1. Name Of The Medicinal Product
Ovranette® 150/30 micrograms Coated Tablets.
2. Qualitative And Quantitative Composition
Each tablet contains 0.15mg levonorgestrel and 0.03mg ethinylestradiol.
For excipients see 6.1
3. Pharmaceutical Form
Coated tablets.
White, shiny, sugar coated-tablet with a smooth surface.
4. Clinical Particulars
4.1 Therapeutic Indications
Oral contraception.
Treatment of endometriosis.
Treatment of spasmodic dysmenorrhoea and premenstrual tension.
Treatment of functional uterine bleeding (menorrhagia, metrorrhagia, metropathia haemorrhatica).
Emergency treatment of acute uterine bleeding.
4.2 Posology And Method Of Administration
For oral administration
Dosage and Administration
First treatment cycle: 1 tablet daily for 21 days, starting with the tablet marked number 1, on the first day of the menstrual cycle. Additional contraception (barriers and spermicides) is not required.
Subsequent cycles: Each subsequent course is started when seven tablet-free days have followed the preceding course. A withdrawal bleed should occur during the 7 tablet-free days.
Changing from another 21 day combined oral contraceptive: The first tablet of Ovranette should be taken on the first day immediately after the end of the previous oral contraceptive course. Additional precautions are not required. A withdrawal bleed should not be expected until the end of the first pack.
Changing from an Every Day (ED) 28 day combined oral contraceptive: The first tablet of Ovranette should be taken on the day immediately after the day on which the last active pill in the ED pack has been taken. The remaining tablets in the ED pack should be discarded. Additional precautions are not required. A withdrawal bleed should not be expected until the end of the first pack.
Changing from a Progestogen-only-Pill (POP): The first tablet of Ovranette should be taken on the first day of menstruation even if the POP for that day has already been taken. The remaining tablets in the POP pack should be discarded. Additional precautions are not required.
Post-partum and post-abortum use: After pregnancy, combined oral contraception can be started in non-lactating women 21 days after a vaginal delivery, provided that the patient is fully ambulant and there are no puerperal complications. If the pill is started later than 21 days after delivery, then alternative contraception (barriers and spermicides) should be used until oral contraception is started and for the first 7 days of pill-taking. If unprotected intercourse has taken place after 21 days post partum, then oral contraception should not be started until the first menstrual bleed after childbirth. After miscarriage or abortion oral contraception may be started immediately.
Other indications
Endometriosis: Continuous treatment with two tablets daily.
Spasmodic dysmenorrhoea, premenstrual tension: Dosage as for oral contraception.
Functional uterine bleeding: Two tablets are taken daily on a cyclic basis as for oral contraception. In the first one or two cycles it may be necessary to give four tablets, or in exceptional cases, five.
Emergency treatment of acute uterine bleeding: Four tablets are given initially and, if necessary, 4-8 tablets daily.
Elderly: Not applicable
Children: Not applicable
Special Circumstances Requiring Additional Contraception
Missed Pills: If a tablet is delayed, it should be taken as soon as possible, and if it is taken within 12 hours of the correct time, additional contraception is not needed. Further tablets should then be taken at the usual time. If the delay exceeds 12 hours, the last missed pill should be taken when remembered, the earlier missed pills left in the pack and normal pill-taking resumed. If one or more tablets are omitted from the 21 days of pill-taking, addition contraception (barriers and spermicides) should be used for the next 7 days of pill-taking. In addition, if one or more pills are missed during the last 7 days of pill-taking, the subsequent pill-free interval should be disregarded and the next pack started the day after taking the last tablet from the previous pack. In this case, a period should not be expected until the end of the second pack. If the patient does not have a period at the end of the second pack, she must return to her doctor to exclude the possibility of pregnancy.
Gastro-intestinal upset: Vomiting or diarrhoea may reduce the efficacy by preventing full absorption. Additional contraception (barriers and spermicides) should be used during the stomach upset and for the 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 case, a period should not be expected until the end of the second pack. If the patient does not have a period at the end of the second pack, she must return to her doctor to exclude the possibility of pregnancy.
Mild laxatives do not impair contraceptive action.
Interaction with other drugs:
Some drugs may reduce the efficacy of oral contraceptives (refer to “4.5. Interaction with other medicaments and other forms of interaction.”). It is, therefore, advisable to use non
4.3 Contraindications
1. Suspected pregnancy
2. History of confirmed venous thromboembolism (VTE). Family history of idiopathic VTE. Other known risk factors for VTE.
3. Arterial thrombotic disorders and a history of these conditions, disorders of lipid metabolism and other conditions in which, in individual cases, there is known or suspected to be a much increased risk of thrombosis.
4. Sickle-cell anaemia
5. Acute or severe chronic liver diseases. Dubin-Johnson syndrome. Rotor syndrome. History, during pregnancy, of idiopathic jaundice or severe pruritis.
6. History of herpes gestationis.
7. Mammary or endometrial carcinoma, or a history of these conditions.
8. Abnormal vaginal bleeding of unknown cause.
9. Deterioration of otosclerosis during pregnancy.
4.4 Special Warnings And Precautions For Use
Warnings:
1. Venous and Arterial Thrombosis and Thromboembolism
Use of COCs is associated with an increased risk of venous and arterial thrombotic and thromboembolic events.
Minimising exposure to oestrogens and progestogens is in keeping with good principles of therapeutics. For any particular oestrogen/progestogen combination, the dosage regimen prescribed should be one that contains the least amount of oestrogen and progestogen that is compatible with a low failure rate and the needs of the patient.
Unless clinically indicated otherwise, new users of COCs should be started on preparations containing less than 50μg of oestrogen.
Venous Thrombosis and Thromboembolism
Use of COCs increases the risk of venous thrombotic and thromboembolic events. Reported events include deep venous thrombosis and pulmonary embolism.
The use of any COC carries an increased risk of venous thrombotic and thromboembolic events compared with no use. The excess risk is highest during the first year a woman ever uses a combined oral contraceptive. This increased risk is less than the risk of venous thrombotic and thromboembolic events associated with pregnancy which is estimated as 60 cases per 100,000 woman-years. Venous thromboembolism is fatal in 1-2% of cases.
Some epidemiological studies have reported a greater risk of VTE for women using combined oral contraceptives containing desogestrel or gestodene (the so-called third generation pills) than for women using pills containing levonorgestrel (the so-called second generation pills).
The spontaneous incidence of VTE in healthy non-pregnant women (not taking any oral contraceptive) is about 5 cases per 100,000 women per year. The incidence in users of the second generation pills (such as Ovranette) is about 15 per 100,000 women per year of use. The incidence in users of third generation pills is about 25 cases per 100,000 women per year of use; this excess incidence has not been satisfactorily explained by bias or confounding. The level of all these risks of VTE increases with age and is likely to be further increased in women with other known risk factors of VTE.
All this information should be taken into account when prescribing this COC. When counselling on the choice of contraceptive method(s) all of the above information should be considered.
The risk of venous thrombotic and thromboembolic events is further increased in women with conditions predisposing for venous thrombosis and thromboembolism. Caution must be exercised when prescribing COCs for such women.
Examples of predisposing conditions for venous thrombosis are:
2 or over)
The relative risk of post-operative thromboembolic complications has been reported to be increased two- or four-fold with the use of COCs (see reasons for discontinuation).
Since the immediate post-partum period is associated with an increased risk of thromboembolism, COCs should be started no earlier than day 28 after delivery or second-trimester abortion.
Arterial Thrombosis and Thromboembolism
The use of COCs increases the risk or arterial thrombotic and thromboembolic events. Reported events include myocardial infarction and cerebrovascular events (ischaemic and haemorrhagic stroke).
The risk of arterial thrombotic and thromboembolic events is further increased in women with underlying risk factors.
Caution must be exercised when prescribing COCs for women with risk factors for arterial thrombotic and thromboembolic events.
Examples of risk factors for arterial thrombotic and thromboembolic event are:
2)
COC users with migraine (particularly migraine with aura) may be at increased risk of stroke.
There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism
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.
2. 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.
3. The possibility cannot be ruled out that certain chronic diseases may occasionally deteriorate during the use of combined oral contraceptives. (See 'Precautions').
4. Malignant liver tumours have been reported on rare occasions in long
5. 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).
Reasons for stopping oral contraception immediately:
1. Occurrence of migraine in patients who have never previously suffered from it. Exacerbation of pre
2. Any kind of acute disturbance of vision.
3. Suspicion of thrombosis or infarction including symptoms such as unusual pains in or swelling of the legs, stabbing pains on breathing, persistent cough or coughing blood, pain or tightness in the chest.
4. Six weeks before elective operations, or treatment of varicose veins by sclerotherapy and during immobilisation, e.g. after accidents, etc.
5. Significant rise in blood
6. Jaundice.
7. Clear exacerbation of conditions known to be capable of deteriorating during oral contraception or pregnancy.
8. 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.
If oral contraception is stopped for any reason and pregnancy is not desired, it is recommended that alternative non-hormonal methods of contraception (such as barriers or spermicides) are used to ensure contraceptive protection is maintained.
Precautions:
1. 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 contraindications (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.
2. Before starting treatment, pregnancy must be excluded.
3. The following conditions require careful observation during medication: a history of severe depressive states, varicose veins, diabetes, hypertension, epilepsy, otosclerosis, multiple sclerosis, porphyria, tetany, disturbed liver function, gall
4. The risk of the deterioration of chloasma, which is often not fully reversible, is reduced by the avoidance of excessive exposure to sunlight.
Menstrual changes:
1. Reduction of menstrual flow: This is not abnormal and it is to be expected in some patients.
2. Missed menstruation: Occasionally withdrawal bleeding may not occur at all. If the tablets have been taken correctly, pregnancy is very unlikely but should be ruled out before a new course of tablets is started.
Intermenstrual bleeding:
Very light “spotting” or heavier “break through bleeding” may occur during tablet-taking, especially in the first few cycles. It appears to be generally of no significance, except where it indicates errors of tablet-taking, or where the possibility of interaction with other drugs exists. However, if irregular bleeding is persistent an organic cause should be considered.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Some drugs accelerate the metabolism of oral contraceptives when taken concurrently and these include barbiturates, phenytoin, phenylbutazone and rifampicin. Other drugs suspected of having the capacity to reduce the efficacy of oral contraceptives include ampicillin and other antibiotics. It is therefore, advisable to use non-hormonal methods of contraception (barriers and spermicides). Please refer to “4.2 Posology and Method of Administration, Interaction with other drugs”.
The response to metyrapone is less pronounced in women taking oral contraceptives.
ACTH function test remains unchanged. Reduction in corticosteriod excretion and elevation or plasma corticosteriods are due to increased cortisol binding capacity of plasma proteins.
Serum protein-bound iodine levels should not be used for evaluation of thyroid function as levels may rise due to increased thyroid hormone binding capacity of plasma proteins.
Erythrocyte sedimentation may be accelerated in absence of any disease due to change in proportion of plasma protein fractions. Increases in plasma copper, iron and alkaline phosphatase have been recorded.
The herbal remedy, St John's Wort (Hypericum perforatum) should not be taken concomitantly with this medicine as it could potentially lead to a loss of contraceptive effect.
4.6 Pregnancy And Lactation
Pregnancy is a reason for stopping administration 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. After pregnancy, combined oral contraception can be started in non-lactating women 21 days after vaginal delivery, provided that the patient is fully ambulant and there are no puerperal complications.
Please refer to recommended dosage schedule: Post-partum and post-abortum use.
Administration of oestrogens to lactating women may decrease the quantity or quality of the milk.
4.7 Effects On Ability To Drive And Use Machines
None known.
4.8 Undesirable Effects
See 'Special Warnings and Special Precautions for Use'.
There is an increased risk of venous thromboembolism for all women using a combined oral contraceptive. For information on differences in risk between oral contraceptives, see Section 4.4.
Occasional side-effect may include nausea, vomiting, headaches, breast tenderness, irregular bleeding or missed bleeds, changed body weight or libido, depressive moods, chloasma and altered serum lipid profile.
4.9 Overdose
There have been no reports of serious ill
There are no specific antidotes and further treatment should be symptomatic.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Ethinylestradiol is a synthetic oestrogen which has actions and uses similar to those of oestradiol, but is much more potent.
Norgestrel is a progestational agent with actions similar to those of progesterone. It is more potent as an inhibitor of ovulation than norethisterone and has androgenic activity.
5.2 Pharmacokinetic Properties
Ethinylestradiol is absorbed by the gastro-intestinal tract. It is only slowly metabolised and excreted in the urine.
Norgestrel is absorbed from the gastrointestinal tract. Metabolites are excreted in the urine and faeces as glucuronide and sulphate conjugates.
5.3 Preclinical Safety Data
Nothing of relevance to the prescriber.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Core: lactose, maize starch, povidone 25, magnesium stearate, talc, purified water.
Coating: sucrose, polyethylene glycol 6000, calcium carbonate, talc, povidone 90, purified water, white wax and wax carnauba.
6.2 Incompatibilities
None known.
6.3 Shelf Life
36 months.
6.4 Special Precautions For Storage
Store at or below room temperature.
6.5 Nature And Contents Of Container
Aluminium foil and PVC blister packs of 21 tablets.
Cartons containing 1, 3 and 50 blisters.
6.6 Special Precautions For Disposal And Other Handling
Not applicable.
7. Marketing Authorisation Holder
Pfizer Limited
Ramsgate Road
Sandwich
Kent
CT13 9NJ
United Kingdom
8. Marketing Authorisation Number(S)
PL 00057/1283
9. Date Of First Authorisation/Renewal Of The Authorisation
11 August 2011
10. Date Of Revision Of The Text
August 2011
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