Risk Evaluation and Mitigation Strategy (REMS)
Because of the risk of QT prolongation, Torsades de pointes, and sudden death, CAPRELSA is available only through a restricted distribution program called the CAPRELSA REMS Program. Only prescribers and pharmacies certified with the program are able to prescribe and dispense CAPRELSA.
To prescribe CAPRELSA, you must enroll in the CAPRELSA REMS Program and complete the prescriber training program to be certified to prescribe CAPRELSA. Sanofi Genzyme will regularly evaluate compliance and reserves the right to contact you from time to time as a requirement of the CAPRELSA REMS Program.
CAPRELSA is distributed by Biologics, Inc., an oncology specialty pharmacy. After you are certified, you may submit your prescription to Biologics, with required information about your patient, and a pharmacist will contact you.
Dosing and Dose Reductions1
The recommended dose of CAPRELSA is 300 mg taken orally once daily until disease progression or unacceptable toxicity occurs.
(Tablet not actual size)
Once a Day
- CAPRELSA may be taken with or without food.
- Do not take a missed dose within 12 hours of the next dose.
- Do not crush CAPRELSA tablets. The tablets can be dispersed in 2 ounces of water by stirring for approximately 10 minutes (will not completely dissolve). Do not use other liquids for dispersion. Swallow immediately after dispersion. Mix any remaining residue with 4 additional ounces of water and swallow.
- The dispersion can also be administered through nasogastric or gastrostomy tubes.
For adverse reactions:
- The 300 mg daily dose can be reduced to 200 mg (two 100 mg tablets) and then to 100 mg for Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or greater toxicities.
Interrupt CAPRELSA for the following:
- QTcF greater than 500 ms: Resume at a reduced dose when the QTcF returns to less than 450 ms.
- CTCAE Grade 3 or greater toxicity: Resume at a reduced dose when the toxicity resolves or improves to CTCAE Grade 1.
For recurrent toxicities:
- Reduce the dose of CAPRELSA to 100 mg after resolution or improvement to CTCAE Grade 1 severity, if continued treatment is warranted.
For patients with renal impairment
- Reduce the starting dose to 200 mg in patients with moderate (creatinine clearance ≥30 to <50 mL/min) and severe (creatinine clearance <30 mL/min) renal impairment.
For patients with hepatic impairment
- CAPRELSA is not recommended for use in patients with moderate and severe hepatic impairment.
Because of the 19-day half-life, adverse reactions, including a prolonged QT interval, may not resolve quickly. Monitor appropriately.
- CAPRELSA [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2013.
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 and sudden death have occurred in patients receiving CAPRELSA
- Do not use CAPRELSA in patients with hypocalcemia, hypokalemia, hypomagnesemia, or long QT syndrome. Correct hypocalcemia, hypokalemia and/or hypomagnesemia prior to CAPRELSA administration
- Monitor electrolytes periodically
- Avoid drugs known to prolong the QT interval
- Only prescribers and pharmacies certified with the restricted distribution program are able to prescribe and dispense CAPRELSA
- Do not use in patients with congenital long QT syndrome
- CAPRELSA can prolong the QT interval in a concentration-dependent manner. Torsades de pointes, ventricular tachycardia and sudden deaths have occurred in patients treated with CAPRELSA
- Do not start CAPRELSA treatment 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
- Stop CAPRELSA in patients who develop a QTcF greater than 500 ms until QTcF returns to less than 450 ms. Dosing of CAPRELSA can then be resumed at a reduced dose
- Because of the risk of QT prolongation, obtain an ECG and serum potassium, calcium, magnesium, and thyroid-stimulating hormone (TSH) at baseline, 2-4 weeks and 8-12 weeks after starting treatment with CAPRELSA, and every 3 months thereafter. Following any dose reduction or interruptions greater than 2 weeks, conduct QT assessments as described above
- Severe skin reactions (including Stevens-Johnson syndrome and Toxic Epidermal Necrolysis), some leading to death, have occurred in patients treated with CAPRELSA. For severe skin reactions, refer patients for urgent medical advice. Systemic therapies e.g., steroids, may be appropriate in such cases and permanent discontinuation of CAPRELSA is recommended
- Photosensitivity reactions can occur during CAPRELSA treatment and up to 4 months after treatment discontinuation
- Interstitial lung disease (ILD) or pneumonitis, including fatalities, has occurred in patients treated with CAPRELSA. Interrupt CAPRELSA for acute or worsening pulmonary symptoms and discontinue CAPRELSA if ILD is confirmed
- Ischemic cerebrovascular events, including fatalities, occurred in patients treated with CAPRELSA. 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, including fatalities, occurred in patients treated with CAPRELSA. Do not administer CAPRELSA to patients with a recent history of hemoptysis of ≥1/2 teaspoon of red blood. Discontinue CAPRELSA in patients with severe hemorrhage
- Heart failure, including fatalities, occurred in patients treated with CAPRELSA. Monitor for signs and symptoms of heart failure. Consider discontinuation of CAPRELSA in patients with heart failure. Heart failure may not be reversible upon stopping CAPRELSA
- Diarrhea of Grade 3 or greater severity occurred in patients receiving CAPRELSA. If diarrhea occurs, carefully monitor serum electrolytes and ECGs to enable early detection of QT prolongation resulting from dehydration. Interrupt CAPRELSA for severe diarrhea and upon improvement resume CAPRELSA at a reduced dose
- Increased dosing of thyroid replacement therapy was required in 49% of CAPRELSA-treated patients. Obtain TSH at baseline, at 2-4 weeks and 8-12 weeks after starting treatment with CAPRELSA, and every 3 months thereafter. If signs or symptoms of hypothyroidism occur, examine thyroid hormone levels and adjust thyroid replacement therapy accordingly
- Hypertension, including hypertensive crisis, has occurred in patients treated with CAPRELSA. Monitor all patients for hypertension. Dose reduction or interruption for hypertension may be necessary. If hypertension cannot be controlled, do not resume CAPRELSA
- Reversible posterior leukoencephalopathy syndrome (RPLS) has occurred in patients treated with CAPRELSA. Consider this syndrome 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 also had hypertension. Discontinue CAPRELSA treatment in patients with RPLS
- Avoid administration of CAPRELSA with anti-arrhythmic drugs and other drugs that may prolong the QT interval
- Vandetanib exposure is increased in patients with impaired renal function. Reduce the starting dose to 200 mg in patients with moderate to severe renal impairment and monitor the QT interval 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, as safety and efficacy have not been established
- CAPRELSA can cause fetal harm when administered to a pregnant woman. Women of childbearing potential should avoid pregnancy and be advised that they must use effective contraception during CAPRELSA treatment and for at least 4 months following the last dose of CAPRELSA
- The most commonly reported adverse drug reactions (>20%) seen with CAPRELSA and with a between arm difference of ≥5% are diarrhea/colitis (57%), rash (53%), acneiform dermatitis (35%), hypertension (33%), nausea (33%), headache (26%), upper respiratory tract infections (23%), decreased appetite (21%), and abdominal pain (21%)
- 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
Indications and Usage
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 CAPRELSA in patients with indolent, asymptomatic or slowly progressing disease only after careful consideration of the treatment related risks of CAPRELSA.
To report suspected adverse reactions, visit www.fda.gov/safety/medwatch or call 1‑800‑FDA‑1088.
You may also contact Sanofi Genzyme at 1-800-745-4447, option 2.