Jakavi

Disease-related splenomegaly or symptoms in adults w/ primary myelofibrosis (MF) (chronic idiopathic MF), post polycythaemia vera (PV) MF or post essential thrombocythaemia MF. PV in adults who are resistant to or intolerant of hydroxyurea. Acute or chronic graft versus host disease (GvHD) in patients ≥12 yr who have inadequate response to corticosteroids or other systemic therapies.

MF Recommended starting dose: Platelet count >200,000/mm³ 20 mg bd, 100,000 to 200,000/mm³ 15 mg bd, 75,000 to <100,000/mm³ 10 mg bd, 50,000 to <75,000/mm³ 5 mg bd. Patient w/ hepatic & severe renal impairment Reduce dose by approx 50% to be administered bd. Patient w/ ESRD on haemodialysis Single dose of 15-20 mg or 2 doses of 10 mg given 12 hr apart, to be administered post-dialysis & only on the day of haemodialysis. PV Recommended starting dose: 10 mg bd. Dose reduction should be considered if Hb decreases <12 g/dL & is recommended if it decreases <10 g/dL. Patient w/ hepatic & severe renal impairment 5 mg bd. Patient w/ ESRD on haemodialysis Single dose of 10 mg or 2 doses of 5 mg given 12 hr apart, to be administered post-dialysis & only on the day of haemodialysis. MF & PV May increase doses by max of 5 mg bd, up to max dose of 25 mg bd, if efficacy is considered insufficient & blood counts are adequate. Do not increase starting dose w/in the 1st 4 wk of treatment & thereafter no more frequently than at 2-wk intervals. Acute & chronic GvHD Recommended starting dose: 10 mg bd. Patient w/ thrombocytopenia, neutropenia, or elevated total bilirubin after standard supportive therapy (including growth-factors, anti-infective therapies, & transfusions); liver involvement & increased total bilirubin (>3x ULN) 1 dose level reduction step is recommended (10 mg bd to 5 mg bd or 5 mg bd to 5 mg once daily). Patient w/ severe renal impairment 5 mg bd.

May be taken with or without food.

Hypersensitivity. Pregnancy & lactation.

Risk of haematological adverse drug reactions (including thrombocytopenia, anaemia, & neutropenia). CBC (including WBC differential count) must be performed before initiating therapy, & should be monitored every 2-4 wk until doses are stabilised, & then as clinically indicated. Discontinue treatment in MF patients w/ platelet count <50,000/mm³ or ANC <500/mm³. Risk of developing serious bacterial, mycobacterial, fungal, viral & other opportunistic infections. Screen patients for HBV & active & latent TB before starting treatment. Seek treatment in case of early signs & symptoms of herpes zoster. Reports of progressive multifocal leukoencephalopathy (PML). If PML is suspected, further dosing must be suspended until PML has been excluded. Associated w/ increases in lipid parameters (including total cholesterol, HDL-C, LDL-C, & triglycerides). Lipid monitoring & treatment of dyslipidaemia is recommended. Reports of major adverse cardiac events, DVT & pulmonary embolism. Prior to initiating or continuing therapy, the benefits & risks for the individual patient should be considered particularly in patients ≥65 yr, patients who are current or past long-time smokers, & patients w/ history of ASCVD or other CV risk factors. Reports of lymphoma & non-melanoma skin cancers (including basal cell, squamous cell, & Merkel cell carcinoma). Periodic skin exam is recommended for patients who are at increased risk for skin cancer. Risk of withdrawal effects. Gradual dose tapering may be considered. Concomitant use w/ strong CYP3A4 inhibitors, dual CYP3A4 & CYP2C9 inhibitors, & cytoreductive therapies. Should not be taken by patients w/ rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Patients who experience dizziness after intake should refrain from driving or using machines. Caution in patients w/ renal or hepatic impairment. Women of child-bearing potential should use effective contraception during treatment. MF & PV: Safety & efficacy have not been established in childn & adolescents ≤18 yr. PV: No data available for patients w/ ESRD on peritoneal dialysis or continuous venovenous haemofiltration. GvHD: No data for patients w/ ESRD. Safety & efficacy have not been established in patients <12 yr.

Anaemia, thrombocytopenia, neutropenia; increased ALT & AST. MF: Bruising, other bleeding (including epistaxis, post-procedural haemorrhage, haematuria), dizziness; hypertriglyceridaemia. PV: Wt gain, dizziness, headache; hypercholesterolaemia. Acute GvHD: Cytomegalovirus infection, sepsis, UTI; hypercholesterolaemia. Chronic GvHD: HTN, headache, UTI; hypercholesterolaemia.

Increased C_max & AUC w/ strong CYP3A4 inhibitors (eg, boceprevir, clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, voriconazole); dual CYP2C9 & CYP3A4 inhibitors (eg, fluconazole); mild or moderate CYP3A4 inhibitors (eg, ciprofloxacin, erythromycin, amprenavir, atazanavir, diltiazem, cimetidine). Decreased AUC w/ CYP3A4 inducers (eg, avasimibe, carbamazepine, phenobarb, phenytoin, rifabutin, rifampicin, St. John's wort). Increased systemic exposure of P-gp & BCRP substrates (eg, dabigatran etexilate, ciclosporin, rosuvastatin, & potentially digoxin).

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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