Paclitaxel 6mg/Ml Concentrate For Solution For Infusion
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The following information is intended for medical or healthcare professionals only:
25mm
Please refer to the Summary of Product Characteristics for further information
Name of the medicinal product
Paclitaxel 6 mg/ml concentrate for solution for infusion. Instructions for use and handling
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, 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 loss of sterile integrity.
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 for 27 hours at 25°C.
PACLITAXEL 6 mg/ml CONCENTRATE FOR SOLUTION FOR INFUSION
Read all of this leaflet carefully before you receive this medicine.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If any of the side effects get serious, or if you notice any side effects not listed in this leaflet,
• please tell your doctor or nurse.
1. What Paclitaxel is and what it is used for
2. Before you receive Paclitaxel
3. How to receive Paclitaxel
4. Possible side effects
5. How to store Paclitaxel
6. Further information
WHAT PACLITAXEL IS AND WHAT IT IS USED FOR
Paclitaxel belongs to a group of drugs called taxanes, which are anti-cancer medicines.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage time and conditions prior to use are the responsibility of the user. Diluted solutions should not be refrigerated. After dilution the solution is for single use only.
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 inspected regularly and the infusion should be stopped if precipitation is present.
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.
To minimise 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. Use of filter devices (e.g. IVEX-2®) which incorporate short inlet and/or outlet plasticized PVC tubing has not resulted in significant leaching of DEHP.
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.
Paediatric use: Paclitaxel is not recommended for use in children below 18 years due to lack of data on safety and efficacy.
Incompatibilities
Macrogolglycerol ricinoleate can result in DEHP [di-(2-ethylhexyl) phthalate] leaching from plasticized polyvinyl chloride (PVC) containers at levels which increase with time and concentration. Consequently, the preparation, storage and administration of diluted Paclitaxel should be carried out using non-PVC-containing equipment.
Shelf life and storage conditions
Vial: 2 years (if unopened)
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Paclitaxel is used:
• for either the first or second-line treatment of breast and ovarian cancer
• to treat a certain type of lung cancer known as non-small cell lung carcinoma.
Paclitaxel may be given on its own or in combination with other medicines.
0 BEFORE YOU RECEIVE PACLITAXEL
Do not receive Paclitaxel if you:
• are allergic (hypersensitive) to paclitaxel or any of the other ingredients of this medicine
• are pregnant, planning on becoming pregnant or breast-feeding
• have been told that you have a low number of white blood cells in your blood.
Take special care with Paclitaxel
Tell your doctor or nurse before you start to take this medicine if you:
• notice marked allergic reaction which may cause shortness of breath, dizziness (caused by low blood pressure), swelling of the face or rash
• have heart disease or liver problems (if liver damage is severe, paclitaxel is not recommended)
• have had or need to have radiation therapy
• have been told that you have a low number of platelets in your blood
• suffer from alcoholism (please see important information about some of the ingredients of Paclitaxel)
• experience tingling, burning or numbness in your fingers and/or toes
• develop diarrhoea during or shortly after treatment with this product as your colon could be inflamed.
Your doctor may want to monitor your blood and heart function while you are treated with Paclitaxel.
Taking other medicines
Please tell your doctor or nurse if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
The following drugs may increase the level of paclitaxel in the blood:
• erythromycin (antibiotic)
• fluoxetine (used to treat nervous disorders such as depression)
• gemfibrozil (used to prevent heart disease)
• nelfinavir and ritonavir (antiviral treatments for HIV/AIDS infection).
The following drugs may decrease the level of paclitaxel in the blood:
• rifampicin (antibiotic)
• carbamazepine, phenytoin and phenobarbital (used to control epilepsy)
• efavirenz and nevirapine (antiviral treatments for HIV/AIDS infection).
Pregnancy and breast-feeding
Paclitaxel is not recommended if you are pregnant, planning to become pregnant or breast-feeding. Ask your doctor or nurse for advice before taking any medicine.
Driving and using machines
Paclitaxel is not expected to affect your ability to
drive or operate machinery, but you should be aware that it contains a small amount of alcohol. You should take care if you need to drive immediately after having a Paclitaxel injection.
Important information about some of the ingredients of Paclitaxel
• This medicinal product contains 50% ethanol (alcohol). It may be harmful to those suffering from alcoholism.
• The alcohol content should be taken into account if you are in a high risk group such as patients with liver disease or epilepsy.
0 HOW TO RECEIVE PACLITAXEL
You should have had a blood test recently, and your doctor should have checked the results of this test to make sure you can receive your course of treatment.
You will be given steroid, antihistamine and H2 antagonist tablets before having the Paclitaxel injection.
Paclitaxel will be administered by a doctor or nurse. Paclitaxel will be given into a vein from an intravenous drip. Other medicines, such as cisplatin and trastuzumab, may be given to you at the same time as Paclitaxel.
Your doctor will decide your dose which is calculated depending on your body size, height and weight.
The dosage instructions for specific types of cancer are given below:
• Ovarian cancer
First-line treatment: You will either be given 175 mg/m2 intravenously over 3 hours or 135 mg/m2 over 24 hours. This will be followed by 75 mg/m2 of cisplatin. The dose will be repeated every 3 weeks.
Second-line treatment: The usual dose is 175 mg/m2 over 3 hours. The dose will be repeated every 3 weeks.
• Breast cancer
First or second-line treatment: The usual dose is given after trastuzumab, and is 175 mg/m2 given intravenously over 3 hours. The dose will be repeated every 3 weeks.
• Advanced non-small cell lung carcinoma
The usual dose is 175 mg/m2 given over 3 hours followed by 80 mg/m2 of cisplatin. The dose will be repeated every 3 weeks.
Children and adolescents
• Children and adolescents under 18 years old should not be treated with Paclitaxel.
If you receive more Paclitaxel than you should
As a doctor or nurse will be giving you your medicine, it is unlikely that you will receive an incorrect dose. Tell your doctor or nurse if you have any concerns about the amount of medicine that you receive.
If you have any further questions on the use of this product, ask your doctor or nurse.
0 POSSIBLE SIDE EFFECTS
Like all medicines, Paclitaxel can cause side effects, although not everybody gets them.
If any of the following happen tell your doctor or nurse immediately:
• difficulty breathing and swelling of the lips, face and neck, rash, itching, shortness of breath, abnormal heart beat, low blood pressure (feeling dizzy or faint)
• severe blistering or bleeding of the lips, eyes, nose, mouth or genitals
• severe skin reactions causing skin scaling, blistering and peeling.
The following side effects have been reported:
Very Common side-effects which may affect more than 1 person in 10 are listed below:
• nausea, vomiting, diarrhoea
• soreness of the mouth or tongue
• hair loss
• joint or muscle weakness, pain, aching or loss of sensation in the limbs
• an impairment in blood cell production called myelosuppression, that can result in anaemia (a reduction in red blood cells), reduced ability to fight infection and bruising or bleeding
• infection - this may be associated with low
blood cell count resulting from receiving paclitaxel
• tingling, burning or numbness in your fingers and/or toes
• low blood pressure which may cause you to feel light-headed, particularly when standing up.
Common side-effects which may affect more than
1 person in 100 are listed below:
• slow heart-beat
• temporary mild changes to the nails and skin
• injection site reactions (local swelling, pain, redness, hardening of tissues, extravasation (leaking of drug outside the vein) resulting in cellulitis (painful swelling and redness).
Uncommon side-effects which may affect more
than 1 person in 1000 are listed below:
• allergic reactions (e.g., rash, chills, back pain, chest pain, abdominal pain, rapid heart rate, oain in hands and feet, excessive sweating, high Dlood pressure, breathing difficulty and low blood pressure)
• serious bacterial infection develops in the blood
• fainting
• heart attack
• obstruction of a blood vessel by a blood clot
• inflammation of a vein, sometimes accompanied by a clot
• yellowing of whites of eyes and skin.
Rare side-effects which may affect less than 1
person in 1000 are listed below:
• pneumonia
• peritonitis, the symptoms you may feel are like abdominal pain, vomiting, fever, rapid heart beat, feeling thirsty, chills and not passing any urine or passing much less than normal
• effect on nerves that control the muscles, resulting in muscle weakness in arms and legs (motor neuropathy)
• heart failure
• problems with your lungs such as inflammation or accumulation of fluids, which may make it difficult to breathe
• blood clot in the lungs which causes chest pain and breathlessness
• scarring of the lungs which causes shortness of breath
• abdominal pain, bloating and constipation, abdominal tenderness, blood in stool, feeling unwell, vomiting, perforation of the wall of your bowel, a feeling of urgency to move your bowels
• inflammation of your pancreas
• itching, skin rash/redness
• dehydration
• loss of energy
• accumulation of fluid in the whole body (oedema)
• general feeling of being unwell
• increase in blood creatinine (this can be detected from your blood test).
Very Rare side-effects which may affect less than
1 person in 10000 are listed below:
• acute leukaemia (blood cancer) or related condition (myelodysplastic syndrome) which your doctor will check for
• loss of appetite
• confusion
• dizziness
• headache
• fits
• brain disorder
• severe bowel or abdominal pain or dizziness when standing up which may be caused by a disease of the nervous system
• difficulty in controlling movements
• visual disturbances
• loss of hearing or ringing in the ears, a feeling of dizziness or "spinning"
• palpitations or chest pain
• shock
• cough
• blood clot in the major veins that drain blood from the intestine
• infection of colon characterised by offensivesmelling diarrhoea, fever, and abdominal pain
• pain and tenderness in the right lower quadrant of the abdomen, accompanied by fever, diarrhoea, nausea and vomiting which may be caused by a disease called neutropenic colitis
• abdominal pain which may be caused by accumulation of fluid in the abdomen (ascites)
• inflammation of the gullet
• damage to the liver which may be severe (hepatic necrosis). This may have an effect on brain function (hepatic encephalopathy)
• serious illness with blistering of the skin, mouth, eyes and genitals, skin reaction causing skin peeling, red itchy skin, nettle rash
• detachment of the nail from the nail bed (you are advised to wear protection on your hands and feet when exposed to the sun).
Not known: frequency cannot be estimated from the available data
• increased uric acid, potassium, phosphate in blood, decreased calcium in blood and renal failure which may be caused by a disease called Tumour Lysis Syndrome
• accumulation of fluid within the retina
• visual disturbance such as sparks, lights or colours arising in the absence of light and observed when the eyes are closed, appearance of spots or small shapes floating in vision field or cloudy vision
• inflammation of the veins just under the skin, usually in the legs may be caused by a disease called Phlebitis
• inflammation and thickening of the skin caused by a disease called Scleroderma
• fever, pain in your joints and muscles and rash, which may be signs of the auto immune disease, SLE (systemic lupus erythematosus).
The following side effects have been reported as more severe when Paclitaxel is given in combination with trastuzumab:
• chills, fever, cough
• joint pain, rigid muscles
• heart failure, increased heart rate, heart dysfunction rarely associated with death
• nose bleed, runny and itchy nose, inflammation of the sinuses
• acne, rash, blisters caused by the herpes simplex virus
• difficulty sleeping
• diarrhoea
• infection
• accidental injuries
• reaction at the injection site.
The following side effects have been reported as more severe when Paclitaxel is given in combination with cisplatin:
• joint and muscle pain
• hypersensitivity reactions
• damage to the nerves.
The following side effect has been reported if Paclitaxel is given in combination with radiation therapy:
• an increased risk of developing pneumonitis, which is a form of lung inflammation and may cause coughing and difficulty breathing.
If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or nurse.
0 HOW TO STORE PACLITAXEL
Keep out of the reach and sight of children.
Do not store above 25°C or transfer to another container. Do not refrigerate or freeze diluted solutions.
Do not use Paclitaxel after the expiry date that is stated on the outer packaging. The expiry date refers to the last day of that month.
Return all unused medicines to your pharmacist for safe disposal.
0 FURTHER INFORMATION
What Paclitaxel contains:
• The active ingredient is paclitaxel.
• The other ingredients are macrogol glycerol ricinoleate, ethanol and citric acid.
What Paclitaxel looks like and contents of the pack:
• Paclitaxel comes as a concentrate for solution for infusion. It is a clear, colourless or slightly yellow, viscous solution.
• Each glass vial contains 30, 100, 150 or 300 mg of Paclitaxel as a 6 mg/ml solution.
Marketing Authorisation Holder and Manufacturer
The Marketing Authorisation holder is Teva UK Limited, Eastbourne, BN22 9AG.
The company responsible for manufacture is TEVA Pharmaceutical Works Private Limited Company, Tancsics Mihaly UTCA 82, Godollo, HU-2100, Hungary.
This leaflet was last revised: August 2011 PL 00289/1260
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Chemical and physical in-use stability has been demonstrated for 28 days at 25°C. 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.
Diluted solutions: chemical and physical in-use stability of the solution prepared for infusion has been demonstrated for 27 hours at 25°C.
Before and after opening: Do not store above 25°C. Store in original package in order to protect from light.
Diluted solutions: Do not refrigerate or freeze diluted solutions.
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25mm