Caprelsa
Vandetanib · Tablet, Film Coated · Oral
Uses
1 INDICATIONS AND USAGE 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. 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
The recommended dose of CAPRELSA is 300 mg taken orally once daily until disease progression or unacceptable toxicity occurs. 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. 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 ) 2.1 Dosage Adjustment 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: Corrected QT interval, Fridericia (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. Adverse events including QT interval prolongation should be monitored closely as they may not resolve fully until approximately three plasma half-lives of the drug. Monitor appropriately [see Warnings and Precautions (5.1) , (5.2) , (5.3) , (5.4) , (5.5) , (5.6) , (5.7) , and (5.9) ] . For Patients with Renal Impairment Reduce the starting dose to 200 mg in patients with moderate (creatinine clearance ≥30 to <50 mL/min) renal impairment [see Warnings and Precautions (5.12) and Use in Specific Populations (8.6) ] . For Patients with Hepatic Impairment CAPRELSA is not recommended for use in patients with moderate and severe hepatic impairment [see Use in Specific Populations (8.7) ] .
Dosage forms and strengths
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. 100 mg and 300 mg tablets ( 3 )
Contraindications
Do not use in patients with congenital long QT syndrome [see Boxed Warning ] . 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 necrolysis and Stevens-Johnson syndrome, some fatal. Discontinue CAPRELSA for severe skin reactions. ( 2.1 , 5.2 ) Interstitial lung disease (ILD), including fatalities: investigate unexplained non-specific respiratory signs and symptoms. Discontinue CAPRELSA for confirmed ILD. ( 2.1 , 5.3 ) Ischemic cerebrovascular events, hemorrhage, heart failure, diarrhea, hypertension, and reversible posterior leukoencephalopathy syndrome: Discontinue or interrupt CAPRELSA. ( 2.1 , 5.4 , 5.5 , 5.6 , 5.7 , 5.9 , 5.10 ) Impaired wound healing: Withhold for at least 1 month prior to elective surgery. Do not administer CAPRELSA for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of treatment with CAPRELSA after resolution of wound healing complications has not been established. ( 5.14 ) Embryo-fetal toxicity: Can cause fetal harm. Advise women of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.15 , 8.1 ) Osteonecrosis, including osteonecrosis of the jaw: Withhold CAPRELSA for 1 month prior to scheduled dental surgery and permanently discontinue if osteonecrosis occurs ( 5.16 , 6.2 ). 5.1 QT Prolongation and Torsades de Pointes CAPRELSA can prolong the QT interval in a concentration-dependent manner [see Clinical Pharmacology (12.2) ] . 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 is greater than 450 ms. Do not administer CAPRELSA 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. Vandetanib exposure is increased in patients with impaired renal function. Reduce the starting dose to 200 mg in patients with moderate renal impairment and monitor QT interval frequently. Obtain an ECG and serum potassium, calcium, magnesium and TSH at baseline, 2 to 4 weeks and 8 to 12 weeks after starting treatment with CAPRELSA, and every 3 months thereafter. Monitor electrolytes and ECGs more frequently in patients who experience diarrhea. Following any dose reduction for QT prolongation or any dose interruption greater than 2 weeks, conduct QT assessments as described above. Maintain serum potassium levels of 4 mEq/L or higher (within normal range) and maintain serum magnesium and calcium levels within normal ranges to reduce the risk of QT prolongation. Avoid using CAPRELSA with drugs known to prolong the QT interval [see Warnings and Precautions (5.11) and Drug Interactions (7.4) ] . If such drugs are given to patients already receiving CAPRELSA and no alternative therapy exists, perform ECG monitoring of the QT interval more frequently. Stop CAPRELSA in patients who develop a QTcF greater than 500 ms until the QTcF returns to less than 450 ms. Dosing of CAPRELSA can then be resumed at a reduced dose [see Dosage and Administration (2.1) ] . 5.2 Severe Skin Reactions Severe and sometimes fatal skin reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome, have occurred in patients treated with CAPRELSA. Permanently discontinue CAPRELSA for severe skin reactions and refer the patient for urgent medical evaluation. Systemic therapies such as corticosteroids may be required. Photosensitivity reactions can occur during CAPRELSA treatment and up to 4 months after treatment discontinuation. 5.3 Interstitial Lung Disease Interstitial Lung Disease (ILD) or pneumonitis, including fatalities, has occurred in patients treated with CAPRELSA. Consider a diagnosis of ILD in patients presenting with non-specific respiratory signs and symptoms. Interrupt CAPRELSA for acute or worsening pulmonary symptoms. Discontinue CAPRELSA if ILD is confirmed. 5.4 Ischemic Cerebrovascular Events Ischemic cerebrovascular events, including fatalities, occurred in patients treated with CAPRELSA. In the randomized medullary thyroid cancer (MTC) study, ischemic cerebrovascular events occurred more frequently with CAPRELSA compared to placebo (1.3% compared to 0%). 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. 5.5 Hemorrhage 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. 5.6 Heart Failure 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. 5.7 Diarrhea Diarrhea of Grade 3 or greater severity occurred in 11% of patients receiving CAPRELSA in the randomized MTC study. If diarrhea occurs, carefully monitor serum electrolytes and ECGs to reduce the risk and enable early detection of QT prolongation resulting from dehydration [see Warnings and Precautions (5.1) ] . Interrupt CAPRELSA for severe diarrhea. Upon improvement, resume CAPRELSA at a reduced dose [see Dosage and Administration (2.1) ] . 5.8 Hypothyroidism In the randomized MTC study in which 90% of the patients enrolled had prior thyroidectomy, increased dosing of thyroid replacement therapy was required in 49% of CAPRELSA-treated patients compared to 17% of placebo-treated patients.
Side effects
The following serious adverse reactions are discussed elsewhere in the label: QT Prolongation and Torsades de Pointes [see Boxed Warning , Warnings and Precautions (5.1) ] Severe Skin Reactions [see Warnings and Precautions (5.2) ] Interstitial Lung Disease [see Warnings and Precautions (5.3) ] Ischemic Cerebrovascular Events [see Warnings and Precautions (5.4) ] Hemorrhage [see Warnings and Precautions (5.5) ] Heart Failure [see Warnings and Precautions (5.6) ] Diarrhea [see Warnings and Precautions (5.7) ] Hypothyroidism [see Warnings and Precautions (5.8) ] Hypertension [see Warnings and Precautions (5.9) ] Reversible Posterior Leukoencephalopathy Syndrome [see Warnings and Precautions (5.10) ] Renal Failure [see Warnings and Precautions (5.12) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.15) ] Osteonecrosis [see Warnings and Precautions (5.16) ] The most common adverse drug reactions (>20%) seen with CAPRELSA and with a between-arm difference of ≥5 % have been diarrhea/colitis, rash, acneiform dermatitis, hypertension, nausea, headache, upper respiratory tract infections, decreased appetite and abdominal pain. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, Contact Sanofi Genzyme at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Patients with unresectable locally advanced or metastatic medullary thyroid cancer were treated with CAPRELSA 300 mg (n=231) or Placebo (n=99). The population exposed to CAPRELSA was 58% male, 94% white, and had a median age of 50 years. The data described below reflect a median exposure to CAPRELSA for 607 days. The most commonly reported adverse drug reactions which occurred in >20% of CAPRELSA-treated patients and with a between-arm difference of ≥5% included, in order of decreasing frequency: diarrhea/colitis, rash, acneiform dermatitis, hypertension, nausea, headache, upper respiratory tract infection, decreased appetite, and abdominal pain. Among CAPRELSA-treated patients, dose interruption occurred in 109 (47%) and dose reduction occurred in 83 (36%). Adverse reactions led to study treatment discontinuation in 28 of 231 patients (12%) receiving CAPRELSA and in 3 of 99 patients (3.0%) receiving placebo. Adverse reactions leading to permanent discontinuation in 2 or more (≥0.9%) patients treated with CAPRELSA were: asthenia (1.7%), rash (1.7%), diarrhea (0.9%), fatigue (0.9%), pyrexia (0.9%), elevated creatinine (0.9%), QT prolongation (0.9%), and hypertension (0.9%). Table 1: Per-Patient Incidence of Selected Adverse Reactions Occurring at a Higher Incidence in CAPRELSA-Treated Patients During Randomized Treatment (Between-Arm Difference of ≥5% [All Grades] CTCAE version 3 was used to grade adverse events. ) System Organ Class CAPRELSA 300 mg Placebo Preferred Term N=231 N=99 All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Gastrointestinal Disorders Diarrhea/Colitis 57 11 27 2 Nausea 33 1 16 0 Abdominal Pain Includes abdominal pain, abdominal pain upper, lower abdominal pain, and abdominal discomfort. 21 3 11 0 Vomiting 15 1 7 0 Dyspepsia 11 0 4 0 Dry Mouth 9 0 3 0 Skin and Cutaneous Disorders Rash Includes rash, rash (erythematous, generalized, macular, maculopapular, papular, pruritic, and exfoliative), dermatitis, dermatitis bullous, generalized erythema, and eczema. 53 5 12 0 Dermatitis Acneiform/Acne 35 1 7 0 Dry Skin 15 0 5 0 Photosensitivity Reaction 13 2 0 0 Pruritus 11 1 4 0 Nail abnormalities Includes nail disorder, nail bed inflammation, nail bed tenderness, paronychia, nail bed infection, and nail infection. 9 0 0 0 Alopecia 8 N/A 0 N/A Vascular Disorders Hypertension/Hypertensive Crisis/Accelerated Hypertension 33 9 5 1 Nervous System Disorders Headache 26 1 9 0 Dysgeusia 8 0 3 0 General Disorders Fatigue Included in Table 1 due to the increased incidence of severe fatigue in the CAPRELSA group compared to the placebo group. 24 6 23 1 Infections Upper Respiratory Tract Infections Includes laryngitis, nasopharyngitis, pharyngitis, sinusitis, upper respiratory tract infection, acute sinusitis, rhinitis, and tracheitis. 23 0 16 0 Metabolic and Nutritional Disorders Decreased Appetite 21 4 12 0 Hypocalcemia 11 2 3 0 Investigations ECG QT Prolonged 69% had QT prolongation >450 ms and 7% had QT prolongation >500 ms by ECG using Fridericia correction. 14 8 1 1 Eye Disorders Corneal Abnormalities Includes corneal edema, corneal opacity, corneal dystrophy, corneal pigmentation, keratopathy, arcus lipoides, corneal deposits, and acquired corneal dystrophy. 13 0 1 0 Blurred Vision 9 0 1 0 Renal Disorders Proteinuria 10 0 2 0 Psychiatric Disorders Depression 10 2 3 0 Endocrine Disorders Hypothyroidism 6 0 0 0 Musculoskeletal Disorders Muscle Spasms 6 0 1 0 Other Clinically Relevant Adverse Effects In patients with medullary thyroid cancer treated with CAPRELSA or placebo (NCT00410761), clinically important uncommon adverse drug reactions included pancreatitis (0.4% vs 0%), intestinal perforation (0.4% vs 0%), and heart failure (0.9% vs 0%). Blurred vision was commonly reported (9% vs 1%) in this trial. Scheduled slit lamp examinations revealed corneal opacities (vortex keratopathies) in treated patients, which can lead to halos and decreased visual acuity. Perform ophthalmologic examination, including slit lamp examination, in patients who report visual changes. Grade 1 to 2 bleeding events were also more common in patients receiving CAPRELSA compared to placebo (14% vs 7%).
Drug interactions
Avoid the use of strong CYP3A4 inducers because they may decrease CAPRELSA exposure. ( 7.1 ) Avoid the use of agents that prolong the QT interval. ( 5.11 ) 7.1 Effect of CYP3A4 Inducers on CAPRELSA Rifampicin, a strong CYP3A4 inducer, decreased vandetanib plasma concentrations. Avoid concomitant use of known strong CYP3A4 inducers during CAPRELSA therapy. Avoid concomitant use of St. John's wort because it can decrease vandetanib exposure unpredictably [see Clinical Pharmacology (12.3) ] . 7.2 Effect of CAPRELSA on OCT2 Transporter CAPRELSA increased plasma concentrations of metformin that is transported by the organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering CAPRELSA with drugs that are transported by OCT2 [see Clinical Pharmacology (12.3) ] . 7.3 Effect of CAPRELSA on Digoxin CAPRELSA increased plasma concentrations of digoxin. Use caution and closely monitor for toxicities when administering CAPRELSA with digoxin [see Clinical Pharmacology (12.3) ] . 7.4 Drugs that Prolong the QT Interval Avoid concomitant use of CAPRELSA with agents that may prolong the QT interval [see Warnings and Precautions (5.11) ] .
Use in specific populations
8.1 Pregnancy 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 C max ), 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 C max 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 C max 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. 8.2 Lactation 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. 8.3 Females and Males of Reproductive Potential 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) ] . 8.4 Pediatric Use Safety and efficacy of CAPRELSA in pediatric patients have not been established. 8.5 Geriatric Use 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. 8.6 Renal Impairment 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) ] . 8.7 Hepatic Impairment 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) ] .
Pregnancy
8.1 Pregnancy 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 C max ), 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 C max 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 C max 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.
Pediatric use
8.4 Pediatric Use Safety and efficacy of CAPRELSA in pediatric patients have not been established.
Geriatric use
8.5 Geriatric Use 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.
Overdosage
In the event of an overdose, monitor patients closely for QTc prolongation. Adverse events including QT interval prolongation should be monitored closely as they may not resolve fully until approximately three plasma half-lives of the drug.
Description
Vandetanib has the chemical name N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl) methoxy]quinazolin-4-amine. The structural and molecular formulas are: C 22 H 24 BrFN 4 O 2 Vandetanib has a molecular weight of 475.36 g/mol. Vandetanib exhibits pH-dependent solubility, with increased solubility at lower pH. Vandetanib is practically insoluble in water with a value of 0.008 mg/mL at 25°C (77°F). CAPRELSA tablets for daily oral administration are available in two dosage strengths containing either 100 mg or 300 mg of vandetanib. The tablet cores contain the following inactive ingredients: calcium hydrogen phosphate dihydrate, crospovidone, magnesium stearate, microcrystalline cellulose, and povidone. The tablet film-coat contains the following inactive ingredients: hypromellose 2910, macrogol 300, and titanium dioxide E171. Chemical Structure
Mechanism of action
12.1 Mechanism of Action In vitro studies have shown that vandetanib inhibits the tyrosine kinase activity of the EGFR and VEGFR families, RET, BRK, TIE2, and members of the EPH receptor and Src kinase families. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment. In addition, the N-desmethyl metabolite of the drug, representing 7 to 17.1% of vandetanib exposure, has similar inhibitory activity to the parent compound for VEGF receptors (KDR and Flt-1) and EGFR. In vitro , vandetanib inhibited epidermal growth factor (EGF)-stimulated receptor tyrosine kinase phosphorylation in tumor cells and endothelial cells and VEGF-stimulated tyrosine kinase phosphorylation in endothelial cells. In vivo , vandetanib administration reduced tumor cell-induced angiogenesis, tumor vessel permeability, and inhibited tumor growth and metastasis in mouse models of cancer.
How supplied
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). 16.1 Storage and Handling 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.
Storage
16.1 Storage and Handling 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.
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). QT Prolongation and Torsades de Pointes Advise patients to contact their healthcare provider in the event of syncope, pre-syncopal symptoms, and cardiac palpitations. Advise patients that their healthcare provider will monitor their electrolytes and ECGs during treatment [see Warnings and Precautions (5.1) ] . Severe Skin Reactions Advise patients to contact their healthcare provider in the event of skin reactions or rash [see Warnings and Precautions (5.2) ] . Interstitial Lung Disease (ILD) Advise patients to contact their health care provider in the event of sudden onset or worsening of breathlessness, persistent cough or fever [see Warnings and Precautions (5.3) ] . Diarrhea Advise patients to contact their healthcare provider in the event of diarrhea [see Warnings and Precautions (5.7) ] . Reversible Posterior Leukoencephalopathy Syndrome (RPLS) Advise patients to contact their healthcare provider in the event of seizures, headaches, visual disturbances, confusion or difficulty thinking [see Warnings and Precautions (5.10) ] . Impaired Wound Healing Advise patients that CAPRELSA may impair wound healing. Advise patients to inform their healthcare provider of any planned surgical procedure [see Warnings and Precautions (5.14) ] . Osteonecrosis Advise patients regarding good oral hygiene practices and to have preventive dentistry performed prior to treatment with CAPRELSA and throughout treatment with CAPRELSA and to inform their healthcare provider of any planned dental procedures. Advise patients to immediately contact their healthcare provider for signs or symptoms associated with osteonecrosis [see Warnings and Precautions (5.16) ] . Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus. Advise females to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, during treatment with CAPRELSA [see Use in Specific Populations (8.1) , (8.3) ] . Advise females of reproductive potential to use effective contraception during treatment with CAPRELSA and for 4 months after the last dose [see Use in Specific Populations (8.3) ] . Advise males with female partners of reproductive potential to use effective contraception during treatment with CAPRELSA and for 4 months after the last dose [see Use in Specific Populations (8.3) ] . Lactation Advise women not to breastfeed during treatment with CAPRELSA and for 4 months after the last dose [see Use in Specific Populations (8.2) ] . Photosensitivity Advise patients to use appropriate sun protection due to the increased susceptibility to sunburn while taking CAPRELSA and for at least 4 months after drug discontinuation [see Warnings and Precautions (5.2) ] . Administration Advise patients that CAPRELSA can be taken with or without food and not to crush CAPRELSA tablets [see Clinical Pharmacology (12.3) ] .
Label text from the FDA structured product label by Genzyme Corporation (revised Apr 23, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Vandetanib in 2 products
Caprelsa NDC products (2)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 58468-7820 | Vandetanib 100 mg/1 Tablet, Film Coated | Genzyme Corporation | NDA |
| 58468-7840 | Vandetanib 300 mg/1 Tablet, Film Coated | Genzyme Corporation | NDA |
Frequently asked questions
What is Caprelsa used for?
1 INDICATIONS AND USAGE 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. CAPRELSA is a kinase inhibitor indicated for the…
What are the side effects of Caprelsa?
The following serious adverse reactions are discussed elsewhere in the label: QT Prolongation and Torsades de Pointes [see Boxed Warning , Warnings and Precautions (5.1) ] Severe Skin Reactions [see Warnings and Precautions (5.2) ] Interstitial Lung Disease [see Warnings and Precautions (5.3) ] Ischemic Cerebrovascular Events [see Warnings and Precautions (5.4) ] Hemorrhage [see Warnings and… See the full label for the complete list.
Who makes Caprelsa?
Caprelsa is listed by 1 labeler in the FDA NDC directory, including Genzyme Corporation.