Estracyt Kapseln 艾去适 (磷酸雌莫司汀胶囊)

【Function and indication】
Estramustine phosphate capsules are indicated for advanced prostate cancer, especially hormone-refractory prostate cancer. They can be used as first-line treatment for patients whose prognostic factors show poor response to simple hormone therapy.

【Model and specification】
Hard capsule 140mg/tablet.

【Usage and dosage】
The dosage range is 7-14mg per kilogram of body weight (4-8 capsules per day), taken in 2 or 3 times. The recommended initial dose is at least 10mg per kilogram of body weight, 4-6 capsules. It should be swallowed with a glass of water at least one hour before or two hours after a meal. Milk, dairy products and drugs containing calcium, magnesium and aluminum (such as antacids) cannot be taken at the same time as this product. If it is ineffective after 4-6 weeks of observation after administration, the drug should be withdrawn.

【Clinical study】
Pharmacological action:

Estramustine phosphate is an anti-prostate cancer drug with a dual mechanism of action, which is effective in treating advanced prostate cancer.

The entire molecule is an antimitotic agent. After the carbamate is hydrolyzed, the metabolite-mediated release of estrogen exerts an anti-gonadotropin effect. Mild clinical side effects are due to the binding of estramustine to proteins in tumor tissue, resulting in drug accumulation at the target site. Estramustine phosphate also has mild estrogenic and anti-gonadotropin properties.

This product hardly produces bone marrow suppression at the usual therapeutic dose. This product is effective for patients who have not received drug treatment in the past and for patients who are ineffective with conventional hormone therapy.

Toxicology studies:

The LD50 of estramustine phosphate for oral administration to mice and rats exceeds 2000mg/kg. The LD50 of mice and rats for intravenous injection is 440mg and 192mg/kg respectively, and the LD50 of dogs is 400mg/kg-800mg/kg. After a single dose, the main target sites are the blood lymphatic system, endocrine system, and reproductive organs of males and females.

Repeated dose toxicity studies have been conducted in rats, dogs, and monkeys. The major target sites of oral and intravenous administration of estramustine phosphate in these animals are the hemolymphatic system, the endocrine system, and the reproductive organs of both males and females. The changes in target organs produced in dogs and monkeys are primarily related to the estrogenic effects of the compound, while rats exhibit both estrogenic and cytotoxic effects. No studies have been conducted on the reproductive and carcinogenicity of estramustine phosphate, nor have complete mutagenicity studies. However, as with other estrogens and antimitotic agents, estramustine phosphate has toxicity to reproductive organs and potential mutagenicity and carcinogenicity that should be noted.

[Precautions]
Estramustine phosphate capsules should be used with caution in patients with a history of thrombophlebitis, thrombosis, or thromboembolism, especially when associated with estrogen therapy. It should also be used with caution in patients with cerebrovascular and coronary artery disease. [u]Glucose tolerance [/u] – Diabetic patients should be carefully monitored when receiving this product because glucose tolerance may be impaired. [u] Increased blood pressure [/u] – Blood pressure should be measured regularly because of the possibility of hypertension. [u] Fluid retention [/u] – Patients treated with this drug have been reported to have worsening of existing or newly diagnosed peripheral edema and worsening of congestive heart disease; fluid retention may also affect other symptoms such as epilepsy, migraine or renal insufficiency, so careful observation is required. [u] Calcium/phosphorus metabolism [/u] – Because this drug may affect calcium and phosphorus metabolism, it should be used with caution in patients with bone metabolic diseases associated with hypercalcemia and in patients with renal insufficiency. When patients have liver damage, this drug may be poorly metabolized and should be used with caution in such patients. The patient’s liver function should also be checked regularly.

Note: Because estrogen-containing drugs can affect the relevant endocrine system and liver function, the corresponding laboratory indicators will also be affected.

Immunosuppressive Effects/Increased Susceptibility to Infections – Live or attenuated vaccines may cause serious or fatal infections in patients who are immunocompromised by chemotherapy drugs including estramustine. Patients receiving estramustine should avoid live vaccines. Killed or inactivated vaccines can be given, but the immune response to these vaccines may be reduced.

Like most anti-tumor immunosuppressants, this product has been shown to be carcinogenic in animals and under certain experimental conditions. In addition, although the Ames test did not show any mutagenic effects of estramustine phosphate, estradiol and nitrogen mustard have been found to be mutagenic. Complete blood counts and liver function tests should be performed regularly.

Effects on the ability to drive and operate machines
No negative effects on the patient’s ability to operate machines or drive have been reported.

Contraindications
Capsules: Estramustine phosphate will precipitate in the presence of calcium, magnesium, or aluminum salts.

[Adverse Reactions and Contraindications]
The most common adverse reactions include gynecomastia and impotence; nausea/vomiting; fluid retention/edema. The most serious adverse reactions include: thromboembolism, ischemic heart disease and congestive heart failure, and rarely, angioedema.

The adverse reactions reported by MedDRA system organ class are as follows:
Blood and lymphatic system disorders: anemia, leukopenia and thrombocytopenia are rare
Immune system disorders: hypersensitivity reactions
Metabolism and nutrition disorders: fluid retention
Psychiatric disorders: confusion and depression are rare
Nervous system disorders: headache and lethargy are rare
Cardiac disorders: congestive heart failure, ischemic heart disease, myocardial infarction
Vascular disorders: hypertension, thromboembolism
Gastrointestinal disorders: nausea and vomiting, diarrhea (especially in the first 2 weeks of treatment)
Hepatobiliary disorders: impaired liver function
Skin and subcutaneous tissue disorders: allergic rash
Angioedema (Quincke’s edema, laryngeal edema) is rare. In most reported events, including one fatal case, patients were taking ACE inhibitors at the same time. If angioedema occurs during treatment with this product, the drug should be discontinued immediately.
Musculoskeletal and connective tissue disorders: muscle weakness is rare
Reproductive system and breast disorders: gynecomastia, impotence
Rare transient increases in blood transaminase and bilirubin levels have been reported.

[Contraindications]
Estramustine phosphate capsules should not be used in the following patients
· Known allergy to estradiol or nitrogen mustard drugs
· Previous severe leukopenia and/or thrombocytopenia
· Severe liver disease
· Severe cardiovascular disease: complications caused by ischemic, thromboembolic or fluid retention

[Pregnant women use]
Estradiol and nitrogen mustard are known to be mutagenic, so men undergoing treatment should take contraceptive measures.
Not suitable for pregnant and lactating women.

[Children use]
This product is contraindicated for children.