Iclusig

Adults w/ chronic, accelerated or blast phase chronic myeloid leukaemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib & for whom subsequent treatment w/ imatinib is not clinically appropriate; or who have T315I mutation; Philadelphia chromosome +ve acute lymphoblastic leukaemia (Ph+ ALL) who are resistant to dasatinib; who are intolerant to dasatinib & for whom subsequent treatment w/ imatinib is not clinically appropriate; or who have T315I mutation. Newly diagnosed Ph+ ALL in combination w/ chemotherapy.

CML, Ph+ ALL in patients resistant/intolerant to dasatinib or other TKIs; or who have T315I mutation Initially 45 mg once daily. Patient w/ chronic phase-CML who have achieved major cytogenetic response Reduce dose to 15 mg. Newly diagnosed Ph+ ALL Initially 30 mg once daily in combination w/ chemotherapy w/ reduction to 15 mg once daily upon achievement of MRD -ve (≤0.01% BCR::ABL1/ABL1) CR at the end of induction. Patient w/ loss of MRD negativity Re-escalate dose to previously tolerated dose of up to 30 mg once daily. Pre-existing hepatic impairment (Child-Pugh A, B, or C) in patients w/ chronic, accelerated or blast phase CML & Ph+ ALL Reduce starting dose to 30 mg once daily.

May be taken with or without food: Swallow whole, do not crush/dissolve.

Hypersensitivity.

Not to be used in patients w/ history of MI, prior revascularization or stroke. Discontinue treatment in patients who develop serious heart failure. Consider discontinuation of treatment if complete haematologic response has not occurred by 3 mth. Interrupt treatment in case of arterial occlusion; thromboembolism; VTE; if posterior reversible encephalopathy syndrome is diagnosed. Interrupt treatment & evaluate patients for renal artery stenosis in the event of significant worsening, labile or treatment-resistant HTN; evidence of pancreatitis if lipase elevations are accompanied by abdominal symptoms; serious or severe haemorrhage. Temporarily interrupt treatment if HTN is not medically controlled. Withhold treatment in case of severe adverse reactions. Interrupt, reduce dose or discontinue treatment based on recurrence/severity of neuropathy, fluid retention or cardiac arrhythmia. Severe (Grade 3 or 4) thrombocytopenia, neutropenia & anaemia; arterial occlusions, including fatal MI, stroke, retinal arterial & venous occlusions w/ permanent visual impairment or vision loss, large arterial vessels of brain stenosis, severe peripheral vascular disease; treatment-emergent HTN (including hypertensive crisis) & associated w/ confusion, headache, chest pain, or shortness of breath; formation of aneurysms &/or artery dissections; ALT, AST bilirubin & alkaline phosphatase elevations; GI haemorrhage & subdural hematoma; hepatitis B reactivation in patients who are chronic carriers of virus; acute hepatic failure or fulminant hepatitis leading to liver transplant; clinically significant effect on QT; peripheral neuropathy; serious ocular toxicities leading to blindness or blurred vision; fatal & serious fluid retention events; cardiac arrhythmias including tachycardia, syncope, atrial fibrillation & supraventricular tachycardia. Increasing age & history of ischaemia, HTN, diabetes or hyperlipidaemia; serious TLS & hyperuricemia. Patients w/ & w/o CV risk factors, including <50 yr; history of pancreatitis or alcohol abuse & aneurysm. Monitor & manage BP during treatment. Monitor active HBV infection throughout & for several mth following termination of therapy. Assess CV status & manage risk factors before starting treatment including history & physical exam. Manage severe or very severe hypertriglyceridemia. Perform CBC every 2 wk for 1st 3 mth & then mthly or as clinically indicated; ophth exam including fundoscopy if decreased or blurred vision occur. Check serum lipase every 2 wk for 1st 2 mth & then periodically thereafter; LFTs prior to treatment initiation & monitor periodically. Test patients for HBV before treatment initiation. Monitor patients for symptoms of neuropathy eg, hypoesthesia, hyperesthesia, paresthesia, discomfort, burning sensation, neuropathic pain or weakness; fluid retention; signs & symptoms of slow heart rate (fainting, dizziness) or rapid heart rate (chest pain, palpitations or dizziness). Ensure adequate hydration & treat high uric acid levels prior to therapy. Not to be taken in patients w/ galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Concomitant use w/ moderate & strong CYP3A inhibitors & inducers; anti-clotting agents in patients who may be at risk of bleeding. Minor influence on ability to drive & use machines. Renal impairment (estimated CrCl <50 mL/min) or ESRD. Closely monitor patients w/ moderate or severe hepatic impairment (Child-Pugh B or C). Women of childbearing potential should use effective contraception during treatment. Advise men not to father a child during treatment. Pregnancy. Discontinue breast-feeding during treatment. Paed <18 yr.

URTI; anaemia, decreased platelet & neutrophil count; decreased appetite; insomnia; headache, dizziness; HTN; dyspnoea, cough; abdominal pain, diarrhoea, vomiting, constipation, nausea, increased lipase; increased ALT & AST; rash, dry skin, pruritus; bone & back pain, arthralgia, myalgia, pain in extremity, muscle spasms; fatigue, asthenia, peripheral oedema, pyrexia, pain. Pneumonia, sepsis, folliculitis, cellulitis; pancytopenia, febrile neutropenia, decreased WBC & lymphocyte count; hypothyroidism; dehydration, fluid retention, hypocalcaemia, hyperglycaemia, hyperuricaemia, hypophosphataemia, hypertriglyceridaemia, hypokalaemia, decreased wt, hyponatraemia; CVA, cerebral infarction, peripheral neuropathy, lethargy, migraine, hyper- & hypoaesthesia, paraesthesia, transient ischaemic attack; blurred vision, dry eye, periorbital & eyelid oedema, conjunctivitis, visual impairment; cardiac failure, MI, CHF, CAD, angina pectoris, pericardial effusion, atrial fibrillation, decreased ejection fraction, acute coronary syndrome, atrial flutter; peripheral arterial occlusive disease, ischaemia & artery stenosis, intermittent claudication, DVT, hot flush, flushing; pulmonary embolism, pleural effusion, epistaxis, dysphonia, pulmonary HTN; pancreatitis, increased blood amylase, GERD, stomatitis, dyspepsia, abdominal distension & discomfort, dry mouth, gastric haemorrhage; increased blood bilirubin, blood alkaline phosphatase & γ-glutamyltransferase; pruritic & exfoliative rash, erythema, alopecia, skin exfoliation, night sweats, hyperhidrosis, petechiae, ecchymosis, skin pain, exfoliative dermatitis, hyperkeratosis, skin hyperpigmentation; musculoskeletal, neck & musculoskeletal chest pain; erectile dysfunction; chills, flu-like illness, non-cardiac chest pain, mass, face oedema. SJS.

Increased serum conc w/ strong CYP3A inhibitors eg, ketoconazole, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole & grapefruit juice. Decreased serum conc w/ strong CYP3A inducers eg, rifampicin, carbamazepine, phenobarb, phenytoin, rifabutin, rifampicin & St. John's wort. Increased plasma conc of P-gp (eg, digoxin, dabigatran, colchicine, pravastatin) or BCRP substrates (eg, MTX, rosuvastatin, sulfasalazine).

Targeted Cancer Therapy

L01EA05 - ponatinib ; Belongs to the class of BCR-ABL tyrosine kinase inhibitors. Used in the treatment of cancer.

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