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SUTENT

 * Generic Name: sunitinib malate
 * Brand Name: Sutent
 * Drug Class: Antineoplastics, VEGF Inhibitor, Antineoplastic Tyrosine Kinase
   Inhibitors

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 9/9/2021

home drugs a-z list sutent (sunitinib malate) drug

   
   
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 * Sutent User Reviews


DRUG SUMMARY

WHAT IS SUTENT?

Sutent (sunitinib malate) is a multi-kinase inhibitor indicated for the
treatment of gastrointestinal stromal tumor after disease progression on, or
intolerance to imatinib mesylate, for advanced renal cell carcinoma, and for
progressive, well-differentiated pancreatic neuroendocrine tumors in patients
with unresectable, locally advanced or metastatic disease. Sutent is available
in generic form.

WHAT ARE SIDE EFFECTS OF SUTENT?

Side effects of Sutent include:

 * unusual or unpleasant taste in the mouth
 * cough
 * nausea
 * vomiting
 * upset stomach
 * constipation
 * dry skin
 * changes in skin or hair color (yellow skin or lighter skin/hair)
 * hair loss
 * joint pain
 * back pain
 * fatigue
 * tiredness
 * weakness
 * fever
 * diarrhea
 * mouth pain/sores
 * abdominal pain
 * rash or other skin changes such as dry or cracked skin
 * blisters or rash on hands or feet
 * loss of appetite
 * pain or swelling in the arms or legs
 * numbness or tingling of the arms or legs
 * shortness of breath
 * bleeding
 * watery eyes
 * swelling around the eyes
 * chest pain
 * general ill feeling, or
 * uneven heart rate.

Tell your doctor if you have serious side effects of Sutent including:

 * headache,
 * easy bruising or bleeding,
 * swelling ankles or feet,
 * unusual weight changes,
 * cold or heat intolerance,
 * unusual tiredness,
 * black or bloody stools,
 * vomit that looks like coffee grounds,
 * coughing up blood,
 * slow wound healing,
 * jaw pain,
 * toe/joint/back pain,
 * painful urination,
 * cloudy/pink/bloody urine,
 * changes in the amount of urine,
 * muscle weakness/cramping/twitching,
 * signs of low blood sugar (such as hunger, shakiness, fast heartbeat,
   sweating),
 * mental/mood changes (such as decreased alertness, irritability, nervousness),
   or
 * vision changes (such as decreased vision).

DOSAGE FOR SUTENT

The recommended dose of Sutent (strengths available are 12.5, 25 and 50mg
tablets). Sutent may be taken without food. Dose modification depends on the
type of cancer treated and is determined by the treating doctor. Severe side
effects include hepatotoxicity.

WHAT DRUGS, SUBSTANCES, OR SUPPLEMENTS INTERACT WITH SUTENT?

Sutent may interact with dexamethasone, imatinib, isoniazid, nefazodone, St.
John's wort, antibiotics, antifungals, barbiturates, heart or blood pressure
medications, HIV/AIDS medicines, medicines to treat narcolepsy, medications to
treat osteoporosis or Paget's disease of bone, seizure medications, or
grapefruit and grapefruit juice. Tell your doctor all medications and
supplements you use.

SUTENT DURING PREGNANCY AND BREASTFEEDING

Sutent is not recommended for use during pregnancy; it may harm a fetus. It is
unknown if Sutent passes into breast milk. Because of the possible risk to the
infant, breastfeeding while using Sutent is not recommended

ADDITIONAL INFORMATION

Our Sutent (sunitinib malate) Side Effects Drug Center provides a comprehensive
view of available drug information on the potential side effects when taking
this medication.


FDA DRUG INFORMATION

 * Drug Description
 * Indications & Dosage
 * Side Effects
 * Drug Interactions
 * Warnings & Precautions
 * Overdose & Contraindications
 * Clinical Pharmacology
 * Medication Guide

WARNING

HEPATOTOXICITY

Hepatotoxicity has been observed in clinical trials and postmarketing
experience. Hepatotoxicity may be severe, and in some cases, fatal. Monitor
hepatic function and interrupt, reduce, or discontinue dosing as recommended
[see WARNINGS AND PRECAUTIONS].


DESCRIPTION FOR SUTENT

SUTENT, an oral multi-kinase inhibitor, is the malate salt of sunitinib.
Sunitinib malate is described chemically as Butanedioic acid, hydroxy-, (2S)-,
compound with N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2oxo-
3H-indol-3-ylidine)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (1:1). The
molecular formula is C22H27FN4O2 • C4H6O5 and the molecular weight is 532.6
Daltons.

The chemical structure of sunitinib malate is:







Sunitinib malate is a yellow to orange powder with a pKa of 8.95. The solubility
of sunitinib malate in aqueous media over the range pH 1.2 to pH 6.8 is in
excess of 25 mg/mL. The log of the distribution coefficient (octanol/water) at
pH 7 is 5.2.

SUTENT (sunitinib malate) capsules are supplied as printed hard shell capsules
containing sunitinib malate equivalent to 12.5 mg, 25 mg, 37.5 mg or 50 mg of
sunitinib together with mannitol, croscarmellose sodium, povidone (K-25) and
magnesium stearate as inactive ingredients.

The orange gelatin capsule shells contain titanium dioxide and red iron oxide.
The caramel gelatin capsule shells contain titanium dioxide, red iron oxide,
yellow iron oxide, and black iron oxide. The yellow gelatin capsule shells
contain titanium dioxide and yellow iron oxide. The white printing ink contains
shellac, propylene glycol, sodium hydroxide, povidone, and titanium dioxide. The
black printing ink contains shellac, propylene glycol, potassium hydroxide, and
black iron oxide.




USES FOR SUTENT

GASTROINTESTINAL STROMAL TUMOR

SUTENT is indicated for the treatment of adult patients with gastrointestinal
stromal tumor (GIST) after disease progression on or intolerance to imatinib
mesylate.

ADVANCED RENAL CELL CARCINOMA

SUTENT is indicated for the treatment of adult patients with advanced renal cell
carcinoma (RCC).

ADJUVANT TREATMENT OF RENAL CELL CARCINOMA

SUTENT is indicated for the adjuvant treatment of adult patients at high risk of
recurrent RCC following nephrectomy.

ADVANCED PANCREATIC NEUROENDOCRINE TUMORS

SUTENT is indicated for the treatment of progressive, well-differentiated
pancreatic neuroendocrine tumors (pNET) in adult patients with unresectable
locally advanced or metastatic disease.


DOSAGE FOR SUTENT

RECOMMENDED DOSAGE FOR GIST AND ADVANCED RCC

The recommended dosage of SUTENT for gastrointestinal stromal tumor (GIST) and
advanced renal cell carcinoma (RCC) is 50 mg taken orally once daily, on a
schedule of 4 weeks on treatment followed by 2 weeks off (Schedule 4/2) until
disease progression or unacceptable toxicity. SUTENT may be taken with or
without food.

RECOMMENDED DOSAGE FOR ADJUVANT TREATMENT OF RCC

The recommended dosage of SUTENT for the adjuvant treatment of RCC is 50 mg
taken orally once daily, on a schedule of 4 weeks on treatment followed by 2
weeks off (Schedule 4/2), for nine 6-week cycles. SUTENT may be taken with or
without food.

RECOMMENDED DOSAGE FOR PNET

The recommended dosage of SUTENT for pancreatic neuroendocrine tumors (pNET) is
37.5 mg taken orally once daily until disease progression or unacceptable
toxicity. SUTENT may be taken with or without food.

DOSAGE MODIFICATIONS FOR ADVERSE REACTIONS

To manage adverse reactions, the recommended dosage modifications are provided
in Table 1. Table 2 provides the recommended dosage reductions of SUTENT for
adverse reactions.

Table 1: Recommended Dosage Reductions of SUTENT for Adverse Reactions

Indications GIST RCC pNET Advanced RCC Adjuvant RCC First dose reduction 37.5 mg
once daily 37.5 mg once daily 37.5 mg once daily 25 mg once daily Second dose
reduction 25 mg once daily 25 mg once daily NA NA



Table 2: Recommended Dosage Modifications for SUTENT for Adverse Reactions

Adverse Reaction Severity Dosage Modifications for SUTENT Hepatotoxicity [see
WARNINGS AND PRECAUTIONS] Grade 3
 * Withhold until resolution to Grade 0 to 1 or baseline.
 * Resume at a reduced dose.
 * For recurring Grade 3 permanently discontinue.

Grade 4
 * Permanently discontinue.

Cardiovascular events [see WARNINGS AND PRECAUTIONS] Asymptomatic cardiomyopathy
(left ventricular ejection fraction greater than 20% but less than 50% below
baseline or below the lower limit of normal if baseline was not obtained)
 * Withhold until resolution to Grade 0 to 1 or baseline.
 * Resume at reduced dose.

Clinically manifested congestive heart failure (CHF)
 * Permanently discontinue.

Hypertension [see WARNINGS AND PRECAUTIONS] Grade 3
 * Withhold until resolution to Grade 0 to 1 or baseline.
 * Resume at a reduced dose.

Grade 4
 * Permanently discontinue.

Hemorrhagic events [see WARNINGS AND PRECAUTIONS] Grade 3 or 4
 * Withhold until resolution to Grade 0 to 1 or baseline.
 * Either resume at a reduced dose or discontinue depending on the severity and
   persistence of adverse reaction.

Thrombotic microangiopathy [see WARNINGS AND PRECAUTIONS] Any Grade
 * Permanently discontinue.

Proteinuria or Nephrotic syndrome [see WARNINGS AND PRECAUTIONS] 3 or more grams
proteinuria in 24 hours in the absence of nephrotic syndrome
 * Withhold until resolution to Grade 0 to 1 or baseline.
 * Resume at a reduced dose

Nephrotic syndrome or recurrent proteinuria of 3 or more grams per 24 hours
despite dose reductions
 * Permanently discontinue

Dermatological toxicities Erythema multiforme (EM), Stevens-Johnson syndrome
(SJS), toxic epidermal necrolysis (TEN), Necrotizing fasciitis [see WARNINGS AND
PRECAUTIONS] Any Grade
 * Permanently discontinue.

Reversible posterior leukoencephalopathy syndrome [see WARNINGS AND PRECAUTIONS]
Any Grade
 * Permanently discontinue.

Osteonecrosis of the jaw [see WARNINGS AND PRECAUTIONS] Any Grade
 * The safety of resumption of SUTENT after osteonecrosis has not been
   established.
 * Either resume at a reduced dose or discontinue depending on the severity and
   persistence of the adverse reaction.

Impaired wound healing [see WARNINGS AND PRECAUTIONS] Any Grade
 * The safety of resumption of SUTENT after resolution of wound healing has not
   been established.
 * Either resume at a reduced dose or discontinue depending on the severity and
   persistence of the adverse reaction.



DOSAGE MODIFICATION FOR DRUG INTERACTIONS

STRONG CYP3A4 INHIBITORS

Select an alternate concomitant medication with no or minimal enzyme inhibition
potential. If coadministration of SUTENT with a strong CYP3A4 inhibitor cannot
be avoided, consider a dose reduction for SUTENT to a minimum dosage as follows
[see DRUG INTERACTIONS]:

 * GIST and RCC: 37.5 mg orally once daily, on a schedule of 4 weeks on
   treatment followed by 2 weeks off (Schedule 4/2)
 * pNET: 25 mg orally once daily

STRONG CYP3A4 INDUCERS

Select an alternate concomitant medication with no or minimal enzyme induction
potential. If coadministration of SUTENT with a strong CYP3A4 inducer cannot be
avoided, consider a dose increase for SUTENT to a maximum dosage as follows:

 * GIST and RCC: 87.5 mg orally once daily, on a schedule of 4 weeks on
   treatment followed by 2 weeks off (Schedule 4/2)
 * pNET: 62.5 mg orally once daily

If the dose of SUTENT is increased, monitor patients carefully for adverse
reactions [see DRUG INTERACTIONS].

DOSAGE MODIFICATION FOR END-STAGE RENAL DISEASE PATIENTS ON HEMODIALYSIS

No starting dose adjustment is required in patients with end-stage renal disease
(ESRD) on hemodialysis. However, given the decreased exposure compared to
patients with normal renal function, subsequent doses may be increased gradually
up to 2-fold based on safety and tolerability [see CLINICAL PHARMACOLOGY].


HOW SUPPLIED

DOSAGE FORMS AND STRENGTHS

Capsules, hard gelatin:

 * 12.5 mg sunitinib: orange cap and orange body, printed with white ink
   “Pfizer” on the cap and “STN 12.5 mg” on the body.
 * 25 mg sunitinib: caramel cap and orange body, printed with white ink “Pfizer”
   on the cap and “STN 25 mg” on the body.
 * 37.5 mg sunitinib: yellow cap and yellow body, printed with black ink
   “Pfizer” on the cap and “STN 37.5 mg” on the body.
 * 50 mg sunitinib: caramel top and caramel body, printed with white ink
   “Pfizer” on the cap and “STN 50 mg” on the body.

STORAGE AND HANDLING

SUTENT 12.5 mg capsules are supplied as hard gelatin capsule with orange cap and
orange body, printed with white ink “Pfizer” on the cap, “STN 12.5 mg” on the
body:

Bottles of 28 capsules: NDC 0069-0550-38

SUTENT 25 mg capsules are supplied as hard gelatin capsule with caramel cap and
orange body, printed with white ink “Pfizer” on the cap, “STN 25 mg” on the
body:

Bottles of 28 capsules: NDC 0069-0770-38

SUTENT 37.5 mg capsules are supplied as hard gelatin capsule with yellow cap and
yellow body, printed with black ink “Pfizer” on the cap, “STN 37.5 mg” on the
body:

Bottles of 28 capsules: NDC 0069-0830-38

SUTENT 50 mg capsules are supplied as hard gelatin capsule with caramel cap and
caramel body, printed with white ink “Pfizer” on the cap, “STN 50 mg” on the
body:

Bottles of 28 capsules: NDC 0069-0980-38

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F
to 86°F) [see USP Controlled Room Temperature].

Distributed by: Pfizer Labs, Division of Pfizer Inc., IN, IN 10017. Revised: Aug
2021


SIDE EFFECTS FOR SUTENT

The following clinically significant adverse reactions are described elsewhere
in the labeling.

 * Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
 * Cardiovascular Events [see WARNINGS AND PRECAUTIONS]
 * QT Interval Prolongation and Torsade de Pointes [see WARNINGS AND
   PRECAUTIONS]
 * Hypertension [see WARNINGS AND PRECAUTIONS]
 * Hemorrhagic Events [see WARNINGS AND PRECAUTIONS]
 * Tumor Lysis Syndrome [see WARNINGS AND PRECAUTIONS]
 * Thrombotic Microangiopathy [see WARNINGS AND PRECAUTIONS]
 * Proteinuria [see WARNINGS AND PRECAUTIONS]
 * Dermatologic Toxicities [see WARNINGS AND PRECAUTIONS]
 * Reversible Posterior Leukoencephalopathy Syndrome [see WARNINGS AND
   PRECAUTIONS]
 * Thyroid Dysfunction [see WARNINGS AND PRECAUTIONS]
 * Hypoglycemia [see WARNINGS AND PRECAUTIONS]
 * Osteonecrosis of the Jaw [see WARNINGS AND PRECAUTIONS]
 * Impaired Wound Healing [see WARNINGS AND PRECAUTIONS]

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.

The pooled safety population described in the Warnings and Precautions reflect
exposure to SUTENT in 7527 patients with GIST, RCC (advanced and adjuvant), or
pNET. In this pooled safety population, the most common adverse reactions (≥25%)
were fatigue/asthenia, diarrhea, mucositis/stomatitis, nausea, decreased
appetite/anorexia, vomiting, abdominal pain, hand-foot syndrome, hypertension,
bleeding events, dysgeusia/altered taste, dyspepsia, and thrombocytopenia.

GASTROINTESTINAL STROMAL TUMOR

The safety of SUTENT was evaluated in Study 1, a randomized, double-blind,
placebo-controlled trial in which previously treated patients with GIST received
SUTENT 50 mg daily on Schedule 4/2 (n=202) or placebo (n=102). Median duration
of blinded study treatment was 2 cycles for patients on SUTENT (mean: 3.0;
range: 1-9) and 1 cycle (mean; 1.8; range: 1-6) for patients on placebo at the
time of the interim analysis.

Permanent discontinuation due to an adverse reaction occurred in 7% of patients
in the SUTENT arm. Dose reductions occurred in 11% and dose interruptions
occurred in 29% of patients who received SUTENT.

Table 3 summarizes the adverse reactions for Study 1.

Table 3: Adverse Reactions Reported in ≥10% of GIST Patients Who Received SUTENT
in the Double-Blind Treatment Phase and More Commonly Than in Patients Given
Placebo* in Study 1

Adverse Reaction GIST SUTENT
(N=202) Placebo
(N=102) All Grades % Grade 3-4 % All Grades % Grade 3-4 % Any Adverse Reaction
94 56 97 51 Gastrointestinal Diarrhea 40 4 27 0 Mucositis/stomatitis 29 1 18 2
Constipation 20 0 14 2 Metabolism/Nutrition Anorexiaa 33 1 29 5 Asthenia 22 5 11
3 Dermatology Skin discoloration 30 0 23 0 Rash 14 1 9 0 Hand-foot syndrome 14 4
10 3 Neurology Altered taste 21 0 12 0 Cardiac Hypertension 15 4 11 0
Musculoskeletal Myalgia/limb pain 14 1 9 1 * Common Terminology Criteria for
Adverse Events (CTCAE), version 3.0. Abbreviations: GIST=gastrointestinal
stromal tumor; N=number of patients.
a Includes decreased appetite.



Other clinically relevant adverse reactions included oral pain other than
mucositis/stomatitis in 6%; hair color changes in 7%; alopecia in 5% of patients
who received SUTENT.

Table 4 summarizes the laboratory abnormalities in Study 1.

Table 4: Laboratory Abnormalities Reported in ≥10% of GIST Patients Who Received
SUTENT or Placebo in the Double-Blind Treatment Phase* in Study 1

Laboratory Abnormality GIST SUTENT
(N=202) Placebo
(N=102) All Grades*% Grade 3-4*,a% All Grades*% Grade 3-4*,b% Any Laboratory
Abnormality 34 22 Hematology Neutrophils decreased 53 10 4 0 Lymphocytes
decreased 38 0 16 0 Platelets decreased 38 5 4 0 Hemoglobin decreased 26 3 22 2
Gastrointestinal AST/ALT increased 39 2 23 1 Lipase increased 25 10 17 7
Alkaline phosphatase increased 24 4 21 4 Amylase increased 17 5 12 3 Total
bilirubin increased 16 1 8 0 Indirect bilirubin increased 10 0 4 0
Renal/Metabolic Creatinine increased 12 1 7 0 Potassium decreased 12 1 4 0
Sodium increased 10 0 4 1 Cardiac Decreased LVEF 11 1 3 0 * Common Terminology
Criteria for Adverse Events (CTCAE), version 3.0. Abbreviations: ALT=alanine
aminotransferase; AST=aspartate aminotransferase; GIST=gastrointestinal stromal
tumor; LVEF=left ventricular ejection fraction; N=number of patients.
a Grade 4 laboratory abnormalities in patients on SUTENT included alkaline
phosphatase (1%), lipase (2%), creatinine (1%), potassium decreased (1%),
neutrophils (2%), hemoglobin (2%), and platelets (1%).
b Grade 4 laboratory abnormalities in patients on placebo included amylase (1%),
lipase (1%), and hemoglobin (2%).



After an interim analysis, the study was unblinded and patients on the placebo
arm were given the opportunity to receive open-label SUTENT [see Clinical
Studies]. For 241 patients randomized to the SUTENT arm, including 139 who
received SUTENT in both the double-blind and open-label phases, the median
duration of SUTENT treatment was 6 cycles (mean: 8.5; range: 1-44). For the 255
patients who ultimately received open-label SUTENT treatment, median duration of
treatment was 6 cycles (mean: 7.8; range: 1-37) from the time of the unblinding.

Permanent discontinuation due to an adverse reaction occurred in 20% of patients
who received SUTENT. Dosage interruption occurred in 46% and dose reduction
occurred in 28% of patients who received SUTENT.

The most common Grade 3 or 4 adverse reactions in patients who received SUTENT
in the open-label phase were fatigue (10%), hypertension (8%), asthenia (5%),
diarrhea (5%), hand-foot syndrome (5%), nausea (4%), abdominal pain (3%),
anorexia (3%), mucositis (2%), vomiting (2%), and hypothyroidism (2%).

ADVANCED RENAL CELL CARCINOMA

The safety of SUTENT was evaluated in Study 3, a double-blind, active-controlled
trial in which previously untreated patients with locally advanced or metastatic
RCC received SUTENT 50 mg daily on Schedule 4/2 (n=375) or interferon alfa 9
million International Units (MIU) (n=360). The median duration of treatment was
11.1 months (range: 0.4 to 46.1) for SUTENT treatment and 4.1 months (range: 0.1
to 45.6) for interferon alfa treatment.

Permanent discontinuation due to an adverse reaction occurred in 20% of patients
in the SUTENT arm. Dose interruptions occurred in 54% and dose reductions
occurred in 52% of patients who received SUTENT.

Table 5 summarizes the adverse reactions for Study 3.

Table 5: Adverse Reactions Reported in ≥10% of Patients With RCC Who Received
SUTENT or Interferon Alfa* in Study 3

Adverse Reaction Treatment-Naive RCC SUTENT
(N=375) Interferon Alfa
(N=360) All Grades % Grade 3-4a % All Grades % Grade 3-4b % Any Adverse Reaction
99 77 99 55 Gastrointestinal Diarrhea 66 10 21 <1 Nausea 58 6 41 2
Mucositis/stomatitis 47 3 5 <1 Vomiting 39 5 17 1 Dyspepsia 34 2 4 0 Abdominal
painc 30 5 12 1 Constipation 23 1 14 <1 Dry mouth 13 0 7 <1 Oral pain 14 <1 1 0
Flatulence 14 0 2 0 GERD/reflux esophagitis 12 <1 1 0 Glossodynia 11 0 1 0
Hemorrhoids 10 0 2 0 Constitutional Fatigue 62 15 56 15 Asthenia 26 11 22 6
Fever 22 1 37 <1 Weight decreased 16 <1 17 1 Chills 14 1 31 0 Chest Pain 13 2 7
1 Influenza like illness 5 0 15 <1 Metabolism/Nutrition Anorexiad 48 3 42 2
Neurology Altered tastee 47 <1 15 0 Headache 23 1 19 0 Dizziness 11 <1 14 1
Hemorrhage/Bleeding Bleeding, all sites 37 4f 10 1 Cardiac Hypertension 34 13 4
<1 Edema peripheral 24 2 5 1 Ejection fraction decreased 16 3 5 2 Dermatology
Rash 29 2 11 <1 Hand-foot syndrome 29 8 1 0 Skin discoloration/yellow skin 25 <1
0 0 Dry skin 23 <1 7 0 Hair color changes 20 0 <1 0 Alopecia 14 0 9 0 Erythema
12 <1 1 0 Pruritus 12 <1 7 <1 Musculoskeletal Pain in extremity/limb discomfort
40 5 30 2 Arthralgia 30 3 19 1 Back pain 28 5 14 2 Respiratory Cough 27 1 14 <1
Dyspnea 26 6 20 4 Nasopharyngitis 14 0 2 0 Oropharyngeal pain 14 <1 2 0 Upper
respiratory tract infection 11 <1 2 0 Endocrine Hypothyroidism 16 2 1 0
Psychiatric Insomnia 15 <1 10 0 Depressiong 11 0 14 1 * Common Terminology
Criteria for Adverse Events (CTCAE), version 3.0. Abbreviations: ARs=adverse
reactions; N=number of patients; RCC=renal cell carcinoma.
a Grade 4 ARs in patients on SUTENT included back pain (1%), arthralgia (<1%),
dyspnea (<1%), asthenia (<1%), fatigue (<1%), limb pain (<1%), and rash (<1%).
b Grade 4 ARs in patients on interferon alfa included dyspnea (1%), fatigue
(1%), abdominal pain (<1%), and depression (<1%).
CIncludes flank pain.
d Includes decreased appetite.
e Includes ageusia, hypogeusia, and dysgeusia.
f Includes 1 patient with Grade 5 gastric hemorrhage.
g Includes depressed mood.



Table 6 summarizes the laboratory abnormalities in Study 3.

Table 6: Laboratory Abnormalities Reported in ≥10% of RCC Patients Who Received
SUTENT or Interferon Alfa in Study 3

Laboratory Abnormality Treatment-Naive RCC SUTENT (N=375) Interferon Alfa
(N=360) All Grades* % Grade 3-4*,a % All Grades* % Grade 3-4*,b % Hematology
Hemoglobin decreased 79 8 69 5 Neutrophils decreased 77 17 49 9 Platelets
decreased 68 9 24 1 Lymphocytes decreased 68 18 68 26 Renal/Metabolic Creatinine
increased 70 <1 51 <1 Creatine kinase increased 49 2 11 1 Uric acid increased 46
14 33 8 Calcium decreased 42 1 40 1 Phosphorus decreased 31 6 24 6 Albumin
decreased 28 1 20 0 Glucose increased 23 6 15 6 Sodium decreased 20 8 15 4
Glucose decreased 17 0 12 <1 Potassium increased 16 3 17 4 Calcium increased 13
<1 10 1 Potassium decreased 13 1 2 <1 Sodium increased 13 0 10 0
Gastrointestinal AST increased 56 2 38 2 Lipase increased 56 18 46 8 ALT
increased 51 3 40 2 Alkaline phosphatase increased 46 2 37 2 Amylase increased
35 6 32 3 Total bilirubin increased 20 1 2 0 Indirect bilirubin increased 13 1 1
0 * Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.
Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase;
N=number of patients; RCC=renal cell carcinoma.
a Grade 4 laboratory abnormalities in patients on SUTENT included uric acid
(14%), lipase (3%), neutrophils (2%), lymphocytes (2%), hemoglobin (2%),
platelets (1%), amylase (1%), ALT (<1%), creatine kinase (<1%), creatinine
(<1%), glucose increased (<1%), calcium decreased (<1%), phosphorous (<1%),
potassium increased (<1%), and sodium decreased (<1%).
b Grade 4 laboratory abnormalities in patients on interferon alfa included uric
acid (8%), lymphocytes (2%), lipase (1%), neutrophils (1%), amylase (<1%),
calcium increased (<1%), glucose decreased (<1%), potassium increased (<1%), and
hemoglobin (<1%).



LONG-TERM SAFETY IN RCC

The long-term safety of SUTENT in patients with metastatic RCC was analyzed
across 9 completed clinical studies conducted in the first-line,
bevacizumab-refractory, and cytokine-refractory treatment settings. The analysis
included 5739 patients, of whom 807 (14%) were treated for at least 2 years and
365 (6%) for at least 3 years. Prolonged treatment with SUTENT did not appear to
be associated with new types of adverse reactions. There appeared to be no
increase in the yearly incidence of adverse reactions at later time points.
Hypothyroidism increased during the second year of treatment with new cases
reported up to year 4.

ADJUVANT TREATMENT OF RCC

The safety of SUTENT was evaluated in S-TRAC, a randomized, double-blind,
placebo-controlled trial in which patients who had undergone nephrectomy for RCC
received SUTENT 50 mg daily on Schedule 4/2 (n=306) or placebo (n=304). The
median duration of treatment was 12.4 months (range: 0.13 to 14.9) for SUTENT
and 12.4 months (range: 0.03 to 13.7) for placebo.

Permanent discontinuation due to an adverse reaction occurred in 28% of patients
in the SUTENT arm. Adverse reactions leading to permanent discontinuation in >2%
of patients include hand-foot syndrome and fatigue/asthenia. Dosing
interruptions occurred in 54% and dose reductions occurred in 46% of patients
who received SUTENT.

Table 7 summarizes the adverse reactions in S-TRAC.

Table 7: Adverse Reactions Reported in ≥10% of Patients With RCC Who Received
SUTENT and More Commonly Than in Patients Given Placebo* in S-TRAC

Adverse Reaction Adjuvant Treatment of RCC SUTENT
(N=306) Placebo
(N=304) All Grades % Grade 3-4 % All Grades % Grade 3-4 % Any Adverse Reaction
99 60 88 15 Gastrointestinal Mucositis/Stomatitisa 61 6 15 0 Diarrhea 57 4 22 <1
Nausea 34 2 15 0 Dyspepsia 27 1 7 0 Abdominal painb 25 2 9 <1 Vomiting 19 2 7 0
Constipation 12 0 11 0 Constitutional Fatigue/Asthenia 57 8 34 2 Localized
edemac 18 <1 <1 0 Pyrexia 12 <1 6 0 Dermatology Hand-foot syndrome 50 16 10 <1
Rashd 24 2 12 0 Hair color changes 22 0 2 0 Skin discoloration/Yellow skin 18 0
1 0 Dry skin 14 0 6 0 Cardiac Hypertensione 39 8 14 1 Edema/Peripheral edema 10
<1 7 0 Neurology Altered tastef 38 <1 6 0 Headache 19 <1 12 0 Endocrine
Hypothyroidism/TSH increased 24 <1 4 0 Hemorrhage/Bleeding Bleeding events, all
sitesg 24 <1 5 <1 Metabolism/Nutrition Anorexia/Decreased appetite 19 <1 5 0
Musculoskeletal Pain in extremity 15 <1 7 0 Arthralgia 11 <1 10 0 * Common
Terminology Criteria for Adverse Events (CTCAE), version 3.0. Abbreviations:
ARs=adverse reactions; N=number of patients; RCC=renal cell carcinoma.
a Includes mucosal inflammation, stomatitis aphthous ulcer, mouth ulceration,
tongue ulceration, oropharyngeal pain, and oral pain.
b Includes abdominal pain, abdominal pain lower, and abdominal pain upper.
cIncludes edema localized, face edema, eyelid edema, periorbital edema, swelling
face, and eye edema.
d Includes dermatitis, dermatitis psoriasiform, exfoliative rash, genital rash,
rash, rash erythematous, rash follicular, rash generalized, rash macular, rash
maculopapular, rash papular, and rash pruritic.
e Includes hypertension, blood pressure increased, blood pressure systolic
increased, blood pressure diastolic increased, and  hypertensive crisis.
f Includes ageusia, hypogeusia, and dysgeusia.
g Includes epistaxis, gingival bleeding, rectal hemorrhage, hemoptysis, anal
hemorrhage, upper gastrointestinal hemorrhage, and  hematuria.



Grade 4 adverse reactions in patients on SUTENT included hand-foot syndrome
(1%), fatigue (<1%), abdominal pain (< 1%), stomatitis (<1%), and pyrexia (<
1%).

Grade 3-4 laboratory abnormalities that occurred in ≥2% of patients receiving
SUTENT include neutropenia (13%), thrombocytopenia (5%), leukopenia (3%),
lymphopenia (3%), elevated alanine aminotransferase (2%), elevated aspartate
aminotransferase (2%), hyperglycemia (2%), and hyperkalemia (2%).

ADVANCED PANCREATIC NEUROENDOCRINE TUMORS

The safety of SUTENT was evaluated in Study 6, a randomized, double-blind,
placebo-controlled trial in which patients with progressive pNET received SUTENT
37.5 mg once daily (n=83) or placebo (n=82). The median number of days on
treatment was 139 days (range: 13-532 days) for patients on SUTENT and 113 days
(range: 1-614 days) for patients on placebo. Nineteen patients (23%) on SUTENT
and 4 patients (5%) on placebo were on study for >1 year.

Permanent discontinuation due to an adverse reaction occurred in 22% in the
SUTENT arm. Dose interruptions occurred in 30% and dose reductions occurred in
31% of patients who received SUTENT.

Table 8 summarizes the adverse reactions in Study 6.

Table 8: Adverse Reactions Reported in ≥10% of Patients With pNET Who Received
SUTENT and More Commonly Than in Patients Given Placebo* in Study 6

Adverse Reaction pNET SUTENT
(N=83) Placebo
(N=82) All Grades % Grade 3-4a % All Grades % Grade 3-4 % Any Adverse Reaction
99 54 95 50 Gastrointestinal Diarrhea 59 5 39 2 Stomatitis/oral syndromesb 48 6
18 0 Nausea 45 1 29 1 Abdominal painc 39 5 34 10 Vomiting 34 0 31 2 Dyspepsia 15
0 6 0 Constitutional Asthenia 34 5 27 4 Fatigue 33 5 27 9 Weight decreased 16 1
11 0 Dermatology Hair color changes 29 1 1 0 Hand-foot syndrome 23 6 2 0 Rash 18
0 5 0 Dry skin 15 0 11 0 Cardiac Hypertension 27 10 5 1 Hemorrhage/Bleeding
Bleeding eventsd 22 0 10 4 Epistaxis 21 1 5 0 Neurology Dysgeusia 21 0 5 0
Headache 18 0 13 1 Psychiatric Insomnia 18 0 12 0 Musculoskeletal Arthralgia 15
0 6 0 * Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.
Abbreviations: N=number of patients; pNET=pancreatic neuroendocrine tumors.
a Grade 4 adverse reactions in patients on SUTENT included fatigue (1%).
b Includes aphthous stomatitis, gingival pain, gingivitis, glossitis,
glossodynia, mouth ulceration, oral discomfort, oral pain, tongue ulceration,
mucosal dryness, mucosal inflammation, and dry mouth.
cIncludes abdominal discomfort, abdominal pain, and abdominal pain upper.
d Includes hematemesis, hematochezia, hematoma, hemoptysis, hemorrhage, melena,
and metrorrhagia.



Table 9 summarizes the laboratory abnormalities in Study 6.

Table 9: Laboratory Abnormalities Reported in ≥10% of Patients With pNET Who
Received SUTENT in Study 6

Laboratory Abnormality pNET SUTENT Placebo All Grades*% Grade 3-4*,a % All
Grades* % Grade 3-4*,b % Gastrointestinal AST increased 72 5 70 3 Alkaline
phosphatase increased 63 10 70 11 ALT increased 61 4 55 3 Total bilirubin
increased 37 1 28 4 Amylase increased 20 4 10 1 Lipase increased 17 5 11 4
Hematology Neutrophils decreased 71 16 16 0 Hemoglobin decreased 65 0 55 1
Platelets decreased 60 5 15 0 Lymphocytes decreased 56 7 35 4 Renal/Metabolic
Glucose increased 71 12 78 18 Albumin decreased 41 1 37 1 Phosphorus decreased
36 7 22 5 Calcium decreased 34 0 19 0 Sodium decreased 29 2 34 3 Creatinine
increased 27 5 28 5 Glucose decreased 22 2 15 4 Potassium decreased 21 4 14 0
Magnesium decreased 19 0 10 0 Potassium increased 18 1 11 1 * The denominator
used to calculate the rate varied from 52 to 82 for SUTENT and 39 to 80 for
Placebo based on the number of patients with a baseline value and at least one
post-treatment value. Common Terminology Criteria for Adverse Events (CTCAE),
version 3.0.
Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase;
N=number of patients; pNET=pancreatic neuroendocrine tumors.
a Grade 4 laboratory abnormalities in patients on SUTENT included creatinine
(4%), lipase (4%), glucose decreased (2%), glucose increased (2%), neutrophils
(2%), ALT (1%), AST (1%), platelets (1%), potassium increased (1%), and total
bilirubin (1%).
b Grade 4 laboratory abnormalities in patients on placebo included creatinine
(3%), alkaline phosphatase (1%), glucose increased (1%), and lipase (1%).



VENOUS THROMBOEMBOLIC EVENTS

In pooled safety population, 3.5% of patients experienced a venous
thromboembolic event, including Grade 3-4 in 2.2% of patients.

PANCREATIC FUNCTION

Pancreatitis was observed in 1 patient (1%) in the pNET study, 5 patients (1%)
in the treatment-naive RCC study, and 1 patient (<1%) in the adjuvant treatment
for RCC study on SUTENT.

POSTMARKETING EXPERIENCE

The following adverse reactions have been identified during postapproval use of
SUTENT. Because these reactions are reported voluntarily from a population of
uncertain size, it is not always possible to reliably estimate their frequency
or establish a causal relationship to drug exposure.

 * Blood and lymphatic system disorders: hemorrhage associated with
   thrombocytopenia*.
 * Gastrointestinal disorders: esophagitis.
 * Hepatobiliary disorders: cholecystitis, particularly acalculous
   cholecystitis.
 * Immune system disorders: hypersensitivity reactions, including angioedema.
 * Infections and infestations: serious infection (with or without
   neutropenia)*. The infections most commonly observed with SUTENT include
   respiratory, urinary tract, skin infections, and sepsis/septic shock.
 * Musculoskeletal and connective tissue disorders: fistula formation, sometimes
   associated with tumor necrosis and/or regression*; myopathy and/or
   rhabdomyolysis with or without acute renal failure*.
 * Renal and urinary disorders: renal impairment and/or failure*.
 * Respiratory disorders: pulmonary embolism*, pleural effusion*.
 * Skin and subcutaneous tissue disorders: pyoderma gangrenosum, including
   positive de-challenges.
 * Vascular disorders: arterial (including aortic) aneurysms, dissections*, and
   rupture*; arterial thromboembolic events*. The most frequent events included
   cerebrovascular accident, transient ischemic attack, and cerebral infarction.
 * General disorders and administration site conditions: impaired wound healing.
   *including some fatalities


DRUG INTERACTIONS FOR SUTENT

EFFECT OF OTHER DRUGS ON SUTENT

STRONG CYP3A4 INHIBITORS

Co-administration with strong CYP3A4 inhibitors may increase sunitinib plasma
concentrations [see CLINICAL PHARMACOLOGY]. Select an alternate concomitant
medication with no or minimal enzyme inhibition potential. Consider a dose
reduction for SUTENT when it is co-administered with strong CYP3A4 inhibitors
[see DOSAGE AND ADMINISTRATION].

STRONG CYP3A4 INDUCERS

Co-administration with strong CYP3A4 inducers may decrease sunitinib plasma
concentrations [see CLINICAL PHARMACOLOGY]. Select an alternate concomitant
medication with no or minimal enzyme induction potential. Consider a dose
increase for SUTENT when it must be co-administered with CYP3A4 inducers [see
DOSAGE AND ADMINISTRATION].

DRUGS THAT PROLONG QT INTERVAL

SUTENT is associated with QTc interval prolongation [see WARNINGS AND
PRECAUTIONS, CLINICAL PHARMACOLOGY]. Monitor the QT interval with ECGs more
frequently in patients who require treatment with concomitant medications known
to prolong the QT interval.


WARNINGS FOR SUTENT

Included as part of the PRECAUTIONS section.


PRECAUTIONS FOR SUTENT

HEPATOTOXICITY

SUTENT can cause severe hepatotoxicity, resulting in liver failure or death. In
the pooled safety population, liver failure occurred in <1% of patients in
clinical trials. Liver failure include jaundiced, elevated transaminases and/or
hyperbilirubinemia in conjunction with encephalopathy, coagulopathy, and/or
renal failure.

Monitor liver function tests (alanine aminotransferase [ALT], aspartate
aminotransferase [AST], and bilirubin) at baseline, during each cycle, and as
clinically indicated. Interrupt SUTENT for Grade 3 hepatotoxicity until
resolution to Grade ≤1 or baseline, then resume SUTENT at a reduced dose.

Discontinue SUTENT in patients with Grade 4 hepatotoxicity, in patients without
resolution of Grade 3 hepatotoxicity, in patients who subsequently experience
severe changes in liver function tests and in patients who have other signs and
symptoms of liver failure. Safety in patients with ALT or AST >2.5 x upper limit
of normal (ULN) or with >5 x ULN and liver metastases has not been established.

CARDIOVASCULAR EVENTS

Cardiovascular events, including heart failure, cardiomyopathy, myocardial
ischemia, and myocardial infarction, some of which were fatal, have been
reported.

In pooled safety population, 3% of patients experienced heart failure; 71% of
the patients with heart failure were reported as recovered. Fatal cardiac
failure was reported in <1% of patients.

In the adjuvant treatment of RCC study, 11 patients experienced Grade 2
decreased ejection fraction (left ventricular ejection fraction [LVEF] 40% to
50% and a 10% to 19% decrease from baseline). In 3 of these 11 patients, the
ejection fractions arm did not return to ≥50% or baseline by the time of last
measurement. No patients who received SUTENT were diagnosed with CHF.

Patients who presented with cardiac events within 12 months prior to SUTENT
administration, such as myocardial infarction (including severe/unstable
angina), coronary/peripheral artery bypass graft, symptomatic CHF,
cerebrovascular accident or transient ischemic attack, or pulmonary embolism
were excluded from SUTENT clinical studies. Patients with prior anthracycline
use or cardiac radiation were also excluded from some studies. It is unknown
whether patients with these concomitant conditions may be at a higher risk of
developing left ventricular dysfunction.

Consider monitoring LVEF at baseline and periodically as clinically indicated.
Carefully monitor patients for clinical signs and symptoms of congestive heart
failure (CHF). Discontinue SUTENT in patients who experience clinical
manifestations of CHF. Interrupt SUTENT and/or reduce the dose in patients
without clinical evidence of CHF who have an ejection fraction of greater than
20% but less than 50% below baseline or below the lower limit of normal if
baseline ejection fraction was not obtained.

QT INTERVAL PROLONGATION AND TORSADE DE POINTES

SUTENT can cause QT interval prolongation in a dose-dependent manner, which may
lead to an increased risk for ventricular arrhythmias including Torsade de
Pointes. Torsade de Pointes was observed in <0.1% of patients.

Monitor patients who are at higher risk of developing QT interval prolongation,
including patients with a history of QT interval prolongation, patients who are
taking antiarrhythmics, or patients with relevant pre-existing cardiac disease,
bradycardia, or electrolyte disturbances. Consider periodic monitoring of
electrocardiograms and electrolytes (i.e., magnesium, potassium) during
treatment with SUTENT.

Monitor QT interval more frequently when SUTENT is concomitantly administered
with strong CYP3A4 inhibitors or drugs known to prolong QT interval. Consider
dose reducing SUTENT [see DOSAGE AND ADMINISTRATION, DRUG INTERACTIONS].

HYPERTENSION

In the pooled safety population, 29% of patients experienced hypertension. Grade
3 hypertension was reported in 7% of patients, and Grade 4 hypertension was
reported in 0.2%.

Monitor blood pressure at baseline and as clinically indicated. Initiate and/or
adjust antihypertensive therapy as appropriate. In cases of Grade 3
hypertension, withhold SUTENT until resolution to Grade ≤1 or baseline, then
resume SUTENT at a reduced dose. Discontinue SUTENT in patients with who develop
Grade 4 hypertension.

HEMORRHAGIC EVENTS AND VISCUS PERFORATION

Hemorrhagic events, some of which were fatal, have involved the gastrointestinal
tract, respiratory tract, tumor, urinary tract, and brain. In the pooled safety
population, 30% of patients experienced hemorrhagic events, including Grade 3 or
4 in 4.2% of patients. Epistaxis was the most common hemorrhagic event and
gastrointestinal hemorrhage was the most common Grade 3-5 event.

Tumor-related hemorrhage was observed in patients treated with SUTENT. These
events may occur suddenly, and in the case of pulmonary tumors, may present as
severe and life-threatening hemoptysis or pulmonary hemorrhage. Pulmonary
hemorrhage, some with a fatal outcome, was observed in patients treated with
SUTENT for metastatic RCC, GIST, and metastatic lung cancer. SUTENT is not
approved for use in patients with lung cancer.

Serious, sometimes fatal, gastrointestinal complications including
gastrointestinal perforation, have been reported in patients with
intra-abdominal malignancies treated with SUTENT.

Include serial complete blood counts (CBCs) and physical examinations with the
clinical assessment of hemorrhagic events. Interrupt SUTENT for Grade 3 or 4
hemorrhagic events until resolution to Grade ≤1 or baseline, then resume SUTENT
at a reduced dose.

Discontinue SUTENT in patients without resolution of Grade 3 or 4 hemorrhagic
events.

TUMOR LYSIS SYNDROME

Tumor Lysis Syndrome (TLS), some fatal, occurred in clinical trials and has been
reported in postmarketing experience, primarily in patients with RCC or GIST.
Patients generally at risk of TLS are those with high tumor burden prior to
treatment. Monitor these patients for TLS and manage as appropriate.

THROMBOTIC MICROANGIOPATHY

Thrombotic Microangiopathy (TMA), including thrombotic thrombocytopenic purpura
and hemolytic uremic syndrome, sometimes leading to renal failure or a fatal
outcome, occurred in clinical trials and in postmarketing experience of SUTENT
as monotherapy and administered in combination with bevacizumab. SUTENT is not
approved for use in combination with bevacizumab.

Discontinue SUTENT in patients developing TMA. Reversal of the effects of TMA
has been observed after SUTENT was discontinued.

PROTEINURIA

Proteinuria and nephrotic syndrome have been reported. Some of these cases have
resulted in renal failure and fatal outcomes.

Monitor patients for the development or worsening of proteinuria. Perform
baseline and periodic urinalyses during treatment, with follow up measurement of
24-hour urine protein as clinically indicated. Interrupt SUTENT and dose reduce
for 24-hour urine protein of 3 or more grams. Discontinue SUTENT for patients
with nephrotic syndrome or repeat episodes of 24-hour urine protein of 3 or more
grams despite dose reductions. The safety of continued SUTENT treatment in
patients with moderate to severe proteinuria has not been evaluated.

DERMATOLOGIC TOXICITIES

Severe cutaneous adverse reactions have been reported, including erythema
multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis
(TEN), some of which were fatal. Permanently discontinue SUTENT for these severe
cutaneous adverse reactions.

Necrotizing fasciitis, including fatal cases, has been reported in patients
treated with SUTENT, including of the perineum and secondary to fistula
formation. Discontinue SUTENT in patients who develop necrotizing fasciitis.

REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME

Reversible posterior leukoencephalopathy syndrome (RPLS) has been reported in
<1% of patients, some of which were fatal. Patients can present with
hypertension, headache, decreased alertness, altered mental functioning, and
visual loss, including cortical blindness. Magnetic resonance imaging is
necessary to confirm the diagnosis. Discontinue SUTENT in patients developing
RPLS.

THYROID DYSFUNCTION

Hyperthyroidism, some followed by hypothyroidism, have been reported in clinical
trials and through postmarketing experience of SUTENT.

Monitor thyroid function at baseline, periodically during treatment and as
clinically indicated. Monitor patients closely for signs and symptoms of thyroid
dysfunction, including hypothyroidism, hyperthyroidism, and thyroiditis, during
treatment with SUTENT. Initiate and/or adjust therapies for thyroid dysfunction
as appropriate.

HYPOGLYCEMIA

SUTENT can result in symptomatic hypoglycemia, which may lead to loss of
consciousness, or require hospitalization. In the pooled safety population,
hypoglycemia occurred in 2% of the patients treated with SUTENT. Hypoglycemia
has occurred in clinical trials in 2% of the patients treated with SUTENT for
advanced RCC (Study 3) and GIST (Study 1) (n=577) and in approximately 10% of
the patients treated with SUTENT for pNET (Study 6) (n=83). For patients being
treated with SUTENT for pNET, pre-existing abnormalities in glucose homeostasis
were not present in all patients who experienced hypoglycemia. Reductions in
blood glucose levels may be worse in patients with diabetes.

Check blood glucose levels at baseline, regularly during treatment, as
clinically indicated and after discontinuation of SUTENT. In patients with
diabetes, assess if antidiabetic therapies need to be adjusted to minimize the
risk of hypoglycemia.

OSTEONECROSIS OF THE JAW

Osteonecrosis of the Jaw (ONJ) occurred in patients treated with SUTENT.
Concomitant exposure to other risk factors, such as bisphosphonates or dental
disease/invasive dental procedures, may increase the risk of ONJ. Perform an
oral examination prior to initiation of SUTENT and periodically during SUTENT
therapy. Advise patients regarding good oral hygiene practices. Withhold SUTENT
treatment for at least 3 weeks prior to scheduled dental surgery or invasive
dental procedures, if possible. Withhold SUTENT for development of ONJ until
complete resolution. The safety of resumption of SUTENT after resolution of
osteonecrosis of the jaw has not been established.

IMPAIRED WOUND HEALING

Impaired wound healing has been reported in patients who received SUTENT [see
ADVERSE REACTIONS].

Withhold SUTENT for at least 3 weeks prior to elective surgery. Do not
administer for at least 2 weeks following major surgery and until adequate wound
healing. The safety of resumption of SUTENT after resolution of wound healing
complications has not been established.

EMBRYO-FETAL TOXICITY

Based on findings from animal studies and its mechanism of action, SUTENT can
cause fetal harm when administered to pregnant woman. Administration of
sunitinib to pregnant rats and rabbits during the period of organogenesis
resulted in teratogenicity at approximately 5.5 and 0.3 times the combined
systemic exposure [combined area under the curve (AUC) of sunitinib plus its
active metabolite] in patients administered the recommended daily dose (RDD) of
50 mg, respectively.

Advise pregnant women of the potential risk to a fetus. Advise females of
reproductive potential to use effective contraception during treatment with
SUTENT and for 4 weeks following the final dose [see Use In Specific
Populations].

PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

HEPATOTOXICITY

Inform patients of the signs and symptoms of hepatotoxicity. Advise patients to
contact their healthcare provider immediately for signs or symptoms of
hepatotoxicity [see WARNINGS AND PRECAUTIONS].

CARDIOVASCULAR EVENTS

Advise patients to contact their healthcare provider if they develop symptoms of
heart failure [see WARNINGS AND PRECAUTIONS].

QT PROLONGATION AND TORSADE DE POINTES

Inform patients of the signs and symptoms of QT prolongation. Advise patients to
contact their healthcare provider immediately in the event of syncope,
pre-syncopal symptoms, and cardiac palpitations [see WARNINGS AND PRECAUTIONS].

HYPERTENSION

Inform patients of the signs and symptoms of hypertension. Advise patients to
undergo routine blood pressure monitoring and to contact their health care
provider if blood pressure is elevated or if they experience signs or symptoms
of hypertension [see WARNINGS AND PRECAUTIONS].

HEMORRHAGIC EVENTS

Advise patients that SUTENT can cause severe bleeding. Advise patients to
immediately contact their healthcare provider for bleeding or symptoms of
bleeding [see WARNINGS AND PRECAUTIONS].

GASTROINTESTINAL DISORDERS

Advise patients that gastrointestinal disorders such as diarrhea, nausea,
vomiting, and constipation may develop during SUTENT treatment and to seek
immediate medical attention if they experience persistent or severe abdominal
pain because cases of gastrointestinal perforation and fistula have been
reported in patients taking SUTENT [see WARNINGS AND PRECAUTIONS, ADVERSE
REACTIONS].

DERMATOLOGIC EFFECTS AND TOXICITIES

Advise patients that depigmentation of the hair or skin may occur during
treatment with SUTENT due to the drug color (yellow). Other possible
dermatologic effects may include dryness, thickness or cracking of skin, blister
or rash on the palms of the hands and soles of the feet. Severe dermatologic
toxicities including Stevens-Johnson syndrome, Toxic Epidermal Necrolysis,
erythema multiforme, and necrotizing fasciitis have been reported. Advise
patients to immediately inform their healthcare provider if severe dermatologic
reactions occur [see WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS].

REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME

Inform patients of the signs and symptoms of reversible posterior
leukoencephalopathy syndrome. Advise patients to contact their healthcare
provider if they develop symptoms of reversible posterior leukoencephalopathy
syndrome [see WARNINGS AND PRECAUTIONS].

THYROID DYSFUNCTION

Advise patients that SUTENT can cause thyroid dysfunction. Advise patient to
contact their healthcare provider if symptoms of abnormal thyroid function occur
[see WARNINGS AND PRECAUTIONS].

HYPOGLYCEMIA

Advise patients that SUTENT can cause severe hypoglycemia and may be more severe
in patients with diabetes taking antidiabetic medications. Inform patients of
the signs, symptoms, and risks associated with hypoglycemia. Advise patients to
immediately inform their healthcare provider if severe signs or symptoms of
hypoglycemia occur [see WARNINGS AND PRECAUTIONS].

OSTEONECROSIS OF THE JAW

Advise patients regarding good oral hygiene practices 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 of the jaw [see WARNINGS AND PRECAUTIONS].

IMPAIRED WOUND HEALING

Advise patients that SUTENT impairs wound healing. Advise patients to inform
their healthcare provider of any planned surgical procedures [see WARNINGS AND
PRECAUTIONS].

CONCOMITANT MEDICATIONS

Advise patients to inform their healthcare providers of all concomitant
medications, including over-the-counter medications and dietary supplements [see
DRUG INTERACTIONS].

EMBRYO-FETAL TOXICITY

Advise pregnant women of the potential risk to a fetus. Advise females of
reproductive potential to inform their healthcare provider of a known or
suspected pregnancy [see WARNINGS AND PRECAUTIONS, Use In Specific
 Populations].

Advise females of reproductive potential to use effective contraception during
treatment and for 4 weeks after receiving the last dose of SUTENT [see Use In
Specific Populations].

Advise males with female partners of reproductive potential to use effective
contraception during treatment and for 7 weeks after receiving the last dose of
SUTENT [see Use In Specific Populations].

LACTATION

Advise women not to breastfeed during treatment with SUTENT and for at least 4
weeks after the last dose [see Use In Specific Populations].

INFERTILITY

Advise patients that SUTENT may impair male and female fertility [see Use In
Specific Populations, Nonclinical Toxicology].

MISSED DOSE

Advise patients that miss a dose of SUTENT by less than 12 hours to take the
missed dose right away. Advise patients that miss a dose of SUTENT by more than
12 hours to take the next scheduled dose at its regular time.

This product’s labeling may have been updated. For the most recent prescribing
information, please visit http://www.pfizer.com.

NONCLINICAL TOXICOLOGY

CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY

The carcinogenic potential of sunitinib has been evaluated in 2 species: rasH2
transgenic mice and Sprague-Dawley rats. There were similar positive findings in
both species. In rasH2 transgenic mice, gastroduodenal carcinomas and/or gastric
mucosal hyperplasia, as well as an increased incidence of background
hemangiosarcomas were observed at sunitinib daily doses of ≥25 mg/kg/day in
studies of 1 or 6 months duration. No proliferative changes were observed in
rasH2 transgenic mice at 8 mg/kg/day. Similarly, in a 2-year rat carcinogenicity
study, administration of sunitinib in 28-day cycles followed by 7-day dose-free
periods resulted in findings of duodenal carcinoma at doses as low as 1
mg/kg/day [approximately 0.9 times the combined AUC (combined systemic exposure
of sunitinib plus its active metabolite) in patients administered the RDD of 50
mg]. At the high dose of 3 mg/kg/day (approximately 8 times the combined AUC in
patients administered the RDD of 50 mg), the incidence of duodenal tumors was
increased and was accompanied by findings of gastric mucous cell hyperplasia and
by an increased incidence of pheochromocytoma and hyperplasia of the adrenal
gland.

Sunitinib did not cause genetic damage when tested in in vitro assays [bacterial
mutation (Ames test), human lymphocyte chromosome aberration] and an in vivo rat
bone marrow micronucleus test.

In a female fertility and early embryonic development study, female rats were
administered oral sunitinib (0.5, 1.5, 5 mg/kg/day) for 21 days prior to mating
and for 7 days after mating. Preimplantation loss was observed in females
administered 5 mg/kg/day (approximately 5 times the combined AUC in patients
administered the RDD of 50 mg). No adverse effects on fertility were observed at
doses ≤1.5 mg/kg/day (approximately equal to the combined AUC in patients
administered the RDD of 50 mg). In addition, effects on the female reproductive
system were identified in a 3-month oral repeat-dose monkey study (2, 6, 12
mg/kg/day). Ovarian changes (decreased follicular development) were noted at 12
mg/kg/day (approximately 5 times the combined AUC in patients administered the
RDD of 50 mg), while uterine changes (endometrial atrophy) were noted at ≥2
mg/kg/day (approximately 0.4 times the combined AUC in patients administered the
RDD of 50 mg). With the addition of vaginal atrophy, the uterine and ovarian
effects were reproduced at 6 mg/kg/day (approximately 0.8 times the combined AUC
in patients administered the RDD of 50 mg) in a 9-month monkey study (0.3, 1.5,
and 6 mg/kg/day administered daily for 28 days followed by a 14-day respite).

In a male fertility study, no reproductive effects were observed in male rats
dosed with 1, 3, or 10 mg/kg/day oral sunitinib for 58 days prior to mating with
untreated females. Fertility, copulation, conception indices, and sperm
evaluation (morphology, concentration, and motility) were unaffected by
sunitinib at doses ≤10 mg/kg/day (approximately ≥26 times the combined AUC in
patients administered the RDD of 50 mg).

USE IN SPECIFIC POPULATIONS

PREGNANCY

RISK SUMMARY

Based on animal reproduction studies and its mechanism of action, SUTENT can
cause fetal harm when administered to a pregnant woman [see CLINICAL
PHARMACOLOGY]. There are no available data in pregnant women to inform a
drug-associated risk. In animal developmental and reproductive toxicology
studies, oral administration of sunitinib to pregnant rats and rabbits
throughout organogenesis resulted in teratogenicity (embryolethality,
craniofacial and skeletal malformations) at 5.5 and 0.3 times the combined AUC
(the combined systemic exposure of sunitinib plus its active metabolite) in
patients administered the recommended daily doses (RDD) of 50 mg, respectively
(see Data). Advise females of reproductive potential of the potential risk to a
fetus.

The estimated background risk of major birth defects and miscarriage for the
indicated populations are unknown. All pregnancies have a background risk of
birth defect, loss, or other adverse outcomes. In the U.S. general population,
the estimated background risk of major birth defects and miscarriages in
clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

DATA

Animal Data

In a female fertility and early embryonic development study, female rats were
administered oral sunitinib (0.5, 1.5, 5 mg/kg/day) for 21 days prior to mating
and for 7 days after mating. Embryolethality was observed at 5 mg/kg/day
(approximately 5 times the combined AUC in patients administered the RDD of 50
mg).

In embryo-fetal developmental toxicity studies, oral sunitinib was administered
to pregnant rats (0.3, 1.5, 3, 5 mg/kg/day) and rabbits (0.5, 1, 5, 20
mg/kg/day) during the period of organogenesis. In rats, embryolethality and
skeletal malformations of the ribs and vertebrae were observed at the dose of 5
mg/kg/day (approximately 5.5 times the combined AUC in patients administered the
RDD of 50 mg). No adverse fetal effects were observed in rats at doses ≤3
mg/kg/day (approximately 2 times the combined AUC in patients administered the
RDD of 50 mg). In rabbits, embryolethality was observed at 5 mg/kg/day
(approximately 3 times the combined AUC in patients administered the RDD of 50
mg), and craniofacial malformations (cleft lip and cleft palate) were observed
at ≥1 mg/kg/day (approximately 0.3 times the combined AUC in patients
administered the RDD of 50 mg).

Sunitinib (0.3, 1, 3 mg/kg/day) was evaluated in a pre-and postnatal development
study in pregnant rats. Maternal body weight gains were reduced during gestation
and lactation at doses ≥1 mg/kg/day (approximately 0.5 times the combined AUC in
patients administered the RDD of 50 mg). At 3 mg/kg/day (approximately 2 times
the combined AUC in patients administered the RDD of 50 mg), reduced neonate
body weights were observed at birth and persisted in the offspring of both sexes
during the preweaning period and in males during postweaning period. No adverse
developmental effects were observed at doses ≤1 mg/kg/day.

LACTATION

There is no information regarding the presence of sunitinib and its metabolites
in human milk. Sunitinib and its metabolites were excreted in rat milk at
concentrations up to 12-fold higher than in plasma (see Data). Because of the
potential for serious adverse reactions in breastfed infants, advise women not
to breastfeed during treatment with SUTENT and for at least 4 weeks after the
last dose.

DATA

Animal Data

In lactating female rats administered 15 mg/kg, sunitinib and its metabolites
were excreted in milk at concentrations up to 12-fold higher than in plasma.

FEMALES AND MALES OF REPRODUCTIVE POTENTIAL

SUTENT can cause fetal harm when administered to a pregnant woman [see Use In
Specific Populations].

PREGNANCY TESTING

Verify pregnancy status of females of reproductive potential prior to initiating
treatment with SUTENT.

CONTRACEPTION

Females

Advise females of reproductive potential to use effective contraception during
treatment with SUTENT and for at least 4 weeks after the last dose.

Males

Based on findings in animal reproduction studies, advise males with female
partners of reproductive potential to use effective contraception during
treatment with SUTENT and for 7 weeks after the last dose.

INFERTILITY

Based on findings in animals, SUTENT may impair male and female fertility [see
Nonclinical Toxicology].

PEDIATRIC USE

The safety and effectiveness of SUTENT in pediatric patients have not been
established. Safety and pharmacokinetics of sunitinib were assessed in an
open-label study (NCT00387920) in pediatric patients 2 years to <17 years of age
(n=29) with refractory solid tumors. In addition, efficacy, safety and
pharmacokinetics of sunitinib was assessed in another open-label study
(NCT01462695) in pediatric patients 2 years to <17 years of age (n=27) with
high-grade glioma or ependymoma. The maximum tolerated dose (MTD) normalized for
body surface area (BSA) was lower in pediatric patients compared to adults.
Sunitinib was poorly tolerated in pediatric patients. The occurrence of
dose-limiting cardiotoxicity prompted an amendment of the NCT00387920 study to
exclude patients with previous exposure to anthracyclines or cardiac radiation.
No responses were reported in patients in either of the trials.

Apparent clearance and volume of distribution normalized for BSA for sunitinib
and its active major metabolite were lower in pediatrics as compared to adults.

The effect on open tibial growth plates in pediatric patients who received
SUTENT has not been adequately studied. See Juvenile Animal Toxicity Data below.

JUVENILE ANIMAL TOXICITY DATA

Physeal dysplasia was present in cynomolgus monkeys with open growth plates
treated with sunitinib for ≥3 months (3 month dosing 2, 6, 12 mg/kg/day; 8
cycles of dosing 0.3, 1.5, 6.0 mg/kg/day) at doses that were >0.4 times the
combined AUC (the combined systemic exposure of sunitinib plus its active
metabolite) in patients administered the RDD of 50 mg. The no-effect level
(NOEL) was 1.5 mg/kg/day in monkeys treated intermittently for 8 cycles, but was
not identified in monkeys treated continuously for 3 months. In developing rats
treated continuously for 3 months (1.5, 5.0, and 15.0 mg/kg) or 5 cycles (0.3,
1.5, and 6.0 mg/kg/day), bone abnormalities consisted of thickening of the
epiphyseal cartilage of the femur and an increase of fracture of the tibia at
doses ≥5 mg/kg (approximately 10 times the combined AUC in patients administered
the RDD of 50 mg). Additionally, tooth caries were present in rats at >5 mg/kg.
The incidence and severity of physeal dysplasia were dose related and reversible
upon cessation of treatment; however, findings in the teeth were not. In rats,
the NOEL in bones was ≤2 mg/kg/day.

GERIATRIC USE

Of the 7527 patients with GIST, RCC (advanced and adjuvant), or pNET who
received SUTENT, 32% were 65 years and older, and 7% were 75 years and older.
Patients aged 65 years of age and older had a higher incidence of Grade 3 or 4
adverse reactions (67%) than younger patients (60%).

In the GIST study, 73 (30%) of the patients who received SUTENT were 65 years
and older. In the mRCC study, 152 (41%) of patients who received SUTENT were 65
years and older. No overall differences in safety or effectiveness were observed
between these patients and younger patients.

In the pNET study, 22 (27%) of the patients who received SUTENT were 65 years
and older. Clinical studies of SUTENT did not include sufficient numbers of
patients with pNET to determine if patients 65 years of age and older respond
differently than younger patients.

HEPATIC IMPAIRMENT

No dose adjustment is required in patients with mild or moderate (Child-Pugh
Class A or B) hepatic impairment [see CLINICAL PHARMACOLOGY]. SUTENT was not
studied in patients with severe (Child-Pugh Class C) hepatic impairment.

RENAL IMPAIRMENT

No dose adjustment is recommended in patients with mild (CLcr 50 to 80 mL/min),
moderate (CLcr 30 to <50 mL/min), or severe (CLcr <30 mL/min) renal impairment
who are not on dialysis [see CLINICAL PHARMACOLOGY].

No dose adjustment is recommended for patients with end-stage renal disease
(ESRD) on hemodialysis [see CLINICAL PHARMACOLOGY].


OVERDOSE INFORMATION FOR SUTENT

Treatment of overdose with SUTENT should consist of general supportive measures.
There is no specific antidote for overdosage with SUTENT. If indicated,
elimination of unabsorbed drug should be achieved by emesis or gastric lavage.
Cases of accidental overdose have been reported; these cases were associated
with adverse reactions consistent with the known safety profile of SUTENT, or
without adverse reactions. In nonclinical studies, mortality was observed
following as few as 5 daily doses of 500 mg/kg (3000 mg/m²) in rats. At this
dose, signs of toxicity included impaired muscle coordination, head shakes,
hypoactivity, ocular discharge, piloerection, and gastrointestinal distress.
Mortality and similar signs of toxicity were observed at lower doses when
administered for longer durations.


CONTRAINDICATIONS FOR SUTENT

None.


CLINICAL PHARMACOLOGY FOR SUTENT

MECHANISM OF ACTION

Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases
(RTKs), some of which are implicated in tumor growth, pathologic angiogenesis,
and metastatic progression of cancer. Sunitinib was evaluated for its inhibitory
activity against a variety of kinases (>80 kinases) and was identified as an
inhibitor of platelet-derived growth factor receptors (PDGFRα and PDGFRβ),
vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3), stem
cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony
stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived
neurotrophic factor receptor (RET). Sunitinib inhibition of the activity of
these RTKs has been demonstrated in biochemical and cellular assays, and
inhibition of function has been demonstrated in cell proliferation assays. The
primary metabolite exhibits similar potency compared to sunitinib in biochemical
and cellular assays.

Sunitinib inhibited the phosphorylation of multiple RTKs (PDGFRβ, VEGFR2, KIT)
in tumor xenografts expressing RTK targets in vivo and demonstrated inhibition
of tumor growth or tumor regression and/or inhibited metastases in some
experimental models of cancer. Sunitinib demonstrated the ability to inhibit
growth of tumor cells expressing dysregulated target RTKs (PDGFR, RET, or KIT)
in vitro and to inhibit PDGFRβ-and VEGFR2-dependent tumor angiogenesis in vivo.

PHARMACODYNAMICS

EXPOSURE-RESPONSE RELATIONSHIP

Based on population pharmacokinetic/pharmacodynamic analyses, there were
relationships between changes in different pharmacodynamic endpoints (i.e.,
safety and efficacy endpoints) over time and sunitinib plasma exposures.

CARDIAC ELECTROPHYSIOLOGY

SUTENT can cause QT interval prolongation in a dose-dependent manner, which may
lead to an increased risk for ventricular arrhythmias including Torsade de
Pointes [see WARNINGS AND PRECAUTIONS].

PHARMACOKINETICS

The pharmacokinetics of sunitinib and sunitinib malate have been evaluated in
healthy subjects and in patients with solid tumors.

Sunitinib AUC and Cmax increase proportionately over a dose range of 25 mg to
100 mg (0.5 to 2 times the approved RDD of 50 mg). The pharmacokinetics were
similar in healthy subjects and in patients with a solid tumor, including
patients with GIST and RCC. No significant changes in the pharmacokinetics of
sunitinib or the primary active metabolite were observed with repeated daily
administration or with repeated cycles. With repeated daily administration,
sunitinib accumulates 3-to 4-fold while the primary metabolite accumulates 7-to
10-fold. Steady-state concentrations of sunitinib and its primary active
metabolite are achieved within 10 to 14 days. By Day 14, combined plasma
concentrations of sunitinib and its active metabolite ranged from 63 to 101
ng/mL.

ABSORPTION

Following oral administration of sunitinib, the time to maximum plasma
concentration (Tmax) ranged from 6 to 12 hours.

Effect Of Food

The administration of a single dose of SUTENT 50 mg with a high-fat,
high-calorie meal (consisting of approximately 150 protein calories and 500 to
600 fat calories) in healthy subjects had no clinically significant effect on
SUTENT or active metabolites exposure.

DISTRIBUTION

The apparent volume of distribution (Vd/F) for sunitinib is 2230 L. Binding of
sunitinib and its primary active metabolite to human plasma protein in vitro is
95% and 90%, respectively, with no concentration dependence in the range of 100
to 4000 ng/mL.

ELIMINATION

Following administration of a single oral dose in healthy subjects, the terminal
half-lives of sunitinib and its primary active metabolite are approximately 40
to 60 hours and 80 to 110 hours, respectively. Sunitinib total oral clearance
(CL/F) ranged from 34 to 62 L/h with an interpatient variability of 40%.

Metabolism

Sunitinib is metabolized primarily by CYP3A4 to its primary active metabolite,
which is further metabolized by CYP3A4. The primary active metabolite comprises
23% to 37% of the total exposure. After a radiolabeled dose, sunitinib and its
active metabolite were the major compounds identified in plasma, accounting for
92% of radioactivity.

Excretion

After a radiolabeled dose of sunitinib, approximately 61% of the dose was
recovered in feces and 16% in urine.

Sunitinib and its primary active metabolite were the major compounds identified
in urine and feces, representing 86% and 74% of radioactivity, respectively.

SPECIFIC POPULATIONS

No clinically significant differences in the pharmacokinetics of sunitinib or
the primary active metabolite were observed based on age (18 to 84 years), body
weight (34 to 168 kg), race (White, Black, or Asian), sex, Eastern Cooperative
Oncology Group (ECOG) score, mild (Child-Pugh Class A) or moderate (Child-Pugh
Class B) hepatic impairment.

PATIENTS WITH RENAL IMPAIRMENT

No clinically significant differences in the pharmacokinetics of sunitinib or
its active metabolite were predicted or observed in patients with mild (CLcr 50
to 80 mL/min), moderate (CLcr 30 to <50 mL/min), or severe (CLcr <30 mL/min)
renal impairment who are not on dialysis, compared to patients with normal renal
function (CLcr >80 mL/min). Although sunitinib was not eliminated through
hemodialysis, the sunitinib systemic exposure was 47% lower in patients with end
stage renal disease (ESRD) on hemodialysis compared to patients with normal
renal function.

DRUG INTERACTION STUDIES

CLINICAL STUDIES

Effect Of Strong CYP3A4 Inhibitors On Sunitinib

Co-administration of a single SUTENT dose with ketoconazole (strong CYP3A4
inhibitor) increased the combined sunitinib and its active metabolite Cmax and
AUC0-inf by 49% and 51%, respectively, in healthy subjects.

Effect Of Strong CYP3A4 Inducers On Sunitinib

Co-administration of a single SUTENT dose with rifampin (strong CYP3A4 inducer)
reduced the combined sunitinib and its active metabolite Cmax and AUC0-inf by
23% and 46%, respectively in healthy subjects.

IN VITRO STUDIES

In vitro studies in human hepatocytes and microsomes indicated that sunitinib
and the primary active metabolite do not induce CYP1A2, CYP2E1, and CYP3A4/5, or
inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1,
CYP3A4/5, and CYP4A9/11 at clinically relevant concentrations.

CLINICAL STUDIES

GASTROINTESTINAL STROMAL TUMOR

STUDY 1

Study 1 (NCT#00075218) was a 2-arm, international, randomized, double-blind,
placebo-controlled trial of SUTENT in patients with GIST who had disease
progression during prior imatinib mesylate (imatinib) treatment or who were
intolerant of imatinib. The objective was to compare time-to-tumor progression
(TTP) in patients receiving SUTENT plus best supportive care versus patients
receiving placebo plus best supportive care. Other objectives included
progression-free survival (PFS), objective response rate (ORR), and overall
survival (OS). Patients were randomized (2:1) to receive either 50 mg SUTENT or
placebo orally, once daily, on Schedule 4/2 until disease progression or
withdrawal from the study for another reason. Treatment was unblinded at the
time of disease progression. Patients randomized to placebo were then offered
crossover to open-label SUTENT and patients randomized to SUTENT were permitted
to continue treatment per investigator judgment.

At the time of a prespecified interim analysis, the intent-to-treat (ITT)
population included 312 patients. Two hundred seven (207) patients were
randomized to the SUTENT arm and 105 patients were randomized to the placebo
arm. Demographics were comparable between the SUTENT and placebo groups with
regard to age (69% versus 72% <65 years for SUTENT versus placebo,
respectively), sex (male: 64% versus 61%), race (White: 88% both arms, Asian: 5%
both arms, Black: 4% both arms, remainder not reported), and performance status
(ECOG 0: 44% versus 46%, ECOG 1: 55% versus 52%, and ECOG 2: 1% versus 2%).
Prior treatment included surgery (94% versus 93%) and radiotherapy (8% versus
15%). Outcome of prior imatinib treatment was also comparable between arms with
intolerance (4% versus 4%), progression within 6 months of starting treatment
(17% versus 16%), or progression beyond 6 months (78% versus 80%) balanced.

The planned interim efficacy and safety analysis was performed after 149 TTP
events had occurred. There was a statistically significant advantage for SUTENT
over placebo in TTP, meeting the primary endpoint. Efficacy results are
summarized in Table 10 and the Kaplan-Meier curve for TTP is shown in Figure 1.

Table 10: GIST Efficacy Results From Study 1 (Double-Blind Treatment Phase)

Efficacy Parameter SUTENT
(N=207) Placebo
(N=105) p-value (log-rank test) HR (95% CI) Time-to-tumor progressiona [median,
weeks (95% CI)] 27.3
(16.0, 32.1) 6.4
(4.4, 10.0) <0.0001* 0.33
(0.23, 0.47) Progression-free survivalb [median, weeks (95% CI)] 24.1
(11.1, 28.3) 6.0
(4.4, 9.9) <0.0001 0.33
(0.24, 0.47) Objective response rate (PR) [%, (95% CI)] 6.8
(3.7, 11.1) 0 0.006c * A comparison is considered statistically significant if
the p-value is <0.00417 (O’Brien Fleming stopping boundary). Abbreviations:
CI=confidence interval; GIST=gastrointestinal stromal tumor; HR=hazard ratio;
N=number of patients; PR=partial response.
a Time from randomization to progression; deaths prior to documented progression
were censored at time of last radiographic evaluation.
b Time from randomization to progression or death due to any cause.
c Pearson chi-square test.



Figure 1: Kaplan-Meier Curve of TTP in GIST Study 1 (Intent-to-Treat Population)





Abbreviations: CI=confidence interval; GIST=gastrointestinal stromal tumor;
N=number of patients; TTP=time-to-tumor progression.

The final ITT population enrolled in the double-blind treatment phase of the
study included 243 patients randomized to the SUTENT arm and 118 patients
randomized to the placebo arm. After the primary endpoint was met at the interim
analysis, the study was unblinded, and patients on the placebo arm were offered
open-label SUTENT treatment. Ninety-nine (99) of the patients initially
randomized to placebo crossed over to receive SUTENT in the open-label treatment
phase. At the protocol specified final analysis of OS, the median OS was 72.7
weeks for the SUTENT arm and 64.9 weeks for the placebo arm [hazard ratio
(HR)=0.876, 95% confidence interval (CI) (0.679, 1.129)].

STUDY 2

Study 2 was an open-label, multi-center, single-arm, dose-escalation study
conducted in patients with GIST following progression on, or intolerance to
imatinib. Following identification of the recommended regimen (50 mg once daily
on Schedule 4/2), 55 patients in this study received the 50 mg dose of SUTENT on
treatment Schedule 4/2. Partial responses (PR) were observed in 5 of 55 patients
(9.1% PR rate; 95% CI: 3.0%, 20.0%).

RENAL CELL CARCINOMA

TREATMENT-NAïVE

Study 3 (NCT#00083889) was a multi-center, international, randomized study
comparing single-agent SUTENT with interferon alfa was conducted in patients
with treatment-naïve RCC. The objective was to compare PFS in patients
receiving SUTENT versus patients receiving interferon alfa. Other endpoints
included ORR, OS, and safety. Seven hundred fifty (750) patients were randomized
(1:1) to receive either 50 mg SUTENT once daily on Schedule 4/2 or to receive
interferon alfa administered subcutaneously at 9 million international units
(MIU) 3 times a week. Patients were treated until disease progression or
withdrawal from the study.

The ITT population included 750 patients, 375 randomized to SUTENT and 375
randomized to interferon alfa. Demographics were comparable between the SUTENT
and interferon alfa groups with regard to age (59% versus 67% <65 years for
SUTENT versus interferon alfa, respectively), sex (male: 71% versus 72%), race
(White: 94% versus 91%, Asian: 2% versus 3%, Black: 1% versus 2%, remainder not
reported), and performance status (ECOG 0: 62% versus 61%, ECOG 1: 38% each arm,
ECOG 2: 0 versus 1%). Prior treatment included nephrectomy (91% versus 89%) and
radiotherapy (14% each arm). The most common site of metastases present at
screening was the lung (78% versus 80%, respectively), followed by the lymph
nodes (58% versus 53%, respectively) and bone (30% each arm); the majority of
the patients had multiple (2 or more) metastatic sites at baseline (80% versus
77%, respectively).

There was a statistically significant advantage for SUTENT over interferon alfa
in the endpoint of PFS (see Table 11 and Figure 2). In the prespecified
stratification factors of lactate dehydrogenase (LDH) (>1.5 ULN versus ≤1.5
ULN), ECOG performance status (0 versus 1), and prior nephrectomy (yes versus
no), the hazard ratio favored SUTENT over interferon alfa. The ORR was higher in
the SUTENT arm (see Table 11).

Table 11: Treatment-Naïve RCC Efficacy Results (Interim Analysis) from Study 3

Efficacy Parameter SUTENT
(N=375) Interferon Alfa
(N=375) p-value (log-rank test) HR (95% CI) Progression-free survivala [median,
weeks (95% CI)] 47.3
(42.6, 50.7) 22.0
(16.4, 24.0) <0.000001b 0.415
(0.320, 0.539) Objective response ratea [%, (95% CI)] 27.5
(23.0, 32.3) 5.3
(3.3, 8.1) <0.001c NA Abbreviations: CI=confidence interval; HR=hazard ratio;
N=number of patients; NA=not applicable; RCC=renal cell carcinoma.
a Assessed by blinded core radiology laboratory; 90 patients’ scans had not
been read at time of analysis.
b A comparison is considered statistically significant if the p-value is <0.0042
(O’Brien Fleming stopping boundary).
cPearson chi-square test.



Figure 2: Kaplan-Meier Curve of PFS in Treatment-Naïve RCC Study 3
(Intent-to-Treat Population)





Abbreviations: CI=confidence interval; IFN-α=interferon-alfa; N=number of
patients; PFS=progression-free survival; RCC=renal cell carcinoma.

At the protocol-specified final analysis of OS, the median OS was 114.6 weeks
for the SUTENT arm and 94.9 weeks for the interferon alfa arm (HR=0.821; 95% CI:
0.673, 1.001). The median OS for the interferon alfa arm includes 25 patients
who discontinued interferon alfa treatment because of disease progression and
crossed over to treatment with SUTENT as well as 121 patients (32%) on the
interferon alfa arm who received post-study cancer treatment with SUTENT.

CYTOKINE-REFRACTORY

The use of single-agent SUTENT in the treatment of cytokine-refractory RCC was
investigated in 2 single-arm, multi-center studies. All patients enrolled into
these studies experienced failure of prior cytokine-based therapy. In Study 4
(NCT#00077974), failure of prior cytokine therapy was based on radiographic
evidence of disease progression defined by response evaluation criteria in solid
tumors (RECIST) or World Health Organization (WHO) criteria during or within 9
months of completion of 1 cytokine therapy treatment (interferon alfa,
interleukin-2, or interferon alfa plus interleukin-2; patients who were treated
with interferon alfa alone must have received treatment for at least 28 days).
In Study 5 (NCT#00054886), failure of prior cytokine therapy was defined as
disease progression or unacceptable treatment-related toxicity. The endpoint for
both studies was ORR. Duration of response (DR) was also evaluated.

One hundred and six patients (106) were enrolled into Study 4 and 63 patients
were enrolled into Study 5. Patients received 50 mg SUTENT on Schedule 4/2.
Therapy was continued until the patients met withdrawal criteria or had
progressive disease. The baseline age, sex, race, and ECOG performance statuses
of the patients were comparable between Studies 4 and 5. Approximately 86%-94%
of patients in the 2 studies were White. Men comprised 65% of the pooled
population. The median age was 57 years and ranged from 24 to 87 years in the
studies. All patients had an ECOG performance status <2 at the screening visit.

The baseline malignancy and prior treatment history of the patients were
comparable between Studies 4 and 5. Across the 2 studies, 95% of the pooled
population of patients had at least some component of clear-cell histology. All
patients in Study 4 were required to have a histological clear-cell component.
Most patients enrolled in the studies (97% of the pooled population) had
undergone nephrectomy; prior nephrectomy was required for patients enrolled in
Study 4. All patients had received 1 previous cytokine regimen. Metastatic
disease present at the time of study entry included lung metastases in 81% of
patients. Liver metastases were more common in Study 4 (27% versus 16% in Study
5) and bone metastases were more common in Study 5 (51% versus 25% in Study 4);
52% of patients in the pooled population had at least 3 metastatic sites.
Patients with known brain metastases or leptomeningeal disease were excluded
from both studies.

The ORR and DR data from Studies 4 and 5 are provided in Table 12. There were 36
PRs in Study 4 as assessed by a core radiology laboratory for an ORR of 34.0%
(95% CI: 25.0%, 43.8%). There were 23 PRs in Study 5 as assessed by the
investigators for an ORR of 36.5% (95% CI: 24.7%, 49.6%). The majority (>90%) of
objective disease responses were observed during the first 4 cycles; the latest
reported response was observed in Cycle 10. DR data from Study 4 is premature as
only 9 of 36 patients (25%) responding to treatment had experienced disease
progression or died at the time of the data cutoff.

Table 12: Cytokine-Refractory RCC Efficacy Results from Study 4 and Study 5

Efficacy Parameter Study 4
(N=106) Study 5
(N=63) Objective response rate 34.0a 36.5b [%, (95% CI)1 (25.0, 43.8) (24.7,
49.6) Duration of response NR* 54b [median, weeks (95% CI)] (42.0, *) (34.3,
70.1) *Data not mature enough to determine upper confidence limit.
Abbreviations: CI=confidence interval; N=number of patients; NR=not reached;
RCC=renal cell carcinoma.
a Assessed by blinded core radiology laboratory.
b Assessed by investigators.



ADJUVANT TREATMENT

In the adjuvant treatment setting, SUTENT was investigated in S-TRAC
(NCT#00375674), a multi-center, international, randomized, double-blind,
placebo-controlled, trial in patients with high risk of recurrent RCC following
nephrectomy. Patients were required to have clear cell histology and high risk
of recurrence defined as ≥T3 and/or N+ tumors. Six hundred fifteen (615)
patients were randomized 1:1 to receive either 50 mg SUTENT once daily on
Schedule 4/2 or placebo. Patients were treated for 9 cycles (approximately 1
year), or until disease recurrence, unacceptable toxicity, or withdrawal of
consent.

Demographics were generally comparable between the SUTENT and placebo arms with
regard to age (median age 58 years), sex (73% male), and race (84% White, 12%
Asian and 4% Other). At randomization, most patients had an ECOG performance
status of 0 (74% SUTENT and 72% placebo). The remainder of the patients had an
ECOG performance status of 1; 1 patient on SUTENT had a performance status of 2.

The major efficacy outcome measure was disease-free survival (DFS) in patients
receiving SUTENT versus placebo as assessed by blinded independent central
review (BICR). Overall survival was an additional endpoint. There was a
statistically significant improvement in DFS in patients who were treated with
SUTENT compared to placebo (Table 13 and Figure 3). Prespecified subgroup
analyses are presented in Table 14. At the time of the DFS analysis, overall
survival data were not mature, with 141/615 (23%) patient deaths.

Table 13: Disease-free Survival Results as Assessed by BICR in Adjuvant RCC
(Intent to Treat Population) from S-TRAC

SUTENT
N=309 Placebo
N=306 p-valuea HRa (95% CI) Median DFS [years (95% CI)1 6.8 (5.8, NR) 5.6 (3.8,
6.6) 0.03 0.76 (0.59, 0.98) DFS Events 113 (36.6%) 144 (47.1%) 5 Year DFS Rate
59.3% 51.3% a P-value based on log-rank test stratified by University of
California Los Angeles Integrated Staging System (UISS) prognostic group; HR
based on a Cox proportional hazard model stratified by UISS prognostic group
Abbreviations: BICR=blinded independent central review; CI=confidence interval;
DFS=disease-free survival; HR=hazard ratio; N=number of patients; RCC=renal cell
carcinoma.



Table 14: Disease-free Survival by Baseline Disease Characteristics

Number of Events/ Total n/N Median DFS [years (95% CI)] HRa (95% CI) SUTENT
Placebo SUTENT Placebo T3 Intermediateb 35/115 46/112 NR
(5.2, NR) 6.4
(4.7, NR) 0.82
(0.53, 1.28) T3 Highc 63/165 79/166 6.8
(5.0, NR) 5.3
(2.9, NR) 0.77
(0.55, 1.07) T4/Node Positived 15/29 19/28 3.5 (1.2, NR) 1.7
(0.4, 3.0) 0.62
(0.31, 1.23) Abbreviations: CI=confidence interval; DFS=disease-free survival;
HR=hazard ratio; N=number of patients; n=number of events; NR=not reached
a HR based on a Cox proportional hazards model
b T3 Intermediate: T3, N0 or NX, M0, any Fuhrman’s grade, ECOG PS 0 OR T3, N0
or NX, M0, Fuhrman’s grade 1, ECOG PS ≥ 1
c T3 High: T3, N0 or NX, M0, Fuhrman’s grade ≥ 2, ECOG PS ≥ 1
d T4/Node Positive: T4, N0 or NX, M0, any Fuhrman’s grade, any ECOG PS OR Any
T, N1-2, M0, any Fuhrman’s grade, any ECOG PS



Figure 3: Kaplan-Meier Curve of Disease-free Survival as Assessed by BICR
(Intent-to-Treat Population)





Abbreviations: BICR=blinded independent central review; CI=confidence interval;
N=number of patients.

PANCREATIC NEUROENDOCRINE TUMORS

Study 6 (NCT#00428597) was a multi-center, international, randomized,
double-blind, placebo-controlled study of single-agent SUTENT conducted in
patients with unresectable pNET. Patients were required to have documented
RECIST-defined disease progression within the prior 12 months and were
randomized (1:1) to receive either 37.5 mg SUTENT (N=86) or placebo (N=85) once
daily without a scheduled off-treatment period. The primary objective was to
compare PFS in patients receiving SUTENT versus patients receiving placebo.
Other endpoints included OS, ORR, and safety. Use of somatostatin analogs was
allowed in the study.

Demographics were comparable between the SUTENT and placebo groups.
Additionally, 49% of SUTENT patients had nonfunctioning tumors vs 52% of placebo
patients, and 92% patients in both arms had liver metastases. A total of 66% of
SUTENT patients received prior systemic therapy compared with 72% of placebo
patients and 35% of SUTENT patients had received somatostatin analogs compared
with 38% of placebo patients. Patients were treated until disease progression or
withdrawal from the study. Upon disease progression or study closure, patients
were offered access to SUTENT in a separate extension study.

As recommended by the Independent Data Monitoring Committee, the study was
terminated prematurely prior to the prespecified interim analysis. This may have
led to an overestimate of the magnitude of PFS effect. A clinically significant
improvement for SUTENT over placebo in PFS was seen by both investigator and
independent assessment. A hazard ratio favoring SUTENT was observed in all
subgroups of baseline characteristics evaluated. OS data were not mature at the
time of the analysis. There were 9 deaths in the SUTENT arm and 21 deaths in the
placebo arm. A statistically significant difference in ORR favoring SUTENT over
placebo was observed. Efficacy results are summarized in Table 15 and the
Kaplan-Meier curve for PFS is in Figure 4.

Table 15: pNET Efficacy Results from Study 6

Efficacy Parameter SUTENT
(N=86) Placebo
(N=85) p-value HR (95% CI) Progression-free survival [median, months (95% CI)]
10.2
(7.4, 16.9) 5.4
(3.4, 6.0) 0.000146a 0.427
(0.271, 0.673) Objective response rate P/o, (95% CI)] 9.3
(3.2, 15.4) 0 0.0066b NA Abbreviations: CI=confidence interval; HR=hazard ratio;
N=number of patients; NA=not applicable; pNET=pancreatic neuroendocrine tumors.
a 2-sided unstratified log-rank test.
b Fisher’s Exact test.



Figure 4: Kaplan-Meier Curve of PFS in the pNET Study 6





Abbreviations: CI=confidence interval; N=number of patients;
PFS=progression-free survival; pNET=pancreatic neuroendocrine tumors.


PATIENT INFORMATION FOR SUTENT

SUTENT®
(su TENT) (sunitinib malate) capsules

What is the most important information I should know about SUTENT?

SUTENT can cause serious side effects including:

 * Severe liver problems, that can lead to death. Tell your healthcare provider
   right away if you develop any of the following signs and symptoms of liver
   problems during treatment with SUTENT:
   * itching
   * yellow eyes or skin
   * dark urine
   * pain or discomfort in the right upper stomach area

Your healthcare provider should do blood tests to check your liver function
before you start taking and during treatment with SUTENT. Your healthcare
provider may temporarily stop, reduce your dose, or permanently stop treatment
with SUTENT if you develop liver problems. See “What are the possible side
effects of SUTENT?” for more information about side effects.

What is SUTENT?

SUTENT is a prescription medicine used to treat:

 * a rare cancer of the stomach, bowel, or esophagus called gastrointestinal
   stromal tumor (GIST) and when:
   * you have taken the medicine imatinib mesylate and it did not stop the
     cancer from growing, or
   * you cannot take imatinib mesylate.
 * advanced kidney cancer (advanced renal cell carcinoma or RCC).
 * adults with kidney cancer that has not spread (localized), and who are at
   high risk of RCC coming back again after having kidney surgery.
 * a type of pancreatic cancer called pancreatic neuroendocrine tumors (pNET),
   that has progressed and cannot be treated with surgery.

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

Before taking SUTENT tell your healthcare provider about all of your medical
conditions, including if you:

 * have any heart problems
 * have high blood pressure
 * have thyroid problems
 * have a history of low blood sugar or diabetes
 * have kidney function problems (other than cancer)
 * have liver problems
 * have any bleeding problem
 * plan to have surgery or have had a recent surgery. You should stop taking
   SUTENT at least 3 weeks before planned surgery. See “What are the possible
   side effects of SUTENT?”
 * have seizures
 * have or have had pain in the mouth, teeth or jaw, swelling or sores inside
   the mouth, numbness or a feeling of heaviness in the jaw, or loosening of a
   tooth
 * are pregnant or plan to become pregnant. SUTENT can harm your unborn baby.

Females who are able to become pregnant:

 * * Your healthcare provider should do a pregnancy test before you start
     treatment with SUTENT.
   * You should use effective birth control (contraception) during treatment and
     for at least 4 weeks after your last dose of SUTENT.
 * Tell your healthcare provider right away if you become pregnant or think you
   are pregnant during treatment with SUTENT.

Males with female partners who are able to become pregnant should use effective
birth control (contraception) during treatment and for 7 weeks after your last
dose of SUTENT. SUTENT may cause fertility problems in males and females. Tell
your healthcare provider if this is a concern for you.

 * are breastfeeding or plan to breastfeed. Do not breastfeed during treatment
   with SUTENT and for at least 4 weeks (1 month) after the last dose.

Tell all of your healthcare providers and dentists that you are taking SUTENT.
They should talk to the healthcare provider who prescribed SUTENT for you,
before you have any surgery, or medical or dental procedure.

Tell your healthcare provider about all the medicines you take, including
prescription medicines and over-the-counter medicines, vitamins, and herbal
supplements. Using SUTENT with certain other medicines can cause serious side
effects.

You may have an increased risk of severe jawbone problems (osteonecrosis) if you
take SUTENT and a bisphosphonate medicine. Especially tell your healthcare
provider if you are taking or have taken an osteoporosis medicine.

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 SUTENT?

 * Take SUTENT exactly the way your healthcare provider tells you.
 * Take SUTENT 1 time each day with or without food.
 * If you take SUTENT for GIST or RCC, you will usually take your medicine for 4
   weeks (28 days) and then stop for 2 weeks (14 days). This is 1 cycle of
   treatment. You will repeat this cycle for as long as your healthcare provider
   tells you to.
 * If you take SUTENT for pNET, take it 1 time each day until your healthcare
   provider tells you to stop.
 * Do not drink grapefruit juice or eat grapefruit during your treatment with
   SUTENT. They may cause you to have too much SUTENT in your body.
 * Your healthcare provider may do blood tests before each cycle of treatment to
   check you for side effects.
 * If you miss a dose of SUTENT by less than 12 hours, take the missed dose
   right away. If you miss a dose of SUTENT by more than 12 hours, just take
   your next dose at your regular time. Do not make up the missed dose. Tell
   your healthcare provider about any missed dose.
 * Call your healthcare provider right away, if you take too much SUTENT.

What are possible side effects of SUTENT?

SUTENT may cause serious side effects, including:

 * See “What is the most important information I should know about SUTENT?”
 * Heart problems. Heart problems may include heart failure, heart attack and
   heart muscle problems (cardiomyopathy) that can lead to death. Tell your
   healthcare provider if you feel very tired, are short of breath, or have
   swollen feet and ankles.
 * Abnormal heart rhythm changes. Changes in the electrical activity of your
   heart called QT prolongation can cause irregular heart beats that can be life
   threatening. Your healthcare provider may do electrocardiograms and blood
   tests (electrolytes) to watch for these problems during your treatment with
   SUTENT. Tell your healthcare provider right away if you feel dizzy, faint, or
   have abnormal heartbeats during your treatment with SUTENT
   * you feel faint or lightheaded, or you pass out
   * dizziness
   * feel your heart beat is irregular or fast
 * High blood pressure. High blood pressure is common with SUTENT and may
   sometimes be severe. Follow your healthcare provider’s instructions about
   having your blood pressure checked regularly. Call your healthcare provider
   if your blood pressure is high, or if you have any of the following signs or
   symptoms of high blood pressure:
   * severe headache
   * lightheadedness
   * dizziness
   * change in vision

Your healthcare provider may prescribe medicine for you to treat high blood
pressure, if needed.

 * Bleeding problems. Bleeding is common with SUTENT, but SUTENT can also cause
   severe bleeding problems that can lead to death. Your healthcare provider
   will monitor you for bleeding and may do blood tests if needed. Call your
   healthcare provider right away if you have any of these symptoms or a serious
   bleeding problem during treatment with SUTENT, including:
   * painful, swollen stomach (abdomen)
   * bloody urine
   * vomiting blood
   * headache
   * coughing up blood
   * change in your mental status
   * black, sticky stools
 * Serious stomach and intestinal problems, that can sometimes lead to death.
   Some people have had tears in their stomach or intestine (perforation), or
   have developed an abnormal opening between the stomach and intestine
   (fistula). Get medical help right away if you get stomach-area (abdominal)
   pain that does not go away or is severe during treatment with SUTENT.
 * Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer
   cells and may lead to death. TLS can cause kidney failure and the need for
   dialysis treatment, abnormal heart rhythm, seizure, and sometimes death. Your
   healthcare provider may do blood tests to check you for TLS.
 * Abnormal changes in the brain (Reversible Posterior Leukoencephalopathy
   Syndrome [RPLS]). RPLS can cause a collection of symptoms including headache,
   confusion, and vision loss. Some people who have taken SUTENT have developed
   RPLS that can lead to death.
 * Thrombotic microangiopathy (TMA) including thrombotic thrombocytopenia
   purpura (TTP) and hemolytic uremic syndrome (HUS). TMA is a condition that
   involves injury to the smallest blood vessels, and blood clots that can
   happen while taking SUTENT. TMA is accompanied by a decrease in red cells and
   cells that are involved with clotting. TMA may harm your body’s organs such
   as the brain and kidneys, and can sometimes lead to death.
 * Protein in your urine. Some people who have taken SUTENT have developed
   protein in their urine, and in some cases, kidney problems that can lead to
   death. Your healthcare provider will check you for this problem.
 * Serious skin and mouth reactions. Treatment with SUTENT has caused severe
   skin reactions that can lead to death, including:
   * severe rash with blisters or peeling of the skin.
   * painful sores or ulcers on the skin, lips or inside the mouth.
   * tissue damage (necrotizing fasciitis).

If you have any signs or symptoms of severe skin reactions, stop taking SUTENT
and call your healthcare provider or get medical help right away.

 * Thyroid problems. Your healthcare provider may do tests to check your thyroid
   function during SUTENT treatment. Tell your healthcare provider if you have
   any of the following signs and symptoms during your treatment with SUTENT:
   * tiredness that gets worse and does not go away
   * fast heat rate
   * weight gain or weight loss
   * loss of appetite
   * feeling depressed
   * problems with heat
   * irregular menstrual periods or no menstrual
   * feeling nervous or agitated, tremors periods
   * sweating
   * headache
   * nausea or vomiting
   * hair loss
   * diarrhea
 * Low blood sugar (hypoglycemia). Low blood sugar can happen with SUTENT, and
   may cause you to become unconscious, or you may need to be hospitalized. Low
   blood sugar with SUTENT may be worse in people who have diabetes and take
   antidiabetic medicines. Your healthcare provider should check your blood
   sugar levels regularly during treatment with SUTENT and may need to adjust
   the dose of your antidiabetic medicines. Call your healthcare provider right
   away if you have any of the following signs or symptoms of low blood sugar
   during your treatment with SUTENT:
   * headache
   * irritability
   * drowsiness
   * hunger
   * weakness
   * fast heart beat
   * dizziness
   * sweating
   * confusion
   * feeling jittery
 * Jawbone problems (osteonecrosis). Severe jawbone problems have happened in
   some people who take SUTENT. Certain risk factors such as taking a
   bisphosphonate medicine or having dental disease may increase your risk of
   getting osteonecrosis. Your healthcare provider may tell you to see your
   dentist before you start taking SUTENT. Your healthcare provider may tell you
   to avoid dental procedures, if possible, during your treatment with SUTENT,
   especially if you are receiving a bisphosphonate medicine into a vein
   (intravenous). Tell your healthcare provider if you plan to have any dental
   procedures before or during treatment with SUTENT.
   * You should stop taking SUTENT at least 3 weeks before planned dental
     procedures.
   * Your healthcare provider should tell you when you may start taking SUTENT
     again after dental procedures.
 * Wound healing problems. Wound healing problems have happened in some people
   who take SUTENT. Tell your healthcare provider if you plan to have any
   surgery before or during treatment with SUTENT.
   * You should stop taking SUTENT at least 3 weeks before planned surgery.
   * Your healthcare provider should tell you when you may start taking SUTENT
     again after surgery.

Your healthcare provider may temporarily stop, reduce your dose, or permanently
stop treatment with SUTENT if you develop serious side effects.

Common side effects of SUTENT include:

 * tiredness
 * weakness
 * diarrhea
 * pain, swelling or sores inside of your mouth
 * nausea
 * loss of appetite
 * indigestion
 * vomiting
 * stomach-area (abdominal) pain
 * blisters or rash on the palms of your hands and soles of your feet
 * high blood pressure
 * taste changes
 * low platelet counts

The medicine in SUTENT is yellow, and it may make your skin look yellow. Your
skin and hair may get lighter in color. SUTENT may also cause other skin
problems including: dryness, thickness or cracking of the skin.

These are not all of the possible side effects of SUTENT. Call your doctor for
medical advice about side effects. You may report side effects to FDA at
1-800-FDA-1088.

How do I store SUTENT?

 * Store SUTENT at room temperature, between 68°F to 77°F (20°C to 25°C).

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

General information about the safe and effective use of SUTENT.

Medicines are sometimes prescribed for purposes other than those listed in a
Medication Guide. Do not use SUTENT for a condition for which it was not
prescribed. Do not give SUTENT to other people, even if they have the same
symptoms that you have. It may harm them. You can ask your healthcare provider
or pharmacist for information about SUTENT that is written for health
professionals.

What are the ingredients in SUTENT?

Active ingredient: sunitinib malate

Inactive ingredients: mannitol, croscarmellose sodium, povidone (K-25), and
magnesium stearate.

Orange gelatin capsule shells: titanium dioxide, and red iron oxide.

Caramel gelatin capsule shells: titanium dioxide, red iron oxide, yellow iron
oxide, and black iron oxide.

Yellow gelatin capsule shells: titanium dioxide and yellow iron oxide.

White printing ink: shellac, propylene glycol, sodium hydroxide, povidone, and
titanium dioxide.

Black printing ink: shellac, propylene glycol, potassium hydroxide and black
iron oxide.

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


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