Sindaxel

Paclitaxel.

Excipients/Inactive Ingredients: Citric acid, anhydrous; macrogolglycerol ricinoleate; ethanol, anhydrous.

This medicinal product is used for treatment of cancer. It can be cancer in the ovaries or breast cancer (advanced or spreading ovarian cancer, advanced or spreading breast cancer). This medicinal product may also be used for a special cancer in the lungs (advanced non-small-cell lung cancer, NSCLC) in patients who cannot be treated with surgery and/or radiotherapy. Paclitaxel may also be used for a special cancer, called Kaposi's sarcoma, which may be associated with AIDS (Acquired Immuno-Deficiency Syndrome) caused by an HIV disease) where other treatments i.e. liposomal anthracyclines have not worked.
Paclitaxel works by stopping cell division and is used to prevent the growth of cancer cells.

The doctor will decide how much Paclitaxel the patient will be given. It is given under the supervision of a doctor, who can give the patient more information. The dose will depend on the type and the extent of the cancer, and the body surface in square metres (m²) which is calculated from the height and weight. The dose the patient receives will also depend on results of the blood tests.
Paclitaxel solution has to be diluted before being given to the patient.
Paclitaxel is given by infusion (a drip) into a vein for 3 hours. Treatment is usually repeated every three weeks. Treatment of AIDS-related Kaposi's sarcoma is repeated every other week.
Depending on the type and severity of the cancer the patient will receive Paclitaxel either alone or in combination with another anticancer agent.
Each time before Paclitaxel is given, the patient will be given other medicines (premedication) such as dexamethasone, diphenhydramine and cimetidine, or ranitidine.
This is necessary to decrease the risk of severe allergic (hypersensitive) reactions (see Side Effects).

If the patient is given too much Paclitaxel: The 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 diarrhea.

Do not use Paclitaxel: if the patient is allergic (hypersensitive) to paclitaxel or any of the other ingredients. One of the ingredients, macrogolglycerol ricinoleate, can cause severe allergic reactions;
if the patient is pregnant or breast-feeding;
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 the patient has a serious uncontrolled infection.

Take special care with Paclitaxel: If the patient has heart disease or liver problems;
When diarrhoea occurs during or shortly after treatment with paclitaxel (pseudomembranous colitis);
If the patient has Kaposi's sarcoma and severe inflammation of the mucous membrane (membranes lining the passages of the body that open to the outside) occurs;
If the patient has had nerve problems in the hands or in feet, such as numbness, tingling or burning (peripheral neuropathy);
If the patient has blood problems, such as changes in the number of some cells;
If Paclitaxel is given to the patient in combination with radiotherapy of the lung.
Driving and using machines: There is no reason why the patient cannot continue driving between courses of Paclitaxel but the patient 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, the patient should not drive or use machines if he/she feels dizzy or light-headed.

Pregnancy: Do not use Paclitaxel if the patient thinks she is pregnant or the patient is 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 months after treatment. Tell the doctor immediately if the patient does become pregnant.
Breast-feeding: Paclitaxel should not be used when the patient is breast-feeding. The patient should stop breast feeding while the patient is being treated with Paclitaxel. Do not restart breast feeding until the doctor tells the patient it is safe to do so. Ask the doctor or pharmacist for advice before taking any medicine.

Like all medicines, Paclitaxel can cause side effects, although not everybody gets them. The following side effects may occur after treatment with Paclitaxel infusion.
The most frequent side effects are hair loss and decreased blood cell count. The hair grows back and the blood cell count returns to normal after the patient have finished the paclitaxel treatment.
If any of the following happens, tell the doctor immediately: Any abnormal bruising, bleeding, or signs of infections such as a sore throat and high temperature.
Severe allergic reaction - the patient 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 the patient may feel the patient is going to faint.
Breathlessness and dry cough due to damage to the lung.
Reaction at the injection site, e.g. local swelling, pain, redness.
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.
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 1 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 1 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 the 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 1 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 cases 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 multiforme 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, please tell the doctor or pharmacist.

Please tell the doctor or pharmacist if the patient is taking or has recently taken any other medicines, including medicines the patient has 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 the patient is 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.

Paclitaxel contains: Alcohol (ethanol) approximately 50% by volume, that is up to about 20 g per dose. This is equivalent to half a litre of beer per dose or a large glass (210ml) of wine per dose. This amount may be dangerous for patients suffering from alcoholism and for high risk patients including those with liver problems or epilepsy (fits). The amount of alcohol in this product may alter the effects of other medicines.
Macrogolglycerol ricinoleate, which can cause severe allergic (hypersensitivity) reactions.
Instructions for use: Cytostatic Agent: 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. Opened containers, like injection vials and infusion bottles and used canules, syringes, catheters, tubes, and residuals of cytostatics should be considered as hazardous waste and undergo disposal according to local guidelines for the handling of hazardous waste.
3. 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.
4. In the event of Paclitaxel contact with the skin, the area should be rinsed with plenty of running water and then washed with soap and water. In case of contact with mucous membranes, wash the contacted area thoroughly with water. If the patient has any discomfort, contact a doctor.
5. In case of contact of Paclitaxel with eyes, wash them thouroughly with plenty of cold water. Contact an ophthalmologist immediately.
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 vial 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 (see section "Incompatibilities" as follows).
Prior to infusion, Paclitaxel 6mg/ml concentrate for solution for infusion must be diluted, using aseptic techniques. The following solutions for infusion can be used for dilution: 0.9% Sodium Chloride solution for infusion, or 5% Glucose solution for infusion, or 5% Glucose and 0.9% Sodium Chloride solution for infusion, or 5% Glucose in Ringer's solution for infusion, to a final concentration of 0.3 to 1.2mg/ml.
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.
Upon preparation, solutions 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.
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 μm. (No significant losses in potency have 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 regurlarly inspected and the infusion should be stopped if precipitation is present.

Stability and storage conditions: Store the vial in 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. An expiry date is given on the outer carton and vial label of the product. It should not be used after this date.
After opening: 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.
Chemical and physical in-use stability of the solution prepared for infusion has been demonstrated at 5°C and at 25°C for 7 days when diluted in a 5% glucose solution and 5% glucose in Ringer solution for injection and for 14 days when diluted in sodium chloride 0.9%. 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 usually should not be more than 24 hours at 2-8°C, unless the dilution is performed in controlled and validated aseptic conditions. After the dilution, the solution is for single use.
Incompatibilities: To minimise patient exposure to plasticizer DEHP (di-2-ethylhexyl phtalate), which may be leached from plasticised PVC infusion bags, sets, or other medical instruments, diluted paclitaxel solutions should be stored in non-PVC bottles (glass, polypropene) or plastic bags (polypropene, polyolefin) and administered through polyethene-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.
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.

Cytotoxic Chemotherapy

L01CD01 - paclitaxel ; Belongs to the class of taxanes from plant alkaloids and other natural products. Used in the treatment of cancer.

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