Erika-35 (Tablets) Instructions for Use

Marketing Authorization Holder

Mylan Laboratories, Limited (India)

ATC Code

G03HB01 (Cyproterone and estrogens)

Active Substances

Cyproterone (Rec.INN registered by WHO)

Ethinylestradiol (Rec.INN registered by WHO)

Dosage Form

Erika-35

Film-coated tablets, 2 mg+0.035 mg: 21 or 63 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets yellow-orange in color, round, biconvex; the appearance of the tablet on the cross-section is a core of white or almost white color.

Excipients: granulated lactose – 53.373 mg, anhydrous colloidal silicon dioxide – 0.15 mg, colloidal aluminum dioxide – 0.04 mg, povidone K-25 – 2 mg, sodium carboxymethyl starch (type A) – 1.2 mg, magnesium stearate – 1.16 mg.

Composition of the sugar coating povidone K-90 – 0.495 mg, talc – 6.613 mg, glycerol – 0.24 mg, sucrose – 10.941 mg, calcium carbonate – 1.329 mg, macrogol 6000 – 0.185 mg, titanium dioxide – 0.167 mg, iron oxide red dye – 0.006 mg, iron oxide yellow dye – 0.024 mg, carnauba wax – 0.002 mg.

21 pcs. – blisters (1) – cardboard packs.
21 pcs. – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Monophasic oral contraceptive with antiandrogenic properties

Pharmacotherapeutic Group

Combined contraceptive agent (estrogen + antiandrogen)

Pharmacological Action

A low-dose monophasic oral combined hormonal contraceptive with antiandrogenic properties, the mechanism of action of which is manifested in the inhibition of the gonadotropic function of the pituitary gland and suppression of ovulation, as well as a change in the properties of cervical secretion, as a result of which it becomes impermeable to spermatozoa.

In women taking combined oral contraceptives (COCs), the cycle becomes more regular, the pain and intensity of menstrual-like bleeding decrease, thereby reducing the risk of iron deficiency anemia. In addition, there is evidence that the risk of developing endometrial cancer and ovarian cancer is reduced.

Cyproterone acetate, being a competitive antagonist of androgen receptors, inhibits the synthesis of androgens and reduces their concentration in the blood due to an antigonadotropic effect. The antigonadotropic effect of cyproterone acetate is enhanced by ethinylestradiol, which also regulates the synthesis of sex hormone-binding globulin (SHBG) in the blood plasma. Taking this into account, the concentration of unbound, biologically available androgen in the blood decreases. Against the background of taking the drug Erika-35, the increased secretion of the sebaceous glands, which contributes to the occurrence of acne and seborrhea, decreases. The disappearance of acne usually occurs after 3-4 months of therapy. Hair loss, often accompanying seborrhea, also decreases during the same treatment period. The use of the drug Erika-35 reduces mild manifestations of hirsutism (in particular, excessive facial hair growth) in women of reproductive age. But this effect occurs after longer treatment.

Along with the antiandrogenic action described above, cyproterone acetate has a progestogenic action.

Pharmacokinetics

Cyproterone acetate

Absorption

After oral administration, cyproterone acetate is rapidly and completely absorbed. Its C_max in blood plasma is 15 ng/ml and is reached 1.6 h after a single application. The absolute bioavailability of cyproterone acetate is approximately 88%.

Distribution

Cyproterone acetate is almost completely bound to albumin in blood plasma. Only 3.5-4% of the total concentration of cyproterone acetate remains unbound. The ethinylestradiol-induced increase in SHBG concentration does not affect the binding of cyproterone acetate to plasma proteins. During cyclic use, the maximum C_ss of cyproterone acetate in blood plasma is achieved in the second half of the cycle.

Metabolism

Cyproterone acetate is almost completely metabolized by hydroxylation and conjugation. The main metabolite in blood plasma is the 15β-hydroxy derivative. The plasma clearance rate is approximately 3.6 ml/min/kg.

Excretion

The concentration of cyproterone acetate in the blood serum decreases in two phases, with T_1/2 of 0.8 h and 2.3-3.3 days. Some part of the dose is excreted unchanged. Metabolites are excreted by the kidneys and through the intestine in a ratio of 1:2. The T_1/2 of metabolites is 1.8 days. Given the long T_1/2 of cyproterone acetate from plasma, its accumulation in plasma can be observed during one therapy cycle with a factor of 2-2.5.

Ethinylestradiol

Absorption

When taken orally, Ethinylestradiol is rapidly and completely absorbed. C_max in blood plasma, which is approximately 71 pg/ml, is reached after 1.6 h. During absorption and the “first pass” through the liver, ethinylestradiol is metabolized, resulting in its bioavailability of about 45% when taken orally.

Distribution

Ethinylestradiol binds to albumin (approximately 98%) and induces an increase in the concentration of SHBG in blood plasma. C_ss is achieved in the second half of the intake cycle, when the concentration of the active substance in the blood serum is 60% higher compared to a single dose.

Metabolism

Ethinylestradiol undergoes presystemic conjugation, both in the small intestinal mucosa and in the liver. It is metabolized mainly by aromatic hydroxylation, resulting in a large number of hydroxylated and methylated metabolites, both free and conjugates with glucuronides and sulfates. The plasma clearance rate is 2.37 ml/min/kg.

Excretion

The concentration of ethinylestradiol in the blood serum decreases in 2 phases with T_1/2 of approximately 1 h and 10-20 h, respectively. Ethinylestradiol is not excreted from the body unchanged; its metabolites are excreted by the kidneys and through the intestine in a ratio of 4:6. The T_1/2 of metabolites is approximately 24 h.

Indications

• Contraception in women with signs of androgenization;
• Treatment of androgen-dependent diseases in women: moderate acne (especially widespread forms and forms accompanied by seborrhea, inflammation or the formation of papulopustular or nodulocystic acne), androgenic alopecia and mild forms of hirsutism.

ICD codes

Dosage Regimen

The tablets should be taken orally in the order indicated on the package, daily at approximately the same time, with a small amount of water.

Take 1 tab./day continuously for 21 days. Taking tablets from the next package should be started after a 7-day break in taking the tablets, during which a withdrawal menstrual-like bleeding usually occurs, which, as a rule, begins on the 2-3rd day after taking the last tablet and may not end before starting to take tablets from a new package.

The drug Erika-35 should be taken regularly to ensure effective contraception and achieve a therapeutic effect. If any other hormonal contraceptive was used before starting Erika-35, its use should be discontinued. The dosage regimen of Erika-35 coincides with the dosage regimen of most other oral hormonal contraceptives.

Irregular use of the drug can lead to acyclic bleeding, reduced contraceptive effectiveness and therapeutic effect.

Starting Erika-35

If no hormonal contraceptives were taken in the previous month, taking Erika-35 should be started on the 1st day of the menstrual cycle (i.e., on the 1st day of menstrual bleeding). It is allowed to start taking on the 2nd-5th day of the menstrual cycle, but in this case, it is recommended to additionally use a barrier method of contraception during the first 7 days of taking tablets from the first package.

Switching from other COCs, vaginal ring or contraceptive patch

It is preferable to start taking Erika-35 on the day after taking the last hormonal tablet from the previous package, but in no case later than the next day after the usual 7-day break (for preparations containing 21 tablets) or after taking the last inactive tablet (for preparations containing 28 tablets per package). Taking Erika-35 should be started on the day of removal of the vaginal ring or patch, but no later than the day when a new ring should be inserted or a new patch should be applied.

Switching from progestogen-only contraceptives (mini-pills, injectable forms, implant) or from a progestogen-releasing intrauterine contraceptive

You can switch from mini-pills to taking Erika-35 on any day (without a break), from an implant or an intrauterine contraceptive with a progestogen – on the day of its removal, from an injectable form – from the day when the next injection should be made. In all cases, it is necessary to additionally use a barrier method of contraception during the first 7 days of taking the tablets.

After a first trimester abortion

A woman can start taking the drug immediately – on the day of the abortion. If this condition is met, the woman does not need additional contraception.

After childbirth or a second trimester abortion

Taking the drug should be started no earlier than 21-28 days after childbirth or a second trimester abortion. It is possible to start using the drug at this time and after childbirth – in the absence of breastfeeding. If the intake is started later, it is necessary to additionally use a barrier method of contraception during the first 7 days of taking the tablets. However, if the woman has already been sexually active, pregnancy must be ruled out before starting the drug or it is necessary to wait for the first menstruation.

Taking missed tablets

If the delay in taking the drug was less than 12 hours, contraceptive protection is not reduced. The woman should take the tablet as soon as possible, the next tablet is taken at the usual time. If the delay in taking the tablets was more than 12 hours, contraceptive protection may decrease. The more tablets are missed and the closer the miss is to the 7-day break in taking the tablets, the greater the likelihood of pregnancy. In this case, the following two basic rules can be followed

1) taking 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 regulation.

Accordingly, the following recommendations can be given if the delay in taking the tablets was more than 12-36 hours

• First week of taking the drug – the woman should take the last missed tablet as soon as possible, 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 (for example, a condom) should be used for the next 7 days. If sexual intercourse took place during the week before missing the tablet, the possibility of pregnancy must be considered;
• Second week of taking the drug – the woman should take the last missed tablet as soon as possible, 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 7 days preceding the first missed tablet, there is no need to use additional contraceptive measures. Otherwise, as well as if two or more tablets are missed, it is necessary to additionally use barrier methods of contraception (for example, a condom) for 7 days;
• Third week of taking the drug – the risk of pregnancy increases due to the upcoming break in taking the tablets, however, if all tablets were taken correctly during the 7 days preceding the first missed tablet, there is no need to use additional contraceptive methods.

It is necessary to strictly adhere to one of the following two options

1. The woman should take the last missed tablet as soon as possible, as soon as she remembers (even if this means taking two tablets at the same time). The next tablets are taken at the usual time until the tablets from the current package run out. The next package should be started immediately. Withdrawal bleeding is unlikely until the second package is finished, but spotting and breakthrough bleeding may be noted while taking the tablets.

2. The woman can also stop taking the tablets from the current package. Then she should take a break for 7 days, including the day of missing the tablet, and then start taking tablets from a new package. If a woman missed taking tablets and then during the break she does not have withdrawal bleeding, pregnancy must be ruled out.

Recommendations in case of gastrointestinal disorders

If vomiting or diarrhea occurs within 4 hours after taking the tablet, absorption may be incomplete, and accordingly, additional measures to prevent unwanted pregnancy should be taken. In such cases, one should be guided by the above recommendations for missed tablets.

Changing the day of the start of menstrual-like bleeding

In order to delay the onset of withdrawal bleeding, the woman should continue taking tablets from the new package of Erika-35 immediately after all tablets from the previous package have been taken, without a break in taking. Tablets from this package can be taken for as long as necessary (including until the package runs out). While taking the drug from the second package, the woman may experience spotting or breakthrough uterine bleeding. Resumption of taking the drug from a new pack should be after the usual 7-day break.

In order to move the day of the start of menstrual-like bleeding to another day of the week, it is necessary to shorten the nearest break in taking the tablets by as many days as necessary. The shorter the interval, the higher the risk that the woman will not have withdrawal bleeding, and subsequently spotting and breakthrough bleeding will be noted while taking tablets from the second package (as in the case of delaying bleeding).

Duration of drug use

The duration of taking Erika-35 depends on the need for contraception and the severity of androgenization symptoms. Basically, the drug is taken for several months. The effectiveness of the effect on acne and seborrhea usually occurs faster than the effect on hirsutism and alopecia. The drug should be continued for at least another 3-4 courses after the signs of hyperandrogenization have disappeared. If the disease recurs after a few weeks or months after stopping the tablets, treatment with Erika-35 can be resumed. In case of resumption of taking the drug (after a break of 4 weeks or more), the increased risk of venous thromboembolism (VTE) should be taken into account.

Use of the drug in special groups of patients

The drug Erika-35 can be used in adolescents only after the onset of regular menstrual cycles after menarche.

The drug Erika-35 is not indicated for use after menopause.

The drug Erika-35 is contraindicated in patients with severe liver diseases until liver function tests return to normal.

The drug Erika-35 has not been specifically studied in patients with impaired renal function. The available data do not suggest a change in treatment in such patients.

Adverse Reactions

The frequency of occurrence of side effects was classified as follows: common (≥1/100), uncommon (≥1/1000 and <1/100), rare (<1/1000).

From the organ of vision rare – contact lens intolerance.

From the digestive system common – nausea, abdominal pain; uncommon – vomiting, diarrhea.

From the immune system rare – hypersensitivity reactions.

From metabolism common – weight gain; uncommon – fluid retention; rare – weight loss.

From the CNS common – headache; uncommon – migraine.

Mental disorders common – decreased/mood swings; uncommon – decreased libido; rare – increased libido.

From the reproductive system and mammary glands common – breast pain/engorgement, vaginal bleeding/spotting (in the first three cycles of taking the tablets); uncommon – breast enlargement; rare – vaginal discharge, nipple discharge.

From the skin and its appendages uncommon – rash, urticaria; rare – erythema nodosum, erythema multiforme.

The following side effects have been reported during the use of COCs (which include the drug Erika-35)

• Thrombosis or thromboembolism (including myocardial infarction, stroke, deep vein thrombosis, pulmonary embolism, thrombosis or thromboembolism of hepatic, mesenteric, renal arteries and veins, retinal arteries);
• Arterial hypertension;
• Visual impairment;
• Dizziness;
• Pancreatitis;
• Cholecystitis;
• Hyperglyceridemia;
• Impaired glucose tolerance;
• Changes in liver function tests;
• Crohn’s disease and ulcerative colitis;
• Hormone-dependent tumors;
• Liver tumors (benign and malignant);
• Chloasma (especially in case of a history of chloasma during pregnancy);
• Acyclic spotting, more often in the first months of taking the drug;
• Onset or exacerbation of jaundice and/or pruritus associated with cholestasis, cholelithiasis, porphyria, systemic lupus erythematosus (SLE), hemolytic-uremic syndrome, Sydenham’s chorea, herpes in pregnancy, hearing loss due to otosclerosis, cervical cancer;
• Worsening of symptoms of hereditary angioedema.

Contraindications

The drug Erika-35 is contraindicated in the presence of any of the conditions/diseases listed below. If any of these conditions develop for the first time while taking the drug, it should be discontinued immediately.

• Current or history of thromboses (venous and arterial) and thromboembolism (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);
• Current or history of conditions preceding thrombosis (including transient ischemic attacks, angina pectoris);
• Identified predisposition to venous or arterial thrombosis, including resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant);
• History of migraine with focal neurological symptoms;
• Diabetes mellitus with diabetic angiopathy;
• Multiple or severe risk factors for venous or arterial thrombosis, including vascular, cerebral or coronary artery disease, uncontrolled arterial hypertension, complicated heart valve lesions, pulmonary hypertension, atrial fibrillation, subacute bacterial endocarditis, major surgical intervention with prolonged immobilization, extensive trauma, obesity (body mass >30 kg/m²);
• Current or history of pancreatitis with severe hypertriglyceridemia;
• Severe liver diseases (until liver function test parameters normalize and for three months after these parameters return to normal);
• Current or history of liver tumors (benign or malignant);
• Identified hormone-dependent malignant diseases (including of the genital organs or mammary glands) or suspicion thereof;
• Vaginal bleeding of unknown origin;
• Pregnancy or suspected pregnancy;
• Period of lactation (breastfeeding);
• Smoking at the age of 35 years and older;
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• Hypersensitivity to the drug components.

With caution

If any of the conditions/diseases listed below are currently present, the potential risk and expected benefit of using COCs should be carefully weighed in each individual case

• Risk factors for thrombosis and thromboembolism: smoking; thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the immediate relatives; obesity; dyslipoproteinemia; arterial hypertension; migraine (without focal neurological symptoms); heart valve diseases; cardiac rhythm disorders; prolonged immobilization; major surgical interventions; age over 35 years in non-smoking women; smoking at any age, varicose veins and superficial thrombophlebitis, porphyria, postpartum period in non-breastfeeding women;
• Other diseases in which peripheral circulatory disorders may be noted: diabetes mellitus without vascular involvement; systemic lupus erythematosus (SLE); hemolytic-uremic syndrome; Crohn’s disease and ulcerative colitis; sickle cell anemia; congenital hyperbilirubinemias (Gilbert’s syndrome, Dubin-Johnson syndrome, Rotor syndrome);
• Hypertriglyceridemia;
• Superficial vein phlebitis;
• Liver diseases with normal liver function test parameters;
• Diseases that first occurred or worsened during pregnancy or during previous use of sex hormones (e.g., jaundice, cholestasis, gallbladder diseases, otosclerosis with hearing impairment, history of herpes in pregnancy, Sydenham’s chorea).

Use in Pregnancy and Lactation

The drug Erika-35 is contraindicated during pregnancy and the period of breastfeeding.

If pregnancy is detected while taking Erika-35, the drug should be discontinued immediately.

Cyproterone acetate passes into breast milk, therefore the use of Erika-35 is contraindicated during breastfeeding.

Use in Hepatic Impairment

The drug Erika-35 is contraindicated in patients with severe liver diseases until liver function parameters normalize.

Use in Renal Impairment

The drug Erika-35 has not been specifically studied in patients with renal impairment. Available data do not suggest a change in treatment for such patients.

Pediatric Use

The drug Erika-35 can be used in adolescents only after the onset of regular menstrual cycles following menarche.

Geriatric Use

The drug Erika-35 is not indicated for use after menopause.

Special Precautions

Medical examinations

Before starting or resuming the use of Erika-35, it is necessary to review the patient’s life history, family history, perform a thorough general medical (including measurement of blood pressure, heart rate, determination of body mass index) and gynecological examination, including breast examination and cytological examination of a cervical smear (Pap test), and rule out pregnancy. In addition, blood clotting system disorders should be ruled out. The scope of additional tests and the frequency of follow-up examinations is determined individually. Usually, follow-up examinations should be performed at least once every 6 months. The woman should be informed that Erika-35 does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

If a woman has recently developed hirsutism and it is significantly pronounced, a differential diagnosis should be performed to identify the possible cause of the disease (androgen-producing tumor, adrenal hormone deficiency). If any of the specified conditions, diseases and risk factors are currently present, then the potential risk and expected benefit of using COCs should be carefully weighed in each individual case and discussed with the woman before she decides to start taking the drug. If risk factors worsen, intensify, or first appear, discontinuation of the drug may be required.

Cardiovascular system diseases

There is evidence of an increased incidence of venous and arterial thromboses and thromboembolisms (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke) when taking COCs.

The risk of developing venous and arterial thromboembolic complications is highest during the first year of taking such drugs. An increased risk exists during initial use of COCs or resumption of use of the same or different COCs (after a break in taking the drug of 4 weeks or more).

Data from a large prospective study involving 3 groups of women show that this increased risk is present mainly during the first 3 months.

The overall risk of venous and arterial thromboembolic complications in women taking low-dose COCs (<50 mcg ethinylestradiol) is 2-3 times higher than in women who do not take COCs and are not pregnant, and it remains lower compared to the risk of thromboembolic complications during pregnancy and childbirth.

Very rarely, VTE can lead to disability or death.

Thromboembolic complications can occur with the use of any COCs.

Extremely rarely, when using COCs, thrombosis of other blood vessels occurs, for example, hepatic, cerebral or retinal veins or arteries, mesenteric, renal vessels. There is no consensus regarding the connection between the occurrence of these events and the use of COCs.

Symptoms of deep vein thrombosis include: swelling of the lower limb or along a vein in the lower limb, pain or tenderness in the lower limb only when standing or walking, a feeling of warmth in the lower limb, redness or discoloration of the skin of the lower limb.

Symptoms of pulmonary embolism include: sudden shortness of breath or rapid breathing; sudden cough, including with hemoptysis; acute chest pain that may worsen with deep breathing; feeling of anxiety; severe dizziness; rapid heartbeat; cardiac arrhythmia.

Arterial thromboembolism can lead to stroke, vascular occlusion, or myocardial infarction. Symptoms of stroke: sudden weakness or loss of sensation in the face, limbs, especially on one side; sudden confusion; disorientation and dysarthria; sudden complete or partial loss of vision; sudden gait disturbance; dizziness; impaired coordination of movements; sudden severe or prolonged headache for no apparent reason; loss of consciousness or fainting with or without an epileptic seizure.

Other signs of vascular occlusion: sudden pain, swelling and slight blueness of the extremities, “acute abdomen” symptom complex.

Symptoms of myocardial infarction: pain, discomfort, feeling of heaviness, squeezing or fullness in the chest, arm or behind the breastbone; discomfort radiating to the back, jaw, larynx, arm, stomach; cold sweat; nausea, vomiting; dizziness; severe weakness; feeling of anxiety; shortness of breath; rapid heartbeat; cardiac arrhythmia.

Arterial thromboembolism can be fatal.

The risk of thrombosis (venous and/or arterial) and thromboembolism increases

• With age;
• In smokers (with an increase in the number of cigarettes or increasing age, the risk further increases, especially in women over 35 years old);

In the presence of

• Family history (i.e., venous or arterial thromboembolism in close relatives or parents at a relatively young age). In case of hereditary predisposition, the woman should be examined by an appropriate specialist to decide on the possibility of taking COCs;
• Obesity (BMI >30 kg/m²);
• Prolonged immobilization, major surgical interventions, any surgery on the lower limbs or extensive trauma. In these situations, it is necessary to discontinue the use of COCs (in case of planned surgery, at least 4 weeks before it) and not resume intake for 2 weeks after the end of immobilization;
• Dyslipoproteinemia;
• Arterial hypertension;
• Migraine;
• Heart valve diseases;
• Atrial fibrillation.

The question of the possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial.

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

Peripheral circulatory disorders can also be observed in diabetes mellitus, SLE, 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 COCs (which may precede cerebrovascular disorders) should be the basis for immediate discontinuation of these drugs.

Biochemical indicators indicating a hereditary or acquired predisposition to venous or arterial thrombosis include: resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

When assessing the risk-benefit ratio, it should be taken into account that adequate treatment of the corresponding condition can reduce the associated risk of thrombosis. It should also be taken into account that the risk of thrombosis and thromboembolism during pregnancy is higher than when taking low-dose oral contraceptives (<50 mcg ethinylestradiol).

Tumors

There are reports of a slight increase in the risk of developing cervical cancer with long-term use of COCs. However, a connection with taking COCs has not been proven. Controversy remains regarding the extent to which these data are related to cervical pathology or sexual behavior characteristics (less frequent use of barrier contraceptive methods). The most significant risk factor for cervical cancer is persistent papillomavirus infection.

A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of breast cancer diagnosed in women currently taking COCs (relative risk 1.24). The increased risk gradually disappears within 10 years after stopping these drugs. Since breast cancer is rare in women under 40 years of age, the increase in the number of breast cancer diagnoses in women currently taking or recently taking COCs is insignificant relative to the overall risk of this disease. The relationship between the development of breast cancer and taking COCs has not been proven. The observed increase in risk may also be a consequence of careful monitoring and earlier diagnosis of breast cancer in women using COCs. In women who have ever taken COCs, earlier stages of breast cancer are detected than in women who have never taken them.

In rare cases, the development of benign, and in extremely rare cases, malignant liver tumors has been observed during the use of COCs, which in some cases led to life-threatening intra-abdominal bleeding. This should be taken into account when conducting a differential diagnosis in case of severe abdominal pain, liver enlargement or signs of intra-abdominal bleeding.

Other conditions

In women with hypertriglyceridemia (or a family history of this condition), the risk of developing pancreatitis may increase while taking COCs.

Although a slight increase in blood pressure has been described in many women taking COCs, clinically significant increases in blood pressure have been rare. However, if a persistent, clinically significant increase in blood pressure develops while taking COCs, these drugs should be discontinued and treatment for arterial hypertension should be initiated. COC use may be continued if normal blood pressure values are achieved with antihypertensive therapy.

The following conditions have been reported to develop or worsen both during pregnancy and when taking COCs, but their connection with taking COCs has not been proven: jaundice and/or pruritus associated with cholestasis; cholelithiasis; porphyria; SLE; hemolytic-uremic syndrome; Sydenham’s chorea; herpes in pregnancy; hearing loss associated with otosclerosis. Cases of Crohn’s disease and ulcerative colitis during the use of COCs have also been described.

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

The development of chloasma is possible when using the drug, especially in women with a history of chloasma of pregnancy. Women prone to chloasma while taking COCs should avoid prolonged exposure to the sun and ultraviolet radiation.

In acute or chronic liver dysfunction, it may be necessary to discontinue the drug until liver function parameters return to normal.

A relapse of cholestatic jaundice, which first developed during pregnancy or previous use of sex hormones, requires discontinuation of COCs.

Although COCs can affect insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in patients with diabetes using low-dose COCs (<50 mcg ethinylestradiol). Nevertheless, women with diabetes require careful monitoring of blood glucose concentration during the use of the drug.

The effectiveness of COCs may be reduced if tablets are missed, in case of gastrointestinal disorders, or as a result of drug interactions.

Effect on the menstrual cycle

During the use of COCs, irregular (acyclic) bleeding (spotting or breakthrough bleeding) may be observed, especially during the first months of use. Therefore, the assessment of any irregular bleeding should be carried out only after an adaptation period of approximately 3 cycles.

If irregular bleeding recurs or develops after previous regular cycles, a thorough examination should be carried out to rule out malignant neoplasms or pregnancy. In some women, withdrawal bleeding may not occur during the break in taking the pills. If the COCs were taken as directed, pregnancy is unlikely. However, if the COCs were taken irregularly before, or if two consecutive withdrawal bleedings are absent, then pregnancy must be ruled out before continuing to take the drug.

Effect on laboratory test parameters

Taking COCs may affect the results of some laboratory tests, including liver, kidney, thyroid, adrenal function parameters, plasma transport protein levels, carbohydrate metabolism parameters, coagulation and fibrinolysis parameters. The changes usually do not exceed the normal range.

Effect on the ability to drive vehicles and mechanisms

No effect of the drug Erika-35 on the ability to drive vehicles and mechanisms has been identified.

Overdose

There is no data on serious disorders in case of overdose of the drug Erika-35. In case of overdose, the following symptoms may occur: nausea, vomiting, vaginal bleeding.

Treatment: there is no specific antidote, symptomatic therapy should be carried out.

Drug Interactions

Interactions between oral contraceptives and other drugs can lead to acyclic bleeding and/or reduced contraceptive effectiveness.

Effect on hepatic metabolism: interactions may occur with drugs that induce hepatic microsomal enzymes (e.g., hydantoins, barbiturates, primidone, carbamazepine, rifampicin; and possibly also oxcarbazepine, topiramate, felbamate, phenytoin, ritonavir, griseofulvin and preparations containing St. John’s wort), which can lead to an increase in the clearance of sex hormones.

Effect on enterohepatic circulation according to some studies, some antibiotics (e.g., penicillins and tetracycline) may reduce the enterohepatic circulation of estrogens, thereby reducing the concentration of ethinylestradiol.

Women who are taking any of the above-mentioned drugs should temporarily additionally use a barrier method of contraception or choose another method of contraception. When using inducers of microsomal enzymes concurrently, the barrier method of contraception should be used throughout the course of treatment and for 28 days after discontinuation of treatment. For long-term courses of drugs that induce microsomal enzymes, consideration should be given to choosing a different method of contraception. Women using antibiotics (except for rifampicin and griseofulvin, which also induce microsomal enzymes) should use a barrier method of contraception throughout the course of treatment and for 7 days after the end of therapy. If the period during which the barrier method of contraception is used continues after the end of the tablets in the package, then the tablets from the next package of the drug must be started without the usual interval in intake.

Oral contraceptives may affect the metabolism of other medicinal products. Accordingly, their plasma and tissue concentrations may increase (e.g., cyclosporine) or decrease (e.g., lamotrigine).

To determine a possible interaction, it is necessary to consult the instructions for medical use of the respective medicinal products.

Storage Conditions

The drug should be stored in a dry, light-protected place, out of the reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life is 3 years.

Dispensing Status

The drug is dispensed 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.