Aidee: composition and presentation
One film-coated tablet contains 2 mg of dienogest and 0.03 mg of ethinylestradiol. The pack holds 21 active tablets and no placebo at all: three weeks of tablets, then a seven-day break. In this Aidee differs from medicines of the same composition supplied in a 28-tablet blister, where the last seven contain no hormones.
The tablets contain lactose, so the medicine is not used in the rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption syndrome. It has no or negligible influence on the ability to drive and to operate machinery.
How Aidee works
This is a combined oral contraceptive in which dienogest acts as the progestogen and ethinylestradiol as the oestrogen. The contraceptive effect is made up of several factors, the most important being inhibition of ovulation and changes in the cervical mucosa. Dienogest is a nortestosterone derivative, and in vitro its affinity for the progesterone receptor is 10–30 times weaker than that of other synthetic progestogens.
In vivo studies in animals, on the other hand, showed strong progestogenic and antiandrogenic activity; dienogest shows no significant androgenic, mineralocorticoid or glucocorticoid activity. It is precisely the antiandrogenic profile that sets it apart from older-generation progestogens and explains why preparations with dienogest are tolerated differently from levonorgestrel products at the same oestrogen dose.
Indications
Oral contraception. That is the only indication: treatment of acne, registered for some other preparations of the same composition, does not appear among Aidee's indications.
The decision to prescribe it should be governed by the risk factors of the individual patient — above all those linked to venous thromboembolic disease — and also by the level of that risk with this medicine compared with other combined contraceptives. The choice therefore does not come down to dose and convenience of the regimen: it is a risk assessment made before the first prescription.
Method of use and dosage
The tablets are taken in the order shown on the blister, every day at roughly the same time, with enough liquid. One tablet a day is taken for 21 consecutive days, after which a seven-day break follows, during which withdrawal bleeding usually occurs. It begins 2–3 days after the last tablet and may not have finished by the time the next pack starts: the new pack is begun strictly on the eighth day, whether or not the bleeding continues.
- if no hormonal contraception was used in the previous month, the tablets are started on the first day of the natural cycle, that is on the first day of menstrual bleeding;
- effectiveness falls if tablets are missed, if there are stomach and bowel disturbances, and if certain other medicines are taken at the same time — these are the three main reasons for losing contraceptive protection;
- in some women no withdrawal bleeding occurs during the break: if the regimen was not fully followed and the bleeding was absent once or twice, pregnancy must be excluded.
Spotting and intermenstrual bleeding are possible with any combined preparation, especially in the first months, so it is worth judging their cause after an adaptation period of about three cycles. If, on the other hand, they persist after cycles have already become regular, the cause is looked for outside the hormones and investigations are ordered to rule out a tumour or a pregnancy. The rules for a missed tablet are set out in the full summary of product characteristics.
Contraindications
Combined contraceptives are not used in the states listed below, and if any of them appears for the first time during use, the medicine is stopped at once. The first group is venous thrombosis: venous thromboembolic disease itself now, including while on anticoagulants, or in the past; a known predisposition to it — activated protein C resistance including factor V Leiden, antithrombin III, protein C or protein S deficiency; major surgery with prolonged immobilisation in the past; high risk from several factors together.
The second group is arterial events and severe metabolic disorders.
- myocardial infarction and angina as its forerunner, stroke and transient ischaemic attack — both now and at any earlier time;
- a laboratory-confirmed tendency to arterial thrombosis: raised homocysteine, anticardiolipin antibodies, lupus anticoagulant; and also migraine that has at any time run with focal neurological symptoms;
- several vascular risk factors together, or one severe one: diabetes that has affected the vessels, severely raised blood pressure, a severe lipoprotein disorder;
- past or current pancreatitis on a background of severely raised triglycerides; severe liver damage for as long as its parameters have not returned to normal; liver tumours; severe or acutely developed renal failure; tumours whose growth depends on sex hormones;
- genital bleeding of unestablished cause; allergy to the components of the tablet; pregnancy, including a suspected one.
Special warnings and precautions
The main warning is expressed in numbers. Taking any combined contraceptive increases the risk of venous thromboembolism: over a year it develops in about 2 women out of 10 000 who use no such products and are not pregnant, and in 6–12 out of 10 000 on products containing less than 50 µg of ethinylestradiol. The lowest risk goes with products containing levonorgestrel, norgestimate or norethisterone; on limited data the risk with dienogest products may be similar to that of levonorgestrel, but the exact level has not been established. Venous thromboembolism is fatal in 1–2% of cases, and the annual number of cases among contraceptive users is lower than that expected in pregnancy and the postpartum period.
The risk is highest in the first year of use, and there is evidence that it rises when the tablets are restarted after a break of 4 weeks or more. The factors that raise it are: obesity with a body mass index above 30, prolonged immobilisation including a flight longer than 4 hours, operations on the lower limbs and pelvis, serious injuries, thromboembolism in a parent, brother or sister, especially before the age of 50, tumours, lupus, inflammatory bowel disease and age over 35. Before planned surgery the tablets are stopped at least 4 weeks in advance and are not resumed until two weeks after mobility is regained. Arterial risk is raised by the same age and obesity, and further by smoking — smokers over 35 are advised to use another method — by family history, by worsening migraine during use, by diabetes and by atrial fibrillation.
| What has happened | How it shows itself |
| Deep vein thrombosis | one-sided swelling of the leg or foot, or along the vein; pain in the leg felt only when standing or walking; increased warmth in the affected leg; redness or discoloration of the skin |
| Pulmonary embolism | sudden unexplained breathlessness or rapid breathing; a sudden bout of coughing, sometimes with blood; sharp chest pain; dizziness; a fast or irregular heartbeat |
| Stroke | sudden numbness or weakness of the muscles of the face, arm or leg, especially on one side; sudden difficulty walking, loss of balance or coordination; disorientation, difficulty speaking or understanding; sudden difficulty seeing; a sudden severe headache with no visible cause; loss of consciousness |
Interactions with other medicines
Interactions of oral contraceptives with other medicines show themselves in two ways: as intermenstrual bleeding and as loss of contraceptive protection. The main mechanism is induction of microsomal enzymes, which increases the clearance of sex hormones.
- the inducers are hydantoin, barbiturates, primidone, carbamazepine, rifampicin, and probably also oxcarbazepine, topiramate, felbamate, griseofulvin, rifabutin, St John's wort and a number of anti-HIV medicines — ritonavir, efavirenz, nevirapine, nelfinavir;
- for the whole time inducers are taken and for a further 28 days a barrier method is needed, and with long-term treatment by them another non-hormonal method; if that period of extra protection runs past the end of a pack, the next one is started at once, without the seven-day break;
- according to clinical studies some antibiotics — penicillins, tetracyclines — reduce the enterohepatic circulation of oestrogens and hence of ethinylestradiol; with them, apart from rifampicin and griseofulvin, a barrier method is needed for a further 7 days after the course ends;
- in the other direction: the contraceptive changes the metabolism of other substances, so that the concentration of ciclosporin rises and that of lamotrigine falls; dienogest itself does not inhibit cytochrome P450 enzymes.
Laboratory tests are a separate matter: steroid contraceptives alter the biochemical parameters of liver, thyroid, adrenal and kidney function, the concentration of transport proteins and lipids, and the parameters of carbohydrate metabolism and clotting. The values usually stay within the normal range, but it is worth telling the doctor that the medicine is being taken.
Pregnancy and breastfeeding
In pregnancy the medicine is not indicated, and if pregnancy is confirmed during use it is stopped immediately. Extensive epidemiological studies have shown neither an increase in the frequency of congenital malformations in the children of women who took combined oral contraceptives before becoming pregnant, nor a teratogenic effect when these products were used inadvertently during pregnancy. Animal studies showed adverse effects during pregnancy and lactation, but general experience with combined products in pregnancy does not point to such effects in humans.
It is separately noted that when the tablets are restarted after a break in the postpartum period the increased risk of venous thromboembolism must be taken into account. Combined contraceptives may reduce the amount of milk and change its composition, and small doses of the hormones and their metabolites are excreted in milk and may affect the child. The medicine is therefore not used until the child has been weaned.
Adverse reactions
An increased risk of venous and arterial thrombosis has been observed in users of combined contraceptives, including myocardial infarction, stroke, transient ischaemic attack and pulmonary embolism. The remaining events are distributed by frequency as follows.
- common: headache, breast pain, acne, hair loss, rash, itching;
- uncommon: vaginal inflammation and candidiasis, increased appetite, low mood, migraine, dizziness, rises and falls in blood pressure, abdominal pain, nausea, vomiting, diarrhoea, abnormal withdrawal bleeding and intermenstrual bleeding, painful periods, ovarian cysts, change in body weight;
- rare: uterine fibroid, anaemia, virilism, depression, insomnia, aggression, stroke and cerebral circulatory disturbances, visual disturbances, sudden hearing loss, arterial and venous thromboembolic disorders, asthma, dermatitis, chloasma, hirsutism, cervical dysplasia, adnexal cysts, raised triglycerides;
- frequency not known: mood swings, decreased and increased sex drive, inability to wear contact lenses, urticaria, erythema, oedema from fluid retention.
Of the long-term risks the leaflet discusses three. Some epidemiological studies showed an increased risk of cervical cancer with long-term use in women infected with human papillomavirus, though the contribution of other factors is unknown. A meta-analysis of 54 epidemiological studies showed a slightly raised relative risk of breast cancer in current users — 1.24 — which gradually disappears within 10 years of stopping; a causal relationship is not proved by those studies. Finally, benign and, more rarely still, malignant liver tumours have been described in rare cases, in isolated instances leading to life-threatening bleeding into the abdominal cavity: with acute pain in the upper abdomen or an enlarged liver, such a tumour is considered separately.
Overdose
The acute oral toxicity of ethinylestradiol and dienogest is low.
In overdose nausea, vomiting and, in young girls, slight vaginal bleeding may occur. In most cases no specialist treatment is required; supportive treatment is given if needed.
How to get an Aidee prescription online
The medicine is available on prescription, and before it is first prescribed or restarted after a break the doctor takes a full history including the family history, excludes pregnancy, measures blood pressure and carries out an examination. They are obliged to discuss separately the risk of venous and arterial thrombosis, the signs that call for immediate help, and how this medicine compares in risk with other combined products.
For the online consultation prepare information about thromboses, heart attacks and strokes in yourself and in your parents, brothers or sisters, especially those that happened before the age of 50, about migraine with focal symptoms, smoking, weight, blood pressure, diabetes, liver and kidney disease, pancreatitis, tumours and planned operations, as well as a list of the medicines you take — antiepileptics, rifampicin, anti-HIV drugs, St John's wort and antibiotics. Remember, too, what the medicine does not do: hormonal contraception gives no protection against HIV and other sexually transmitted infections. The doctor will assess these circumstances and, if there are no contraindications, will issue an electronic prescription.
