IMATINIB MESYLATE

IMATINIB MESYLATE (i-ma'ti-nib) Gleevec Classifications: antineoplastic; monoclonal antibody; tyrosine kinase inhibitor (tki); signal transductor inhibitor (sti); Therapeutic: antineoplastic; monoclonal antibody; tki Prototype: Gefitinib Pregnancy Category: D

Availability

100 mg capsule

Action

Tyrosine kinase inhibitor and signal transductor inhibitor (STI); STIs interfere with intracellular signaling pathways that are involved in the development of malignancies. Imatinib inhibits abnormal Bcr-Abl tyrosine kinase created by the Philadelphia chromosome abnormality in chronic myeloid leukemia (CLM). Tyrosine kinase is required for activation of a wide variety of intracellular activities vital to cell functioning and intracellular metabolic pathways.

Therapeutic Effect

Inhibits WBC cell proliferation and induces cell death in Bcr-Abl tyrosine kinase positive cells as well as in newly formed leukemic cells. Thus, it interferes with progression of chronic myeloid leukemia (CML).

Uses

Treatment of CML in blast crisis, or in chronic phase after failure of interferon-alpha therapy; unresectable and/or metastatic malignant gastrointestinal stromal tumors (GISTs).

Unlabeled Uses

Acute lymphocytic leukemia (ALL), soft tissue sarcoma.

Contraindications

Hypersensitivity to imatinib or any of its components; viral infections, including herpes and chickenpox; intramuscular injections with concurrent thrombocytopenia; pregnancy (category D), lactation; children <3 y.

Cautious Use

History of hypersensitivity to other monoclonal antibodies; hepatic or renal impairment; bleeding, bone marrow suppression; cardiac disease; dental disease, dental work; older adults, females of childbearing age; fungal infections; GI bleeding; heart failure; hepatic disease; herpes infection, immunosuppression, infection; jaundice; neutropenia; peripheral edema, renal disease; thrombocytopenia, vaccination, varicella, viral infection; concurrent administration of drugs which are CYP3A4 inhibitors (i.e., ketoconazole, itraconazole, erythromycin, clarithromycin).

Route & Dosage

CML Chronic Phase Adult: PO 400–800 mg q.d. with a meal and large glass of water Child (>3 y): PO 260 mg/m2/d in 1 or 2 divided dose(s) (max: 340 mg/m2/d) CML Accelerated Phase or Blast Crisis Adult: PO 600 mg q.d. with a meal and large glass of water GISTs Adult: PO 400–600 mg q.d. times up to 24 mo Hepatic Impairment Reduce dose to 300 mg q.d. (chronic) or 400 mg q.d. (accelerated, blast crisis).

Administration

Oral

• Give with meal and large glass of water (at least 8 oz).
• Store at 15°–30° C (59°–86° F).

Adverse Effects (≥1%)

Body as a Whole: Fluid retention, edema, fatigue, weight gain, fever, night sweats, weakness. CNS: CNS hemorrhage, headache. GI: Nausea, vomiting, diarrhea, GI hemorrhage, dyspepsia, abdominal pain, constipation, anorexia, increased AST, ALT, and bilirubin. Hematologic: Hemorrhage, neutropenia, thrombocytopenia, petechiae, epistaxis, pancytopenia (rare), thrombocytopenia (rare). Metabolic: Hypokalemia. Musculoskeletal: Muscle cramps, pain, arthralgia, myalgia. Respiratory: Cough, dyspnea, pharyngitis, pneumonia. Skin: Rash, pruritus.

Interactions

Drug: Clarithromycin, erythromycin, ketoconazole, itraconazole may increase imatinib levels and toxicity; carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin may decrease imatinib levels; may increase levels of benzodiazepines, dihydropyridine, calcium channel blockers (e.g., nifedipine), warfarin. Herbal: St. John's wort may decrease imatinib levels.

Pharmacokinetics

Absorption: Well absorbed, 98% reaches systemic circulation. Peak: 2–4 h. Metabolism: Primarily by CYP3A4 in liver. Elimination: Primarily in feces. Half-Life: 18 h imatinib, 40 h active metabolite.

Nursing Implications

Assessment & Drug Effects

• Monitor for S&S of fluid retention. Weigh daily and report rapid weight gain immediately.
• Lab tests: CBC with platelet count and differential weekly times 1 mo, biweekly for the 2nd mo, periodically thereafter as clinically indicated; baseline and monthly AST, ALT, alkaline phosphatase, bilirubin; periodic serum creatinine and electrolytes.
• Withhold drug and notify physician for any of the following: bilirubin >3 times ULN, AST/ALT >5 times ULN; treatment may be reinstituted when bilirubin <1.5 times ULN and AST/ALT <2.5 times ULN.
• Review concurrent medications. Consult physician about switching patients taking warfarin to low-molecular weight or standard heparin. Patients taking ketoconazole and other CYP3A4 inhibitors may experience increased adverse drug reactions.

Patient & Family Education

• Do not take any OTC drugs (e.g., acetaminophen, St. John's wort) without consulting physician.
• Report any S&S of bleeding immediately to physician (e.g., black tarry stool, bright red or coke colored urine, bleeding from gums).
• Report immediately to physician any unexplained change in mental status.
• Use effective means of contraception while taking this drug. Women of childbearing age should avoid becoming pregnant.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug