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Imatinib

Class
Targeted therapy
Subclass
Tyrosine kinase inhibitors
Generic name
Imatinib mesylate
Brand names
Gleevec®
Common formulations
Tablet
Dosage and administration
Adults patients
Acute lymphoblastic leukemia • Philadelphia chromosome-positive, newly diagnosed
•
600 mg PO daily until disease progression or unacceptable toxicity
Administered in combination with chemotherapy.
Chronic eosinophilic leukemia
•
Start at: 100 mg PO daily
•
Maintenance: 400 mg PO daily
Chronic myeloid leukemia • Philadelphia chromosome-positive, chronic phase, newly diagnosed
•
400 mg PO daily until disease progression or unacceptable toxicity
Chronic myeloid leukemia • Philadelphia chromosome-positive, chronic phase, failure of interferon-alpha therapy
•
400 mg PO daily
Consider increasing to 600 mg daily in patients with disease progression at any time.
Chronic myeloid leukemia • Philadelphia chromosome-positive, accelerated phase or blast phase
•
600 mg PO daily until disease progression or unacceptable toxicity
Titrate dosage to 800 mg per day, given as 400 mg orally BID, in the absence of significant toxicity in patients with disease progression at any time.
Gastrointestinal stromal tumors • Adjuvant setting
•
400 mg PO daily
Gastrointestinal stromal tumors • Unresectable, metastatic
•
Maintenance: 400 mg PO daily
•
Maximum: 800 mg per day
Hypereosinophilic syndrome
•
400 mg PO daily
Systemic mastocytosis without C-KIT D816V mutation • Aggressive
•
400 mg PO daily
Indications for use
Labeled indications
Adults
•
Treatment of acute lymphoblastic leukemia (Philadelphia chromosome-positive, newly diagnosed)
•
Treatment of chronic eosinophilic leukemia
•
Treatment of chronic myeloid leukemia (Philadelphia chromosome-positive, accelerated phase or blast phase)
•
Treatment of chronic myeloid leukemia (Philadelphia chromosome-positive, chronic phase, failure of interferon-alpha therapy)
•
Treatment of chronic myeloid leukemia (Philadelphia chromosome-positive, chronic phase, newly diagnosed)
•
Treatment of dermatofibrosarcoma protuberans (unresectable, reccurent)
•
Treatment of gastrointestinal stromal tumors (adjuvant setting)
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Treatment of gastrointestinal stromal tumors (unresectable, metastatic)
•
Treatment of hypereosinophilic syndrome
•
Treatment of myelodysplastic/myeloproliferative disease (associated with PDGFR rearrangements)
•
Treatment of systemic mastocytosis without C-KIT D816V mutation (aggressive)
Safety risks
Warnings and precautions
ALF, jaundice, hyperbilirubinemia
•
Maintain a high level of suspicion, as cases of fatal liver failure and severe liver injury requiring liver transplants have been reported with the use of imatinib mesylate.
Chemotherapy-induced bone marrow suppression
•
Use caution in patients with a history of myelosuppression or cytopenias.
Congestive HF, LV dysfunction
•
Use extreme caution in patients with advanced age or co-morbidities, including previous medical history of cardiac disease.
Edema, fluid retention
•
Use caution in patients taking high dose of imatinib mesylate and those with age greater than 65 years.
Gastrointestinal bleeding, gastrointestinal ulceration
•
Maintain a high level of suspicion, as imatinib mesylate has been associated with these side effects.
Hypothyroidism
•
Use caution in thyroidectomy patients undergoing levothyroxine replacement during treatment.
Nephrotoxicity
•
Use extreme caution in patients with pre-existing renal impairment, cardiac failure, diabetes mellitus, and hypertension.
Neutropenia, thrombocytopenia, opportunistic infections
•
Use extreme caution in patients with risk factors for bone marrow suppression.
Peripheral edema
•
Use caution in patients with blast- or accelerated-phase chronic myelogenous leukemia.
Reactivation of viral infections
•
Use extreme caution in patients with a history of varicella zoster, other herpes infection.
Somnolence
•
Use caution in patients performing activities requiring mental alertness, such as driving or operating machinery.
Specific populations
Renal impairment
CrCl 40-59 mL/min
•
Use with caution. Maximal dose of 600 mg. Monitor serum creatinine. Monitor for fluid retention.
CrCl 20-39 mL/min
•
Use with caution. Reduce dose by 50%. Maximal dose of 400 mg. Monitor serum creatinine. Monitor for fluid retention.
CrCl < 20 mL/min
•
Use with caution. Reduce dose by 50%. Maximal dose of 400 mg. Monitor serum creatinine. Monitor for fluid retention.
Renal replacement therapy
Continuous renal replacement
•
Use with caution. Monitor serum creatinine. Monitor for fluid retention.
Intermittent hemodialysis
•
Use with caution. Monitor serum creatinine. Monitor for fluid retention.
Peritoneal dialysis
•
Use with caution. Monitor serum creatinine. Monitor for fluid retention.
Hepatic impairment
Child-Pugh A (mild)
•
Use acceptable. No dose adjustment required. Monitor serum aminotransferases. Monitor for toxicity.
Child-Pugh B (moderate)
•
Use acceptable. No dose adjustment required. Monitor serum aminotransferases. Monitor for toxicity.
Child-Pugh C (severe)
•
Reduce dose by 25%. Monitor serum aminotransferases. Monitor for toxicity.
Pregnancy and breastfeeding
Pregnancy
All trimesters • Australia Category: D, D
•
Avoid use. Evidence of fetal harm in humans. This drug can harm a developing fetus.
•
Advise female patients of reproductive potential to use adequate contraception during therapy and for 14 days after.
•
Verify negative pregnancy status in females of reproductive potential prior to initiating therapy.
•
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.
Breastfeeding
Do not use during breastfeeding.
Unknown drug levels in breastfed infants.
No overt adverse effects reported in breastfed infants.
Adverse reactions
Very common > 10%
•
Anemia, ↓ WBC count, ↓ platelet count, dysgeusia, hyperlacrimation, lethargy, abdominal pain, asthenia, fatigue, malaise, weight loss, rhinitis, watermelon stomach
Common 1-10%
•
Anasarca, ascites, blepharitis, breast enlargement, bullous pemphigoid, cataract, cheilitis, conjunctivitis, ↓ blood lymphocyte count, ↓ serum albumin, ↓ serum calcium, ↓ serum magnesium, ↓ serum phosphate, ↓ serum potassium, ↓ serum sodium, dehydration, ecchymosis, erythema multiforme, erythema multiforme, erythema nodosum, esophagitis, folliculitis, gastroesophageal reflux disease, gastritis, gastrointestinal bleeding, gout, gynecomastia, heart failure, hearing loss, hepatitis, hyperhidrosis, hypertension, hyperthyroidism, hyphema, hypotension, hypothyroidism, intracranial hemorrhage, ↑ ICP, ↑ blood eosinophil count, ↑ blood glucose, ↑ liver enzymes, ↑ serum TBIL, ↑ serum amylase, ↑ serum potassium, ↑ serum uric acid, jaundice, low oxygen levels, lymphadenopathy, macular edema, menorrhagia, migraine, oral ulcers, pancreatitis, pancytopenia, panniculitis, papilledema, peptic ulcer disease, pericardial effusion, peripheral edema, peripheral neuropathy, petechiae, pharyngitis, photosensitivity of skin, pleural effusion, pulmonary edema, purpura, renal failure, anorexia, arthralgia, back pain, belching, blurred vision, bone pain, chest pain, chills, constipation, cough, ↓ libido, diarrhea, dizziness, dry mouth, dyspepsia, dysphagia, dyspnea, erectile dysfunction, eye pain, fever, flatulence, hair loss, headache, hematemesis, hematuria, ↑ appetite, itching, melena, memory impairment, menstrual irregularity, muscle cramps, musculoskeletal pain, myalgia, nausea, night sweats, nosebleed, palpitations, skin flushing, skin rash, somnolence, syncope, tinnitus, urinary frequency, vertigo, vomiting, weakness, weight gain, restless legs syndrome, retinal hemorrhage, skin discoloration, skin exfoliation, stomatitis, subdural hematoma, tachycardia, testicular swelling, tremor, urticaria, vasculitis, xerophthalmia
Uncommon < 1%
•
Atrial fibrillation, acute liver failure, acute generalized exanthematous pustulosis, acute rhinosinusitis, angioedema, aplastic anemia, cardiac arrest, cardiac tamponade, cerebral edema, colitis, exacerbation of arrhythmia, hemolytic anemia, hepatic necrosis, ileus, influenza virus infection, nail discoloration, optic neuritis, pneumonitis, pulmonary fibrosis, pulmonary hypertension, angina pectoris, anxiety, confusion, depression, insomnia, paresthesia, skin dryness, Stevens-Johnson syndrome, vesicular rash
Unknown frequency
•
Anaphylactic shock, clastogenesis, DRESS syndrome, growth restriction, lichen planus pemphigoides, nephrotoxicity, osteonecrosis, palmar-plantar erythrodysesthesia, pemphigus vulgaris, pericarditis, pseudoporphyria, rhabdomyolysis, stomach perforation, thromboembolism, thrombosis, thrombotic microangiopathy, toxic epidermal necrolysis, tumor lysis syndrome
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