Sunitinib-native - instructions for use, dose, side effects, contraindications

Active substanceSunitinibSunitinib

Similar drugsTo uncover

Sunitinib-native

capsules inwards

NATIVA, LLC Russia

Sutent®

capsules inwards

Pfizer Italy Sr.L. Italy

Dosage form: & nbspcapsules

Composition:

For 1 capsule:

Component	Amount, mg
Component	12.5 mg	25 mg	50 mg
Active substance:
Sunitiniba Malate	16,7	33,4	66,8
(in terms of sunitinib)	(12,5)	(25,0)	(50,0)
Excipients:
Mannitol	80,0	39,7	79,3
Croscarmellose sodium	6,6	5,0	10,0
Povidone To 30	5,6	4,2	8,4
Magnesium stearate	1,1	1,2	2,5
Hard gelatin capsules
Composition of capsules,%:
Capsule body:
Gelatin	Up to 100%	Up to 100%	Up to 100%
Titanium dioxide	1	1,3333	0,5
Dye iron oxide yellow	0,5	0,7	-
Iron Oxide Red Dye Oxide	-	0,09	1,5
Capsule cap:
Gelatin	Up to 100%	Up to 100%	Up to 100%
Titanium dioxide	1	1,3333	0,5
Dye iron oxide yellow	0,5	0,7	-
Iron Oxide Red Dye Oxide	-	0,09	1,5

Description:

Dosage of 12.5 mg: hard gelatin capsules No. 4, yellow body, yellow lid.

Dosage of 25 mg: hard gelatin capsules No. 3, orange body, orange lid.

Dosage 50 mg: hard gelatin capsules number 2, the body of red-brown color, the lid of a red-brown color.

Contents of capsules - powder or granules from yellow to orange.

Pharmacotherapeutic group:Antitumor agent - protein tyrosine kinase inhibitor

ATX: & nbsp

L.01 Antineoplastic agents

Pharmacodynamics:

Sunitinib is able to simultaneously inhibit the receptors of various tyrosine kinases (RTK) involved in tumor growth, pathological angiogenesis and metastasis formation. It exhibits inhibitory activity against many kinases (> 80 kinases). It has been shown that it is a potent inhibitor of platelet-derived growth factor receptors (PDGFRα and PDGRFβ), receptors of the growth factor of the vascular endothelium (VEGRF1, VEGRF2 and VEGRF3), the stem cell factor receptor (KIT), the receptor Fms-like tyrosine kinase-3 (FLT), the colony-stimulating factor receptor (CSF-1R) and the receptor of the neurotrophic glial factor (RET). The activity of the main metabolite was similar to that of sunitinib.

Sunitinib inhibited the phosphorylation of many RTKs (PDGRFβ, VEGRF2 and KIT) in xenografts of tumors expressing target RTC in vivo, and demonstrated suppression of tumor growth or its regression and / or suppression of metastases on experimental models of various tumors. Sunitinib demonstrated the ability to inhibit the growth of tumor cells expressing the deregulated target RTC (PDGFR, RET or KIT), in vitro and PDGRFβ- and VEGRF2-dependent angiogenesis in vivo.

Pharmacokinetics:

Suction

Sunitinib is well absorbed when taken orally. Time to reach the maximum concentration (C_mOh) is 6-12 hours (T_mOh) after administration. Food intake does not affect the bioavailability of sunitinib.

Distribution

The binding of sunitinib and its main metabolite with plasma proteins is 95% and 90%, respectively, without an explicit dependence on the concentration in the range of 100 to 4000 ng / ml. The value of the calculated volume of distribution in tissues (Vd/F) is 2230 liters.

Metabolism

The metabolism of sunitinib is mainly carried out by isoenzyme CYP3A4, the enzyme cytochrome P450, resulting in the formation of the main active metabolite, which is further metabolized by the same isoenzyme CYP3A4. The proportion of active metabolite is 23-37% of the area under the concentration-time curve (AUC).

With repeated daily use, there is a 3-4-fold accumulation of sunitinib and a 7-10-fold accumulation of its main metabolite. Equilibrium concentrations of sunitinib and its main active metabolite are achieved after 10-14 days. By day 14, the total concentration of sunitinib and its main active metabolite in blood plasma is 62.9-101 ng / ml.With repeated daily administration or repeated cycles with different dosing regimens, no significant changes in the pharmacokinetics of sunitinib and its main active metabolite were detected.

Excretion

After a single oral intake, the elimination half-life (T_1/2) of sunitinib and its main active metabolite is 40-60 and 80-110 hours, respectively. Sunitinib is excreted mainly with feces (61%). Through the kidneys, approximately 16% of the administered dose of sunitinib is excreted unchanged and in the form of metabolites. The total clearance for oral administration is 34-62 l / h.

Pharmacokinetics in selected patient groups

Age, weight, creatinine clearance, race, sex, or grade according to the classification of the Eastern Joint Oncology Group (scale ECOG) do not have a clinically significant effect on the pharmacokinetics of sunitinib and its active metabolite.

Body weight and quality of life: Population pharmacokinetic analysis showed that there is no need to correct the initial dose of sunitinib depending on body weight and quality of life on a scale ECOG.

Floor: The available data show that the apparent clearance of sunitinib in women may be 30% lower than in men, but this difference does not require correction of the initial dose of sunitinib.

Patients with impaired renal function

After taking a single dose of sunitinib, its plasma concentration in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min) was the same as in patients with normal renal function (creatinine clearance greater than 80 ml / min). Although sunitinib is not excreted from the patient's body by hemodialysis, its plasma concentration in patients suffering from severe renal insufficiency and being on hemodialysis was 47% lower than in patients with normal renal function.

Patients with hepatic impairment

After taking a single dose of sunitinib, its plasma concentrations in patients with mild hepatic insufficiency (class A on the Child-Pugh scale), patients with moderate-to-moderate hepatic insufficiency (class B on the Child-Pugh scale), and patients with normal liver function were the same.

Indications:

- Gastrointestinal stromal tumors (GISO) in the absence of the effect of imatinib therapy due to resistance or intolerance;

- common and / or metastatic renal cell carcinoma in patients who have not previously received specific treatment;

- common and / or metastatic renal cell carcinoma in the absence of the effect of cytokine therapy;

- unresectable or metastatic highly differentiated neuroendocrine pancreatic tumors in adults with progression of the disease.

Contraindications:

- Hypersensitivity to sunitinib or any other component of the drug;

- pregnancy and the period of breastfeeding;

- age to 18 years (effectiveness and safety of sunitinib not established);

- hepatic failure of severe severity.

Carefully:

Sunitinib should be used with caution in patients with lengthening interval QT in the history, to the patients taking antiarrhythmic medicines, or to patients with the corresponding diseases of the heart, bradycardia or electrolyte balance disorders, as well as in renal or hepatic insufficiency.

Care must be taken to reduce the dose of sunitinib while taking potent inhibitors of the isoenzyme CYP3A4, which can increase the concentration of sunitinib in the blood plasma.

Pregnancy and lactation:

The use of sunitinib in pregnancy and during breastfeeding is contraindicated.

Fertility

Sunitinib therapy can adversely affect the fertility of men and women. During and for at least three months after discontinuing drug therapy Sunitinib-native it is necessary to use reliable methods of contraception.

Dosing and Administration:

Inside. The intake of the drug is not dependent on food intake.

Gastrointestinal stromal tumors in the absence of the effect of imatinib therapy due to resistance or intolerance

The recommended dose of the drug Sunitinib-native is 50 mg per day inside for 4 weeks, followed by a break of 2 weeks (4/2 mode). The full cycle of therapy is, therefore, 6 weeks.

Prevalent and / or metastatic renal cell carcinoma in patients who have not previously received a specific treatment, or in the absence of the effect of cytokine therapy

The recommended dose of the drug Sunitinib-native is 50 mg per day inside for 4 weeks, followed by a break of 2 weeks (4/2 mode). The full cycle of therapy is, therefore, 6 weeks.

Unresectable or metastatic highly differentiated neuroendocrine pancreatic tumors in adults with progression of the disease

The recommended dose of the drug Sunitinib-native is 37.5 mg daily without interruption.

If the drug was missed, you should not make up the missed dose. The patient should take the usual prescribed dose the next day.

Depending on the individual tolerability and safety, the daily dose of the drug Sunitinib-native can be reduced or increased by 12.5 mg and should not exceed 75 mg and not less than 25 mg for patients with gastrointestinal and renal cell tumors. Depending on the individual intolerance, a temporary discontinuation of the drug may be required Sunitinib-native.

For patients with unresectable or metastatic neuroendocrine tumors of the pancreas, the dose of the drug Sunitinib-native should not be more than 50 mg per day.

When there are signs of disease progression, the use of the drug Sunitinib-native should be discontinued.

It is necessary to avoid simultaneous application of the drug Sunitinib-native with potential isoenzyme inhibitors CYP3A4, such as ketoconazole. In cases where this can not be done, it may be necessary to reduce the daily dose of the drug Sunitinib-native a minimum of 37.5 mg per day for gastrointestinal stromal tumors and metastatic renal cell carcinoma and a minimum of 25 mg per day for neuroendocrine pancreatic tumors.

Also, joint use of the drug should be avoided Sunitinib-native with potential isoenzyme inducers CYP3A4, such as rifampicin. In cases where this can not be done, an increase in the daily dose of the drug may be required Sunitinib-native, which should be carried out in stages, by 12.5 mg (up to 87.5 mg per day for gastrointestinal stromal tumors and metastatic renal cell carcinoma and up to 62.5 mg per day for neuroendocrine pancreatic tumors), based on careful monitoring of drug tolerance.

Use in children: efficacy and safety of the Sunitinib-native drug in children is not established.

Use in elderly and elderly patients: correction of the dose is not required. Use in patients with impaired liver function: in patients with mild and moderate hepatic insufficiency (class A, B according to the Child-Pugh classification), correction of the dose of Sunitinib-native is not required. Patients with severe degree of hepatic insufficiency (class C according to the Child-Pugh classification) Sunitinib-native preparation is not recommended.

Use in patients with impaired renal function: patients with mild, moderate and severe renal failure (including hemodialysis) do not require correction of the initial dose of Sunitinib-native. Further dose selection in this category of patients should be carried out depending on individual tolerability.

Side effects:

The most important serious side effects associated with treatment with sunitinib were: pulmonary embolism (1%), thrombocytopenia (1%), tumor bleeding (0.9%), febrile neutropenia (0.4%), increased blood pressure (0 , 4%), renal failure, heart failure, intestinal perforation.

The most frequent side effects of all degrees,There were fatigue, gastrointestinal disturbances such as diarrhea, nausea, stomatitis, dyspepsia and vomiting, as well as skin pigmentation disorder, rash, palmar-plantar erythrodysesthesia syndrome, dry skin , hair color changes, inflammation of mucous membranes, asthenia, taste disorders and anorexia.

Side effects associated with treatment with sunitinib, noted in clinical studies of sunitinib in at least> 5% of patients with solid tumors, are listed below and systematized according to system-organ classes, frequency and severity. Within each group, side effects are arranged in order of decreasing severity.

The incidence of adverse reactions is estimated as follows: "very frequent" ≥10%; "often" ≥ 1% and <10%, "infrequently" ≥0.1% and <1%, "rarely" ≥ 0.01% <0.1%, "very rarely" - <0.01%.

Violations of the blood and lymphatic system: Often - Anemia, neutropenia, thrombocytopenia; often - leukopenia, lymphopenia, a decrease in the concentration of hemoglobin; infrequently - pancytopenia.

Disorders from the gastrointestinal tract: Often - taste distortion, 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, bleeding gums, dysphagia, ulceration of the oral mucosa, cheilitis, pain in the anus, hemorrhoids, rectal bleeding, belching; infrequently - pancreatitis; rarely - gastrointestinal perforation.

Disturbances from the skin and subcutaneous tissues: Often - Skin discolouration, palmar-plantar syndrome (erythrodysesthesia), rash (erythematous, spotty, papular, pancreas, generalized, psoriasis-like), blisters, hair color changes, dry skin, erythema; often - alopecia, skin peeling, skin itch, exfoliative dermatitis, nail growth disorder, yellowing of skin, hyperkeratosis, acne, hyperpigmentation of skin, eczema; rarely - Stevens-Johnson syndrome.

Disturbances from musculoskeletal and connective tissue: often - pain in the extremities, arthralgia, myalgia, muscle spasm, back pain, muscle weakness.

Disturbances from the nervous system: Often - headache; often - dizziness, paresthesia, insomnia or increased drowsiness, peripheral neuropathy.

Heart Disease: often - reduction of the left ventricular ejection fraction (LVEF); infrequently - heart failure, including chronic failure, a violation of the function of the left ventricle, pericardial effusion; rarely - prolongation of QT interval, flicker and atrial flutter as "pirouette".

Vascular disorders: Often - Increased blood pressure; often - venous thromboembolism (pulmonary embolism, deep vein thrombosis), "hot flashes" of blood.

Disorders from the kidneys and urinary tract: often - chromaturia (change in color of urine); infrequently acute renal failure.

Disturbances from the respiratory system, chest and mediastinal organs: very often - nosebleeds, cough; often - dyspnea, laryngeal pain, pleural effusion, dryness of the mucous membrane of the nasal cavity; infrequently - hemoptysis.

Disorders from the endocrine system: often - hypothyroidism, increasing the concentration of thyroid-stimulating hormone.

Disturbances on the part of the organ of sight: often - increased tear, periorbital edema, edema of the eyelids.

Laboratory and instrumental data: Often - increased lipase activity in blood serum; often - Increased activity of "liver" enzymes, increased creatinine concentration in blood plasma, increased activity of creatine phosphokinase and amylase in the blood serum, increased concentration of uric acid in blood plasma, weight loss.

General disorders and disorders at the site of administration: 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 - tumor lysis syndrome (in some cases, with a fatal outcome).

In patients with metastases to the brain or with reversible leukoencephalopathy syndrome, cases of seizures, in some cases fatal, are described.

Results of postmarketing studies of sunitinib

During the application of sunitinib after its registration the following undesirable phenomena were recorded:

Violations of the blood and lymphatic system: 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.

Disturbances from the respiratory system, chest and mediastinal organs: reported cases of pulmonary embolism, sometimes with a lethal outcome.

Disorders from the endocrine system: in clinical studies of sunitinib and during post-marketing application of sunitinib, rare cases of hyperthyroidism with transition to hypothyroidism were recorded; infrequently - thyroiditis.

Immune system disorders: hypersensitivity reactions, including angioedema.

Infectious and parasitic diseases: reported cases of serious infections (including neutropenia), some of which ended in a fatal outcome. Infections that 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 (eg, 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.

Disturbances from musculoskeletal and connective tissue: there are reports of rare cases of myopathy and / or rhabdomyolysis in combination or without combination with acute renal failure, with rare cases of death. 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.

Disturbances from the nervous system: there are reports of cases of disorders of taste sensitivity, including agesia.

Disorders from the kidneys and urinary tract: there are reports of kidney / renal failure, some of which have been fatal. Reported cases of proteinuria and rare cases of nephrotic syndrome.

Heart Disease: reported cases of cardiomyopathy, some of which culminated in death.

Vascular disorders: there are reports of cases of arterial thromboembolism (in some cases fatal) in patients taking sunitinib. 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. Reports were received of cases of bleeding, sometimes fatal, including gastrointestinal bleeding, bleeding from the respiratory tract and hemorrhages in the brain.

Disturbances from the skin and subcutaneous tissues: there are reports of rare cases of gangrenous pyoderma, erythema multiforme, toxic epidermal necrolysis.

Disorders from the gastrointestinal tract: esophagitis.

Disturbances from the liver and bile ducts: hepatitis.

Overdose:

When an overdose of sunitinib treatment is symptomatic, there is no specific antidote. If necessary, it is recommended to induce vomiting or to wash the stomach.

Interaction:

Drugs that increase the concentration of sunitinib in blood plasma Joint use of a single dose of sunitinib with an inhibitor of isoenzyme CYP3A4, ketoconazole, increases C_mOh and AUC_0-∞ sunitinib complex and the main active metabolite of 49% and 51% respectively.

The use of sunitinib in conjunction with other isoenzyme inhibitors CYP3A4 (e.g., ritonavir, itraconazole, erythromycin, clarithromycin or grapefruit juice) may increase its concentration. It is necessary to avoid joint intake of inhibitors of isoenzyme CYP3A4 with sunitinib or select an alternative drug with minimal ability to inhibit isozyme CYP3A4. If this is not possible, it is likely to be necessary to reduce the daily dose of sunitinib 12.5 mg to 37.5 mg per day with gastrointestinal stromal tumors and metastatic RCC, and up to 25 mg per day with neuroendocrine tumors of the pancreas.

Drugs that reduce the concentration of sunitinib in the blood plasma

Joint use of a single dose of sunitinib with an isoenzyme inducer CYP3A4, rifampicin, decreases C_mOh and AUC_0-∞ complex of sunitinib and the main active metabolite by 23% and 46% respectively.

Application of sunitinib in conjunction with other isoenzyme inducers CYP3A4 (eg, dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital or St. John's wort) can lead to a decrease in the concentration of sunitinib. It should avoid joint intake of isoenzyme inducers CYP3A4 with sunitinib or should choose an alternative drug with a minimum ability to induce isoenzyme CYP3A4. If this is not possible, it will probably be necessary to increase the dose of 12.5 mg of sunitinib by monitoring the patient's tolerability. The daily dose in this case should not exceed 87.5 mg with gastrointestinal stromal tumors and metastatic renal cell carcinoma and 62.5 mg with neuroendocrine tumors of the pancreas.

Special instructions:

Treatment with drug Sunitinib-native should be carried out under the supervision of a doctor who has experience working with antitumor drugs.

At the beginning of each cycle of drug therapy Sunitinib-native a complete analysis of hematologic parameters should be carried out.

Hemorrhage, neoplastic bleeding

There are reports of cases of bleeding, sometimes fatal, including gastrointestinal bleeding, bleeding from the respiratory tract, tumors, urinary tract and hemorrhages in the brain.These phenomena can occur unexpectedly, and in the case of tumoral foci in the lungs manifest in the form of severe or life-threatening hemoptysis or pulmonary hemorrhage. There are reports of the development of pulmonary hemorrhage (in some cases, fatal) in patients taking sunitinib for renal cell cancer, gastrointestinal tumors or non-small cell lung cancer.

Important: sunitinib It is not intended for the treatment of non-small cell lung cancer.

Periodically, it is necessary to conduct a medical examination and evaluate blood indicators for the early detection of the first signs of bleeding and the application of the necessary therapeutic measures. With concomitant therapy with anticoagulants, blood coagulability should be monitored. Nasal bleeding associated with sunitinib therapy was the most common type of bleeding in patients with solid tumors and occurred in 8% of cases. It was noted in half the cases in patients with hemorrhagic complications.

Dysfunction of the heart

The relationship between inhibition of tyrosine kinase receptor (RTK) and cardiac function has not been studied.Unknown subjected whether patients whose cases of cardiovascular disease within the last 12 months before the destination sunitinib treatment have been reported, such as myocardial infarction (including severe / unstable angina), coronary / peripheral bypass surgery, symptomatic congestive heart failure, cerebrovascular complications or transient ischemic disorders or pulmonary embolism, greater risk for left ventricular dysfunction associated with treatment. When the drug is prescribed Sunitinib-native This category of patients should carefully assess the risk / benefit ratio.

During drug therapy Sunitinib-native patients should be periodically examined for signs of clinical signs and symptoms of chronic heart failure (CHF). LVEF is recommended to be evaluated before the start of therapy, and also periodically during treatment. When clinical signs of CHF appear, treatment with sunitinib should be discontinued. In the absence of clinical signs of heart failure, but with the parameters LVEF of less than 50% or a decrease of this parameter over 20% compared to baseline (beforetherapy), the dose of the drug Sunitinib-native it is recommended to reduce or stop taking the drug.

Interval lengthening QT

At concentrations about 2 times higher than therapeutic, sunitinib contributes to the lengthening of the interval QTcF (Frederick correction). The clinical significance of this effect is unclear and depends on the risk factors and the susceptibility of the individual patient. Sunitinib should be used with caution in patients with lengthening the interval QT in anamnesis, in patients taking antiarrhythmic drugs, or in patients with the corresponding heart disease, bradycardia or electrolyte balance disorders. Care must be taken to reduce the dose of sunitinib while taking potent inhibitors of the CYP3A4 isoenzyme, which can increase the concentration of sunitinib in plasma. Before the initiation of therapy and during treatment with sunitinib, ECG monitoring is recommended.

Arterial hypertension

Patients should be examined for increased blood pressure, using standard methods of control. In patients with severe form of hypertension, which can not be treated,Sunthinib therapy is temporarily discontinued. Therapy is resumed as soon as hypertension can be suppressed.

Thyroid dysfunction

It is recommended to monitor all patients during sunitinib therapy for the development of thyroid dysfunction. Patients with signs and / or symptoms of thyroid dysfunction should undergo laboratory monitoring. A background study of laboratory parameters of thyroid function in patients with hypothyroidism or hyperthyroidism is also recommended. Treatment of patients with hypothyroidism is carried out in accordance with standard medical practice before the initiation of sunitinib therapy.

Disturbances from the skin and subcutaneous tissues

Patients should be warned that during the treatment with sunitinib, a discoloration of the skin may be observed due to the presence of a dye (yellow) in the preparation. There may also be a discoloration of the hair or skin.

Disorders from the gastrointestinal tract

Since the use of sunitinib may cause nausea and vomiting, preventive administration of antiemetics should be considered.When diarrhea occurs, antidiarrhoeic agents are prescribed.

Dysfunction of the pancreas

During treatment with the drug Sunitinib-native periodically it is necessary to check the activity of lipase and amylase in the blood serum. If there are or are signs of pancreatitis, regular medical supervision is necessary.

Symptoms of reversible posterior leukoencephalopathy

Patients with brain metastases, convulsions history and / or signs / symptoms reversible rear leukoencephalopathy, such as rise in blood pressure, headache, confusion, impaired mental activity, vision loss, including cortical blindness, should be monitored by standard methods, including monitoring of blood pressure. If these symptoms appear on the background of therapy, it is recommended to temporarily stop taking the drug Sunitinib-native. After the disappearance of the symptoms, treatment can be resumed according to the decision of the attending physician.

Thrombotic microangiopathy

When thrombotic microangiopathy occurs, temporary discontinuation of sunitinib treatment is recommended.After the disappearance of the symptoms, treatment can be resumed according to the decision of the attending physician.

Impaired renal function

A background study of kidney function before treatment is recommended, as well as monitoring of kidney function during sunitinib therapy. The safety of sunitinib in patients with moderate or severe proteinuria was not assessed. In patients with nephrotic syndrome, treatment with sunitinib should be discontinued.

Impaired liver function

During therapy with sunitinib, there were cases of liver failure, sometimes with a fatal outcome. Indicators of functional "hepatic" tests (alanine aminotransferase, aspartate aminotransferase, bilirubin concentration) should be monitored before sunitinib therapy begins, during each therapy cycle and in the presence of clinical indications. With the development of side effects on the part of the liver of grade 3 and 4, you should stop taking the drug. If the symptoms of hepatotoxicity are not resolved, the drug should be discontinued.

Hematologic disorders

There are reports of a decrease in the number of neutrophils of 3 and 4 degrees of severity (in 13.1% and 0.9%respectively). Reduction in the number of platelets of 3 and 4 degrees of severity was noted in 4% and 0.5% of cases, respectively. The cases listed were not cumulative, usually reversible and did not lead to the abolition of therapy. In some cases development of fatal bleeding in combination with thrombocytopenia was noted.

Tumor lysis syndrome

Patients with a large tumor mass (before starting treatment with sunitinib) should be under close medical supervision, since they have the greatest risk of developing a tumor lysis syndrome.

Delayed wound healing

Against the background of the application of sunitinib, there were cases of delayed healing of wounds. AT If it is necessary to carry out extensive surgical intervention, a temporary suspension is recommended. There are limited data on the time after the operation, after which you can resume therapy. Therefore, the decision to resume therapy should be taken based on an assessment of the wound after the operation.

Osteonecrosis of the jaw

Against the background of application of sunitinib, there were cases of development of the osteonecrosis of the jaw.Most of the cases were observed in patients on the background of intravenous bisphosphonates, the reception of which is a risk factor for the development of osteonecrosis of the jaw. Caution should be exercised while applying sunitinib and intravenous forms of bisphosphonates.

In addition, invasive procedures for oral diseases are also risk factors for osteonecrosis of the jaw. Before starting therapy with sunitinib, a dental examination of the patient should be performed. In patients receiving sunitinib, previously received intravenous therapy with bisphosphonates, should avoid invasive procedures in the oral cavity whenever possible.

Hypersensitivity reactions and angioedema

If angioedema develops as a result of a hypersensitivity reaction, sunitinib therapy should be discontinued and standard treatment should be prescribed.

Fistula formation

In the formation of fistula therapy, sunitinib should be discontinued. There are limited data on the use of sunitinib after fistula formation.

Cardiomyopathy

In postmarketing studies of sunitinib, there were cases of impaired cardiac function (sometimes with a fatal outcome),such as heart failure, cardiomyopathy, myocardial dysfunction. Based on this information, it is suggested that the use of suntinib may increase the risk of cardiomyopathy. In patients treated with sunitinib, there were no other risk factors for the development of cardiomyopathy, except for the effects of sunitinib itself.

Impact on fertility

Based on the results of preclinical studies of sunitinib, it can be concluded that sunitinib therapy can adversely affect the fertility of men and women. During and for at least three months after discontinuation of sunitinib therapy, reliable contraceptive methods should be used.

Effect on the ability to drive transp. cf. and fur:

No data on the effect of the drug Sunitinib-native on the ability to drive vehicles and mechanisms. In the case of development of undesirable reactions from the musculoskeletal and connective tissue, the organs of vision or the nervous system when the drug is used Sunitinib-native should refrain from the management of vehicles and mechanisms, as well as from other potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Capsules, 12.5 mg, 25 mg and 50 mg.

Packaging:

For 7 capsules in a contour mesh box made of aluminum foil foil and PVC film.

For 28 or 30 capsules in cans of polyethylene terephthalate, sealed with polyethylene lids.

4 contour squares, 1 bank along with instructions for use in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004193

Date of registration:16.03.2017

Expiration Date:16.03.2022

The owner of the registration certificate:NATIVA, LLC NATIVA, LLC Russia

Manufacturer: & nbsp

NATIVA, LLC Russia

Information update date: & nbsp07.04.2017

Illustrated instructions

Instructions

Sunitinib-native (Sunitinib-nativ)