Farmak #Antineoplastic_and_immunomodulating_agents #Antineoplastic #HEALTH_CARE
Pharmacological properties
Pharmacodynamics. Flutafarm is a non-steroidal antiandrogenic preparation. it is able to block cellular androgen receptors, mimicking the effect of orchiectomy and preventing testicular and adrenal androgens from stimulating the growth of malignant tumors (adenocarcinomas) of the prostate gland in androgen-sensitive tissues. this leads to inhibition of the proliferation of epithelial tumor cells and contributes to a decrease in the size and density of the prostate itself and metastases in tissues in patients with prostate cancer.
In women with hyperandrogenic conditions, accompanied by infertility and disorders of the ovarian-menstrual cycle (for example, scleropolycystic ovary syndrome), Flutapharm blocks the pathogenic effect of endogenous androgens on the ovaries and other reproductive organs, as well as on the hypothalamic-pituitary system. Due to this, the severity of symptoms of hyperandrogenism (hirsutism) in patients decreases, menstruation resumes, folliculogenesis and menstrual cycle improve, which probably leads to the restoration of fertile potential in some patients.
Pharmacokinetics. Flutamide is well absorbed in the gastrointestinal tract. Cmax in the blood is observed 2 hours after oral administration. It is rapidly metabolized to form an active metabolite - 2-hydroxyflutamide and other substances. T½ of the active metabolite is 5-6 hours. It is eliminated mainly in the urine. In 2 days, 91% of the administered dose is excreted from the body, in 3 days - 98% of the administered dose.
Indications
Treatment of locally advanced or metastatic prostate cancer as monotherapy (with or without orchiectomy) or in combination with LGHR agonists in patients who have not previously received any treatment at all, or in patients who do not respond or who have developed resistance to hormonal therapy.
As part of complex therapy for locally limited prostate cancer stage B2-C2 (T2b-T4) to reduce tumor volume, enhance tumor control and increase the period between exacerbations of the disease.
Treatment of women with functional hyperandrogenism, accompanied by disorders of the ovarian-menstrual cycle, hirsutism, scleropolycystic ovary syndrome and infertility.
Application
Flutapharm should be prescribed to patients with prostate cancer as monotherapy (after or without orchiectomy) or in combination with lgrg agonists, 1 tablet (250 mg) 3 times a day every 8 hours.In the case of combination therapy with lgrg agonists, both preparations can be prescribed simultaneously or flutapharma is started 24 hours before the first dose of the lgrg agonist.
In the case of radiation therapy, Flutapharm should be prescribed 8 weeks before its start and continue taking the preparation throughout the entire course of radiation therapy.
For women with hyperandrogenic conditions, Flutapharm should be administered orally ½ tablet (125 mg) 3 times a day for 3–6 months. Take with or after meals. It is mandatory to use non-hormonal contraceptives, in particular, barrier ones.
Contraindications
Hypersensitivity to flutamide or other components of the preparation. For women, additional contraindications to taking flutapharma are organic hyperandrogenism (tumors of the ovaries and adrenal cortex), severe liver failure (baseline liver enzymes should be assessed before starting treatment).
Side effects
With monotherapy
Reproductive system: gynecomastia and / or breast pain, sometimes accompanied by galactorrhea. These reactions disappear after stopping treatment or reducing the dose of the preparation. The incidence of gynecomastia is significantly reduced with concomitant use of LHRH agonists. Decreased libido, decreased sperm count.
Infections and invasions: herpes zoster.
Blood and lymphatic system: edema, ecchymosis, lymphostasis.
Immune system: lupus-like syndrome.
Mental disorders: depression, anxiety, agitation, anxiety.
Nervous system: insomnia, headache, dizziness.
Organ of vision: blurred vision.
Respiratory system: dyspnea, cough.
Digestive tract: diarrhea, nausea, vomiting, increased appetite, gastrointestinal dysfunction, pain in the stomach, ulcerative pain, heartburn, constipation, anorexia, thirst.
Hepatobiliary system: increased activity of liver enzymes, transient liver dysfunction, jaundice, hepatitis.
Skin and subcutaneous tissue: itching, rash.
General disorders: increased fatigue, malaise, weakness, fever, chest pain.
Violations of the cardiovascular system occur much less frequently compared with the use of diethylstilbestrol.
With combination therapy
Reproductive system: decreased libido, impotence, hot flashes, gynecomastia.
Benign and malignant tumors:
neoplasms in the mammary glands in men.
Digestive system: diarrhea, nausea, vomiting, nonspecific gastrointestinal disorders, abdominal pain.
Blood and lymphatic system: anemia, leukopenia, thrombocytopenia, edema, hemolytic anemia, macrocytic anemia, methemoglobinemia, sulfhemoglobinemia. Thromboembolism is possible.
Metabolic disorders, trophic disorders: anorexia, hyperglycemia, exacerbation of diabetes mellitus.
Mental disorders: depression, anxiety, anxiety, neurosis.
Nervous system: drowsiness, confusion, irritability.
Cardiovascular system: AH. There have been isolated cases of thrombophlebitis, pulmonary embolism and myocardial infarction.
Respiratory system: shortness of breath, interstitial lung lesions.
Hepatobiliary system: jaundice, hepatitis, cholestatic jaundice, hepatoencephalopathy, hepatonecrosis, liver dysfunction, usually reversible after the end of therapy; occasional deaths have been reported due to severe liver damage.
Skin and subcutaneous tissue: rashes, photosensitivity reactions, including erythema, ulceration, bullous eruptions, epidermal necrolysis.
Musculoskeletal system and connective tissue: arthralgias, myalgias, neuromuscular symptoms (including muscle weakness, paresthesias, convulsions).
Urinary system: dysuria, a change in the frequency of urination, a change in the color of urine to amber and yellow-green, which may be associated with flutamide and / or its metabolites.
General disorders: sensation of heat.
Laboratory indicators: an increase in the levels of liver enzymes, bilirubin, residual urea nitrogen in the blood plasma, an increase in the level of creatinine in the blood plasma.
In addition, the following side effects were noted during the use of the preparation: hemolytic anemia, macrocytic anemia, methemoglobinemia, sulfhemoglobinemia, photosensitivity reactions (including erythema, ulcer formation, bullous rashes and epidermal necrolysis) and changes in urine color to amber and yellow-green, which can be associated with flutamide and / or its metabolites. Cholestatic jaundice, hepatic encephalopathy, and liver necrosis may also occur. Liver dysfunction, usually reversible, after discontinuation of therapy; however, there have been reports of death due to severe liver damage associated with the use of flutamide.
Reported extremely rare cases of hyperglycemia and worsening of the course of diabetes mellitus.
Changes in laboratory test results were noted, which included liver dysfunction, increased blood urea nitrogen levels, and isolated cases of increased plasma creatinine levels.
Special instructions
Patients should be under constant medical supervision. special attention should be paid to the effect of the preparation on liver function and spermatogenesis in patients who have not undergone orchiectomy (surgical or medical).
Treatment with the preparation should not be started if the levels of hepatic transaminases in the blood plasma are 2-3 times higher than the upper limit of the norm. Monitoring of liver function should be carried out during the entire period of preparation treatment. Plasma transaminase levels should be determined before starting flutamide therapy, monthly during the first 4 months of taking the preparation, periodically thereafter and at the first symptoms of liver dysfunction (for example, itching, dark urine, nausea, vomiting, fatigue, anorexia, jaundice, pain in right hypochondrium or incomprehensible flu-like symptoms). If jaundice appears or the activity of hepatic transaminases is 2-3 times higher than normal (in the absence of liver metastases, confirmed by biopsy), flutamide should be stopped immediately and liver function should be carefully monitored until the situation is clarified.
Patients should see a doctor immediately when the first symptoms of liver dysfunction appear, such as pruritus, dark urine, nausea, vomiting, persistent anorexia, yellowing of the sclera and skin, tenderness in the right hypochondrium, and flu-like symptoms.
Liver damage is usually reversible after discontinuation of therapy, and in some patients even after dose reduction.
Flutamide is excreted mainly by the kidneys; therefore, dose adjustment may be required in patients with renal insufficiency.
Since plasma levels of testosterone and estradiol increase during treatment with flutamide, fluid retention in body tissues is possible. Therefore, flutamide should be used with caution in patients with heart disease. In addition, an increase in estradiol levels may increase the risk of thromboembolism.
In patients without orchiectomy who have been treated with flutamide for a long time, it is necessary to periodically determine the sperm count.
Patients with latent or actual glucose-6-phosphate deficiency may develop methemoglobinemia. In the event of cyanosis, methemoglobinemia, the possible factor of excess dose should be taken into account.
Flutamide contains lactose, so patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not take the preparation.
When combined therapy with Flutapharm and an LHRH agonist, the possible side effects of each preparation must be taken into account.
Patients should be informed that flutamide and medicinal products intended for medical castration must be used in combination and that they should not be discontinued or the dose changed without first consulting a doctor.
Before using Flutapharma, women need to exclude organic hyperandrogenism (tumors of the ovaries and adrenal cortex).
Alcohol should not be consumed during treatment.
The ability to influence the reaction rate when driving or working with other mechanisms. Until the individual patient's response to the preparation is clarified, one should refrain from driving vehicles or other mechanisms, given that during treatment with flutamide, increased fatigue, sometimes dizziness, drowsiness and visual disturbances were observed.
Use during pregnancy and lactation. When using the preparation, women should pay special attention to preventing pregnancy with the help of non-hormonal, in particular barrier, contraceptives. In case of a positive pregnancy test, the preparation should be stopped immediately. Sexual intercourse with the aim of the desired pregnancy can be resumed no earlier than 48 hours after the last dose of Flutapharma.
Children. The preparation should not be used to treat children.
Interactions
In patients receiving warfarin for a long time, after the start of monotherapy with flutamide, an increase in prothrombin time is observed. therefore, the combined use of flutapharm and warfarin requires careful monitoring of prothrombin time and, possibly, correction of anticoagulant doses.
Flutamide can slow down the metabolism of GCS.
Avoid the concomitant use of flutamide with potentially hepatotoxic preparations.
When flutamide is used simultaneously with theophylline, an increase in the concentration of theophylline in blood plasma is possible.
Excessive alcohol consumption should be avoided during treatment with flutamide.
Overdose
A single dose of flutamide that would cause overdose symptoms or be life-threatening has not been established.
In case of overdose, dialysis is ineffective, given the high degree of binding of flutamide to blood plasma proteins.
As with the treatment of an overdose of any preparation, the possibility of taking several preparations at the same time should be considered. In case of overdose, if there is no spontaneous vomiting, vomiting should be induced. Gastric lavage may be required.
Shown are standard supportive measures with constant monitoring of the patient and vital functions.
Storage conditions
In a dark place at a temperature not exceeding 25 ° c.
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