30 mg concentrate and liquid for infusion, solution
temsirolimus
What Torisel is and what it is used for
Torisel contains the active substance temsirolimus.
Temsirolimus is a selective inhibitor of the enzyme mTOR (mammalian target of rapamycin) and works by blocking the growth and division of tumor cells.
Torisel is used to treat the following types of cancer in adults:
- Advanced kidney cancer.
- Previously treated mantle cell lymphoma, a type of cancer that affects the lymph nodes.
What you need to know before you are given Torisel
Do not use Torisel
- if you are allergic to temsirolimus, polysorbate 80, or any of the other ingredients (listed in section 6.1).
- if you are allergic to sirolimus (used to prevent the body from rejecting transplanted kidneys), as sirolimus is released from temsirolimus in the body.
- if you have mantle cell lymphoma and liver problems.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before you are given Torisel
- if you are allergic to antihistamines or cannot use antihistamines for any other medical reason. Antihistamine is given to prevent an allergic reaction to Torisel, including some life-threatening and rarely fatal allergic reactions. Discuss options with your doctor
- if you have or have had tumor disease of the brain or spinal cord, bleeding problems or bruising or if you are using medicines that prevent blood clotting (eg warfarin and acenocoumarol). Torisel may increase the risk of brain bleeding. Tell your doctor if you take blood-thinning medicines or have any bleeding or bruising while being treated with Torisel
- if you have shortness of breath, cough, and/or fever. Torisel can weaken your immune system. You may have an increased risk of infection in your blood, skin, upper respiratory tract (including pneumonia ), and/or urinary tract while you are being treated with Torisel. Tell your doctor if you experience new or worsening symptoms, or if you are taking or have recently taken medicines that weaken the immune system
- if you have or have had an inflammation of the lungs. Torisel can cause non-specific interstitial pneumonitis. Some patients had no or minimal symptoms. For this reason, your doctor may recommend an examination of the lungs with computed tomography or chest X-ray before and during your treatment with Torisel. Talk to your doctor immediately if you develop any new or worsening respiratory symptoms such as shortness of breath or difficulty breathing
- if you drink alcohol or are an alcoholic. Torisel contains alcohol and may be harmful to those who drink alcohol or suffer from alcoholism. Tell your doctor if you have alcohol problems (see section “Torisel contains ethanol [alcohol]”)
- if you have or have had problems with your kidneys. Your doctor will monitor your kidney function if you have or have had liver problems. Tell your doctor if you develop any of the following symptoms of liver problems during treatment with Torisel; itching, yellow eyes or skin, dark urine, and pain or discomfort on the right side of the upper stomach region. Your doctor will take blood tests to check your liver function and may then lower the Torisel dose
- if you have or have had high cholesterol because Torisel can cause an increase in triglycerides and/or cholesterol. This may mean that you need treatment with lipid-lowering agents (medicines used to lower cholesterol levels in the blood)
- if you are going to have surgery or have recently had surgery. Torisel may increase the risk of problems with wound healing. You will usually have to stop treatment with Torisel if you are going to have surgery. Your doctor will decide when to start treatment with Torisel again.
- if you plan to be vaccinated during treatment with Torisel. The vaccination may have less effect or certain vaccinations should be completely avoided during treatment with Torisel
- if you are over 65, you run an increased risk of experiencing certain side effects, e.g. swelling of the face, diarrhea, pneumonia, anxiety, depression, shortness of breath, reduced number of white blood cells, muscle pain, changes in taste, upper respiratory tract infection, fluid accumulation in the pleura, ulcers and inflammation of the mouth and/or gastrointestinal tract and runny nose, dizziness, and infection
- Torisel can raise blood sugar levels and worsen diabetes mellitus. This can lead to a need for treatment with insulin and/or diabetes medication in tablet form. Tell your doctor if you experience a strong increase in thirst or an increase in the amount of urine and an increased need to pass water
- Torisel can reduce the number of the type of blood cells that allow the blood to clot and that defend the body in case of infection. This may give rise to an increased risk of bleeding/bruising and infection (see section “Possible side effects”)
- if you have or have had eye problems such as cataracts. Your doctor may refer you for an eye examination before or during treatment with Torisel
- if you are given Torisel, you may be at increased risk of cancer, e.g. skin cancer and cancer of the lymph nodes ( lymphoma )
- if you are given Torisel, you may be at increased risk of a heart attack. Tell your doctor if you experience symptoms such as pain, pressure in the chest, arms, shoulders, or jaw, shortness of breath, nausea, anxiety, sweating, or dizziness.
Talk to your doctor, pharmacist, or nurse if you have any questions.
Children and young people
This medicine is not intended for children and adolescents under 18 years of age. Advanced kidney cancer and mantle cell lymphoma are not relevant for these patients and do not affect other cancer types.
Other medicines and Torisel
Tell your doctor or pharmacist if you are using, have recently used, or might be using other medicines.
Some medicines can interfere with the breakdown ( metabolism ) of Torisel and therefore dose adjustment of Torisel may be required. You must inform your doctor or pharmacist if you are using any of the following:
- Protease inhibitors are used in the treatment of human immunodeficiency virus ( HIV ).
- Antibiotics (including rifampin) or antifungals (including itraconazole, ketoconazole, and voriconazole) are used to treat infections.
- Nefazodone or selective serotonin reuptake inhibitors ( SSRIs ) are used to treat depression.
- Antiepileptics, including carbamazepine, phenytoin, and phenobarbital.
- Rifabutin is used to treat infections in people with HIV and other diseases.
- Herbal medicines or herbal remedies containing St. John’s wort ( Hypericum perforatum ) are used to treat mild depression.
- Angiotensin-converting enzyme (ACE) inhibitors (such as enalapril, ramipril, and lisinopril) or calcium channel blockers (such as amlodipine) are used to treat high blood pressure or other cardiovascular problems.
- Amphiphilic drugs are used to treat heart arrhythmias (rhythm disorders) (such as amiodarone ) or statins are used to treat elevated blood fats ( cholesterol ).
- Sunitinib is used to treat kidney cancer.
- Medicines that are P-gp substrates (eg digoxin , vincristine, colchicine, dabigatran, lenalidomide and paclitaxel).
- Cannabidiol (used, among other things, for the treatment of epileptic seizures).
Torisel with food, drink, and alcohol
Grapefruit and grapefruit juice may increase blood concentrations of Torisel and should be avoided.
Pregnancy, breastfeeding, and fertility
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor before being given this medicine.
Torisel has not been studied in pregnant women and must not be used during pregnancy unless necessary.
Women of childbearing potential must avoid becoming pregnant by using an effective method of contraception during ongoing treatment with Torisel. Men with partners of childbearing potential should use medically acceptable contraception while being treated with Torisel.
Women should not breastfeed during treatment with Torisel, as the agent may affect the growth and development of the child.
Torisel contains alcohol ( ethanol ). If you are pregnant or breastfeeding your child, you should consult a doctor or pharmacist before using this medicine.
Torisel contains propylene glycol. If you are pregnant, do not use the medicine except on the doctor’s recommendation (see “Torisel contains propylene glycol”). Propylene glycol can pass into breast milk. If you are breastfeeding, do not use the medicine except on the doctor’s recommendation (see “Torisel contains propylene glycol”).
Driving ability and use of machinery
Torisel probably does not affect the ability to drive and use machines. However, nausea and vomiting, and difficulty falling asleep or staying asleep are among the very common side effects of this medicine. Be especially careful if you drive or use machines if you feel nauseous and are vomiting or if you have difficulty falling asleep or staying asleep.
For patients receiving the higher dose of Torisel for the treatment of mantle cell lymphoma, the amount of alcohol in this medicine may impair their ability to drive or use machines (see the section below “Torisel contains ethanol [alcohol]”).
Torisel contains alcohol (ethanol)
This medicine contains alcohol ( ethanol ), in an amount equivalent to 18 ml of beer or 7 ml of wine per 25 mg dose. Patients who receive the higher dose of 175 mg Torisel for the initial treatment of mantle cell lymphoma may achieve an ethanol amount equivalent to 122 ml of beer or 49 ml of wine per dose. This is harmful if you are dependent on alcohol and should be taken into account by pregnant or breastfeeding women, children, and high-risk groups such as patients with liver disease or epilepsy.
The amount of alcohol in this medicine probably has no effects on adults and adolescents, and its effect on children is probably not noticeable. It may have some effect in infants and younger children, e.g. somnolence. If you are dependent on alcohol, consult a doctor or pharmacist before using this medicine.
The amount of alcohol in this medicine can affect the effectiveness of other medicines. Tell your doctor or pharmacist if you are using other medicines.
The amount of alcohol in this medicine can impair your ability to drive and use machines or affect the effectiveness of other medicines (see sections “Warnings and precautions” and “Ability to drive and use machines”).
Torisel contains propylene glycol
Torisel contains 503.3 mg of propylene glycol per 25 mg dose, corresponding to 201.33 mg/ml in the pre-diluted product. If your child is younger than 5 years, contact a doctor or pharmacist before the child uses the medicine, especially if the child is receiving other medicines that contain propylene glycol or alcohol. If you are pregnant or breastfeeding, or if you have impaired liver function or impaired kidney function, do not use the medicine except on the recommendation of a doctor. The doctor may want to do extra checks during the treatment.
How to use Torisel
Torisel must always be prepared and given by a doctor or other healthcare professional in the form of an intravenous infusion (drip into a vein).
You should receive an injection of antihistamine (to prevent an allergic reaction to Torisel) directly into the vein about 30 minutes before you receive your dose of Torisel.
The Torisel concentrate must first be diluted with 1.8 ml of the supplied liquid to achieve a concentration of 10 mg/ml before administration in sodium chloride 9 mg/ml (0.9%) solution for injection (see dilution instructions at the end of the package leaflet).
For advanced kidney cancer, the recommended dose is 25 mg given as a drip over 30 to 60 minutes once a week.
For mantle cell lymphoma, the recommended dose is 175 mg given as a drip over 30 to 60 minutes once a week for 3 weeks followed by a dose of 75 mg once a week given as a drip over 30 to 60 minutes.
Treatment with Torisel should be continued until you no longer benefit from the treatment or until unacceptable side effects occur.
As this medicine is prepared and administered by healthcare professionals, it is unlikely that you would receive too much or miss a dose.
If you are concerned about this, tell your doctor immediately.
If you have any further questions about this medicine, ask your doctor, pharmacist, or nurse.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them. Side effects may be more pronounced with the higher dose of 175 mg per week during the initial treatment of mantle cell lymphoma.
The most important side effects that you may experience during treatment with Torisel are listed below. Seek immediate medical attention if you experience any of these.
Allergic reactions
You should immediately contact a doctor or nurse if you get symptoms of angioedema, such as swelling of the face, tongue, throat, and difficulty breathing. If you experience any of these symptoms during treatment with Torisel, the doctor or nurse will stop the infusion.
Cerebral hemorrhage
You should seek medical attention immediately if you feel confused, abnormally tired, have difficulty speaking or swallowing, and if your pupils are of different sizes. These symptoms can be caused by brain bleeding.
Puncture, tear, or hole in the intestine
You should seek medical attention immediately if you have acute abdominal pain, high fever, nausea, and vomiting, or blood in the stool. These symptoms can be caused by holes in the intestine.
Kidney failure
You should immediately seek medical attention if you have general swelling, shortness of breath, or fatigue. These symptoms can be caused by a sudden decrease in kidney function.
Embolism in the lung
You should seek medical attention immediately if you have shortness of breath, chest pain, coughing up blood, rapid pulse, nausea, fainting, sweating, wheezing, and sticky or bluish skin. These symptoms can be caused by a blood clot in your lungs.
You must also inform your doctor immediately
- if you have a cough, chest pain, or difficulty breathing. Your doctor may refer you for a chest X-ray.
- if the number of white blood cells in your blood has decreased. This can increase your risk of getting a fever and infection.
- if the number of platelets (the type of blood cell that allows the blood to clot) has decreased. This can increase the risk of bleeding in your body.
- if you have increased levels of cholesterol and triglycerides in your blood.
- if you experience abnormal thirst or an increased frequency or quantity of urination. Your doctor may prescribe insulin and/or oral antidiabetic medications.
- if you have recently had an operation. Your doctor may delay treatment with Torisel until the wound has completely healed as this medicine may affect the healing process of existing wounds.
Other side effects of Torisel may include
Very common side effects (may affect more than 1 in 10 patients)
General weakness, chills, swelling caused by fluid retention, pain (including abdominal, back, chest, and joint pain), stomach discomfort (nausea, vomiting), diarrhea, constipation, headache, fever, mouth ulcers, and inflammation and/or digestive tract, cough, pneumonia, nosebleeds, rash, itching, dry skin, decreased appetite, shortness of breath, low blood potassium (which can cause muscle weakness), low red blood cell count, decreased white blood cell count associated with increased risk of infection, high blood sugar, high cholesterol, high triglycerides, abscesses, infection (including eye infection er, flu, viral infections, bronchitis ), abnormal kidney function (including kidney failure ), changes in blood test values that show how the kidneys are working, altered sense of taste, difficulty sleeping, low platelet count which can cause bleeding and bruising.
Common side effects (may affect 1 to 10 patients in 100)
Rhinitis, redness and swelling of the gums, sore mouth (including ulcers inside the mouth), bloating in the stomach, sore throat, high blood pressure , red eyes including watery eyes, loss of taste, redness and swelling of the hair follicles in the skin, allergic reactions , severe scaly skin, increased clotting of the blood (including venous thrombosis ), low calcium in the blood, low phosphate in the blood, upper respiratory tract infection, pneumonia , fluid in the chest cavity, blood infection, dehydration, taste disturbance, depression, numbness and tingling in the skin, dizziness, sleepiness , bleeding (from the lips, mouth, stomach or intestines), inflammation in the stomach lining, difficulty swallowing, bleeding in the skin (bruises), minor bleeding, nail disease, acne , yeast infection, fungal infection, urinary tract infection, cystitis , changed values of blood tests that show the way the liver works, high blood fat values other than triglycerides , diabetes , muscle pain.
Uncommon side effects (may affect 1 to 10 patients in 1,000)
Pericardial fluid (accumulation of fluid in the pericardium which in some cases may require drainage and reduce the heart’s ability to pump blood)
Bleeding in the brain in patients with brain tumors or patients treated with blood thinners, bleeding in the eyes.
Pulmonary embolism, perforation of the intestine, problems with wound healing after surgery, inflammation, and swelling of the vocal cords.
Rare side effects (may affect up to 1 in 1,000 patients)
Lung infection caused by Pneumocystis jiroveci (Pneumocystis jiroveci – pneumonia ).
Side effects that have been reported (occurring in an unknown number of users)
Swelling of the face, lips, tongue, or throat may cause difficulty in breathing.
Serious reactions in the skin and/or mucous membranes may include painful blisters and fever ( Stevens-Johnson syndrome).
Unexplained muscle pain, tenderness, or weakness that may indicate muscle damage ( rhabdomyolysis ).
How Torisel should be stored
Store out of sight and reach of children.
Use before the expiry date which is stated on the vial label and the carton. The expiration date is the last day of the specified month.
Store in a refrigerator (2 °C–8 °C).
Do not freeze.
Store vials in the outer carton. Light sensitive.
After initial dilution of the concentrate with 1.8 ml of the supplied liquid, the solution can be stored at a maximum of 25 °C for up to 24 hours and should be protected from light before further dilution.
After further dilution of the mixture with concentrate-liquid with sodium chloride 9 mg/ml (0.9%) solution for injection, the solution can be stored for up to 6 hours at a maximum of 25 °C, protected from light.
Medicines must not be thrown into the drain or among the household waste. Ask the pharmacist how to dispose of medicines that are no longer used. These measures will help to protect the environment.
Contents of the packaging and other information
Contents declaration
- The active substance is temsirolimus.
Each vial of concentrate contains 30 mg of temsirolimus.
After the first dilution of the concentrate with 1.8 ml of the supplied liquid, the concentration of temsirolimus is 10 mg/ml.
- Other ingredients in the concentrate are anhydrous ethanol, all -rac-α- tocopherol (E 307), propylene glycol (E 1520), and citric acid (E 330). The liquid contains polysorbate 80 (E 433), macrogol 400, and anhydrous ethanol (see section 2 “Torisel contains alcohol [ethanol] and Torisel contains propylene glycol”).
Appearance and package sizes of the medicine
Torisel is a concentrate and liquid for infusion and solution.
The concentrate is a clear, colorless pale yellow solution. The liquid is a clear to slightly cloudy light yellow to yellow solution. The solutions are essentially free of visible particles.
Each package of Torisel contains a glass vial with 1.2 ml of concentrate for infusion, and solution and a glass vial with 2.2 ml of liquid.
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium
Manufacturer
Wyeth Lederle Srl
Via Franco Gorgone
Zona Industriale
95100 Catania
Italy
For further information about this medicinal product, contact the representative of the marketing authorization holder:
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