Ivosidenib + azacitidine

Ivosidenib + azacitidine is a combination of two medicines. Your haematology team might recommend it for you if:

• You are newly diagnosed with AML AND
• You have a genetic change in a gene called IDH1 AND
• Intensive chemotherapy is not suitable for you

Ivosidenib

Ivosidenib is a targeted medicine. It blocks an abnormal version of a protein called IDH1. This abnormal protein can stop cells growing properly. This can lead to the development of cancer. Blocking the protein can help kill cancer cells.

The brand name for ivosidenib is Tibsovo.

Azacitidine

Azacitidine is a chemotherapy medicine that can turn on genes that have been turned off. This includes cancer-suppressing genes that are often turned off in AML cells. Azacitidine can also stop AML cells from making proteins. This can stop cancer cells growing and dividing.

Brand names for azacitidine injections include:

• Azacitidine betapharm
• Azacitidine Sandoz
• Azacitidine Seacross
• Azacitidine Tillomed
• Vidaza

Back to top

Before starting ivosidenib + azacitidine, your medical team will carry out checks to make sure it is suitable for you. These might include:

• A heart tracing (ECG) to check the electrical activity of your heart
• Blood tests to measure your blood counts
• Blood tests to check your liver and kidney function
• Bone marrow tests
• A pregnancy test

Things to tell your haematology team

Before starting treatment, tell your medical team if you have heart, kidney or liver problems. This is because ivosidenib can affect how your heart, kidneys and liver work.

Some medicines or drugs may interact with ivosidenib. It is important to tell your team about any medicines you are taking. This includes medicines you have bought yourself, without a prescription. Examples include:

• Some antibiotic, antifungal and antiviral medicines
• Some medicines used to lower your cholesterol levels
• Some medicines used after organ transplants, known as immunosuppressants
• Some medicines to help stop you feeling or being sick
• Some medicines used for cancer
• Some medicines that affect your heartbeat
• Some medicines used for type 2 diabetes
• Warfarin, a medicine used to prevent blood clots
• Some medicines used to treat severe pain or to stop you feeling pain in surgery
• Pimozide, a medicine used to treat schizophrenia
• Methadone, a medicine used for severe pain, or morphine or heroin addiction
• Omeprazole, a medicine used to treat stomach ulcers and acid reflux
• Furosemide, a medicine used to treat a build up of fluid known as oedema
• Lamotrigine, a medicine used to treat epilepsy

Back to top

You will receive treatment in a cycle of 28 days. On some days you will have ivosidenib + azacitidine. On some days you will only have ivosidenib.

Dose

Your medical team will let you know what dose you are on, but below are the most common doses that are used.

Ivosidenib

Most adults with AML take two 250mg ivosidenib tablets every day. You usually take both at the same time each day.

Your medical team may suggest a different dose. This will depend on your circumstances and any other medicines you are taking. They will tell you what dose they recommend for you.

Azacitidine

Your doctor will work out the best dose of azacitidine for you. Your dose will be based on your height, weight and how well you respond to treatment. They will tell you what dose they recommend for you.

Back to top

There are several precautions to be aware of when you are having your treatment.

• Azacitidine injections may make you feel tired or weak. They can also make it difficult to concentrate. Take care if you are driving or using tools or machinery.
• Azacitidine can affect how well your kidneys work. If you stop peeing, or you’re peeing less than usual, tell your doctor straight away.

Back to top

Ivosidenib + azacitidine may harm unborn babies.

• If you could get pregnant, it is important to use effective contraception. You need to do this while you are having ivosidenib + azacitidine and for 6 months after you stop. The treatment might affect hormonal contraceptive pills or devices. So it is important to use a barrier method like a condom, diaphragm or cap.
• If you could make someone pregnant, it is important to use effective contraception. You need to do this while you are having ivosidenib + azacitidine and for 3 months after you stop.
• If you think you might be pregnant, tell your medical team as soon as possible. They may recommend stopping ivosidenib + azacitidine for a while. They could also recommend switching to a different treatment.
• If you are planning to get pregnant, or make someone pregnant, tell your medical team. They can discuss your treatment options with you.

Breastfeeding

Scientists are not sure if ivosidenib + azacitidine passes into breast milk. If it does, it could be a risk for breastfed babies or children. You should not breastfeed when having ivosidenib + azacitidine.

Back to top

During your treatment with ivosidenib + azacitidine you will have:

• Regular blood tests
• A heart tracing (ECG) every week at first, and then every month

You may also have occasional bone marrow tests or other tests. Your medical team will let you know what tests you will need and how often.

Your medical team will use the results of these tests to:

• Check how well ivosidenib + azacitidine is working for you
• Make sure your blood counts have not dropped too low
• Check how well your liver and kidneys are working
• Check the electrical activity of your heart
• Check the levels of salts in your blood

Differentiation syndrome

Ivosidenib + azacitidine might sometimes cause a serious problem called differentiation syndrome. This can happen if recovering white blood cells release too many immune chemicals. This can trigger a severe reaction.

Your medical team will monitor you for signs of differentiation syndrome. If it happens, it can be treated with steroids.

Back to top

You usually carry on having ivosidenib + azacitidine unless:

• It has not worked well enough
• It stops working well
• You are having side effects that are difficult to cope with

If this happens, your doctor might adjust your dose, stop your treatment or suggest different treatment.

You may get some side effects while you are having ivosidenib + azacitidine.

Some people may have very few side effects, whereas other people experience more serious side effects.

Tell your medical team if you get any side effects. They may be able to suggest things to help.

If you are getting side effects that are difficult to cope with, your medical team might suggest:

• Temporarily stopping treatment
• Lowering your dose of ivosidenib + azacitidine
• Delaying your next azacitidine treatment cycle

The most common serious side effects for people having ivosidenib + azacitidine include:

• Differentiation syndrome. This can cause symptoms like:
  • Fever, cough, shortness of breath, wheezing.
  • Weight gain.
  • Swelling of your arms, legs and neck.
  • A build up of fluid around your heart. This can cause shortness of breath, difficulty breathing when lying down and chest pain.
  • A build up of fluid around your lungs which can cause chest pain, cough and shortness of breath.
  • Low blood pressure.
  • Kidney failure which can cause you to be sick or feel tired or exhausted.
• A low platelet count. This might lead to unexpected bruising or bleeding, like nosebleeds, bleeding gums, blood spots or rashes.

Very common side effects affect more than 10 in every 100 people who are having ivosidenib + azacitidine.

Very common side effects include:

• A low level of some white blood cells. This makes you more likely to get infections and can mean that any infections you do get are more serious.
• A high level of some other white blood cells.
• Finding it hard to fall asleep or stay asleep.
• Headache.
• Dizziness.
• Being sick.
• Pain in your arms, wrists, shoulders or hands.
• Pain in your legs, ankles or feet.
• Joint pain.
• Back pain.
• Your heart taking longer to recover after each heartbeat. This might show on an ECG or might cause symptoms such as:
  • Blackouts, fainting or losing consciousness.
  • Fits (seizures).
  • A fast, irregular heartbeat.

Back to top

Common side effects affect more than 1 but less than 10 out of every 100 people who are having ivosidenib + azacitidine.

Common side effects include:

• A low level of some white blood cells
• Nerve damage. This can cause symptoms like:
  • Numbness and tingling in your feet or hands
  • Burning, stabbing or shooting pain in your legs, feet, arms or hands
  • Loss of balance and co-ordination
  • Muscle weakness, especially in your feet
• Painful mouth or throat

Back to top

If ivosidenib + azacitidine are not working well, your medical team might suggest:

• Altering your treatment cycle
• Changing your dose
• Stopping treatment if your blood counts drop

If this is not suitable for you, or does not work, they will talk to you about your treatment options.

Back to top