Logynon^® coated tablets

Calendar pack containing 6 light brown tablets, 5 white tablets and 10 ochre-coloured tablets containing the following ingredients:

Each light brown tablet (Phase I) contains:

For full list of excipients, see section 6.1

Coated tablets

Each Phase I tablet is light brown

Each Phase II tablet is white

Each Phase III tablet is ochre

Oral contraception and the recognised gynaecological indications for such oestrogen-progesterone combinations.

First treatment cycle: 1 tablet daily for 21 days, starting on the first day of the menstrual cycle. Contraceptive protection begins immediately.

Subsequent cycles: Tablet taking from the next pack of Logynon is continued after a 7-day interval, beginning on the same day of the week as the first pack.

Changing from 21-day combined oral contraceptives: The first tablet of Logynon should be taken on the first day immediately after the end of the previous oral contraceptive course. Additional contraceptive precautions are not required.

Changing from a combined Every Day pill (28 day tablets):

Logynon should be started after taking the last active tablet from the Every Day Pill pack. The first Logynon tablet is taken the next day. Additional contraceptive precautions are not then required.

Changing from a progestogen-only pill (POP):

The first tablet of Logynon should be taken on the first day of bleeding, even if a POP has already been taken on that day. Additional contraceptive precautions are not then required. The remaining progestogen-only pills should be discarded.

Post-partum and post-abortum use: After pregnancy, oral contraception can be started 21 days after a vaginal delivery, provided that the patient is fully ambulant and there are no puerperal complications. Additional contraceptive precautions will be required for the first 7 days of tablet taking. Since the first post-partum ovulation may precede the first bleeding, another method of contraception should be used in the interval between childbirth and the first course of tablets. After a first-trimester abortion, oral contraception may be started immediately in which case no additional contraceptive precautions are required.

Special circumstances requiring additional contraception

Incorrect administration:

A single delayed tablet should be taken as soon as possible, and if this can be done within 12 hours of the correct time, contraceptive protection is maintained.

With longer delays, additional contraception is needed. Only the most recently delayed tablet should be taken, earlier missed tablets being omitted, and additional non-hormonal methods of contraception (except the rhythm or temperature methods) should be used for the next 7 days, while the next 7 tablets are being taken. Additionally, therefore, if tablet(s) have been missed during the last 7 days of a pack, there should be no break before the next pack is started. In this situation, a withdrawal bleed should not be expected until the end of the second pack. Some breakthrough bleeding may occur on tablet taking days but this is not clinically significant. If the patient does not have a withdrawal bleed during the tablet-free interval following the end of the second pack, the possibility of pregnancy must be ruled out before starting the next pack.

Gastro-intestinal upset:

Vomiting or diarrhoea may reduce the efficacy of oral contraceptives by preventing full absorption. Tablet-taking from the current pack should be continued. Additional non-hormonal methods of contraception (except the rhythm or temperature methods) should be used during the gastro-intestinal upset and for 7 days following the upset. If these 7 days overrun the end of a pack, the next pack should be started without a break. In this situation, a withdrawal bleed should not be expected until the end of the second pack. If the patient does not have a withdrawal bleed during the tablet-free interval following the end of the second pack, the possibility of pregnancy must be ruled out before starting the next pack. Other methods of contraception should be considered if the gastro-intestinal disorder is likely to be prolonged.

Children:

Not applicable

Elderly:

Not applicable

1. Pregnancy

2. Severe disturbances of liver function, jaundice or persistent itching during a previous pregnancy, Dubin-Johnson syndrome, Rotor syndrome, previous or existing liver tumours

3. Existing or previous arterial or venous thrombotic or embolic processes, conditions which predispose to them e.g. disorders of the clotting processes, valvular heart disease and atrial fibrillation

4. Sickle-cell anaemia

5. Mammary or endometrial carcinoma, or a history of these conditions

6. Severe diabetes mellitus with vascular changes

7. Disorders of lipid metabolism

8. History of herpes gestationis

9. Deterioration of otosclerosis during pregnancy

10. Undiagnosed abnormal vaginal bleeding

11. Hypersensitivity to any of the components of Logynon.

Warnings: There is a general opinion, based on statistical evidence that users of combined oral contraceptives experience, more often than non-users, venous thromboembolism, arterial thrombosis, including cerebral and myocardial infarction, and subarachnoid haemorrhage. Full recovery from such disorders does not always occur, and it should be realised that in a few cases they are fatal. How often these disorders occur in users of the modern low-dose pills is not known, but there are reasons for suggesting that they may occur less often than with older pills.

Certain factors may entail some risk of thrombosis, e.g. smoking, obesity, varicose veins, cardiovascular diseases, diabetes, and migraine. The suitability of a combined oral contraceptive should be judged according to the severity of such conditions in the individual case, and should be discussed with the patient before she decides to take it. The risk of arterial thrombosis associated with combined oral contraceptives increases with age, and this risk is aggravated by cigarette-smoking. The use of combined oral contraceptives by women in the older age-group, especially those who are cigarette smokers, should therefore be discouraged and alternative methods used.

In addition if there is a history in the family of thromboembolic diseases at a young age (e.g. deep vein thrombosis, heart attack or stroke) disturbances of the coagulation system must be ruled out before the pill is prescribed.

Numerous epidemiological studies have been reported on the risks of ovarian, endometrial, cervical and breast cancer in women using combined oral contraceptives. The evidence is clear that combined oral contraceptives offer substantial protection against both ovarian and endometrial cancer.

An increased risk of cervical cancer in long-term users of combined oral contraceptives has been reported in some studies, but there continues to be controversy about the extent to which this is attributable to the confounding effects of sexual behaviour and other factors.

A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR = 1.24) of having breast cancer diagnosed in women who are currently using combined oral contraceptives (COCs). The observed pattern of increased risk may be due to an earlier diagnosis of breast cancer in COC users, the biological effects of COCs or a combination of both. The additional breast cancers diagnosed in current users of COCs or in women who have used COCs in the last ten years are more likely to be localised to the breast than those in women who never used COCs.

Breast cancer is rare among women under 40 years of age whether or not they take COCs. Whilst this background risk increases with age, the excess number of breast cancer diagnoses in current and recent COC users is small in relation to the overall risk of breast cancer (see bar chart).

The most important risk factor for breast cancer in COC users is the age women discontinue the COC; the older the age at stopping, the more breast cancers are diagnosed. Duration of use is less important and the excess risk gradually disappears during the course of the 10 years after stopping COC use such that by 10 years there appears to be no excess.

The possible increase in risk of breast cancer should be discussed with the user and weighed against the benefits of COCs taking into account the evidence that they offer substantial protection against the risk of developing certain other cancers (e.g. ovarian and endometrial cancer).

Estimated cumulative numbers of breast cancers per 10,000 women diagnosed in 5 years of use and up to 10 years after stopping COCs, compared with numbers of breast cancers diagnosed in 10,000 women who had never used COCs

The possibility cannot be ruled out that certain chronic diseases may occasionally deteriorate during the use of combined oral contraceptives (see 'Precautions').

In rare cases benign and, in even rarer cases, malignant liver tumours leading in isolated cases to life-threatening intra-abdominal haemorrhage have been observed after the use of hormonal substances such as those contained in Logynon. If severe upper abdominal complaints, liver enlargement or signs of intra-abdominal haemorrhage occur, the possibility of a liver tumour should be included in the differential diagnosis.

In rare cases benign and, in even rarer cases, malignant liver tumours leading in isolated cases to life-threatening intra-abdominal haemorrhage have been observed after the use of hormonal substances such as those contained in Logynon. If severe upper abdominal complaints, liver enlargement or signs of intra-abdominal haemorrhage occur, the possibility of a liver tumour should be included in the differential diagnosis.

Reasons for stopping oral contraception immediately:

1. Occurrence for the first time, or exacerbation, of migrainous headaches or unusually frequent or unusually severe headaches

2. Sudden disturbances of vision or hearing or other perceptual disorders

3. First signs of thrombophlebitis or thromboembolic symptoms (e.g. unusual pains in or swelling of the leg(s), stabbing pains on breathing or coughing for no apparent reason). Feeling of pain and tightness in the chest

4. Six weeks before an elective major operation (e.g. abdominal, orthopaedic), any surgery to the legs, medical treatment for varicose veins or prolonged immobilisation, e.g. after accidents or surgery. Do not restart until 2 weeks after full ambulation. In case of emergency surgery, thrombotic prophylaxis is usually indicated e.g. subcutaneous heparin

5. Onset of jaundice, hepatitis, itching of the whole body

6. Increase in epileptic seizures

7. Significant rise in blood pressure

8. Onset of severe depression

9. Severe upper abdominal pain or liver enlargement

10. Clear exacerbation of conditions known to be capable of deteriorating during oral contraception or pregnancy

11. Pregnancy is a reason for stopping immediately because it has been suggested by some investigations that oral contraceptives taken in early pregnancy may slightly increase the risk of foetal malformations. Other investigations have failed to support these findings. The possibility therefore cannot be excluded, but it is certain that if a risk exists at all, it is very small.

Precautions: Assessment of women prior to starting oral contraceptives (and at regular intervals thereafter) should include a personal and family medical history of each woman. Physical examination should be guided by this and by the contraindication (section 4.3) and Warnings (section 4.4) for this product. The frequency and nature of these assessments should be based upon relevant guidelines and should be adapted to the individual woman, but should include measurement of blood pressure and, if judged appropriate by the clinician, breast, abdominal and pelvic examination including cervical cytology.

The following conditions require strict medical supervision during medication with oral contraceptives. Deterioration or first appearance of any of these conditions may indicate that use of the oral contraceptive should be discontinued: diabetes mellitus, or a tendency towards diabetes mellitus (e.g. unexplained glycosuria), hypertension, varicose veins, a history of phlebitis, otosclerosis, multiple sclerosis, epilepsy, porphyria, tetany, disturbed liver function, Sydenham's chorea, renal dysfunction, family history of clotting disorders, obesity, family history of breast cancer and patient history of benign breast disease, history of clinical depression, systemic lupus erythematosus, uterine fibroids and migraine, gall-stones, cardiovascular diseases, chloasma, asthma, an intolerance of contact lenses, or any disease that is prone to worsen during pregnancy

Some women may experience amenorrhoea or oligomenorrhoea after discontinuation of oral contraceptives, especially when these conditions existed prior to use. Women should be informed of this possibility.

Lactose and Sucrose Intolerance

Each light brown tablet (Phase I) contains 33.07 mg lactose and 19.297 mg sucrose per tablet. Each white tablet (Phase II) contains 33.035 mg lactose and 19.66 mg sucrose per tablet. Each ochre tablet (Phase III) contains 32.995 mg lactose and 19.223 mg sucrose per tablet. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, fructose intolerance or glucose-galactose malabsorption or sucrase-isomaltase should not take this medicine.

Hepatic enzyme inducers such as barbiturates, phenobarbitone, phenytoin, phenobarbitone, phenytoin, phenylbutazone, rifampicin, carbamazepine and griseofulvin can impair the efficacy of Logynon.

For women receiving long-term therapy with hepatic enzyme inducers, another method of contraception should be used. The use of antibiotics may also reduce the efficacy of Logynon, possibly by altering the intestinal flora.

Women receiving short courses of enzyme inducers or broad spectrum antibiotics should take additional, non-hormonal (except rhythm or temperature method) contraceptive precautions during the time of concurrent medication and for 7 days afterwards. If these 7 days overrun the end of a pack, the next pack should be started without a break. In this situation, a withdrawal bleed should not be expected until the end of the second pack. If the patient does not have a withdrawal bleed during the tablet-free interval following the end of the second pack, the possibility of pregnancy must be ruled out before resuming with the next pack. With rifampicin, additional contraceptive precautions should be continued for 4 weeks after treatment stops, even if only a short course was administered.

The requirement for oral antidiabetics or insulin can change as a result of the effect on glucose tolerance.

The herbal remedy St John's wort (Hypericum perforatum) should not be taken concomitantly with Logynon ED as this could potentially lead to a loss of contraceptive effect.

Logynon is not indicated during pregnancy. If pregnancy occurs during treatment with Logynon, further intake must be stopped. However, extensive epidemiological studies have revealed neither an increased risk of birth defects in children born to women who used COCs prior to pregnancy, nor a teratogenic effect when COCs were taken inadvertently during early pregnancy.

The use of Logynon during lactation may lead to a reduction in the volume of milk produced and to a change in its composition. Minute amounts of the active substances are excreted with the milk. Mothers who are breast-feeding may be advised instead to use another method of contraception.

None known

In rare cases, headaches, gastric upsets, nausea, vomiting, breast tenderness, changes in body weight, changes in libido, depressive moods can occur.

In predisposed women, use of Logynon can sometimes cause chloasma which is exacerbated by exposure to sunlight. Such women should avoid prolonged exposure to sunlight.

Individual cases of poor tolerance of contact lenses have been reported with use of oral contraceptives. Contact lens wearers who develop changes in lens tolerance should be assessed by an ophthalmologist.

Menstrual changes:

1. Reduction of menstrual flow:

2. Missed menstruation:

Intermenstrual bleeding: 'Spotting' or heavier 'breakthrough bleeding' sometimes occur during tablet taking, especially in the first few cycles, and normally cease spontaneously. Logynon should therefore, be continued even if irregular bleeding occurs. If irregular bleeding is persistent, appropriate diagnostic measures to exclude an organic cause are indicated and may include curettage. This also applies in the case of spotting which occurs at irregular intervals in several consecutive cycles or which occurs for the first time after long use of Logynon.

Effect on blood chemistry: The use of oral contraceptives may influence the results of certain laboratory tests including biochemical parameters of liver, thyroid, adrenal and renal function, plasma levels of carrier proteins and lipid/lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. Laboratory staff should therefore be informed about oral contraceptive use when laboratory tests are requested.

Overdosage may cause nausea, vomiting and, in females, withdrawal bleeding. There are no specific antidotes and treatment should be symptomatic.

Logynon is an oestrogen-progestogen combination which acts by inhibiting ovulation by suppression of the mid-cycle surge of luteinising hormone, the inspissation of cervical mucus so as to constitute a barrier to sperm, and the rendering of the endometrium unreceptive to implantation.

Levonorgestrel

Orally administered levonorgestrel is rapidly and completely absorbed. Following ingestion of 0.125mg levonorgestrel together with 0.03mg ethinylestradiol (which represents the combination with the highest levonorgestrel content of the tri-step formulation), maximum drug serum levels of about 4.3ng/ml are reached at 1.0 hour. Thereafter, levonorgestrel serum levels decrease in two phases characterised by half-lives of 0.4 hours and about 22 hours. For levonorgestrel, a metabolic clearance rate from serum of about 1.5ml/min/kg was determined. Levonorgestrel is not excreted in unchanged form but as metabolites. Levonorgestrel metabolites are excreted at about equal proportions with urine and faeces. The biotransformation follows the known pathways of steroid metabolism. No pharmacologically active metabolites are known.

Levonorgestrel is bound to serum albumin and to SHBG. Only 1.4% of the total serum drug levels are present as free steroid, but 55% are specifically bound to SHBG. The relative distribution (free, albumin-bound, SHBG-bound) depends on the SHBG concentrations found in the serum. Following induction of the binding protein, the SHBG-bound fraction increases while the unbound fraction decreases.

Following daily repeated administration of Logynon, levonorgestrel concentrations in the serum increase by a factor of about 4. Steady-state conditions are reached during the second half of a treatment cycle. The pharmacokinetics of levonorgestrel are influenced by SHBG levels. Under treatment with Logynon, an increase in the serum levels of SHBG by a factor of about 2 occurs during a treatment cycle. Due to the specific binding of levonorgestrel to SHBG, the increase in SHBG levels is accompanied by an almost parallel increase in levonorgestrel serum levels. The absolute bioavailability of levonorgestrel was determined to be almost 100% of the dose administered.

Ethinylestradiol

Orally administered ethinylestradiol is rapidly and completely absorbed. Following ingestion of 0.03mg ethinylestradiol together with 0.125mg levonorgestrel, maximum drug serum levels of about 116pg/ml are reached at 1.3 hours. Thereafter, ethinylestradiol serum levels decrease in two phases characterised by half-lives of 1-2 hours. Thereafter, ethinylestradiol serum levels decrease in two phases characterised by half-lives of 1-2 hours and about 20 hours. For technical reasons, these parameters can only be calculated following the administration of higher doses. For ethinylestradiol an apparent volume of distribution of about 5 l/kg and a metabolic clearance rate of about 5ml/min/kg were determined. Ethinylestradiol is highly but non-specifically bound to serum albumin. About 2% of drug levels are present unbound. During absorption and first liver passage, ethinylestradiol is metabolised resulting in a reduced absolute oral bioavailability. Unchanged drug is not excreted. Ethinylestradiol metabolites are excreted at a urinary to biliary ratio of 4:6 with a half-life of about 1day.

Due to the half-life of the terminal disposition phase from serum and the daily ingestion, steady –state serum levels are reached after 3 – 4 days and are higher by 30-40% as compared to a single dose. The absolute bioavailability of ethinylestradiol is subject to considerable interindividual variation. Following oral administration, the mean bioavailability was found to be about 40 – 60 % of the administered dose.

During established lactation, 0.02% of the daily maternal dose could be transferred to the newborn via milk.

The systemic availability of ethinylestradiol might be influenced in both directions by other drugs. There is, however, no interaction with high doses of vitamin C. Ethinylestradiol induces the hepatic synthesis of SHBG and CBG (corticoid binding globulin) during continuous use. The extent of SHBG induction, however, depends on the chemical structure and the dose of the co-administered progestogen. During treatment with Logynon, SHBG concentrations in the serum increased from about 76nmol/l to 164nmol/l and the serum concentrations of CBG increased from about 48µg/ml to 111µg/ml.

There are no preclinical safety data which could be of relevance to the prescriber and which are not already included in other sections of the SmPC.

Lactose

Maize Starch

Povidone

Talc

Magnesium Stearate (E572)

Sucrose

Macrogol

Calcium carbonate (E170)

Titanium Dioxide (E171)

Glycerol (E422)

Montan Glycol Wax

Ferric Oxide Pigment, Yellow (E172)

Ferric Oxide Pigment, Red (E172)

None known.

60 months

Not applicable

6 phase I tablets, 5 phase II tablets and 10 phase III tablets are packed in each aluminium foil and PVC blister pack.

Pack sizes (no. tablets), 21, 5 x 21, 50 x 21.

No special requirements.

Bayer plc

Bayer House

Strawberry Hill

Newbury

Berkshire RG14 1JA

Trading as Bayer plc, Bayer Schering Pharma

PL 00010/0540

06 March 2009

18 July 2011

POM