1. Name Of The Medicinal Product
Marvelon
2. Qualitative And Quantitative Composition
Desogestrel B.P. 150 micrograms
Ethinylestradiol Ph. Eur 30 micrograms
3. Pharmaceutical Form
Tablets
4. Clinical Particulars
4.1 Therapeutic Indications
Oral contraception.
4.2 Posology And Method Of Administration
4.2.1 How to take Marvelon
One tablet is taken daily at the same time,(preferably in the evening) without interruption for 21 days, followed by a break of 7 tablet-free days. Each subsequent pack is started after the 7 tablet-free days have elapsed. Additional contraceptive precautions are not then required.
4.2.2 How to start Marvelon
It is preferable that tablet intake from the first pack is started on the first day of menstruation in which case no extra contraceptive precautions are necessary.
If menstruation has already begun, (that is 2, 3, or 4 days previously), tablet taking should commence on day 5 of the menstrual period. In this case additional contraceptive precautions must be taken for the first 7 days of tablet taking.
If menstruation began more than 5 days previously then the patient should be advised to wait until her next menstrual period before starting to take Marvelon.
Post-Partum Administration
Following childbirth oral contraceptive administration to non-breast feeding mothers should be started 21 days post-partum in which case no additional contraceptive precautions are required.
If intercourse has taken place post-partum, oral contraceptive use should be delayed until the first day of the first menstrual period.
If post-partum administration of Marvelon begins more than 21 days after delivery then additional contraceptive precautions are required for the first 7 days.
N.B. Mothers who are breast feeding should be advised not to use the combined pill since this may reduce the amount of breast-milk, but may be advised instead to use a progestogen-only pill (POP).
After miscarriage or abortion administration should start immediately in which case no additional contraceptive precautions are required.
Changing from a 21 day pill or another 22 day pill to Marvelon:
All tablets in the old pack should be finished. The first Marvelon tablet is taken the next day i.e. no gap is left between taking tablets nor does the patient need to wait for her period to begin. Tablets should be taken as instructed in 'How to take Marvelon'. Additional contraceptive precautions are not required. The patient will not have a period until the end of the first Marvelon pack, but this is not harmful, nor does it matter if she experiences some bleeding on tablet-taking days.
Changing from a combined Every Day Pill (28 day tablets) to Marvelon:
Marvelon should be started after taking the last active tablet from the 'Every Day Pill' pack (i.e. after taking 21 or 22 tablets). The first Marvelon tablet is taken the next day i.e. no gap is left between taking tablets nor does the patient need to wait for her period to begin. One tablet is taken daily at the same time, without interruption for 21 days, followed by a 7 day tablet-free period. Each subsequent pack is started after the 7 day tablet-free period has elapsed. Additional contraceptive precautions are not required. Remaining tablets from the Every Day (ED) pack should be discarded. The patient will not have a period until the end of the first Marvelon pack, but this is not harmful, nor does it matter if she experiences some bleeding on tablet-taking days.
Changing from a Progestogen-only Pill (POP or Mini Pill) to Marvelon:
The first Marvelon tablet should be taken on the first day of the period, even if the patient has already taken a mini pill on that day. One tablet is taken daily at the same time, without interruption for 21 days, followed by a 7 day tablet-free period. Each subsequent pack is started after the 7 day tablet-free period has elapsed. Additional contraceptive precautions are not then required. All the remaining progestogen-only pills in the mini pill pack should be discarded.
If the patient is taking a (mini) pill, then she may not always have a period, especially when she is breast feeding. The first Marvelon tablet should be taken on the day after stopping the mini pill. All remaining pills in the mini pill packet must be discarded. Additional contraceptive precautions must be taken for the first seven days.
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4.2.3 How to skip a period
To skip a period, a new pack of Marvelon should be started on the day after finishing the current pack (the patient skips the tablet-free days). Tablet-taking should be continued in the usual way. During the use of the second pack she may experience slight spotting or break-through bleeding but contraceptive protection will not be diminished provided there are no tablet omissions. The next pack of Marvelon is started after the usual 7 tablet-free days, regardless of whether the period has completely finished or not.
4.2.4 Advice in case of missed pills
The reliability of Marvelon may be reduced if tablets are forgotten:
If the forgotten tablet is taken within 12 hours, no further precautions are necessary, further tablets should be taken at the usual time.
If one or more tablets are forgotten for more than 12 hours, contraceptive protection will be reduced. The patient should take the last forgotten tablet, even if this means taking two tablets in one day, and then continue to take tablets at the normal time. Additional contraceptive precautions should be taken for the next seven days, and the patient should follow 'the 7-day rule'. (See section 4.4; Special warnings and special precautions for use: Reduced Reliability).
4.2.5 Advice in case of Vomiting or Diarrhoea
If after tablet intake vomiting or diarrhoea occurs, a tablet may not be absorbed properly by the body. If the symptoms disappear within 12 hours of tablet-taking, the patient should take an extra tablet from a spare pack and continue with the rest of the pack as usual. However, if the symptoms continue beyond those 12 hours, additional contraceptive precautions are necessary for any sexual intercourse during the stomach or bowel upset and for the following 7 days (the patient must be advised to follow '7-day rule'). (See section 4.4; Special warnings and special precautions for use: Reduced Reliability).
4.3 Contraindications
• Pregnancy or suspected pregnancy (that cannot yet be excluded) or breast feeding.
• Moderate to severe hypertension
• Hyperlipoproteinaemia
• Arterial thrombosis present or in history (e.g. myocardial infarction, cerebrovascular accident).
• In addition the presence of more than one of the risk factors for arterial disease (See 4.4 Special warnings and special precautions for use; The Pill and Thrombosis).
• History of confirmed venous thromboembolism (VTE); Family history of idiopathic VTE. Other known risk factors for VTE. (See 4.4 Special warnings and special precautions for use; The Pill and Thrombosis).
• Diabetes mellitus with vascular involvement
• Severe liver disease, cholestatic jaundice or hepatitis (viral or non-viral), or a history of these conditions if the results of liver function tests have failed to return to normal, and for 3 months after liver function tests have been found to be normal; a history of jaundice of pregnancy or jaundice due to the use of steroids, Rotor syndrome and Dubin-Johnson syndrome, hepatic cell tumours and porphyria.
• Cholelithiasis
• Known or suspected estrogen-dependent tumours, (See 4.4 Special warnings and special precautions for use: The Pill and Cancer); endometrial hyperplasia; undiagnosed vaginal bleeding.
• Systemic lupus erythematosus or a history of this condition.
• A history during pregnancy or previous use of steroids of:
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• Hypersensitivity to any of the components of Marvelon
4.4 Special Warnings And Precautions For Use
Relative Contraindications
If any of the conditions listed below is present, the benefits of COC use must be weighed against the possible risks for each individual woman and discussed with her before she decides to start using it. The patient should be kept under close supervision. In case of aggravation, exacerbation or appearance of any of these conditions or risk factors whilst the patient is taking the Pill, it's use should be discontinued, alternative non-hormonal methods of contraception used (not rhythm or temperature methods) and medical advice sought without delay.
• Disorders of coagulation.
• Other conditions associated with an increased risk of circulatory disease such as latent or overt cardiac failure, renal dysfunction, or a history of these conditions.
• Epilepsy or a history of this condition.
• Migraine or a history of this condition.
• A history of cholelithiasis.
• Presence of any risk factor for estrogen-dependent tumours; estrogen-sensitive gynaecological disorders such as uterine fibromyomata and endometriosis (See below; The Pill and cancer).
• Diabetes mellitus.
• Severe depression or a history of this condition. If this is accompanied by a disturbance in tryptophan metabolism, administration of vitamin B6 might be of therapeutic value.
• Sickle cell haemoglobinopathy, since under certain circumstances, e.g. during infections or anoxia, estrogen-containing preparations may induce thromboembolic process in patients with this condition.
• If the results of liver function tests become abnormal, use should be discontinued.
The Pill and Thrombosis
• Some epidemiological studies have suggested an association between the use of COCs and an increased risk of arterial and venous thrombotic and thromboembolic diseases such as myocardial infarction, stroke, deep venous thrombosis, and pulmonary embolism. These events occur rarely.
• An increased risk of venous thromboembolic disease (VTE) associated with the use of oral contraceptives is well established. The excess risk of VTE is highest during the first year a woman ever uses a combined oral contraceptive. It is smaller than the risk associated with pregnancy, which has been estimated at 60 cases per 100,000 pregnancies. 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 second generation pills is about 15 per 100,000 women per year. 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 for VTE such as obesity.
• Thrombosis has very rarely been reported to occur in other veins or arteries, e.g. hepatic, mesenteric, renal or retinal, in COC users. There is no consensus as to whether the occurrence of these events is associated with the use of COCs.
• The risk of thromboembolism (venous and/or arterial) increases with:
- age
- smoking (with heavier smoking and increasing age the risk further increases, especially in women over 35 years of age)
- a positive family history (i.e. venous or arterial thromboembolism ever in a sibling or parent at a relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any COC use
- obesity (body mass index over 30kg/m2)
- dyslipoproteinaemia,
- hypertension
- valvular heart disease
- atrial fibrillation
- diabetes
- prolonged immobilisation, major surgery, any surgery to the legs, or major trauma. In these situations it is advisable to discontinue COC use (in the case of elective surgery at least four weeks in advance) and not to resume until two weeks after complete remobilisation.
• There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism.
• The increased risk of thromboembolism in the puerperium must be considered.
• Other medical conditions which have been associated with adverse circulatory events include diabetes mellitus, systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell disease.
• An increase in frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation of the COC.
• Biochemical factors that may be indicative of hereditary or acquired predisposition for venous or arterial thrombosis include Activated Protein C (APC) resistance, hyper homocysteinaemia, antithrombin-III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
• When considering risk/benefit the physician should take into account that adequate treatment of a condition may reduce the associated risk of thrombosis and that the risk associated with pregnancy is higher than that associated with COC use.
• Signs and symptoms of a thrombotic event may include:
• sudden severe pain in the chest, whether or not reaching to the left arm;
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- sudden partial or complete loss of vision or diplopia
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The Pill and Cancer
• The use of estrogen-containing oral contraceptives may promote growth of existing sex steroid dependent tumours. For this reason, the use of these oral contraceptives in patients with such tumours is contraindicated.
• 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
• Malignant hepatic tumours have been reported on rare occasions in long-term users of oral contraceptives. Benign hepatic tumours have also been associated with oral contraceptive usage. A hepatic tumour should be considered in the differential diagnosis when upper abdominal pain, enlarged liver or signs of intra-abdominal haemorrhage occur.
Reduced reliability
When Marvelon is taken according to the directions for use the occurrence of pregnancy is highly unlikely. However, the reliability of oral contraceptives may be reduced under the following circumstances:
Forgotten Tablets
Provided she is less than 12 hours late in taking her tablet the patient should take it as soon as she remembers. Further tablets should be taken at the usual time. Marvelon will still give contraceptive protection during this cycle.
If she is more than 12 hours late in taking one or more tablets then she will not be protected for the next 7 days.
If one or more tablets are forgotten for more than 12 hours, contraceptive protection will be reduced. The patient should take the last forgotten tablet, even if this means taking two tablets in one day, and then continue to take tablets at the normal time. Additional contraceptive precautions should be taken for the next 7 days, and the patient should follow the '7-day rule'.
Vomiting or Diarrhoea
If after tablet intake vomiting or diarrhoea occurs, a tablet may not be absorbed properly by the body. If the symptoms disappear within 12 hours of tablet-taking, the patient should take an extra tablet from a spare pack and continue with the rest of the pack as usual. However, if the symptoms continue beyond those 12 hours, additional contraceptive precautions are necessary for any sexual intercourse during the stomach or bowel upset and for the following 7 days (the patient must be advised to follow '7-day rule').
If the patient is taking certain other medicines
If the patient is taking any of the medicines given in the 'Interactions' section she should be advised to follow the '7-day rule':
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If after taking Marvelon for several months there is a sudden occurrence of spotting or breakthrough bleeding (not observed in previous cycles) or the absence of withdrawal bleeding, contraceptive effectiveness may be reduced. If withdrawal bleeding fails to occur and none of the above mentioned events has taken place, pregnancy is highly unlikely and oral contraceptive use can be continued until the end of the next pack.( If withdrawal bleeding fails to occur at the end of the second cycle, tablet intake should be discontinued and pregnancy excluded before oral contraceptive use can be resumed.) However, if withdrawal bleeding is absent and any of the above mentioned events has occurred, tablet intake should be discontinued and pregnancy excluded before oral contraceptive use can be resumed.
Medical Examination/consultation
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.
Caution should be observed when prescribing oral contraceptives to young women whose cycles are not yet established.
Chloasma
Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation whilst taking this preparation.
Laboratory Tests
The use of steroids may influence the results of certain laboratory tests. In the literature, at least a hundred different parameters have been reported to possibly be influenced by oral contraceptive use, predominantly by the estrogenic component. Among these are: biochemical parameters of the liver, thyroid, adrenal and renal function, plasma levels of (carrier) proteins and lipid/lipoprotein fractions and parameters of coagulation and fibrinolysis.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Irregular cycles and reduced reliability of oral contraceptives may occur when these preparations are used concomitantly with drugs such as anti-convulsants, barbiturates, antibiotics, (e.g. tetracyclines, ampicillin, rifampicin, etc.), griseofulvin, the herbal remedy St Johns Wort, activated charcoal and certain laxatives.
Special consideration should be given to patients being treated with antibiotics for acne. They should be advised to use a non-hormonal method of contraception, or to use an oral contraceptive containing a progestogen showing minimal androgenicity, which have been reported as helping to improve acne without using an antibiotic.
Oral contraceptives may diminish glucose tolerance and increase the need for insulin or other antidiabetic drugs in diabetics.
4.6 Pregnancy And Lactation
Marvelon is contraindicated for use during pregnancy or suspected pregnancy and in mothers who are breast-feeding.
4.7 Effects On Ability To Drive And Use Machines
No observed effects.
4.8 Undesirable Effects
Adverse Reactions
Various adverse reactions have been associated with oral contraceptive use. The serious reactions are dealt with in more detail. The first appearance of symptoms indicative of any one of these reactions necessitates immediate cessation of oral contraceptive use while appropriate diagnostic and therapeutic measures are undertaken.
• Serious adverse reactions
Some epidemiological studies have suggested an association between the use of COCs and an increased risk of arterial and venous thrombotic and thromboembolic diseases such as myocardial infarction, stroke, deep venous thrombosis, and pulmonary embolism. These events occur rarely.
Thrombosis has very rarely been reported to occur in other veins or arteries, e.g. hepatic, mesenteric, renal or retinal, in COC users. There is no consensus as to whether the occurrence of these events is associated with the use of COCs.
The use of estrogen-containing oral contraceptives may promote growth of existing sex steroid dependent tumours. For this reason, the use of these oral contraceptives in patients with such tumours is contraindicated.
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).
See also section 4.4 Special warnings and special precautions for use; The Pill and Thrombosis, and The Pill and Cancer.
The use of oral contraceptives may sometimes lead to the development of cholestatic jaundice or cholelithiasis.
On rare occasions the use of oral contraceptives may trigger or reactivate systemic lupus erythematosus.
A further rare complication of oral contraceptive use is the occurrence of Sydenhams' chorea which can be reversed by discontinuing the pill. The majority of cases of oral-contraceptive-induced chorea show a pre-existing predisposition which often relates to acute rheumatism.
• Other Adverse Reactions
- Cardiovascular system
rise of blood pressure. If hypertension develops, treatment should be discontinued.
- Genital tract
intermenstrual bleeding, post-medication amenorrhoea, changes in cervical secretion, increase in size of uterine fibromyomata, aggravation of endometriosis and certain vaginal infections, e.g. candidiasis
- Breast
tenderness, pain, enlargement, secretion.
- Gastro-intestinal tract
nausea, vomiting, cholelithiasis, cholestatic jaundice.
- Skin
erythema nodosum, rash, chloasma
- Eyes
discomfort of the cornea if contact lenses are used.
- CNS
headache, migraine, mood changes, depression.
- Metabolic
fluid retention, change in body weight, reduced glucose tolerance.
4.9 Overdose
There have been no reports of serious ill-effects from overdosage even when a considerable number of tablets have been taken by a small child. In general, it is therefore unnecessary to treat overdosage. However, if overdosage is discovered within two or three hours and is large, then gastric lavage can be safely used. There are no antidotes and further treatment should be symptomatic.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Marvelon is an oral contraceptive combination containing 150 micrograms desogestrel and 30 micrograms ethinylestradiol.
Ethinylestradiol is a well known synthetic estrogen.
Desogestrel is a synthetic progestogen. After oral administration it has a strong ovulation-inhibiting activity, a strong progestational and anti-estrogenic activity, no estrogenic activity, very weak androgenic/anabolic activity.
5.2 Pharmacokinetic Properties
After oral administration, desogestrel shows rapid absorption, followed by distribution throughout the body, and subsequent excretion, not resulting in retention of the drug and/or its metabolites. The freely extractable fraction in serum of volunteers contains desogestrel, 3-keto-desogestrel and polar metabolites. The level of the unchanged drug decreases rapidly and the level of the biologically active 3-keto-metabolite is still measurable 24 hours after dosing.
5.3 Preclinical Safety Data
The results of pre-clinical studies do not add to the information included in the other sections of the SmPC.
6. Pharmaceutical Particulars
6.1 List Of Excipients
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6.2 Incompatibilities
Not applicable.
6.3 Shelf Life
3 years
6.4 Special Precautions For Storage
Do not store above 25°C. Store blisters in the original pouches.
6.5 Nature And Contents Of Container
Push-through packs of 21 white tablets each. Tablets are round, biconvex and 6 mm in diameter. They are coded on one side TR5 and on the reverse side Organon*. The pack is PVC/Al blister consisting of aluminium foil with a heat-seal coating and a PVC film. Each blister is packed in a printed aluminium pouch. The pouch is packed in a printed cardboard box together with the package leaflet (1, 3, or 50 pouches per box). Not all pack sizes may be marketed
6.6 Special Precautions For Disposal And Other Handling
See Section 4.2.
7. Marketing Authorisation Holder
Organon Laboratories Ltd
Cambridge Science Park
Milton Road
Cambridge
CB4 OFL,
U.K.
8. Marketing Authorisation Number(S)
PL 0065/0071
9. Date Of First Authorisation/Renewal Of The Authorisation
04 November 1981 / 16 March 2009
10. Date Of Revision Of The Text
May 2011
11 LEGAL CATEGORY
Prescription Only Medicine
RU M0101.071.008
Marvelon/UK/05-11/2
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