CAPRELSA- vandetanib tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

VANDETANIB (UNII: YO460OQ37K) (VANDETANIB - UNII:YO460OQ37K)

Available from:

Genzyme Corporation

INN (International Name):

VANDETANIB

Composition:

VANDETANIB 100 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

CAPRELSA is 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. Do not use in patients with congenital long QT syndrome [see Boxed Warning] . Risk Summary Based on its mechanism of action and findings in animals, CAPRELSA can cause fetal harm when administered to a pregnant woman. There are no available human data on CAPRELSA use in pregnant women to inform a drug-associated risk. Vandetanib is embryotoxic, fetotoxic, and induced fetal malformations in rats at exposures less than or equal to those expected at the recommended human dose of 300 mg/day. Advise patients of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal data In reproductive toxicity studies, administration of vandetanib to female rats prior to mating and through the first week of pregnancy at a dose of 25 mg/kg/day (approximately equal to the human exposure at the 300 mg clinical dose based on Cmax ), there were increases in pre-implantation loss and post-implantation loss resulting in a reduction in the number of live embryos. During organogenesis, vandetanib caused an increase in post-implantation loss, including occasional total litter loss at a dose of 25 mg/kg/day. At doses greater than 10 mg/kg/day (approximately 0.4 times the human Cmax at the 300 mg clinical dose) treatment with vandetanib resulted in increases in late embryofetal death and decreases in fetal birth weight. A no-effect level for malformations was not identified in this study. Administration of vandetanib at doses greater than or equal to 1 mg/kg/day (approximately 0.03 times the human Cmax at the 300 mg clinical dose) resulted in dose dependent increases in both malformations of the heart vessels and skeletal variations including delayed ossification of the skull, vertebrae, and sternum, indicating delayed fetal development. In a rat prenatal and postnatal development study, at doses (1 and 10 mg/kg/day) producing mild maternal toxicity during gestation and/or lactation, vandetanib decreased pup survival and reduced postnatal pup growth. Reduced postnatal pup growth was associated with a delay in physical development. Risk Summary There are no data on the presence of vandetanib or its metabolites in human milk, the effects on the breastfed child or on milk production. Vandetanib was present in the milk of lactating rats (see Data) . Because of the potential for serious adverse reactions from CAPRELSA in breastfed children, advise lactating women not to breastfeed during treatment with CAPRELSA and for 4 months after the last dose. Data Animal data In nonclinical studies, vandetanib was excreted in rat milk and found in plasma of pups following dosing to lactating rats. Vandetanib transfer in breast milk resulted in relatively constant exposure in pups due to the long half-life of the drug. Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating treatment with CAPRELSA [see Use in Specific Populations (8.1)] . Contraception CAPRELSA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Females Advise females of reproductive potential to use effective contraception during treatment with CAPRELSA and for 4 months after the last dose. Males Advise males with female partners of reproductive potential to use effective contraception during treatment with CAPRELSA and for 4 months after the last dose. Infertility There are no data on the effect of CAPRELSA on human fertility. Results from animal studies indicate that vandetanib can impair male and female fertility [see Nonclinical Toxicology (13.1)] . Safety and efficacy of CAPRELSA in pediatric patients have not been established. The MTC study of CAPRELSA did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently compared to younger patients. Vandetanib exposure is increased in patients with impaired renal function. Reduce the starting dose to 200 mg in patients with moderate (creatinine clearance ≥30 to <50 mL/min) renal impairment [see Dosage and Administration (2.1), Warnings and Precautions (5.12), and Clinical Pharmacology (12.3)] . Vandetanib is not recommended for use in patients with severe renal impairment (clearance below 30 mL/min) [see Warnings and Precautions (5.12)] . Patients with end-stage renal disease requiring dialysis were not studied [see Adverse Reactions (6.1)] . The pharmacokinetics of CAPRELSA were evaluated after a single dose of 800 mg in subjects with mild (n=8), moderate (n=7), and severe (n=6) hepatic impairment and normal hepatic function (n=5). Subjects with mild (Child-Pugh class A), moderate (Child-Pugh class B), and severe (Child-Pugh class C) hepatic impairment had comparable mean AUC and clearance values to those 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 and severe hepatic impairment, as safety and efficacy have not been established [see Dosage and Administration (2.1) and Warnings and Precautions (5.13)] .

Product summary:

100 mg Tablets available in bottles containing 30 tablets (NDC 58468-7820-3). 300 mg Tablets available in bottles containing 30 tablets (NDC 58468-7840-3). CAPRELSA tablets should be stored at room temperature between 68°F and 77°F (20°C and 25°C); excursions permitted to 59°F–86°F (15°C-30°C) [See USP controlled room temperature]. Procedures for proper handling and disposal of anticancer drugs should be considered. A guideline on this subject has been published.1 Do not crush CAPRELSA tablets.

Authorization status:

New Drug Application

Patient Information leaflet

Genzyme Corporation
----------
This Medication Guide has been approved by the
U.S. Food and Drug Administration.
Revised: March 2024
MEDICATION GUIDE
CAPRELSA® (kap-rel-sah)
(vandetanib)
tablets
Read this Medication Guide before you start taking CAPRELSA and each
time you get a refill. There
may be new information. This Medication Guide does not take the place
of talking to your healthcare
provider about your medical condition or treatment.
What is the most important information I should know about CAPRELSA?
CAPRELSA can cause a change in the electrical activity of your heart
called QT prolongation, which can
cause irregular heartbeats and that may lead to death. You should not
take CAPRELSA if you have had a
condition called long QT syndrome since birth.
Your healthcare provider should perform tests to check the levels of
your blood potassium, calcium,
magnesium, and thyroid-stimulating hormone (TSH), as well as the
electrical activity of your heart with
a test called an electrocardiogram (ECG). You should have these tests:
•
Before starting CAPRELSA
•
Regularly during CAPRELSA treatment:
•
2 to 4 weeks after starting CAPRELSA
•
8 to 12 weeks after starting CAPRELSA
•
every 3 months thereafter
•
if your healthcare provider changes your dose of CAPRELSA
•
if you start taking medicine that causes QT prolongation
•
as instructed by your healthcare provider
Your healthcare provider may stop your CAPRELSA treatment for a while
and restart you at a lower
dose if you have QT prolongation.
Call your healthcare provider right away if you feel faint,
light-headed, or feel your heart beating
irregularly during treatment with CAPRELSA. These may be symptoms
related to QT prolongation.
CAPRELSA is only available through a restricted program called the
CAPRELSA Risk Evaluation and
Mitigation Strategy (REMS) Program. For more information about the
CAPRELSA REMS Program, call
1-800-817-2722 or go to www.caprelsa.com.
See "What are the possible side effects of CAPRELSA?" for more
information about side effects.

Summary of Product characteristics

CAPRELSA- VANDETANIB TABLET, FILM COATED
GENZYME CORPORATION
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
CAPRELSA SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR CAPRELSA.
CAPRELSA (VANDETANIB) TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2011
WARNING: QT PROLONGATION, TORSADES DE POINTES, AND SUDDEN DEATH
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
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 (5.1, 5.16).
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. (1)
Use CAPRELSA in patients with indolent, asymptomatic or slowly
progressing disease only after careful
consideration of the treatment related risks of CAPRELSA. (1)
DOSAGE AND ADMINISTRATION
300 mg once daily. (2)
CAPRELSA may be taken with or without food. (2)
Dosage reduction may be necessary in the event of severe toxicities or
QTc interval prolongation. (2.1)
The starting dose is 200 mg in patients with moderate renal
impairment. (2.1)
DOSAGE FORMS AND STRENGTHS
100 mg and 300 mg tablets (3)
CONTRAINDICATIONS
Do not use in patients with congenital long QT syndrome. (4)
WARNINGS AND PRECAUTIONS
Prolonged QT interval, torsades de pointes, and sudden death: Monitor
electrocardiograms and levels
of serum potassium, calcium, magnesium and TSH. Reduce CAPRELSA dose
as appropriate. (2.1, 5.1)
Severe skin reactions, including toxic epidermal n