Estracyt (Capsules) Instructions for Use

Marketing Authorization Holder

Pharmacia Italia, S.p.A. (Italy)

ATC Code

L01XX11 (Estramustine)

Active Substance

Estramustine (Rec.INN registered by WHO)

Dosage Forms

	Estracyt	Capsules 140 mg: 40 or 100 pcs.
		Lyophilisate for preparation of solution for intravenous administration 300 mg: 10 vials in a set with solvent

Dosage Form, Packaging, and Composition

Capsules gelatin, white, opaque; the capsule contents are a white powder.

Excipients: sodium lauryl sulfate, talc, magnesium stearate, colloidal anhydrous silicon dioxide.

40 pcs. – dark glass bottles (1) – cardboard packs.
100 pcs. – dark glass bottles (1) – cardboard packs.

Excipients: meglumine, mannitol.

Solvent water for injections – 8 ml.

Glass vials (10) in a set with solvent (amp. 10 pcs.) – cardboard packs.

Clinical-Pharmacological Group

Antineoplastic drug

Pharmacotherapeutic Group

Antineoplastic agent, alkylating compound

Pharmacological Action

Estracyt (a conjugate of estradiol and nitrogen mustard) is an antineoplastic drug with a dual mechanism of action. It has been established that estrone and estradiol (resulting from the biotransformation of estramustine phosphate) have antigonadotropic activity and cause a decrease in testosterone levels, similar to that after surgical castration.

During the dephosphorylation of Estracyt, Estramustine is formed, which is then biotransformed into Estramustine. These metabolites have an antimitotic effect by inhibiting the formation of microtubules in metaphase and destroying them in the interphase of mitosis.

Pharmacokinetics

Distribution and metabolism

After IV administration, unchanged estramustine phosphate is detected in blood plasma, but it is rapidly biotransformed to form estramustine and then estramustine, which is the main metabolite present in plasma. The binding of estramustine and estramustine to plasma proteins is high. Estramustine and Estramustine undergo further biotransformation to form estrogens – estradiol and estrone.

After administration of the drug, Estramustine and Estramustine are found in human prostate tumor tissue. The concentrations of estramustine and estramustine in tumor tissue are higher than in plasma. This may be due to the fact that Estramustine and Estramustine are absorbed by prostate tissue due to their binding to a specific protein that has been found in prostate tumor tissue.

Excretion

Estramustine and Estramustine are excreted in bile and feces and are not detected in urine. Estradiol and estrone undergo further metabolism and are partially excreted in the urine.

Indications

• Late stages of prostate cancer, especially when refractory to hormonal therapy;
• Primary therapy for prostate cancer in the presence of prognostic factors indicating possible low effectiveness of hormonal therapy.

ICD codes

Dosage Regimen

The dose of Estracyt for oral administration can range from 7 to 14 mg/kg of body weight in 2-3 doses (4-8 capsules/day). The recommended initial dose is 4-6 capsules/day to achieve a dose of at least 10 mg/kg of body weight.

Capsules should be taken at least 1 hour before meals or 2 hours after meals, with water. Do not take Estracyt simultaneously with medicines containing calcium, magnesium, or aluminum (including antacids), or simultaneously with the consumption of milk or dairy products.

The recommended dose of Estracyt in injection form is 5 mg/kg of body weight (300-450 mg) daily for 3 weeks, then 300 mg twice a week as maintenance therapy.

If there is no effect from therapy conducted for 4-6 weeks, the drug should be discontinued.

Method of solution preparation and administration

The contents of 1 vial of Estracyt (300 mg) are dissolved in 8 ml of water for injections, slowly adding the contents of the ampoule with solvent to the vial with the powder for injection. The vial should not be shaken.

Estracyt has a local irritant effect, so it should be administered IV slowly with a thin needle into a peripheral vein or through a central venous catheter.

Estracyt can be diluted in 250 ml of a 5% glucose solution and administered IV by drip over no more than 3 hours.

Adverse Reactions

From the endocrine system common – gynecomastia, impotence.

From the digestive system common – nausea, vomiting (especially during the first 2 weeks of treatment); possible – diarrhea, impaired liver function.

From the cardiovascular system fluid retention, coronary artery disease (including myocardial infarction), congestive heart failure, thromboembolism, arterial hypertension.

From the hematopoietic system rare – anemia, leukopenia and thrombocytopenia.

From the CNS rare – muscle weakness, depression, headache, confusion, lethargy.

Allergic reactions skin rash, angioedema (Quincke’s edema and laryngeal edema). In many cases, patients were simultaneously receiving ACE inhibitors with Estracyt.

Local reactions at the site of IV administration – phlebitis.

Contraindications

• Severe liver diseases;
• Severe cardiovascular diseases, such as coronary artery disease, thromboembolism and complications caused by fluid retention in the body;
• Hypersensitivity to estradiol derivatives and/or nitrogen mustard.

Use in Hepatic Impairment

Contraindicated in severe liver diseases.

Special Precautions

Estracyt should be used by physicians experienced in the use of antineoplastic drugs.

Estracyt should be prescribed with caution to patients with a history of thrombophlebitis, thrombosis or thromboembolic disorders (especially those associated with the use of estrogens); with cerebral vascular atherosclerosis or coronary pathology.

Due to possible decreased glucose tolerance, patients with diabetes mellitus should be under strict supervision during treatment with Estracyt.

In patients with arterial hypertension, systematic blood pressure monitoring is necessary.

When using Estracyt, fluid retention in the body is possible, so patients with epilepsy, migraine or impaired renal function that progresses in case of fluid retention require special attention.

Estracyt is prescribed with caution to patients with metabolic bone lesions accompanied by hypercalcemia, as well as to patients with renal failure, because the drug may affect calcium or phosphorus metabolism.

The drug is prescribed with caution to patients with impaired liver function, as it may be insufficiently metabolized in such patients. Regular monitoring of laboratory parameters of liver function is required.

Estramustine is known to be mutagenic, therefore, when using Estracyt, patients of childbearing age should use reliable methods of contraception.

Since some endocrine and liver functions are affected by estrogen-containing drugs, this may be reflected in the corresponding values of laboratory parameters.

When preparing the solution, contact of Estracyt with the skin should be avoided. If this occurs, the contact area should be thoroughly washed with cold water and soap and the materials used should be destroyed by incineration.

Overdose

Symptoms possible intensification of side effects, especially from the digestive system.

Treatment gastric lavage and symptomatic therapy are performed. For 6 weeks after an overdose of Estracyt, blood counts and liver functional status should be monitored.

Drug Interactions

Clinical studies have shown that estrogens increase both the therapeutic activity and toxicity of tricyclic antidepressants, possibly by inhibiting their metabolism.

With simultaneous administration of Estracyt and drugs containing calcium, magnesium or aluminum, a significant decrease in the absorption of estramustine is possible due to the formation of insoluble salts with polyvalent metal ions.

With simultaneous use of Estracyt and ACE inhibitors, the likelihood of developing angioedema increases.

Pharmaceutical incompatibility

Saline solution is not recommended for the preparation of estramustine injection solution due to precipitation.

Storage Conditions

The drug in capsule form should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 5 years.

The lyophilized powder should be stored out of the reach of children at a temperature not exceeding 25°C (77°F). Shelf life – 3 years. The prepared infusion solution must be used within 12 hours when stored at room temperature and within 24 hours when stored at a temperature from 2°C (35.6°F) to 8°C (46.4°F).

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.