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

Logo DEMULEN® 28 Tablets
SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

DEMULEN® 28 Tablets

COMPOSITION:
21 tablets each containing ethynodiol diacetate 1 mg and ethinyloestradiol 0,05 mg, as well as 7 inert spacer tablets.

PHARMACOLOGICAL CLASSIFICATION:
A 18.3 Ovulation controlling agents.

PHARMACOLOGICAL ACTION:
Oestrogen/oestrogen compounds such as DEMULEN 28 reduce the gonadotrophin content of, and secretion by the anterior pituitary gland, as a consequence of which ovulation does not occur. There are also variations in the amount and consistency of the cervical, mucus which remains scanty and viscous, presenting a barrier to the free passage of sperm. The nature of the endometrium is also altered but the importance of these changes has yet to be clarified.

INDICATIONS:
Demulen is indicated for oral contraception.

CONTRA-INDICATIONS:
Oral contraceptives should not be used in women with any of the following conditions: thrombophlebitis or thromboembolic disorders; a past history of deep vein thrombophlebitis or thromboembolic disorders; cerebral vascular disease, myocardial infarction or coronary artery disease, or a past history of these conditions; known or suspected carcinoma of the breast; known or suspected oestrogen-dependent neoplasia; undiagnosed abnormal genital bleeding; past or present, benign or malignant liver tumours among women who developed these tumours during the use of oral contraceptives or other oestrogen-containing products: known or suspected pregnancy.

DOSAGE AND DIRECTIONS FOR USE:
One tablet daily from the first Sunday after onset of menstruation (beginning on the same day if the patient's period begins on Sunday) until 21 white tablets have been taken. The patient then takes the seven placebo tablets, one on each of the next seven days. The last tablet is taken on a Saturday. The next 28-day cycle is begun on the next day, Sunday.

In the case of missed tablets, the patient should be instructed to take the omitted tablet as soon as it is remembered and take the next one at the usual time. If two consecutive tablets are missed, the dosage should be doubled for the next two days. The regular schedule should then be resumed. If the patient has omitted more that two tablets. DEMULEN 28 should be discontinued and alternative contraceptive measures should be taken until menstruation occurs or the possibility of pregnancy is excluded. Omission of placebo tablets does not impair contraceptive protection.

The protection provided by this method is continuous. It is not, however, advisable to rely on the method alone for protection during the first two weeks of taking the tablets (this applies only when taking oral contraceptive tablets for the first time, or starting again after an interval of a month or more).

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Oral contraceptives have been associated with an increased risk of thromboembolism, stroke, deep vein thrombosis, pulmonary; embolism, myocardial infarction, transient ischaemic attacks and subarachnoid haemorrhage. Risk has been reported to be related to the dose of both the oestrogen and the progestogen. The occurrence of myocardial infarction is related to the number of underlying risk factors for coronary artery disease, (cigarette-smoking, hypertension, hypercholesterolaemia, obesity, diabetes and a history of pre-eclampsia toxaemia) regardless of whether or not oral contraceptives are used. An increase in blood pressure has been reported in patients receiving oral contraceptives. The amount of increase may correlate directly with increasing dosage of progestogen.

Oral contraceptive failure may occur with concomitant antibiotic therapy. For maximal protection, additional non-hormonal contraception should be recommended for the duration of antibiotic therapy and for seven days afterwards, those on longterm antibiotic therapy may only take extra precautions for the first two weeks of antibiotic therapy.

Spotting and breakthrough bleeding are possible signs of diminished contraceptive effectiveness.

Cigarette-smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Persistence of risk after discontinuing use of oral contraceptives has been reported for circulatory disease in general, for non-rheumatic heart disease, and for cerebrovascular disease (including subarachnoid haemorrhage, cerebral thrombosis and transient ischaemic attacks).

In all cases of abnormal uterine bleeding or amenorrhoea, a diagnosis should be established before initiating treatment with DEMULEN 28 in order to rule out the presence of an organic lesion. There is now evidence that oestrogens increase the risk of carcinoma of the endometrium in humans. Although some epidemiological studies have suggested an increased risk of breast cancer or of cervical dysplasia, erosion and carcinoma in long-term pill users, cause and effect have not been established. Pre-existing uterine fibromyomas may increase in size under the influence of oestrogen/progestogen combinations. It is possible that the incidence of gallbladder disease may be increased by oral contraceptives. Benign hepatic adenomas and carcinomas, although rare, have been reported with the use of oral contraceptives.

Discontinue treatment with DEMULEN 28 if there is unexplained gradual or sudden, partial or complete, loss of vision or any evidence of ocular changes, or onset or aggravation of migraine or development of headache of a new pattern which is recurrent, persistent or severe.

Several reports suggest an association between foetal exposure to female sex steroids, including oral contraceptives, and congenital abnormalities. Therefore, pregnancy should be ruled out before continuing treatment in any patient who has missed two consecutive periods.

Active ingredients of oestrogen/progestogen combinations have been detected in the milk of mothers taking such drugs. The effect on breast-fed infants has not been determined.

Tests of endocrine, hepatic and thyroid function, as well as coagulation tests, may be affected by treatment with DEMULEN 28.

Because surgery is more likely to be associated with an increased incidence of thrombotic side-effects, administration of DEMULEN 28 should be discontinued at least 4 weeks prior to elective surgery or during periods of prolonged immobilization. In addition to those mentioned above, the following side effects have been reported with oral contraceptives: nausea and vomiting; gastrointestinal symptoms (eg. abdominal cramps and bloating); breakthrough bleeding; spotting; change in menstruation dysmenorrhoea, amenorrhoea during and after use; infertility after discontinuation; oedema; chloasma or melasma, which may persist when the drug is discontinued; breast changes: tenderness, enlargement and secretion; changes in weight (increase or decrease): change in cervical erosion and secretion; endocervical hyperplasia; possible diminution in lactation when given immediately postpartum; cholestatic jaundice; migraine; Raynaud’s disease; increase in size of uterine leiomyomata; rash (allergic); mental depression; reduced tolerance to carbohydrates; vaginal candidiasis; change in corneal curvature (steepening); and intolerance to contact lenses.

There is evidence of an association between the following conditions and the use of oral contraceptives, although confirmatory studies have not been done: mesenteric thrombosis, Budd-Chiari syndrome, neuro-ocular lesions (eg. retinal thrombosis and optic neuritis).

The following adverse reactions or conditions have been reported in users of oral contraceptives, and the association has neither been confirmed nor refuted: premenstrual-like syndrome, cataracts, changes in libido, chorea, changes in appetite, cystitis-like syndrome, headache, paraesthesia, nervousness, dizziness, auditory disturbances, rhinitis, fatigue, backache, hirsutism, loss of scalp hair, erythema multiforme, erythema nodosum, haemorrhagic eruption, haemolytic uraemic syndrome, malignant hypertension, itching, vaginitis, porphyria, impaired renal function, acute renal failure (sometimes irreversible), premature ventricular contractions, pulmonary hypertension, thrombotic thrombocytopenic purpura, anaemia, pancreatitis, hepatitis, colitis, gingivitis, dry socket, lupus erythematosus, rheumatoid arthritis, pituitary tumours (eg. adenoma) with amenorrhoea and/or galactorrhoea, malignant; melanoma; endometrial, cervical and breast carcinoma (see above).

Drug Interactions:
The following drugs may interact with oral contraceptives to render them less effective and increase the incidence of breakthrough bleeding: rifampicin, isoniazid, ampicillin, neomycin, penicillin V, tetracycline, chloramphenicol, sulphonamides, nitrofurantoin, griseofulvin, barbiturates, phenytoin, primidone, phenylbutazone. Analgesics, tranquillizers and anti-migraine preparations. Oral contraceptives may alter the effectiveness of other types of drugs, such as oral anti-coagulants, anti-convulsants, tranquillizers (eg. diazepam), tricyclic anti-depressants, antihypertensive agents, (eg. guanethidine), theophylline, caffeine, vitamins, hypoglycaemic agents, clofibrate, glucocorticoids and acetaminophen.

KNOWN SYMPTOMS OF OVERDOSE AND PARTICULARS OF ITS TREATMENT:
Fatal overdosage has not been reported, but overdosage may be manifested by nausea, vomiting; breast engorgement and vaginal bleeding. Gastric lavage may not be necessary but demulcents such as milk, egg white or bismuth hydroxide can be helpful.

IDENTIFICATION:
DEMULEN 28, active tablets are white 6,35 mm in diameter, round, bi-convex, uncoated tablets, engraved "SEARLE”above “163”on both sides.

Spacers are round, orange tablets with “SEARLE”stamped on one side.

PRESENTATION:
DEMULEN 28 tablets are supplied in foil blister packs.

STORAGE INSTRUCTIONS:
Store DEMULEN 28 in a dry place below 25°C. Keep out of reach of children.

REFERENCE NUMBER:
H1947 (Act 101/1965)

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
G.D Searle (South Africa) (Pty) Ltd.
14 Mandy Road
Reuven
Johannesburg

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
13 February 1975

Code 4075 (ICR 7692RI)-7-9/93

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