1. Name Of The Medicinal Product
Estracyt Capsules.
2. Qualitative And Quantitative Composition
Estramustine phosphate 140 mg as estramustine sodium phosphate.
3. Pharmaceutical Form
White, hard, gelatin capsules.
4. Clinical Particulars
4.1 Therapeutic Indications
Carcinoma of the prostate, especially in cases unresponsive to, or relapsing after, treatment by conventional oestrogens (stilboestrol, polyoestradiol phosphate etc.) or by orchidectomy.
4.2 Posology And Method Of Administration
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.
4.3 Contraindications
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.
4.4 Special Warnings And Precautions For Use
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
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
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.
4.6 Pregnancy And Lactation
Not applicable.
4.7 Effects On Ability To Drive And Use Machines
No adverse effects on a patient's ability to drive or operate heavy machinery have been reported.
4.8 Undesirable Effects
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
4.9 Overdose
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.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
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.
5.2 Pharmacokinetic Properties
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.
5.3 Preclinical Safety Data
No particular information is presented given the experience gained with the use of estramustine phosphate sodium in humans over the past several years.
6. Pharmaceutical Particulars
6.1 List Of Excipients
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).
6.2 Incompatibilities
None that are relevant.
6.3 Shelf Life
60 months in brown glass bottles.
6.4 Special Precautions For Storage
Store out of the sight and reach of children.
The product is stable at storage conditions of 25oC + 2oC/60%RH (long term) and 40oC + 2oC/75%RH (short term). Therefore the product does not require any special storage precautions within EU countries (Climactic zone 2).
6.5 Nature And Contents Of Container
Brown glass bottle containing 100 capsules.
6.6 Special Precautions For Disposal And Other Handling
No special instructions.
7. Marketing Authorisation Holder
Pharmacia Limited
Ramsgate Road, Sandwich, Kent
CT13 9NJ
UK
8. Marketing Authorisation Number(S)
PL 00032/0316
9. Date Of First Authorisation/Renewal Of The Authorisation
25 May 2002/13 Nov 2008
10. Date Of Revision Of The Text
13 November 2008
Legal Category: POM
Ref: ES 4_0
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