Elliade: composition and dosage form
Elliade is a combined oral contraceptive in which the oestrogen is not ethinylestradiol but estradiol valerate. The 28-day blister is made up of five kinds of film-coated tablets arranged in a strictly defined order.
| Colour | How many | What is inside |
|---|---|---|
| Dark yellow | 2 | 3 mg of valerate |
| Pink | 5 | 2 mg of valerate and 2 mg of dienogest |
| Light yellow | 17 | 2 mg of valerate and 3 mg of dienogest |
| Brown | 2 | 1 mg of valerate |
| White | 2 | No active substances |
The oestrogen dose falls as the pack goes on, while the progestogen first appears, rises and disappears before the placebo. Colour here is a dose marker rather than decoration: a disturbed order changes the hormonal background of the cycle.
How Elliade works
The contraceptive effect is made up of several mechanisms, the most important of which are considered to be suppression of ovulation and changes in cervical secretion and in the lining of the womb. In a three-cycle study the treatment held back follicular development in most women, and ovarian activity returned to its former level within one cycle after withdrawal.
Reliability is measured by the Pearl index, the number of pregnancies per hundred women per year of use. In women aged 18 to 50 method failure alone gave 0.42 (upper limit of the confidence interval 0.77), and together with patient error 0.79 (up to 1.23). In the 18 to 35 subgroup the figures are higher: 0.51 and 1.01. The gap between those two lines is precisely the price of forgotten tablets, vomiting and unaccounted interactions.
Indications
There is a single indication: oral contraception. The product information lists no therapeutic indication, although the clinical trials also enrolled women with heavy menstrual bleeding without organic changes. The conclusion is simple: if heavy periods are the main complaint, that is what should be discussed with a doctor, rather than choosing a contraceptive in the hope of a side benefit.
Prescribing is only possible after an individual assessment of risk factors, above all venous thromboembolism, and taking into account how that risk compares with other combined contraceptives. There are no data on use below the age of 18, and after the menopause the product is not indicated.
How to take it and dosage
One tablet a day for 28 days in a row, at roughly the same time. There are no breaks between packs: the next blister begins the day after the last tablet of the previous one, and withdrawal bleeding usually falls on the last tablets and may run into the new pack. The starting point depends on what came before: with no hormonal contraception in the past month, the first day of menstruation; after another combined product, the day after the last active tablet, and after a ring or a patch, the day it is removed; after a progestogen-only product, any day, or the day an implant, a system or an injection is replaced; after a first-trimester miscarriage, straight away, and after childbirth, between days 21 and 28. In every case except the first two, a barrier method is needed for the first nine days.
| What happened | What happens to protection | What to do |
|---|---|---|
| A white tablet was missed | Unchanged | Throw it away so the hormone-free interval is not extended |
| Less than 12 hours late | Preserved | Take it at once and the next one at the usual time |
| More than 12 hours late | May be reduced | Take it immediately, even if that means two in a day, and add protection according to the rules for that day of the cycle |
| Vomiting within the first 3–4 hours or severe diarrhoea | Absorption incomplete | Take another one within 12 hours and, if the upset drags on, use an additional method |
No more than two tablets a day may be taken. Missing active tablets between the third and the ninth day, or forgetting to start a pack, after intercourse in the preceding seven days means pregnancy is possible, and the more so the closer the miss is to the placebo phase. The rules for extra protection by day of the cycle are referred to the full product characteristics, so they should be worked through with the leaflet at hand. In severe liver disease the product is contraindicated, and in renal impairment it has not been studied.
Contraindications
Most of the bans are built around blood clotting. Venous thromboembolism, whether current — including when treated with anticoagulants — or past, be it deep vein thrombosis or pulmonary embolism, rules out prescribing, as does a known inherited or acquired predisposition to it: activated protein C resistance, antithrombin III deficiency, protein C or protein S deficiency. The same applies to major surgery with prolonged immobilisation and to a combination of factors adding up to high risk. The arterial side is a mirror image: current or past arterial disorders and their prodromes such as angina, stroke and transient ischaemic attack in the history, antiphospholipid antibodies, migraine with focal neurological symptoms, diabetes with vascular complications and severe hypertension.
The second group concerns the liver and hormone-dependent tissues: liver tumours now or in the past, severe liver disease until liver tests return to normal, and tumours dependent on sex steroids, including suspected ones. Separately there are genital bleeding of unexplained origin and intolerance of the ingredients. Any of these conditions appearing for the first time during treatment calls for immediate withdrawal.
Special warnings and precautions
Any combined contraceptive raises the likelihood of venous thromboembolism. Over a year it develops in about 2 women out of 10,000 who do not use such products and are not pregnant, and in 6 to 12 out of 10,000 on products containing less than 50 µg of ethinylestradiol; in 1 to 2% of cases the outcome is fatal. Limited data suggest that with estradiol valerate combined with dienogest the risk is roughly the same as with other combined products, including those containing levonorgestrel. It is highest in the first year of use and when treatment is resumed after a break of four weeks or more, and it is increased by obesity, prolonged immobilisation, major surgery, flights longer than four hours, thrombosis in close relatives before the age of 50 and age over 35. Before planned surgery the tablets are stopped four weeks in advance and resumed two weeks after mobility is regained. Smokers over 35 are advised to use another method, and worsening migraine may herald a cerebral event and is grounds for immediate withdrawal.
- Leg: swelling of the calf or along a vein, pain sometimes felt only on walking, local warmth, reddened skin. If the vessel closes in the eye, vision is disturbed painlessly and may be lost almost at once.
- Lungs: sudden breathlessness, cough, sometimes with blood, sharp chest pain, an irregular heartbeat.
- Brain: numbness or weakness on one side, loss of balance, disturbed speech, an abrupt visual disorder, fainting.
- Heart: pain or pressure behind the breastbone and in the arm radiating to the back and jaw, sweating, extreme weakness.
Use for longer than five years may raise the risk of cervical cancer, and a meta-analysis of 54 studies showed a small increase in the relative risk of breast cancer (RR = 1.24) that fades within ten years of stopping and without a proven causal link. Liver tumours have rarely been described, occasionally with bleeding into the abdominal cavity, so severe pain in the upper abdomen needs to be looked into. Low mood and depression are a known reaction to hormonal contraception, and a change of mood is worth discussing with a doctor. Irregular bleeding in the first months is ordinary: intermenstrual bleeding was recorded in every cycle in 10 to 18% of women and absent menstruation in about 15% of cycles, so regularity cannot be judged before three cycles. A tablet contains no more than 50 mg of lactose, and contraception does not protect against sexually transmitted infections.
Drug interactions
The greatest danger comes from inducers of microsomal enzymes: they speed up the clearance of sex hormones, which shows itself as intermenstrual bleeding and loss of protection, and the induction lasts for about four more weeks after the inducer is stopped. They include barbiturates, carbamazepine, phenytoin, primidone, rifampicin, and among HIV medicines ritonavir, nevirapine and efavirenz, as well as preparations containing St John's wort. In a study with rifampicin the daily area under the curve for dienogest fell by 83% and for estradiol by 44%. Throughout such treatment and for 28 days afterwards a barrier method is needed; if the course ends later than the tablets in the blister, the new pack is started at once, skipping the placebo, and with long-term inducer use it is more sensible to change contraception altogether.
Dienogest is a CYP3A4 substrate, so inhibitors of the enzyme work the other way: ketoconazole raised the daily area under the curve for dienogest 2.9-fold and for estradiol 1.6-fold, erythromycin 1.6-fold and 1.3-fold, although the clinical significance is unknown. HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors can both raise and lower hormone levels, so in case of doubt a barrier method is added. With direct-acting regimens against hepatitis C, a rise in ALT above five times the upper limit of normal was noticeably more common in women taking products with ethinylestradiol; with estradiol the rate was as in women on no oestrogen at all, but the data are scarce. The reverse influence also exists: ciclosporin levels may rise and lamotrigine levels fall, while liver, thyroid and kidney tests and clotting parameters shift, usually staying within the normal range.
Pregnancy and breastfeeding
The product serves to prevent pregnancy and is not used once pregnancy has occurred: on discovering it, the tablets are stopped immediately. Anxiety about the child already conceived, however, is largely unfounded: in large epidemiological studies of combined contraceptives containing ethinylestradiol no increase was found in the rate of congenital malformations among children of women who had used them before conception, nor any teratogenic effect from unintentional use during pregnancy.
For breastfeeding the answer is negative: combined products reduce the amount of milk and change its composition, and small amounts of contraceptive steroids and their metabolites pass into it and may affect the child. In returning to the tablets after childbirth, it is also taken into account that the risk of venous thromboembolism is already raised in the puerperium.
Adverse reactions
The most frequently reported were acne, breast tenderness, headache, intermenstrual bleeding, nausea and weight gain, while venous thromboembolism and arterial thromboembolic disorders are recognised as serious reactions. The list was gathered from five phase three trials: 2,266 women used the product for contraception and another 264 had uterine bleeding without organic changes.
- Genital sphere and breasts: common — absent menstruation, breast tenderness, painful periods, intermenstrual bleeding; uncommon — breast nodules, cervical dysplasia, ovarian cyst.
- Nervous system and psyche: common — headache; uncommon — dizziness, migraine, low mood, insomnia, reduced libido; rare — anxiety, aggression.
- Digestion and liver: common — abdominal pain and nausea; uncommon — diarrhoea, vomiting, raised liver enzymes; rare — dyspepsia, cholecystitis.
- Skin: common — acne; uncommon — hair loss, sweating, itching, rash; rare — chloasma, hirsutism, pigmentation disorders.
- Vessels and heart: uncommon — hot flushes, hypertension; rare — venous thromboembolism, arterial disorders, myocardial infarction, phlebitis.
Flare-ups of Crohn's disease, ulcerative colitis, epilepsy, porphyria and cholestatic jaundice on combined contraceptives have been described, but there are no unequivocal data in favour of a causal link.
Overdose
The product has no antidote, and help in overdose is symptomatic. No reports of serious harmful consequences have been received so far, so this is a matter of unpleasant sensations rather than of danger.
What appears after taking an excess of tablets containing active substances is nausea and vomiting, and in young girls slight vaginal bleeding is possible. It is worth remembering the standing limit as well: even when making up for a missed dose, no more than two tablets a day may be taken.
How to get a prescription for Elliade online
Elliade has no therapeutic indication: the only reason to take it is contraception, so prescribing comes down to weighing benefit against risk in the individual woman. The product information requires that before starting and before resuming treatment a full history, including the family history, is taken, pregnancy is excluded, blood pressure is measured, an examination is carried out and the signs of thrombosis are explained to the woman.
The questionnaire starts with the vessels: thrombosis in the woman herself and in relatives before the age of 50, inherited clotting disorders, migraine and its character, smoking, age, body mass index and blood pressure. Then come the liver, diabetes, planned operations and immobility, breastfeeding, and finally concomitant medicines — antiepileptics, rifampicin, HIV and hepatitis C drugs and St John's wort. The doctor studies the answers and, where there are sufficient grounds, issues an electronic prescription as a code for a Polish pharmacy; where there are contraindications or a combination of thrombotic risk factors, it will be refused.
