The contraceptive action of LEVLEN ED is based on the interaction between a number of factors the most important of which are the inhibition of ovulation, the inspissation of cervical mucus so as to constitute a barrier to sperm and the rendering of the endometrium unreceptive to implantation.

Both substances are absorbed rapidly and completely after oral administration. Maximum plasma levels are reached after approx. 1 hour.

The two steroids are eliminated mainly as metabolites: levonorgestrel renally (50-60%) and with the bile (40-50%) with a half-life of approx. 24 hours, ethinylestradiol renally (40%) and with the bile (60%) with a half-life of approx. 24 hours.

Oral contraception.

First treatment course

1 tablet daily for 28 days starting in the red section of the memo-pack on the first day of bleeding, the initial tablet being the one marked with the appropriate day of the week.

The time of day at which the tablet is taken is immaterial, but once the patient has selected a particular time she should stick to it e.g. after breakfast or the evening meal.

Each subsequent course is started in the red section on the day after the previous one has been finished.

Changing from other oral contraceptives

The first tablet of LEVLEN ED should be taken on the first day immediately after the end of the previous oral contraceptive course. Additional (non-hormonal) precautions other than the rhythm, temperature or cervical mucus methods, should also be used for the first 14 days when changing product.

Oral contraceptives can be prescribed post-partum or post-abortum as soon as the first normal biphasic cycle has occurred. If a further pregnancy is contraindicated for medical reasons, medication with oral contraceptives must be initiated by the 12th (but not before the 7th) day post-partum or by the 5th day post-abortum at the latest. Because of the non-hormonal bridging tablets the 28 tablet memo-pack is not suitable for this purpose.

Tablet taking should not be interrupted if intermenstrual bleeding occurs. Slight bleeding will usually stop spontaneously, but if it persists it can be arrested - as can also intermenstrual bleeding of menstrual intensity - by the additional administration of 0.02 - 0.04mg ethinylestradiol daily for 4 - 5 days. This medication should not, however, be continued beyond the last hormonal tablet of a LEVLEN ED memo-pack.

Should breakthrough bleeding persist or recur, a thorough examination including curettage is indicated to exclude organic factors.

For the LEVLEN ED memo-pack, errors in taking the 7 large tablets (the 2 tablets immediately before the red section and the first five tablets in the red section) can, of course, be ignored.

If a single small active tablet is delayed it should be taken as soon as possible. Contraceptive protection is maintained if the delayed tablet is taken within 12 hours of the correct time.

If one or more of the small active tablets have been forgotten only the most recently delayed tablet should be taken and the earlier missed tablets omitted. Additional contraception such as the barriers and spermicides should be used for the next 7 days while the next active tablets are being taken.

If the 7 day's additional contraception will extend beyond the Friday before the red section, (i.e. the last active tablet in the current memo-pack), the LEVLEN ED user should take the tablets up to and including the Friday, and start a new memo-pack next day with the Saturday tablet in the red section, i.e. the first active tablet.

Vomiting and diarrhoea may reduce efficacy by preventing full absorption. Barriers and spermicides should be used until 7 days after the upset; (mild laxatives do not impair contraceptive action). If those 7 days overrun the Friday just before the red section in the current LEVLEN ED memo-pack, the user should omit the 7 inactive tablets (as above).

Some medicines accelerate the metabolism of oral contraceptives taken concurrently (see "Interactions"). It is, therefore, advisable to use non-hormonal methods of contraception (except the rhythm, temperature, or cervical - mucus methods) in addition to the oral contraceptive as long as an extremely high degree of protection must be provided during treatment with some medicines.

Missed period

If, in exceptional cases, bleeding fails to occur while the tablets in the red section are being taken, tablet taking is provisionally to be stopped and pregnancy is to be excluded before continuation of treatment.

Pregnancy, severe disturbances of liver function, jaundice or persistent itching during a previous pregnancy, Dubin-Johnson syndrome, Rotor syndrome, previous or existing hepatic tumours, existing or previous thromboembolic processes in arteries or veins and states which predispose to such diseases (e.g. disturbances of the clotting system with a tendency towards the thrombosis, certain heart diseases), existing thrombophlebitis, sickle - cell anaemia, known or suspected carcinoma of the breast or genital organs or suspected oestrogen-dependent neoplasia, severe diabetes with vascular changes, disturbances of lipometabolism, a history of herpes of pregnancy, otosclerosis with deterioration during pregnancy, undiagnosed vaginal bleeding, hemiplegic migraine.

The physician should be alert to the earliest manifestations of thrombotic disorders and medication should be discontinued immediately should any of these occur.

If there is a sudden, partial or complete loss of vision or if there is a sudden onset of proptosis, diplopia or migraine, medication should be discontinued and examination made. If examination reveals papilloedema or retinal vascular lesions the medication should be discontinued.

Further reasons for immediate discontinuation are immobilisation (e.g. following accidents), onset of jaundice, onset of anicteric hepatitis, itching of the whole body, increase in epileptic seizures, significant rise in blood pressure, pregnancy.

Oral contraceptive medication should be discontinued at least six weeks prior to elective surgery because of the danger of thrombosis.

According to the present state of knowledge, an association between the use of progestogen-oestrogen combinations and an increased risk of venous and arterial thromboembolic diseases cannot be ruled out.

The risk of thrombotic and cardiac effects from oral contraceptives increases with age and is aggravated by cigarette smoking.

About six months should elapse after the regression of virus hepatitis before preparations such as LEVLEN ED are used.

In rare cases, benign and in even rarer cases, malignant liver tumours leading in isolated cases to life-threatening intraabdominal haemorrhage have been observed after the use of hormonal substances such as those contained in LEVLEN ED. If severe upper abdominal complaints, liver enlargement or signs of intraabdominal haemorrhage occur, a liver tumour should be included in the differential-diagnostic considerations and, if necessary, the preparation withdrawn.

Irregular tablet - taking, vomiting or intestinal disorders with diarrhoea, very rare metabolic disturbances or prolonged simultaneous use of certain medical preparations (cf. "Interactions") can affect the contraceptive action. It is, therefore, advisable to use non-hormonal methods of contraception (excepting the rhythm and temperature methods) in the cycle concerned. If the condition reducing the efficacy of the preparation is protracted, other methods of contraception should be considered.

Before starting on LEVLEN ED, a thorough general medical (including blood pressure measurement, urine test for sugar and, if necessary, special liver tests) and gynaecological (including breasts and cytological smear) examination must be conducted to detect any diseases requiring treatment or risks. The family case history should be carefully noted. Disturbances of the clotting system must be ruled out if any members of the family have suffered from thromboembolic diseases (e.g. deep vein thrombosis, stroke, myocardial infarction) already at a young age. Pregnancy must be excluded.

As a precaution, control examinations should be conducted at intervals of about 6 months during long-term treatment with the tablets.

Concurrent use of antibiotics or anticonvulsants may reduce the effective concentrations of the steroids and hence impair the contraceptive effect.

Under the influence of oral contraceptives pre-existing uterine fibroids may increase in size.

Patients with conditions such as cardiac or renal dysfunction, diabetes or a tendency to diabetes, high blood pressure, varicose veins, a history of phlebitis, otosclerosis, multiple sclerosis, epilepsy, migraine, porphyria, tetany or chorea minor require careful observation whilst on oral contraceptive therapy.

Patients with a history of depression should be carefully observed and the medication discontinued if serious depression recurs.

A decrease in glucose tolerance occurs in a significant number of patients on oral contraceptives.

Susceptible women may experience a rise in blood pressure during therapy.

Toxicity studies of the two ingredients individually and in combination including teratogenicity, mutagenicity and carcinogenicity have been conducted in vitro and in various animal species. No findings were raised which could restrict the use of LEVLEN ED in man.

LEVLEN ED is contraindicated in pregnancy.

Active ingredients of oral contraceptives have been detected in the milk of mothers receiving these medicines and the effect on breast-fed infants is unknown. Suppression of lactation may occur.

When using LEVLEN ED during lactation it has to be considered that milk production may be reduced during the initial period of use. In addition, minute amounts of substance are excreted with the milk.

In general contraception is only indicated during long periods of lactation, as menstrual cycles do not usually occur during short periods of lactation.

Nausea, vomiting, abdominal cramps, breakthrough bleeding, breast changes, changes in menstrual flow, changes in cervical erosion and cervical secretions, amenorrhoea during and after treatment, anovulation post treatment, cholestatic jaundice, pruritus, allergic rash, photosensitivity, poor tolerance of contact lenses, alopecia, chloasma, erythema multiforme, erythema nodosum, haemorrhagic eruption, hirsuitism, headache, depressive moods, migraine, dizziness, drowsiness, changes in appetite, body weight and libido can occur.

Some medicines may reduce the effectiveness of oral contraceptives. These include phenylbutazone, griseofulvin, rifampicin, barbiturates, certain antibiotics, hydantoins. The requirements for oral antidiabetics or insulin can change.

Oral contraceptives may cause alterations in certain laboratory estimations. A medicine free period of two months may be required before some of these parameters return to normal.

With the following tests abnormal results may reflect a biological interference with the test analyte and not an impairment of organ function:

The glucose tolerance test is usually impaired. Fasting blood glucose levels may also be raised.

Although free thyroxine levels are unaffected, an increase in thyroid binding globulin means that other estimations of thyroid function may be erroneous.

Lipid metabolism may be affected with changed serum levels of HDL, cholesterol, triglycerides and phospholipids being observed.

Urinary pregnanediol levels may be decreased.

Serum albumin levels are usually decreased (along with the associated calcium levels).

Analytical interference is observed with the Zimmerman test for urinary 17-keto and 17-ketogenic steroids.

With the following tests abnormal results may indicate impairment of organ function:

liver - increase in serum transaminases, alkaline phosphotases, gamma glutamyl transpeptidase, bilirubin and binding proteins;

clotting factors - increase in factors II, V, IX, X, XII and especially VII; decrease of antithrombin III.

Nil.

Pharmaceutical Precautions

Shelf-life: 5 years

Special precautions for storage: Store below 25°C

Medicine Classification

Prescription Medicine

Package Quantities

Three calendar packs of 28 tablets.

Further Information

Nil.