lar event.
5.5 Hemorrhag
Serious hemorrhagic events, which in some cases were fatal, have been observed with CAPRELSA. There were no fatal bleeding events in the randomized MTC study. 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.
5.6 Heart Failure
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.
5.7 Diarrhea
Diarrhea was observed in patients who received CAPRELSA. Routine anti-diarrheal agents are recommended. Diarrhea may cause electrolyte imbalances. Since QT prolongation is seen with CAPRELSA, serum electrolytes and ECGs should be carefully monitored in patients with diarrhea. [see Warnings and Precautions (5.1)] If severe diarrhea develops, CAPRELSA treatment should be stopped until diarrhea improves. Upon improvement, treatment with CAPRELSA should be resumed at a reduced dose [see Dosage and Administration (2.1)].
5.8 Hypothyroidism
In the randomized MTC study where 90% of the patients enrolled had prior thyroidectomy, increases in the dose of the thyroid replacement therapy were required in 49% of the patients randomized to CAPRELSA compared to 17% of the patients randomized to placebo. Thyroid-stimulating hormone (TSH) should be obtained 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.
5.9 Hypertension
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 [see Dosage and Administration, (2.1)].
5.10 Reversible posterior leukoencephalopathy syndrome
Reversible posterior leukoencephalopathy syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by an MRI of the brain, 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.
5.11 Drug Interactions
The administration of CAPRELSA with agents that are strong CYP3A4 inducers should be avoided [see Dosage and Administration (2.3)and Drug Interactions (7.1)].
The administration of CAPRELSA with anti-arrhythmic drugs (including, but not limited to amiodarone, disopyramide, procainamide, sotalol, dofetilide) and other drugs that may prolong the QT interval (including but not limited to cloroquine, clarithromycin, dolasetron, granisetron, haloperidol, methadone, moxifloxacin, and pimozide) should be avoided [see Drug Interactions (7.3)].
5.12 Renal Impairment
CAPRELSA exposure is increased in patient |
