NOW FDA APPROVED:CAVHANZA™ (nilotinib) Orally Disintegrating Tablets (ODT)

• Substitution with Other Nilotinib Products and Risk of Medication Errors: CAVHANZA may not be substitutable with other nilotinib products, including other nilotinib tablets, on a milligram per milligram basis. When switching patients between other nilotinib products and CAVHANZA, a dose conversion is required. Confirm that the intended nilotinib product is being prescribed and dispensed.

• Myelosuppression: Treatment with CAVHANZA can cause Grade 3/4 thrombocytopenia, neutropenia, and anemia. Monitor complete blood count (CBC) during therapy and manage by treatment interruption or dose reduction.

• Cardiac and Arterial Vascular Occlusive Events: Cardiovascular events, including arterial vascular occlusive events have been reported in newly diagnosed CML patients and observed in the postmarketing reports of patients receiving nilotinib therapy. Evaluate cardiovascular status, monitor and manage cardiovascular risk factors during CAVHANZA therapy.

• Pancreatitis and Elevated Serum Lipase: CAVHANZA can cause increases in serum lipase. Patients with a previous history of pancreatitis may be at greater risk of elevated serum lipase. If lipase elevations are accompanied by abdominal symptoms, interrupt dosing and consider appropriate diagnostics to exclude pancreatitis.

• Hepatotoxicity: CAVHANZA may result in hepatotoxicity as measured by elevations in bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase. Grade 3-4 elevations of bilirubin, AST, and ALT have been reported, with higher frequency in pediatric patients. Monitor hepatic function tests monthly or as clinically indicated.

• Electrolyte Abnormalities: CAVHANZA can cause hypophosphatemia, hypokalemia, hyperkalemia, hypocalcemia, and hyponatremia. Correct electrolyte abnormalities prior to initiating CAVHANZA and monitor periodically during therapy.

• Tumor Lysis Syndrome: Tumor lysis syndrome (TLS) cases have been reported in nilotinib treated patients with resistant or intolerant CML. Maintain adequate hydration and correct uric acid levels prior to initiating therapy with CAVHANZA.

• Hemorrhage: Serious hemorrhagic events, including fatal events, have occurred in patients with CML treated with nilotinib. Hemorrhage from any site may occur. Advise patients to report signs and symptoms of bleeding and medically manage as needed.

• Fluid Retention: Monitor patients for signs of unexpected rapid weight gain, severe fluid retention and symptoms of respiratory or cardiac compromise during CAVHANZA treatment. Manage medically.

• Effects on Growth and Development in Pediatric Patients: Growth retardation has been reported in pediatric patients treated with nilotinib. Monitor growth and development in pediatric patients.

• Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception during treatment and for 14 days after the last dose.

• Treatment Discontinuation: Monitor BCR‑ABL transcript levels in patients who discontinue CAVHANZA using an FDA‑authorized test with sensitivity ≥ MR4.5, reinitiate treatment within 4 weeks following loss of major molecular response (or loss of MR4.0 in patients resistant or intolerant to prior imatinib), and in patients who reinitiate therapy, monitor CBC and BCR‑ABL transcripts until response is re‑established, with mutation testing if MMR is not achieved after 3 months.

• QT prolongation and sudden deaths have been reported. Increases in QTcF greater than 60 msec from baseline and QTcF values exceeding 500 msec were observed in clinical studies. See Boxed Warning and Warnings and Precautions.
• Serious adverse reactions included thrombocytopenia, neutropenia, anemia, febrile neutropenia, pneumonia, intracranial hemorrhage, leukopenia, and elevated lipase.
• The most common non‑hematologic adverse reactions (≥10%) reported in clinical studies of nilotinib included rash, pruritus, headache, nausea, fatigue, alopecia, myalgia, abdominal pain, constipation, diarrhea, cough, arthralgia, nasopharyngitis, pyrexia, night sweats and vomiting.
• Hematologic adverse reactions included myelosuppression, with thrombocytopenia, neutropenia, and anemia being commonly reported.
• Adverse reactions leading to treatment discontinuation occurred in approximately 10–16% of patients, with higher rates observed in patients with resistant or advanced‑phase disease.
• Additional adverse reactions identified postmarketing with nilotinib include thrombotic microangiopathy, facial paralysis, and osteonecrosis.

Strong CYP3A Inhibitors: Avoid concomitant use of strong CYP3A inhibitors with CAVHANZA. If concomitant use cannot be avoided, reduce CAVHANZA dose.

Nilotinib is a CYP3A substrate. Concomitant use with a strong CYP3A inhibitor increases nilotinib exposure which may increase the risk of adverse reactions.

Strong CYP3A Inducers: Avoid concomitant use of strong CYP3A inducers with CAVHANZA. Nilotinib is a CYP3A substrate. Concomitant use with a strong CYP3A inducer decreases nilotinib exposure which may reduce CAVHANZA efficacy.

Drugs that prolong QT interval: Avoid coadministration of CAVHANZA with agents that may prolong the QT interval, such as anti-arrhythmic drugs.

Pregnancy: CAVHANZA can cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. Females of reproductive potential should have a pregnancy test prior to starting treatment.

Lactation: There are no data on the presence of nilotinib or its metabolites in human milk or its effects on a breastfed child or on milk production. However, nilotinib is present in the milk of lactating rats. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with CAVHANZA and for 14 days after the last dose.

Pediatric use: CAVHANZA is not approved for use in pediatric patients. For pediatric growth and development, growth retardation has been reported in pediatric patients treated with nilotinib.

Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation’s TASIGNA (nilotinib) capsules. However, due to Novartis Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

Geriatric use: No major differences for safety were observed in patients greater than or equal to 65 years of age as compared to patients less than 65 years.