SUTENT SIDE EFFECTS

  • Generic Name: sunitinib malate
  • Brand Name: Sutent
  • Drug Class: Antineoplastics, VEGF Inhibitor, Antineoplastic Tyrosine Kinase Inhibitors
Last updated on MDtodate: 10/12/2022

SIDE EFFECTS

The following serious adverse reactions are discussed in greater detail in other sections of the labeling.

  • Hepatotoxicity
  • Cardiovascular Events
  • QT Interval Prolongation and Torsade de Pointes
  • Hypertension ]
  • Hemorrhagic Events
  • Tumor Lysis Syndrome (TLS)
  • Thrombotic Microangiopathy
  • Proteinuria
  • Dermatologic Toxicities
  • Thyroid Dysfunction
  • Hypoglycemia
  • Osteonecrosis of the Jaw (ONJ)
  • Wound Healing

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 data described in the Warnings and Precautions reflect exposure to SUTENT (N = 7527) in GIST, advanced RCC, adjuvant treatment of RCC, and pNET. In this database, the most common adverse reactions (≥25%) are fatigue/asthenia, diarrhea, mucositis/stomatitis, nausea, decreased appetite/anorexia, vomiting, abdominal pain, hand-foot syndrome, hypertension, bleeding events, dysgeusia/altered taste, dyspepsia, and thrombocytopenia.

The data below reflect exposure to SUTENT in 966 patients who participated in the treatment phase of randomized trials of GIST (n=202), advanced RCC (n=375), adjuvant treatment of RCC (n=306), and pNET (n=83).

Gastrointestinal Stromal Tumor (GIST)

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. 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, nonfatal 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 1 in ≥10% of GIST Patients Who Received SUTENT in the Double-Blind Treatment Phase and More Commonly Than in Patients Given Placebo*

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
Cardiac
  Hypertension 15 4 11 0
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
Musculoskeletal
  Myalgia/limb pain 14 1 9 1
Metabolism/Nutrition
  Anorexiaa 33 1 29 5
  Asthenia 22 5 11 3
* Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.
Abbreviations: GIST=gastrointestinal stromal tumor; N=number of patients.
a Includes decreased appetite.

 

In the double-blind treatment phase of GIST Study 1, 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 1 in ≥10% of GIST Patients Who Received SUTENT or Placebo in the Double-Blind Treatment Phase*

Laboratory Parameter GIST
SUTENT (N=202) Placebo (N=102)
All Grades*
%
Grade 3-4*,a
%
All Grades*
%
Grade 3-4*,b
%
Any 68 (34) 22 (22)
Gastrointestinal
  AST/ALT 39 2 23 1
  Lipase 25 10 17 7
  Alkaline phosphatase 24 4 21 4
  Amylase 17 5 12 3
  Total bilirubin 16 1 8 0
  Indirect bilirubin 10 0 4 0
Cardiac
  Decreased LVEF 11 1 3 0
Renal/Metabolic
  Creatinine 12 1 7 0
  Potassium decreased 12 1 4 0
  Sodium increased 10 0 4 1
Hematology
  Neutrophils 53 10 4 0
  Lymphocytes 38 0 16 0
  Platelets 38 5 4 0
  Hemoglobin 26 3 22 2
* 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 treatment. 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%).

Advanced Renal Cell Carcinoma (RCC)

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 IFN-α 9 million International Units (MIU) (n=360). 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 Study 3 in ≥10% of Patients With RCC Who Received SUTENT or IFN-α*

Adverse Reaction Treatment-Naive RCC
SUTENT (N=375) IFN-α (N=360)
All Grades
%
Grade 3-4a
%
All Grades
%
Grade 3-4b
%
Any Adverse Reaction 99 77 99 55
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
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 51 12 1
  Constipation 23 1 14 <1
  Dry mouth 13 0 7 <1
  GERD/reflux esophagitis 12 <1 1 0
  Flatulence 14 0 2 0
  Oral pain 14 <1 1 0
  Glossodynia 11 0 1 0
  Hemorrhoids 10 0 2 0
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
Neurology
  Altered tasted 47 <1 15 0
  Headache 23 1 19 0
  Dizziness 11 <1 14 1
Musculoskeletal
  Back pain 28 5 14 2
  Arthralgia 30 3 19 1
  Pain in extremity/limb discomfort 40 5 30 2
Endocrine
  Hypothyroidism 16 2 1 0
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
Metabolism/Nutrition
  Anorexiae 48 3 42 2
Hemorrhage/Bleeding
  Bleeding, all sites 37 4f 10 1
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; IFN=interferon-α; 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 IFN-α included dyspnea (1%), fatigue (1%), abdominal pain (<1%), and depression (<1%).
c Includes flank pain.
d Includes ageusia, hypogeusia, and dysgeusia.
e Includes decreased appetite.
f Includes 1 patient with Grade 5 gastric hemorrhage.
g Includes depressed mood.

 

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

Table 4. Laboratory Abnormalities Reported in Study 3 in ≥10% of Treatment-Naive RCC Patients Who Received SUTENT or IFN-α

Laboratory Parameter Treatment-Naive RCC
SUTENT (N=375) IFN-α (N=360)
All Grades*
%
Grade 3-4*,a
%
All Grades*
%
Grade 3-4*,b
%
Gastrointestinal
  AST 56 2 38 2
  ALT 51 3 40 2
  Lipase 56 18 46 8
  Alkaline phosphatase 46 2 37 2
  Amylase 35 6 32 3
  Total bilirubin 20 1 2 0
  Indirect bilirubin 13 1 1 0
Renal/Metabolic
  Creatinine 70 <1 51 <1
  Creatine kinase 49 2 11 1
  Uric acid 46 14 33 8
  Calcium decreased 42 1 40 1
  Phosphorus 31 6 24 6
  Albumin 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
Hematology
  Neutrophils 77 17 49 9
  Hemoglobin 79 8 69 5
  Platelets 68 9 24 1
  Lymphocytes 68 18 68 26
  Leukocytes 78 8 56 2
* Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.
Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; IFN=interferon-α; 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 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%).

 

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 (n=306) on Schedule 4/2 or placebo (n=304). The median duration of treatment was 12.4 months (range: 0.13-14.9) for SUTENT and 12.4 months (range: 0.03-13.7) for placebo. Permanent discontinuation due to an adverse reaction occurred in 28% of patients on SUTENT and 6% on placebo. Adverse reactions leading to permanent discontinuation in >2% of patients include hand-foot syndrome and fatigue/asthenia. Dosing interruptions or delays occurred in 166 (54%) and 84 (28%) patients on SUTENT and placebo, respectively. One hundred forty patients (45.8%) out of 306 patients in the SUTENT arm and 15 patients (5%) out of 304 patients in the placebo arm had dose reductions.

Table 5 compares the incidence of common (≥10%) treatment-emergent adverse reactions for patients receiving SUTENT versus placebo.

Table 5. Adverse Reactions Reported in S-TRAC in ≥10% of Patients With RCC Who Received SUTENT and More Commonly Than in Patients Given Placebo*

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

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 daily continuous dosing (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. 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 6 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 6. Adverse Reactions Reported in the pNET Study 6 in ≥10% of Patients Who Received SUTENT and More Commonly Than in Patients Given Placebo*

Adverse Reaction pNET
SUTENT (N=83) Placebo (N=82)
All Grades
%
Grade 3-4a
%
All Grades
%
Grade 3-4b
%
Any Adverse Reaction 99 54 95 50
Constitutional
  Asthenia 34 5 27 4
  Fatigue 33 5 27 9
  Weight decreased 16 1 11 0
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
Cardiac
  Hypertension 27 10 5 1
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
Neurology
  Dysgeusia 21 0 5 0
  Headache 18 0 13 1
Musculoskeletal
  Arthralgia 15 0 6 0
Psychiatric
  Insomnia 18 0 12 0
Hemorrhage/Bleeding
  Bleeding eventsd 22 0 10 4
  Epistaxis 21 1 5 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.
Includes abdominal discomfort, abdominal pain, and abdominal pain upper.
d Includes hematemesis, hematochezia, hematoma, hemoptysis, hemorrhage, melena, and metrorrhagia.

 

Table 7 provides common (≥10%) treatment-emergent laboratory abnormalities.

Table 7. Laboratory Abnormalities Reported in the pNET Study 6 in ≥10% of Patients Who Received SUTENT

Laboratory Parameter pNET
SUTENT Placebo
N All Grades* % Grade 3-4*,a % N All Grades* % Grade 3-4*,b %
  AST increased 82 72 5 80 70 3
  ALT increased 82 61 4 80 55 3
  Alkaline phosphatase increased 82 63 10 80 70 11
  Total bilirubin increased 82 37 1 80 28 4
  Amylase increased 74 20 4 74 10 1
  Lipase increased 75 17 5 72 11 4
Renal/Metabolic
  Glucose increased 82 71 12 80 78 18
  Albumin decreased 81 41 1 79 37 1
  Phosphorus decreased 81 36 7 77 22 5
  Calcium decreased 82 34 0 80 19 0
  Sodium decreased 82 29 2 80 34 3
  Creatinine increased 82 27 5 80 28 5
  Glucose decreased 82 22 2 80 15 4
  Potassium decreased 82 21 4 80 14 0
  Magnesium decreased 52 19 0 39 10 0
  Potassium increased 82 18 1 80 11 1
Hematology
  Neutrophils decreased 82 71 16 80 16 0
  Hemoglobin decreased 82 65 0 80 55 1
  Platelets decreased 82 60 5 80 15 0
  Lymphocytes decreased 82 56 7 80 35 4
* 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 patients treated with SUTENT (N=7527) for GIST, advanced RCC, adjuvant treatment of RCC and pNET, 3.5% of patients experienced a venous thromboembolic event; 2.2% Grade 3-4.

Reversible Posterior Leukoencephalopathy Syndrome

There have been reports (<1%), some fatal, of patients presenting with seizures and radiological evidence of reversible posterior leukoencephalopathy syndrome (RPLS). 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 healthcare provider.

Pancreatic Function

Pancreatitis was observed in 5 patients (1%) receiving SUTENT for treatment-naive RCC compared to 1 patient (<1%) receiving IFN-α. In a trial of patients receiving adjuvant treatment for RCC, 1 patient (<1%) on SUTENT and none on placebo experienced pancreatitis. Pancreatitis was observed in 1 patient (1%) receiving SUTENT for pNET and 1 patient (1%) receiving placebo.

Postmarketing 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.

Blood and lymphatic system disorders: hemorrhage associated with thrombocytopenia*. Suspension of SUTENT is recommended; following resolution, treatment may be resumed at the discretion of the treating healthcare provider.

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

Renal and urinary disorders: renal impairment and/or failure*.

Respiratory disorders: pulmonary embolism*, pleural effusion*.

Skin and subcutaneous tissue disorders: pyoderma gangrenosum, including positive dechallenges.

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.

*including some fatalities

 

SRC: NLM .