Imatinib

Imatinib interferes with the growth of some cancer cells.

Imatinib is used to treat certain types of leukemia (blood cancer), bone marrow disorders, and skin cancer, or certain tumors of the stomach and digestive system.

Imatinib may also be used for purposes not listed in this medication guide.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

You should not use imatinib if you are allergic to it.

To make sure imatinib is safe for you, tell your doctor if you have:

• liver disease;
• kidney disease;
• underactive thyroid, recent or upcoming thyroid surgery;
• heart disease, congestive heart failure;
• history of stomach ulcer or bleeding; or
• if you are receiving chemotherapy.

Do not use imatinib if you are pregnant. It could harm the unborn baby. Use effective birth control to prevent pregnancy, and tell your doctor if you become pregnant during treatment.

It is not known whether imatinib passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Imatinib can affect growth in children. Talk with your doctor if you think your child is not growing at a normal rate while using this medicine.

• Store imatinib tablets at room temperature between 15 and 30°C (59-86°F), in a tightly sealed container to protect from moisture.
• Keep this and all medications out of the reach of children.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Imatinib should be taken with a meal. Do not take imatinib on an empty stomach.

Take imatinib with a full glass of water.

You may dissolve the imatinib tablet in water or apple juice to make swallowing easier.

Do not crush, chew, or break an imatinib tablet. The medicine from a crushed or broken pill can be dangerous if it gets in your eyes, mouth, or nose, or on your skin. If this occurs, wash your skin with soap and water or rinse your eyes with water. Ask your doctor or pharmacist how to safely handle and dispose of a crushed or broken tablet.

Imatinib can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests.

You will also need frequent tests to check your liver function.

Do not stop using imatinib without your doctor's advice.

Store at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Many drugs can interact with imatinib. Not all possible interactions are listed here. Tell your doctor about all your medications and any you start or stop using during treatment with imatinib, especially:

• bosentan;

• dihydroergotamine or ergotamine;

• fentanyl (Abstral, Actiq, Fentora, Duragesic, Lazanda, Onsolis);

• nefazodone;

• pimozide;

• St. John's wort;

• an antibiotic--clarithromycin, erythromycin, telithromycin;

• antifungal medicine--itraconazole, ketoconazole, posaconazole, voriconazole;

• antiviral medicine to treat hepatitis C or HIV/AIDS--atazanavir, boceprevir, cobicistat (Stribild, Tybost), delavirdine, efavirenz, fosamprenavir, indinavir, nelfinavir, nevirapine, ritonavir, saquinavir, telaprevir;

• a blood thinner--warfarin, Coumadin, Jantoven;

• heart medicine--nicardipine, quinidine;

• medicine to prevent organ transplant rejection--cyclosporine, sirolimus, tacrolimus;

• seizure medication--carbamazepine, fosphenytoin, oxcarbazepine, phenobarbital, phenytoin, primidone; or

• tuberculosis medication--isoniazid, rifabutin, rifampin, rifapentine.

This list is not complete and many other drugs can interact with imatinib. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

It is very important that your doctor check your progress at regular visits to make sure that imatinib is working properly. Blood tests may be needed to check for unwanted effects. Be sure to keep all appointments.

Using imatinib while you are pregnant can harm your unborn baby. Use a highly effective form of birth control (especially if you are a sexually active female patient) during treatment and for 14 days after your last dose to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Serious skin reactions can occur during treatment with imatinib. Check with your doctor right away if you have blistering, peeling, or loosening of the skin, red skin lesions, severe acne or skin rash, sores or ulcers on the skin, or fever or chills while you are using imatinib.

Some serious side effects such as black, tarry stools, severe stomach pain, or vomiting of blood or material that looks like coffee grounds can occur during treatment with imatinib.

While you are being treated with imatinib, and after you stop treatment with it, do not have any immunizations (vaccinations) without your doctor's approval. Imatinib may lower your body's resistance and there is a chance you might get the infection the immunization is meant to prevent. In addition, other persons living in your household should not take oral polio vaccine since there is a chance they could pass the polio virus on to you. Also, avoid persons who have recently taken oral polio vaccine. Do not get close to them and do not stay in the same room with them for very long. If you cannot take these precautions, you should consider wearing a protective face mask that covers the nose and mouth.

Imatinib can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

If you are rapidly gaining weight, having chest pain or discomfort, extreme tiredness or weakness, difficulty with breathing, uneven heartbeat, or excessive swelling of the hands, wrist, ankles, or feet, check with your doctor immediately. These may be symptoms of heart problems or your body keeping too much water.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, unusual tiredness or weakness, or yellow eyes or skin. These could be symptoms of a serious liver problem.

imatinib may cause slow growth. If your child is using imatinib, the doctor will need to keep track of your child's height and weight to make sure that your child is growing properly.

imatinib may cause a serious type of reaction called tumor lysis syndrome. Your doctor may give you a medicine to help prevent this. Call your doctor right away if you have a decrease or change in urine amount, joint pain, stiffness, or swelling, lower back, side, or stomach pain, a rapid weight gain, swelling of the feet or lower legs, or unusual tiredness or weakness.

imatinib may cause dizziness, drowsiness, or trouble in seeing clearly. Make sure you know how you react to imatinib before you drive, use machines, or do other jobs that require you to be alert or able to see well.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Each Imatinib mesylate film-coated tablet contains 100 mg or 400 mg of Imatinib free base.

100 mg Tablets

Brownish orange, slightly biconvex, round film-coated tablets with functional scoring, engraved "IMA" over score "100" on one side, "APO" on the other side

Available as follows:
NDC 50268-426-12 (10 Tablets per card, 2 cards per carton).

400 mg Tablets

Brownish orange, capsule shaped, biconvex film-coated tablets with functional scoring, engraved "IMA" score "400" on one side, "APO" on the other side

Available as follows:
NDC 50268-427-12 (5 Tablets per card, 4 cards per carton).

Storage and Handling

Store at 20º to 25ºC (68º to 77ºF); excursions permitted from 15 to 30ºC (59 to 86ºF) [see USP Controlled Room Temperature]. Protect from moisture.

Imatinib mesylate is an antineoplastic product. Follow special handling and disposal procedures.1  

Imatinib mesylate tablets should not be crushed. Direct contact of crushed tablets with the skin or mucous membranes should be avoided. If such contact occurs, wash thoroughly as outlined in the references. Personnel should avoid exposure to crushed tablets.

Acute lymphoblastic leukemia: Treatment of relapsed or refractory Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) in adults

Treatment of newly diagnosed Ph+ ALL in children (in combination with chemotherapy)

Aggressive systemic mastocytosis: Treatment of aggressive systemic mastocytosis without D816V c-Kit mutation as determined by an approved test (or c-Kit mutational status unknown) in adults

Chronic myeloid leukemia: Treatment of Ph+ chronic myeloid leukemia (CML) in chronic phase (newly diagnosed) in adults and children

Treatment of Ph+ CML in blast crisis, accelerated phase, or chronic phase after failure of interferon-alfa therapy

Dermatofibrosarcoma protuberans: Treatment of unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans (DFSP) in adults

Gastrointestinal stromal tumors: Treatment of Kit (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST)

Adjuvant treatment of Kit (CD117)–positive GIST following complete gross resection

Hypereosinophilic syndrome and/or chronic eosinophilic leukemia: Treatment of hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) in adult patients who have the FIP1L1–platelet-derived growth factor (PDGF) receptor alpha fusion kinase (mutational analysis or fluorescent in situ hybridization [FISH] demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGF receptor alpha fusion kinase negative or unknown

Myelodysplastic/Myeloproliferative diseases: Treatment of myelodysplastic syndrome/myeloproliferative diseases (MDS/MPD) associated with PDGF receptor gene rearrangements as determined by an approved test in adults

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to imatinib or any component of the formulation

Note: Treatment may be continued until disease progression or unacceptable toxicity. The optimal duration of therapy for CML in complete remission is not yet determined. Imatinib is associated with a moderate emetic potential; antiemetics may be recommended to prevent nausea and vomiting (Dupuis, 2011).

Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) (newly diagnosed): Children ≥1 year and Adolescents: Oral: 340 mg/m2/day (in combination with chemotherapy); maximum: 600 mg daily

Ph+ chronic myeloid leukemia (CML), chronic phase, newly diagnosed: Children ≥1 year and Adolescents: Oral: 340 mg/m2/day; maximum: 600 mg daily

Dosage adjustment with concomitant strong CYP3A4 inducers: Avoid concomitant use of strong CYP3A4 inducers (eg, dexamethasone, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin); if concomitant use cannot be avoided, increase imatinib dose by at least 50% with careful monitoring.

Dosage adjustment for hepatotoxicity: Refer to “Hepatic Impairment” dosing.

Dosage adjustment for hematologic adverse reactions: Refer to dosing adjustment for toxicity.

Dosage adjustment for nonhematologic adverse reactions: Refer to dosing adjustment for toxicity.

Avoid grapefruit juice.

Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Protect from moisture.

An oral suspension (40 mg/mL) prepared using imatinib 400 mg tablets and Ora-Sweet is stable for up to 14 days at both room temperature and 4°C (39.2°F) (Li 2016).

-Mild or moderate hepatic impairment: No adjustment recommended.
-Severe hepatic impairment: Reduce the dose by 25%.

Administration advice:
-This drug should be taken with a meal and a large glass of water.
-Doses of 400 mg or 600 mg should be administered once daily, and a dose of 800 mg should be administered as 400 mg twice a day.
-For patients unable to swallow the film-coated tablets, the tablets may be dispersed in a glass of water or apple juice. The required number of tablets should be placed in the appropriate volume of beverage (approximately 50 mL for a 100 mg tablet, and 200 mL for a 400 mg tablet) and stirred with a spoon. The suspension should be administered immediately after complete disintegration of the tablet(s).
-For daily dosing of 800 mg and above, dosing should be accomplished using the 400 mg tablet to reduce exposure to iron.

Monitoring:
-Complete blood counts, liver function, and weight.
-Caution is recommended in patients with cardiac disease or cardiac risk factors. -Any patient with symptoms consistent with cardiac failure should be evaluated and treated as appropriate.