Gleevec

Imatinib is used to treat certain types of leukemia (cancer that begins in the white blood cells) and other cancers and disorders of the blood cells. Imatinib is also used to treat certain types of gastrointestinal stromal tumors (GIST; a type of tumor that grows in the walls of the digestive passages and may spread to other parts of the body). Imatinib is also used to treat dermatofibrosarcoma protuberans (a tumor that forms under the top layer of skin) when the tumor cannot be removed surgically, has spread to other parts of the body, or has come back after surgery. Imatinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells.

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Dosage Forms And Strengths

Very dark yellow to brownish orange, film-coated tablets, round, biconvex with bevelled edges, debossed with “NVR” on one side, and “SA” with score on the other side

Very dark yellow to brownish orange, film-coated tablets, ovaloid, biconvex with bevelled edges, debossed with “400” on one side with score on the other side, and “SL” on each side of the score

Very dark yellow to brownish orange, film-coated tablets, ovaloid, biconvex with bevelled edges, debossed with “gleevec” on one side and score on the other side.

Storage And Handling

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

Very dark yellow to brownish orange, film-coated tablets, round, biconvex with bevelled edges, debossed with “NVR” on one side, and “SA” with score on the other side.

Bottles of 90 tablets - NDC 0078-0401-34

Very dark yellow to brownish orange, film-coated tablets, ovaloid, biconvex with bevelled edges, debossed with “400” on one side with score on the other side, and “SL” on each side of the score.

Bottles of 30 tablets - NDC 0078-0438-15

Very dark yellow to brownish orange, film-coated tablets, ovaloid, biconvex with bevelled edges, debossed with “gleevec” on one side and score on the other side.

Unit Dose (blister pack of 30) - NDC 0078-0649-30

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture.

Dispense in a tight container, USP.

Do not crush Gleevec tablets. Avoid direct contact of crushed tablets with the skin or mucous membranes. If such contact occurs, wash thoroughly as outlined in the references. Avoid exposure to crushed tablets.

REFERENCES

1. OSHA Hazardous Drugs. OSHA. [Accessed on 20-September-2013, from http://www.osha.gov/SLTC/hazardousdrugs/index.html]

Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936. Revised: Sep 2017

Gleevec is a prescription medication used to treat various types of cancers including:

• certain types of leukemia (cancer that begins in the white blood cells) and other cancers of the blood cells.
• gastrointestinal stromal tumors (GIST; a type of tumor that grows in the walls of the digestive passages and may spread to other parts of the body). 
• dermatofibrosarcoma protuberans (a tumor that forms under the top layer of skin) when the tumor cannot be removed surgically, has spread to other parts of the body, or has come back after surgery. 

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

• Novartis Pharmaceuticals Corporation

Talk to your doctor about grapefruit and grapefruit juice. These foods can interfere with how Gleevec is absorbed by your body.

If you take too much Gleevec, call your local Poison Control Center or seek emergency medical attention right away. Symptoms of overdose may include muscle cramps, and swollen or bloated stomach.

• Store Gleevec 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.

Antineoplastic agent; an inhibitor of Bcr-Abl tyrosine kinase.1

Contraindications

• Known hypersensitivity to imatinib or any ingredient in the formulation.1

Warnings/Precautions

Warnings

May cause fetal harm;1 teratogenicity and embryolethality demonstrated in animals.1 Avoid pregnancy during therapy.1 If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.1

Major Toxicities

Bullous skin reactions, including erythema multiforme and Stevens-Johnson syndrome, reported.1 If dermatologic toxicity occurs, discontinue imatinib.1 Has been reinitiated in some patients at a reduced dosage (with or without concomitant corticosteroids or antihistamines) following resolution or lessening of the bullous skin reaction.1

Risk of severe superficial edema (e.g., rapid weight gain, facial edema, anasarca),1 5 6 severe fluid retention (i.e., pleural effusion, pericardial effusion, pulmonary edema, ascites),1 8 10 cardiac tamponade, cerebral edema, increased intracranial pressure, and papilledema (including fatalities).1

The incidence of edema and fluid retention appears to be increased in CML patients in blast crisis, in patients receiving higher dosages (i.e., 600 mg daily), and in geriatric patients.1

Monitor signs (e.g., body weight) and symptoms of fluid retention regularly.1 If severe fluid retention develops, withhold imatinib therapy and provide appropriate treatment until complete resolution occurs.1

Nausea, vomiting, and diarrhea occur frequently.1 GI perforation, sometimes fatal, reported rarely.1

Administer with food and a large glass of water to minimize GI irritation.1

Risk of grade 3 or 4 hemorrhage, GI bleeds, and/or intratumoral bleeds.1 GI bleeds may have originated from GI tumor sites.1

Risk of grade 3 or 4 neutropenia,1 5 8 anemia, or thrombocytopenia.1 5 8 Cytopenias reported less frequently in patients with newly diagnosed CML; higher frequency of grade 3 or 4 neutropenia and thrombocytopenia in patients with blast crisis or accelerated phase CML than in patients with chronic phase CML.1 In pediatric patients with CML, grade 3 or 4 cytopenias (neutropenia, thrombocytopenia, and anemia) usually occurred within the first several months of therapy.1

Monitor CBCs weekly during the first month of therapy, every other week during the second month, and periodically (e.g., every 2–3 months) thereafter as clinically indicated.1 If hematologic toxicity occurs, withhold therapy.1 (See Hematologic Toxicity under Dosage and Administration.)

Risk of grade 3 or 4 hyperbilirubinemia and elevations in alkaline phosphatase, ALT, and AST (grade 3 or 4 severity).1 10 Fatal hepatic failure occurred in at least one patient who received imatinib concomitantly with acetaminophen.1 8

Monitor liver function tests (i.e., transaminases, bilirubin, alkaline phosphatase) prior to initiation of therapy and monthly thereafter or as clinically indicated.1 If liver function test results are abnormal, withhold imatinib and/or reduce imatinib dosage.1 (See Hepatic Toxicity under Dosage and Administration.)

Severe CHF and left ventricular dysfunction reported, mostly in geriatric patients or patients with a history of cardiac disease.1 17 Monitor such patients carefully; evaluate and treat any patient with manifestations of cardiac failure.1 17

In patients with HES and cardiac involvement, initiation of imatinib has been associated with cardiogenic shock or left ventricular dysfunction;20 a this condition reportedly was reversible with administration of systemic corticosteroids, circulatory support measures, and temporary discontinuance of imatinib.a Consider performing echocardiogram and determining serum troponin concentration in patients with elevated eosinophil concentrations (including patients with HES/CEL or patients with MDS/MPD or ASM associated with high eosinophil concentrations).20 a If either is abnormal, consider prophylactic use of systemic corticosteroids for 1–2 weeks concomitantly with imatinib upon initiation of therapy.20 a

Hypophosphatemia associated with altered bone and mineral metabolism has been reported in patients receiving imatinib for CML or GIST.1 21

General Precautions

Consider potential toxicities suggested by animal studies, specifically, hepatic and renal toxicity and immunosuppression.1 Severe hepatic and renal toxicity observed in animals receiving imatinib for as little as 2 weeks.1 Immunosuppression reported in animals receiving imatinib for up to 39 weeks.1

Cardiomyopathy (e.g., cardiac hypertrophy and dilatation, resulting in cardiac insufficiency), chronic progressive nephropathy, and preputial gland papilloma reported in animals receiving imatinib for up to 2 years.a

Specific Populations

Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Distributed into milk in rats; drug concentration approximately threefold higher in milk than in plasma.1 Discontinue nursing because of potential risk in nursing infants.1

Safety and efficacy demonstrated only in children with newly diagnosed, recurrent, or resistant Ph+ chronic phase CML.1 The overall safety profile in 93 pediatric patients studied was similar to that in adult patients; however, musculoskeletal pain occurred less frequently in pediatric patients than in adults, and peripheral edema was not reported.1 Most frequently reported adverse effects include nausea and vomiting.1 a

No data in children <2 years of age.1

In patients with CML, no substantial differences in safety and efficacy relative to younger patients were observed, with the exception of a higher incidence of edema.1 Formal evaluation has not been performed in patients with GIST, but no obvious differences in safety and efficacy relative to younger patients observed.1

Increased exposure to imatinib and its major active metabolite observed in patients with severe hepatic impairment.1 Close monitoring recommended in these patients.1 (See Hepatic Impairment under Dosage and Administration.)

Safety and efficacy not established; use with caution.1 8

Common Adverse Effects

In patients with CML,1 nausea,1 8 10 vomiting,1 8 10 diarrhea,1 8 10 edema,1 8 10 muscle cramps,1 10 musculoskeletal pain,1 rash.1

In patients with ALL,a adverse effects similar to those reported in patients with CML (e.g., mild nausea,a vomiting,a diarrhea,a myalgia,a muscle cramps,a rash).a

In patients with MDS/MPD, nausea,a diarrhea,a muscle cramp,a anemia,a fatigue,a arthralgia,a periorbital edema.a

In patients with ASM, diarrhea,a nausea,a ascites,a muscle cramps,a dyspnea,a fatigue,a peripheral edema,a anemia,a pruritus,a rash,a lower respiratory tract infection.a

In patients with HES/CEL, adverse effects similar to those reported in patients with other hematologic malignancies (e.g., GI/cutaneous/musculoskeletal disorders).a

In patients with DFSP, nausea,a fatigue,a periorbital edema,a peripheral edema,a ocular edema,a diarrhea,a vomiting,a rash,a increased lacrimation,a anemia,a facial edema,a pyrexia,a exertional dyspnea,a rhinitis,a anorexia.a

In patients with GIST,1 edema,1 8 10 nausea,1 8 10 diarrhea,1 8 10 abdominal pain,1 muscle cramps,1 10 fatigue,1 rash.1 5 6 8 10

Other adverse effects occurring in ≥10% of patients: GI/CNS/tumor hemorrhage,1 headache,1 dyspepsia,1 8 joint pain,1 weight increase,1 cough,1 flatulence,1 constipation,1 nasopharyngitis,1 pharyngolaryngeal pain,1 night sweats,1 pruritus,1 hypokalemia,1 pneumonia,1 upper respiratory tract infection,1 dizziness,1 insomnia,1 depression,1 rigors,1 back pain,1 asthenia,1 influenza,1 taste disturbance,1 anxiety,1 liver toxicity,1 chest pain,1 sinusitis,1 loose stools.1

The incidence of neutropenia and grade 1 or 2 superficial edema, headache, nausea, rigors, vomiting, rash, and fatigue appears to be higher in women than in men.1

Imatinib is used alone or together with other medicines to treat different types of cancer or bone marrow conditions. It prevents or stops the growth of cancer cells and is called an antineoplastic (cancer) agent. Imatinib is used for these conditions:

• Aggressive systemic mastocytosis (ASM)
• Chronic eosinophilic leukemia (CEL)
• Dermatofibrosarcoma protuberans (DFSP)
• Gastrointestinal stromal tumors (GIST)
• Hypereosinophilic syndrome (HES)
• Myelodysplastic syndrome (MDS)
• Myeloproliferative diseases (MPD)
• Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL)
• Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML)

This medicine is available only with your doctor's prescription.

• If you have an allergy to imatinib or any other part of Gleevec (imatinib).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are taking warfarin.
• If you are breast-feeding. Do not breast-feed while you take this medicine or for 1 month after you stop Gleevec.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Gleevec with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

None. 

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

100 mg Tablets

Very dark yellow to brownish orange, film-coated tablets, round, biconvex with bevelled edges, debossed with “NVR” on one side, and “SA” with score on the other side.

Bottles of 90 tablets………………………………….NDC 0078-0401-34

400 mg Tablets

Very dark yellow to brownish orange, film-coated tablets, ovaloid, biconvex with bevelled edges, debossed with “400” on one side with score on the other side, and “SL” on each side of the score.

Bottles of 30 tablets…………………………………NDC 0078-0438-15

400 mg Tablets

Very dark yellow to brownish orange, film-coated tablets, ovaloid, biconvex with bevelled edges, debossed with “Gleevec” on one side and score on the other side.

Unit Dose (blister pack of 30) ………………………NDC 0078-0649-30

Storage and Handling

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture.

Dispense in a tight container, USP.

Do not crush Gleevec tablets. Avoid direct contact of crushed tablets with the skin or mucous membranes. If such contact occurs, wash thoroughly as outlined in the references. Avoid exposure to crushed tablets.