Names and pronunciation
(im-ah-tin′ib) Gleevec
Source page 685
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Individual generic drug information
Extracted information for imatinib only.
(im-ah-tin′ib) Gleevec
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Func. class.: Antineoplastic— miscellaneous
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Chem. class.: Protein-tyrosine kinase I inhibitor
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ACTION: Inhibits Bcr-Abl tyrosine kinase created in patients with chronic myeloid leukemia (CML), also inhibits tyrosine kinases
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USES: Treatment of CML; Philadel- phia chromosome–positive (Ph+) in blast-cell crisis or in chronic failure; gastrointestinal stromal tumors (GIST) positive for c-Kit; chronic eosinophilic leukemia, (CEL) Ph+ acute lymphocytic leukemia, dermatofibrosarcoma protu- berans, myelodysplastic syndrome, sys- temic mastocytosis, HES
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Extracted information for imatinib only.
CONTRAINDICATIONS: Preg- nancy, hypersensitivity Precautions: Breastfeeding, children, geriatric patients, cardiac/renal/hepatic disease, GI bleeding, bone marrow sup- pression, infection, thrombocytopenia, neutropenia, immunosuppression
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SIDE EFFECTS CNS: Headache, dizziness, insomnia, subdural hematoma, CNS hemorrhage CV: Hemorrhage, heart failure, cardiac tamponade, cardiac toxicity EENT: Blurred vision, conjunctivitis GI: Nausea, hepatotoxicity, vomiting, dyspepsia, anorexia, abdominal pain, GI perforation, diarrhea HEMA: Neutropenia, thrombocytopenia, bleeding, hypereosinophilia INTEG: Rash, pruritus, alopecia, photo- sensitivity, drug rash with eosinophilia and systemic symptoms (DRESS) META: Fluid retention, hypokalemia, edema MISC: Fatigue, epistaxis, pyrexia, night sweats, increased weight, flulike symptoms, hypothyroidism, tumor lysis syndrome MS: Cramps, pain, arthralgia, myalgia RESP: Cough, dyspnea, nasopharyngitis, pneumonia, pleural effusion
Source page 686
INTERACTIONS Increase: imatinib concentrations— CYP3A4 inhibitors (ketoconazole, itra- conazole, erythromycin, clarithromycin) Increase: plasma concentrations of simva statin, calcium channel blockers, ergots Increase: plasma concentration of warfa- rin; avoid use with warfarin; use low- molecular-weight anticoagulants instead Decrease: imatinib concentrations— CYP3A4 inducers (dexamethasone, phenytoin, carBAMazepine, rifAMPin, PHENobarbital) Drug/Herb Decrease: imatinib concentration—St. John’s wort Drug/Food Increase: effect of grapefruit juice, avoid use Drug/Lab Test Increase: bilirubin, amylase, LFTs Decrease: albumin, calcium, potassium, sodium, phosphate, platelets, neutro- phils, leukocytes, lymphocytes
Source pages 686, 687
Extracted information for imatinib only.
DOSAGE AND ROUTES For the treatment of Ph+ CML chronic phase as initial therapy • Adult: PO 400 mg/day, continue as long as beneficial; may increase to 600 mg/day in the absence of severe adverse reactions and severe non–leukemia- related neutropenia or thrombo cytopenia • Adolescent/child >2 yr: PO 340 mg/ m2/day, max 600 mg/day; the daily dose may be given as a single dose or split into 2 doses given once in the morning and once in the evening Ph+ acute lymphocytic leukemia (ALL) • Adult: PO 600 mg every day, continue as long as beneficial GIST • Adult: PO 400-600 mg every day, may increase to 400 mg bid Adjuvant treatment of Kit (CD117)- positive GIST after complete gross resection • Adult: PO 400 mg/day HES/CEL • Adult: PO 400 mg/day in those who are FIPL1L-PDGFR α-fusion kinase nega- tive or unknown; for HES/CEL patients with demonstrated FIP1L1-PDGFR α- fusion kinase, 100 mg/day, may increase to 400 mg MDS/MPD • Adult: PO 400 mg/day Aggressive systemic mastocytosis (ASM) without D816V c-Kit mutation or with c-Kit mutation status unknown • Adult: PO 400 mg/day DFSP • Adult: PO 400 mg twice daily Renal dose • Adult: PO CCr 40-59 mL/min, max 600 mg/day; CCr 20-39 mL/min, decrease initial dose by 50%, max 400 mg/day; CCr <20 mL/min, use with caution, 100 mg/day Hepatic dose • Adult: PO Total bilirubin 1.5-3 × ULN and any AST, decrease initial dose to 400 mg/day; total bilirubin >3 × ULN and any AST, decrease initial dose to 300 mg/day
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Available forms: Tabs 100, 400 mg
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Administer: • With meal and large glass of water to decrease GI symptoms; doses of 800 mg should be given as 400 mg bid • Tab may be dispersed in a glass of water or apple juice, use 50 mL of liquid for 100-mg tab, 200-mL liquid for 400- mg tab • Use low-molecular-weight anticoagulant for anticoagulant if needed, not warfarin • Continue as long as beneficial • Store at 77°F (25°C)
Source page 686
Extracted information for imatinib only.
Assess: • Bone marrow suppression: ANC, platelets; during chronic phase, if ANC <1 × 109/L and/or platelets <50 × 109/L, stop until ANC >1.5 × 109/L and platelets >75 × 109/L; during accelerated phase/blast crisis, if ANC <0.5 × 109/L and/or plate lets <10 × 109/L, determine whether cy topenia related to biopsy/aspirate; if not, reduce dose by 200 mg; if cytopenia continues, reduce dose by another 100 mg; if cytopenia continues for 4 wk, stop product until ANC ≥1 × 109/L • Monitor CBC weekly for first month, biweekly next month and periodically thereafter; may cause neutropenia (2-3 wk) and thrombocytopenia (3-4 wk) and anemia; may need dosage decrease or discontinuation • Renal toxicity: if bilirubin >3 × UNL, withhold imatinib until bilirubin levels re turn to <1.5 × UNL • DRESS: swelling of face, fever, rash, later hepatitis, myocarditis may occur, discontinue if present (rare) • Hepatotoxicity: monitor LFTs before and during treatment monthly; if liver transami nases >5 × UNL, withhold imatinib until transaminase levels return to <2.5 × UNL • Signs of fluid retention, edema: weigh, monitor lung sounds, assess for edema; some fluid retention is dose dependent • Pregnancy/breastfeeding: do not use in pregnancy, breastfeeding
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Evaluate: • Therapeutic response: decrease in leu- kemic cells or size of tumor
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To report adverse reactions immedi- ately: shortness of breath, swelling of extremities, bleeding • About reason for treatment, expected results • That effect on male infertility is unknown • Not to stop or change dose • To avoid hazardous activities until re- sponse is known, dizziness may occur • To take with food and water; for those unable to swallow tabs, to mix in liquid (30 mL for 100 mg); after dissolved, stir and consume; avoid grapefruit juice • To avoid OTC products unless ap- proved by prescriber • To notify prescriber if pregnancy is I planned or suspected; not to breastfeed; to use effective contraception
Source page 687
Extracted information for imatinib only.
PHARMACOKINETICS Well absorbed (98%); protein binding 95%; metabolized by CYP3A4; excreted in feces, small amount in urine; peak 2-4 hr; duration 24 hr (imatinib), 40 hr (metabolite); half-life 18-40 hr
Source page 686
Filter the extracted dose blocks for this individual drug.
For the treatment of Ph+ CML chronic phase as initial therapy
• Adult: PO 400 mg/day, continue as long as beneficial; may increase to 600 mg/day in the absence of severe adverse reactions and severe non–leukemia- related neutropenia or thrombo cytopenia
Candidate age grouping · source pages 685, 686
For the treatment of Ph+ CML chronic phase as initial therapy
• Adult: PO 600 mg every day, continue as long as beneficial GIST
Candidate age grouping · source pages 685, 686
For the treatment of Ph+ CML chronic phase as initial therapy
• Adult: PO 400-600 mg every day, may increase to 400 mg bid Adjuvant treatment of Kit (CD117)- positive GIST after complete gross resection
Candidate age grouping · source pages 685, 686
For the treatment of Ph+ CML chronic phase as initial therapy
• Adult: PO 400 mg/day HES/CEL
Candidate age grouping · source pages 685, 686
For the treatment of Ph+ CML chronic phase as initial therapy
• Adult: PO 400 mg/day in those who are FIPL1L-PDGFR α-fusion kinase nega- tive or unknown; for HES/CEL patients with demonstrated FIP1L1-PDGFR α- fusion kinase, 100 mg/day, may increase to 400 mg MDS/MPD
Candidate age grouping · source pages 685, 686
For the treatment of Ph+ CML chronic phase as initial therapy
• Adult: PO 400 mg/day Aggressive systemic mastocytosis (ASM) without D816V c-Kit mutation or with c-Kit mutation status unknown
Candidate age grouping · source pages 685, 686
For the treatment of Ph+ CML chronic phase as initial therapy
• Adult: PO 400 mg/day DFSP
Candidate age grouping · source pages 685, 686
For the treatment of Ph+ CML chronic phase as initial therapy
• Adult: PO 400 mg twice daily Renal dose
Candidate age grouping · source pages 685, 686
For the treatment of Ph+ CML chronic phase as initial therapy
• Adult: PO CCr 40-59 mL/min, max 600 mg/day; CCr 20-39 mL/min, decrease initial dose by 50%, max 400 mg/day; CCr <20 mL/min, use with caution, 100 mg/day Hepatic dose
Candidate age grouping · source pages 685, 686
For the treatment of Ph+ CML chronic phase as initial therapy
• Adult: PO Total bilirubin 1.5-3 × ULN and any AST, decrease initial dose to 400 mg/day; total bilirubin >3 × ULN and any AST, decrease initial dose to 300 mg/day
Candidate age grouping · source pages 685, 686