Yaz®: composition and pharmaceutical form
A pack of Yaz® contains 28 film-coated tablets and falls into two parts. Twenty-four light pink tablets are active: each contains 3 mg of drospirenone and 0.02 mg of ethinylestradiol as a clathrate with betadex. The remaining four tablets are white and contain no active substances — they are placebo.
That ratio is precisely what sets the medicine apart: the cycle has 24 active tablets rather than 21, as in the more familiar scheme. The hormone-free interval is shortened to four days, and this affects how reliably follicular maturation is suppressed.
How Yaz® works
The contraceptive effect is made up of several mechanisms, the main ones being suppression of ovulation and changes in the endometrium that make implantation unlikely.
The advantage of the 24-day scheme has been shown by direct comparison: in a study over three menstrual cycles, drospirenone 3 mg plus ethinylestradiol 0.02 mg in a 24-day regimen suppressed follicular development better than the same combination in a 21-day regimen. When dosing errors were deliberately modelled in the third cycle, ovulatory activity returned more often precisely in women on the 21-day scheme. After the medicine was stopped, ovarian function returned to baseline in 91.8% of the women on the 24-day regimen.
Indications
Yaz® is intended for oral contraception.
The decision to prescribe is not made on the wish to avoid pregnancy alone, but after an individual assessment of a particular woman's risk factors — above all the risk of venous thromboembolism, including the additional risk tied to this very medicine compared with other combined hormonal contraceptives.
Method of use and dosage
The tablets are taken daily at roughly the same time of day, in the order shown on the pack, with a little liquid if needed. The scheme is simple: one tablet a day for 28 days in a row, with no breaks between packs — the new one is started the day after the last tablet of the previous pack.
Withdrawal bleeding usually begins 2–3 days after switching to the placebo tablets (the last row in the pack) and may not have finished by the start of the new pack — this is the normal course of the cycle on the medicine, not a reason to interrupt it. The details of what to do after a missed tablet, when switching contraceptive and after childbirth are set out in the full leaflet, and they are worth discussing with the doctor in advance rather than at the moment a tablet has already been missed.
Contraindications
Combined hormonal contraceptives are not used in the conditions listed below. If any of them appears for the first time while the medicine is being taken, it is withdrawn immediately.
- venous thromboembolism, current or past, including deep vein thrombosis and pulmonary embolism;
- inherited or acquired predisposition to venous thrombosis: activated protein C resistance (including factor V Leiden), antithrombin III deficiency, protein C deficiency;
- arterial thromboembolic disorders, current or past: myocardial infarction, angina as a prodrome, stroke, transient ischaemic attack in the history;
- predisposition to arterial thrombosis, including hyperhomocysteinaemia and antiphospholipid antibodies;
- migraine with focal neurological symptoms in the history;
- major surgery with prolonged immobilisation, as well as a combination of several thrombosis risk factors;
- diabetes mellitus with vascular complications, severe arterial hypertension, severe dyslipoproteinaemia;
- severe liver disease or liver tumours, severe or acute renal failure, hormone-dependent malignancies, genital bleeding of unknown origin, hypersensitivity to the components.
Special warnings and precautions
The key question when choosing this medicine is thrombotic risk, and it is worth understanding it in numbers. In women who take no hormonal contraception and are not pregnant, venous thromboembolism develops in about 2 per 10,000 a year. On contraceptives containing levonorgestrel it is about 6 per 10,000, and on those containing drospirenone, Yaz® among them, about 9–12 per 10,000. The risk is highest in the first year of use and rises when use is resumed after a break of 4 weeks or more. In 1–2% of cases venous thromboembolism is fatal. For comparison: during pregnancy and after childbirth this risk is higher than on any of the medicines listed.
What raises the risk and when the medicine is withdrawn
- obesity: the risk grows with the body mass index, especially above 30 kg/m²;
- prolonged immobilisation, major surgery, any operation on the lower limbs or in the pelvis, neurosurgery, severe trauma;
- temporary immobilisation, including a flight lasting more than 4 hours;
- before planned surgery the medicine is stopped at least 4 weeks beforehand and resumed no earlier than 2 weeks after mobility is regained, using another contraceptive method meanwhile;
- a combination of several risk factors is more dangerous than their simple sum — in that case the medicine is contraindicated;
- if venous or arterial thrombosis is suspected the medicine is stopped at once;
- if anticoagulant therapy has been started another contraceptive method is needed: coumarins have a teratogenic effect;
- when taken together with aldosterone antagonists or potassium-sparing diuretics, plasma potassium is checked during the first cycle.
Signs that call for urgent help
One-sided swelling of a leg, leg pain that worsens on exertion, sudden breathlessness, a cough with no clear cause, chest pain, acute weakness or numbness of one half of the body, disturbed speech or vision — all of these are reasons to seek medical help immediately. Separately, rare thromboses of unusual sites are worth remembering: hepatic, mesenteric and renal vessels and those of the retina.
Drug interactions
The main practical problem is medicines that speed up the metabolism of sex hormones and thereby reduce the contraceptive effect. These include barbiturates, bosentan, carbamazepine, phenytoin, primidone, rifampicin, ritonavir, nevirapine and efavirenz, and probably also felbamate, griseofulvin, oxcarbazepine, topiramate and herbal products with St John's wort. Enzyme induction develops within a few days, peaks within a few weeks and persists for about 4 weeks after withdrawal.
For the duration of such treatment and for 28 days afterwards an additional barrier method is needed; if the course ends later than the active tablets of the current pack, the placebo is skipped and the next pack is started right away. With prolonged use of inducers it is better to switch to a non-hormonal method. Strong CYP3A4 inhibitors work the other way: ketoconazole increased the area under the curve for drospirenone 2.7-fold, and etoricoxib raised the ethinylestradiol concentration 1.4–1.6-fold. The medicine itself also affects other drugs — the concentration of ciclosporin may rise and that of lamotrigine fall. HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors can both raise and lower hormone levels, so where there is doubt a barrier method is added.
Pregnancy and breastfeeding
The medicine is not used during pregnancy. If pregnancy occurs while it is being taken, it is stopped immediately. Large epidemiological studies have found no increase in the frequency of congenital malformations in children of women who took combined contraceptives before conception, and have shown no teratogenic effect from accidental use in early pregnancy.
Combined contraceptives affect lactation: they reduce the amount of milk and change its composition, and small amounts of hormones and their metabolites pass into the milk and may act on the child. For that reason they are usually not recommended until breastfeeding has ended. When resuming after childbirth the increased risk of venous thromboembolism in the postpartum period must be taken into account.
Adverse effects
The most common are mood changes, headache, nausea, breast tenderness, irregular uterine bleeding and absence of menstruation. Irregular bleeding usually stops on its own if the medicine is continued.
- uncommon: depression, nervousness, drowsiness, dizziness, paraesthesia, migraine, varicose veins, raised blood pressure;
- uncommon in digestion: abdominal pain, vomiting, dyspepsia, flatulence, diarrhoea;
- uncommon in the skin and genital sphere: acne, itching, rash, vaginal candidiasis, pelvic pain, breast enlargement, menstrual cycle disorders, vaginal dryness, reduced libido, weight gain;
- rare: anaemia, thrombocytopenia, allergic reactions, hyperkalaemia, hyponatraemia, insomnia, tachycardia, phlebitis, fainting;
- rare but severe: venous thromboembolism and arterial thromboembolic disorders, including myocardial infarction, stroke and transient ischaemic attack;
- rare: pain in the gallbladder area and cholecystitis, chloasma, eczema, hair loss, erythema nodosum;
- rare in the genital organs: pain during intercourse, vulvovaginitis, ovarian and breast cysts, cervical polyp;
- frequency not known: hypersensitivity, erythema multiforme.
Serious conditions are noted separately: arterial hypertension, liver tumours, acute or chronic liver dysfunction sometimes requiring withdrawal until the parameters normalise, and in women with an inherited predisposition oestrogens may provoke angioedema. Breast cancer is detected somewhat more often in women taking oral contraceptives, but under the age of 40 it is rare, so the absolute increase is small and a causal link has not been established.
Overdose
No cases of overdose with the medicine have been described so far. Judging by general experience with combined oral contraceptives, taking an excessive number of active tablets may cause nausea, vomiting and, in young girls, slight vaginal bleeding.
There is no antidote and treatment is symptomatic. Such a situation usually needs no separate intervention, but it is worth telling the doctor about it in order to establish whether protection against pregnancy has been maintained.
How to get a prescription for Yaz® online
Yaz® is a prescription-only medicine and is prescribed after an assessment of individual risk factors, above all thrombotic ones. During the online consultation the doctor will go through your history, concomitant diseases and the medicines you take and decide whether this product suits you or whether a contraceptive from another group makes more sense.
If there are no contraindications, the doctor will issue an electronic prescription with which the medicine can be collected at a pharmacy, and will explain what to do after a missed tablet and with which symptoms the medicine must be stopped at once.
