These highlights do not include all the information needed to use SUNITINIB MALATE CAPSULES safely and effectively. See full prescribing information for SUNITINIB MALATE CAPSULES. SUNITINIB malate capsules, for oral use Initial U.S. Approval: 2006

WARNING: HEPATOTOXICITY

BOXED WARNING SECTION

Hepatotoxicity may be severe, and in some cases, fatal. Monitor hepatic function and interrupt, dose reduce, or discontinue sunitinib as recommended [see Warnings and Precautions (5.1)] .

1 INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

2 DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

3 DOSAGE FORMS AND STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

12.5 mg capsules Hard gelatin capsule with opaque reddish brown cap and opaque reddish brown body, self-lock capsule, imprinted with ‘RM53’ on cap and ‘RM53’ on body in white ink, containing yellow to orange colored powder. 25 mg capsules Hard gelatin capsule with opaque caramel cap and opaque reddish brown body, self-lock capsule, imprinted with ‘RM54’ on cap and ‘RM54’ on body in white ink, containing yellow to orange colored powder. 37.5 mg capsules Hard gelatin capsule with opaque yellow cap and opaque yellow body, self-lock capsule, imprinted with ‘RM55’ on cap and ‘RM55’ on body in black ink, containing yellow to orange colored powder. 50 mg capsules Hard gelatin capsule with opaque caramel cap and opaque caramel body, self-lock capsule, imprinted with ‘RM56’ on cap and ‘RM56’ on body in white ink, containing yellow to orange colored powder.

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

None.

5 WARNINGS AND PRECAUTIONS

WARNINGS AND PRECAUTIONS SECTION

6 ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

The following clinically significant adverse reactions are described elsewhere in the labeling. Hepatotoxicity [see Warnings and Precautions (5.1)] Cardiovascular Events [see Warnings and Precautions (5.2)] QT Interval Prolongation and Torsade de Pointes [see Warnings and Precautions (5.3)] Hypertension [see Warnings and Precautions (5.4)] Hemorrhagic Events [see Warnings and Precautions (5.5)] Tumor Lysis Syndrome [see Warnings and Precautions (5.6)] Thrombotic Microangiopathy [see Warnings and Precautions (5.7)] Proteinuria [see Warnings and Precautions (5.8)] Dermatologic Toxicities [see Warnings and Precautions (5.9)] Reversible Posterior Leukoencephalopathy Syndrome [see Warnings and Precautions (5.10)] Thyroid Dysfunction [see Warnings and Precautions (5.11)] Hypoglycemia [see Warnings and Precautions (5.12)] Osteonecrosis of the Jaw [see Warnings and Precautions (5.13)] Impaired Wound Healing [see Warnings and Precautions (5.14)]

7 DRUG INTERACTIONS

DRUG INTERACTIONS SECTION

8 USE IN SPECIFIC POPULATIONS

USE IN SPECIFIC POPULATIONS SECTION

10 OVERDOSAGE

OVERDOSAGE SECTION

Treatment of overdose with sunitinib should consist of general supportive measures. There is no specific antidote for overdosage with sunitinib. 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 sunitinib, or without adverse reactions. In nonclinical studies, mortality was observed following as few as 5 daily doses of 500 mg/kg (3000 mg/m 2 ) 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.

11 DESCRIPTION

DESCRIPTION SECTION

Sunitinib is a kinase inhibitor present in sunitinib malate capsules as the malate salt. Sunitinib malate is described chemically as N-[2-(Diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide, compound with (S)-2-hydroxybutanedioic acid. The molecular formula is C 22 H 27 FN 4 O 2 .C 4 H 6 O 5 and the molecular weight is 532.57 Daltons. The chemical structure of sunitinib malate is: Sunitinib malate is light yellow to brownish orange colored 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 the range of 12 to 70 mg/mL. The log of the distribution coefficient (octanol/water) at pH 7 is 5.2. Sunitinib malate capsules are supplied as printed hard shell capsules containing 12.5 mg, 25 mg, 37.5 mg or 50 mg of sunitinib (equivalent to 16.7 mg, 33.4 mg, 50.1 mg, or 66.8 mg of sunitinib malate, respectively) together with croscarmellose sodium, magnesium stearate, mannitol and povidone (K-30) as inactive ingredients. The reddish brown gelatin capsule shells contain ferric oxide red and titanium dioxide. The caramel gelatin capsule shells contain ferric oxide red, ferric oxide yellow, ferrosoferric oxide and titanium dioxide. The yellow gelatin capsule shells contain ferric oxide yellow and titanium dioxide. The white printing ink contains potassium hydroxide, shellac and titanium dioxide. The black printing ink contains ferrosoferric oxide, potassium hydroxide and shellac.

12 CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

NONCLINICAL TOXICOLOGY SECTION

14 CLINICAL STUDIES

CLINICAL STUDIES SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

HOW SUPPLIED SECTION

12.5 mg capsules Hard gelatin capsule with opaque reddish brown cap and opaque reddish brown body, self-lock capsule, imprinted with ‘RM53’ on cap and ‘RM53’ on body in white ink, containing yellow to orange colored powder; available in: Bottles of 28 capsules with child-resistant closure: NDC 63304-091-27 Carton of 28 capsules (4 x 7 Unit-dose): NDC 63304-091-86 25 mg capsules Hard gelatin capsule with opaque caramel cap and opaque reddish brown body, self-lock capsule, imprinted with ‘RM54’ on cap and ‘RM54’ on body in white ink, containing yellow to orange colored powder; available in: Bottles of 28 capsules with child-resistant closure: NDC 63304-092-27 Carton of 28 capsules (4 x 7 Unit-dose): NDC 63304-092-86 37.5 mg capsules Hard gelatin capsule with opaque yellow cap and opaque yellow body, self-lock capsule, imprinted with ‘RM55’ on cap and ‘RM55’ on body in black ink, containing yellow to orange colored powder; available in: Bottles of 28 capsules with child-resistant closure: NDC 63304-093-27 Carton of 28 capsules (4 x 7 Unit-dose): NDC 63304-093-86 50 mg capsules Hard gelatin capsule with opaque caramel cap and opaque caramel body, self-lock capsule, imprinted with ‘RM56’ on cap and ‘RM56’ on body in white ink, containing Yellow to orange colored powder ; available in: Bottles of 28 capsules with child-resistant closure: NDC 63304-094-27 Carton of 28 capsules (4 x 7 Unit-dose): NDC 63304-094-86 Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP Controlled Room Temperature]. Keep out of reach of children.

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

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 (5.1)] . Cardiovascular Events Advise patients to contact their healthcare provider if they develop symptoms of heart failure [see Warnings and Precautions (5.2)] . 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 (5.3)] . 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 (5.4)] . Hemorrhagic Events Advise patients that sunitinib malate capsules can cause severe bleeding. Advise patients to immediately contact their healthcare provider for bleeding or symptoms of bleeding [see Warnings and Precautions (5.5)] . Gastrointestinal Disorders Advise patients that gastrointestinal disorders such as diarrhea, nausea, vomiting, and constipation may develop during sunitinib malate capsules 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 sunitinib malate capsules [see Warnings and Precautions (5.5), and Adverse Reactions (6.1)]. Dermatologic Effects and Toxicities Advise patients that depigmentation of the hair or skin may occur during treatment with sunitinib malate capsules 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 (5.9), and Adverse Reactions (6.1)]. 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 (5.10)] . Thyroid Dysfunction Advise patients that sunitinib malate capsules can cause thyroid dysfunction. Advise patient to contact their healthcare provider if symptoms of abnormal thyroid function occur [see Warnings and Precautions (5.11)] . Hypoglycemia Advise patients that sunitinib malate capsules 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 (5.12)] . 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 (5.13)] . Impaired Wound Healing Advise patients that sunitinib malate capsules impairs wound healing. Advise patients to inform their healthcare provider of any planned surgical procedures [see Warnings and Precautions (5.14)] . Concomitant Medications Advise patients to inform their healthcare providers of all concomitant medications, including over-the-counter medications and dietary supplements [see Drug Interactions (7)] . 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 (5.15), Use in Specific Populations (8.1)] . Advise females of reproductive potential to use effective contraception during treatment and for 4 weeks after receiving the last dose of sunitinib malate capsules [see Use in Specific Populations (8.3)] . Advise males with female partners of reproductive potential to use effective contraception during treatment and for 7 weeks after receiving the last dose of sunitinib malate capsules [see Use in Specific Populations (8.3)] . Lactation Advise women not to breastfeed during treatment with sunitinib malate capsules and for at least 4 weeks after the last dose [see Use in Specific Populations (8.2)] . Infertility Advise patients that sunitinib malate capsules may impair male and female fertility [see Use in Specific Populations (8.3), Nonclinical Toxicology (13.1)] . Missed Dose Advise patients that miss a dose of sunitinib malate capsules by less than 12 hours to take the missed dose right away. Advise patients that miss a dose of sunitinib malate capsules by more than 12 hours to take the next scheduled dose at its regular time. Manufactured by: Sun Pharmaceutical Industries Ltd. Survey No. 1012, Dadra-396 193, U.T. of D & NH and Daman & Diu, India. Distributed by: Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512 October 2023 FDA-05

Medication Guide

SPL MEDGUIDE SECTION

MEDICATION GUIDE Sunitinib Malate (soo ni’ ti nib mal’ ate) Capsules Rx only What is the most important information I should know about sunitinib malate capsules? Sunitinib malate capsules 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 sunitinib malate capsules: 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 sunitinib malate capsules. Your healthcare provider may temporarily stop, reduce your dose, or permanently stop treatment with sunitinib malate capsules if you develop liver problems. See “What are the possible side effects of sunitinib malate capsules?” for more information about side effects. What are sunitinib malate capsules? Sunitinib malate capsules are 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 sunitinib malate capsules are safe and effective in children. Before taking sunitinib malate capsules 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 sunitinib malate capsules at least 3 weeks before planned surgery. See “What are the possible side effects of sunitinib malate capsules?” 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. Sunitinib malate capsules 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 sunitinib malate capsules. You should use effective birth control (contraception) during treatment and for at least 4 weeks after your last dose of sunitinib malate capsules. Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with sunitinib malate capsules. 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 sunitinib malate capsules. Sunitinib malate capsules 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 sunitinib malate capsules and for at least 4 weeks (1 month) after the last dose. Tell all of your healthcare providers and dentists that you are taking sunitinib malate capsules. They should talk to the healthcare provider who prescribed sunitinib malate capsules 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 sunitinib malate capsules with certain other medicines can cause serious side effects. You may have an increased risk of severe jawbone problems (osteonecrosis) if you take sunitinib malate capsules 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 sunitinib malate capsules? Take sunitinib malate capsules exactly the way your healthcare provider tells you. Take sunitinib malate capsule 1 time each day with or without food. If you take sunitinib malate capsules 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 sunitinib malate capsules 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 sunitinib malate capsules. They may cause you to have too much sunitinib malate 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 sunitinib malate capsules by less than 12 hours, take the missed dose right away. If you miss a dose of sunitinib malate capsules 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 sunitinib malate capsules. What are possible side effects of sunitinib malate capsules? Sunitinib malate capsules may cause serious side effects, including: See “ What is the most important information I should know about sunitinib malate capsules? ” 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 sunitinib malate capsules Tell your healthcare provider right away if you feel dizzy, faint, or have abnormal heartbeats during your treatment with sunitinib malate capsules 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 sunitinib malate capsules, 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 dizziness lightheadedness change in vision Your healthcare provider may prescribe medicine for you to treat high blood pressure, if needed. Bleeding problems . Bleeding is common with sunitinib malate capsules, but sunitinib malate capsules 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 sunitinib malate capsules, including: painful, swollen stomach (abdomen) bloody urine vomiting blood coughing up blood headache 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 d...

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 63304-091-27 Sunitinib Malate Capsules 12.5 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 28 Capsules SUN PHARMA

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 63304-092-27 Sunitinib Malate Capsules 25 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 28 Capsules SUN PHARMA

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 63304-093-27 Sunitinib Malate Capsules 37.5 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 28 Capsules SUN PHARMA

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 63304-094-27 Sunitinib Malate Capsules 50 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 28 Capsules SUN PHARMA