Tasigna200 mg

Tasigna is a second-generation oral tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukemia (CML) that is Philadelphia chromosome-positive (Ph+).

Established / FDA-approved indications

• Newly diagnosed Ph+ CML in chronic phase (CML-CP), in adults and in pediatric patients aged 1 year and older.
• Ph+ CML in chronic phase or accelerated phase in adult patients resistant to or intolerant of prior therapy that included imatinib.

Tasigna is not indicated for Philadelphia chromosome-negative CML or other leukemias, and is used only under the supervision of a physician experienced in the management of leukemia.

Tasigna is an orally administered, second-generation BCR-ABL tyrosine kinase inhibitor (TKI) used for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). It is structurally related to imatinib but binds the BCR-ABL kinase domain with higher affinity, making it effective in many cases where imatinib has failed or is not tolerated.

Because Tasigna is an oncology drug with a boxed warning for cardiac risk, it must be prescribed, dosed, and monitored by a specialist experienced in the management of CML.

Antineoplastic agent - BCR-ABL tyrosine kinase inhibitor (targeted oncology therapy); Tasigna belongs to this class.

Nilotinib selectively inhibits the BCR-ABL tyrosine kinase, the constitutively active fusion protein produced by the Philadelphia chromosome translocation in chronic myeloid leukemia. By competitively binding the ATP-binding site of BCR-ABL, Nilotinib blocks downstream signaling that drives proliferation of leukemic cells, promoting apoptosis, including in many imatinib-resistant cell lines.

Nilotinib also has activity against other kinases such as KIT and PDGFR. Following oral administration, Nilotinib is absorbed and undergoes extensive hepatic metabolism primarily via CYP3A4, with elimination mainly through feces.

CYP3A4 interactions

Tasigna is metabolized primarily by CYP3A4. Co-administration with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) increases Tasigna plasma concentration and QT-prolongation risk; such combinations should be avoided. Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort) reduce Tasigna efficacy and should also be avoided.

QT-prolonging drugs

Concomitant use of Tasigna with other drugs known to prolong the QT interval (e.g., certain antiarrhythmics, some antipsychotics, some antimicrobials) increases the risk of serious ventricular arrhythmia and should be avoided (see Contraindications and Precautions).

Gastric pH-altering agents

Antacids and H2-receptor antagonists can reduce absorption of Tasigna if taken too close together; dosing should be separated. Proton pump inhibitors may reduce Tasigna exposure more substantially, and concomitant use should be discussed with the prescriber.

Food and grapefruit

Food, especially high-fat food, and grapefruit products significantly increase Tasigna absorption and associated QT risk (see Administration).

Very common

• Nausea, diarrhea or constipation, vomiting
• Headache
• Rash, pruritus, dry skin
• Fatigue
• Musculoskeletal pain, myalgia
• Elevated liver enzymes and bilirubin
• Low blood counts (thrombocytopenia, neutropenia, anemia)

Serious (see Precautions and Warnings for full detail)

• QT prolongation and sudden cardiac death
• Myelosuppression
• Pancreatitis (elevated lipase/amylase)
• Hepatotoxicity
• Cardiovascular events, including peripheral arterial occlusive disease
• Fluid retention

Patients taking Tasigna should report unusual symptoms such as palpitations, fainting, severe abdominal pain, or yellowing of the skin or eyes to their physician immediately.

Tasigna can cause fetal harm based on its mechanism of action and animal reproduction data. It should be used during pregnancy only if clearly needed and the potential benefit justifies the potential risk to the fetus; women of reproductive potential should use effective contraception during treatment with Tasigna and for a period after stopping, as advised by their physician. It is not known whether Tasigna passes into breast milk; because of the potential for serious adverse reactions in a nursing infant, breastfeeding is not recommended during treatment with Tasigna. Always consult a physician before use in pregnancy or while breastfeeding.

QT prolongation and sudden death (boxed warning)

Tasigna can prolong the QT interval and has been associated with sudden cardiac death. Baseline ECG monitoring is required before starting Tasigna, with a follow-up ECG approximately 7 days after initiation and periodically thereafter, and after any dose adjustment. Serum potassium and magnesium must be corrected before starting and monitored during treatment. Concomitant use of strong CYP3A4 inhibitors and other QT-prolonging drugs should be avoided (see Interaction and Contraindications). Tasigna must be taken on an empty stomach (see Administration).

Myelosuppression

Thrombocytopenia, neutropenia, and anemia can occur with Tasigna; complete blood counts should be monitored regularly, especially during the first months of treatment.

Hepatotoxicity

Elevations in liver enzymes and bilirubin have been reported with Tasigna; liver function should be monitored periodically.

Pancreatitis

Lipase and amylase elevations and pancreatitis have been reported; monitor lipase periodically and evaluate promptly for abdominal pain.

Cardiovascular events

Peripheral arterial occlusive disease and other ischemic cardiovascular events have been reported with Tasigna; assess cardiovascular risk factors before and during treatment.

Fluid retention and hepatitis B reactivation

Fluid retention (including pleural/pericardial effusion) may occur. Patients should be screened for hepatitis B before starting Tasigna, as reactivation has been reported with BCR-ABL inhibitors.

Tasigna should only be prescribed and monitored by a physician experienced in the treatment of leukemia, given the need for specialist oncologic oversight.

Overdose of Tasigna may worsen known adverse effects, particularly QT prolongation, myelosuppression, and gastrointestinal effects. There is no specific antidote for Tasigna. In case of suspected overdose, seek immediate medical attention or contact the nearest hospital emergency department or a poison control center. Cardiac monitoring (ECG) and general supportive care should be provided under medical supervision.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Renal impairment

Tasigna is eliminated primarily by hepatic metabolism; formal dose adjustment in renal impairment has not been established, but caution and monitoring are advised, particularly in severe impairment.

Hepatic impairment

A reduced starting dose of Tasigna is recommended in patients with hepatic impairment, with closer monitoring for QT prolongation and hepatotoxicity.

Elderly

No overall differences in safety or efficacy of Tasigna have been observed compared with younger adults, but greater sensitivity in some older individuals cannot be ruled out; use with appropriate monitoring.

Pediatric

See Pediatric Uses.

Tyrosine kinase inhibitor; antineoplastic agent; BCR-ABL inhibitor - the class to which Nilotinib belongs.

Nilotinib is a selective inhibitor of the BCR-ABL tyrosine kinase, the constitutively active fusion protein produced by the Philadelphia chromosome translocation in chronic myeloid leukemia. By binding to the ATP-binding site of BCR-ABL, Nilotinib blocks its kinase activity, thereby inhibiting proliferation and inducing apoptosis in BCR-ABL-positive leukemic cells, including many cell lines resistant to imatinib. Nilotinib also inhibits other kinases including KIT and PDGFR, though its primary clinical use relates to BCR-ABL inhibition.

D

Tasigna is approved for use in pediatric patients 1 year of age and older with newly diagnosed Ph+ CML in chronic phase, dosed by body surface area under specialist supervision (see Dosage and Administration). Safety and efficacy of Tasigna in children younger than 1 year, and in pediatric patients with resistant/intolerant or accelerated-phase disease, have not been established. Growth and development should be monitored closely in pediatric patients receiving long-term Tasigna therapy, as effects on growth have been observed with long-term tyrosine kinase inhibitor use.