Estracyt Capsules.

Estramustine phosphate 140 mg as estramustine sodium phosphate.

White, hard, gelatin capsules.

Carcinoma of the prostate, especially in cases unresponsive to, or relapsing after, treatment by conventional oestrogens (stilboestrol, polyoestradiol phosphate etc.) or by orchidectomy.

Adult and the elderly

Dosage range may be from 1 to 10 capsules a day by mouth. The capsules should be taken not less than 1 hour before or 2 hours after meals. The capsules should not be taken with milk or milk products. Standard starting dosage is 4-6 capsules a day in divided doses with later adjustment according to response and gastrointestinal tolerance.

Children

Estracyt should not be administered to children.

Use in patients with peptic ulceration, or those with severe liver dysfunction or myocardial insufficiency.

Use in children.

Use in patients hypersensitive to oestradiol or nitrogen mustard.

Use with caution in patients with moderate to severe bone marrow depression, thrombophlebitis, thrombosis, thromboembolic disorders, cardiovascular disease, coronary artery disease and congestive heart failure.

Caution should also be exercised in patients with diabetes, hypertension, epilepsy, hepatic and renal impairment and diseases associated with hypercalcaemia. Blood counts, liver function tests and serum calcium in hypercalcaemia should be performed at regular intervals. Patients with prostate cancer and osteoblastic metastases are at risk of hypocalcaemia and should have calcium levels closely monitored.

Immunosuppreant Effects/Increased Susceptibility to Infections - Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic agents including estramustine, may result in serious or fatal infections. Vaccination with a live vaccine should be avoided in patients receiving estramustine. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished

Milk, milk products or drugs containing calcium may impair the absorption of Estracyt and should not be taken simultaneously with Estracyt.

An interaction between Estracyt and ACE-inhibitors, possibly leading to an increased risk of angioneurotic oedema cannot be excluded.

Not applicable.

No adverse effects on a patient's ability to drive or operate heavy machinery have been reported.

The most common adverse reactions include gynaecomastia and impotence, nausea/vomiting and fluid retention/oedema.

The most serious reactions are thromboembolism, ischaemic heart disease, congestive heart failure and, rarely and angioneurotic oedema.

Reported reactions arranged according to MedDRA System Organ System are the following:

Blood and lymphatic system disorders: Anemia, leukopenia, thrombocytopenia rarely occur.

Immune system disorders: Hypersensitivity reaction

Metabolism and nutrition disorders: Fluid retention

Psychiatric disorders: Confusion and depression rarely occur.

Nervous system disorders: Headache and lethargy rarely occur

Cardiac disorders: Congestive heart failure, ischemic heart disease, myocardial infarction

Vascular disorders: Hypertension, thromboembolism

Gastrointestinal disorders: Nausea and vomiting, diarrhea (particularly during the first two weeks of treatment)

Hepato-biliary disorders: Impairment of liver function

Skin and subcutaneous tissue disorders: Allergic skin rash.

Angioneurotic edema (Quincke edema, larynx edema) can rarely occur. In many reported cases, including a fatal one, patients were concomitantly receiving ACE-inhibitors. Therapy with Estracyt is to be immediately discontinued should angioneurotic edema occur.

Musculoskeletal and connective tissue disorders: Muscular weakness rarely occurs.

Reproductive system and breast disorders: Gynecomastia, impotence

There is no specific antidote. Treatment is symptomatic and supportive and in the event of dangerously low red cell, white cell or platelet count, whole blood should be given as necessary. Liver function should be monitored.

ATC Code: L01XX11

Estracyt is a chemical compound of oestradiol and nitrogen mustard. It is effective in the treatment of advanced prostatic carcinoma.

Estracyt has a dual mode of action. The intact molecule acts as an anti-miotic agent; after hydrolysis of the carbamate ester, the metabolites act to bridge the released oestrogens and exert an anti-gonadotrophic effect. The low level of clinical side effects may be due to the fact that estramustine binds to a protein present in the tumour tissue, so resulting in accumulation of the drug at the target site. Estracyt also has weak oestrogenic and anti-gonadotrophic properties.

Estracyt causes little or no bone marrow depression at usual therapeutic dosage. Estracyt is effective in patients who have not previously received drug therapy, as well as in those who have shown no response to conventional hormone treatment.

Estramustine phosphate sodium is rapidly dephosphorylated in the intestine and prostate to estramustine and estromustine, which accumulate in the prostatic tissue. The plasma half-lives of these metabolites are 10 - 20 hours. Estramustine and estromustine are further metabolised before excretion.

No particular information is presented given the experience gained with the use of estramustine phosphate sodium in humans over the past several years.

Talcum, sodium lauryl sulphate, colloidal silicon dioxide, magnesium stearate, titanium dioxide (E171), hard gelatin capsule, black ink (containing black iron oxide (E172), propylene glycol (E1520) and shellac).

None that are relevant.

60 months in brown glass bottles.

Store out of the sight and reach of children.

The product is stable at storage conditions of 25^oC + 2^oC/60%RH (long term) and 40^oC + 2^oC/75%RH (short term). Therefore the product does not require any special storage precautions within EU countries (Climactic zone 2).

Brown glass bottle containing 100 capsules.

No special instructions.

Pharmacia Limited

Ramsgate Road, Sandwich, Kent

CT13 9NJ

UK

PL 00032/0316

25 May 2002/13 Nov 2008

13 November 2008

Legal Category: POM

Ref: ES 4_0