INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo OESTRADIOL IMPLANTS 20 mg
                RU 2130.040.003
SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

OESTRADIOL IMPLANTS 20 mg

COMPOSITION
Implants of 20 mg oestradiol.

PHARMACOLOGICAL CLASSIFICATION
A/21.8.1/Oestrogens

PHARMACOLOGICAL ACTION
Oestradiol pellets, when inserted subcutaneously, provide a slow release of the natural oestrogen, oestradiol.

INDICATIONS
Oestrogen deficiency symptoms associated with the natural or surgical menopause.

CONTRA-INDICATIONS
- Pregnancy or women who may become pregnant.
- Cardiovascular or cerebrovascular disorders, e.g. thrombophlebitis, thrombo embolic processes or a history of these conditions.
- Hypertension. Migraine.
- Liver disease or a history of this condition if the results of the liver function tests have failed to return to normal; cholestatic jaundice; a history of jaundice of pregnancy or jaundice due to estrogen use; Rotor syndrome and Dubin Johnson syndrome.
- Known or suspected estrogen dependant tumours.
- Endometrial hyperplasia.
- Undiagnosed vaginal bleeding.
- Haemoglobinopathies.
- Porphyria.
- Hyperlipoproteinaemia as well as other risk factors predisposing to cardiovascular disorders.
- A history during pregnancy or previous estrogen use of severe pruritus or herpes gestationis or a deterioration of otosclerosis.

WARNINGS
If any signs of thrombo embolic processes occur, the pellet should be removed immediately. In patients using estrogen containing preparations the risk of deep vein thrombosis may be increased when undergoing major surgery or prolonged immobilization.
The pellet should be removed if liver function tests become abnormal.

DOSAGE AND DIRECTIONS FOR USE
Oestrogen deficiency symptoms:
The initial dose is 20 - 40 mg depending on individual requirements. Frequency of replacement depends on the duration of activity of the pellets administered and the severity of symptoms. Patients require a further pellet when symptoms return, usually every 4 to 8 months.
In women with an intact uterus, oestrogen therapy should be combined with an adequate dosage of a progestational agent at regular intervals, for example for 10 to 14 days every month, to protect the endometrium from oestrogen induced hyperplasia.
N.B. Since the rate of release of the active substance depends on the surface area of the pellet, the dosage is not only determined by the total implanted dose, but also by the number of separate pellets, sited on separate tracks.
Administration:
Oestradiol implants should be inserted subcutaneously (either by using a trocar and canula or by open surgery) into an area where there is relatively little movement, such as the lower abdominal wall or the buttock. Insertion is made under local anaesthesia and the wound is closed either with an adhesive dressing or a fine suture. The implants must be placed subcutaneously to facilitate removal if necessary.

SIDE EFFECTS AND SPECIAL PRECAUTIONS
The following adverse effects have been associated with oestrogen therapy:
- Genito - urinary tract
  Intermenstrual bleeding, endometrial proliferation, excessive production of cervical mucus, increase in size of uterine fibromyomata, aggravation of endometriosis.
- Breast
  Tenderness, pain, enlargement, galactorrhoea.
- Gastro intestinal tract
  Nausea, vomiting, cholelithiasis, cholestatic jaundice.
- Cardiovascular system
  Thrombosis, rise of blood pressure, fluid and salt retention.
- Skin
  Chloasma, erythema nodosum, rash.
- Eyes
  Discomfort of the cornea if contact lenses are used.
- Central nervous system
  Headache, migraine, mood changes.
- Various
  Reduced glucose tolerance and change in body mass.
  Case reports have been published on benign hepatic tumours.
Precautions
In the presence of severe varicose veins the benefits of oestrogen containing preparations must be weighed against the possible risks.
There are reports indicating an association between the use of oestrogen containing preparations and the occurrence of cholelithiasis.
Pain in the breasts or excessive production of cervical mucus may be indicative of too high a dosage.
Chloasma is occasionally seen during the use of oestrogen and/or progestagen containing preparations, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun while taking this preparation.
The use of oestrogen containing preparations may influence the result of certain laboratory tests.
During prolonged treatment with oestrogen containing preparations periodic medical and gynaecological examinations are advisable.
Patients with any of the following conditions should be monitored:
- Latent or overt cardiac failure, renal dysfunction, hypertension, epilepsy or migraine (or a history of these conditions), since aggravation or recurrence may be induced.
- Sickle cell haemoglobinopathy, since under certain circumstances, e.g. during infections or anoxia, oestrogen containing preparations may induce thrombo embolic processes in patients with these conditions.
- Diabetes, since oestrogens may diminish the glucose tolerance and increase the need for insulin or other antidiabetic medicines;
- Oestrogen sensitive gynaecological disorders, e.g. uterine fibromyomata which may increase in size, and endometriosis which may be aggravated during oestrogen treatment.
  Some retrospective studies suggest that an association exists between the prolonged continuous administration of certain unopposed oestrogens to postmenopausal women and an increased risk of endometrial carcinoma.
- Depression.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
The acute toxicity of oestradiol in animals is very low. In the event of overdosage the pellets should be removed.

IDENTIFICATION
White to pale brown, opaque or translucent cylinder in a sealed glass tube, secured by a white, wool plug.
The 20 mg implant has a diameter of 2,15 mm

PRESENTATION
Each sterile implant is supplied singly, in a sealed glass tube, held in position by a plug of white coloured, non absorbant wool.

STORAGE INSTRUCTIONS
Keep below 30°C and protect from light.
Keep out of reach of children.

REGISTRATION NUMBER:
G/21.8.1/3191

NAME AND BUSINESS ADDRESS OF THE APPLICANT
Donmed Pharmaceuticals (Pty) Ltd
Donmed House, Cambridge Place
cnr Kirkby & Oxford Roads
Bedfordview 2007

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
18 October 1989

Under license of NV Organon, The Netherlands

                RU 2130.040.003

Updated on this site: March 2004
Source: Pharmaceutical Industry

SAEPI HOME PAGE      TRADE NAME INDEX      GENERIC NAME INDEX      FEEDBACK
Information presented by Malahyde Information Systems © Copyright 1996-2004