Chronic Myeloid Leukemia Drug Summary

Drug	Dosage	Remarks
Busulfan	In combination with Cyclophosphamide as a conditioning regimen prior to allo-HCT: 0.8 mg/kg IV via central venous catheter as a 2-hour infusion 6 hourly for 4 consecutive days Total dose: 16 doses	Adverse Reactions CNS effects (headache, insomnia, anxiety, dizziness, depression); CV effects (hypertension, chest pain, thrombosis, tachycardia, vasodilation); GI effects (nausea/vomiting, stomatitis, anorexia, diarrhea, abdominal pain, dyspepsia, constipation, dry mouth, rectal disorder, abdominal enlargement); Respiratory effects (rhinitis, lung disorder, cough, epistaxis, dyspnea); Metabolic effects (hyperglycemia, hypokalemia, hypocalcemia, hypomagnesemia, hyperbilirubinemia, SGPT elevation, increased creatinine); Other effects (fever, asthenia, chills, rash, pruritus, edema) Special Instructions Use with caution in patients with bronchopulmonary dysplasia with pulmonary fibrosis, cellular dysplasia, history of seizure disorder or head trauma or patients on other potentially epileptogenic drugs, prior radiotherapy, ≥3 cycles of chemotherapy or prior progenitor cell transplant Monitor for signs and symptoms of cardiac tamponade, infection, bleeding
Cyclophosphamide	50 mg PO 24 hourly on days 1-21  Cycled every 28 days	Adverse Reactions GI effects (nausea/vomiting, anorexia, mucositis); CNS effect (headache); GU effect (acute hemorrhagic cystitis or urinary fibrosis); Dermatologic effects (alopecia, rash); Hematologic effect (leukopenia); Respiratory effects (rhinorrhea, nasal congestion); Other effects (fertility impairment, renal tubular necrosis, SIADH may occur with doses >50 mg/kg)  Special Instructions Use with caution in patients with hepatic or renal impairment
Cytarabine	Blast crisis of CML: 2-3 g/m2 BSA IV infusion over 1-3 hours 12 hourly x 4-12 doses	Adverse Reactions CNS effects (dementia, neurotoxicity); Dermatologic effect (rashes); GI effects (GI disturbances, GI hemorrhage, esophagitis, oral/anal ulceration); Other effects (hepatic/renal dysfunction, conjunctivitis, flu-like syndrome, anaphylactoid reactions) Potentially fatal: Convulsions, cerebellar dysfunction, respiratory distress syndrome, GI perforation, bone marrow suppression Special Instructions Use with caution in patients with renal/hepatic dysfunction, severe infections, pre-existing drug-induced bone marrow suppression Monitor WBC, platelet count, serum uric acid levels, renal/hepatic function
Hydroxyurea  (Hydroxycarbamide)	Initial dose: 40 mg/kg PO 24 hourly Resistant CML: 20-30 mg/kg PO 24 hourly single dose	Adverse Reactions Hematologic effect (bone marrow depression [leukopenia, anemia, occasionally thrombocytopenia]); CNS effects (headache, dizziness, convulsions, disorientation); Other effects (temporary renal tubular function impairment, dermatologic reactions) Special Instructions Use with caution in patients with renal dysfunction Contraindicated in patients with known bone marrow suppression (eg leukopenia, thrombocytopenia and severe anemia) Close monitoring of kidney and liver function, CBC and bone marrow exam is advised Interrupt therapy until values rise significantly to normal level Avoid concomitant use with Didanosine and Stavudine
Omacetaxine mepesuccinate	Chronic or accelerated phase CML Initial dose: 1.25 mg/m2 SC 12 hourly x 14 consecutive days of a 28-day cycle, repeated every 28 days Maintenance dose: 1.25 mg/m2 SC 12 hourly x 7 consecutive days of a 28-day cycle	Adverse Reactions Hematologic effects (lymphopenia, bone marrow failure, febrile neutropenia); GI effects (diarrhea, nausea/vomiting, constipation, abdominal pain, GI hemorrhage); Musculoskeletal effects (arthralgia, back pain, myalgia, extremity pain); CNS effects (headache, insomnia, anorexia); Respiratory effects (cough, epistaxis); Dermatologic effects (alopecia, rash, inj site reactions); Other effects (asthenia, fatigue, pyrexia, peripheral edema, glucose intolerance, hyperglycemia) Potentially fatal: Severe anemia, neutropenia, cerebral hemorrhage, thrombocytopenia Special Instructions Use with caution in patients with diabetes mellitus (DM) or risk for DM Monitor CBC during induction and initial maintenance therapy then every 2 weeks thereafter or as clinically indicated; blood glucose frequently; signs of bleeding or infection

Drug	Dosage	Remarks
Interferon alpha-2b  (Interferon alfa-2b)	4-5 MIU/m2 SC 24 hourly Continue at the max tolerated dose to maintain remission	Adverse Reactions GI effects (nausea/vomiting, diarrhea, dry mouth, taste alteration); CNS effects (headache, insomnia, depression, confusion, suicidal ideation); Musculoskeletal effects (pain, arthralgia, myalgia); Other effects (fever, hypotension, alopecia, increased sweating) Special Instructions Use with caution in patients with pulmonary disease, DM, coagulopathy, severe myelosuppression, liver/kidney transplant Contraindicated in patients with severe renal dysfunction or CrCl <50 mL/min, chronic hepatic disease, history of cardiac disease, advanced stages of cancer, pre-existing psychiatric condition, thyroid dysfunction, psoriasis

Drug	Dosage	Remarks
Asciminib	Chronic phase Ph+ CML: 80 mg PO 24 hourly or 40 mg PO 12 hourly Chronic phase Ph+ CML with T315I mutation:  200 mg PO 12 hourly	Adverse Reactions Respiratory effect (upper respiratory tract infection); Hematologic effects (decreased platelet count, decreased neutrophil count, decreased hemoglobin); GI effects (nausea, diarrhea); Metabolic effects (increased triglycerides, increased creatine kinase, increased alanine aminotransferase, increased lipase, increased amylase); Other effects (musculoskeletal pain, fatigue, rash) Special Instructions Use with caution in patients with myelosuppression, pancreatic disease, history of cardiovascular risk factors, hypertension Monitor blood pressure, CV status, CBC, serum lipase and amylase
Bosutinib	Newly diagnosed chronic phase Ph+ CML: 400 mg PO 24 hourly Chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy: 500 mg PO 24 hourly May increase dose to 600 mg/day in patients who do not reach complete hematologic response by week 12 and without grade 3 or greater adverse reactions	Adverse Reactions GI effects (nausea/vomiting, diarrhea, abdominal pain, increase hepatic enzymes); Hematologic effects (thrombocytopenia, anemia, neutropenia); Respiratory effects (dyspnea, cough, infection, nasopharyngitis); Musculoskeletal effects (arthralgia, back pain); CNS effects (headache, dizziness); Dermatologic effects (rashes, pruritus); Other effects (fatigue, pyrexia, edema, asthenia, decreased appetite) Special Instructions To be taken with food Monitor CBC, liver enzymes monthly for the first 3 months then as needed Adjust dose or discontinue treatment with Bosutinib if with signs of toxicity: Discontinue if transaminase ≥3x ULN w/ bilirubin >2x ULN and alkaline phosphatase <2x ULN Withhold if with grade 3-4 diarrhea Adjust dose if with ANC <1,000 x 106/L and platelet <50,000 x 106/L
Dasatinib	Chronic phase CML:  100 mg PO 24 hourly Accelerated, myeloid or lymphoid blast phase CML: 140 mg PO 24 hourly	Adverse Reactions Hematologic effects (myelosuppression, hemorrhage, other bleeding-related events); CV effects (QT prolongation, cardiac adverse reactions, pulmonary arterial hypertension [PAH]); GI effects (diarrhea, nausea); Other effects (fluid retention, headache, dyspnea, skin rash, fatigue, pyrexia, febrile neutropenia, infection, pneumonia) Special Instructions Use with caution in patients taking anticoagulants or antiplatelet, concomitant antiarrhythmics or QT-prolonging drugs and cumulative high-dose anthracycline therapy, those with known fluid retention, QT prolongation or congenital long QT syndrome, hypokalemia or hypomagnesemia, risk factors or history of cardiac disease Monitor CBC in patients with myelosuppression as it may cause platelet dysfunction and hemorrhage Discontinue if PAH develops
Imatinib mesylate  (Imatinib mesilate)	Chronic phase CML: 400 mg PO 24 hourly Accelerated or blast phase CML: 600 mg PO 24 hourly Max dose: 800 mg/day Reduce initial dose to 50% in patients with moderate renal impairment (CrCL 20-39 mL/min) Moderate renal impairment: Dose should not exceed 400 mg Mild renal impairment (CrCl 40-59 mL/min): Dose should not exceed 600 mg	Adverse Reactions Hematologic effects (neutropenia, thrombocytopenia, anemia, pancytopenia, hemorrhage); GI effects (nausea/vomiting, diarrhea, flatulence, abdominal distension, gastroesophageal reflux, constipation, dry mouth, gastritis, increased hepatic enzymes, dyspepsia, abdominal pain, taste disturbance, anorexia); CNS effects (headache, insomnia, dizziness, paresthesia, hypoesthesia); Ophthalmologic effects (periorbital edema, eyelid edema, increased lacrimation, conjunctival hemorrhage, conjunctivitis, dry eye, blurred vision); Respiratory effects (dyspnea, epistaxis, cough); Musculoskeletal effects (muscle spasm or cramps, myalgia, arthralgia, bone pain, joint swelling); Dermatologic effects (dermatitis, eczema, rash, pruritus, face edema, dry skin, erythema, alopecia, night sweats); Other effects (flushing,fluid retention, edema, fatigue, weakness, anasarca, chills, rigors, decreased/increased weight, pyrexia) Special Instructions Use with caution in patients with hepatic or renal impairment, history of cardiac disease or renal failure, severe fluid retention, GI hemorrhage and tumor lysis syndrome Monitor weight, liver function and full blood count regularly, TSH levels in thyroidectomy patients under Levothyroxine replacement, GI symptoms at the start of treatment Clinically significant dehydration and high uric acid levels should be corrected prior to initiation
Nilotinib	First-line treatment of newly diagnosed Ph+ CML in chronic phase: 300 mg PO 12 hourly Ph+ CML in chronic and accelerated phase resistant to or intolerant to prior therapy:  400 mg PO 12 hourly	Adverse Reactions GI effects (nausea/vomiting, constipation, diarrhea, upper abdominal pain, dyspepsia, anorexia); Musculoskeletal effects (myalgia, arthralgia, muscle spasms, bone pain, pain in extremity, fatigue, asthenia, peripheral edema); CNS effect (headache); Dermatologic effects (rash, pruritus, dry skin, alopecia, erythema) Special Instructions Use with caution in patients with myelosuppression, history of pancreatitis and heart disease or with significant cardiac risk factors, total gastrectomy, galactose intolerance and severe lactase deficiency or glucose-galactose malabsorption Ensure adequate fluid intake and measure uric acid levels prior to therapy Monitor for signs of severe fluid retention and assess lipid profile and blood glucose prior to and during treatment Test the levels of hepatic transaminases, bilirubin, serum lipase and amylase monthly Perform CBC every 2 weeks for the first 2 months, then monthly thereafter Avoid in patients with hypokalemia, hypomagnesemia, long QT syndrome, recent MI, CHF, unstable angina or bradycardia and those taking antiarrhythmic medications as QTc prolongation may develop
Ponatinib	Chronic phase CML Initial dose: 45 mg PO 24 hourly May decrease dose to 15-30 mg PO 24 hourly if with major cytogenic response	Adverse Reactions GI effects (pancreatitis, GI upset, hepatic failure); Metabolic effects (hypocalcemia, hyperglycemia, hyperuricemia, hypophosphatemia, hypertriglyceridemia, hypokalemia); CNS effects (headache, migraine, dizziness, vision disturbance); CV effects (hypertension, CVA, cardiac failure, thrombosis, myocardial infarction); Hematologic effects (decreased platelets/WBCs, anemia, febrile neutropenia, pancytopenia); Other effects (muscle pain, rash, impaired fertility, myelosuppression) Special Instructions Use with caution in patients with hepatic or mild-moderate renal impairment, MI within the past 3 months, unstable angina, history of stroke, hypertension, DM, hyperlipidemia Monitor CV status, CBC, LFTs, serum lipase

All dosage recommendations are for non-elderly adults with normal renal and hepatic function unless otherwise stated.   
Not all products are available or approved for above use in all countries.  
Products listed in the Drug Summary are based on indications stated in the locally approved product monographs.   
Please refer to local product monographs in Related MIMS Drugs for country-specific prescribing information.