Latest & Greatest
Continued from page 18
diabetes without the dangers of hypoglycemia.
The plan was developed after soliciting
input from a range of industry stakeholders, garnering more than 450 responses.
The agency will be tracking progress of
the plan over the next five years.
Source: National Institutes of Health news release, December 16, 2015.
Medicare Launches
New Tool to Analyze
High-Cost Drugs
The Centers for Medicare & Medicaid
Services (CMS) has launched its online
“Medicare Drug Spending Dashboard”
in an effort to increase transparency and
address the affordability of prescription
drugs in the United States.
The Dashboard allows the public to
compare 80 prescription drugs covered
under both Medicare Part D and Part B,
including drugs with high spending on
a per-user basis, high spending for the
program overall, and those with high
unit-cost increases in recent years.
The drugs included on the Dashboard
represent 33 percent of all Medicare Part
D drug spending and 71 percent of Medi-
TASIGNA® (nilotinib) Capsules for oral use
Initial U.S. Approval: 2007
BRIEF SUMMARY: Please see package insert for full prescribing
information.
WARNING: QT PROLONGATION AND SUDDEN DEATHS
• Tasigna prolongs the QT interval. Prior to Tasigna administration and
periodically, monitor for hypokalemia or hypomagnesemia and correct
deficiencies (5.2). Obtain ECGs to monitor the QTc at baseline, seven
days after initiation, and periodically th ereafter, and following any
dose adjustments (5.2, 5.3, 5.7, 5.15).
• Sudden deaths have been reported in patients receiving nilotinib (5.3).
Do not administer Tasigna to patients with hypokalemia, hypomagnesemia, or long QT syndrome (4, 5.2).
• Avoid use of concomitant drugs known to prolong the QT interval and
strong CYP3A4 inhibitors (5.8).
• Avoid food 2 hours before and 1 hour after taking the dose (5.9).
1 INDICATIONS AND USAGE
1.1 Newly Diagnosed Ph+ CML-CP
Tasigna (nilotinib) is indicated for the treatment of adult patients with
newly diagnosed Philadelphia chromosome positive chronic myeloid
leukemia (Ph+ CML) in chronic phase. The effectiveness of Tasigna is
based on major molecular response and cytogenetic response rates [see
Clinical Studies (14.1) in the full prescribing information].
1.2 Resistant or Intolerant Ph+ CML-CP and CML-AP
Tasigna is indicated for the treatment of chronic phase and accelerated
phase Philadelphia chromosome positive chronic myelogenous leukemia
(Ph+ CML) in adult patients resistant or intolerant to prior therapy that
included imatinib. The effectiveness of Tasigna is based on hematologic
and cytogenetic response rates [see Clinical Studies (14.2) in the full
prescribing information].
4 CONTRAINDICATIONS
Do not use in patients with hypokalemia, hypomagnesemia, or long
QT syndrome [see Boxed Warning].
5 WARNINGS AND PRECAUTIONS
5.1 Myelosuppression
Treatment with Tasigna can cause Grade 3/4 thrombocytopenia, neutropenia and anemia. Perform complete blood counts every 2 weeks for the first
2 months and then monthly thereafter, or as clinically indicated. Myelosuppression was generally reversible and usually managed by withholding
Tasigna temporarily or dose reduction [see Dosage and Administration
(2.2) in the full prescribing information].
5.2 QT Prolongation
Tasigna has been shown to prolong cardiac ventricular repolarization as
measured by the QT interval on the surface ECG in a concentrationdependent manner [see Adverse Reactions (6.1), Clinical Pharmacology
(12.6) in the full prescribing information]. Prolongation of the QT interval can result in a type of ventricular tachycardia called torsade de
pointes, which may result in syncope, seizure, and/or death. ECGs
should be performed at baseline, 7 days after initiation of Tasigna, and
periodically as clinically indicated and following dose adjustments [see
Warnings and Precautions (5.15)].
Tasigna should not be used in patients who have hypokalemia, hypomagnesemia or long QT syndrome. Before initiating Tasigna and periodically, test electrolyte, calcium and magnesium blood levels. Hypokalemia
or hypomagnesemia must be corrected prior to initiating Tasigna and
these electrolytes should be monitored periodically during therapy [see
Warnings and Precautions (5.15)].
Significant prolongation of the QT interval may occur when Tasigna is
inappropriately taken with food and/or strong CYP3A4 inhibitors and/or
medicinal products with a known potential to prolong QT. Therefore,
coadministration with food must be avoided and concomitant use with
strong CYP3A4 inhibitors and/or medicinal products with a known potential to prolong QT should be avoided [see Warnings and Precautions (5.8,
5.9)]. The presence of hypokalemia and hypomagnesemia may further
prolong the QT interval [see Warnings and Precautions (5.7, 5.15)].
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. The relative early
occurrence of some of these deaths relative to the initiation of nilotinib
suggests the possibility that ventricular repolarization abnormalities may
have contributed to their occurrence.
79892ha_t.indd 4
care Part B drug spending in 2014. The
tool displays relevant spending, use, and
trend data, and also includes consumerfriendly information on the drug product
descriptions, manufacturer, and uses.
Products have been selected from each
respective program area based on the following criteria:
• The drug is ranked as one of the top
15 drugs as defined by total program
5.4 Cardiac and Arterial Vascular Occlusive Events
Cardiovascular events, including arterial vascular occlusive events, were
reported in a randomized, clinical trial in newly diagnosed CML patients
and observed in the postmarketing reports of patients receiving nilotinib
therapy. With a median time on therapy of 60 months in the clinical trial,
cardiovascular events, including arterial vascular occlusive events,
occurred in 9.3% and 15.2% of patients in the Tasigna 300 and 400 mg
bid arms, respectively, and in 3.2% in the imatinib arm. These included
cases of cardiovascular events including ischemic heart disease-related
cardiac events (5.0% and 9.4% in the Tasigna 300 mg and 400 mg bid
arms respectively, and 2.5% in the imatinib arm), peripheral arterial
occlusive disease (3.6% and 2.9% in the Tasigna 300 mg and 400 mg bid
arms respectively, and 0% in the imatinib arm), and ischemic cerebrovascular events (1.4% and 3.2% in the Tasigna 300 mg and 400 mg bid
arms respectively, and 0.7% in the imatinib arm). If acute signs or symptoms of cardiovascular events occur, advise patients to seek immediate
medical attention. The cardiovascular status of patients should be evaluated and cardiovascular risk factors should be monitored and actively
managed during Tasigna therapy according to standard guidelines [see
Dosage and Administration (2.2) in the full prescribing information].
5.5 Pancreatitis and Elevated Serum Lipase
Tasigna 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.
Test serum lipase levels monthly or as clinically indicated.
5.6 Hepatotoxicity
Tasigna may result in hepatotoxicity as measured by elevations in bilirubin,
AST/ALT, and alkaline phosphatase. Monitor hepatic function tests monthly
or as clinically indicated [see Warnings and Precautions (5.15)].
5.7 Electrolyte Abnorm alities
The use of Tasigna can cause hypophosphatemia, hypokalemia, hyperkalemia, hypocalcemia, and hyponatremia. Correct electrolyte abnormalities prior to initiating Tasigna and during therapy. Monitor these
electrolytes periodically during therapy [see Warnings and Precautions
(5.15)].
5.8 Drug Interactions
Avoid administration of Tasigna with agents that may increase nilotinib
exposure (e.g., 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). Should treatment with any of
these agents be required, interrupt therapy with Tasigna. If interruption
of treatment with Tasigna is not possible, patients who require treatment
with a drug that prolongs QT or strongly inhibits CYP3A4 should be
closely monitored for prolongation of the QT interval [see Boxed Warning, Dosage and Administration (2.2), Drug Interactions (7.2) in the full
prescribing information].
5.9 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) in the full prescribing information].
5.10 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)
in the full prescribing information].
5.11 Tumor Lysis Syndrome
Tumor lysis syndrome cases have been reported in Tasigna treated
patients with resistant or intolerant CML. Malignant disease progression,
high WBC counts and/or dehydration were present in the majority of
these cases. Due to potential for tumor lysis syndrome, maintain adequate hydration and correct uric acid levels prior to initiating therapy
with Tasigna.
5.12 Hemorrhage
In a randomized trial in patients with newly diagnosed Ph+ CML in
chronic phase comparing Tasigna and imatinib, Grade 3 or 4 hemorrhage occurred in 1.1% of patients in the Tasigna 300 mg bid arm, in
1.8% patients in the Tasigna 400 mg bid arm, and 0.4% of patients in
the imatinib arm. GI hemorrhage occurred in 2.9% and 5.1% of patients
in the Tasigna 300 mg bid and 400 mg bid arms and in 1.4% of patients
in the imatinib arm, respectively. Grade 3 or 4 events occurred in 0.7%
9/11/15 10:00 PM