Daylette: composition and form
One film-coated tablet contains 3 mg of drospirenone and 0.02 mg of ethinylestradiol. The pack covers 28 days, and that matters here: the last row of the blister is green placebo tablets with no active substances in them. There is therefore no break in taking the tablets at all — the usual pause has been replaced by days with empty tablets.
That design of the pack solves one problem: it removes from the regimen the week in which a woman takes nothing and easily loses count. The tablets follow the order shown on the blister, every day and at roughly the same time, swallowed with a little liquid if needed.
How Daylette works
The contraceptive effect is made up of several factors, the most important being suppression of ovulation and changes in the endometrium. The progestogen half here is drospirenone, and it differs from the usual progestogens by a set of extra properties: at therapeutic doses it has antiandrogenic and slight antimineralocorticoid action, but no oestrogenic and no glucocorticoid activity. That is precisely why its pharmacological profile is close to that of natural progesterone. The antimineralocorticoid property also leaves a laboratory trace: drospirenone raises plasma renin activity and the aldosterone concentration.
| Measure at 6 months | Combination | Placebo |
| Reduction in inflammatory lesions | 49.3% | 33.7% |
| Reduction in non-inflammatory lesions | 40.6% | 22.1% |
| Reduction in total lesion count | 44.6% | 28.1% |
| "Clear" or "almost clear" skin on the ISGA scale | 18.6% | 6.8% |
The figures in the table come from two multicentre, double-blind, randomised placebo-controlled studies in women with moderate acne vulgaris; the difference from placebo was 15.6%, 18.5%, 16.5% and 11.8% respectively, and was statistically significant. It follows from the antiandrogenic action of drospirenone, and in the section on adverse reactions moderate acne is named outright as the second context in which this combination is used.
Indications
There is exactly one indication: oral contraception. Everything said about acne sits in the section on action and describes properties of the drospirenone and ethinylestradiol combination, but it is not an indication in its own right — the product information does not propose prescribing the medicine "for spots".
In practice this means that an improvement in the skin can be treated as an accompanying effect if contraception is needed for its own sake, but not as a reason to start. The decision is the doctor's, and they weigh it not by the state of the skin but by the list of contraindications, one of the longest among combined contraceptives.
Administration and dosage
The regimen is simple to the point of bareness: one tablet a day for 28 days in a row, without a single break. Each next pack is begun the day after the last tablet of the previous one, so that taking them never stops as long as contraception continues. The order of the tablets on the blister must not be changed: it is what sets which day the woman gets hormones and which day placebo.
Withdrawal bleeding usually starts on the second or third day after moving on to the green placebo tablets of the last row and may not be over by the start of the new pack. That is neither a fault nor a reason to delay the next blister: in a regimen without a break, the new pack begins regardless of whether the bleeding continues.
Contraindications
Most of the prohibitions concern the vessels and clotting. The medicine is not given in venous thrombosis now or in the past — deep vein thrombosis, pulmonary embolism; in arterial thrombosis now or in the past, myocardial infarction for instance, or with its prodromal signs such as angina and transient ischaemic attacks; in stroke now or in the history. Here belong too a serious risk factor or several for arterial thrombosis — diabetes with vascular damage, severe hypertension, severe dyslipoproteinaemia — and a predisposition to thrombosis: resistance to activated protein C, deficiency of antithrombin III, protein C or protein S, hyperhomocysteinaemia, antiphospholipid antibodies.
The second group concerns the internal organs, and one item in it sets this medicine apart from other combined contraceptives — severe or acute renal failure, a ban that follows from the properties of drospirenone. Beside it stand severe liver disease now or in the past until liver tests return to normal, liver tumours, and pancreatitis with severe hypertriglyceridaemia now or in the history. The third group is the hormone-dependent and the unexplained: the presence or suspicion of a malignant sex-hormone-dependent tumour, vaginal bleeding of unestablished cause, migraine with focal neurological symptoms in the history, and hypersensitivity to the components.
Special warnings and precautions
About venous thromboembolism the product information is unusually careful in its conclusions. It is known that the risk is highest in the first year of using any combined contraceptive and that with a low oestrogen dose it runs from 20 cases per 100 000 woman-years for second-generation preparations to 40 for third-generation ones, while in women using no contraception it is 5 to 10; 1-2% end in death. A large three-arm prospective cohort study showed that in women on the combination of ethinylestradiol with drospirenone at 0.03 and 3 mg the frequency lies in the same range as with levonorgestrel. But then comes an explicit caveat: the risk with this particular medicine is not currently known. The symptoms calling for immediate medical attention are listed in detail: one-sided pain or swelling of the leg, sudden chest pain, breathlessness, a fit of coughing, an unusually severe headache, loss of vision or double vision, disturbed speech, weakness or numbness of one half of the body, an "acute abdomen". The risk is raised by age, family history, obesity, prolonged immobility and surgery — before a planned operation the tablets are stopped 4 weeks in advance and resumed no earlier than 2 weeks after mobility returns.
The second thread is potassium, and it is specific to drospirenone. The progestogen component of the medicine is an aldosterone antagonist with potassium-sparing properties, but in most cases no rise in potassium is to be expected. In a clinical study, however, in some patients with mild or moderate renal impairment who were also taking potassium-sparing medicines, serum potassium rose slightly, though not significantly. That is why in renal failure, with a baseline potassium near the upper limit of normal and especially alongside potassium-sparing medicines, potassium is checked during the first treatment cycle. Of the rest: a meta-analysis of 54 studies showed a slightly raised relative risk of breast cancer in current users — 1.24 — which disappears within 10 years of stopping; with use of more than 5 years an increased risk of cervical cancer was noted, though how much sexual behaviour and human papillomavirus contribute to those results is unknown. In hereditary angioedema, oestrogens from outside can worsen its manifestations.
Interactions with other medicines
The main mechanism is induction of liver enzymes, which speeds the clearance of sex hormones; the result is intermenstrual bleeding and loss of contraceptive effect. Belonging here are phenytoin, barbiturates, primidone, carbamazepine, rifampicin, bosentan, HIV medicines — ritonavir and nevirapine — and probably also oxcarbazepine, topiramate, felbamate, griseofulvin and St John's wort. Maximum induction comes after about 10 days but persists for at least 4 weeks after treatment ends. Hence the back-up rules: on a short course, of up to a week, of any inducer other than rifampicin, a barrier method is used as well during the course and for 7 days afterwards; with rifampicin, the whole course and 28 days after; with other antibiotics, up to 7 days after finishing. It is stated separately that if such treatment continues once the active tablets run out, the green placebo tablets are discarded and the new pack begun at once, and that with inducers taken long term a switch to a non-hormonal method is recommended.
The second part of the interactions is no longer about enzymes but about potassium and the laboratory. The main metabolites of drospirenone are formed without the involvement of cytochrome P-450, so inhibitors of that system probably do not affect its metabolism, and the risk of drospirenone itself at 3 mg affecting the metabolism of other medicines is considered small — this was checked with omeprazole, simvastatin and midazolam. No significant effect on serum potassium was shown alongside ACE inhibitors or non-steroidal anti-inflammatory drugs in patients without renal failure. But with aldosterone antagonists and potassium-sparing diuretics no studies have been done, and in that case potassium is measured in the very first cycle. Finally, contraceptive steroids distort a range of laboratory parameters — liver, thyroid, adrenal and renal, transport proteins, coagulation — though the shifts usually stay within normal limits.
Pregnancy and breastfeeding
In pregnancy the medicine is not indicated, and if pregnancy occurs while it is being taken it is withdrawn at once. Large-scale epidemiological studies found neither a raised risk of congenital defects in the children of women who took combined contraceptives before conception, nor a teratogenic effect from unintentional use during pregnancy. In animal studies adverse effects during gestation and lactation were nevertheless found, and they cannot be entirely ruled out in humans, although general experience with such products does not point to them. On the drospirenone and ethinylestradiol combination itself there is too little data to draw conclusions about the effect on pregnancy and on the state of the fetus or newborn.
With breastfeeding the position is clearer. Combined contraceptives can affect lactation, reducing the amount of milk and changing its composition, so they are usually not recommended until the child is fully weaned. Small amounts of contraceptive steroids and their metabolites do pass into the milk and may affect the child.
Adverse reactions
Commonly there are emotional lability, headache, nausea, breast pain, uterine bleeding and absence of menstruation. Uncommonly: depression, reduced sex drive, nervousness, drowsiness, dizziness, paraesthesia, migraine, varicose veins, a rise in blood pressure, abdominal pain, vomiting, dyspepsia, bloating, gastritis, diarrhoea, acne, itching, rash, back and limb pain, muscle cramps, vaginal candidiasis, pelvic pain, breast enlargement, vaginal discharge, hot flushes, menstrual disorders, weakness, sweating, oedema and weight gain.
The rare reactions form a long list: candidiasis, anaemia, thrombocythaemia, allergic reaction, endocrine disorders, appetite changes, hyperkalaemia and hyponatraemia, insomnia, tremor, conjunctivitis and dry eyes, tachycardia, phlebitis, nosebleed, fainting, gallbladder pain and inflammation, melasma, eczema, hair loss, erythema nodosum, breast and ovarian cysts, cervical polyps, endometrial atrophy. Set out separately are the serious reactions common to the whole class: venous and arterial thromboembolic disease, hypertension, liver tumours, and also conditions whose link with use has not been established — Crohn's disease, ulcerative colitis, epilepsy, migraine, uterine fibroids, porphyria, systemic lupus erythematosus, herpes gestationis, Sydenham's chorea, cholestatic jaundice. Breast cancer is diagnosed somewhat more often in women using contraception, but since it is rare before the age of 40 the increase in the number of cases is small, and the causal link is unknown.
Overdose
No cases of overdose with drospirenone and ethinylestradiol preparations have been described so far. The possible manifestations have to be inferred from general experience with other combined contraceptives: with an excess of active tablets, nausea, vomiting and slight vaginal bleeding in young girls are possible.
There is no antidote and further treatment should be symptomatic. One practical conclusion matters: a muddled tablet order or one tablet taken over the mark calls for no urgent measures, but neither does it cancel the regimen — taking them continues by the blister rather than being "shifted" back.
How to get a prescription for Daylette online
This medicine has a feature the doctor asks about separately: drospirenone retains potassium, so the kidneys weigh as much in the questionnaire as the vessels do. At e-zdrowie.com you fill in a medical questionnaire, the doctor examines the answers and, if the medicine is suitable, issues an electronic prescription: the code arrives by message, and with it any Polish pharmacy will hand over the pack.
Start with the kidneys: any kidney disease, dialysis, recent tests with abnormalities, and whether you take potassium-sparing diuretics or aldosterone antagonists — those combinations are not forbidden, but they require potassium to be checked in the first cycle. Then comes the vascular block: past thrombosis and pulmonary embolism, heart attack and stroke — your own and in close relatives at a young age — known clotting disorders, severe hypertension, diabetes with complications. Describe the liver: hepatitis, tumours, pancreatitis with high triglycerides. Do not leave out migraine, and state whether it comes with focal neurological symptoms: that is no longer a warning but a ban. And list the medicines that speed up the elimination of hormones — antiepileptics, rifampicin, HIV drugs, St John's wort.
