DIETHYLSTILBESTROL

Posology Adults:

Management of prostatic carcinoma: 1 - 3 mg daily.

Paediatric population Children:

Diethylstilbestrol should not be used in children.

Special populations Elderly:

The recommended adult dose is appropriate. 4 below. Diethylstilbestrol stimulates breast tissue in males, breast bud irradiation may be offered before treatment. 4 below Method of administration For oral administration.

Diethylstilbestrol has been used for many years and has been found to cause serious adverse effects which have greatly limited its use. There is limited clinical trial data on adverse reactions relating to the use of diethylstilbestrol in men with carcinoma of the prostate.

The following adverse reactions have been reported from post-marketing experience over many years. Many of the reactions are dose related and, from the data available, it is not possible to indicate their frequency (see table below).

System Organ Class Adverse reactions (frequency unknown) Metabolism and nutrition disorders sodium retention, fluid retention Eye disorders corneal irritation in patients wearing contact lenses Psychiatric disorders mood altered Nervous system disorders headache, migraine Vascular disorders thrombosis, cerebral thrombosis, coronary artery thrombosis, embolism, hypertension Gastrointestinal disorders nausea, vomiting Hepatobiliary disorders cholelithiasis, jaundice cholestatic Skin and subcutaneous tissue disorders rash, erythema nodosum, chloasma Reproductive system and breast disorders in both sexes, breast discomfort, breast tenderness, breast pain, breast enlargement, breast discharge.

In men, gynaecomastia, testicular atrophy, impotence Investigations glucose tolerance decreased, weight increased As high doses of diethylstilbestrol in early pregnancy have caused vaginal carcinoma in female offspring 16-20 years later, it should not be used in pre- menopausal women.

As with other oestrogens the following hormonal disturbances may occur in women, diethylstilbestrol may cause an increase in the size of uterine fibromyomata, endometrial proliferation and/or an aggravation or recurrence of endometriosis and an excessive production of cervical mucous.

The risk of endometrial neoplasia is increased significantly. Other effects may be withdrawal bleeding in women. In the event of prolonged usage there is an increased risk of endometrial carcinoma. Hypercalcaemia and bone pain may occur in women treated for breast cancer.

Thromboembolic complications are frequent and patients treated with diethylstilbestrol should be given prophylaxis with aspirin (75 mg daily). The use of diethylstilbestrol may cause tenderness, pain, enlargement and secretion of milk-like fluid from the breast.

Breast bud irradiation should be considered before treatment with diethylstilbestrol. Care should be taken when administering diethylstilbestrol preparations to patients with cardiac failure; hypertension; diabetes; epilepsy; migraine; depression; contact lenses; cholelithiasis; or if there are any evidence of renal impairment, hepatic impairment; a history of, or with cholestatic jaundice from any cause.

During treatment with diethylstilbestrol blood pressure should be monitored at regular intervals and if hypertension develops treatment should be stopped. In addition, if surgery is contemplated or signs or symptoms of thrombosis develop treatment should be discontinued.

This is because of the significant increase in risk of deep vein thrombosis in the presence of high oestrogen activity. In patients who suffer from diabetes, glucose tolerance may be lowered, and the need for insulin or other anti-diabetic drugs may be increased.

In thyroid disease or investigations of thyroid function, thyroid hormone binding globulin may be increased leading to increased circulating total thyroid hormone, which may lead to difficulty in interpreting thyroid function tests.

Patient with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.

Diethylstilbestrol is a synthetic non-steroidal oestrogen hormone which due to its carcinogenic potential is only justified in the management of malignant disease. Diethylstilbestrol should not be used in children or young adults because of its carcinogenic potential.

Diethylstilbestrol is strongly contra-indicated in those who are pregnant (it is not suitable for pre-menopausal women). It is also contra-indicated in the following conditions; oestrogen dependent neoplasms especially of the genital tract; pre- menopausal carcinoma of the breast; endometrial hyperplasia or uterine fibromyomata (fibroids).

Diethylstilbestrol should not be given where there is undiagnosed vaginal bleeding; a history of herpes gestationis; porphyria; moderate to severe hypertension; severe or active liver disease; hyperlipoproteinaemia; any cardiovascular or cerebrovascular disorder or a history of thrombo-embolism or conditions predisposing to it such as sickle cell anaemia, untreated polycythaemia and pulmonary hypertension.