Jakavi

Ruxolitinib phosphate

Disease-related splenomegaly or symptoms in patients w/ high or intermediate risk myelofibrosis including primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. Patients w/ polycythemia vera who are resistant to or intolerant of hydroxyurea. Patients aged ≥12 yr w/ acute graft versus host disease or chronic graft versus host disease (GvHD) w/ inadequate response to corticosteroids or other systemic therapies.

Myelofibrosis Initial dose: Platelet count >200,000/mm³ 20 mg bid, 100,000 to 200,000/mm³ 15 mg bid, 75,000/mm³ to <100,000/mm³ 10 mg bid, 50,000/mm³ to <75,000/mm³ 5 mg bid. May increase dose by 5 mg bid up to max of 25 mg bid if efficacy is insufficient & blood counts are adequate. Dose reduction: 25 mg bid dose at time of platelet decline w/ platelet count of 100,000/mm³ to <125,000/mm³ 20 mg bid, 75,000/mm³ to <100,000/mm³ 10 mg bid, 50,000/mm³ to <75,000/mm³ 5 mg bid. 20 mg bid dose at time of platelet decline w/ platelet count of 100,000/mm³ to <125,000/mm³ 15 mg bid, 75,000/mm³ to <100,000/mm³ 10 mg bid, 50,000/mm³ to <75,000/mm³ 5 mg bid. 15 mg bid dose at time of platelet decline w/ platelet count of 75,000/mm³ to <100,000/mm³ 10 mg bid, 50,000/mm³ to <75,000/mm³ 5 mg bid. 10 mg bid dose at time of platelet decline w/ platelet count of 50,000/mm³ to <75,000/mm³ 5 mg bid. Polycythemia vera Initially 10 mg bid. Consider dose reduction if Hb decreases <10-12 g/dL. May increase dose by 5 mg bid up to max of 25 mg bid if efficacy is insufficient & blood counts are adequate. GvHD Initially 10 mg bid. Patient w/ thrombocytopenia, neutropenia or elevated total bilirubin 1 dose level reduction (from 10 mg bid to 5 mg bid or 5 mg bid to 5 mg once daily). Severe renal impairment Reduce starting dose based on platelet count by approx 50% for myelofibrosis patients & 5 mg bid for polycythemia vera or GvHD patients. Patient on dialysis Myelofibrosis Initially 15 or 20 mg single dose based on platelet counts w/ subsequent single doses only after each dialysis session. Patient w/ ESRD on hemodialysis Polycythemia vera 10 mg single dose or 2 doses of 5 mg given 12 hr apart on post-dialysis & only on the day of haemodialysis. Hepatic impairment Reduce starting dose based on platelet count by approx 50% for myelofibrosis & GvHD patients, & 5 mg bid for polycythemia vera patients.

May be taken with or without food.

Hypersensitivity.

Interrupt treatment for platelet counts <50,000/mm³ or ANC <500/mm³; Hb <8 g/dL. Consider dose modifications or interruption of treatment for patients developing anemia. Not to be started until active serious infections have resolved. Suspend dosing if progressive multifocal leukoencephalopathy (PML) is suspected. Thrombocytopenia, anemia, neutropenia (ANC <500/mm³); serious bacterial, mycobacterial, fungal, viral & other opportunistic infections; TB; hepatitis B viral load (HBV-DNA titre) increases, w/ & w/o ALT & AST elevations in chronic HBV patients; herpes zoster; PML; non-melanoma skin cancers including basal cell, squamous cell, & Merkel cell carcinoma; increase in total cholesterol, HDL, LDL & triglycerides. W/drawal effects. Patients w/ low platelet counts (<200,000/mm³). Blood transfusion in patients developing anemia. Perform CBC before initiating therapy & monitor during treatment. Assess patients for risk of developing serious infections. Evaluate patients for active & inactive (latent) TB before starting treatment. Periodic skin exam for patients at increased risk for skin cancer. Monitor lipid & treat dyslipidemia. Avoid abrupt discontinuation. Concomitant use w/ strong CYP3A4 inhibitors or dual moderate CYP2C9 & CYP3A4 enzyme inhibitors eg, fluconazole. ESRD on dialysis patients. Severe renal impairment. Sexually active females of reproductive potential should use effective contraception (<1% pregnancy rates) during treatment. Not recommended during pregnancy. Not to breastfeed during treatment. Ped patients <12 yr.

UTI, herpes zoster, pneumonia, cytomegalovirus infections, sepsis; anemia, thrombocytopenia, neutropenia, pancytopenia; hypercholesterolemia, hypertriglyceridemia, wt gain; dizziness, headache; constipation, increased lipase & amylase, nausea; bruising; increased ALT & AST; HTN; increased blood creatine phosphokinase; increased blood creatinine. Flatulence.

Increased AUC & prolonged t_½ w/ strong CYP3A4 inhibitors eg, ketoconazole. Increased AUC w/ erythromycin; fluconazole. Decreased AUC & t_½ w/ rifampin.

Targeted Cancer Therapy

L01EJ01 - ruxolitinib ; Belongs to the class of Janus-associated kinase (JAK) inhibitors. Used in the treatment of cancer.

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