Sutent Side Effects

Please note - some side effects for Sutent may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Sutent - for the Consumer

Sutent

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Sutent:

Arm or leg discomfort; back pain; changes in taste; constipation; diarrhea; dizziness; dry, thick, or cracked skin; headache; indigestion; mild loss of appetite or stomach pain; mouth or tongue pain, swelling, soreness, or irritation; nausea; skin or hair discoloration; stomach upset; tiredness; trouble sleeping; vomiting; weakness; weight loss.

Seek medical attention right away if any of these SEVERE side effects occur when using Sutent:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); black, tarry, or bloody stools; blistering or rash on the palms of hands and soles of feet; bloody urine; calf or leg pain, redness, swelling, or tenderness; chest pain; coughing up blood; decreased urination; fainting; fast, slow, or irregular heartbeat; fever, chills, or persistent cough or sore throat; joint pain; mental or mood changes (eg, decreased alertness, depression, irritability, nervousness); muscle pain, tenderness, or weakness; numbness of an arm or leg; numbness or tingling of the hands or feet; seizures; severe or persistent headache, dizziness, stomach pain, back pain, tiredness, or weakness; shortness of breath; swelling of the hands, ankles, feet, or legs; symptoms of liver problems (eg, dark urine, loss of appetite, pale stools, yellowing of the eyes or skin); symptoms of stroke (eg, confusion, one-sided weakness, slurred speech, vision problems); symptoms of thyroid problems (eg, changes in menstrual period, excessive sweating, hair loss, increased appetite, increased sensitivity to hot or cold conditions, sudden weight changes, tremors, worsening tiredness); unusual or severe bruising or bleeding (eg, bleeding gums, nosebleeds); vision changes or vision loss; vomiting blood or vomit that looks like coffee grounds.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

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Sutent Side Effects - for the Professional

Sutent

The data described below reflect exposure to Sutent in 660 patients who participated in the double-blind treatment phase of a placebo-controlled trial (n=202) for the treatment of GIST [see Clinical Studies (14.1)], an active-controlled trial (n=375) for the treatment of RCC [see Clinical Studies (14.2)] or a placebo-controlled trial (n=83) for the treatment of pNET [see Clinical Studies (14.3)]. The GIST and RCC patients received a starting oral dose of 50 mg daily on Schedule 4/2 in repeated cycles, and the pNET patients received a starting oral dose of 37.5 mg daily without scheduled off-treatment periods.

The most common adverse reactions (≥20%) in patients with GIST, RCC or pNET are fatigue, asthenia, fever, diarrhea, nausea, mucositis/stomatitis, vomiting, dyspepsia, abdominal pain, constipation, hypertension, peripheral edema, rash, hand-foot syndrome, skin discoloration, dry skin, hair color changes, altered taste, headache, back pain, arthralgia, extremity pain, cough, dyspnea, anorexia, and bleeding. The potentially serious adverse reactions of hepatotoxicity, left ventricular dysfunction, QT interval prolongation, hemorrhage, hypertension, thyroid dysfunction, and adrenal function are discussed in Warnings and Precautions (5). Other adverse reactions occurring in GIST, RCC and pNET studies are described below.

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.

Adverse Reactions in GIST Study A

Median duration of blinded study treatment was two cycles for patients on Sutent (mean 3.0, range 1–9) and one cycle (mean 1.8, range 1–6) for patients on placebo at the time of the interim analysis. Dose reductions occurred in 23 patients (11%) on Sutent and none on placebo. Dose interruptions occurred in 59 patients (29%) on Sutent and 31 patients (30%) on placebo. The rates of treatment-emergent, non-fatal adverse reactions resulting in permanent discontinuation were 7% and 6% in the Sutent and placebo groups, respectively.

Most treatment-emergent adverse reactions in both study arms were Grade 1 or 2 in severity. Grade 3 or 4 treatment-emergent adverse reactions were reported in 56% versus 51% of patients on Sutent versus placebo, respectively, in the double-blind treatment phase of the trial. Table 1 compares the incidence of common (≥10%) treatment-emergent adverse reactions for patients receiving Sutent and reported more commonly in patients receiving Sutent than in patients receiving placebo.

Table 1. Adverse Reactions Reported in Study A in at Least 10% of GIST Patients who Received Sutent in the Double-Blind Treatment Phase and More Commonly Than in Patients Given Placebo*

Adverse Reaction, n (%)	GIST
	Sutent (n=202)		Placebo (n=102)
	All Grades	Grade 3/4	All Grades	Grade 3/4
* Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 † Includes decreased appetite
Any		114 (56)		52 (51)
Gastrointestinal
Diarrhea	81 (40)	9 (4)	27 (27)	0 (0)
Mucositis/stomatitis	58 (29)	2 (1)	18 (18)	2 (2)
Constipation	41 (20)	0 (0)	14 (14)	2 (2)
Cardiac
Hypertension	31 (15)	9 (4)	11 (11)	0 (0)
Dermatology
Skin discoloration	61 (30)	0 (0)	23 (23)	0 (0)
Rash	28 (14)	2 (1)	9 (9)	0 (0)
Hand-foot syndrome	28 (14)	9 (4)	10 (10)	3 (3)
Neurology
Altered taste	42 (21)	0 (0)	12 (12)	0 (0)
Musculoskeletal
Myalgia/limb pain	28 (14)	1 (1)	9 (9)	1 (1)
Metabolism/Nutrition
Anorexia†	67 (33)	1 (1)	30 (29)	5 (5)
Asthenia	45 (22)	10 (5)	11 (11)	3 (3)

In the double-blind treatment phase of GIST Study A, oral pain other than mucositis/stomatitis occurred in 12 patients (6%) on Sutent versus 3 (3%) on placebo. Hair color changes occurred in 15 patients (7%) on Sutent versus 4 (4%) on placebo. Alopecia was observed in 10 patients (5%) on Sutent versus 2 (2%) on placebo.

Table 2 provides common (≥10%) treatment-emergent laboratory abnormalities.

Table 2. Laboratory Abnormalities Reported in Study A in at Least 10% of GIST Patients Who Received Sutent or Placebo in the Double-Blind Treatment Phase*

Laboratory Parameter, n (%)	GIST
	Sutent (n=202)		Placebo (n=102)
	All Grades*	Grade 3/4*†	All Grades*	Grade 3/4*‡
LVEF=Left ventricular ejection fraction
* Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 † 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%). ‡ Grade 4 laboratory abnormalities in patients on placebo included amylase (1%), lipase (1%), and hemoglobin (2%).
Any		68 (34)		22 (22)
Gastrointestinal
AST / ALT	78 (39)	3 (2)	23 (23)	1 (1)
Lipase	50 (25)	20 (10)	17 (17)	7 (7)
Alkaline phosphatase	48 (24)	7 (4)	21 (21)	4 (4)
Amylase	35 (17)	10 (5)	12 (12)	3 (3)
Total bilirubin	32 (16)	2 (1)	8 (8)	0 (0)
Indirect bilirubin	20 (10)	0 (0)	4 (4)	0 (0)
Cardiac
Decreased LVEF	22 (11)	2 (1)	3 (3)	0 (0)
Renal/Metabolic
Creatinine	25 (12)	1 (1)	7 (7)	0 (0)
Potassium decreased	24 (12)	1 (1)	4 (4)	0 (0)
Sodium increased	20 (10)	0 (0)	4 (4)	1 (1)
Hematology
Neutrophils	107 (53)	20 (10)	4 (4)	0 (0)
Lymphocytes	76 (38)	0 (0)	16 (16)	0 (0)
Platelets	76 (38)	10 (5)	4 (4)	0 (0)
Hemoglobin	52 (26)	6 (3)	22 (22)	2 (2)

After an interim analysis, the study was unblinded, and patients on the placebo arm were given the opportunity to receive open-label Sutent treatment [see Clinical Studies (14.1)]. For 241 patients randomized to the Sutent arm, including 139 who received Sutent in both the double-blind and open-label treatment 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 study treatment was 6 cycles (mean 7.8, range 1 – 37) from the time of the unblinding. A total of 118 patients (46%) required dosing interruptions, and a total of 72 patients (28%) required dose reductions. The incidence of treatment-emergent adverse reactions resulting in permanent discontinuation was 20%. The most common Grade 3 or 4 treatment-related adverse reactions experienced by patients receiving Sutent in the open-label treatment 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%).

Adverse Reactions in the Treatment-Naïve RCC Study

The as-treated patient population for the treatment-naive RCC study included 735 patients, 375 randomized to Sutent and 360 randomized to IFN-α. The median duration of treatment was 11.1 months (range: 0.4 – 46.1) for Sutent treatment and 4.1 months (range: 0.1 – 45.6) for IFN-α treatment. Dose interruptions occurred in 202 patients (54%) on Sutent and 141 patients (39%) on IFN-α. Dose reductions occurred in 194 patients (52%) on Sutent and 98 patients (27%) on IFN-α. Discontinuation rates due to adverse reactions were 20% for Sutent and 24% for IFN-α. Most treatment-emergent adverse reactions in both study arms were Grade 1 or 2 in severity. Grade 3 or 4 treatment-emergent adverse reactions were reported in 77% versus 55% of patients on Sutent versus IFN-α, respectively.

Table 3 compares the incidence of common (≥10%) treatment-emergent adverse reactions for patients receiving Sutent versus IFN-α.

Table 3. Adverse Reactions Reported in at Least 10% of Patients with RCC Who Received Sutent or IFN-α*

Adverse Reaction, n (%)	Treatment-Naïve RCC
	Sutent (n=375)		IFN-α (n=360)
	All Grades	Grade 3/4†	All Grades	Grade 3/4‡
* Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 † 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%). ‡ Grade 4 ARs in patients on IFN-α included dyspnea (1%), fatigue (1%), abdominal pain (<1%) and depression (<1%). § Includes flank pain ¶ Includes ageusia, hypogeusia and dysgeusia # Includes decreased appetite Þ Includes one patient with Grade 5 gastric hemorrhage ß Includes depressed mood
Any	372 (99)	290 (77)	355 (99)	197 (55)
Constitutional
Fatigue	233 (62)	55 (15)	202 (56)	54 (15)
Asthenia	96 (26)	42 (11)	81 (22)	21 (6)
Fever	84 (22)	3 (1)	134 (37)	1 (<1)
Weight decreased	60 (16)	1 (<1)	60 (17)	3 (1)
Chills	53 (14)	3 (1)	111 (31)	0 (0)
Chest Pain	50 (13)	7 (2)	24 (7)	3 (1)
Influenza like illness	18 (5)	0 (0)	54 (15)	1 (<1)
Gastrointestinal
Diarrhea	246 (66)	37 (10)	76 (21)	1 (<1)
Nausea	216 (58)	21 (6)	147 (41)	6 (2)
Mucositis/stomatitis	178 (47)	13 (3)	19 (5)	2 (<1)
Vomiting	148 (39)	19 (5)	62 (17)	4 (1)
Dyspepsia	128 (34)	8 (2)	16 (4)	0 (0)
Abdominal pain§	113 (30)	20 (5)	42 (12)	5 (1)
Constipation	85 (23)	4 (1)	49 (14)	1 (<1)
Dry mouth	50 (13)	0 (0)	27 (7)	1 (<1)
GERD/reflux esophagitis	47 (12)	1 (<1)	3 (1)	0(0)
Flatulence	52 (14)	0 (0)	8 (2)	0 (0)
Oral pain	54 (14)	2 (<1)	2 (1)	0 (0)
Glossodynia	40 (11)	0 (0)	2 (1)	0 (0)
Hemorrhoids	38 (10)	0 (0)	6 (2)	0 (0)
Cardiac
Hypertension	127 (34)	50 (13)	13 (4)	1 (<1)
Edema, peripheral	91 (24)	7 (2)	17 (5)	2 (1)
Ejection fraction decreased	61 (16)	10 (3)	19 (5)	6 (2)
Dermatology
Rash	109 (29)	6 (2)	39 (11)	1 (<1)
Hand-foot syndrome	108 (29)	32 (8)	3 (1)	0 (0)
Skin discoloration/ yellow skin	94 (25)	1 (<1)	0 (0)	0 (0)
Dry skin	85 (23)	1 (<1)	26 (7)	0 (0)
Hair color changes	75 (20)	0 (0)	1 (<1)	0 (0)
Alopecia	51 (14)	0 (0)	34 (9)	0 (0)
Erythema	46 (12)	2 (<1)	5 (1)	0 (0)
Pruritus	44 (12)	1 (<1)	24 (7)	1 (<1)
Neurology
Altered taste¶	178 (47)	1 (<1)	54 (15)	0 (0)
Headache	86 (23)	4 (1)	69 (19)	0 (0)
Dizziness	43 (11)	2 (<1)	50 (14)	2 (1)
Musculoskeletal
Back pain	105 (28)	19 (5)	52 (14)	7 (2)
Arthralgia	111 (30)	10 (3)	69 (19)	4 (1)
Pain in extremity/ limb discomfort	150 (40)	19 (5)	107 (30)	7 (2)
Endocrine
Hypothyroidism	61 (16)	6 (2)	3 (1)	0 (0)
Respiratory
Cough	100 (27)	3 (1)	51 (14)	1 (<1)
Dyspnea	99 (26)	24 (6)	71 (20)	15 (4)
Nasopharyngitis	54 (14)	0 (0)	8 (2)	0 (0)
Oropharyngeal Pain	51 (14)	2 (<1)	9 (2)	0 (0)
Upper respiratory tract infection	43 (11)	2 (<1)	9 (2)	0 (0)
Metabolism/Nutrition
Anorexia#	182 (48)	11 (3)	153 (42)	7 (2)
Hemorrhage/Bleeding
Bleeding, all sites	140 (37)	16 (4)Þ	35 (10)	3 (1)
Psychiatric
Insomnia	57 (15)	3 (<1)	37 (10)	0 (0)
Depressionß	40 (11)	0 (0)	51 (14)	5 (1)

Treatment-emergent Grade 3/4 laboratory abnormalities are presented in Table 4.

Table 4. Laboratory Abnormalities Reported in at Least 10% of Treatment-Naïve RCC Patients Who Received Sutent or IFN-α

Laboratory Parameter, n (%)	Treatment-Naïve RCC
	Sutent (n=375)		IFN-α (n=360)
	All Grades*	Grade 3/4*†	All Grades*	Grade 3/4*‡
* Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 † 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%). ‡ Grade 4 laboratory abnormalities in patients on IFN-α included uric acid (8%), lymphocytes (2%), lipase (1%), neutrophils (1%), amylase (<1%), calcium increased (<1%), glucose decreased (<1%), potassium increased (<1%), and hemoglobin (<1%).
Gastrointestinal
AST	211 (56)	6 (2)	136 (38)	8 (2)
ALT	192 (51)	10 (3)	144 (40)	9 (2)
Lipase	211 (56)	69 (18)	165 (46)	29 (8)
Alkaline phosphatase	171 (46)	7 (2)	132 (37)	6 (2)
Amylase	130 (35)	22 (6)	114 (32)	12 (3)
Total bilirubin	75 (20)	3 (1)	8 (2)	0 (0)
Indirect bilirubin	49 (13)	4 (1)	3 (1)	0 (0)
Renal/Metabolic
Creatinine	262 (70)	2 (<1)	183 (51)	1 (<1)
Creatine kinase	183 (49)	9 (2)	40 (11)	4 (1)
Uric acid	173 (46)	54 (14)	119 (33)	29 (8)
Calcium decreased	156 (42)	4 (1)	145 (40)	4 (1)
Phosphorus	116 (31)	22 (6)	87 (24)	23 (6)
Albumin	106 (28)	4 (1)	72 (20)	0 (0)
Glucose increased	86 (23)	21 (6)	55 (15)	22 (6)
Sodium decreased	75 (20)	31 (8)	55 (15)	13 (4)
Glucose decreased	65 (17)	0 (0)	43 (12)	1 (<1)
Potassium increased	61 (16)	13 (3)	61 (17)	15 (4)
Calcium increased	50 (13)	2 (<1)	35 (10)	5 (1)
Potassium decreased	49 (13)	3 (1)	7 (2)	1 (<1)
Sodium increased	48 (13)	0 (0)	38 (10)	0 (0)
Hematology
Neutrophils	289 (77)	65 (17)	178 (49)	31 (9)
Hemoglobin	298 (79)	29 (8)	250 (69)	18 (5)
Platelets	255 (68)	35 (9)	85 (24)	2 (1)
Lymphocytes	256 (68)	66 (18)	245 (68)	93 (26)
Leukocytes	293 (78)	29 (8)	202 (56)	8 (2)

Adverse Reactions in the Phase 3 pNET Study

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. Dose interruptions occurred in 25 patients (30%) on Sutent and 10 patients (12%) on placebo. Dose reductions occurred in 26 patients (31%) on Sutent and 9 patients (11%) on placebo. Discontinuation rates due to adverse reactions were 22% for Sutent and 17% for placebo.

Most treatment-emergent adverse reactions in both study arms were Grade 1 or 2 in severity. Grade 3 or 4 treatment-emergent adverse reactions were reported in 54% versus 50% of patients on Sutent versus placebo, respectively. Table 5 compares the incidence of common (≥10%) treatment-emergent adverse reactions for patients receiving Sutent and reported more commonly in patients receiving Sutent than in patients receiving placebo.

Table 5. Adverse Reactions Reported in the Phase 3 pNET Study in at Least 10% of Patients who Received Sutent and More Commonly Than in Patients Given Placebo*

Adverse Reaction, n (%)	pNET
	Sutent (n=83)		Placebo (n=82)
	All Grades	Grade 3/4†	All Grades	Grade 3/4
* Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 † Grade 4 ARs in patients on Sutent included fatigue (1%). ‡ Includes aphthous stomatitis, gingival pain, gingivitis, glossitis, glossodynia, mouth ulceration, oral discomfort, oral pain, tongue ulceration, mucosal dryness, mucosal inflammation, and dry mouth. § Includes abdominal discomfort, abdominal pain, and abdominal pain upper. ¶ Includes hematemesis, hematochezia, hematoma, hemoptysis, hemorrhage, melena, and metrorrhagia.
Any	82 (99)	45 (54)	78 (95)	41 (50)
Constitutional
Asthenia	28 (34)	4 (5)	22 (27)	3 (4)
Fatigue	27 (33)	4 (5)	22 (27)	7 (9)
Weight decreased	13 (16)	1(1)	9 (11)	0 (0)
Gastrointestinal
Diarrhea	49 (59)	4 (5)	32 (39)	2 (2)
Stomatitis/oral Syndromes‡	40 (48)	5 (6)	15 (18)	0 (0)
Nausea	37 (45)	1 (1)	24 (29)	1 (1)
Abdominal pain§	32 (39)	4 (5)	28 (34)	8 (10)
Vomiting	28 (34)	0 (0)	25 (31)	2 (2)
Dyspepsia	12 (15)	0 (0)	5 (6)	0 (0)
Cardiac
Hypertension	22 (27)	8 (10)	4 (5)	1 (1)
Dermatology
Hair color changes	24 (29)	1 (1)	1 (1)	0 (0)
Hand-foot syndrome	19 (23)	5 (6)	2 (2)	0 (0)
Rash	15 (18)	0 (0)	4 (5)	0 (0)
Dry skin	12 (15)	0 (0)	9 (11)	0 (0)
Neurology
Dysgeusia	17 (21)	0 (0)	4 (5)	0 (0)
Headache	15 (18)	0 (0)	11 (13)	1 (1)
Musculoskeletal
Arthralgia	12 (15)	0 (0)	5 (6)	0 (0)
Psychiatric
Insomnia	15 (18)	0 (0)	10 (12)	0 (0)
Hemorrhage/Bleeding
Bleeding events¶	18 (22)	0 (0)	8 (10)	3 (4)
Epistaxis	17 (21)	1 (1)	4 (5)	0 (0)

Table 6 provides common (≥10%) treatment-emergent laboratory abnormalities.

Table 6. Laboratory Abnormalities Reported in the Phase 3 pNET Study in at Least 10% of Patients Who Received Sutent

Laboratory Parameter, n (%)	pNET
	Sutent			Placebo
	N	All Grades*	Grade 3/4*†	N	All Grades*	Grade 3/4*‡
* Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 † 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%). ‡ Grade 4 laboratory abnormalities in patients on placebo included creatinine (3%), alkaline phosphatase (1%), glucose increased (1%) and lipase (1%).
Gastrointestinal
AST increased	82	59 (72)	4 (5)	80	56 (70)	2 (3)
ALT increased	82	50 (61)	3 (4)	80	44 (55)	2 (3)
Alkaline phosphatase increased	82	52 (63)	8 (10)	80	56 (70)	9 (11)
Total bilirubin increased	82	30 (37)	1 (1)	80	22 (28)	3 (4)
Amylase increased	74	15 (20)	3 (4)	74	7 (10)	1 (1)
Lipase increased	75	13 (17)	4 (5)	72	8 (11)	3 (4)
Renal/Metabolic
Glucose increased	82	58 (71)	10 (12)	80	62 (78)	14 (18)
Albumin decreased	81	33 (41)	1 (1)	79	29 (37)	1 (1)
Phosphorus decreased	81	29 (36)	6 (7)	77	17 (22)	4 (5)
Calcium decreased	82	28 (34)	0 (0)	80	15 (19)	0 (0)
Sodium decreased	82	24 (29)	2 (2)	80	27 (34)	2 (3)
Creatinine increased	82	22 (27)	4 (5)	80	22 (28)	4 (5)
Glucose decreased	82	18 (22)	2 (2)	80	12 (15)	3 (4)
Potassium decreased	82	17 (21)	3 (4)	80	11 (14)	0 (0)
Magnesium decreased	52	10 (19)	0 (0)	39	4 (10)	0 (0)
Potassium increased	82	15 (18)	1 (1)	80	9 (11)	1 (1)
Hematology
Neutrophils decreased	82	58 (71)	13 (16)	80	13 (16)	0 (0)
Hemoglobin decreased	82	53 (65)	0 (0)	80	44 (55)	1 (1)
Platelets decreased	82	49 (60)	4 (5)	80	12 (15)	0 (0)
Lymphocytes decreased	82	46 (56)	6 (7)	80	28 (35)	3 (4)

Venous Thromboembolic Events

Seven patients (3%) on Sutent and none on placebo in the double-blind treatment phase of GIST Study A experienced venous thromboembolic events; five of the seven were Grade 3 deep venous thrombosis (DVT), and two were Grade 1 or 2. Four of these seven GIST patients discontinued treatment following first observation of DVT.

Thirteen (3%) patients receiving Sutent for treatment-naïve RCC had venous thromboembolic events reported. Seven (2%) of these patients had pulmonary embolism, one was Grade 2 and six were Grade 4, and six (2%) patients had DVT, including three Grade 3. One patient was permanently withdrawn from Sutent due to pulmonary embolism; dose interruption occurred in two patients with pulmonary embolism and one with DVT. In treatment-naïve RCC patients receiving IFN-α, six (2%) venous thromboembolic events occurred; one patient (<1%) experienced a Grade 3 DVT and five patients (1%) had pulmonary embolism, all Grade 4. One patient (1%) receiving Sutent for pNET had a venous thromboembolic event reported compared to 5 patients (6%) receiving placebo. The Sutent patient had Grade 2 thrombosis. Two placebo patients had DVT, one was Grade 3, two placebo patients had pulmonary embolism, one was Grade 3 and one was Grade 4, and one placebo patient had Grade 3 jugular thrombosis.

Reversible Posterior Leukoencephalopathy Syndrome

There have been rare (<1%) reports of subjects presenting with seizures and radiological evidence of reversible posterior leukoencephalopathy syndrome (RPLS). None of these subjects had a fatal outcome to the event. Patients with seizures and signs/symptoms consistent with RPLS, such as hypertension, headache, decreased alertness, altered mental functioning, and visual loss, including cortical blindness should be controlled with medical management including control of hypertension. Temporary suspension of Sutent is recommended; following resolution, treatment may be resumed at the discretion of the treating physician.

Pancreatic and Hepatic Function

If symptoms of pancreatitis or hepatic failure are present, patients should have Sutent discontinued. Pancreatitis was observed in 5 (1%) patients receiving Sutent for treatment-naïve RCC compared to 1 (<1%) patient receiving IFN-α. Pancreatitis was observed in 1 (1%) patient receiving Sutent for pNET and 1 (1%) patient receiving placebo. Hepatotoxicity was observed in patients receiving Sutent [See Boxed Warning and Warnings and Precautions (5.1)].

Post-marketing Experience

The following adverse reactions have been identified during post-approval 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.

Cases of serious infection (with or without neutropenia), in some cases with fatal outcome, have been reported.

Cases of myopathy and/or rhabdomyolysis with or without acute renal failure, in some cases with fatal outcome, have been reported. Patients with signs or symptoms of muscle toxicity should be managed as per standard medical practice.

Thrombotic microangiopathy has been reported in patients on Sutent. Suspension of Sutent is recommended; following resolution, treatment may be resumed at the discretion of the treating physician.

Cases of fatal hemorrhage associated with thrombocytopenia have been reported.

Pulmonary embolism, in some cases with fatal outcome, has been reported.

Cases of renal impairment and/or failure, in some cases with fatal outcome, have been reported.

Cases of proteinuria and rare cases of nephrotic syndrome have been reported. Baseline urinalysis is recommended, and patients should be monitored for the development or worsening of proteinuria. The safety of continued Sutent treatment in patients with moderate to severe proteinuria has not been systematically evaluated. Discontinue Sutent in patients with nephrotic syndrome.

Hypersensitivity reactions, including angioedema, have been reported.

Cases of fistula formation, sometimes associated with tumor necrosis and/or regression, in some cases with fatal outcome, have been reported.

Cases of arterial thromboembolic events, sometimes fatal, have been reported in patients treated with Sutent. The most frequent events included cerebrovascular accident, transient ischemic attack and cerebral infarction.

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Side Effects by Body System - for Healthcare Professionals

General

General side effects including fatigue (up to 74%), anorexia (up to 48%), asthenia (up to 34%), fever (up to 18%), and dehydration (up to 11%) have been reported. Cases of serious infection, some with fatal outcome, have also been reported.

Gastrointestinal

Gastrointestinal side effects have included diarrhea (up to 66%), nausea (up to 58%), mucositis/stomatitis (up to 53%), dyspepsia (up to 46%), vomiting (up to 39%), abdominal pain (up to 39%), constipation (up to 34%), flatulence (up to 14%), and glossodynia (up to 11%). Laboratory abnormalities have included increased lipase (up to 56%) and increased amylase (up to 35%).

Hematologic

Hematologic side effects have included bleeding events (up to 37%) and epistaxis (up to 21%). Hematologic laboratory abnormalities have included neutropenia (up to 77%), lymphocytopenia (up to 68%), thrombocytopenia (up to 68%), anemia (up to 79%) and leukopenia (up to 78%). Fatal hemorrhage has also been reported.

Four patients (2%) in the two RCC studies had venous thromboembolic events reported. Two of the patients had pulmonary embolism (both grade 4) and two patients had deep venous thrombosis (DVT) (both grade 3). Dose interruption occurred in one of these cases. Seven patients (3%) on sunitinib in GIST Study A experienced venous thromboembolic events. Five of the seven were grade 3 DVTs, and two were grade 1 or 2. Four of these seven GIST patients discontinued treatment following first observation of DVT. Cases of erythrocytosis and macrocytosis have also been reported.

Postmarketing reports have included arterial thromboembolic events, some with fatal outcomes. The most frequent events included cerebrovascular accident, transient ischemic attack and cerebral infarction. Other postmarketing reports have included pulmonary embolism, some with fatal outcomes, cases of fatal hemorrhage associated with thrombocytopenia, and thrombotic microangiopathy.

Nervous system

Patients with seizures and signs and symptoms consistent with RPLS, such as hypertension, headache, decreased alertness, altered mental functioning, and visual loss, including cortical blindness should be controlled with medical management including control of hypertension. Temporary suspension of sunitinib is recommended. Following resolution, treatment may be resumed at the discretion of the treating physician.

Nervous system side effects have included altered taste (up to 47%), headache (up to 23%), and dizziness (up to 11%).

In clinical studies of sunitinib, seizures have been observed in subjects with radiological evidence of brain metastases. There have also been rare (less than 1%) reports of subjects presenting with seizures and radiological evidence of reversible posterior leukoencephalopathy syndrome (RPLS). None of these subjects had a fatal outcome to the event. A case of transient sunitinib-induced coma has also been reported.

Postmarketing case reports of hyperammonemic encephalopathy have been received.

Hepatic

Hepatic side effects have included liver failure (0.3%), including fatalities. Laboratory abnormalities have included elevated AST (up to 72%), elevated ALT (up to 61%), elevated total bilirubin (up to 37%), and elevated indirect bilirubin (13%).

Hypersensitivity

Hypersensitivity reactions have included angioedema and fistula formation.

Dermatologic

Dermatologic side effects have included skin discoloration (up to 30%), rash (up to 29%), hand-foot syndrome (up to 29%), hair color changes (up to 29%), dry skin (up to 23%), alopecia (up to 14%), erythema (up to 12%), and pruritus (up to 12%). A case of periodic hair depigmentation has also been reported. Other possible dermatologic side effects may include thickness or cracking of the skin, blisters or occasional rash on the palms of the hands and soles of the feet.

Cardiovascular

Cardiovascular side effects have included hypertension (up to 34%) and peripheral edema (up to 24%). Heart failure including fatalities have been reported. Laboratory abnormalities have included decreased left ventricular ejection fraction (up to 16%).

Cardiovascular events, including heart failure, myocardial disorders and cardiomyopathy, some of which were fatal, have been reported through postmarketing experience.

Data from nonclinical (in vitro and in vivo) studies indicate that sunitinib has the potential to inhibit the cardiac action potential repolarization process (e.g., prolongation of QT interval). In GIST Study A, 23 patients (11%) on sunitinib versus 12 (12%) on placebo had observed QT prolongation greater than 20 milliseconds from baseline. No consistent, clinically significant QTc prolongation has been observed in completed clinical studies.

Musculoskeletal

Musculoskeletal side effects including pain in extremity, limb pain, limb discomfort or myalgia (up to 40%), arthralgia (up to 30%), and back pain (up to 28%) have been reported. Cases of myopathy and/or rhabdomyolysis have also been reported.

Patients with signs or symptoms of muscle toxicity should be managed as per standard medical practice.

Respiratory

Respiratory side effects have included cough (up to 27%), dyspnea (up to 26%), nasopharyngitis (up to 14%), oropharyngeal pain (up to 14%), and upper respiratory tract infection (up to 11%).

Renal

Baseline urinalysis is recommended, and patients should be monitored for the development or worsening of proteinuria. The safety of continued sunitinib treatment in patients with moderate to severe proteinuria has not been systematically evaluated. Sunitinib should be discontinued in patients with nephrotic syndrome.

Renal side effects have included laboratory abnormalities in creatinine (up to 70%). Postmarketing reports have included cases of proteinuria, rare cases of nephrotic syndrome, and renal failure, including fatalities.

Metabolic

Metabolic side effects have included laboratory abnormalities such as hyperglycemia (up to 71%), elevated creatine kinase (up to 49%), uric acid (up to 46%), hypoalbuminemia (up to 41%), hypophosphatemia (up to 36%), hypocalcemia (up to 42%), hyponatremia (up to 29%), hypoglycemia (up to 22%), hypokalemia (up to 21%), hypomagnesemia (up to 19%), hyperkalemia (up to 18%), and hypernatremia (up to 13%). Postmarketing reports of hyperammonemia have been received.

Other

Other side effects including appetite disturbance (up to 9%) have been reported.

Ocular

Ocular side effects including periorbital edema (up to 7%) and increased lacrimation (up to 7%) have been reported.

Endocrine

Endocrine side effects including hyperparathyroidism (up to 62%), hypothyroidism (up to 16%) and TSH elevations (up to 2%) have been reported.

Severe fatigue has been reported to be a result of the onset of hypothyroidism.

Patients with symptoms suggestive of hypothyroidism should have laboratory monitoring of thyroid function performed and be treated as per standard medical practice.

Three medical doctors stated in a letter to the New England Journal of Medicine that for their group of 65 patients treated with sunitinib, the incidence of laboratory evidence of thyroid dysfunction was 60% to 70%. They made a general recommendation for monitoring thyroid dysfunction in patients receiving sunitinib or similar compounds.

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