Estramustine - instructions for use, doses, side effects, contraindications

Clinical and pharmacological group: & nbsp

Antineoplastic hormonal agents and hormone antagonists

Included in the formulation

АТХ:

L.01.X.X.11 Estramustine

Pharmacodynamics:

Antitumor agent with alkylating activity. It is a chemical compound of normustine and estradiol. The cytotoxic effect of estramustine is due to the antimitotic activity of normustin and is less pronounced than that of conventional alkylating agents. Has a high tropism to the tissue of the prostate gland.

In the implementation of the action of estramustine, the oppression of the activity of the hypothalamic-pituitary-sex gland system can play a role, leading to a decrease in testosterone concentration in the blood serum.

In therapeutic doses, myelodepression is weak or almost nonexistent. Estrogenic activity of estramustine is less pronounced than that of estradiol. Does not have immunosuppressive action.

Pharmacokinetics:

After ingestion, absorption from the gastrointestinal tract is 75%. Absorption decreases with the use of milk, dairy products and preparations with a high calcium content.

When absorbed into the blood quickly dephosphorylates, then oxidized and hydrolyzed to estromustine, with the formation of estradiol and estrone at low concentrations, and mechlorethamine; metabolism is carried out by conjugation in the liver.

Multiphase elimination.The half-life in the final phase is 20 hours. It is excreted with bile / with feces and is excreted to a small extent by the kidneys.

Indications:

Prostate cancer (late stages), especially in patients with hormone refractory tumors; Primary therapy in patients with prostate cancer with an unfavorable prognosis.

ICD-10

II.C60-C63.C61 Malignant neoplasm of prostate

Contraindications:

Hypersensitivity, acute thrombophlebitis (possibly exacerbated by the presence of estrogen in estramustine, an exception can be made if the mass of the tumor itself is the cause of thromboembolism), thromboembolic complications in the acute phase (including recent myocardial infarction or stroke).

Carefully:

Thrombophlebitis (history), thrombosis or thromboembolic disorders in history (especially if they were observed with estrogen therapy), cerebrovascular insufficiency, ischemic heart disease, chronic heart failure; diabetes mellitus (since glucose tolerance is reduced); bronchial asthma; state,progressing in case of fluid retention (epilepsy, migraine, renal dysfunction), impaired liver function, cholelithiasis, cholestatic hepatitis; infectious diseases, including chicken pox now or recently transferred (including recent contact with the patient), surrounding herpes (risk of severe generalized disease); peptic ulcer of the stomach and duodenum, osteoporosis, bone marrow hypoplasia.

Pregnancy and lactation:

Action category on the fetus by FDA - X. There are no indications for the administration of estramustine to women. Do not use during pregnancy and lactation!

The sexual partners of patients receiving estramustine, it is recommended to use contraceptives.

Dosing and Administration:

Inside, intravenously. Inside (1 hour before or 2 hours after a meal), 600 mg / m² per day (in terms of the basis) in 3 doses or 10-16 mg / kg per day in 3-4 doses. Treatment can be started with intravenous fluid injection 300-450 mg once a day for a maximum of 3 weeks, then go to the inside, or continue injections of 300 mg twice a week. Possible intravenous drip introduction.

Side effects:

From the side cardiovascular system and blood (hematopoiesis, hemostasis): anemia, leukopenia, thrombocytopenia, delay Na⁺ and fluid (edema of the feet or ankles), congestive heart failure, IHD, including myocardial infarction, thromboembolism, arterial hypertension.

From the side organs of the digestive tract: nausea, vomiting, diarrhea, impaired liver function.

From the side nervous system and sense organs: muscle weakness, depression, headache, confusion, drowsiness.

Allergic reactions: rash, angioedema (in many cases, including one with a fatal outcome, patients simultaneously received ACE inhibitors). With the development of angioedema, therapy with estramustine should be stopped immediately.

Other: gynecomastia, impotence; with intravenous administration - itching and burning at the injection site, thrombophlebitis.

Overdose:

Symptoms: increased side effects.

Treatment: gastric lavage, symptomatic therapy. For the next 6 weeks after an overdose, it is necessary to monitor liver function and blood counts.

Interaction:

Calcium and calcium-containing drugs reduce absorption, as calcium binds to estramustine in the gastrointestinal tract and forms an insoluble calcium phosphate salt, which is not absorbed (simultaneous use should be avoided).

With the simultaneous administration of glucocorticoids with estrogens, a change in the metabolism of glucocorticoids and their binding to proteins is possible, which leads to a decrease in clearance, an increase in the half-life, an increase in the therapeutic effect and an increase in the toxic effect of glucocorticoids (during and after simultaneous use, glucocorticoid dose adjustment may be required).

When used simultaneously with hepatotoxic agents, the risk of hepatotoxicity increases.

Inactivated or live viral vaccines - the interval between administration should be from 3 months to 1 year.

During treatment with estrogen, smoking is not recommended because of the increased risk of serious side effects on the cardiovascular system, including stroke, transient cerebral circulation, thrombophlebitis and pulmonary embolism (the risk rises with the increase in the number of cigarettes smoked and with age).

Special instructions:

Estramustine should be prescribed by a doctor who has experience in using antitumor drugs.

Patients with prostate cancer receiving estrogens are at increased risk of thrombosis, including myocardial infarction.Since glucose tolerance can be reduced, patients with diabetes should be closely monitored during treatment.

In connection with the risk of arterial hypertension, periodic monitoring of blood pressure should be performed. In some patients who received estramustine, there was a worsening of peripheral edema or congestive heart failure.

As estramustine can affect the metabolism of calcium or phosphorus, it should be administered with caution to patients with lesions of bone tissue accompanied by hypercalcemia, as well as patients with renal insufficiency.

In the treatment with estramustine, liver function monitoring should be performed regularly at specific intervals.

When working with estramustine, it is necessary to observe the rules for handling cytotoxic substances.

In case of accidental contact with the skin or eyes, immediately wash the skin with soap and water and wash with clean water. then you should always consult a doctor.

During the period of treatment, contraceptive means should be used.

Instructions

Estramustine (Estramustinum)