What causes CML?

Understanding what causes chronic myeloid leukemia (CML)Chronic myeloid leukemia (CML): a slow-developing cancer of the blood in which the body produces uncontrolled numbers of abnormal blood cells starts with understanding the role of chromosomesChromosome: a part of a cell that contains genes, the basic units that carry hereditary information. An individual chromosome can contain hundreds or thousands of genes, structures in your cells that contain DNA and other genetic material. DNA within the chromosomes provides instructions for blood cells to be made in your bone marrowBone marrow: the soft tissue inside bones that produces blood cells.

In CML, the body makes an uncontrolled number of abnormal blood cells. In almost all patients with CML:

When you have CML, the BCR-ABL protein causes the bone marrow to produce more white blood cellsWhite blood cells: blood cells that help fight infections. When the level of a certain type of white blood cell is lower than normal, it is called neutropenia, even when they are not needed. These are mostly damaged or immature. Over time, these extra, unhealthy white blood cells overcrowd healthy white blood cells, red blood cellsRed blood cells: blood cells that carry oxygen to all parts of the body. When red blood cell levels are lower than normal, it is called anemia, and plateletsPlatelets: blood cells that help stop bleeding. When platelet levels are lower than normal, it is called thrombocytopenia. The immature white blood cells are called blast cellsBlast cells: immature white blood cells found in abnormally large numbers in CML patients, or blasts.

Phases of CML

There are 3 phases of CML. They are defined by the percentage of blasts in the bone marrow, compared with other blood cells:

CML Chronic Phase

INDICATIONS AND USAGE

SPRYCEL® (dasatinib) is a prescription medicine used to treat adults who have:

  • newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. The effectiveness of SPRYCEL in these patients is based on a study that measured two types of response to treatment (cytogenetic and molecular) by 1 year. The study is ongoing to find out how SPRYCEL works over a longer period of time
  • Ph+ CML who are no longer benefitting from, or did not tolerate, other treatment including Gleevec® (imatinib mesylate)
  • Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who no longer benefit from, or did not tolerate, other treatment

SPRYCEL® (dasatinib) IMPORTANT SAFETY INFORMATION FOR PATIENTS

It is not known if SPRYCEL is safe and effective in children younger than 18 years old.

Before you take SPRYCEL, tell your healthcare provider if you:

  • have problems with your immune system
  • have liver problems
  • have heart problems
  • are lactose intolerant
  • have any other medical conditions
  • are pregnant or planning to become pregnant. SPRYCEL may harm your unborn baby. Women should not become pregnant
    while taking SPRYCEL. Talk to your healthcare provider right away if you are pregnant or plan to become pregnant
  • are breast-feeding or plan to breast-feed. It is not known if SPRYCEL passes into your breast milk or if it can harm your baby.
    You and your healthcare provider should decide if you will take SPRYCEL or breast-feed. You should not do both

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines,
vitamins, antacids, and herbal supplements.

Especially tell your healthcare provider if you take:

  • medicines that increase the amount of SPRYCEL in your bloodstream, such as: Nizoral® (ketoconazole),
    Sporanox® (itraconazole), Norvir® (ritonavir), Reyataz® (atazanavir sulfate), Crixivan® (indinavir), Viracept® (nelfinavir),
    Nefazodone (serzone®, nefadar), Invirase® (saquinavir), Ketek® (telithromycin), E-mycin® (erythromycin),
    and Biaxin® (clarithromycin).
  • medicines that decrease the amount of SPRYCEL in your bloodstream, such as: Decadron® (dexamethasone),
    Dilantin® (phenytoin), Tegretol® (carbamazepine), Rimactane® (rifampin), and Luminal® (phenobarbital).
  • medicines whose blood levels might change by taking SPRYCEL, such as: Sandimmune® (cyclosporine),
    Alfenta® (alfentanil), Fentanyl® (fentanyl), Orap® (pimozide), Rapamune® (sirolimus), Prograf® (tacrolimus),
    and Ergomar® (ergotamine).

SPRYCEL is best absorbed from your stomach into your bloodstream in the presence of stomach acid. You should avoid
taking medicines that reduce stomach acid, such as:
Tagamet® (cimetidine), Pepcid® (famotidine), Zantac® (ranitidine),
Prilosec® (omeprazole), Protonix® (pantoprazole sodium), Nexium® (esomeprazole), AcipHex® (rabeprazole),
and Prevacid® (lansoprazole).

Medicines that neutralize stomach acid, such as Maalox® (aluminum hydroxide/magnesium hydroxide),
Tums® (calcium carbonate), or Rolaids® (calcium carbonate and magnesia), may be taken up to 2 hours before or 2 hours
after SPRYCEL.

Since SPRYCEL therapy may cause bleeding, tell your healthcare provider if you are using blood thinner medicine, such as
Coumadin® (warfarin sodium) or aspirin.

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get
a new medicine.

Take SPRYCEL exactly as prescribed by your healthcare provider

  • Take SPRYCEL with or without food. Try to take SPRYCEL at the same time each day
  • Swallow SPRYCEL tablets whole with water. Do not break, cut, or crush the tablets
  • You should not drink grapefruit juice while taking SPRYCEL
  • If you miss a dose of SPRYCEL, take your next scheduled dose at its regular time. Do not take two doses at the same time

SPRYCEL may cause serious side effects, including:
  • Low Blood Cell Counts: SPRYCEL may cause low red blood cell counts (anemia), low white blood cell counts (neutropenia),
    and low platelet counts (thrombocytopenia). Your healthcare provider will do blood tests to check your blood cell counts regularly
    during your treatment with SPRYCEL. Call your healthcare provider right away if you have a fever or any signs of an infection
    while taking SPRYCEL
  • Bleeding: SPRYCEL may cause severe bleeding that can lead to death. Call your healthcare provider right away
    if you have:
    • -    unusual bleeding or bruising of your skin
    • -    bright red or dark, tar-like stools
    • -    a decrease in your level of consciousness, headache, or change in speech
  • Your body may hold too much fluid (fluid retention): In severe cases, fluid may build up in the lining of your lungs, the sac
    around your heart, or your stomach cavity. Call your healthcare provider right away if you get any of these symptoms during
    treatment with SPRYCEL:
    • -    swelling all over your body
    • -    weight gain
    • -    shortness of breath and cough
  • Heart problems: SPRYCEL may cause an abnormal heart rate, heart problems, or a heart attack that can lead to death.
    Your healthcare provider will monitor the potassium and magnesium levels in your blood and your heart function
  • Pulmonary Arterial Hypertension (PAH): SPRYCEL may cause high blood pressure in the vessels of your lungs.
    PAH may happen at any time during your treatment with SPRYCEL. Your healthcare provider should check your heart and
    lungs before and during your treatment with SPRYCEL. Call your healthcare provider right away if you have shortness of
    breath, tiredness, or swelling all over your body (fluid retention)

Other common side effects of SPRYCEL therapy include: diarrhea, headache, cough, skin rash, fever, nausea, tiredness, vomiting,
muscle pain, weakness, and infections.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible
side effects of SPRYCEL. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Please read the Patient Information in the full Prescribing Information.