Yasminelle®: composition and pharmaceutical form
From the related product Yasmin this one differs by a single figure: the film-coated tablet contains 3 mg of drospirenone and 0.02 mg of ethinylestradiol instead of 0.03 mg. The progestogen dose is the same, the oestrogen dose is a third lower. It is to that figure that the leaflet's phrase about a «low dose of oestrogens» is tied: the threshold is 0.05 mg, and everything below it is assessed differently on a number of questions — for example, on the effect on the course of diabetes — than the high-dose contraceptives of past decades.
The tablets are monophasic: the composition is identical in all 21 tablets of the pack, and the order of taking them is set by the blister. There is a detail that is rarely noticed but matters for some women: one tablet contains 46 mg of lactose. In rare hereditary galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption syndrome and on a lactose-free diet this amount has to be taken into account.
How Yasminelle® works
A conversation about drospirenone is worth starting not with contraception but with what it resembles. In therapeutic doses this substance has an antiandrogenic and a weak antimineralocorticoid action, yet it lacks oestrogenic, glucocorticoid and antiglucocorticoid activity — thanks to that set of properties its pharmacological profile is close to that of natural progesterone. The antimineralocorticoid component means that drospirenone acts as a weak opponent of aldosterone: it raises plasma renin activity and the aldosterone level and has potassium-sparing properties. From this follows almost everything the leaflet goes on to say about potassium and the kidneys.
The contraceptive effect itself results from the interaction of several factors, the most important of which are suppression of ovulation and changes in the endometrium.
Indications
The medicine has one indication — oral contraception — but in the leaflet it is worded unusually: the decision to prescribe should be taken on the basis of an individual assessment of a particular woman's risk factors. What has to be assessed above all is the risk of venous thromboembolism — both the woman's own risk and the one the medicine itself adds compared with other combined contraceptives.
That wording did not appear by chance. Drospirenone contraceptives do not belong to the group with the lowest thrombotic risk, and the leaflet names Yasminelle® outright among products whose use may be associated with twice the risk compared with the lowest-risk group. That is why the indication here is not «any woman who needs contraception» but the result of a conversation with a doctor.
Method of use and dosage
One tablet is taken a day, at roughly the same time, in the order shown on the blister, with a little liquid if needed. The tablets run for 21 consecutive days, then a 7-day break follows, and only after it is the next pack started.
The break does not work the way many expect. Withdrawal bleeding usually begins two or three days after the last tablet, that is, not straight away, and may well continue after the new pack has been started — this is not a failure and not a reason to stop. The opposite also happens: in some women there is no bleeding in the break at all. If the tablets were taken exactly to schedule, the likelihood of pregnancy is small; but if the schedule was broken, or withdrawal bleeding failed to occur twice in a row, pregnancy must be ruled out before continuing.
Contraindications
Some of the prohibitions have no time limit: they apply always. These are past or current venous thromboembolism — deep vein thrombosis, pulmonary embolism; a known inherited or acquired predisposition to it — resistance to activated protein C including factor V Leiden, antithrombin III deficiency, protein C or protein S deficiency; past or current arterial thrombosis including myocardial infarction and stroke; an inherited or acquired tendency to arterial thrombosis; migraine with focal neurological symptoms in the history; past or present benign and malignant liver tumours; malignant tumours dependent on sex hormones; hypersensitivity to the components; severe or acute renal failure.
The other part of the prohibitions is temporary, and that changes the logic: they close the medicine off not forever but until a certain event. Severe liver disease — until its function tests return to normal. Major surgery with prolonged immobilisation — for a period the leaflet describes precisely: intake is stopped at least four weeks before the planned operation and not resumed earlier than two weeks after mobility is regained. Genital bleeding of unknown cause — until the cause is clarified. And a general rule for the whole list: if any of these conditions appears for the first time while the medicine is being taken, it is stopped immediately.
Special warnings and precautions
Two things raise thrombotic risk more noticeably than the rest, and both are about time rather than about diseases: the risk is highest in the first year of use, and there is evidence that it rises again if the medicine is resumed after a break of four weeks or more. Numbers help to grasp the scale. Of 10,000 women who do not use combined hormonal contraceptives and are not pregnant, venous thromboembolism will develop within a year in about two. Among 10,000 who use a drospirenone contraceptive there will be about nine to twelve, and among those using a levonorgestrel one, about six. In both cases that is less than during pregnancy and after childbirth, but venous thromboembolism proves fatal in 1-2% of cases. The risk is noticeably increased by additional factors, and with several at once the increase is often greater than their simple sum: a body mass index above 30, prolonged immobilisation, surgery and serious injury, a family history of thrombosis in parents or siblings before the age of 50, age above 35. Temporary immobilisation such as a flight longer than four hours also counts as a risk factor. For arterial events the list is its own: age above 35, smoking — women over 35 who smoke are advised to use another method of contraception — hypertension, a body mass index above 30, family history, migraine, diabetes. Worsening migraine or more frequent attacks while taking the medicine may herald a cerebrovascular event and is in itself a reason to stop taking it at once.
The symptoms that call for seeing a doctor immediately and saying that you use a combined contraceptive are worth knowing in advance. Deep vein thrombosis is suggested by swelling of the leg or foot or swelling along a vein, pain or tenderness in the leg, sometimes felt only when standing or walking. Pulmonary embolism — sudden unexplained breathlessness or rapid breathing, a sudden cough, sometimes with blood, sharp chest pain. The remaining warnings are shorter. A slight rise in blood pressure is common, but the medicine has to be withdrawn only if the rise is clinically significant. Chloasma is possible, especially in women who had it in pregnancy — they should avoid sun and ultraviolet radiation. Long use, more than five years, is linked with the risk of cervical cancer; a meta-analysis of 54 studies showed a slight increase in the relative risk of a breast cancer diagnosis — 1.24 — which fades gradually within ten years of stopping. And an important practical reminder: hormonal contraception does not protect against HIV or other sexually transmitted infections.
Drug interactions
Drospirenone has an interaction that other progestogens do not, and it is worth starting with it. Since the substance spares potassium, it has not been studied together with aldosterone antagonists and potassium-sparing diuretics, and in such cases serum potassium is measured in the first treatment cycle.
The second group are medicines that speed up the elimination of sex hormones by inducing liver enzymes; the result is intermenstrual bleeding and loss of contraceptive effect. These are barbiturates, bosentan, carbamazepine, phenytoin, primidone, rifampicin, some HIV medicines — ritonavir, nevirapine, efavirenz — and probably also felbamate, griseofulvin, oxcarbazepine, topiramate and St John's wort preparations. With a short course of such a medicine an additional barrier method is needed — for the whole course and 28 days after it — and if the course lasts longer than the current pack, the next one is started at once, without the usual break; with long-term treatment with inducers a non-hormonal method is recommended. Strong CYP3A4 inhibitors act the other way round: ketoconazole given for ten days increased the area under the curve of drospirenone 2.7-fold and that of ethinylestradiol 1.4-fold. Finally, the contraceptive itself affects other medicines: the concentration of ciclosporin may rise and that of lamotrigine may fall.
Pregnancy and breastfeeding
Let us start with breastfeeding, because here the conclusion is the most definite: combined oral contraceptives may affect lactation by reducing the amount of milk and changing its composition, so they are generally not recommended until breastfeeding has ended. Small amounts of hormones and their metabolites pass into milk and may act on the child.
In pregnancy the medicine is not used, and if pregnancy occurs while taking it, it is stopped without delay. The reassuring part: large epidemiological studies found no increase in the frequency of congenital defects in children of women who had used combined contraceptives before pregnancy, nor any teratogenic effect in children of those who took them unintentionally during pregnancy. Data on Yasminelle® itself in pregnant women are too limited to draw conclusions. Separately, the leaflet reminds: when deciding to resume the medicine after childbirth, account must be taken of the increased risk of venous thromboembolism in the postpartum period.
Adverse reactions
The common reactions are the ones a woman meets in the first months and asks about most often: emotional instability, headache, abdominal pain, acne, breast pain, breast enlargement and tenderness, painful menstruation, bleeding outside the cycle and weight gain. Uncommonly, nausea and vomiting, diarrhoea, constipation, gastroenteritis, depression, nervousness, sleep disorders, paraesthesia, dizziness, visual disturbances, hypertension and hypotension, migraine, allergic reactions, hair loss, eczema, itching, rash, dry skin and seborrhoea occur, as well as a number of gynaecological findings: ovarian cyst, hot flushes, menstrual disorders and absence of menstruation, heavy menstrual bleeding, vaginal candidiasis and inflammation, reduced libido.
Serious reactions are rare, and it is precisely they that set all the caution around this medicine. They are venous and arterial thromboembolism, including infarction, stroke, transient ischaemic attack, venous thrombosis and pulmonary embolism, and also hypertension and liver tumours — the latter rarely, but they are described, and with severe pain in the upper abdomen, an enlarged liver or signs of intra-abdominal bleeding they must be ruled out. Hearing loss, erythema nodosum and erythema multiforme are rarely noted. In women with hereditary angioedema, oestrogens can provoke or worsen its manifestations.
Overdose
No cases of overdose of this medicine itself have been described so far. From experience with other combined oral contraceptives it is known what may be expected: nausea, vomiting and slight vaginal bleeding in young girls.
There is no antidote and treatment is symptomatic. In practice this means that one extra tablet taken by accident requires no emergency measures, but there is also no point in «catching up» on missed doses by taking several tablets at once: the rules for a missed dose are described separately and work differently.
How to get a prescription for Yasminelle® online
This contraceptive belongs to a group with a higher venous risk than levonorgestrel ones, and the risk is highest in the first year of use and when resuming after a break of a month or more. That is why the doctor needs to know your age, whether you smoke, your body mass index, whether there have been thromboses in you and in your parents or siblings before the age of 50, whether there is migraine with neurological symptoms, hypertension, diabetes, liver and kidney disease.
If the answers to these questions point to a high thrombotic risk, the doctor will suggest another method of contraception — for drospirenone products that outcome of a consultation is normal and does not mean you have been refused help. The procedure itself looks like this: Yasminelle® is a prescription medicine, you fill in the questionnaire at e-zdrowie.com yourself, the doctor issues an electronic prescription on the basis of the answers, the code arrives by message, and with it the pack is dispensed at any Polish pharmacy.
