Tasigna

Nilotinib

Adult & ped patients w/ newly diagnosed Philadelphia chromosome +ve chronic myeloid leukemia (Ph+ CML) in chronic phase (CP). Adult patients w/ CP & accelerated phase (AP) Ph+ CML resistant to or intolerant to at least 1 prior therapy including imatinib. Ped patients w/ CP Ph+ CML w/ resistance or intolerance to prior therapy including imatinib.

Adult Newly diagnosed Ph+ CML-CP 300 mg bid, continued as long as clinical benefit is observed or until unacceptable toxicity occurs. Sustained deep molecular response (MR 4.5) in newly diagnosed Ph+ CML-CP May consider treatment discontinuation if deep molecular response is sustained for a min of 1 yr immediately prior to therapy discontinuation in patient treated at 300 mg bid for a min of 3 yr. Re-initiate therapy in patient who lose major molecule response (MMR) w/in 4 wk at 300 mg bid or at a reduced dose level of 400 mg once daily if patient had a dose reduction prior to discontinuation of therapy. Ph+ CML-CP & CML-AP resistant to or intolerant to at least 1 prior therapy including imatinib 400 mg bid, continued as long as benefit is observed or until unacceptable toxicity occurs. Sustained deep molecular response (MR 4.5) in Ph+ CML-CP following prior imatinib therapy May consider treatment discontinuation if deep molecular response is sustained for a min of 1 yr immediately prior to therapy discontinuation in patient treated for a min of 3 yr. Re-initiate therapy in patient w/ confirmed loss of MR 4.0 (2 consecutive measures separated by at least 4 wk showing loss of MR 4.0) or loss of MMR w/in 4 wk either at 300 mg or 400 mg bid. Ped patient Newly diagnosed Ph+ CML-CP or resistant or intolerant Ph+ CML-CP 230 mg/m² bid, rounded to the nearest 50 mg dose (to 400 mg max single dose).

Should be taken on an empty stomach: Avoid food at least 2 hr before & at least 1 hr after a dose. Swallow whole, do not chew/crush. Avoid grapefruit products. For patients unable to swallow cap, content of cap may be dispersed in 1 tsp of applesauce & should be taken immediately. Not more than 1 tsp & no food other than applesauce must be used.

Hypersensitivity.

Thrombocytopenia, neutropenia & anemia (NCI CTC Grade 3/4) in patients w/ imatinib-resistant or intolerant CML & CML-AP; perform CBC every 2 wk for the 1st 2 mth & then mthly thereafter, or as clinically indicated. Risk of developing QT prolongation in patients w/ hypokalemia, hypomagnesemia, long QT syndrome, & uncontrolled or significant cardiac disease including recent MI, CHF, unstable angina or clinically significant bradycardia. Evaluate CV status & monitor CV risk factors; etiology if signs of severe fluid retention appear during treatment. Reactivation of hepatitis B in patients who are chronic carriers. Closely monitor for signs & symptoms of active hepatitis B infection throughout therapy & for several mth following termination of therapy in patients who are carriers of HBV. Monitor BCR-ABL transcript levels in patients eligible for treatment discontinuation. Frequent monitoring of BCR-ABL transcript levels & CBC w/ differential is required to detect possible loss of remission; perform BCR-ABL kinase domain mutation testing if patients fail to achieve MMR after 3 mth of treatment re-initiation. Lipid profiles determination is recommended before initiating treatment, assessed at mth 3 & 6 after initiating therapy, & at least yrly during chronic therapy. Assess glucose levels before initiating & monitor during treatment as clinically indicated. Patients w/ previous history of pancreatitis, total gastrectomy, tumor lysis syndrome. Avoid concomitant use w/ strong CYP3A4 inhibitors &/or medicinal products w/ known potential to prolong QT interval; grapefruit juice & other foods known to inhibit CYP3A4. Concomitant use w/ HMG-CoA reductase inhibitor. Must not be taken in conjunction w/ food. Hepatic impairment. Use of effective contraceptive method in females of reproductive potential during & for up to 2 wk after ending treatment. Pregnancy & lactation. Ped patient <2 yr or w/ Ph+ CML-AP or blast crisis.

Headache; nausea, constipation, diarrhea, vomiting, upper abdominal pain; rash, pruritus, alopecia, dry skin; myalgia, arthralgia, fatigue. Decreased appetite; abdominal pain, dyspepsia; erythema; muscle spasms, bone pain, pain in extremity; asthenia, peripheral edema.

Increased bioavailability w/ strong CYP3A4 inhibitors (including but not limited to ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin, & telithromycin). May reduce exposure w/ CYP3A4 inducers (eg, phenytoin, rifampicin, carbamazepine, phenobarb, & St. John's Wort). Increased systemic exposure of oral midazolam & other drugs primarily metabolized by CYP3A4 (eg, certain HMG-CoA reductase inhibitors). Increased absorption & bioavailability w/ food. CYP3A4 substrates & drugs w/ narrow therapeutic index (eg, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, sirolimus & tacrolimus). Anti-arrhythmics (eg, amiodarone, disopyramide, procainamide, quinidine & sotalol) & other drugs that may prolong the QT interval (eg, chloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin, bepridil & pimozide). Grapefruit juice & other foods known to inhibit CYP3A4.

Targeted Cancer Therapy

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

Rx