Daylla^® (Tablets) Instructions for Use

Marketing Authorization Holder

Gedeon Richter, Ltd. (Hungary)

ATC Code

G03AA12 (Drospirenone and Ethinylestradiol)

Active Substances

Ethinylestradiol (Rec.INN registered by WHO)

Drospirenone (Rec.INN registered by WHO)

Dosage Form

Daylla®

Film-coated tablets, 3 mg+0.02 mg: 21 or 63 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex, with the marking “G73” on one side of the tablet, applied by embossing; the core on the cross-section is white or almost white.

Excipients: lactose monohydrate 48.53 mg, corn starch 16.6 mg, pregelatinized corn starch 9.6 mg, macrogol and polyvinyl alcohol copolymer 1.45 mg, magnesium stearate 0.8 mg.

Film coating composition Opadry II white 85G18490 2 mg: polyvinyl alcohol 0.88 mg, titanium dioxide 0.403 mg, macrogol-3350 0.247 mg, talc 0.4 mg, soy lecithin 0.07 mg.

21 pcs. – blisters (1) made of PVC/PE/PVDC – aluminum foil – cardboard packs.
21 pcs. – blisters (3) made of PVC/PE/PVDC – aluminum foil – cardboard packs.

Clinical-Pharmacological Group

Monophasic oral contraceptive

Pharmacotherapeutic Group

Contraceptive agent (estrogen + progestagen)

Pharmacological Action

The contraceptive effect of Daylla^® is based on the interaction of various factors, the most important of which are inhibition of ovulation and changes in the endometrium.

Daylla^® is a combined oral contraceptive containing Ethinylestradiol and Drospirenone. In therapeutic doses, Drospirenone also has antiandrogenic and weak antimineralocorticoid properties. It is devoid of any estrogenic, glucocorticoid, and antiglucocorticoid activity. This provides drospirenone with a pharmacological profile similar to natural progesterone.

There is evidence of a reduced risk of endometrial and ovarian cancer with the use of combined oral contraceptives.

Pharmacokinetics

Drospirenone

Absorption

When taken orally, Drospirenone is rapidly and almost completely absorbed. After a single oral dose, the maximum serum concentration of drospirenone, equal to 38 ng/ml, is reached within 1-2 hours. Bioavailability ranges from 76 to 85%. Food intake does not affect the bioavailability of drospirenone.

Distribution

After oral administration, the terminal half-life is 31 hours. Drospirenone binds to serum albumin and does not bind to sex hormone-binding globulin (SHBG) or corticosteroid-binding globulin (CBG). 3-5% of the active substance in the serum is present as free steroid. Ethinylestradiol-induced increase in SHBG does not affect the binding of drospirenone to serum proteins. The mean apparent volume of distribution of drospirenone is 3.7±1.2 L/kg.

Metabolism

Drospirenone is extensively metabolized after oral administration. The main metabolites in plasma are the acid forms of drospirenone, derivatives with an open lactone ring, and 4,5-dihydrodrospirenone-3-sulfate, which are formed without the involvement of the cytochrome P450 system. A small amount of drospirenone is metabolized by cytochrome P450 3A4. In vitro, drospirenone inhibits cytochromes P450 3A4, P450 1A1, P450 2C9 and P450 2C19.

Elimination

The metabolic clearance rate of drospirenone in serum is 1.5±0.2 ml/min/kg. Drospirenone is excreted unchanged only in trace amounts. Drospirenone metabolites are excreted by the kidneys and through the intestines in a ratio of approximately 1.2:1.4. The half-life of metabolites excreted by the kidneys and through the intestines is approximately 40 hours.

Steady-state concentration.

The maximum steady-state concentration of drospirenone in serum is reached by day 8 of administration and is approximately 70 ng/ml.

• In renal impairment

The steady-state concentration of drospirenone in serum in women with mild to moderate renal impairment (creatinine clearance CLcr 30-80 ml/min) is comparable to the steady-state concentration in women with normal renal function.

• In hepatic impairment

Drospirenone is well tolerated by patients with mild or moderate hepatic impairment (Child-Pugh class B). The decrease in drospirenone clearance in moderate hepatic impairment does not lead to a significant change in serum potassium concentration. In diabetes and concomitant treatment with spironolactone (two predisposing factors for hyperkalemia), no increase in serum potassium concentration above the upper limit of normal was detected.

Ethinylestradiol

Absorption .

Ethinylestradiol is rapidly and completely absorbed. The maximum concentration of 80-100 pg/ml is reached within 1-2 hours. After presystemic conjugation and presystemic metabolism in the small intestine and liver, the absolute bioavailability is 60%. Concomitant food intake reduces the bioavailability of ethinylestradiol in approximately 25% of women.

Distribution

The serum concentration of ethinylestradiol decreases in two phases, the terminal pharmacokinetic phase is characterized by a half-life of about 24 hours. Ethinylestradiol is strongly but nonspecifically bound to albumin (about 98.5%) and causes an increase in the concentration of SHBG and CBG in the serum. The apparent volume of distribution is approximately 5 L/kg.

Metabolism

Ethinylestradiol undergoes presystemic conjugation in the small intestinal mucosa and in the liver. Ethinylestradiol is primarily metabolized by aromatic hydroxylation to form both free metabolites and conjugates with glucuronic and sulfuric acids.

Ethinylestradiol is completely metabolized. The metabolic clearance rate of ethinylestradiol is 5 ml/min/kg.

Elimination

Ethinylestradiol is practically not excreted unchanged. Ethinylestradiol metabolites are excreted by the kidneys and through the intestines in a ratio of 4:6. The half-life of metabolites is approximately 1 day.

Steady-state concentration

Steady-state concentration is reached during the second half of the treatment cycle.

Indications

• Oral contraception.

ICD codes

Dosage Regimen

How to take Daylla^®

The tablets are taken orally daily, at approximately the same time with a small amount of water, in the order indicated on the blister pack. Take one tablet daily for 21 consecutive days. Each subsequent pack is started after a 7-day break in taking the tablets, during which withdrawal bleeding usually occurs. It usually starts on the 2nd-3rd day after taking the last tablet and may not end before starting a new pack.

How to start taking Daylla^®

• In the absence of taking any hormonal contraceptives (in the previous month), the first tablet from the first pack should be taken on the first day of menstrual bleeding.

• When switching from another combined oral contraceptive, the woman should start taking Daylla^® the day after the usual break in taking or after taking the last tablet of the previous combined oral contraceptive.

When switching from progestogen-only contraceptives (mini-pills, injectable forms, implant) or a progestogen-releasing intrauterine system, a woman can switch from a progestogen mini-pill, implant, or progestogen-releasing intrauterine system on any day – on the day of removal, from an injectable form – from the day the next injection is due. In this case, it is necessary to additionally use a barrier method of contraception during the first 7 days of intake.

After a medical abortion in the first trimester of pregnancy, the 1st tablet can be taken as prescribed by the doctor on the day of termination of pregnancy. If this condition is met, the woman does not need additional means of contraception.

After childbirth or abortion in the second trimester of pregnancy, the woman should be advised to start taking the drug on the 21st-28th day after childbirth or abortion. If intake is started later, it is necessary to additionally use a barrier method of contraception during the first 7 days of taking the tablets. With the onset of sexual activity, pregnancy should be excluded, or the woman should wait for the first menstruation.

Taking missed tablets

If the delay in taking the tablet is less than 12 hours, contraceptive protection is not reduced. The woman should take the tablet as soon as she remembers, the next tablet is taken at the usual time.
If the delay in taking the tablets is more than 12 hours, contraceptive protection may be reduced. In this case, 2 rules should be observed

1. The drug should never be interrupted for more than 7 days.
2. 7 days of continuous tablet intake are required to achieve adequate suppression of the hypothalamic-pituitary-ovarian system.

Recommendations for intake:

Week 1

The woman should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time.

The next tablet is taken at the usual time. Additionally, a barrier method of contraception should be used for the next 7 days. If intercourse took place within the previous 7 days before missing the tablet, the possibility of pregnancy must be considered. The more tablets are missed and the closer this miss is to the 7-day break in taking the drug, the higher the risk of pregnancy.

Week 2

The woman should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time.

The next tablet is taken at the usual time. Provided that the woman has taken the tablets correctly for the 7 days preceding the first missed tablet, there is no need to use additional contraceptive methods. If the woman has missed more than 1 tablet, additional contraceptive methods must be used for the next 7 days.

Week 3

The risk of reduced contraceptive effectiveness increases as the period of placebo tablet use approaches. However, by following the intake regimen, a decrease in contraceptive protection can be avoided. If one of the following options is followed, then there is no need to use additional contraceptive measures, provided that the tablets were taken correctly for 7 days before the first missed tablet. If this is not the case, it is recommended to follow the first of the following options and use additional contraceptive methods for the next 7 days.

1. The woman should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time. The next tablet is taken at the usual time. The intake of tablets from a new pack should be started without a break as soon as the current pack is finished. The woman will probably not have withdrawal bleeding until the end of the second pack, but spotting or withdrawal bleeding may be observed on the days of taking the drug from the second pack.
2. It is also possible to stop taking the tablets from the current pack. In this case, the break in taking the drug can be up to 7 days, including the days of missed tablets; then start taking tablets from the next pack.

If a woman has missed taking tablets, and then does not have withdrawal bleeding during the first normal drug-free interval, pregnancy must be excluded.

Use of the drug in case of gastrointestinal disorder

In case of severe gastrointestinal disorder (vomiting or diarrhea), absorption of the drug may be incomplete, so additional means of contraception must be used.

If vomiting occurs within 3-4 hours after taking an active tablet, an additional tablet from another pack should be taken as soon as possible.

The new tablet should be taken within 12 hours of the usual tablet intake time.

If more than 12 hours have passed, the recommendations regarding missed tablets should be followed.

Taking “missed tablets”

If a woman does not want to change the normal drug intake regimen, she should take, if necessary, an additional tablet (or several tablets) from another pack.

How to delay withdrawal bleeding

To delay the onset of withdrawal bleeding, it is necessary to continue taking the tablets from a new pack of Daylla^® without a break in intake. Delay is possible until the tablets in the second pack are finished. During the extended cycle, spotting or breakthrough uterine bleeding may be noted. Resumption of taking Daylla^® from a new pack should be after the usual 7-day break.

To move the day of the onset of withdrawal bleeding to another day of the week of the usual schedule, the nearest break in taking the tablets should be shortened by as many days as necessary. The shorter the interval, the higher the risk that there will be no withdrawal bleeding, and during the intake of tablets from the second pack, spotting and breakthrough uterine bleeding will be noted (as in the case of delaying the onset of withdrawal bleeding).

Adverse Reactions

The following adverse reactions have been reported during the use of simultaneous administration of drospirenone and ethinylestradiol

Contraindications

• Presence of venous thromboses (deep vein thrombosis, pulmonary embolism), including in history;
• Presence of arterial thromboses (e.g., myocardial infarction) or preceding conditions (e.g., angina pectoris and transient ischemic attack), including in history;
• Complicated valvular heart disease, atrial fibrillation, uncontrolled arterial hypertension;
• Major surgery with prolonged immobilization;
• Smoking (over 35 years of age);
• Hepatic impairment;
• Cerebrovascular diseases, including in history;
• Presence of severe or multiple risk factors for arterial thrombosis: diabetes mellitus with vascular complications; severe arterial hypertension; severe dyslipoproteinemia;
• Hereditary or acquired predisposition to venous or arterial thrombosis, such as resistance to activated protein C (APC), antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant);
• Pancreatitis, including in history, if associated with severe hypertriglyceridemia;
• Severe liver diseases (until liver tests normalize), including in history;
• Severe chronic renal failure or acute renal failure;
• Liver tumors (benign or malignant) currently or in history;
• Hormone-dependent malignant diseases of the genital system (genital organs, mammary glands) or suspicion thereof;
• Vaginal bleeding of unknown origin;
• Migraine with focal neurological symptoms in history;
• Pregnancy or suspicion thereof;
• Lactation period;
• Hypersensitivity to the drug or any of its components;
• Hereditary galactose intolerance, lactase deficiency, glucose-galactose malabsorption. –

With caution

Risk factors for the development of thrombosis and thromboembolism: smoking, obesity, dyslipoproteinemia, controlled arterial hypertension, migraine without focal neurological symptoms, uncomplicated valvular heart defects, hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the immediate relatives); diseases in which peripheral circulation disorders may be noted: diabetes mellitus, systemic lupus erythematosus (SLE), hemolytic-uremic syndrome, Crohn’s disease, ulcerative colitis, sickle cell anemia, superficial phlebitis; hereditary angioedema, hypertriglyceridemia, liver diseases; diseases that first appeared or worsened during pregnancy or during previous use of sex hormones (including jaundice and/or pruritus associated with cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes during pregnancy in history, Sydenham’s chorea, chloasma, postpartum period.

Use in Pregnancy and Lactation

The drug Daylla^® is contraindicated during pregnancy. If a patient becomes pregnant while taking Daylla^®, the drug should be discontinued immediately.

Adverse effects on the course of pregnancy and fetal development cannot be ruled out due to the hormonal action of the active components.

Combined oral contraceptives may reduce the quantity and alter the composition of breast milk. Small amounts of hormonal contraceptives or their metabolites are detected in milk during hormonal contraception and may affect the child. The use of combined oral contraceptives is possible only after complete cessation of breastfeeding.

Use in Hepatic Impairment

Contraindicated in hepatic insufficiency, severe liver diseases (until liver tests normalize), including in the medical history, liver tumors (benign or malignant) currently or in the medical history.

Use in Renal Impairment

Contraindicated in severe chronic renal failure or acute renal failure.

Geriatric Use

Not used.

Special Precautions

Precautions

If any of the conditions/risk factors listed below are currently present, the potential risk and expected benefit of using a combined oral contraceptive should be carefully weighed in each individual case and discussed with the woman before she decides to start taking the drug. In case of worsening, intensification, or first appearance of any of these conditions or risk factors, the woman should consult her doctor, who may decide to discontinue the combined oral contraceptive.

Circulatory system disorders

The frequency of venous thromboembolism (VTE) when using a low-dose estrogen combined oral contraceptive (< 50 mcg ethinylestradiol, such as Daylla^®) is approximately 20 to 40 cases per 100,000 women per year, which is somewhat higher than in women not using hormonal contraceptives (5 to 10 cases per 100,000 women) but lower than in women during pregnancy (60 cases per 100,000 pregnancies).

An additional risk of VTE is noted during the first year of using a combined oral contraceptive. VTE is fatal in 1-2% of cases.

An association has also been identified between the use of combined oral contraceptives and an increased risk of arterial thromboembolism. Extremely rare cases of thrombosis of other blood vessels, for example, hepatic, mesenteric, renal, cerebral and retinal vessels, both arteries and veins, have been described in those taking oral hormonal contraceptives. A causal relationship between the occurrence of these side effects and the use of combined oral contraceptives has not been proven.

Symptoms of venous or arterial thrombosis/thromboembolism of cerebrovascular disease may include

• Unusual unilateral pain and/or swelling of a limb;

• Sudden severe chest pain, with or without radiation to the left arm;

• Sudden shortness of breath;

• Sudden coughing fit;

• Any unusual, severe, prolonged headache; Sudden partial or complete loss of vision; Diplopia;

• Slurred speech or aphasia;

• Dizziness;

• Loss of consciousness with or without a convulsive seizure;

• Weakness or very significant loss of sensation, suddenly appearing in one half or one part of the body;

• Motor disorders;

• “Acute abdomen” syndrome.

The risk of complications associated with VTE when taking combined oral contraceptives increases

• With age;

• In the presence of a family history (venous or arterial thromboembolism in close relatives or parents at a relatively young age); if a hereditary predisposition is suspected, the woman needs a specialist consultation before prescribing a combined oral contraceptive;

• After prolonged immobilization, major surgery, any leg surgery, or extensive trauma. In these situations, it is recommended to stop taking the drug (in the case of planned surgery, at least four weeks before it) and not to resume taking it for two weeks after the end of immobilization. Additionally, antithrombotic therapy may be prescribed if the use of oral hormonal contraceptives was not discontinued within the recommended time frame;

• With obesity (body mass index over 30 kg/m²);

The risk of arterial thrombosis and thromboembolism when taking combined oral contraceptives increases

• With age;

• In smokers (women over 35 years of age are strongly advised not to smoke if they wish to use combined oral contraceptives);

• With dyslipoproteinemia;

• With arterial hypertension;

• With migraine;

• With heart valve diseases;

• With atrial fibrillation.

The presence of one serious risk factor or multiple risk factors for the development of arterial or venous diseases, respectively, may be a contraindication.

Women using combined oral contraceptives should immediately consult a doctor if symptoms of possible thrombosis occur. In cases of suspected thrombosis or confirmed thrombosis, the use of the combined oral contraceptive must be discontinued. An adequate method of contraception must be selected due to the teratogenicity of anticoagulant therapy (coumarins).

The increased risk of thromboembolism in the postpartum period should be taken into account.

Other diseases that are associated with severe vascular pathology include diabetes mellitus, systemic lupus erythematosus, hemolytic-uremic syndrome; chronic inflammatory bowel diseases (Crohn’s disease or ulcerative colitis) and sickle cell anemia.

An increase in the frequency and severity of migraine attacks during the use of combined oral contraceptives (which may precede cerebrovascular disorders) may be grounds for immediate discontinuation of these drugs.

Tumors

The most significant risk factor for cervical cancer is infection with the human papillomavirus. Some epidemiological studies have reported an increased risk of cervical cancer with long-term use of combined oral contraceptives, but there are conflicting opinions regarding the extent to which these findings are related to concomitant factors, such as screening for cervical cancer and the use of barrier contraceptive methods.

There is believed to be a slightly increased relative risk (RR = 1.24) of breast cancer diagnosed in women who were using combined oral contraceptives at the time of the study. The excess risk gradually decreases over the 10 years after stopping combined oral contraceptives. Since breast cancer is rare in women under 40 years of age, the increase in the number of breast cancers diagnosed in recent years in women who have taken or are taking combined oral contraceptives is small relative to the overall risk of breast cancer. These studies do not confirm a causal relationship between the use of combined oral contraceptives and breast cancer. The observed increase in risk may be a consequence of earlier diagnosis of breast cancer in women using combined oral contraceptives, the biological effect of combined oral contraceptives, or a combination of both. Breast cancers in women who had ever used combined oral contraceptives were clinically less pronounced than in women who had never used them.

In rare cases, the development of benign liver tumors has been observed during the use of combined oral contraceptives, and in even rarer cases, malignant ones. In isolated cases, these tumors have caused life-threatening intra-abdominal bleeding. In the differential diagnosis of a liver tumor in a woman taking combined oral contraceptives, the appearance of severe pain in the upper abdomen, liver enlargement, or symptoms of intra-abdominal bleeding should be taken into account.

Other conditions

The progestogen component in Daylla^® is an aldosterone antagonist with potassium-sparing properties. In most cases, no increase in potassium concentration is observed. However, in some patients with mild or moderate renal insufficiency and simultaneous prescription of potassium-sparing drugs when taking drospirenone, the serum potassium concentration increased slightly. Thus, it is recommended to check serum potassium concentration in the first cycle of taking the drug in patients with renal insufficiency and pre-treatment potassium concentrations at the upper limit of normal, as well as with the simultaneous use of drugs that retain potassium in the body.

In women with hypertriglyceridemia or a family history of hypertriglyceridemia, the risk of developing pancreatitis during the use of combined oral contraceptives cannot be ruled out.

Although a slight increase in blood pressure has been described in many women taking combined oral contraceptives, clinically significant increases have been rare. Only in rare cases is immediate discontinuation of combined oral contraceptives necessary. If, during the use of combined oral contraceptives in patients with arterial hypertension, blood pressure values remain persistently elevated or do not decrease with antihypertensive drugs, the use of combined oral contraceptives must be discontinued. If necessary, the use of combined oral contraceptives can be continued if normal blood pressure values are achieved with antihypertensive therapy.

The following conditions develop or worsen both during pregnancy and when taking combined oral contraceptives, but their connection with the use of combined oral contraceptives has not been proven: jaundice, and/or itching associated with cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; Sydenham’s chorea; history of herpes during pregnancy; hearing loss associated with otosclerosis.

In women with hereditary angioedema, exogenous estrogens may cause or worsen symptoms of angioedema.

In acute or chronic liver dysfunction, it may be necessary to discontinue the use of combined oral contraceptives until liver function tests return to normal. Recurrent cholestatic jaundice and/or cholestasis-induced pruritus, which develop for the first time during pregnancy or previous use of sex hormones, require discontinuation of combined oral contraceptives.

Although combined oral contraceptives may affect peripheral insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in patients with diabetes using low-dose combined oral contraceptives (containing < 0.05 mg ethinylestradiol). Nevertheless, women with diabetes should be carefully monitored by a doctor, especially at the beginning of taking combined oral contraceptives.

Worsening of endogenous depression, epilepsy, Crohn’s disease, and ulcerative colitis has also been reported with the use of combined oral contraceptives.

Chloasma may sometimes develop, especially in women with a history of chloasma during pregnancy. Women prone to chloasma while taking combined oral contraceptives should avoid prolonged exposure to the sun and ultraviolet radiation.

The drug Daylla^® contains 48.53 mg of lactose in one tablet. Patients with hereditary galactose intolerance, lactase deficiency, or glucose/galactose malabsorption disorders on a lactose-free diet should not take the drug.

Medical examination/consultation.

Before starting the use of hormonal contraceptives, it is necessary to consult with the attending gynecologist and undergo an appropriate medical examination. Further observation and the frequency of medical examinations are carried out on an individual basis, but at least once every 6 months. Daylla^®, like other combined oral contraceptives, does not protect against HIV infection and other sexually transmitted diseases.

Reduced effectiveness

The effectiveness of combined oral contraceptives may decrease in case of missed tablets, gastrointestinal disorders, or simultaneous use of other medications.

Cycle control

While taking combined oral contraceptives, irregular bleeding (spotting or breakthrough uterine bleeding) may be observed, especially during the first months of use. Therefore, the assessment of any irregular bleeding is significant only after an adaptation period of approximately three cycles.

If irregular bleeding recurs or develops after previous regular cycles, non-hormonal causes should be considered and appropriate diagnostic measures should be taken to rule out malignant neoplasms or pregnancy, including diagnostic curettage.

In some women, withdrawal bleeding may not develop during the break in taking combined oral contraceptives. If combined oral contraceptives were taken according to the instructions for use of the drug, pregnancy is unlikely. However, if combined oral contraceptives were taken irregularly before, or if two consecutive withdrawal bleedings are absent, pregnancy must be ruled out before continuing to take combined oral contraceptives.

Effect on the ability to drive vehicles and mechanisms

The use of the drug Daylla^® does not affect the ability to drive vehicles and other mechanisms.

Overdose

There is no information on overdose. However, nausea, vomiting, spotting or vaginal bleeding may occur. A specific antidote is unknown. Symptomatic treatment should be carried out.

Drug Interactions

Interactions between oral contraceptives and other drugs can lead to breakthrough uterine bleeding and/or reduced contraceptive reliability. The following types of interactions have been described:

Effect on liver metabolism

Some drugs, due to the induction of microsomal enzymes, can increase the clearance of sex hormones (phenytoin, barbiturates, primidone, carbamazepine and rifampicin; oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and the herbal remedy based on St. John’s wort (Hypericum perforatum) may have the same effect.

A possible effect of HIV protease inhibitors (e.g., ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g., nevirapine) and their combinations on liver metabolism has been reported.

Effect on enterohepatic recirculation

Clinical observations show that simultaneous use with some antibiotics, such as penicillins and tetracyclines, reduces the enterohepatic recirculation of estrogens, which can lead to a decrease in the concentration of ethinylestradiol.

Women taking any of the above classes of drugs should use a barrier method of contraception in addition to Daylla^® or switch to any other method of contraception. Women receiving continuous treatment with drugs containing active substances that affect liver microsomal enzymes should additionally use a non-hormonal method of contraception for 28 days after their discontinuation. Women taking antibiotics (other than rifampicin or griseofulvin) should temporarily use a barrier method of contraception in addition to the combined oral contraceptive both during the drug use and for 7 days after its discontinuation. If concomitant use of the drug is started at the end of the Daylla^® package, the next package should be started without the usual break in administration.

The main metabolism of drospirenone in human plasma occurs without the involvement of the cytochrome P450 system. Inhibitors of this enzyme system, therefore, do not affect the metabolism of drospirenone.

Effect of the drug Daylla^® on other drugs.

Oral contraceptives may affect the metabolism of other drugs.

In addition, their concentrations in plasma and tissues may change – both increase (e.g., cyclosporine) and decrease (e.g., lamotrigine).

Based on the results of in vitro inhibition studies and in vivo interaction studies in female volunteers taking omeprazole, simvastatin and midazolam as indicator substrates, an effect of drospirenone at a dose of 3 mg on the metabolism of other active substances is unlikely.

Other interactions

There is a theoretical possibility of an increase in serum potassium concentration in women receiving oral contraceptives simultaneously with other drugs that increase serum potassium concentration: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, some non-steroidal anti-inflammatory drugs (e.g., indomethacin), potassium-sparing diuretics and aldosterone antagonists. However, in a study evaluating the interaction of an ACE inhibitor with the Drospirenone+Ethinylestradiol combination in women with moderate arterial hypertension, no significant difference was found between serum potassium concentrations in women receiving enalapril and placebo.

Laboratory tests

Taking hormonal contraceptives may affect the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function, as well as the concentration of plasma transport proteins such as corticosteroid-binding globulin and lipid/lipoprotein fractions, parameters of carbohydrate metabolism, blood coagulation and fibrinolysis. Changes usually occur within laboratory norms.

Due to its slight antimineralocorticoid activity, Drospirenone increases renin activity and plasma aldosterone concentrations.

Storage Conditions

In a place protected from light at a temperature not exceeding 25°C (77°F). Keep out of reach of children!

Shelf Life

The shelf life is 2 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.