Sutent
Sutent: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Sutent
ATX code: L01XE04
Active ingredient: sunitinib (Sunitinib)
Manufacturer: Pfizer Italia S.r. L. (Pfizer Italia SrL) (Italy)
Description and photo update: 2018-27-11
Prices in pharmacies: from 157,000 rubles.
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Sutent is an anticancer drug.
Release form and composition
Sutent is produced in the form of gelatinous hard capsules, with the Pfizer inscription on the lid (all inscriptions on the lid and body are applied in white ink); the contents of the capsules are orange to yellow granules (7 pcs. in a blister, 28 or 30 pcs. in a high-density polyethylene bottle; in a cardboard box 4 blisters or 1 bottle and instructions for use according to Sutenta):
- dosage 50 mg: light brown-orange body and cap, inscription STN 50 mg on the body;
- dosage of 25 mg: red-brown body, brown-orange cap, inscription STN 25 mg on the body;
- dosage 12.5 mg: body and cap are red-brown, on the body the inscription STN 12.5 mg.
1 capsule contains:
- active substance: sunitinib malate - 66.8; 33.4 or 16.7 mg (corresponds to the content of sunitinib - 50, 25 or 12.5 mg);
- additional components: croscarmellose sodium, mannitol, magnesium stearate, povidone;
- capsule shell: titanium dioxide, gelatin, iron oxide red; additionally for 25 and 50 mg - iron oxide black and yellow;
- ink: povidone, shellac, titanium dioxide.
Pharmacological properties
Pharmacodynamics
Sunitinib is an antitumor agent, an inhibitor of protein tyrosine kinases [PTK (Protein Tyrosine Kinase)] - non-receptor tyrosine kinases located in the cytoplasm of the cell, many of which function in conjunction with receptors. It is capable of simultaneously inhibiting the receptors of various PTKs involved in the processes of tumor growth, pathological angiogenesis and the formation of metastases. The inhibitory activity of the substance is detected against more than 80 kinases. Sunitinib belongs to potent inhibitors of the following receptors: vascular endothelial growth factor (VEGRF1, VEGRF2 and VEGRF3), platelet growth factor (PDGFRα and PDGRFβ), colony-stimulating factor, Fms-like tyrosine kinase-3 (FLT) (RETT-stimulating glial factor) factor a. Its main metabolite has activity similar to that of sunitinib.
The active ingredient Sutenta inhibits the phosphorylation reactions of many RTKs (KIT, VEGRF2, PDGFRβ) in xenografts of tumors expressing target RTKs in vivo, and in experimental models of various tumors inhibits their growth or regression, and / or blocks the development of metastases.
Sunitinib has the ability to inhibit in vitro the growth of tumor cells expressing deregulated target RTKs (RET, PDGFR, or KIT), and in vivo, PDGRFβ- and VEGRF2-dependent angiogenesis.
Pharmacokinetics
When taken orally, the active substance is well absorbed from the gastrointestinal tract (GIT) and after 6–12 hours reaches its maximum concentration (C max) in the blood serum. Food intake does not affect the bioavailability of the drug.
Sunitinib and its metabolite bind to plasma proteins by 95 and 90%, respectively, in the absence of a clear dependence on the level of plasma concentration in the range of 100-4000 ng / ml. The calculated volume of distribution (V d) is 2230 liters, which demonstrates a high degree of substance penetration into tissues.
The metabolic transformation of sunitinib is carried out mainly with the participation of the isoenzyme CYP3A4 - the enzyme of cytochrome P450, which results in the formation of the main active metabolite, the biotransformation of which subsequently occurs with the help of the same isoenzyme CYP3A4. Part of the area under the concentration-time curve (AUC), which is 23–37%, falls on the share of the active metabolite.
Equilibrium concentrations (C ss) of sunitinib and its main active metabolite are reached 10-14 days after ingestion. By the 14th day, the total plasma level of sunitinib and its metabolite is 62.9-101 ng / ml. Against the background of repeated daily use or repeated cycles with different dosing regimen, no significant changes in the pharmacokinetics of sunitinib and its main metabolite were identified.
Sunitinib is excreted mostly in the feces - 61%, as well as approximately 16% of the administered dose in the form of unchanged substance and its metabolites - by the kidneys. When taken orally, the total clearance was 34–62 l / h. In healthy volunteers after a single oral administration of Sutent, the half-life (T 1/2) of sunitinib and its active metabolite is approximately 40-60 and 80-110 hours, respectively. Against the background of repeated daily use of Sutent, 3-4-fold accumulation of the active substance and 7-10-fold accumulation of the main metabolite is noted.
No clinically significant effect on the pharmacokinetic parameters of sunitinib and its active metabolite due to age, weight, race, sex of the patient, or creatinine clearance was found.
According to the available data, it has been determined that in women the apparent clearance of sunitinib may be 30% lower than in men, but this difference has no clinical significance and does not require adjustment of the initial dose of Sutent.
Based on population pharmacokinetic analyzes, there is no need to adjust the starting dose of Sutent based on body weight or the Eastern Allied Oncology Group (ECOG) Quality of Life Index.
Indications for use
- advanced and / or metastatic renal cell carcinoma, in the case of ineffective cytokine therapy;
- advanced and / or metastatic renal cell carcinoma in patients who have not previously received specific treatment;
- gastrointestinal stromal tumors, in case of ineffective treatment with imatinib due to resistance / intolerance;
- unresectable or metastatic highly differentiated neuroendocrine pancreatic tumors with progression of the lesion.
Contraindications
Absolute:
- childhood;
- pregnancy and the period of breastfeeding;
- hypersensitivity to any of the constituents of the drug.
Relative (requires the use of Sutent capsules with extreme caution):
- a history of QT interval prolongation;
- taking antiarrhythmic drugs or the presence of corresponding heart disease, bradycardia (ECG control is recommended before and during treatment);
- renal and / or hepatic impairment;
- electrolyte imbalance;
- a combination with potent inhibitors of the CYP3A4 isoenzyme capable of increasing the plasma concentration of sunitinib in the blood.
Sutent, instructions for use: method and dosage
Sutent capsules are taken orally, regardless of food intake.
Recommended dosage regimen of the drug:
- advanced and / or metastatic renal cell carcinoma in patients who have not previously received specific treatment, or in the absence of an effect from the use of cytokines; gastrointestinal stromal tumors if it is impossible to achieve the effect of imatinib treatment as a result of resistance / intolerance: for 4 weeks in a daily dose of 50 mg, with a further break in use for 2 weeks (therapy regimen 4/2); one treatment cycle in total is 6 weeks;
- unresectable or metastatic highly differentiated neuroendocrine tumors of the pancreas in adults with progression of the lesion: daily, in a continuous mode, at a daily dose of 37.5 mg.
If you skip taking an antineoplastic agent, you should not replenish the missed dose. The next day, it is recommended to use Sutent at the usual dose.
Taking into account individual tolerance and safety, the dose of Sutent can be reduced or increased by 12.5 mg. When treating gastrointestinal and renal cell tumors, the dose of the drug per day should not be higher than 75 mg and below 25 mg. In patients with unresectable or metastatic neuroendocrine tumors of the pancreas, the maximum daily dose should be no more than 50 mg.
Side effects
The most serious and important side effects associated with Sutent therapy include arterial hypertension (0.4%), febrile neutropenia (0.4%), tumor bleeding (0.9%), thrombocytopenia (1%), pulmonary embolism (1%).
Below are the adverse events associated with sunitinib therapy and observed in clinical studies in more than 5% of patients with solid tumors (frequency: very often - ≥1 / 10; often - from ≥1 / 100 to <1/10; infrequently - from ≥1 / 1000 to <1/100; rarely - from ≥1 / 10,000 to <1/1000; extremely rare - ≤1 / 10,000):
- cardiovascular system: very often - increased blood pressure; often - venous thromboembolism (including deep vein thrombosis, pulmonary embolism), decreased left ventricular ejection fraction (LVEF); infrequently - heart failure, impaired left ventricular function, congestive heart failure (CHF); rarely - pirouette-type atrial fibrillation and atrial flutter, lengthening of the QT interval;
- digestive system: very often - dry mouth, flatulence, neuralgia of the tongue (glossodynia), anorexia, abdominal pain, constipation, mucositis, stomatitis, dyspepsia, nausea, diarrhea, vomiting, taste perversion; often - gastroesophageal reflux, pain in the mouth; infrequently - pancreatitis; rarely - gastrointestinal perforation;
- skin and skin appendages: very often - dry skin, discoloration of hair / skin coloration, blisters, erythema, rash (papular, macular, erythematous, psoriasis-like, pityriasis, generalized), palmar-plantar syndrome (erythrodysesthesia); often - peeling of the skin, alopecia, pruritus, exfoliative dermatitis;
- respiratory system: very often - nosebleeds; often - laryngeal-pharyngeal pain, shortness of breath;
- nervous system: very often - headache; often - insomnia / drowsiness, dizziness, depression, paresthesia;
- hematopoietic system: very often - thrombocytopenia, neutropenia, anemia; often - leukopenia;
- urinary system: often - discoloration of urine (chromaturia);
- endocrine system: often - increased thyroid-stimulating hormone levels, hypothyroidism;
- musculoskeletal system: often - pain in the limbs, myalgia, arthralgia;
- others: very often - increased serum lipase activity, increased fatigue, asthenia; often - increased activity in serum of creatine phosphokinase (CPK) and amylase, lacrimation, chills, weight loss, fever, flu, dehydration, periorbital edema, peripheral edema; infrequently - flu-like syndrome, bleeding from tumors; in the presence of brain metastases or reversible leukoencephalopathy syndrome, cases of seizures have been reported.
In the course of post-marketing research, isolated cases of the following side effects of Sutent were recorded:
- endocrine system: hyperthyroidism with transition to hypothyroidism;
- hematopoietic organs: thrombotic microangiopathy (with the development of this reaction, it is necessary to temporarily stop using Sutent, after the resolution of the symptoms, the drug can be resumed by the decision of the attending physician);
- cardiovascular system: cardiomyopathy, sometimes fatal;
- musculoskeletal system: myopathy and / or rhabdomyolysis in combination with or without acute renal failure, with rare cases of death; most of these patients had baseline risk factors and / or used drugs that could provoke such adverse reactions; fistula formation, sometimes associated with tumor necrosis and / or regression, and in some cases fatal;
- immune system: hypersensitivity reactions, including angioedema;
- nervous system: disorders of gustatory sensitivity, including ageusia;
- respiratory organs: pulmonary embolism, sometimes fatal;
- urinary system: proteinuria, nephrotic syndrome; impaired renal function or renal failure, sometimes fatal;
- infections and infestations: serious infections (with or without concomitant neutropenia), some of which have been fatal.
Overdose
Cases of drug overdose have been reported, in which there were adverse reactions consistent with the safety profile of Sutent.
The specific antidote for sunitinib is currently unknown. Treatment for its overdose is prescribed symptomatic, if necessary, induce vomiting or rinse the stomach.
special instructions
Sutent therapy should be performed by a physician experienced in anticancer drugs.
At the beginning of each treatment cycle, it is recommended to perform a detailed blood test.
There are reports of cases of bleeding, sometimes fatal, including from the respiratory tract, gastrointestinal tract, urinary tract, tumors, as well as cerebral hemorrhage. These complications can occur unexpectedly, and in the presence of tumor foci in the lungs, manifest in the form of pulmonary hemorrhage, or life-threatening or severe hemoptysis. For the timely detection of the first symptoms of bleeding and the appointment of appropriate therapeutic measures, it is necessary to periodically carry out a medical examination and assess blood parameters. In the case of concomitant administration of anticoagulants, it is required to monitor blood clotting indicators.
The relationship between cardiac function and RTK inhibition has not been studied. When Sutent is prescribed to patients who have had cardiovascular diseases (symptomatic CHF, severe / unstable angina pectoris, myocardial infarction, coronary / peripheral bypass grafting, pulmonary embolism, transient ischemic disorders, cerebrovascular complications) in the last 12 months prior to starting sunitinib treatment, a careful assessment of the risk / benefit ratio should be carried out.
During therapy, patients need medical supervision to detect possible symptoms and clinical signs of CHF. LVEF should be assessed prior to initiation of treatment and periodically during treatment.
If clinical signs of CHF develop, Sutent should be discontinued. If these symptoms are absent, and LVEF is below 50% or decreased by more than 20% when compared to baseline (before treatment), the dose of sunitinib should be reduced or discontinued.
During therapy, a screening examination of patients for the development of arterial hypertension is required. If a severe form of this disease does not respond to treatment, treatment should be suspended; the course can be resumed only after adequate blood pressure control has been achieved.
In patients with hypothyroidism / hyperthyroidism, a background study of laboratory parameters of the thyroid gland is recommended. Patients with hypothyroidism should receive treatment in accordance with standard medical practice prior to starting the course. All patients taking Sutent should be monitored for thyroid dysfunction. In the presence of signs and / or symptoms of violations of its work, the appointment of laboratory control is necessary.
Patients with brain metastases, indications of a history of seizures and / or with symptoms of reversible posterior leukoencephalopathy (headache, arterial hypertension, mental impairment, lethargy, loss of vision, including cortical blindness) need to be monitored using standard methods, including h. and in the control of blood pressure. If these symptoms develop during therapy, it is recommended to temporarily stop using the Sutent. Once symptoms have resolved, treatment can be resumed at the discretion of the treating physician.
When thrombotic microangiopathy develops, sunitinib treatment should be temporarily discontinued until symptoms of this complication have subsided.
Before conducting therapy with Sutent, a background study of renal function is recommended, and during the course - monitoring of the indicators of its activity. In the presence of moderate to severe proteinuria, the safety of sunitinib has not been evaluated. Patients with nephrotic syndrome need to stop taking the drug.
Influence on the ability to drive vehicles and complex mechanisms
Patients who drive vehicles or work with other complex and potentially dangerous machinery should be aware that dizziness and drowsiness may occur during sunitinib treatment.
Application during pregnancy and lactation
Sutent is contraindicated during pregnancy and lactation. Throughout the entire period of sunitinib therapy, as well as for at least three months after its completion, it is required to use reliable methods of contraception.
According to the results of preclinical studies, treatment with the drug can negatively affect the fertility of men and women.
Pediatric use
The use of Sutent in pediatrics is contraindicated due to the lack of data confirming the safety and efficacy of its administration in children.
With impaired renal function
In the presence of renal failure, Sutent should be used with caution. If the serum creatinine level increases by no more than 2 times the upper limit of normal (UHN), there is no need to adjust the dose of sunitinib.
For violations of liver function
Sutent should be used with caution in patients with hepatic impairment. If the levels of aspartate aminotransferase (ACT) and / or alanine aminotransferase (ALT) increase less than 2.5 times higher than the ULN, or if these indicators increase due to the underlying disease, less than 5 times, a change in the sunitinib dose is not required.
Use in the elderly
Elderly patients do not need to adjust the dose of Sutent.
Drug interactions
Combination of Sutent with CYP3A4 inhibitors: simultaneous administration of a single dose of the drug with ketoconazole in healthy volunteers may increase the AUC and C max of the sunitinib complex and its active metabolite by 51 and 49%, respectively. With the combined use of the drug with other inhibitors of the CYP3A4 isoenzyme, such as itraconazole, ritonavir, clarithromycin, erythromycin or grapefruit juice, an increase in the plasma concentration of sunitinib may be observed. These combinations should be avoided or an alternative drug with a minimal ability to suppress the isoenzyme CYP3A4 should be used. If this cannot be done, it may be necessary to reduce the daily dose of sunitinib by 12.5 mg, but in this case it should not be less than 37.5 mg.
When sunitinib is combined with inducers of the isoenzyme CYP3A4: simultaneous administration of a single dose of the drug with rifampin in healthy volunteers decreases AUC and C maxby 46 and 23%, respectively. When Sutent is combined with CYP3A4 inducers such as phenobarbital, phenytoin, dexamethasone, rifampin, carbamazepine or St. John's wort, the plasma level of sunitinib in the blood may decrease. It is necessary to avoid such combinations or choose a concomitant drug with a minimum ability to stimulate the activity of the isoenzyme CYP3A4. If this cannot be done, then a stepwise increase in the dose of sunitinib by 12.5 mg may be required, with careful monitoring of the drug's tolerance. In this case, the daily dose should not exceed 87.5 mg for the treatment of gastrointestinal stromal tumors and metastatic renal cell carcinoma, and 62.5 mg for the treatment of neuroendocrine pancreatic tumors.
Analogs
The analogues of Sutent are Sunitinib-native, Tarceva, Gleevec, Torizel, Bosulif, Sprysel, Tasigna, Vargatef, Inlita, etc.
Terms and conditions of storage
Store at a temperature not exceeding 25 ° C. Keep out of the reach of children!
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Sutent
According to many reviews, Sutent is an effective drug used in the treatment of gastrointestinal stromal tumors and metastatic kidney cancer. The antitumor agent helps to increase the duration of the relapse-free period, inhibits the growth of metastases, and increases the life expectancy of patients.
However, many patients also note the development of severe side effects during drug therapy. There are reviews that indicate no improvement after taking the drug.
Price for Sutent in pharmacies
The price for Sutent depends on the dosage of the drug and can be (for a pack containing 28 capsules):
- capsules 12.5 mg: 64,000 rubles;
- capsules 25 mg: 120,000-250,000 rubles;
- capsules 50 mg: 145,000-250,000 rubles.
Sutent: prices in online pharmacies
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Drug name Price Pharmacy |
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Sutent 50 mg capsule 28 pcs. RUB 157,000 Buy |
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Sutent capsules 50mg 28pcs RUB 249416 Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
