0.3 to 1.2 mg/ml.
Chemical and physical in-use stability of the solution prepared for infusion has been demonstrated at 2°C to 8°C and at 25°C for 7 days when diluted in 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium chloride Injection, 5% Dextrose in Ringer's Injection and for 14 days when diluted in 0.9% Sodium chloride Injection.
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. After dilution the solution is for single use only.
Upon preparation, solutions may show haziness, which is attributed to the formulation vehicle, and is not removed by filtration. Paclitaxel should be administered through an in line filter with a microporous membrane < 0.22 pm. No significant losses in potency have been noted following simulated delivery of the solution through IV tubing containing an in line filter.
There have been rare reports of precipitation during Paclitaxel infusions, usually towards the end of a 24hr infusion period. Although the cause of this precipitation has not been elucidated, it is probably linked to the supersaturation of the diluted solution. To reduce the precipitation risk, Paclitaxel should be used as soon as possible after dilution and excessive agitation, vibration or shaking should be avoided.
The infusion sets should be flushed thoroughly before use. During infusion, the appearance of the solution should be regularly inspected and the infusion should be stopped if precipitation is present.
Disposal: all items used for preparation, administration or otherwise coming into contact with paclitaxel should undergo disposal according to local guidelines for the handling of cytotoxic compounds.
Administration and dosage
All patients should be premedicated with corticosteroids, antihistamines and H2 antagonists prior to administration. The diluted PACLITAXEL infusion should be administered using non-PVC containing equipment through an in-line filter with a microporous membrane <0.22 pm.
The recommended doses for the intravenous infusion of PACLITAXEL are as follows:
• First-line ovarian cancer:
135 mg/m2 over 24 hours, followed by cisplatin 75 mg/m2; or 175 mg/m2 over 3 hours followed by cisplatin 75 mg/m2;
• Second-line ovarian or breast cancer:
175 mg/m2 over 3 hours;
• Adjuvant breast cancer:
175 mg/m2 over 3 hours; following anthracycline and cyclophosphamide (AC) therapy;
• First-line breast cancer:
220 mg/m2 over 3 hours, 24 hours after doxorubicin (50 mg/m2),
175 mg/m2 over 3 hours, after trastuzumab (see trastuzumab SPC);
• Non-small cell lung cancer:
175 mg/m2 over 3 hours followed by cisplatin 80 mg/m2;
• AIDs related Kaposi's sarcoma:
100 mg/m2 over 3 hours.
There should be a 3-week interval between courses, dependent upon patient tolerance.
PACLITAXEL should not be readministered until the neutrophil count is >1.5x109/L and the platelet count is >100x109/L. Patients experiencing severe neutropenia or severe peripheral neuropathy should be subject to a dose reduction of 20% for subsequent courses.
Storage
After opening before dilution the vials should not be stored above 25°C and should be stored in the original package to protect from light. If refrigerated, a precipitate may form which redissolves with little or no agitation upon reaching room temperature. Product quality is not affected. If the solution remains cloudy, or an insoluble precipitate is noted, the vial should be discarded. Freezing does not adversely affect the product.