CAPRELSA

C₂₂H₂₄BrFN₄O₂

Vandetanib has a molecular weight of 475.36. 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, microcrystalline cellulose, crospovidone, povidone, and magnesium stearate. The tablet film-coat contains the following inactive ingredients: hypromellose 2910, macrogol 300, and titanium dioxide E171.

12. CLINICAL PHARMACOLOGY

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.

12.2 Pharmacodynamics

Cardiac Electrophysiology

In 231 patients with medullary thyroid cancer randomized to receive CAPRELSA 300 mg once daily in the phase 3 clinical trial. CAPRELSA was associated with sustained plasma concentration-dependent QT prolongation. Based on the exposure-response relationship, the mean (90% CI) QTcF change from baseline (ΔQTcF) was 35 (33-36) ms for the 300 mg dose. The ΔQTcF remained above 30 ms for the duration of the trial (up to 2 years). In addition, 36% of patients experienced greater than 60 ms increase in ΔQTcF and 4.3% of patients had QTcF greater than 500 ms. Cases of Torsades de pointes and sudden death have occurred [see Boxed Warning and Warnings and Precautions (5.1, 5.11)].

12.3. Pharmacokinetics

A population pharmacokinetic analysis of CAPRELSA was conducted in 231 patients with MTC following oral administration of 300 mg daily doses. The pharmacokinetics of CAPRELSA at the 300 mg dose in MTC patients are characterized by a mean clearance of approximately 13.2 L/h, a mean volume of distribution of approximately 7450 L, and a median plasma half-life of 19 days.

Absorption

Following oral administration of CAPRELSA, absorption is slow with peak plasma concentrations typically achieved at a median of 6 hours, range 4-10 hours, after dosing. Vandetanib accumulates approximately 8-fold on multiple dosing with steady state achieved in approximately 3 months.

Exposure to vandetanib is unaffected by food

Distribution

Vandetanib binds to human serum albumin and α1-acid-glycoprotein with in vitro protein binding being approximately 90%. In ex vivo plasma samples from colorectal cancer patients at steady state exposure after 300 mg once daily, the mean percentage protein binding was 94%.

Metabolism

Following oral dosing of ¹⁴C-vandetanib, unchanged vandetanib and metabolites vandetanib N-oxide and N-desmethyl vandetanib were detected in plasma, urine and feces. A glucuronide conjugate was seen as a minor metabolite in excreta only. N-desmethyl-vandetanib is primarily produced by CYP3A4 and vandetanib-N-oxide by flavin–containing monooxygenase enzymes FMO1 and FMO3. N-desmethyl-vandetanib and vandetanib-N-oxide circulate at concentrations of approximately 7-17% and 1.4-2.2%, respectively, of those of vandetanib.

Excretion

Within a 21-day collection period after a single dose of ¹⁴C-vandetanib, approximately 69% was recovered with 44% in feces and 25% in urine. Excretion of the dose was slow and further excretion beyond 21 days would be expected based on the plasma half-life.

Vandetanib was not a substrate of hOCT2 expressed in HEK293 cells. Vandetanib inhibits the uptake of the selective OCT2 marker substrate ¹⁴C-creatinine by HEK-OCT2 cells, with a mean IC₅₀ of 2.1 μg/mL. This is higher than vandetanib plasma concentrations (0.81 μg/mL) observed after multiple dosing at 300 mg. Inhibition of renal excretion of creatinine by vandetanib provides an explanation for increases in plasma creatinine seen in human subjects receiving vandetanib.

Specific Populations

Effects of Age and Gender

In a population pharmacokinetic evaluation in cancer patients, no relationship was apparent between oral clearance of vandetanib and patient age or gender.

Ethinicity

Based on a cross-study comparison in a limited number of patients, Japanese (N=3) and Chinese (N=7) patients had average exposures of vandetanib that were higher than Caucasian (N=7) patients receiving the same dose of CAPRELSA.

Pediatric

The pharmacokinetics of vandetanib has not been evaluated in pediatric patients.

Effect of Renal Impairment

The pharmacokinetics of vandetanib were evaluated after a single CAPRELSA dose of 800 mg in six subjects with mild (creatinine clearance = 50 to < 80 mL/min), eight subjects with moderate (creatinine clearance ≥30 to <50 mL/min), six subjects with severe (creatinine clearance < 30 mL/min) renal impairment or and ten subjects with normal (creatinine clearance > 80 mL/min) renal function. Subjects with mild renal impairment had a comparable mean AUC of vandetanib to that with normal renal function. In subjects with moderate or severe renal impairment, the average AUC of vandetanib increased by 39% and 41%, respectively, compared to patients with normal renal function [see Dosage and Administration (2.1), Warnings and Precautions (5.12) and Use in Specific Populations (8.6)].

Drug Interactions

Effect of Other Drugs on CAPRELSA

Strong CYP3A4 inducers: In a cross-over study in 12 healthy volunteers, a single oral 300 mg dose of CAPRELSA was administered alone on day 1 and on day 10 in combination with daily doses of 600 mg of rifampicin (a strong CYP3A4 inducer) given on days 1-31. The coadministration of rifampicin with CAPRELSA decreased the geometric mean AUC_0-504h of vandetanib by 40% (90% confidence interval (CI): 56%, 63%) compared to vandetanib alone. No clinically meaningful change in the mean C_max of vandetanib was observed. The geometric mean AUC_0-504h and C_max of N-desmethylvandetanib increased by 266% and 414%, respectively, in the presence of rifampicin compared with vandetanib alone [see Drug Interactions(7.1) ].

Strong CYP3A4 inhibitors: In a cross-over study in 14 healthy volunteers, a single oral 300 mg dose of CAPRELSA was administered alone and on day 4 in combination with daily doses of 200 mg of itraconazole (a strong CYP3A4 inhibitor) given on days 1-24. No change was observed in the geometric mean AUC_0-504h or C_max of vandetanib when itraconazole was coadministered with CAPRELSA.

Gastric pH elevating agents: In a cross-over study of 14 healthy volunteers, a single oral 300 mg dose of CAPRELSA was administered alone and in combination with five daily doses of 40 mg omeprazole (a protonpump inhibitor). No clinically meaningful change was observed in the geometric mean AUC_0-504h and C_max of vandetanib when omeprazole was coadministered with CAPRELSA.

In a cross-over study of 16 healthy volunteers, a single 300 mg oral dose of CAPRELSA was administered alone and after two oral doses of 150 mg of ranitidine (a H₂ receptor antagonist) administered about 12 hours apart. No change was observed in the geometric mean AUC_0-504h and C_max of vandetanib when ranitidine was coadministered with CAPRELSA.

Effect of CAPRELSA on Other Drugs

Sensitive CYP3A4 substrates: In a cross-over study of 16 healthy volunteers, a single oral 7.5 mg dose of midazolam (as 2 mg/mL oral syrup), a sensitive CYP3A4 substrate, was administered alone and 8 days after receiving a single 800 mg oral dose of CAPRELSA. No change was observed in the geometric mean C_max and AUC_inf of midazolam when CAPRELSA was coadministered with midazolam.

Substrates of OCT2 transporter: In a cross-over study of 13 healthy volunteers, a single 1000 mg oral dose of metformin, a substrate of OCT2, was administered alone and 3 hours after receiving a single 800 mg oral dose of CAPRELSA. The coadministration of CAPRELSA with metformin increased the geometric mean AUC_inf of metformin by 74% (90% CI: 58%, 92%) and geometric mean C_max of metformin by 50% (90% CI: 34%, 67%) compared to metformin alone [see Drug Interactions (7.2) ].

Substrates of P-glycoprotein transporter: In a cross-over study of 14 healthy volunteers, a single oral 0.25 mg dose of digoxin, a substrate of P-glycoprotein, was administered alone and in combination with a single 300 mg oral dose of CAPRELSA. The coadministration of CAPRELSA increased the geometric mean C_max digoxin by 29% (90% CI: 10%, 52%) and the geometric mean of AUC_0-t of digoxin by 23% (90% CI: 12%, 34%) compared to digoxin alone [see Drug Interactions (7.3) ].

13. NONCLINICAL TOXICOLOGY

13.1. Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies have not been conducted with vandetanib. Vandetanib was not mutagenic in vitro in the bacterial reverse mutation (Ames) assay and was not clastogenic in either the in vitro cytogenetic assay using human lymphocytes or in the in vivo rat micronucleus assay.

Based on nonclinical findings, male and female fertility may be impaired by treatment with CAPRELSA. In a fertility study of male rats, vandetanib had no effect on copulation or fertility rate when untreated females were mated with males administered 1, 5, or 20 mg/kg/day of vandetanib (approximately 0.03, 0.22, or 0.40 times, respectively, the AUC in patients with cancer at the recommended human dose of 300 mg/day); however, in the same study there was a slight decrease in the number of live embryos in females mated with males treated at the 20 mg/kg/day dose level and an increase in preimplantation loss in females mated with males administered vandetanib at doses of ≥ 5 mg/kg/day. In a female fertility study, there was a trend towards increased estrus cycle irregularity, a slight reduction in pregnancy incidence and an increase in implantation loss. In a one month repeat-dose toxicity study in rats, there was a decrease in the number of corpora lutea in the ovaries of rats administered 75 mg/kg/day vandetanib (approximately 1.8 times the exposure measured by AUC in patients with cancer at the recommended human dose).

13.2 Animal Toxicology and/or Pharmacology

In an animal model of wound-healing, mice dosed with vandetanib had reduced skin-breaking strength compared with controls. This suggests that CAPRELSA slows but does not prevent wound healing. The appropriate interval between discontinuation of CAPRELSA and subsequent elective surgery required to avoid the risks of impaired wound healing has not been determined.

Nodular masses were observed in a 6-month toxicology study in rats during treatment with ≥5 mg/kg/day vandetanib (approximately 0.22 or 0.40 times, respectively, the AUC in patients with cancer at the recommended human dose of 300 mg/day). Masses were palpable during clinical assessments as early as week 13, were observed in multiple organs, and were associated with hemorrhagic or inflammatory findings.

14. CLINICAL STUDIES

A double-blind, placebo-controlled study randomized patients with unresectable locally advanced or metastatic medullary thyroid cancer to CAPRELSA 300 mg (n=231) versus placebo (n=100).

The primary objective was demonstration of improvement in progression-free survival (PFS) with CAPRELSA compared to placebo. Other endpoints included evaluation of overall survival and overall objective response rate (ORR). Centralized, independent blinded review of the imaging data was used in the assessment of PFS and ORR. Upon objective disease progression based on the investigator’s assessment, patients were discontinued from blinded study treatment and given the option to receive open-label CAPRELSA. Nineteen percent (44/231) of the patients initially randomized to CAPRELSA opted to receive open-label CAPRELSA after disease progression, and 58% (58/100) of the patients initially randomized to placebo opted to receive open-label CAPRELSA after disease progression.

The result of the PFS analysis, based on the central review RECIST assessment, showed a statistically significant improvement in PFS for patients randomized to CAPRELSA (Hazard Ratio (HR) = 0.35; 95% Confidence Interval (CI) = 0.24-0.53; p<0.0001). Analyses in the subgroups of patients who were symptomatic or had progressed within 6 months prior to their enrollment showed similar PFS results (HR = 0.31 95% CI: 0.19, 0.53 for symptomatic patients; HR = 0.41 95% CI: 0.25, 0.66 for patients who had progressed within 6 months prior to enrollment).

At the time of the primary analysis of PFS, 15% of the patients had died and there was no significant difference in overall survival between the two treatment groups. The overall objective response rate (ORR) for patients randomized to CAPRELSA was 44% compared to 1% for patients randomized to placebo. All objective responses were partial responses.

Figure 1- Progression Free Survival

Table 3 - Summary of Key Efficacy Findings

PROGRESSION-FREE SURVIVAL	N N = Number of events/number of randomized patients	Median PFS (95% CI)	HR HR= Hazard Ratio, Cox Proportional Hazards Model	95% CI	p-value Logrank test
CAPRELSA 300 mg	59/231 (26%)	Not reached (22.6 months, NENE = non-estimatable)
			0.35	0.24, 0.53	<0.0001
Placebo	41/100 (41%)	16.4 Months (8.3, 19.7)

15 REFERENCES

“OSHA Hazardous Drugs” (OSHA Technical Manual). OSHA.

16. HOW SUPPLIED/STORAGE AND HANDLING

100 mg Tablets Available in bottles containing 30 tablets (NDC 0310–7820–30).

300 mg Tablets Available in bottles containing 30 tablets (NDC 0310–7840–30).

16.1 Storage and Handling

CAPRELSA tablets should be stored at 25°C (77°F); excursions permitted to 15°C – 30°C (59°F – 86°F) [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.

17. PATIENT COUNSELING INFORMATION

SEE 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 and Stevens-Johnson Syndrome: 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) ].
• •Fetal Toxicity: Because CAPRELSA can cause fetal harm, advise patients of reproductive potential to use effective contraception during therapy and for at least four months following their last dose of CAPRELSA, and to immediately contact their health care provider if pregnancy is suspected or confirmed [see Pregnancy (8.1) , Females and Males of Reproductive Potential (8.8) ].
• •Nursing Infants: Because of the potential for serious adverse reactions in nursing infants from CAPRELSA, advise breast feeding mothers to discontinue nursing while receiving therapy [see Nursing Mothers (8.3) ].
• •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 Pharmacokinetics (12.3) ].

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:
  • o2 to 4 weeks after starting CAPRELSA
  • o8 to 12 weeks after starting CAPRELSA
  • oEvery 3 months thereafter
  • oIf your healthcare provider changes your dose of CAPRELSA
  • oIf you start taking medicine that causes QT prolongation
  • oAs 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 while taking CAPRELSA. These may be symptoms related to QT prolongation.

What is CAPRELSA?

CAPRELSA is a prescription medicine used to treat medullary thyroid cancer that cannot be removed by surgery or that has spread to other parts of the body. It takes a long time to get rid of CAPRELSA from your body and you may be at risk for side effects related to CAPRELSA after you have stopped your treatment.

It is not known if CAPRELSA is safe and effective in children.

Who should not take CAPRELSA?

Do not take CAPRELSA if you have had QT prolongation.

What should I tell my healthcare provider before taking CAPRELSA?

Before you take CAPRELSA, tell your healthcare provider if you:

• •have any heart problems, including a condition called congenital long QT syndrome
• •have an irregular heartbeat
• •take or have stopped taking a medicine that causes QT prolongation
• •have low blood levels of potassium, calcium, or magnesium
• •have high blood levels of thyroid-stimulating hormone
• •have high blood pressure
• •have skin problems
• •have a history of breathing problems
• •have a recent history of coughing up blood or bleeding
• •have diarrhea
• •have liver problems
• •have kidney problems
• •have seizures or are being treated for seizures
• •are pregnant or plan to become pregnant. CAPRELSA can cause harm to your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant.
  • oIf you are able to become pregnant, you should use effective birth control during your treatment with CAPRELSA and for at least 4 months after your last dose of CAPRELSA.
  • oTalk to your healthcare provider about birth control methods to prevent pregnancy while you are taking CAPRELSA.
• •are breastfeeding or plan to breastfeed. It is not known if CAPRELSA passes into your breast milk. You and your healthcare provider should decide if you will take CAPRELSA or breastfeed. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. CAPRELSA and other medicines may affect each other causing side effects.

Especially tell your healthcare provider if you take:

• •St. John’s Wort. You should not take St. John’s Wort while taking CAPRELSA
• •certain medicines that can affect how your liver breaks down medicine
• •a medicine for your heart

Ask your healthcare provider if you are not sure if your medicine is one listed above.

Do not take other medicines while taking CAPRELSA until you have talked with your healthcare provider or pharmacist.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take CAPRELSA?

• •Take CAPRELSA exactly as your healthcare provider tells you to take it. Do not change your dose or stop taking CAPRELSA unless your healthcare provider tells you to.
• •CAPRELSA may be taken with or without food.
• •Swallow CAPRELSA tablets whole with water.
• •Do not crush or chew CAPRELSA tablets. If CAPRELSA tablets are accidentally crushed, contact with skin should be avoided. If contact occurs, wash affected areas well with water.
• •If you cannot swallow CAPRELSA tablets whole:
  • oplace your dose of CAPRELSA in a glass that contains 2 ounces of noncarbonated water (no other liquids should be used).
  • ostir the CAPRELSA tablet(s) and water mixture for about 10 minutes or until the tablet(s) are in very small pieces (the tablets will not completely dissolve).
  • oswallow CAPRELSA and water mixture right away.
  • oif any CAPRELSA and water mixture remains in the glass, mix with an additional 4 ounces of noncarbonated water and swallow the mixture to make sure that you take your full dose of CAPRELSA.
• •If you miss a dose and your next dose is in:
  • oless than 12 hours, take your next dose at the normal time. Do not make up for the missed dose.
  • o12 hours or more, take the missed dose as soon as you remember. Take the next dose at the normal time.

Call your healthcare provider right away if you take too much CAPRELSA.

• •During treatment with CAPRELSA, your healthcare provider should check your blood and heart for side effects. See “What is the most important information I should know about CAPRELSA?”
• •Your healthcare provider should check your blood pressure regularly during your treatment with CAPRELSA.

What should I avoid while taking CAPRELSA?

• •Limit exposure to the sun. CAPRELSA can make your skin sensitive to the sun. While taking CAPRELSA and for 4 months after stopping your CAPRELSA treatment, use sun block and wear clothes that cover your skin, including your head, arms and legs when you go outdoors.
• •Use caution before driving or using machinery. Keep in mind CAPRELSA may make you feel tired, weak, or cause blurred vision.

What are the possible side effects of CAPRELSA?

CAPRELSA may cause serious side effects, including:

• •See “What is the most important information I should know about CAPRELSA?”
• • Serious skin reactions. CAPRELSA can cause a serious skin reaction, called Stevens-Johnson syndrome or other serious skin reactions that may affect any part of your body. These serious skin reactions may be life threatening and you may need to be treated in a hospital. Call your healthcare provider right away if you experience any of these symptoms.
  • oSkin rash or acne
  • oDry skin
  • oItching
  • oBlisters on your skin
  • oBlisters or sores in your mouth
  • oPeeling of your skin
  • oFever
  • oMuscle or joint aches
  • oRedness or swelling of your face, hands, or soles of your feet
• • Breathing problems (interstitial lung disease). CAPRELSA may cause a breathing problem called interstitial lung disease that can lead to death. Tell your healthcare provider right away if you experience sudden or worsening shortness of breath or cough.
• • Stroke. Strokes have been reported in some people who have taken CAPRELSA and in some cases have caused death. Stop taking CAPRELSA and call your healthcare provider right away if you have symptoms of a stroke which may include:
  • onumbness or weakness of the face, arm or leg, especially on one side of the body
  • osudden confusion, trouble speaking or understanding
  • osudden trouble seeing in one or both eyes
  • osudden trouble walking, dizziness, loss of balance or coordination
  • osudden, severe headache
• • Bleeding. Bleeding can happen during your treatment with CAPRELSA. Tell your healthcare provider right away if you have severe bleeding while you are taking CAPRELSA.
• • Heart failure. CAPRELSA can cause heart failure that can lead to death. You may have to stop taking CAPRELSA if you have heart failure. Heart failure may not be reversible after stopping CAPRELSA. Your healthcare provider should monitor you for signs and symptoms of heart failure.
• • Diarrhea. Diarrhea is often a symptom of medullary thyroid cancer. CAPRELSA can also cause diarrhea or make diarrhea worse. Your healthcare provider should check your blood levels to monitor your electrolytes more frequently if you have diarrhea.
• • Thyroid hormones. You can have changes in your thyroid hormone when taking CAPRELSA. Your healthcare provider should monitor your thyroid hormone levels while taking CAPRELSA.
• • High blood pressure (hypertension). If you develop high blood pressure or your high blood pressure gets worse, your healthcare provider may lower your dose of CAPRELSA or tell you to stop taking CAPRELSA until your blood pressure is under control. Your healthcare provider may prescribe another medicine to control your high blood pressure.
• • Reversible Posterior Leukoencephalopathy Syndrome (RPLS). A condition called reversible posterior leukoencephalopathy syndrome can happen while taking CAPRELSA. Call your healthcare provider right away if you have:
  • oheadaches
  • oseizures
  • oconfusion
  • ochanges in vision
  • oproblems thinking

The most common side effects of CAPRELSA include:

• • odiarrhea
  • orash
  • oacne
  • onausea
  • ohigh blood pressure
  • oheadache
  • ofeeling tired
  • oloss of appetite
  • oupper respiratory tract infections
  • ostomach (abdominal) pain

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of CAPRELSA. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store CAPRELSA?

• •Store CAPRELSA tablets at 59°F to 86°F (15°C to 30°C).
• •Safely throw away medicine that is out of date or that you no longer need. Ask your pharmacist how to safely throw away CAPRELSA tablets.

Keep CAPRELSA and all medicines out of the reach of children.

General information about CAPRELSA.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use CAPRELSA for a condition for which it was not prescribed. Do not give CAPRELSA to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes important information about CAPRELSA. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about CAPRELSA that is written for health professionals.

For more information, go to www.caprelsa.com or call 1-800-236-9933.

What are the ingredients in CAPRELSA?

Active ingredient: vandetanib

Inactive ingredients:

• • Tablet core: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, crospovidone, povidone, and magnesium stearate
• • Tablet film-coat: hypromellose 2910, macrogol 300, and titanium dioxide E171

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Distributed by:

AstraZeneca Pharmaceuticals LP

Wilmington, DE 19850

Issued 03/2014

CAPRELSA is a registered trademark of the AstraZeneca group of companies

©AstraZeneca 2013. All Rights Reserved.

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL – 100 mg

NDC 0310-7820-30

30 tablets

Caprelsa®

(vandetanib) tablets

100 mg

Rx only

Dispense the accompanying

Medication Guide to each patient.

AstraZeneca