Myelofibrosis Drug Summary

Drug	Dosage	Remarks
Azacitidine	Initial dose: 75 mg/m2 SC/IV infusion over 10-40 minutes on days 1-7 of a 28-day treatment cycle May increase to 100 mg/m2 if no benefit after 2 cycles and no toxicity Continue until disease progression	Adverse Reactions GI effects (nausea/vomiting, abdominal pain, diarrhea, anorexia, constipation, dyspepsia, mucositis); Hematologic effects (anemia, neutropenia, thrombocytopenia, GI or intracranial hemorrhage, bruising, petechiae); CNS effects (headache, insomnia, dizziness, anxiety); Dermatologic effects (alopecia, itch, rash); Other effects (renal tubular acidosis, elevated serum creatinine, injection site reactions hepatotoxicity, dyspnea, hypokalemia, fever, infection) Special Instructions Contraindicated in patients with advanced malignant hepatic tumor Use with caution in patients with high tumor burden, history of severe chronic heart failure, clinically unstable cardiac disease or pulmonary disease, renal and severe hepatic impairment Monitor CBC, LFTs, electrolytes and renal function at baseline and before each treatment cycle
Busulfan	2-4 mg PO 24 hourly	Adverse Reactions Dose-related bone marrow depression; GI effects (nausea/vomiting, diarrhea, oral ulceration); Hepatic effects (jaundice, hyperbilirubinemia, hepatic veno-occlusive disease); Dermatologic effects (alopecia, hyperpigmentation); Other effects (ovarian suppression and amenorrhea in females, sterility and testicular atrophy in males) Special Instructions Take with chilled liquid Ensure adequate fluid intake Premedication with prophylactic anticonvulsants and antiemetics is recommended if high-dose treatment for HSCT is prescribed Use with caution in patients with compromised bone marrow reserve due to previous radiation therapy, prior chemotherapy or prior stem cell transplantation, history of seizures or taking antiepileptic agents, history of head trauma, renal and hepatic impairment Avoid concomitant administration of live vaccines Monitor CBC during treatment
Decitabine	20 mg/m2 IV infusion over 60 minutes for 5 consecutive days Repeat cycle every 4 weeks for a minimum of 4 cycles	Adverse Reactions Hematologic effects (neutropenia, thrombocytopenia, anemia, leukopenia); GI effects (nausea/vomiting, diarrhea, stomatitis); Other effects (pneumonia, UTI, other infections, pyrexia, septic shock, sepsis, sinusitis, epistaxis) Special Instructions Use with caution in patients with history of severe chronic heart failure or clinically unstable cardiac disease, hepatic and severe renal impairment Monitor CBC and platelet count at baseline and before each treatment cycle Monitor for signs and symptoms of infection and treat promptly
Hydroxyurea (Hydroxycarbamide)	20-30 mg/kg PO as single dose 24 hourly or 80 mg/kg PO single dose 72 hourly Concomitant therapy: 80 mg/kg PO single dose 72 hourly, started at least 7 days before initiation of radiotherapy	Adverse Reactions GI effects (nausea/vomiting, diarrhea, anorexia); Other effects (decreased blood counts, alopecia, headache) Special Instructions May be taken with or without food Contraindicated in patients with hypersensitivity to Hydroxyurea, marked bone marrow depression Use with caution in the elderly Monitor blood counts

Drug	Dosage	Remarks
Fedratinib	Baseline platelet count ≥50,000/mm3: 400 mg PO 24 hourly Reduce or modify dose in the presence of adverse reactions and in patients who become transfusion dependent during therapy	Adverse Reactions CNS effect (fatigue); Metabolic effects (increased amylase, hyponatremia, increased serum lipase); GI effects (nausea/vomiting, diarrhea); Hematologic effects (anemia, thrombocytopenia, neutropenia); Hepatic effects (increased AST and ALT); Other effects (increased serum creatinine, asthenia, muscle spasm) Special Instructions Administration with high-fat meal may reduce the incidence of nausea/vomiting Avoid use in patients with severe hepatic impairment Adjust dose in patients with severe renal impairment Perform CBC at baseline and periodically during treatment Assess thiamine level prior to initiation and periodically during course of treatment Replete thiamine before initiation of treatment if with thiamine deficiency Discontinue temporarily if encephalopathy is suspected (signs and symptoms include ataxia, mental status changes, nystagmus, diplopia) then initiate parenteral Thiamine and monitor until symptoms resolve and thiamine levels normalize Monitor hepatic function, amylase and lipase at baseline and periodically during treatment Discontinue if unable to tolerate 200 mg/day dose
Momelotinib	200 mg PO 24 hourly until disease progression or unacceptable toxicity	Adverse Reactions Hematologic effects (hemorrhage, thrombocytopenia); GI effects (abdominal pain, diarrhea, nausea); CNS effects (dizziness, fatigue, headache); Hepatic effects (increased serum AST, ALT, bilirubin); CV effects (hypotension, peripheral edema); Dermatologic effects (pruritus, skin rash); Other effects (cough, fever, infection, limb pain) Special Instructions Avoid use in patients with active infection Adjust dose in patients with severe hepatic impairment Monitor for signs and symptoms of infection including reactivation of hepatitis B, cardiovascular events, thrombosis and development of secondary malignancies; perform CBC with platelet count and LFTs at baseline and periodically during treatment
Pacritinib	Platelet count <50 x 109/L: 200 mg PO 12 hourly	Adverse Reactions Hematologic effects (anemia, thrombocytopenia); GI effects (diarrhea, nausea); Other effect (peripheral edema) Special Instructions Avoid use in patients with active bleeding, baseline QTc >480 msec Use with caution in patients with diarrhea, thrombocytopenia, major adverse cardiac events, thrombosis, increased risk for secondary malignancies or infection Contraindicated in patients taking strong CYP3A4 inhibitors or inducers
Ruxolitinib	Initial dose: Platelet count 50,000-<100,000/mm3: 5 mg PO 12 hourly Platelet count 100,000-200,000/mm3: 15 mg PO 12 hourly Platelet count >200,000/mm3: 20 mg PO 12 hourly Titrate dose based on efficacy and tolerability after 4 weeks then at 2-week intervals in 5-mg increments 12 hourly Max dose: 25 mg PO 12 hourly	Adverse Reactions Hematologic effects (neutropenia, anemia, thrombocytopenia); CNS effects (headache, dizziness, progressive multifocal leukoencephalopathy); Other effects (increased AST and ALT, bruising, hypercholesterolemia, non-melanoma skin cancers) Special Instructions Interrupt dosing if platelet count <50,000/mm3 or absolute neutrophil count (ANC) <500/mm3 Contraindicated in patients with hypersensitivity to Ruxolitinib Use with caution in patients with hepatic and moderate to severe renal impairment, at risk of hematological adverse reactions (thrombocytopenia, anemia, neutropenia), with TB or at risk for TB and other serious bacterial, fungal and viral infections, chronic hepatitis B infection and in patients taking CYP3A4 inhibitors (eg Fluconazole) Perform CBC with differential at baseline and regularly during the course of treatment; periodic lipid monitoring, renal and hepatic function tests, and skin examination during the course of treatment Patient should be advised about signs and symptoms of herpes zoster and must seek treatment as early as possible Discontinue if without improvement of symptoms or reduction in spleen size after 6 months Avoid sudden withdrawal; taper gradually if discontinuing for reasons other than thrombocytopenia or neutropenia

Drugs for Myelofibrosis-Associated Anemia

Drug	Dosage	Remarks
Danazol	Initial dose: 200 mg PO 12 hourly May increase to 400 mg PO 12 hourly as tolerated Continue for minimum of 3 months and dose may be tapered to minimum effective dose after 6 months	Adverse Reactions Androgenic effects (acne, seborrhea, weight gain, hair loss, voice change, clitoral hypertrophy); Hepatic effects (hepatitis, benign hepatic adenoma, cholestatic jaundice); CNS effects (nervousness, emotional lability, headache); CV effects (palpitations, tachycardia, benign intracranial hypertension); Other effects (interstitial pneumonitis, menstrual disturbances) Special Instructions Contraindicated in patients with thromboembolic disease or history of thrombosis, severe cardiac impairment, severe hepatic or renal impairment, undiagnosed abnormal genital bleeding, androgen-dependent tumor Use with caution in patients with epilepsy, migraine, DM, polycythemia, hypertension and other CV disease, lipoprotein disorder, hepatic or renal impairment Monitor LFTs at baseline and regularly during treatment Screen men for prostate cancer before initiation of therapy and during treatment Monitor for signs and symptoms of intracranial hypertension, androgenic changes and/or fluid retention Perform CBC, lipid panel, renal function tests regularly

Drugs for Myelofibrosis-Associated Anemia

Drug	Dosage	Remarks
Lenalidomide	10 mg PO 24 hourly on days 1-21 of repeated 28-day cycles	Adverse Reactions Hematologic effects (thrombocytopenia, neutropenia, leukopenia, anemia); Respiratory effects (pneumonia, lung infection, bronchitis, nasopharyngitis, cough); CV effects (venous thromboembolism, pulmonary embolism, hypotension, peripheral edema); GI effects (diarrhea, nausea, decreased appetite); CNS effects (insomnia, asthenia, peripheral neuropathy); Other effects (renal failure, muscle spasms, pyrexia, fatigue, back pain, hypocalcemia, pruritus) Special Instructions Avoid use in patients with high tumor burden Use with caution in patients with known risk factors for thromboembolism or MI, hepatic or renal impairment, concomitant use with erythropoietic agents Monitor CBC with differential count, platelet count every week for the first 8 weeks of treatment then every month thereafter Monitor LFTs regularly
Thalidomide	50-200 mg PO 24 hourly	Adverse Reactions CNS effects (severe and irreversible peripheral neuropathy, dizziness, drowsiness, somnolence); CV effects (bradycardia, orthostatic hypotension); Other effects (constipation, hypersensitivity reaction) Special Instructions Should be taken on an empty stomach or at least 1 hour after a meal Use with caution in patients with high tumor burden Monitor CBC with differential count regularly

Drugs for Myelofibrosis-Associated Anemia

Drug	Dosage	Remarks
Darbepoetin alfa	150-300 mcg SC weekly or  500 mcg SC once every 2-3 weeks	Adverse Reactions CV effects (hyper-/hypotension, chest pain, peripheral edema); CNS effects (dizziness, headache); Musculoskeletal effects (myalgia, arthralgia, limb pain); Respiratory effects (cough, dyspnea, bronchitis); Other effects (fatigue, fever, skin reactions, hyperkalemia, infection, transient increase in platelet count, influenza-like symptoms, injection site pain) Special Instructions Contraindicated in patients with uncontrolled hypertension Use with caution in patients with hypertension, history of seizures, hepatic impairment, CV disease, thrombocytosis Monitor BP, hemoglobin, electrolytes and platelet counts regularly
Epoetin alfa	10,000-20,000 units SC 3 times weekly

Drugs for Myelofibrosis-Associated Anemia

Drug	Dosage	Remarks
Luspatercept	1 mg/kg SC 3 weekly	Adverse Reactions GI effects (nausea, diarrhea, abdominal pain); Musculoskeletal effects (musculoskeletal pain, arthralgia); Respiratory effects (cough, dyspnea); CNS effects (headache, dizziness/vertigo); Other effects (fatigue, hypersensitivity) Special Instructions Use with caution in patients with beta thalassemia Monitor BP, for signs and symptoms of thromboembolic events

All dosage recommendations are for non-pregnant and non-breastfeeding women and 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.