Label Changes for:

Tasigna (nilotinib) capsules, 150 mg and 200 mg

September 2013

Changes have been made to the BOXED WARNING, WARNINGS and PRECAUTIONS sections of the safety label.

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

 

September 2013

BOXED WARNING

  • Avoid food 2 hours before and 1 hour after taking the dose (5.8)

5 WARNINGS AND PRECAUTIONS

5.2 QT Prolongation
  • Before initiating Tasigna and periodically, test electrolyte, calcium and magnesium blood levels.
5.3 Sudden Deaths
  • Sudden deaths have been reported in 0.3% of patients with CML treated with nilotinib in clinical studies of 5,661 patients.
5.4 Elevated Serum Lipase
  • Tasigna can cause increases in serum lipase. Patients with a previous history of pancreatitismaybe at greater risk. If lipase elevations ...
5.5 Hepatotoxicity 
  • Tasigna may result in hepatotoxicity as measured by elevations in bilirubin, AST/ALT, and alkaline phosphatase. Monitor hepatic function tests monthly or as clinicallyindicated [see Warnings and Precautions (5.13)].
5.7 Drug Interactions
  • Avoid administration of Tasigna with agents that are strong CYP3A4 inhibitors or anti-arrhythmic drugs (including, but not limited to  amiodarone, disopyramide, procainamide, quinidine and sotalol) and other drugs that may prolong QT interval (including, but not limited  to chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin and pimozide) since nilotinib exposure will be increased. Should treatment with any of these agents be required, interrupt therapy with Tasigna.
5.8 Food Effects
  • The bioavailability of nilotinib is increased with food, thus Tasigna must not be taken with food. No food should be consumed for at  least 2 hours before and for at least 1 hour after the dose is taken. Also avoid grapefruit products and other foods that are known to inhibit CYP3A4 [see Boxed Warning, Drug Interactions (7.2) and Clinical Pharmacology (12.3)].
5.9 Hepatic Impairment
  • Nilotinib exposure is increased in patients with impaired hepatic function. Use a lower starting dose for patients with mild to severe  hepatic impairment (at baseline) and monitor the QT interval frequently [see Dosage and Administration (2.2) and Use in Specific Populations (8.7)].

17 PATIENT COUNSELING INFORMATION

Taking Tasigna

  • Tasigna doses should be taken twice daily approximately 12 hours apart. The capsules should be swallowed whole with water. 
  • If the patient missed a dose of Tasigna, the patient should take the next scheduled dose at its regular time. The patient should not take  two doses at the same time.

MEDICATION GUIDE

  • negative statement “do not take with food”  changed to the positive statement “take Tasigna on an empty stomach”

 

June 2013

 

DRUG INTERACTIONS

Drugs that Affect Gastric pH
  • Nilotinib has pH-dependent solubility, with decreased solubility at higher pH. Drugs such as proton pump inhibitors that inhibit gastric acid secretion to elevate the gastric pH may decrease the solubility of nilotinib and reduce its bioavailability. In healthy subjects, co-administration of a single 400 mg dose of Tasigna with multiple doses of esomeprazole (a proton pump inhibitor) at 40 mg daily decreased the nilotinib AUC by 34%. Increasing the dose of Tasigna when co-administered with such agents is not likely to compensate for the loss of exposure. Since proton pump inhibitors affect pH of the upper GI tract for an extended period, separation of doses may not eliminate the interaction. The concomitant use of proton pump inhibitors with Tasigna is not recommended.
  • In healthy subjects, no significant change in nilotinib pharmacokinetics was observed when a single 400 mg dose of Tasigna was administered ten hours after and two hours before famotidine (an H2 blocker). Therefore, when the concurrent use of a H2 blocker is necessary, it may be administered approximately ten hours before and approximately two hours after the dose of Tasigna.
  • Administration of an antacid (aluminum hydroxide/magnesium hydroxide/simethicone) to healthy subjects, two hours before or two hours after a single 400 mg dose of Tasigna did not alter nilotinib pharmacokinetics. Therefore, if necessary, an antacid may be administered approximately two hours before or approximately two hours after the dose of Tasigna.

 

MEDICATION GUIDE

What should I tell my doctor before starting Tasigna?
  • Tell your doctor about all the medicines you take a medicine to block the amount of acid produced in the stomach (H2 blocker): Take these medicines about 10 hours before you take Tasigna, or about 2 hours after you take Tasigna.
 
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