Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Pfizer Limited, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK
Hypersensitivity to estramustine sodium phosphate, oestradiol or nitrogen mustard or to any of the excipients listed in section 6.1.
Use in patients with peptic ulceration, or those with severe liver dysfunction or myocardial insufficiency.
Use in patients with active thrombosis or thromboembolic disorders or complications related to fluid retention.
Use in children.
Estramustine should be used with caution in patients with a history of thrombophelebitis, thrombosis or thromboembolic disorders, especially if associated with estrogen therapy. Caution should also be used in patients with cardiovascular disease, cerebral vascular disease and coronary artery disease.
Glucose Tolerance – Because glucose tolerance may be decreased, diabetic patients should be carefully followed while receiving estramustine.
Elevated blood pressure-Because hypertension may occur, blood pressure should be monitored periodically.
Fluid retention – Exacerbation of pre-existing or incipient peripheral oedema or congestive heart disease has been seen in some patients receiving estramustine therapy. Other conditions which might be influenced by fluid retention, such as epilepsy, migraine, or renal dysfunction, require careful observation.
Calcium/phosphorous metabolism – Estramustine may influence the metabolism of calcium and phosphorous and should be used with caution in patients with metabolic bone diseases that are associated with hypercalcemia or in patients with renal insufficiency. Serum calcium should be performed at regular intervals. Patients with prostate cancer and osteoblastic metastases are at risk for hypocalcaemia and should have calcium levels closely monitored.
Estramustine may be poorly metabolized in patients with impaired liver function and should be administered with caution in such patients. Liver function tests should be performed at regular intervals.
Note: since certain endocrine and hepatic functions are influenced by estrogen-containing drugs the corresponding laboratory test values will be affected.
Use with caution in patients with moderate to severe bone marrow depression. Blood count should be performed at regular intervals.
Immunosuppressant 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.
Oestrogens have been reported to increase both therapeutic activity and toxicity of tricyclic antidepressants, probably via inhibition of their metabolism.
Milk, milk products or drugs containing calcium, magnesium or aluminium may impair the absorption of Estracyt and simultaneous intake must therefore be avoided. The mechanism behind this interaction is that estramustine forms insoluble salts with polyvalent metal ions.
An interaction between estramustine and ACE-inhibitors, possibly leading to an increased risk of angioedema (see section 4.8) cannot be excluded.
Estradiol and nitrogen mustard are potentially mutagenic, and therefore males undergoing treatment with estramustine should employ contraceptive measures (see section 5.3).
Since Estracyt is indicated for carcinoma of the prostate in males, it is not indicated for women.
The effect of estramustine on the ability to drive or use machinery has not been systematically evaluated.
The most common adverse reactions include gynaecomastia, nausea/vomiting and fluid retention/oedema.
The most serious reactions are embolism, myocardial ischaemia, cardiac failure congestive and angioedema.
Reported reactions arranged according to MedDRA System Organ System are the following:
Very common ≥1/10
Common ≥1/100 to <1/10
Frequency not known (cannot be estimated from available data)
Very common: Anaemia, Leukopenia
Common: Thrombocytopenia
Frequency not known: Hypersensitivity
Very common: Fluid retention
Frequency not known: Confusional state, Depression
Common: Lethargy, Headache
Very common: Cardiac failure congestive
Common: Myocardial infarction
Frequency not known: Myocardial ischaemia
Common: Embolism
Frequency not known: Hypertension
Very common: Nausea and Vomiting*, Diarrhoea*
Very common: Hepatic function abnormal
Frequency not known: Angioedema**, Dermatitis allergic
Frequency not known: Muscular weakness
Very common: Gynaecomastia
Frequency not known: Erectile dysfunction
Frequency not known: Injection site thrombosis (IV solution)
* Particularly during the first two weeks of treatment.
** Angioedema (Quincke oedema, larynx oedema) can occur. In many reported cases, including a fatal one, patients were concomitantly receiving ACE-inhibitors. Therapy with estramustine is to be immediately discontinued should angioedema occur.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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