of the 19-day half-life, adverse reactions including a prolonged QT interval may not resolve quickly. Monitor appropriately [see Warnings and Precautions (5.1-5.7, 5.9)].
The 300-mg daily dose can be reduced to 200 mg (two 100-mg tablets) and then to 100 mg for CTCAE grade 3 or greater toxicities.
2.2 Elderly
No adjustment in starting dose is required for patients over 65 years of age. There are limited data for patients over the age of 75. [see Dosage and Administration (2.4)]
2.3 Concomitant Strong CYP3A4 Inducers
Avoid the concomitant use of strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital). Patients should also avoid taking St. John’s Wort. [see Warnings and Precautions (5.11)and Drug Interactions (7.1)]
2.4 Patients With Renal Impairment
The starting dose should be reduced to 200 mg in patients with moderate (creatinine clearance ≥30 to <50 mL/min) and severe (creatinine clearance <30 mL/min) renal impairment. [see Warnings and Precautions (5.12)and Use in Specific Populations (8.6)]
2.5 Patients with Hepatic Impairment
Single dose pharmacokinetic data from volunteers with hepatic impairment receiving 800 mg suggest that there were no differences in pharmacokinetics compared to patients with normal hepatic function. There are limited data in patients with liver impairment (serum bilirubin greater than 1.5 times the upper limit of normal). CAPRELSA is not recommended for use in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment, as safety and efficacy have not been established.
3. DOSAGE FORMS & STRENGTHS
CAPRELSA 100-mg tablets are white, round, biconvex, film-coated, and intagliated with ‘Z 100‘ on one side and plain on the reverse side.
CAPRELSA 300-mg tablets are white, oval, biconvex, film-coated, and intagliated with ‘Z 300’ on one side and plain on the reverse side.
4. CONTRAINDICATIONS
Do not use in patients with congenital long QT syndrome [see Boxed Warning].
5. WARNINGS AND PRECAUTIONS
5.1 QT Prolongation and Torsades de Pointes
CAPRELSA can prolong the QT interval in a concentration-dependent manner [see Clinical Pharmacology (12.4)]. Torsades de pointes, ventricular tachycardia and sudden deaths have been reported in patients administered CAPRELSA.
CAPRELSA treatment should not be started in patients whose QTcF interval is greater than 450 ms. CAPRELSA should not be given to patients who have a history of Torsades de pointes, congenital long QT syndrome, bradyarrhythmias or uncompensated heart failure. CAPRELSA has not been studied in patients with ventricular arrhythmias or recent myocardial infarction. CAPRELSA exposure is increased in patients with impaired renal function. The starting dose should be reduced to 200 mg in patients with moderate to severe renal impairment and QT interval should be monitored closely.
An ECG and levels of serum potassium, calcium, magnesium and TSH should be obtained at baseline, at 2-4 weeks and 8-12 weeks after starting treatment with CAPRELSA and every 3 months thereafter. Electrolytes and ECGs may require more frequent monitoring in case of diarrhea. Following any dose reduction for QT prolongation, or any dose interruptions greater than 2 weeks, QT assessments should be conducted as described above. Serum potassium levels should be maintained at 4 mEq/L or higher (within normal range) and serum m |
