Important Safety Information, including Boxed WARNING, for CAPRELSA
WARNING: QT PROLONGATION, TORSADES DE POINTES, AND SUDDEN DEATH
- CAPRELSA can prolong the QT interval. Torsades de pointes, ventricular tachycardia, and sudden death have been reported in
patients receiving CAPRELSA
- CAPRELSA should not be used in patients with hypocalcemia, hypokalemia, hypomagnesemia, or long QT
syndrome. Hypocalcemia, hypokalemia and/or hypomagnesemia must be corrected prior to CAPRELSA administration and should be periodically monitored
- Drugs known to prolong the QT interval should be avoided. If a drug known to prolong the QT interval must
be administered, more frequent ECG monitoring is recommended
- Given the half-life of 19 days, ECGs should be obtained to monitor the QT interval at baseline, at
2-4 weeks and 8-12
weeks after starting treatment with CAPRELSA, and every 3 months thereafter. Following any dose reduction for QT prolongation, or any dose interruptions greater than 2 weeks, QT assessment should be conducted as described above.
- Because of the 19-day half-life, adverse reactions including a prolonged QT interval may not resolve quickly.
Monitor appropriately
- Only prescribers and pharmacies certified with the restricted distribution program are able to prescribe and
dispense CAPRELSA
- Do not use CAPRELSA in patients with congenital long QT syndrome
- CAPRELSA treatment should not be started in patients whose QTcF interval (corrected QT
interval, Fridericia) is greater than 450 ms or who have a history of Torsades de pointes,
bradyarrhythmias, or uncompensated heart failure. CAPRELSA has not been studied in patients
with ventricular arrhythmias or recent myocardial infarction
- Patients who develop a QTcF greater than 500 ms should stop taking CAPRELSA until QTcF
returns to less than 450 ms. Dosing of CAPRELSA can be resumed at a reduced dose
- Because of the risk of QT prolongation, ECGs and levels of serum potassium, calcium, magnesium,
and thyroid-stimulating hormone (TSH) should be monitored at baseline, at 2-4 weeks and 8-12
weeks after starting treatment with CAPRELSA, and every 3 months thereafter and following dose
adjustments
- Severe skin reactions (including Stevens-Johnson syndrome), some leading to death, have been
reported and may prompt permanent discontinuation of CAPRELSA. If CTCAE grade 3 or greater
skin reactions occur, CAPRELSA treatment should be stopped until improved. Upon improvement,
consideration should be given to continuing treatment at a reduced dose
- Photosensitivity reactions are increased with CAPRELSA. Patients should be advised to wear
sunscreen and protective clothing when exposed to the sun. Due to the long half-life of
CAPRELSA, use of protective clothing and sunscreen should continue for 4 months after
discontinuation of treatment
- Interstitial lung disease (ILD) has been observed with CAPRELSA and deaths have been reported.
Interrupt CAPRELSA treatment and investigate unexplained dyspnea, cough, and fever
- Ischemic cerebrovascular events have been observed with CAPRELSA and some cases have been
fatal. The safety of resumption of CAPRELSA therapy after resolution of an ischemic
cerebrovascular event has not been studied. Discontinue CAPRELSA in patients who experience a
severe ischemic cerebrovascular event
- Serious hemorrhagic events, which in some cases were fatal, have been observed with
CAPRELSA. Three patients died of fatal bleeding events while on CAPRELSA therapy in clinical
studies. Do not administer CAPRELSA to patients with recent history of hemoptysis of ≥1/2
teaspoon of red blood. Discontinue CAPRELSA in patients with severe hemorrhage
- Heart failure has been observed with CAPRELSA and some cases have been fatal. Discontinuation
of CAPRELSA may be necessary in patients with heart failure. Heart failure may not be reversible
upon stopping CAPRELSA. Monitor for signs and symptoms of heart failure
- Diarrhea has been observed with CAPRELSA. Routine antidiarrheal agents are recommended.
Serum electrolytes and ECGs should be carefully monitored in cases of diarrhea because of the risk
of QT prolongation with CAPRELSA. If severe diarrhea develops, CAPRELSA treatment should
be stopped until diarrhea improves. Upon improvement, treatment with CAPRELSA should be
resumed at a reduced dose
- Increases in the dose of thyroid replacement therapy were required in the randomized medullary
thyroid cancer (MTC) study. TSH should be monitored at baseline, at 2 to 4 weeks and 8 to 12
weeks after starting treatment with CAPRELSA, and every 3 months thereafter. If signs or
symptoms of hypothyroidism occur, thyroid hormone levels should be examined and thyroid
replacement therapy should be adjusted accordingly
- Hypertension, including hypertensive crisis, has been observed with CAPRELSA. All patients
should be monitored for hypertension and it should be controlled as appropriate. Dose reduction or
interruption may be necessary. If high blood pressure cannot be controlled, CAPRELSA should not
be restarted
- Reversible posterior leukoencephalopathy syndrome (RPLS) has been observed with CAPRELSA.
This syndrome should be considered in any patient presenting with seizures, headache, visual
disturbances, confusion, or altered mental function. In clinical studies, three of four patients who
developed RPLS while taking CAPRELSA, including one pediatric patient, also had hypertension.
Discontinuation of CAPRELSA treatment in patients with RPLS should be considered
- The concomitant use of known strong CYP3A4 inducers may reduce drug levels of CAPRELSA
and should be avoided. The administration of CAPRELSA with antiarrhythmic drugs and other
drugs that may prolong the QT interval should be avoided
- CAPRELSA exposure is increased in patients with impaired renal function. The starting dose of
CAPRELSA should be reduced to 200 mg in patients with moderate to severe renal impairment and
the QT interval should be monitored closely. There is no information available for patients with
end-stage renal disease requiring dialysis
- CAPRELSA is not recommended for patients with moderate and severe hepatic impairment, since
safety and efficacy have not been established
- CAPRELSA can cause fetal harm when administered to a pregnant woman. Women of
childbearing potential should be advised to avoid pregnancy while receiving CAPRELSA and for at
least 4 months following treatment
- The most common adverse drug reactions (>20%) seen with CAPRELSA are diarrhea (57%), rash
(53%), acne (35%), nausea (33%), hypertension (33%), headache (26%), fatigue (24%), upper respiratory tract infections (23%), decreased
appetite (21%), and abdominal pain (21%). The most common laboratory abnormalities (>20%)
were decreased calcium (57%), increased ALT (51%), and decreased glucose (24%)
- CAPRELSA REMS Program: Because of the risks of QT prolongation, Torsades de pointes, and
sudden death, CAPRELSA is available only through the CAPRELSA REMS Program. Only
prescribers and pharmacies certified with the restricted distribution program are able to prescribe
and dispense CAPRELSA. To learn about the specific REMS requirements and to enroll in the
CAPRELSA REMS Program call 1-800-236-9933 or visit www.caprelsarems.com
Indication
CAPRELSA is a kinase inhibitor indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.
Use of CAPRELSA in patients with indolent, asymptomatic or slowly progressing disease should be carefully considered because of the treatment related risks of CAPRELSA.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or
call 1-800-FDA-1088.