The most important serious side effects associated with treatment with Sutent® were: pulmonary embolism (1%), thrombocytopenia (1%), tumor bleeding (0.9%), febrile neutropenia (0.4%), increased blood pressure (0.4%), renal failure, heart failure and intestinal perforation. The most common side effects of all degrees associated with treatment with Sutent® (noted in more than 20% of patients) were fatigue, gastrointestinal disturbances such as diarrhea, nausea, stomatitis, dyspepsia and vomiting,as well as skin pigmentation disorder, rash, palmar-plantar erythrodysesthesia syndrome, skin dryness, hair color change, mucosal inflammation, asthenia, taste disorder and anorexia.
Side effects associated with treatment with sunitinib, noted in clinical studies of at least> 5% of patients with solid tumors, are listed below and systematized by system-organ classes, frequency and severity. Within each group, side effects are arranged in order of decreasing severity. Frequency: very often (> 1/10), often (> 1/100 to <1/10), infrequently (> 1/1000 to <1/100), rarely (> 1/10000 to <1/1000), very rarely (<1/10000).
From the hematopoiesis: very often - anemia, neutropenia, thrombocytopenia; often - leukopenia, lymphopenia, a decrease in the concentration of hemoglobin, infrequently - pancytopenia.
On the part of the digestive system: very often - perversion of taste, diarrhea, nausea, vomiting, stomatitis (including aphthous), mucositis, dyspepsia, abdominal pain, anorexia, constipation, glossodinia (tongue neuralgia), flatulence, dryness of the oral mucosa; often - pain in the mouth, bloating, gastroesophageal reflux, decreased appetite, gingival hemorrhage, dysphagia,ulceration of the oral mucosa, cheilitis, pain in the anus, hemorrhoids, rectal bleeding, belching; infrequently - pancreatitis, hepatic insufficiency, cholecystitis, in particular, acalculous cholecystitis; rarely gastrointestinal perforation.
From the skin and skin appendages: very often - a change in the color of the skin, palmar-plantar syndrome (erythrodysesthesia), rash (erythematous, spotted, papular, pancreatic, generalized, psoriasis-like), blisters, hair color changes, dry skin, erythema; often - alopecia, skin peeling, pruritus, exfoliative dermatitis, nail growth disorder, yellowing of skin, hyperkeratosis, acne, hyperpigmentation of skin, eczema; rarely Stevens-Johnson syndrome.
From the musculoskeletal system: often - pain in the extremities, arthralgia, myalgia, muscle spasm, back pain, muscle weakness.
From the nervous system: very often - headache; often - dizziness, paresthesia, insomnia or increased drowsiness, depression, peripheral neuropathy.
From the side of the cardiovascular system: very often - increased blood pressure; often - reduction of the left ventricular ejection fraction (LVEF), venous thromboembolism (pulmonary embolism, deep vein thrombosis), "hot flashes"; infrequently - heart failure, including chronic failure, a violation of the function of the left ventricle, pericardial effusion; rarely - interval lengthening QT, flicker and flutter of the atria like "pirouette".
From the urinary system: often - chromaturia (change in color of urine), infrequently - acute renal failure.
On the part of the respiratory system: very often - nosebleeds, cough; often - dyspnea, laryngeal pain, pleural effusion, dryness of the mucous membrane of the nasal cavity; infrequently hemoptysis.
From the endocrine system: often hypothyroidism, increased concentration of thyroid-stimulating hormone.
From the side of the organ of vision: often - increased tear, periorbital edema, edema of the eyelids.
Laboratory and instrumental data: very often - increased lipase activity in blood serum; often an increase in the activity of "hepatic" enzymes, an increase in the concentration of creatinine in the blood plasma,an increase in the activity of creatine phosphokinase and amylase in the serum, an increase in the concentration of uric acid in the blood plasma, a decrease in body weight.
Other: very often - asthenia / increased fatigue; often - influenza, fever, chills, peripheral edema, dehydration, pain in the chest area; infrequently
bleeding from tumors, delayed healing of wounds; rarely - lysis of the tumor (in some cases - with a lethal outcome). In patients with metastases in the brain or with reversible leukoencephalopathy syndrome, seizures are described, in some cases with a fatal outcome).
Results of post-marketing research
During the application of sunitinib after its registration the following undesirable phenomena were recorded:
From the hematopoiesis: reports of rare cases of thrombotic microangiopathy. In such cases it is recommended to temporarily suspend reception of sunitinib; after resolving the symptoms, the drug may be resumed at the discretion of the attending physician.
On the part of the respiratory system: reported cases of pulmonary embolism, sometimes with a lethal outcome.
From the endocrine system: In clinical trials and during post-marketing use of the drug, rare cases of hyperthyroidism with a transition to hypothyroidism were documented. Infrequently, thyroiditis.
From the immune system: reports on hypersensitivity reactions, including angioedema.
Infections and infestations:
reported cases of serious infections (including against neutropenia), some of which culminated in a fatal outcome. Infections developed with the use of sunitinib are common for cancer patients (often respiratory infections (pneumonia, bronchitis), urinary tract infections, skin infections (eg, inflammation of the subcutaneous fat), abscess (eg, mouth, genital area, anorectal area , skin, limbs, visceral abscess), infrequently sepsis / septic shock). Often, infections can be bacterial (for example, intra-abdominal, osteomyelitis), viral (eg, nasopharyngitis, oral cavity) or fungal (eg oral candidiasis, esophageal candidiasis) nature. There were rare cases of necrotizing fasciitis, including perineal involvement, sometimes with a fatal outcome.
From the musculoskeletal system: there are reports of rare cases of myopathy and / or rhabdomyolysis combined or without a combination with acute renal failure, with rare deaths. Most of these patients had initial risk factors and / or they received concomitant therapy with drugs for which unwanted reactions of this kind are characteristic. There are also reports of cases of fistula formation, sometimes associated with necrosis and / or tumor regression, some of which resulted in death. There were reports of cases of development of necrosis of the jaw against the background of application of sunitinib. Most patients had risk factors for developing jaw necrosis, such as intravenous bisphosphonate and / or previous dental treatment, which required invasive intervention.
From the nervous system: there are reports of cases of disorders of taste sensitivity, including agesia.
From the urinary system:there are reports of kidney / renal failure, some of which have been fatal. Reported cases of proteinuria and rare cases of nephrotic syndrome.
From the cardiovascular system: reported cases of cardiomyopathy, some of which culminated in death. There have been reports of cases of arterial thromboembolism (in some cases fatal) in patients taking Sutent®. The most frequent were: stroke, transient ischemic attack. Risk factors, in addition to the underlying disease and the age of the patient over 65, are: arterial hypertension, diabetes mellitus, thromboembolic complications in anamnesis.
From the skin: there are reports of rare cases of gangrenous pyoderma, erythema multiforme, toxic epidermal necrolysis.
Bleeding: reports have been received of cases of bleeding, sometimes fatal, including gastrointestinal bleeding, bleeding from the respiratory tract, tumors of the urinary tract and cerebral hemorrhages.
On the part of the digestive system: hepatitis; often - esophagitis.