Overview of Ph+ CML

What is Ph+ CML?

Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) is a type of cancer of the bone marrow and blood. In people with Ph+ CML, the bone marrow (the soft tissue inside bones where blood cells are made) produces too many white blood cells and these cells are often immature or damaged. About 4600 Americans were diagnosed with Ph+ CML in 2004, and the median age of diagnosis is 65.

A Closer Look at "Ph+ CML"

"Ph" is an abbreviation for "Philadelphia chromosome," the name given to the abnormal chromosome that can lead to the overproduction of white blood cells. The plus sign (+) means that your laboratory tests show your bone marrow and white blood cells contain the abnormal Philadelphia chromosome. "Chronic" means that it progresses slowly. "Myeloid" refers to the type of white blood cells that are affected. "Leukemia" tells you it is a cancer of the bone marrow and white blood cells.

So, when your doctor says you have Ph+ CML, it means that your bone marrow cells have an abnormal chromosome and your body is producing too many white blood cells. In addition to crowding out normal, healthy cells, these white blood cells often do not function normally.

How does Ph+ CML happen?

The soft tissue inside our bones, called the bone marrow, produces a type of cell called a stem cell. As stem cells mature, they can turn into platelets, red blood cells, or white blood cells. Ph+ CML happens because of changes in the genetic material of these stem cells.

Chromosomes are the parts of our cells that carry our DNA and genes—the things that give us our physical traits, such as blue eyes or brown hair, and that tell our body how to handle all the functions of life, including the process of making blood cells. Humans have 23 pairs of chromosomes. Ph+ CML happens when some genetic material from one chromosome (chromosome 9) switches position with some genetic material from another chromosome (chromosome 22).

The new genetic material on chromosome 22 is called BCR-ABL and leads to abnormalities in your body's process for making blood cells. When chromosome 22 has this abnormal BCR-ABL gene, scientists call it the Philadelphia chromosome. People with Ph+ CML have the BCR-ABL gene in their stem cells and white blood cells. The BCR-ABL gene produces a protein called Bcr-Abl. Scientists distinguish between the name of the gene and protein by how they are written.

The Bcr-Abl protein causes your bone marrow to produce more and more white blood cells and these white blood cells are often damaged. It acts like a switch that keeps your white blood cell production in the "on" position. Normally, your body would stop producing white bloods that weren't needed and damaged blood cells would die off, but the Bcr-Abl protein interferes with these processes. Instead, your bone marrow keeps making damaged white blood cells that, over time, crowd out healthy red blood cells and platelets.

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Scientists do not know exactly why the genetic material switches between the 2 chromosomes and continue to search for causes of Ph+ CML. Although Ph+ CML involves genetic material, be assured that it is not inherited. The abnormal gene is not passed down from parent to child.

Signs and symptoms of Ph+ CML

Some common symptoms of Ph+ CML are:

  • Feeling very tired all the time
  • Bruising easily or bleeding that takes longer to stop than normal
  • Unexplained weight loss
  • Pain in the bones and joints

Many people are diagnosed in the early stage of Ph+ CML and do not have any obvious signs and symptoms. Often Ph+ CML is discovered during a routine blood test when results show the person has an elevated white blood cell count.

Phases of Ph+ CML

    The phases of Ph+ CML are based on the percentage of blast cells (immature white blood cells) as compared with other blood cells in the bone marrow:

  • Chronic phase: no more than 5% of blood cells in the bone marrow sample are blast cells
  • Accelerated phase: between 6% and 30% of blood cells in the sample are blast cells
  • Blast crisis: blast cells make up more than 30% of blood cells in the sample

Monitoring Your Ph+ CML

Learn more about tests that can help monitor whether or not you
are responding to your TASIGNA® (nilotinib) 150-mg or 200-mg capsules treatment or for possible TASIGNA-related side effects.
Monitoring Ph+ CML

Learn more

What Does Intolerance Mean?

What Does Resistance Mean?

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What is the most important information to know about TASIGNA?
TASIGNA can cause a possible life-threatening heart problem called QT prolongation.

QT prolongation causes an irregular heartbeat, which may lead to sudden death.

Your doctor should check your heart with a test called an electrocardiogram (ECG):
 • Before starting TASIGNA
• 7 days after starting TASIGNA
• With any dose changes
• Regularly during TASIGNA treatment

TASIGNA Indications

TASIGNA is a prescription medicine used to treat a type of leukemia called Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) in adults who:

  • Are newly diagnosed with Ph+ CML in chronic phase (CP). The study is ongoing and further data will be required to determine long-term outcomes
  • Are in chronic phase (CP) or accelerated phase (AP) Ph+ CML and are resistant or intolerant to prior therapy that included imatinib

Important Safety Information

Important Information about TASIGNA® (nilotinib)

It is not known if TASIGNA is safe or effective in children.

What is the most important information to know about TASIGNA?

TASIGNA can cause a possible life-threatening heart problem called QT prolongation.
QT prolongation causes an irregular heartbeat, which may lead to sudden death.

Your doctor should check your heart with a test called an electrocardiogram (ECG):

  • Before starting TASIGNA
  • 7 days after starting TASIGNA
  • With any dose changes
  • Regularly during TASIGNA treatment

You may lower your chances for having QT prolongation with TASIGNA if you:

  • Take TASIGNA on an empty stomach
  • DO NOT TAKE TASIGNA WITH FOOD
    • Food can affect the levels of TASIGNA in your body, which can lead to serious side effects
    • Taking TASIGNA on an empty stomach may lower your chances of having a possibly life-threatening heart problem called QT prolongation
    • QT prolongation causes an irregular heartbeat, which may lead to sudden death

Taking TASIGNA:

  • Take TASIGNA at least 2 hours after eating any food
  • After taking TASIGNA, wait at least 1 hour before eating any food
  • Avoid grapefruit, grapefruit juice, and any supplement containing grapefruit extract while taking TASIGNA. Food and grapefruit products increase the amount of TASIGNA in your body
  • Avoid taking other medicines or other supplements with TASIGNA that can also cause QT prolongation

Who should not take TASIGNA?
Do not take if you have:

  • Low levels of potassium or magnesium in your blood
  • Long QTc syndrome

TASIGNA is a prescription medication. TASIGNA comes in 150 mg and 200 mg capsules. Your doctor will prescribe 300 mg of TASIGNA to be taken twice a day for a total daily dose of 600 mg or 400 mg of TASIGNA to be taken twice a day for a total daily dose of 800 mg. Each dose should be taken approximately 12 hours apart.

Swallow TASIGNA capsules whole with water. If you cannot swallow TASIGNA capsules whole, tell your doctor.

  • If you cannot swallow TASIGNA capsules whole:
    • Open the TASIGNA capsules and sprinkle the contents in 1 teaspoon of applesauce (puréed apple).
      • Do not use more than 1 teaspoon of applesauce.
      • Only use applesauce. Do not sprinkle TASIGNA onto other foods.
    • Swallow the mixture right away (within 15 minutes).
  • Do not drink grapefruit juice, eat grapefruit, or take supplements containing grapefruit extract. It may affect the levels of TASIGNA in the blood.
  • If you miss a dose, take your next dose as scheduled. Do not take a double dose to make up for a missed dose.

Before taking TASIGNA

Talk to your doctor or pharmacist about all other medication(s) you may be taking, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements, since they may affect how TASIGNA works and increase your chance of serious and life-threatening side effects.

Tell your doctor if:

  • You have a heart disorder or are taking medication for the heart
  • You have an irregular heartbeat
  • You have QT prolongation or a family history of it
  • You have liver problems
  • You know that you suffer from low blood levels of electrolytes, such as potassium, magnesium, or calcium
  • You have a pancreas disorder
  • You have had a surgical procedure involving the removal of the entire stomach (total gastrectomy)

Also tell your doctor if you are pregnant, breast-feeding, or lactose-intolerant. The TASIGNA capsules contain lactose. Most patients who have mild or moderate lactose intolerance can take TASIGNA.

Call your doctor right away if you faint or have an irregular heartbeat while taking TASIGNA.

 

These can be symptoms of QT prolongation.

Call your doctor immediately if you experience any of these symptoms.

Serious side effects

TASIGNA is sometimes associated with serious side effects, some symptoms of which include:

  • Feeling lightheaded, fainting, or having an irregular heartbeat
  • Unexplained bleeding or bruising
  • Blood in urine or stool
  • Unexplained weakness
  • Yellow skin and eyes
  • Shortness of breath
  • Sudden stomach area pain with nausea and vomiting
  • Sudden headache, changes in your eyesight, not being aware of what is going on around you, and becoming unconscious

Common side effects

Most patients experience side effects at some time. Some common side effects you may experience include:

  • Low blood count
  • Rash
  • Nausea
  • Fever
  • Stomach (abdominal) pain
  • Headache
  • Itching
  • Muscle and joint pain
  • Tiredness
  • Diarrhea
  • Constipation
  • Back pain
  • Muscle spasms
  • Weakness
  • Hair loss
  • Runny or stuffy nose, sneezing, sore throat
  • Cough

Be sure to tell your doctor or pharmacist if you have any side effects during treatment with TASIGNA.

Tell your doctor if you are pregnant or planning to become pregnant. TASIGNA may harm your unborn baby. If you are able to become pregnant, you should use effective birth control during treatment with TASIGNA. Talk to your doctor about the best birth control methods to prevent pregnancy while you are taking TASIGNA.

Tell your doctor if you are breast-feeding or plan to breast-feed. It is not known if TASIGNA passes into your breast milk. You and your doctor should decide if you will take TASIGNA or breast-feed. You should not do both.

If you take too much TASIGNA, call your doctor or poison control center right away.

Your doctor will check your heart, do regular blood tests, and take bone marrow samples during treatment with TASIGNA. These are done to check for side effects with TASIGNA and to see how well TASIGNA is working for you. Your doctor should check your blood to monitor the amount of blood cells (white blood cells, red blood cells, and platelets) during treatment. These should be checked every 2 weeks for the first 2 months and then monthly thereafter, or as considered necessary by your doctor.

Your doctor may have you stop TASIGNA for some time or reduce your dose if you have side effects with it.

Please see accompanying patient information, including Boxed WARNING, and the TASIGNA Medication Guide you received with your prescription.