Femoden^® (Tablets) Instructions for Use

Marketing Authorization Holder

Bayer, AG (Germany)

Manufactured By

Bayer Weimar, GmbH & Co. KG (Germany)

ATC Code

G03AA10 (Gestodene and Ethinylestradiol)

Active Substances

Ethinylestradiol (Rec.INN registered by WHO)

Gestodene (Rec.INN registered by WHO)

Dosage Form

Femoden®

Film-coated tablets, 75 mcg+30 mcg: 21 or 63 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white in color, round in shape.

Excipients: lactose monohydrate, corn starch, povidone 25 thousand, sodium calcium edetate, magnesium stearate.

Shell composition sucrose, povidone 700 thousand, macrogol 6000, calcium carbonate, talc, glycol mountain wax.

21 pcs. – blisters (1) – cardboard packs with first opening control.
21 pcs. – blisters (3) – cardboard packs with first opening control.

Clinical-Pharmacological Group

Monophasic oral contraceptive

Pharmacotherapeutic Group

Combined contraceptive agent (estrogen + gestagen)

Pharmacological Action

Combined oral hormonal contraceptive agent.

The gestagenic component is a derivative of 19-nortestosterone – Gestodene, which exceeds in strength and selectivity of action not only the natural corpus luteum hormone progesterone but also other synthetic gestagens (for example, levonorgestrel). Due to its high activity, Gestodene is used in low doses, in which it does not exhibit androgenic properties and practically does not affect lipid and carbohydrate metabolism.

The estrogenic component of the combination is Ethinylestradiol – a synthetic analogue of the follicular hormone estradiol, which, together with the corpus luteum hormone, regulates the menstrual cycle.

Along with the indicated central and peripheral mechanisms that prevent the maturation of a fertilizable egg, the contraceptive effect is due to a decrease in the susceptibility of the endometrium to the blastocyst, as well as an increase in the viscosity of the mucus located in the cervix, which makes it relatively impenetrable to spermatozoa.

Pharmacokinetics

Gestodene

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract. After a single dose, C_max is noted after 1 hour and is 2-4 ng/ml. Bioavailability is about 99%. Gestodene binds to albumin and sex hormone-binding globulin (SHBG). 1-2% is in plasma in free form, 50-75% is specifically bound to SHBG. An increase in the level of SHBG in the blood, caused by ethinylestradiol, affects the level of gestodene: the fraction bound to SHBG increases and the fraction bound to albumin decreases. The average V_d is 0.7-1.4 l/kg. The pharmacokinetics of gestodene depends on the level of SHBG. The concentration of SHBG in blood plasma under the influence of estradiol increases by 3 times. With daily intake, the concentration of gestodene in blood plasma increases by 3-4 times and reaches a state of saturation in the second half of the cycle. It is metabolized in the liver. The average plasma clearance is 0.8-1.0 ml/min/kg. The concentration of gestodene in blood serum decreases in two phases. T_1/2 in the β-phase is 12-20 hours. Gestodene is excreted only in the form of metabolites, 60% in the urine, 40% in the feces. T_1/2 of metabolites is about 1 day.

Ethinylestradiol

After oral administration, Ethinylestradiol is rapidly and completely absorbed. C_max in blood serum, equal to approximately 65 pg/ml, is achieved in 1-2 hours. During absorption and the “first pass” through the liver, Ethinylestradiol is metabolized, as a result of which its oral bioavailability averages about 45%. Ethinylestradiol is almost completely (approximately 98%), although non-specifically, bound to albumin. Ethinylestradiol induces the synthesis of SHBG. The apparent V_d of ethinylestradiol is 2.8-8.6 l/kg. It undergoes presystemic conjugation, both in the small intestinal mucosa and in the liver. The main metabolic pathway is aromatic hydroxylation. The plasma clearance rate is 2.3-7 ml/min/kg. The decrease in the concentration of ethinylestradiol in the blood serum is biphasic; T_1/2 in the first phase is about 1 hour, in the second phase – 10-20 hours. It is not excreted from the body unchanged. Metabolites of ethinylestradiol are excreted in urine and bile in a ratio of 4:6 with T_1/2 of about 24 hours.

Indications

Oral contraception.

ICD codes

Dosage Regimen

Take one tablet daily at approximately the same time, with a small amount of water.

Follow the blister pack direction arrows. Start with the tablet marked with the correct day of the week or the first tablet of the pack.

Take tablets for 21 consecutive days, followed by a 7-day tablet-free interval. Withdrawal bleeding usually occurs during this break.

Start the next pack on the 8th day after the last tablet from the previous pack, even if bleeding has not finished.

For the first cycle, start taking Femoden on the first day of your menstrual period for immediate contraceptive protection.

If starting after day 1 of menstruation, use an additional barrier method of contraception for the first 7 days of tablet-taking.

If a tablet is taken more than 12 hours late, contraceptive reliability may be reduced. Take the missed tablet as soon as remembered and the next tablet at the usual time.

Use a non-hormonal backup contraceptive method for the next 7 days if the delay exceeds 12 hours. Consult your physician if more than one tablet is missed from the active group.

In case of vomiting or diarrhea within 3-4 hours of taking a tablet, handle it as a missed tablet.

Do not discontinue tablets without medical advice. The regimen remains the same regardless of the occurrence or absence of withdrawal bleeding.

Adverse Reactions

From the cardiovascular system arterial hypertension; rarely – arterial and venous thromboembolism (including myocardial infarction, stroke, deep vein thrombosis of the lower extremities, pulmonary embolism); very rarely – arterial or venous thromboembolism of the hepatic, mesenteric, renal, retinal arteries and veins.

From the senses hearing loss due to otosclerosis.

From the reproductive system acyclic bleeding/vaginal spotting, amenorrhea after drug withdrawal, change in the condition of vaginal mucus, development of inflammatory processes of the vagina, candidiasis, tension, pain, breast enlargement, galactorrhea.

From the digestive system epigastric pain, nausea, vomiting, Crohn’s disease, ulcerative colitis, occurrence or exacerbation of jaundice and/or itching associated with cholestasis, cholelithiasis, hepatitis, liver adenoma.

From the skin and its appendages: erythema nodosum, exudative erythema, rash, chloasma, increased hair loss.

From the nervous system headache, migraine, mood lability, depression.

From the senses hearing loss, increased sensitivity of the cornea (when wearing contact lenses).

From the metabolism fluid retention in the body, change (increase) in body weight, decreased carbohydrate tolerance, hyperglycemia, increased TG levels.

Other: allergic reactions, hemolytic-uremic syndrome, porphyria; rarely – exacerbation of reactive systemic lupus erythematosus; very rarely – Sydenham’s chorea.

Contraindications

Presence of risk factors for venous thromboembolism; presence of risk factors for arterial thromboembolism; severe liver disease (including history) until liver function tests normalize; liver tumor (including history); severe chronic renal failure or acute renal failure; known or suspected hormone-dependent malignant tumors (including genital organs or breast); vaginal bleeding of unknown etiology; pregnancy; lactation period (breastfeeding).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and during the lactation period (breastfeeding).

Special Precautions

The benefits of hormonal contraception should be assessed individually for each woman and discussed with her before starting the use of hormonal contraceptives.

Combined hormonal contraceptives, including fixed combinations of Gestodene/Ethinylestradiol, should be used with caution in conditions that increase the risk of venous or arterial thrombosis/thromboembolism: age over 35 years, smoking, hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the immediate relatives), hemolytic-uremic syndrome, hereditary angioedema, liver diseases, diseases that first appeared or worsened during pregnancy or against the background of previous use of sex hormones (including porphyria, herpes of pregnancy, minor chorea, Sydenham’s chorea, chloasma), obesity (BMI over 30 kg/m²), dyslipoproteinemia, arterial hypertension, migraine, epilepsy, valvular heart disease, atrial fibrillation, prolonged immobilization, extensive surgical intervention, surgical intervention on the lower extremities, severe trauma, varicose veins and superficial thrombophlebitis, postpartum period (non-breastfeeding women /21 days after childbirth/; breastfeeding women after completion of the lactation period), presence of severe depression, (including history), changes in biochemical parameters (activated protein C resistance, hyperhomocysteinemia, antithrombin III deficiency, protein C or S deficiency, antiphospholipid antibodies, including antibodies to cardiolipin, lupus anticoagulant), diabetes mellitus, uncomplicated by vascular disorders, SLE, Crohn’s disease, ulcerative colitis, sickle cell anemia, hypertriglyceridemia (including family history), acute and chronic liver diseases.

In case of suspected or established venous or arterial thromboembolism, the use of combined hormonal contraceptives must be discontinued. In case of initiation of anticoagulant therapy, adequate alternative contraception should be initiated to avoid the teratogenic effect of anticoagulant therapy (coumarins).

The use of any combined oral contraceptive increases the risk of venous thromboembolism.

The results of epidemiological studies have linked the use of combined hormonal contraceptives with an increased risk of arterial thromboembolism (myocardial infarction) or cerebrovascular accident (for example, transient ischemic attack, stroke). Arterial thromboembolic complications can be fatal.

Some epidemiological studies have noted an increased risk of developing cervical cancer in women receiving combined oral contraceptives for more than 5 years. However, there is no consensus on the degree of influence of sexual behavior and other factors, such as the human papillomavirus, on this disease.

In women with hypertriglyceridemia or a hereditary predisposition to it, the risk of pancreatitis may be increased when taking combined oral contraceptives.

Although a slight increase in blood pressure was noted in many women taking combined oral contraceptives, clinically significant increases occurred rarely. Only in these rare cases is immediate discontinuation of combined oral contraceptives justified. If, when taking combined oral contraceptives, blood pressure constantly increases in patients with concomitant arterial hypertension or significantly increased pressure cannot be corrected with antihypertensive drugs, the use of combined oral contraceptives should be discontinued. After normalization of blood pressure with antihypertensive drugs, the use of combined oral contraceptives can be resumed.

During the use of combined oral contraceptives, exacerbation of endogenous depression, epilepsy, Crohn’s disease and ulcerative colitis was observed.

Drug Interactions

Interaction with drugs that induce microsomal enzymes of the cytochrome P450 system is possible, which may increase the clearance of sex hormones, which, in turn, can lead to acyclic “breakthrough” uterine bleeding and/or a decrease in the contraceptive effect.

Substances that increase the clearance of the fixed combination Gestodene/Ethinylestradiol (reduction in effectiveness due to induction of liver enzymes): barbiturates, bosentan, carbamazepine, phenytoin, primidone, rifampicin, drugs for the treatment of HIV – ritonavir, nevirapine, efavirenz and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and preparations containing St. John’s wort (Hypericum perforatum).

When used concomitantly with the fixed combination Gestodene/Ethinylestradiol, many HIV or hepatitis C virus protease inhibitors and non-nucleoside reverse transcriptase inhibitors can either increase or decrease the plasma concentrations of the hormonal components of the combination. In some cases, this effect may be clinically significant.

When using the fixed combination Gestodene/Ethinylestradiol concomitantly with perampanel, vemurafenib, dabrafenib, modafinil or rufinamide, the possibility of reduced contraceptive efficacy due to accelerated metabolism of sex hormones should be considered. It is recommended to use additional methods of contraception (intrauterine devices or condoms) throughout the entire course of concomitant use of the drugs and for 2-6 months after its discontinuation.

Strong and moderate inhibitors of the CYP3A4 isoenzyme, such as azole derivatives of antifungal agents (for example, itraconazole, voriconazole, fluconazole), verapamil, macrolides (for example, clarithromycin, erythromycin), diltiazem and grapefruit juice may increase the plasma concentrations of estrogen or gestagen, or both.

NSAIDs reduce the effectiveness of the fixed combination Gestodene/Ethinylestradiol.

Combined oral contraceptives can affect the metabolism of other drugs, so their concentrations in blood plasma and tissues may increase (for example, cyclosporine) or decrease (for example, lamotrigine).

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.