imatinib mesylate

Action

Inhibits proliferation of Bcr-Abl tyrosine kinase, an abnormal chromosome protein found in most patients with chronic myeloid leukemia (CML). This inhibition suppresses tumor growth.

Availability

Tablets: 100 mg, 400 mg

Indications and dosages

➣ Philadelphia chromosome-positive (Ph+) CML

Adults: During chronic phase, 400 mg P.O. daily as a single dose; during accelerated phase or blast crisis, 600 mg P.O. daily as a single dose. May increase to 600 mg P.O. daily during chronic phase or to 800 mg P.O. daily (400 mg b.i.d.) during accelerated phase or blast crisis in absence of severe adverse drug reaction and severe non-leukemia-related neutropenia or thrombocytopenia in following circumstances: disease progression at any time, failure to achieve satisfactory hematologic response after at least 3 months of treatment, failure to achieve cytogenetic response after 6 to 12 months of treatment, or loss of previously achieved hematologic or cytogenetic response.

➣ Newly diagnosed Ph+ CML

Children: 340 mg/m²/day P.O. as once-daily dose; or, daily dose may be split into two (once in morning and once in evening). Daily dose not to exceed 600 mg.

➣ Ph+ chronic-phase CML recurrent after stem cell transplant or resistant to interferon-alpha therapy

Children: 260 mg/m²/day P.O. as once-daily dose; or, daily dose may be split into two (once in morning and once in evening).

➣ Relapsed/refractory Ph+ acute lymphoblastic leukemia

Adults: 600 mg P.O. daily as single dose

➣ Myelodysplastic/myeloproliferative diseases

Adults: 400 mg P.O. daily as single dose

➣ Aggressive systemic mastocytosis (ASM)

Adults: Recommended dosage is 400 mg P.O. daily as single dose for patients without D816V c-Kit mutation. If c-Kit mutational status is unknown or unavailable, 400 mg daily may be considered for patients with ASM not responding satisfactorily to other therapies. For patients with ASM associated with eosinophilia, a starting dose of 100 mg P.O. daily is recommended. Dosage increase from 100 to 400 mg for these patients may be considered in absence of adverse drug reactions if assessments show insufficient response to therapy.

➣ Hypereosinophilic syndrome/chronic eosinophilic leukemia

Adults: Recommended dosage is 400 mg P.O. daily as single dose

➣ Dermatofibrosarcoma protuberans

Adults: Recommended dosage is 800 mg P.O. daily (given as 400 mg twice daily)

➣ Kit (CD117)-positive unresectable or metastatic malignant GI stromal tumors

Adults: 400 to 600 mg P.O. daily

Dosage adjustment

• Hepatic or hematologic impairment

• Concurrent use of potent CYP3A4 inducers, such as rifampin or phenytoin

Contraindications

• Hypersensitivity to drug or its components

Precautions

Use cautiously in:

• renal or hepatic impairment

• pregnant or breastfeeding patients

• children younger than age 2 (safety and efficacy not established).

Administration

• Give with meal and large glass of water.

• Disperse tablets in glass of water or apple juice for patients unable to swallow tablets. Place required number of tablets in appropriate volume of beverage (approximately 50 ml for 100-mg tablet, and 200 ml for 400-mg tablet) and stir with spoon. Administer suspension immediately after complete disintegration of tablets.

Adverse reactions

CNS: headache, fatigue, asthenia, malaise, insomnia, headache, cerebral hemorrhage

CV: heart failure, ventricular dysfunction

GI: nausea, vomiting, diarrhea, constipation, anorexia, abdominal pain or cramps, dyspepsia, GI hemorrhage

Hematologic: anemia, hemorrhage, neutropenia, thrombocytopenia, gastrointestinal perforation

Hepatic: hepatotoxicity

Metabolic: hypokalemia, fluid retention

Musculoskeletal: myalgia, muscle cramps, musculoskeletal or joint pain

Respiratory: cough, dyspnea, pneumonia

Skin: rash, pruritus, night sweats, petechiae bullous dermatitis, reactions (erythema multiforme, Stevens-Johnson syndrome)

Other: weight gain, edema, fever

Interactions

Drug-drug. Cyclosporine, dihydropyridine calcium channel blockers, pimozide, some HMG-CoA reductase inhibitors, triazolobenzodiazepines: increased blood levels of these drugs

CYP450-3A4 inducers (such as carbamazepine, dexamethasone, phenobarbital, phenytoin): increased metabolism and decreased blood level of imatinib

CYP450-3A4 inhibitors (such as clarithromycin, erythromycin, itraconazole, ketoconazole): decreased metabolism and increased blood level of imatinib

Warfarin: altered warfarin metabolism

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, creatinine, hepatic enzymes: increased values

Hemoglobin, neutrophils, platelets, potassium: decreased values

Drug-herbs. St. John's wort: decreased imatinib effects

Patient monitoring

• Monitor for GI distress. Provide small, frequent meals; consult dietitian if nausea and vomiting persist.

See Monitor CBC before therapy starts and regularly during therapy. Expect to adjust dosage if bone marrow depression occurs.

See Evaluate for signs and symptoms of bleeding, edema, and fluid retention.

• Measure daily weight and fluid intake and output.

• Monitor liver function tests.

Patient teaching

• Advise patient to take with a meal and a large glass of water.

• Instruct patient to avoid potential sources of infection, such as crowds and people with known infections.

• Tell patient drug may cause sudden weight gain and fluid retention. Instruct him to weigh himself daily.

See Advise patient to immediately report sudden weight gain, swelling, difficulty breathing, signs or symptoms of infection, unusual bleeding or bruising, or jaundice.

• Tell patient he'll undergo frequent blood testing to monitor drug effects.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.