Phosphastrol - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

"Estrogens, gestagens, their homologues and antagonists"

Included in the formulation

АТХ:

L.02.A.A.04 Phosphastrol

Pharmacodynamics:

Antitumor agent with estrogenic activity. Penetrating into the tumor tissue, phosphaestrol dephosphorylated by the action of acid phosphatase to form diethylstilbestrol, that passively diffuses into the target cells, form complexes with estrogen receptors and penetrates the cell nucleus where it enhances the synthesis of DNA, RNA, and protein, an increase in pituitary mass, reduced production of gonadotropin-releasing hormone hypothalamus and FSH and lutropin pituitary.

In prostate cancer inhibits lutropina pituitary, binds to cytoplasmic receptors, hormones, inhibits incorporation of thymidine into nucleotides, inhibits aerobic glycolysis, mitosis, growth and migration of tumor cells, the synthesis of androgen exerts a cytostatic effect when androgenozavisimyh neoplastic diseases. Perhaps a direct effect on the testicles, accompanied by a decrease in the concentration of testosterone in the blood plasma.

Pharmacokinetics:After intravenous administration is determined in blood in small quantities in a very short time (about 5 minutes). When ingested quickly absorbed. Unchanged phosphaestrol in the blood is practically not determined. Pharmacologically active is the metabolite diethylstilbestreol, 30-40% of which is sorbed on erythrocytes. Has the effect of the first passage through the liver. It is distributed in most tissues, especially the mammary glands, uterus, vagina, hypothalamus and pituitary gland. Characterized by high affinity for fat tissue. The connection with plasma proteins is moderate or high (50-80% with albumin and globulin binding sex hormones). Biotransformation mainly in the liver (desulphurization, resulfurization, oxidation to less active metabolites and non-steroidal compounds that can interactwith catecholamine receptors of the central nervous system, and rapidly eliminating conjugates with glucuronic acid), to a lesser extent - in muscles, kidneys, gonads, lungs, adipose tissue. Eliminated with feces (90-95% in the form of diethylstilbsterol) for 24 hours. Excessed intestinal liverth recirculation. Elimination slows down with obesity.

Indications:Adenocarcinoma (including metastasizing) of the prostate gland (palliative treatment), metastatic breast cancer, insufficiency of estrogen function.

ICD-10

II.C50.C50 Malignant neoplasm of breast

II.C60-C63.C61 Malignant neoplasm of prostate

IV.E20-E35.E28 Dysfunction of the ovaries

Contraindications:

Hemorrhagic syndrome, recently suffered myocardial infarction, chronic circulatory failure.
Impaired liver function or disease (especially obstructive type).
Hypersensitivity to estrogens or any of the components of the dosage form.
Estrogen-dependent malignant tumors (known or suspected): use of estrogens is contraindicated due to increased risk of progression of the process (especially with prolonged use). Tumors of the chest.
Porphyria.
Visual impairment (including sudden diplopia, proptosis, partial or complete loss of vision), migraine - it is necessary to cancel the drug and conduct a thorough examination if any of these conditions occur. If there is an edema of the nipple of the optic nerve or lesions of the retinal vessels, the treatment with estrogens is stopped.
Thrombophlebitis and thromboembolism.

Carefully:No data.

Pregnancy and lactation:

Recommendations for FDA - category X. Indications for the appointment of fosfestrol women are absent.

There is no information on the penetration into breast milk. Indications for the appointment of fosfestrol women are absent. Do not apply!

Dosing and Administration:Inside 50 mg 3 times a day, if necessary, the dose may be increased; the maximum daily dose is 1 g. Intravenously inject 0.5-1 g of substance diluted in 250-300 ml of 0.9% sodium chloride solution at a rate of 20-30 drops per minute for 5 days. Then they switch to oral maintenance therapy.

Side effects:

At the beginning of treatment - nausea, vomiting, worsening of the general condition. Itching and pain in the anal and genital areas, less often in the face and neck, metastatic nodes. Possible hemorrhages, gynecomastia.

Induction of the development of neoplastic processes in the genitals (in women), liver, exacerbation of cholelithiasis, thromboembolism, decreased glucose tolerance, hypercalcemia, enlargement and thickening of the mammary glands, dyspepsia, cholestatic hepatitis, headache, dizziness, depression, swelling, weight changes body, allergic skin rashes.

From the cardiovascular system: estrogens increase the risk of myocardial infarction, stroke, venous thrombosis, hypertension, thromboembolism of the pulmonary artery.

Overdose:

Not described.

Treatment is symptomatic.

Interaction:

Barbiturates, anxiolytics (tranquilizers), narcotic analgesics, preparations for general anesthesia - acceleration of metabolism fosfestrol.

Bromocriptine - it is necessary to correct its dose.

Hepatotoxic agents [abacavir, aldesleukin, amiodarone, anabolic steroids, androgens, asparaginase, paracetamol (with long-term high-dosage therapy or acute overdose), acitretin, valproic acid, retinol (with chronic overdose), halothane, dapsone, daunorubicin, disulfiram, fat emulsions (with intravenous long-term use), iron preparations (with overdose), zidovudine, gold compounds, ACE inhibitors, HMG-CoA reductase inhibitors, imatinib, itraconazole, carbamazepine, carmustine, ketoconazole (ingestion), co-trimoxazole, lamivudine, mercaptopurine, methotrexate, methyldopa, naltrexone (with prolonged use in high doses), nevirapine, a nicotinic acid (when used in high doses as a hypolipidemic agent in a sustained release dosage form), nilutamide, nitrofurans, NSAIDs, plikamycin, rifampicin, rosiglitazone, sulfonamides (with systemic application), tizanidine, tolcapone, toremifene, tretinoin, phenothiazines, phenytoin, fluconazole, flutamide, cytarabine, epirubicin, erythromycin, ethanol, ethionamide, etretinate], especially dantrolene and isoniazid - increased risk of developing hepatotoxicity and fatal hepatitis with concurrent use; risk with long-term treatment and liver diseases in history.

Glucocorticoids - a change in their metabolism and the degree of binding to proteins, accompanied by a decrease in clearance, an increase in the half-life and increased therapeutic and side effects; may need to adjust the dose of glucocorticoids.

Calcium supplement supplements and agents - increased calcium absorption and relapse of nephrolithiasis in predisposed patients; can be used for therapeutic purposes to increase the mass of bone tissue.

Inhibitors of cytochrome CYP34 (grapefruit juice, itraconazole, ketoconazole, clarithromycin, ritonavir, cimetidine, erythromycin) - an increase in the concentration of estrogens in the blood plasma with parallel application with an increase in their side effects.

Inductors of cytochrome CYP34 (dexamethasone, preparations of St. John's wort perfumed, carbamazepine, meprobamate, rifampicin, phenylbutazone, phenytoin, phenobarbital) - decrease in the concentration of estrogens in blood plasma with simultaneous application, which may reduce their therapeutic effectiveness or cause recurrent uterine bleeding; interaction with transdermal estrogen systems has not been studied.

Corticotropin (with long-term treatment) - increased anti-inflammatory effect of endogenous cortisol, inducible corticotropin, with simultaneous application.

Smoking - increased risk of serious cardiovascular complications (stroke, transient ischemic attacks, thrombophlebitis, pulmonary embolism) in patients receiving high doses of estrogens in the form of contraceptives; the risk increases with increasing duration of smoking, age; it is possible to accelerate the metabolism of estrogens and reduce their estrogenic effect.

Progestins - increased risk of developing breast cancer, impaired metabolism of lipoproteins and glucose tolerance, while using estrogen as compared with monotherapy.

Somatropin - premature closure of bone growth zones with simultaneous application in the pre-pubertal period.

Means that cause pancreatitis, especially didanosine, lamivudine, zalcitabine - increased risk of pancreatitis with simultaneous use, especially if the patient has risk factors (high concentration of triglycerides in the blood plasma); cases of development of pancreatitis in the application of physiological doses of estrogens are not described.

Tamoxifen - the effect on its effectiveness with simultaneous application.

Folic acid and thyroid medications - enhanced action phosphaestrol.

Cyclosporine - estrogens inhibit the metabolism of cyclosporine, increasing its concentration in the blood plasma, which may increase the risk of hepato- and nephrotoxicity; should be combined with great caution under the constant control of the concentration of cyclosporine in blood plasma, liver and kidney function.

Phosphastrol increases the effectiveness of lipid-lowering drugs.

Phosphastrol weakens the effects of male sex hormones, hypoglycemic, diuretic, antihypertensive drugs and anticoagulants.

The concentration in the plasma decreases with the simultaneous use of phenylbutazone and certain antibiotics (ampicillin, rifampicin), which is associated with a change in the microflora in the intestine.

Special instructions:

To reduce the frequency and severity of side effects, intravenous administration of antihistamines is indicated.

During the treatment should be monitored the concentration of alkaline phosphatase in the serum and the study of urine sediment.

Instructions

Phosphastrol (Phosphoestrolum)