CLINICAL NEWS
for use in patients with relapsed multiple
myeloma (MM). This approval would
expand carfilzomib’s current use to treat
patients who have received at least one
prior therapy.
The sNDA acceptance is based on
the results of the phase II, head-tohead ENDEAVOR study that compared
carfilzomib and low-dose dexamethasone with bortezomib and low-dose
dexamethasone in 929 patients with
relapsed MM. Study results indicated
that patients treated with the carfilzomib/dexamethasone combination had
longer PFS (18.7 months vs. 9.4 months;
p<0.0001). Treatment discontinuation
was comparable between both study
cohorts. The most commonly reported
adverse events associated with carfilzomib as a monotherapy included anemia,
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 thereafter, 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.
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.
fatigue, thrombocytopenia, nausea,
pyrexia, decreased platelets, dyspnea,
diarrhea, decreased lymphocyte, headache, decreased hemoglobin, cough, and
peripheral edema.
Carfilzomib is currently FDAapproved for use in combination with
lenalidomide and dexamethasone for
the treatment of MM in patients who
have received one to three prior lines of
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),