Company:

Novartis

Antineoplastic (kinase inhibitor)

Nilotinib (as HCl monohydrate) 200mg; caps; contains lactose.

Chronic and accelerated phase Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) in adults resistant or intolerant to imatinib.

Nilotinib is an inhibitor of Bcr-Abl kinase. Bcr-Abl is a protein produced only by the abnormal Philadelphia chromosome (+) cells that has been implicated as the cause of the overproliferation of the white blood cells in this form of leukemia.

An open-label multicenter study was conducted to evaluate the efficacy and safety of nilotinib in treating patients with imatinib-resistant or imatinib-intolerant Philadelphia chromosome (+) CML. The efficacy endpoint in patients with chronic phase CML was unconfirmed major cytogenetic response, which included complete and partial cytogenetic responses. Of 232 evaluable patients with chronic phase CML, the response rate was 40%. For patients with accelerated phase CML, the efficacy endpoint was confirmed hematologic response. Of 105 patients with accelerated phase CML, the hematologic response rate was 26%. The median duration of response has not yet been determined; studies are ongoing.

Swallow whole on empty stomach. 400mg every 12 hours. See literature for dose adjustments for QT prolongation, hematological and non-hematological toxicities, concomitant strong CYP3A4 inhibitors and inducers.

Not recommended.

Hypokalemia. Hypomagnesemia. Long QT syndrome.

Hereditary galactose intolerance, severe lactase deficiency, glucose-galactose malabsorption: not recommended. Correct electrolyte abnormalities before starting; monitor. Hepatic impairment. History of pancreatitis. Uncontrolled cardiovascular or renal disease. Monitor CBCs every 2 weeks for 1st 2 months then once monthly; monitor ECG at baseline, after 7 days, then periodically and after dose changes. Monitor serum lipase, liver function. Pregnancy (Cat.D) (use adequate contraception), nursing mothers: not recommended.

Avoid drugs that can cause QT prolongation. Avoid strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole), grapefruit. Avoid strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, phenobarbital), St. John’s wort; adjust nilotinib dose if unavoidable. May affect, or be affected by, other drugs metabolized by CYP3A4, 2C8, 2C9, 2D6, UGT1A1, p-glycoprotein.

Rash, pruritus, GI upset, fatigue, headache, constipation, reversible myelosuppression (thrombocytopenia, neutropenia, anemia), pneumonia, febrile neutropenia, intracranial hemorrhage, elevated serum lipase, pyrexia, electrolyte disturbances (hypophosphatemia, hypo- and hyperkalemia, hypocalcemia, hyponatremia); QT prolongation, arrhythmias, sudden death, hepatotoxicity.

Caps—28

12/20/07