Paclitaxel 6 Mg/Ml Concentrate For Solution For Infusion
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PIL FOR
PACLITAXEL 6mg/ml CONCENTRATE FOR SOLUTION FOR INFUSION
PACKAGE LEAFLET: INFORMATION FOR THE USER
Paclitaxel 6mg/ml Concentrate for Solution for Infusion
Paclitaxel
Read all of this leaflet carefully before you start using 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, ask your doctor or pharmacist.
- 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 or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.
What is in this leaflet
1. What Paclitaxel is and what it is used for
2. What you need to know before you use Paclitaxel
3. How to use Paclitaxel
4. Possible side-effects
5. How to store Paclitaxel
6. Contents of the pack and other information
1. WHAT PACLITAXEL IS AND WHAT IT IS USED FOR
Paclitaxel is an anti-cancer medicine. It is used in the treatment of ovarian cancer, breast cancer and non-small cell lung cancer, when surgery and/or radiation therapy cannot be used and in treatment of patients with advanced AIDS-related Kaposi’s sarcoma.
2. WHAT YOU NEED TO KNOW BEFORE YOU USE PACLITAXEL Do not use paclitaxel:
- if you are allergic to paclitaxel, macrogolglycerol ricinoleate or any of the other ingredients of this medicine (listed in section 6)
- if you are breast-feeding
- if your levels of white blood cells (neutrophiles) or blood platelets are low
- if you suffer from Kaposi's sarcoma and at the same time from serious, uncontrolled infections.
PACLITAXEL 6mg/ml CONCENTRATE FOR SOLUTION FOR INFUSION
Warnings and Precautions
Talk to your doctor or pharmacist before taking Paclitaxel
Tell your doctor:
- if you notice marked allergic reactions (e.g. shortness of breath, low blood pressure, swelling or rash)
- if there are signs that your body does not produce enough blood cells (e.g. you may be more prone to bleeding or infections)
- if you suffer from a severe heart disease with a low heart rate and high or low blood pressure
- if you suffer from a disease of peripheral nerves (e.g. tingling or numbness in hands or feet)
- if you know that your liver function is impaired
- if you suffer from Kaposi's sarcoma and severe mucositis, because you should receive a reduced dosage (25%)
- if you are also receiving radiotherapy of your lung
- if you develop severe, prolonged or bloody diarrhoea (symptoms of a pseudomembranous colitis) during or after treatment with Paclitaxel.
Children and adolescents
•Paclitaxel is not recommended for use in children below 18 years due to lack of data on safety and efficacy.
Other medicines and Paclitaxel
Tell your doctor if you are taking, have recently taken or might take any other medicines.
The amount of alcohol in this medicine may alter the effects of other medicines.
Cisplatin:
- may increase kidney damage
- may, when given after paclitaxel, profoundly reduce blood cell numbers.
Caution should be exercised when paclitaxel is administered at the same time with medicines that influence removal of paclitaxel from the body (by the liver, e.g. rifampicin, carbamazepine, phenytoin, phenobarbital, efavirenz, nevirapine, erythromycin, fluoxetine, gemfibrozil).
Medicines for treating AIDS (protease inhibitors): paclitaxel should be given with caution. Doxorubicin: Paclitaxel should be given 24 hours after doxorubicin.
Taking cimetidine before paclitaxel does not influence removal of paclitaxel from the body. Using ketoconazol at the same time does not influence removal of paclitaxel from the body.
Pregnancy and breast feeding
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 6mg/ml CONCENTRATE FOR SOLUTION FOR INFUSION
Pregnancy
If there is a chance that you could become pregnant, use an effective and safe method of contraception during treatment. Paclitaxel should not be used during pregnancy unless clearly necessary.
Women and men of childbearing potential and / or their partners should use contraceptives for at least 6 months after treatment with paclitaxel.
Breast-feeding
Paclitaxel must not be given to you if you are breast-feeding, as paclitaxel might pass into breast milk and affect the baby. 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.
Fertility
Men should seek advice regarding cryoconservation of sperm prior to treatment with Paclitaxel because of the possibility of infertility.
Driving and using machines
The amount of alcohol in this medicine and some of the side-effects may impair your ability to drive or use machines.
Paclitaxel contains macrogolglycerol ricinoleate.
Macrogolglycerol ricinoleate may cause severe allergic reactions.
Paclitaxel contains ethanol (alcohol)
This medicinal product contains 49.9% v/v ethanol (alcohol), i.e. up to 25g per dose, equivalent to 500ml beer or 200ml 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.
3. HOW TO USE PACLITAXEL
Your doctor will decide about the dose of paclitaxel you will receive. This medicine can only be given by nursing staff under the supervision of a doctor with experience in cancer (cytostatic) treatment.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
PACLITAXEL 6mg/ml CONCENTRATE FOR SOLUTION FOR INFUSION
4. POSSIBLE SIDE-EFFECTS
Like all medicines, this medicine can cause side-effects, although not everybody gets them. You should wear sun protection on hands and feet for the duration of your treatment since your skin may be more sensitive to sunlight.
Serious side-effects:
If any of the following happen, tell your doctor immediately:
Very common (may affect more than 1 in 10 people):
- signs of infection, i.e. fever
Common (may affect up to 1 in 10 people):
- reactions at the injection site: with symptoms of swelling, pain, reddening, induration and occasionally inflammation and severe skin damage
Uncommon (may affect up to 1 in 100 people):
- marked allergic reactions requiring treatment with symptoms of low or high blood pressure; swelling of face, lips, tongue and/or throat; shortness of breath, generalized hives, chills; pain of the back, chest, belly and extremities; fast pulse, sweating; allergic shock (very rare)
- septic shock with symptoms of fever, chills, low blood pressure
- severe heart complications (e.g. heart muscle disease): with symptoms of fast or irregular pulse, fainting
- heart attack with symptoms of severe chest pains possibly radiating to jaw or arm, sweating, breathlessness and nausea
Very rare (may affect up to 1 in 10,000 people):
- severe skin diseases: with symptoms of blistering, reddening, detachment, necrosis, hives
- life-threatening allergic reactions (anaphylactic shock).
Not known (frequency cannot be estimated from the available data):
- tumour lysis syndrome (metabolic derangement produced by rapid tumour breakdown as a consequence of therapy.
- disseminated intravascular coagulation (excessive clotting or bleeding throughout your body)
Other side-effects:
Very common (may affect more than 1 in 10 people):
infections (mainly upper airways and urinary tract), reduced blood cell production (which may lead to not enough white and red blood cells and platelets), bleeding, mild allergic reactions (flush and rash), injury of peripheral nerves (leading for instance to tingling or numbness in hands and feet), low blood pressure, digestive tract side-effects (nausea, vomiting, diarrhoea, inflammation of the mucous membranes), hair loss (the majority of cases
PACLITAXEL 6mg/ml CONCENTRATE FOR SOLUTION FOR INFUSION
of hair loss happened less than one month after starting paclitaxel. When it happens, hair loss is pronounced (over 50%) in the majority of patients), joint or muscle pain.
Common (may affect up to 1 in 10 people):
low pulse, temporary and mild nail and skin changes, elevated blood values indicating problems with liver function (elevated AST, SGOT, alkaline phosphatase).
Uncommon (may affect up to 1 in 100 people):
high blood pressure, inflammation of blood veins, blood clots blocking veins, elevated levels of bile pigment in serum.
Rare (may affect up to 1 in 1000 people):
pneumonia, inflammation of the inner belly lining (peritonitis), blood-poisoning (sepsis), severe allergic reactions, nerve damage leading to weakness of the extremeties, shortness of breath, water in the lining around the lung, severe lung disorders (due to damage of lung tissue or reduced blood supply) and insufficient lung function, digestive tract side-effects (bowel obstruction and perforation, bowel inflammation due to reduced blood supply, inflammation of the pancreas), itch, rash, reddening, weakness and tiredness, dehydration, tissue swelling due to water uptake, malaise, elevated blood values indicating kidney injury (elevated creatinine), heart failure, fever accompanied by low white blood cell count (febrile netopenia).
Very rare (may affect up to 1 in 10,000 people):
leukaemia, blood disease due to production of immature cells, loss of appetite, confusion, nervous disorder leading to bowel obstruction and low blood pressure when standing up, epileptic attacks, seizures, brain disease, dizziness, headache, gait disturbances, visual disturbances, hearing damage and loss, noise in the ears, giddiness, heart rhythm disorders e.g. heart hurry, shock, cough, digestive tract side-effects (blood clots in bowel veins, severe bowel inflammation, inflammation of the gullet, constipation), water in the belly, severe liver disorder which may also affect brain function, and nail detachment.
Not known (frequency cannot be estimated from the available data):
- swelling of the macular (macular oedema), flashes of light (photopsia) or vitreous floaters,
- inflammation of a vein (phlebitis),
- hardening of the skin (scleroderma)
- chronic inflammatory connective tissue disorder (systemic lupus erythematosus)
Patients receiving concomitant radiotherapy
Combination with radiation therapy can cause lung inflammation with breathlessness. If you develop persistent cough, experience pain or difficulty breathing or become breathless you should seek medical attention.
Patients with AIDS-related Kaposi’s sarcoma
When patients were treated with paclitaxel, fever and increased serum values of bile pigment and other enzymes, indicating problems with liver function (bilirubin, alkaline phosphatase
PACLITAXEL 6mg/ml CONCENTRATE FOR SOLUTION FOR INFUSION
and AST (SGOT)), were observed very commonly (affects more than 1 user in 10), episodes of bleeding were observed commonly.
Reporting of side effects
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 the Yellow Card Scheme at: 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 PACLITAXEL
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the vial and outer carton after EXP. The expiry date refers to the last day of that month.
Do not freeze.
Your medicine is stored in a pharmacy and is prepared especially for you based on your doctor’s prescription by specialised staff.
6. CONTENTS OF THE PACK AND OTHER INFORMATION
What paclitaxel contains
The active substance is paclitaxel.
1 ml concentrate for solution for infusion contains 6 mg paclitaxel.
1 vial of 5ml contains 30mg paclitaxel.
1 vial of 16.7ml contains 100mg paclitaxel.
1 vial of 25ml contains 150mg paclitaxel.
1 vial of 50ml contains 300mg paclitaxel.
The other ingredients are macrogolglycerol ricinoleate, 49.9% v/v ethanol and citric acid anhydrous.
What paclitaxel looks like and contents of the pack
This medicine is a concentrate for solution for infusion. The concentrate is a clear, colourless or slightly yellow and viscous solution, which is filled in clear glass vials sealed with rubber stoppers.
The packages contain 1 vial of 5ml, 16.7ml, 25ml and 50ml, respectively.
Not all pack sizes may be marketed.
POM
PL 06831/0170 Paclitaxel 6mg/ml Concentrate for Solution for Infusion
Marketing Authorisation Holder
Genus Pharmaceuticals Limited
Linthwaite
Huddersfield
HD75QH
UK
PACLITAXEL 6mg/ml CONCENTRATE FOR SOLUTION FOR INFUSION
Manufacturer
cell pharm GmbH Feodor-Lynen-Str. 35 D-30625 Hannover Germany
This leaflet was last revised in 03/2015.
The following information is intended for medical or health care professionals only: The medicinal product is for single use only. Any unused solution should be discarded.
Handling:
As with all antineoplastic agents, caution should be exercised when handling paclitaxel. 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 or frozen, 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.
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 the loss of sterile integrity.
Preparation for intravenous administration:
Prior to infusion, paclitaxel must be diluted using aseptic techniques in 0.9% sodium chloride solution for infusion, or 5% glucose solution for infusion, or a mixture of 0.9% sodium chloride solution for infusion and 5% glucose solution for infusion, or Ringer’s solution for infusion containing 5% glucose, to a final concentration of 0.3 to 1.2 mg/ml.
Only clear solutions practically free from particles should be used.
For microbial, chemical and physical in-use stability of the diluted solutions see section “Shelf life”.
Upon preparation, solutions may show some 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 intravenous tubing containing an in-line filter.
PACLITAXEL 6mg/ml CONCENTRATE FOR SOLUTION FOR INFUSION
There have been rare reports of precipitation during paclitaxel infusions, usually towards the end of a 24 hour 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.
To minimize patient exposure to DEHP which may be leached from plasticized PVC infusion bags, sets, or other medical instruments, diluted paclitaxel solutions should be stored in non-PVC bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets. The use of filter devices (e.g. IVEX-2®) which incorporate short inlet and/or outlet plasticized PVC tubing has not resulted in any significant leaching of DEHP.
Shelf life:
Shelf life after opening:
The medicinal product should be diluted immediately after opening.
Shelf life after dilution:
Chemical and physical in-use stability of the solution prepared for infusion has been demonstrated:
- for 27 hours at 25°C and ambient lighting conditions, when diluted in 0.9% sodium chloride
solution for infusion, or 5% glucose solution for infusion
- for 24 hours at 25°C and ambient lighting conditions, when diluted in a mixture of 0.9%
sodium chloride solution for infusion and 5% glucose solution for infusion, or Ringer’s solution for infusion containing 5% glucose.
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, unless dilution has taken place in controlled and validated aseptic conditions.
Only clear solutions free from particles should be used.
Disposal:
Any unused product or waste material should be disposed of in accordance with local requirements for cytotoxic compounds.