Everolimus refers to the chemical means of combating the development of malignant tumors.
Forms of release, composition and packaging
Everolimus is available in tablet form with different quantitative composition of the active substance: 2.5 mg, 5 mg and 10 mg.
Tablets are packed in carton boxes in the number of 3, 6 or 9 blisters, in which there are 10 tablets of white or yellowish( cream) shades.
Tablets of the Athlete elongated, flat. On one side of the tablet is an engraving "NBR".
The second side is the identification mark for the quantitative content of everolimus:
- tablets with 2.5 mg are engraved with "LCL";
- tablets with 5 mg have an engraving "5";
- tablets with 10 mg are engraved with "UHE".
In addition to everolimus, tablets with different levels of active substance include excipients:
- dried lactose - from 71.875 mg( 1 part) to 287.5 mg( 4 parts);
- Crospovidone - from 25 mg to 100 mg( proportions 1: 4 persist);
- stearic magnesium - from 0.625 mg to 2.5 mg( the proportions are the same);
- hypromellose( proportionally) - 22.5 mg - 90 mg;
- derivative of toluene with replacement of two hydrogen atoms in the benzene ring with a butyl radical and hydroxo group - 0.055 mg - 0.22 mg;
- lactose in crystalline monohydrate form - 2.45 mg - 9.8 mg.
The manufacturer of all preparations containing everolimus( Affiner and Sertikan) is the Swiss pharmaceutical company Novartis Pharma AG.
Indications for use
In case of low effectiveness of therapeutic agents in the treatment of many forms of malignant neoplasms in the kidneys with metastases to other organs or their absence, drugs with everolimus are prescribed.
Practice shows the effectiveness of the drug in the treatment of malignant neoplasms of the neuroendocrine nature in the lungs, pancreas and digestive system.
In breast cancer after exposure to hormonal agents, it is effective to influence malignant cells with everolimus in combination with an aromatase inhibitor. The drug is better to use in hormone-dependent form in patients of post-menopausal age.
If there is no immediate indication for surgical resection of kidney angiomyolipoma, then everolimus is included in the treatment regimen, provided that the kidney angiomyolipoma is associated with tuberous sclerosis. Tuberous sclerosis is also an indication for the use of everolimus in diagnosing giant-cell astrocytomas subependymalnogo nature.
The essential conditions for the application of everolimus in the latter case are the age of at least 3 years and the absence of the possibility of surgical resection of the tumor.
Drugs with everolimus do not apply for giant-cell astrocytoma subependymalnogo character with hepatic burden classification Child-Pugh 5-15 points( Child A, B and C) in patients 3-18 years.
For patients over 18 years of age, preparations of everolimus are inapplicable with hepatic impairment from 10 to 15 points in the Child-Pugh classification. Age restrictions for the use of everolimus are the younger preschool period( nursery) with sub-ependymal character of giant-cell astrocytomas.
In the absence of subendymal giant cell astrocytomas, drugs with everolimus are not prescribed to patients under the age of 18 years.
In the period of gestation and lactation, everolimus should not be prescribed. If there is an individual intolerance not only to everolimus, but to any derivative of rapamycin. A universal contraindication is the patient's increased sensitivity to the excipients of the drug for better assimilation of everolimus.
It is not recommended to take the drug with everolimus if induction of P-glycoprotein inducers and CYP3A4 isomer is taken during the treatment.
Mechanism of Action Everolimus
Everolimus is an inhibitor of protein tyrosine kinase, has an immunosuppressive effect on the proliferation of malignant cells.
Mediated inhibition of proliferation is associated with an initial exposure to an antigen bound to T lymphocytes. Further specific T-lymphocytes( interleukin-2 and interleukin-15) show inhibition of proliferation, which stops clonal expansion.
Inhibition of reactions is also associated with the intracellular method of signaling the transmission of the proliferation mechanism, blocking the corresponding receptors. Proliferation stops at the phase of interphase, during the presynthetic period G1.
The molecular level of the mechanism of action of everolimus is associated with the formation of the "everolimus protein FKBP-12" complex. The protein is localized in the cytoplasm of cells. The effect of everolimus is due to the inhibition of the formation of ATP by the enzyme p70 S6 kinase.
In turn, the p70 S6 kinase is formed by an enzymatic reaction with the participation of the m-TOR protein. The initial inhibition of proliferation reactions is attributed, for this reason, to the blocking of the activity of the m-TOR protein.
Although the mechanism of action of everolimus is different from the pharmacodynamics of cyclosporine with similar efficacy, the joint use of two drugs reliably acts on the proliferation of affected cells, as shown in models with allotransplantation.
In addition to the T-lymphocytic pathway of proliferation, the effect of everolimus on cells not associated with hematopoiesis( smooth muscle cells of internal organs) has been revealed. The pathogenesis of chronic rejection of former endothelial cells caught in the neointimal lesion zone is also explained by proliferative changes.
Fibroblasts, endotheliocytes, blood vessel myocytes, tumor cells are sensitive to the effects of everolimus on growth factor during proliferation.
The progress of diseases with these forms of cancer after the use of everolimus was absent for 5 months. More than a third of patients after the administration of everolimus progress of a cancerous tumor stopped for 6 months.
Instructions for use
Everolimus take 1 tablet a day, preferring the morning hours( on an empty stomach or after taking unbuttoned food).
The tablet should be taken up by a cold cleaned water mill. Do not take the tablet with chewing, crushing and other violation of its integrity.
In case of a patient's physical impossibility of taking a pill, it is placed in a glass of cold water, diluted thoroughly with it and drunk. After taking the solution of everolimus, water is poured into the beaker and it is drunk, entraining the remains of the active substance and providing the desired concentration of the solution suitable for absorption in the stomach.
The treatment schedule for everolimus is individual: the drug is discontinued after the disappearance of clinical symptoms or the appearance of a sign of poor toxicity tolerance.
In most cases of cancer, the usual daily dose is 10 mg for a single dose. With the development of severe toxic reactions, the dosage of everolimus is reduced by a factor of 2 or further use of the drug is canceled.
In patients with subependymal giant cell astrocytoma, the dosage is calculated starting at 4.5 mg / m2.Calculation of the surface of the body is carried out according to the Dubois formula.
In the absence of toxic reactions, the concentration of everolimus in the blood is determined 2 weeks after the first intake. Concentration should not exceed 15 ng / ml, but should not be less than 3 ng / ml. At a concentration of everolimus below 3ng / ml, the dosage of the drug is increased.
Side effects of
The drug has side effects from virtually all functional systems of the body. The degree of manifestation of side effects should be evaluated by the attending physician and corrected in due time by the treatment regimen.
Although no cases of overdose have been reported, treatment after an excessive dose of everolimus should be aimed at eliminating overdose symptoms. The dose of everolimus, not exceeding 70 mg per day, is tolerated by the body satisfactorily.
Monitoring of kidney function during the treatment period is ongoing. When a high concentration of daily creatinine is found in the patient's urine, the treatment regimen is corrected, reducing the dosage of cyclosporine.
With daily monitoring of urinalysis, the stability of the rapamycin derivative is monitored.
It should be noted that vaccination with the use of everolimus is undesirable due to a decrease in the effectiveness of the procedure.
It is not recommended to consume grapefruit and other citrus juices in bulk at the time of treatment.
The reverse effect is observed with the use of calcium channel blockers( nicardipine), antifungal agents( fluconazole), macrolide antibiotics( azithromycin), protease inhibitors( amprenavir).
The drug is classified as expensive, so the number of patients' reviews of everolimus is absent. The available reviews have a 100% character of improving the condition and reducing the aggressiveness of the tumor.
Tablets Afinitora in pharmacies detect the price variability associated with the amount of active substance in them. Tablets of 2.5 mg cost about 93 thousand rubles, 5 mg - 123 000 rubles, 10 mg - 171 000 rubles.
From the trade names of preparations containing everolimus, 2 are known: Serikan and the Athlete.
Analogues of everolimus coincide with synonyms and generics.
Conditions for dispensing from pharmacies
In the pharmacy, the drug with everolimus is dispensed according to the prescription of an oncologist.
Storage Conditions and Shelf Life
The temperature for storing the drug should not be above 30 degrees. Otsalnye conditions for storage are standard for all preparations: dry environment, protected from direct sunlight.
Video about Everolimus in hormone-dependent breast cancer: