Tasigna

Nilotinib HCl

Newly diagnosed Philadelphia chromosome +ve chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) in adults. CP & accelerated phase (AP) Philadelphia chromosome +ve chronic myelogenous leukemia (Ph+ CML) in adults resistant to or intolerant to at least 1 prior therapy including imatinib.

Adult Newly diagnosed Ph+ CML-CP Recommended dose: 300 mg bid at approx 12 hr interval. Ph+ CML-CP & CML-AP resistant or intolerant to at least 1 prior therapy including imatinib Recommended dose: 400 mg bid at approx 12 hr interval.

Should be taken on an empty stomach: Swallow whole. May open cap & disperse contents in 1 tsp of applesauce. Take immediately.

Hypersensitivity.

Consider discontinuation of treatment in patients confirmed to express typical BCR-ABL transcripts, e13a2/b2a2 or e14a2/b3a2. Withhold therapy temporarily or reduce dose in case of myelosuppression. Interrupt therapy in case lipase elevations are accompanied by abdominal symptoms. Not to be used in patients w/ hypokalemia, hypomagnesemia, or long QT syndrome. Thrombocytopenia, neutropenia, anemia. QT interval prolongation; CV events; fluid retention eg, pleural effusion, pulmonary edema & pericardial effusion; hepatitis B reactivation; serum lipase elevation; tumor lysis syndrome. Hypokalemia & hypomagnesemia. Ventricular repolarization abnormalities. Test patients for hepatitis B infection before initiating treatment. Closely monitor patients who are HBV carriers for signs & symptoms of active hepatitis B infection throughout therapy & for several mth following termination of therapy. Patients w/ cardiac disorders; history of pancreatitis; total gastrectomy; at risk of developing QT prolongation eg, w/ long QT syndrome or uncontrolled or significant cardiac disease including recent MI, CHF, unstable angina or clinically significant bradycardia. Correct hypokalemia or hypomagnesemia before treatment & monitor periodically. Obtain ECGs to monitor QTc at baseline, 7 days after initiation & periodically thereafter. Perform CBC every 2 wk for the 1st 2 mth & then mthly thereafter; BCR-ABL kinase domain mutation testing in patients who fail to achieve major molecular response after 3 mth of treatment re-initiation. Evaluate CV status & monitor CV risk factors; etiology of severe fluid retention during treatment. Investigate unexpected, rapid wt gain. Monitor BCR-ABL transcript levels in patients eligible for treatment discontinuation. Assess BCR-ABL transcript levels before & during treatment discontinuation; blood glucose before treatment initiation & monitor during treatment. Frequently monitor BCR-ABL transcript levels & CBC w/ differential. Determine lipid profiles before treatment & assess at mth 3 & 6 after initiating therapy, & at least yrly during chronic therapy. Galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption. Avoid concomitant use w/ QT prolonging drugs (eg, anti-arrhythmics) & strong CYP3A4 inhibitors; grapefruit juice & foods. Concomitant use w/ potent CYP3A4 inducers. Renal (serum creatinine conc >1.5x ULN) & hepatic impairment. Females of reproductive potential should use effective method of contraception (<1% pregnancy rates) during & for up to 2 wk after treatment. Pregnancy. Not to breastfeed during treatment & for 2 wk after last dose. Childn & adolescents <18 yr.

Headache; nausea, constipation, diarrhoea, vomiting, upper abdominal pain; rash, pruritus, alopecia, dry skin; myalgia, arthralgia; fatigue; hypophosphataemia; hyperbilirubinaemia; increased ALT, AST, lipase, blood triglycerides, lipoprotein & total cholesterol. Decreased appetite, electrolyte imbalance (including hypomagnesaemia, hyperkalaemia, hypokalaemia, hyponatraemia, hypocalcaemia, hypercalcaemia, hyperphosphataemia), DM, hyperglycaemia, hypercholesterolaemia, hyperlipidaemia, hypertriglyceridaemia; abdominal pain, discomfort & distension, dyspepsia, pancreatitis, dysgeusia, flatulence; erythema, night sweats, eczema, urticaria, hyperhidrosis, contusion, acne, dermatitis (including allergic, exfoliative & acneiform); muscle spasms, bone, chest, musculoskeletal, back, neck & flank pain, pain in extremity, muscular weakness; asthenia, peripheral oedema, pyrexia, chest pain (including non-cardiac chest pain) & discomfort, pain, malaise; folliculitis, URTI (including pharyngitis, nasopharyngitis, rhinitis); skin papilloma; leukopenia, eosinophilia, febrile neutropenia, pancytopenia, lymphopenia; depression, insomnia, anxiety; dizziness, peripheral neuropathy, hypoaesthesia, paraesthesia; eye haemorrhage & pruritus, periorbital oedema, conjunctivitis, dry eye (including xerophthalmia); vertigo; angina pectoris, arrhythmia (including AV block, cardiac flutter, extrasystoles, atrial fibrillation, tachycardia, bradycardia), palpitations, prolonged ECG QT; HTN, flushing; dyspnoea, exertional dyspnoea, epistaxis, cough, dysphonia; abnormal hepatic function; pollakiuria; decreased Hb, wt, & globulins, increased blood amylase, creatine phosphokinase, alkaline phosphatase & insulin, γ-glutamyltransferase, wt.

Increased AUC of & w/ imatinib. Increased bioavailability w/ strong CYP3A4 inhibitor ketoconazole. Avoid concomitant use w/ strong CYP3A4 inhibitors eg, ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin, telithromycin; anti-arrhythmic medicines (eg, amiodarone, disopyramide, procainamide, quinidine, sotalol) & other QT prolonging drugs (eg, chloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin, bepridil, pimozide); grapefruit juice & foods. Decreased AUC w/ rifampicin. Decreased plasma conc w/ CYP3A4 inducers eg, phenytoin, rifampicin, carbamazepine, phenobarb, St. John's Wort. Decreased absorption w/ esomeprazole. Increased systemic exposure of oral midazolam; other drugs metabolized by CYP3A4 (eg, certain HMG-CoA reductase inhibitors). Concomitant use w/ CYP3A4 substrates & drugs w/ narrow therapeutic index (eg, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, sirolimus, tacrolimus); warfarin.

Targeted Cancer Therapy

L01EA03 - nilotinib ; Belongs to the class of BCR-ABL tyrosine kinase inhibitors. Used in the treatment of cancer.

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