Nilotinib

Therapy should be initiated by a physician experienced in the diagnosis and treatment of CML. Treatment continued as long as clinical benefit is observed or until unacceptable toxicity occurs. If a dose is missed, the patient should not take an additional dose but take the usual prescribed next dose. Administration: take on an empty stomach — no food for at least 2 hours before and at least 1 hour after the dose; swallow capsules whole with water (US label section 2.1; the UK SPC section 4.4 also warns that taking nilotinib with food may significantly prolong the QT interval). Dose adjustment for haematological toxicity not related to the underlying leukaemia: for adults on 300 mg twice daily (newly diagnosed chronic phase) or 400 mg twice daily (imatinib resistant/intolerant chronic phase), if ANC <1.0 x 10^9/l and/or platelets <50 x 10^9/l, interrupt nilotinib and monitor blood count; resume within 2 weeks at the prior dose if counts recover; if counts remain low, a dose reduction to 400 mg once daily may be required. For imatinib resistant/intolerant accelerated phase CML on 400 mg twice daily, the corresponding thresholds are ANC <0.5 x 10^9/l and/or platelets <10 x 10^9/l. Treatment-free remission (TFR): discontinuation may be considered in eligible adult Ph+ chronic phase patients treated with nilotinib for a minimum of 3 years who have a deep molecular response (MR4.5) sustained for at least one year; requires monthly BCR-ABL transcript and full blood count monitoring for one year, then every 6 weeks in year 2, then every 12 weeks. Patients who lose MMR must re-initiate treatment within 4 weeks — at 300 mg twice daily (or 400 mg once daily if the dose had been reduced before discontinuation) in first-line patients, or at either 300 mg or 400 mg twice daily in post-imatinib patients. PAEDIATRIC: dosing is individualised by body surface area, not by body weight — the recommended dose is 230 mg/m2 twice daily, rounded to the nearest 50 mg (maximum single dose 400 mg). SPC dosing scheme: up to 0.32 m2 = 50 mg; 0.33-0.54 m2 = 100 mg; 0.55-0.76 m2 = 150 mg; 0.77-0.97 m2 = 200 mg; 0.98-1.19 m2 = 250 mg; 1.20-1.41 m2 = 300 mg; 1.42-1.63 m2 = 350 mg; 1.64 m2 or greater = 400 mg. There is no experience below 2 years of age, no data in newly diagnosed patients below 10 years, and limited data in imatinib resistant/intolerant patients below 6 years. Verify all paediatric dosing against a children's formulary. Hepatic impairment: US label advises a reduced starting dose in patients with baseline hepatic impairment.