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 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 or nurse.
- 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 or nurse. 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 prevents the growth of certain cancer cells, especially in certain types of ovary, breast, and lung cancer and Kaposi's sarcoma.
Paclitaxel is used to treat:
Ovarian cancer
• As initial therapy in combination with the platinum-containing medicine, cisplatin
• 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 in patients for whom anthracyclines therapy is suitable, or with a medicine called trastuzumab.
• As an additional treatment, following initial 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.
Advanced 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.
2. What you need to know before you use Paclitaxel
Please read the following information carefully, as there may be situations where treatment with
paclitaxel may not suitable for you, or where special care is needed.
Do not use Paclitaxel
• if you are allergic (hypersensitive) to paclitaxel or any of the other ingredients especially macrogolglycerol ricinoleate (castor oil) of this medicine (listed in section 6).
• if you are breast-feeding
• if your white blood cell count is too low (neutrophils). This is measured by healthcare personnel.
• if you have a serious and uncontrolled infection and Paclitaxel is used to treat Kaposi’s sarcoma.
If any of these apply to you, talk to your doctor before starting treatment with Paclitaxel.
Warnings and precautions
To minimise allergic reactions, you will be given other medicines before you receive Paclitaxel.
Tell your doctor immediately if you have any of the following:
• If you have heart conduction problems.
• If you had previous radiation to the chest (because it may increase the risk of lung inflammation).
• If you have severe liver problems; in that case the use of Paclitaxel is not recommended.
• 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 if you develop any of the following after receiving this medicine
• 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 may be necessary
• If you develop severe or consistent diarrhoea, with fever and stomach pain, during or shortly after the treatment with Paclitaxel. Your colon could be inflamed (pseudomembranous colitis).
Paclitaxel should always be administered into veins. Administration of Paclitaxel in the arteries can
cause inflammation of the arteries, and you can suffer from pain, swelling, redness and heat.
Talk to your doctor, pharmacist or nurse before using Paclitaxel.
Children and adolescents
Paclitaxel is not recommended for use in children and adolescents (under 18 years of age).
Other medicines and Paclitaxel
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other
medicines including medicines obtained without prescription. This is because Paclitaxel or the other
medicine may not work as well as expected, or you may be more likely to get a side effect.
Interaction means that different medicines may influence each other. Interaction may occur and your doctor needs to know when using Paclitaxel together with:
• Cisplatin (to treat cancer): Paclitaxel must be given before cisplatin. Your renal function may need to be checked more frequently.
• Doxorubicin (to treat cancer): Paclitaxel must be administered 24 hours after doxorubicin, to avoid high level of doxorubicin in your body.
• Efavirenz, nevirapine, ritonavir, nelfinavir, or other protease-inhibitors, which are used in HIV treatments. A dose adjustment of Paclitaxel may be necessary.
• Erythromycin, an antibiotic, fluoxetine, an antidepressant or gemfibrozil, used for lowering cholesterol. A dose reduction of Paclitaxel may be necessary.
• Rifampicin, an antibiotic used for tuberculosis. A dose increase of Paclitaxel may be necessary.
• Carbamazepine, phenytoin or phenobarbital, used for epilepsy.
Pregnancy, breast-feeding and fertility
Tell your doctor if you are pregnant or think you may be pregnant before receiving treatment with Paclitaxel. 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. Female and male patients of fertile age, and/or their partners should use effective contraceptions for at least 6 months after treatment with paclitaxel.
Male patients should seek advice regarding cryoconservation of sperm prior to treatment with paclitaxel because of the possibility of irreversible infertility.
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. Do not restart breast-feeding unless your doctor has allowed you to.
Driving and using machines
Remember that this medicine contains some alcohol and it may be unwise to drive immediately after a course of treatment (see section “Paclitaxel contains ethanol and macrogolglycerol ricinoleate” below). As in all cases, you should not drive if you feel dizzy or light-headed.
Discuss with your doctor, pharmacist or nurse if you are unsure about anything.
Paclitaxel contains ethanol and macrogolglycerol ricinoleate
This medicinal product contains 50% (volume) ethanol (alcohol) i.e. up to 20 g per average dose, equivalent to half a litre of beer, or 210 ml of wine per dose. This may be harmful to patients 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 also alter the effects of other medicines.
This medicinal product also contains macrogolglycerol ricinoleate (a type of castor oil), which may cause severe allergic reactions. If you are allergic to castor oil, talk to your doctor before you receive Paclitaxel.
3. How to use Paclitaxel
Your doctor will decide how many doses you will be given. Paclitaxel will be given under supervision of a doctor, who can give you more information.
Dose
The dose will depend on the type and the degree of difficulty of the cancer and on your height and weight from which the doctor will work out your body surface area. Paclitaxel is given into a vein (intravenous use) from an intravenous drip over 3 hours. Paclitaxel is usually given every 3 weeks (2 weeks in patients with Kaposi's sarcoma).
Pre-medication
You will be pre-medicated with several different medicinal products (dexamethasone and diphenhydramine or chlorphenamine and cimetidine or ranitidine) before every treatment with Paclitaxel.
Pre-medication is necessary to decrease the risk of severe hypersensitive reactions (see section 4. “Possible side effects - uncommon”).
Use in children and adolescents
Paclitaxel is not recommended for use in children and adolescents below 18 years of age due to lack of data on safety and efficacy.
If you are given more Paclitaxel than you should
There is no known antidote for Paclitaxel overdose. You will receive treatment of your symptoms.
If a dose of Paclitaxel has been missed
If you think a dose has been missed let your doctor or nurse know.
A double dose should not be given if a dose has been forgotten.
If you stop using Paclitaxel
Your doctor will decide when to stop treatment with paclitaxel.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor immediately if you notice any signs of allergic reactions. These may include one or more of the following:
• flushing,
• skin reactions,
• itching,
• chest tightness,
• shortness or difficulty in breathing,
• swelling.
These can all be signs of serious side effects.
Tell your doctor immediately:
• 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.
Other side effects include:
Very common side effects (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)
• hair loss
• 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 side effects (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 side effects (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, inflammation of a vein (phlebitis), 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) and high blood pressure.
Rare side effects (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, sudden blockage in a lung artery (pulmonary embolism), swelling and scarring of the lungs (lung fibrosis), inflammation of the lungs (interstitial pneumonia), build up of fluid between tissue in the lungs and the chest cavity (pleural effusion)
• bowel obstruction, bowel perforation, inflammation of colon (ischaemic colitis), inflammation of the pancreas (pancreatitis)
• the urge to itch (pruritus), rash, skin redness (erythema)
• blood poisoning (sepsis), inflammation of the lining of the abdominal cavity (peritonitis)
• fever, dehydration, weakness, swelling, feeling unwell
• serious and potentially fatal hypersensitivity reactions (anaphylactic reactions)
• tests may show: increase in blood creatinine indicating renal function impairment
• cardiac failure
Very rare side effects (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), a spinning feeling
• cough
• blood clot in a blood vessel of abdomen and bowel (mesenteric thrombosis), inflammation of colon sometimes with persistent severe diarrhoea (pseudo-membranous colitis, neutropenic colitis), swelling of the abdomen (dropsy, ascites), inflammation of the oesophagus (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))
• confusion.
Not known (frequency cannot be estimated from the available data):
• occurrence of metabolic complications after cancer treatment (tumor lysis syndrome)
• fluid and protein deposits on or under the macula of the eye and cause it to thicken and swell (macular oedema)
• presence of perceived flashes of light (photopsia)
• deposits of various size, shape, consistency, refractive index and motility within the eye’s vitrous humour (vitreous floaters)
• vein inflammation (phlebitis)
• chronic systemic autoimmune disease (primarily of the skin) characterized by hardening, vascular alterations and auto-antibodies (scleroderma)
• systemic autoimmune disease that can affect any part of the body (systemic lupus erythematosus)
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.
This medicinal product does not require any special temperature storage condition.
Keep the vial in the outer carton in order to protect from light.
Do not use this medicine after the expiry date which is stated on the carton and vial after EXP.The expiry date refers to the last day of that month.
Do not use this medicine if you notice a cloudy solution or an insoluble precipitate.
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
6. Contents of the pack and other information
What Paclitaxel contains
- The active substance is paclitaxel. Each ml contains 6 mg of paclitaxel.
- The other ingredients are ethanol anhydrous, macrogolglycerol ricinoleate and citric acid anhydrous.
What Paclitaxel looks like and contents of the pack
Paclitaxel is a clear, colourless to slightly yellow, viscous solution free from visible particles.
5 ml glass vial type I (flint tubular vial) with a grey rubber stopper and light yellow flip off aluminium seal, containing 5 ml of concentrate equivalent to 30 mg of paclitaxel.
20 ml glass vial type I (flint tubular vial) with a grey rubber stopper and light blue flip off aluminium seal, containing 16.7 ml of concentrate equivalent to 100 mg of paclitaxel.
50 ml glass vial type I (flint moulded vial) with a grey rubber stopper and light yellow flip off aluminium seal, containing 50 ml of concentrate equivalent to 300 mg of paclitaxel.
Pack Sizes:
1 x 5 ml vial 1 x 20 ml vial 1 x 50 ml vial
Not all pack sizes may be marketed
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder Mylan
Potters Bar, Hertfordshire, EN6 1TL, United Kingdom Manufacturer
Agila Specialties Polska Sp.z.o.o.
10, Daniszewska Str 03-230 Warsaw Poland
This leaflet was last revised in 11/2014
The following information is intended for healthcare professionals only:
Instructions for use
CYTOSTATIC AGENT
1. Handling of Paclitaxel
As with all cytostatic agents, caution should be exercised when handling Paclitaxel. Dilution should be carried out under aseptic conditions by trained personnel in a designated area. Precautions should be taken to avoid contact with the skin and mucous membranes. Following topical exposure, tingling, burning and erythema have been observed. Upon inhalation, dyspnoea, chest pain, burning throat and nausea have been reported.
Protection instructions for preparation of Paclitaxel solution for infusion :
1. Protective chamber should be used and protective gloves as well as protective gown should be worn. If there is no protective chamber available mouth cover and goggles should be used.
2. Pregnant women or women would may become pregnant should not handle this product
3. Opened containers, like injection vials and infusion bottles and used canules, syringes, catheters, tubes, and residuals of cytotoxic agents should be considered as hazardous waste and undergo disposal according to local guidelines for the handling of HAZARDOUS WASTE.
4. Follow the instructions below in case of spillage:
• protective clothing should be worn
• broken glass should be collected and placed in the container for HAZARDOUS WASTE
• contaminated surfaces should be flushed properly with copious amounts of cold water
• the flushed surfaces should then be wiped thoroughly and the materials used for wiping should be disposed as HAZARDOUS WASTE
5. In the event of contact of Paclitaxel concentrate for solution for infusion with the skin, the area should be rinsed with plenty of running water and then washed with soap and water. If you have any discomfort, contact a doctor.
6. In the event of contact of Paclitaxel concentrate for solution for infusion with the mucous membranes, these should be flushed thoroughly with water. If you have any discomfort, contact a doctor.
7. In case of contact of Paclitaxel concentrate for solution for infusion with the eyes, wash them thoroughly with plenty of cold water. Contact an ophthalmologist immediately.
2. Preparation of infusion solution:
So called “closed system”, e.g. the Chemo-Dispensing Pin device or similar devices, should not be used for withdrawal of the doses from injection vials since they can cause the vial stopper to collapse, resulting in loss of sterile integrity.
Prior to infusion, Paclitaxel 6 mg/ml concentrate for solution for infusion must be diluted, using aseptic techniques. The following solution for infusion can be used for dilution to a final concentration of 0.3 to 1.2 mg/ml:
• 0.9% Sodium Chloride Injection or
• 5% Glucose Injection or
• 5% Glucose and 0.9% Sodium Chloride Injection or
• 5% Glucose in Ringer’s solution for infusion.
The diluted solution is supersaturated with regards to paclitaxel (there have been rare reports of precipitation in connection with 24-hour period of infusion). Therefore excessive agitation or vibration should be avoided.
Upon preparation, solution may show haziness, which is attributed to the formulation vehicle, and is not removed by filtration. In order to reduce the precipitation risk the diluted Paclitaxel infusion should be used as soon as possible after dilution.
3. Infusion technique
Paclitaxel infusion solution should be administered as intravenous infusion.
Paclitaxel should be administered through an in-line filter with a microporous membrane < 0.22 pm. No significant loss in potency has been noted following simulated delivery of the solution through iv tubing containing an “in-line” filter.
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.
4. Stability and storage conditions
Unopened Paclitaxel vials for injection should be stored in the outer carton in order to protect from light. Following multiple needle entries and product withdrawal, paclitaxel maintains chemical and physical in-use stability for 28 days at 25 °C. Other in-use storage times and conditions are the responsibility of the user.
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.
After dilution
Chemical and physical in-use stability has been demonstrated for 14 days at 2- 8°C and 25°C when diluted in 0.9% sodium chloride injection, for 7 days at 2-8°C and 25°C when diluted in 5% glucose injection, for 72 hours at 25°C when diluted in 5% glucose and 0.9% sodium chloride injection or 5% glucose in Ringer’s solution.
From a microbiological point of view, the dilution should be used immediately, unless the method of dilution precludes the risk of microbial contamination. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user. After dilution the solution is for single use only.
5. Incompatibilities
To minimise patient exposure to DEHP (di-2-ethylhexyl phthalate), which may be leached from the plasticised PVC infusion bags, sets, or other medical instruments, diluted paclitaxel solution 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 (eg. IVEX-2®) which incorporate short inlet and/or outlet plasticised PVC tubing has not resulted in significant leaching of DEHP.
6. 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.