About Tasigna

How to Dose

Tasigna should be dosed 400 mg twice daily (taken as two 200-mg capsules, approximately every 12 hours). The capsules should be swallowed whole with water.

No food should be consumed for at least 2 hours before the dose is taken and no additional food should be consumed for at least one hour after the dose is taken.

• In patients experiencing neutropenia or thrombocytopenia, therapy may be temporarily withheld for up to 2 weeks
  • If the AE resolves within 2 weeks, resume therapy at the previously prescribed dose
  • If the AE persists, reducing the dose to 400 mg once daily is recommended

Important Considerations

Myelosuppression

• Treatment with Tasigna is associated with Grade 3/4 thrombocytopenia (27%), neutropenia (15%), and anemia (13%). Occurrence is more frequent in patients with accelerated phase CML.
• Complete blood counts should be performed every 2 weeks for the first 2 months of treatment with Tasigna and then monthly thereafter, or as clinically indicated.
• Myelosuppression is generally reversible and usually can be managed by temporarily withholding or reducing the dose of Tasigna.

QT prolongation

• In vitro data suggest that nilotinib has the potential to prolong cardiac ventricular repolarization (QT interval). In the Phase II study in imatinib-resistant and intolerant CML patients in chronic and accelerated phase, the change from baseline in mean time-averaged QTcF interval at steady state was 6 and 8 msec, respectively. QTcF of >500 msec was observed in <1% of these patients.
• In a healthy volunteer study with exposures that were comparable to the exposures observed in Ph+ CML patients, the time-averaged mean placebo-subtracted QTcF change from baseline was 7 msec (CI ± 4 msec). No subject had a QTcF >450 msec. Additionally, no clinically relevant arrhythmias were observed during the trial. In particular, no episodes of torsades de pointes (transient or sustained) were observed.
• Tasigna should be used with caution in Ph+ CML patients who have or may develop QTc prolongation. These include patients with hypokalemia or hypomagnesemia, patients with congenital long QT syndrome, patients taking antiarrhythmic medicines  such as amiodarone, disopyramide, procainamide, quinidine and sotalol or other drugs that may lead to QT prolongation such as chloroquine, halofantrine, clarithromycin, haloperidol and methadone, and cumulative high-dose anthracycline therapy.
• Hypokalemia or hypomagnesemia must be corrected prior to administration of Tasigna.

Food effects

• The bioavailability of nilotinib is increased by food. Tasigna should not be taken in conjunction with food and should be taken at least 2 hours after a meal. No food should be consumed for at least 1 hour after the dose is taken.
• Grapefruit juice and other foods that are known to inhibit CYP3A4 should be avoided with Tasigna.

Drug interactions

• Drugs that may increase serum concentrations:
• The administration of Tasigna with agents that are strong CYP3A4-inhibitors (including, but not limited to, ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin, and telithromycin) should be avoided if at all possible. Should treatment with any of these agents be required, it is recommended that therapy with Tasigna be interrupted if possible. If transient interruption of treatment with Tasigna is not possible, close monitoring of the individual for prolongation of the QT interval is indicated.
• The absorption of Tasigna is increased if it is taken with food, resulting in higher serum concentration.
• Drugs that may decrease serum concentrations:
  • Inducers of CYP3A4 activity could increase the metabolism of nilotinib and thereby decrease serum concentrations of nilotinib.
  • The concomitant administration of medications that induce CYP3A4 (including phenytoin, rifampicin, carbamazepine, phenobarbital, and St. John’s Wort) may reduce exposure to nilotinib. In Ph+ CML patients for whom CYP3A4 inducers are indicated, alternative agents with less enzyme induction potential should be considered.
• Drugs that may have their concentration altered:
  • Nilotinib is a competitive inhibitor of CYP3A4, CYP2C8, CYP2C9, CYP2D6 and UGT1A1 in vitro, potentially increasing the concentrations of drug eliminated by these enzymes.
  • Single-dose administration of Tasigna with midazolam (a CYP3A4 substrate) to healthy subjects increased midazolam exposure by 30 percent.
  • Caution should be exercised when coadministering Tasigna with substrates of these enzymes having a narrow therapeutic index.
  • Since warfarin is metabolized by CYP2C9 and CYP3A4 it should be given with caution to patients taking Tasigna. Other medications for anticoagulation should be considered.
• Anti-arrhythmic medicines and other drugs that may prolong QT
  • Nilotinib should be used with caution in patients who have or may develop prolongation of QT including those patients taking anti-arrhythmic medicines or other drugs that lead to QT prolongation.

Pregnancy and Lactation

• Patients should be advised that the use of Tasigna during pregnancy may cause harm to the fetus. Tasigna should not be taken during pregnancy unless necessary.
• Male patients, and female patients of childbearing potential, must use effective contraception during treatment with Tasigna.
• Women taking Tasigna should not breastfeed.

Serum lipase

• Elevation in serum lipase has been observed. Caution is recommended in patients with previous history of pancreatitis.

Lactose

• The capsules contain lactose, and Tasigna is therefore not recommended for patients with rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.

COMMON SIDE EFFECTS OF TASIGNA

• The majority of adult patients who received Tasigna in clinical studies experienced adverse events at some time. Most adverse events were mild to moderate in severity.
• The most frequent nonhematologic drug-related adverse events (all grades) were rash (26%), pruritus (22%), nausea (19%), fatigue (16%), headache (15%), constipation (11%), and diarrhea (10%).
• The most frequent hematologic toxicities (all grades) included thrombocytopenia (27%), neutropenia (15%), and anemia (13%).
• Supportive care may help management of some mild-to-moderate adverse events so that the prescribed dose can be maintained whenever possible.

• Prescribing Tasigna
• Tasigna Efficacy
• Tasigna Safety and Tolerability
• European Summary of Product Characteristics
• Tasigna Mechanism of Action
• How to Dose