15 mg, 30 mg, 45 mg film-coated tablets
ponatinib
1. What Iclusig is and what it is used for
Iclusig is used to treat adults with the following types of leukemia who no longer benefit from treatment with other drugs or have a specific genetic disorder called a T315I mutation:
- chronic myeloid leukemia (CML): a blood cancer that means that there are too many abnormal white blood cells in the blood and in the bone marrow (where blood cells are formed)
- Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL): a type of leukemia that involves the presence of too many immature white blood cells in the blood and in the blood-forming bone marrow . In this type of leukemia , part of the DNA (genome) has changed so that it forms an abnormal chromosome, the Philadelphia chromosome.
Iclusig belongs to a group of medicines called tyrosine kinase inhibitors. In patients with CML and Ph + ALL, changes in the DNA (genome) trigger a signal that tells the body to produce abnormal white blood cells. Iclusig blocks this signal, thereby stopping the production of these cells.
2. What you need to know before taking Iclusig
Do not take Iclusig
- if you are allergic to ponatinib or any of the other ingredients of this medicine (listed in section 6).
Warnings and cautions
Talk to your doctor or pharmacist before taking Iclusig if you have
- a disease of the liver or pancreas or has impaired kidney function. Your doctor may need to take extra safety precautions.
- abused alcohol.
- had a heart attack or stroke .
- had a blood clot.
- had renal artery stenosis (narrowing of vessels one to one or both kidneys).
- heart problems, including heart failure , irregular heartbeat and QT prolongation.
- high blood pressure .
- or has had an aneurysm (enlargement and weakening of a vessel wall) or a rupture of a vessel wall.
- had problems with bleeding.
- if you have ever had or may have a hepatitis B infection . The reason for this is that Iclusig can cause your hepatitis B to become active again, which in some cases can be fatal. Patients will be closely monitored by their physician for signs of this infection before starting treatment.
The doctor takes/performs:
- an assessment of your heart function and your arteries and veins
- a complete blood statusThis will be repeated every two weeks for the first 3 months after starting treatment. Later it is done every month or according to the doctor’s instructions.
- controls of a serum protein called lipase .
A serum protein called lipase will be checked every two weeks for the first 2 months and then regularly. You may need to discontinue treatment or reduce the dose of Iclusig if your lipase level is high. - Liver
tests Liver function tests will be performed regularly according to your doctor’s instructions.
A condition in the brain called posterior reversible encephalopathy syndrome (PRES) has been reported in patients treated with ponatinib. Symptoms include sudden, severe headaches, confusion, seizures, and vision changes. Talk to your doctor immediately if you experience any of these symptoms during treatment with ponatinib, as it may be serious.
Children and young people
Do not give this medicine to children under 18 years of age as there are no data available for children.
Other drugs and Iclusig
Tell your doctor or pharmacist if you have recently taken or might take any other medicines.
The following medicines may affect or be affected by Iclusig:
- ketoconazole , itraconazole, voriconazole : medicines used to treat fungal infections
- indinavir, nelfinavir, ritonavir, said kv inavir : drugs against HIV – infection
- clarithromycin , telithromycin , troleandomycin : drugs for bacterial infections
- nefazodone : an antidepressant
- St. John’s wort : an herbal remedy for depression
- carbamazepine : a drug for epilepsy , euphoria / depression and certain pain conditions
- phenobarbital , phenytoin : antiepileptic drugs
- rifabutin , rifampicin : medicines to treat tuberculosis or certain other infections you
- digoxin : a drug for heart failure
- dabigatran : a drug that prevents the formation of blood clots
- colchicine : a drug for gout attacks
- pravastatin , rosuvastatin : drugs that lower elevated cholesterol levels
- methotrexate : a drug for severe joint inflammation ( rheumatoid arthritis ), cancer and the skin disease psoriasis
- sulfasalazine : a drug for severe colitis and rheumatoid arthritis.
Iclusig with food and drink
Avoid grapefruit products, e.g. grapefruit juice.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
- Information on contraceptives for men and womenFertile women receiving Iclusig should avoid becoming pregnant. Men treated with Iclusig are advised not to have children during treatment. An effective method of contraception should be used during treatment.
Use Iclusig during pregnancy only if your doctor tells you it is absolutely necessary , as there is a potential risk to the unborn baby. - Breast-feeding
Stop breast-feeding during treatment with Iclusig. It is not known if Iclusig passes into breast milk.
Driving and using machines
You should be especially careful when driving or using machines as patients taking Iclusig may experience visual disturbances, dizziness, drowsiness, and fatigue.
Iclusig contains lactose
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
How to take Iclusig
Always take this medicine exactly as your doctor or pharmacist has told you. Ask your doctor or pharmacist if you are unsure.
Iclusig treatment should be prescribed by a doctor who has experience in the treatment of leukemia.
Iclusig is available as:
- a 45 mg film-coated tablet of the recommended dose of a
- a 15 mg film-coated tablet and a 30 mg film-coated tablet to make dose adjustments.
The recommended starting dose is a 45 mg film-coated tablet once daily.
Your doctor may reduce your dose or ask you to temporarily stop taking Iclusig if:
- an appropriate response to the treatment has been achieved
- The number of white blood cells called neutrophils decreases
- the number of platelets ( platelets ) decreases
- a severe side effect , which does not affect the blood, occurs
- inflammation of the pancreas.
- elevated levels of the protein are lipase or amylase in the blood
- you have problems with the heart or blood vessels.
- you have a liver disease.
Iclusig treatment can be resumed with the same dose or a lower dose when a side effect has passed or is under control. Your doctor may evaluate your response to treatment at regular intervals.
Method of use
Swallow the tablets whole with a glass of water. The tablets can be taken with or without food. The tablets must not be crushed or dissolved.
Do not swallow the container with desiccant contained in the bottle.
Usage time
You must take Iclusig every day for as long as it is prescribed. This is a long-term treatment.
If you take more Iclusig than you should
Talk to your doctor immediately if this happens.
If you forget to take Iclusig
Do not take a double dose to make up for a forgotten dose. Take the next dose at the usual time.
If you stop taking Iclusig
Do not stop taking Iclusig without your doctor’s permission.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Patients over the age of 65 are more likely to experience side effects.
Seek medical attention immediately if you get any of the following serious side effects.
If you get any abnormal results from blood tests, contact your doctor immediately.
Serious adverse s ( common: may affect up to 1 in 10):
- pneumonia (may cause difficulty breathing)
- inflammation of the pancreas. Tell your doctor immediately if you get inflammation of the pancreas. The symptoms are severe pain in the abdomen and back.
- fever, often with other signs of infection due to decreased white blood cell count
- heart attack (symptoms include: sudden palpitations, chest pain, shortness of breath)
- changes in blood levels:
- decreased number of red blood cells (symptoms include: weakness, dizziness, fatigue)
- decreased platelet count (symptoms include: increased tendency to bleed or bruise)
- decreased number of white blood cells called neutrophils (symptoms include: increased susceptibility to infection )
- elevated levels of the serum protein called lipase
- heart rhythm disorder, abnormal heart rate
- heart failure (symptoms include: weakness, fatigue, swollen legs)
- unpleasant pressure, congestion, compression or pain in the middle of the chest ( angina pectoris ) or pain in the chest that is not related to the heart
- high blood pressure
- narrowing of the artery in the brain
- problems with the blood vessels in the heart muscle
- blood infection
- swollen or red area of skin that feels hot and tender ( cellulite )
- dehydration
- breathing difficulties
- fluid in the thorax (may cause difficulty breathing)
- diarrhea
- blood clot in a deep vein, sudden narrowing of a vein, blood clot in a blood vessel in the lung (symptoms include: hot flashes, redness of the skin, redness of the face, difficulty breathing)
- stroke (symptoms include difficulty speaking or moving, drowsiness, migraines , abnormal sensations)
- blood circulation problems (symptoms include: pain in legs or arms, feeling of cold in the extremities of the limbs )
- blood clot in the major artery are carrying blood to the head and neck (carotid artery)
- constipation
- decreased sodium content in the blood
- increased susceptibility to bleeding or bruising
Other possible side effects that may occur with the following frequencies are:
Very common side effects are (can occur in more than 1 in 10):
- upper respiratory tract infection (may cause difficulty breathing)
- reduced appetite
- insomnia
- headache, dizziness
- cough
- diarrhea, vomiting, nausea
- elevated levels in the blood of several liver enzymes called:
- alanine aminotransferase
- aspartate aminotransferase
- rash, dry skin, itching
- pain in the skeleton, joints, muscles, back, arms or legs, muscle spasms
- fatigue, accumulation of fluid in the arms and / or legs, fever, pain
Common side effects are (may affect up to 1 in 10):
- inflammation in the hair follicles, swollen, red area of the skin or under the skin that feels hot and tender
- impaired thyroid function
- fluid accumulation in the body
- low levels of calcium , phosphate or potassium in the blood
- elevated levels of blood sugar and uric acid in the blood, high blood fat values of triglyceride s
- weight loss
- mini- stroke
- nerve disorders in the arms and / or legs (often causes numbness and pain in hands and feet)
- lethargy , migraine
- increased or decreased sensation or sensitivity, abnormal sensations, e.g. tingling, crawling and itching
- blurred vision, dry eyes, eye infection , visual disturbance
- tissue swelling in the eyelids or around the eyes due to fluid accumulation
- palpitation
- pain in one or both legs when walking or exercising, which passes after a few minutes of rest
- hot flashes, reddening of the skin
- nosebleeds, difficulty speaking, high blood pressure in the blood vessels of the lungs
- elevated levels in the blood of liver and pancreatic enzymes:
- amylase
- alkaline phosphatase
- gamma ‑ glutamyltransferase
- heartburn caused by reflux of stomach acids, inflammation of the mouth, swollen stomach or discomfort or indigestion, dry mouth
- bleeding in the stomach (symptoms include: abdominal pain, bloody vomiting)
- elevated levels of bilirubin (the yellow breakdown substance of the blood pigment) in the blood (symptoms include: dark amber urine)
- pain in skeletal system or neck
- skin rash, scaly skin, abnormal thickening of the skin, redness , bruising, pain in the skin, changes in skin color, hair loss
- swelling of the face due to excess fluid
- night sweats, increased sweating
- inability to get or maintain an erection
- chills, flu-like illness
Less common side effects are (may affect up to 1 in 100):
- metabolic disorders caused by the degradation products of dying cancer cells
- bleeding in the brain
- narrowing of blood vessels in the eye
- heart problems, left-sided chest pain, left ventricular dysfunction
- narrowing of the blood vessels, poor blood circulation, sudden rise in blood pressure
- renal artery stenosis (narrowing of vessels to one or both kidneys)
- circulatory problems in the spleen
- liver damage, jaundice (symptoms include: yellowish skin and yellow eyes)
- headache, confusion, seizures and loss of vision, which can be symptoms of a condition in the brain called posterior reversible encephalopathy syndrome (PRES).
No known frequency (can not be calculated from the available data)
- recurrence (reactivation) of hepatitis B infection when you have previously had hepatitis B (a liver infection)
- troublesome skin rash with blisters or scaly skin that spreads throughout the body and causes fatigue. Tell your doctor immediately if you get these symptoms.
- an enlargement and weakening of a vessel wall or a rupture in a vessel wall ( aneurysms and arterial dissections).
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist, or nurse. This also applies to any side effects not mentioned in this information. You can also report side effects directly to the Medical Products Agency. By reporting side effects, you can help increase drug safety information.
5. How to store Iclusig
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 can label and carton after EXP. dat. The expiration date is the last day of the specified month.
Store in the original package. Sensitive to light.
The jar contains a sealed plastic container that contains a desiccant in the form of a molecular sieve. The container must remain in the jar. Do not swallow the container with desiccant.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
6. Contents of the packaging and other information
Content declaration
- The active substance is ponatinib.One 15 mg film-coated tablet contains 15 mg ponatinib (as ponatinib hydrochloride).One 30 mg film-coated tablet contains 30 mg of ponatinib (as ponatinib hydrochloride).One 45 mg film-coated tablet contains 45 mg of ponatinib (as ponatinib hydrochloride).
- The other ingredients are lactose monohydrate , microcrystalline cellulose, sodium starch glycolate , colloidal anhydrous silicon, magnesium stearate, talc, macrogol 4000, polyvinyl alcohol, titanium dioxide (E171). See section 2 “Iclusig contains lactose”.
What the medicine looks like and contents of the pack
Iclusig film-coated tablets are white, round, and rounded on the top and bottom.
Iclusig 15 mg film-coated tablets are approximately 6 mm in diameter with “A5” on one side.
Iclusig 30 mg film-coated tablets are approximately 8 mm in diameter with “C7” on one side.
Iclusig 45 mg film-coated tablets are approximately 9 mm in diameter with “AP4” on one side.
Iclusig is supplied in plastic jars, each containing a container with a desiccant in the form of a molecular sieve. The jars are packed in a box.
Cans of Iclusig 15 mg contain either 30, 60, or 180 film-coated tablets.
Cans of Iclusig 30 mg contain 30 film-coated tablets.
Cans of Iclusig 45 mg contain either 30 or 90 film-coated tablets.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Incyte Biosciences Distribution BV
Paasheuvelweg 25
1105 BP Amsterdam
Netherlands
Manufacturer
Haupt Pharma Amareg GmbH
Donaustaufer Str. 378
93055 Regensburg
Germany
Incyte Biosciences Distribution BV
Paasheuvelweg 25
1105 BP Amsterdam
Netherlands
Tjoapack Netherlands BV
Nieuwe Donk 9
4879 AC Etten-Leur
Netherlands