Oralcon (Tablets) Instructions for Use

Marketing Authorization Holder

Mylan Laboratories, Limited (India)

ATC Code

G03AA07 (Levonorgestrel and Ethinylestradiol)

Active Substances

Ethinylestradiol (Rec.INN registered by WHO)

Levonorgestrel (Rec.INN registered by WHO)

Dosage Form

Oralcon

Film-coated tablets, 150 mcg+30 mcg: 21 or 63 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets (sugar-coated) white, round, biconvex; the cross-section shows a white or almost white core.

Excipients: granular lactose (lactose – 81.5%, sucrose – 9.58%, corn starch – 8.92%, disodium edetate – 0.023%, methylparaben – 0.134%) – 58.319 mg, potassium polacrilin – 1 mg, magnesium stearate – 0.5 mg.

Composition of the sugar coating: ethylcellulose – 0.325 mg, purified talc – 10.53 mg, acacia gum – 1.77 mg, disodium edetate – 0.00585 mg, sucrose – 15.61 mg, microcrystalline cellulose – 0.22 mg, titanium dioxide – 0.28 mg, macrogol 6000 (polyethylene glycol 6000) – 0.268 mg.

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

Clinical-Pharmacological Group

Monophasic oral contraceptive

Pharmacotherapeutic Group

Contraceptive agent (estrogen + progestagen)

Pharmacological Action

Oralcon is a low-dose monophasic oral combined estrogen-progestogen contraceptive drug.

The contraceptive effect of Oralcon is achieved through complementary mechanisms, the most important of which are suppression of ovulation and an increase in the viscosity of cervical mucus, making it impenetrable to sperm.

In women taking combined oral contraceptives, the menstrual cycle becomes more regular, and the pain and intensity of withdrawal bleeding are reduced, thereby lowering one of the risk factors for the development of iron deficiency anemia.

Furthermore, there is evidence that the risk of endometrial cancer and ovarian cancer is reduced.

With correct use, the Pearl index (an indicator reflecting the pregnancy rate per 100 women per year of contraceptive use) is less than 1. If tablets are missed or used incorrectly, the Pearl index may increase.

Pharmacokinetics

Levonorgestrel

Absorption

After oral administration, Levonorgestrel is rapidly and completely absorbed; its C_max in plasma, equal to 3-4 ng/ml, is reached in about 1 hour. The bioavailability of levonorgestrel upon oral administration is almost complete.

Distribution

Levonorgestrel binds to plasma albumin and to sex hormone-binding globulin (SHBG). Only about 1.3% of the total plasma concentration is in the free form; about 64% is specifically bound to SHBG and about 34% is non-specifically bound to albumin.

The induction of SHBG synthesis by ethinylestradiol affects the binding of levonorgestrel to plasma proteins, causing an increase in the fraction bound to SHBG and a decrease in the fraction bound to albumin. The apparent V_d of levonorgestrel is about 184 L after a single dose.

With daily administration of the drug, the plasma concentration of levonorgestrel increases approximately 3-4 times, reaching a steady-state concentration in the second half of the course of administration.

The pharmacokinetics of levonorgestrel are influenced by the concentration of SHBG, which increases approximately 1.7 times when levonorgestrel is used together with ethinylestradiol. At steady-state concentration, the clearance rate decreases to about 0.7 ml/min/kg.

Metabolism

Levonorgestrel is almost completely metabolized. The plasma clearance rate is approximately 1.3-1.6 ml/min/kg.

Excretion

The plasma concentration of levonorgestrel decreases in a biphasic manner. The terminal T_1/2 is about 20-23 hours. Levonorgestrel is not excreted unchanged, but only as metabolites, which are excreted by the kidneys and through the intestines in a ratio of approximately 1:1.

Ethinylestradiol

Absorption

After oral administration, Ethinylestradiol is rapidly and completely absorbed. C_max in plasma, equal to approximately 95 pg/ml, is reached within 1-2 hours. During absorption and the “first pass” through the liver, Ethinylestradiol is metabolized, resulting in an average oral bioavailability of about 45% (individual variations within 20-65%).

Distribution

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.

With daily oral administration of Oralcon, the plasma concentration of ethinylestradiol increases slightly, reaching a maximum value of 114 pg/ml at the end of the course. Given the variable terminal T_1/2 and daily oral administration, the steady-state concentration is reached approximately after one week.

Metabolism

Ethinylestradiol 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.

Excretion

The decrease in the plasma concentration of Ethinylestradiol is biphasic; the first phase is characterized by a T_1/2 of about 1 hour, the second by 10-20 hours. It is not excreted unchanged from the body. Metabolites of ethinylestradiol are excreted by the kidneys and through the intestines in a 4:6 ratio with a T_1/2 of about 24 hours.

Indications

• Prevention of unwanted pregnancy (contraception);
• Hormone-dependent functional disorders of the menstrual cycle.

ICD codes

Dosage Regimen

Take orally with a small amount of water.

1 tablet approximately at the same time each day, starting from the first day of the cycle and then “following the arrow” as indicated on the package. Take continuously for 21 days. The next package is started after a 7-day break in taking the tablets, during which withdrawal bleeding usually occurs. Bleeding typically begins on the 2nd-3rd day after taking the last tablet and may continue until the start of the new package.

If no other hormonal contraceptives were taken in the previous month

The drug is started on the 1st day of the menstrual cycle (i.e., the first day of menstrual bleeding). It is possible to start on days 2-5 of the menstrual cycle; however, in this case, it is recommended to additionally use a barrier method of contraception during the first 7 days of taking Oralcon tablets from the first package.

Switching from other combined oral contraceptives, vaginal ring, or patch

It is recommended to start taking Oralcon on the day after taking the last active tablet from the previous package of another contraceptive, but no later than the day after the 7-day break.

In case of previous use of a vaginal ring or patch, start taking Oralcon 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 applied.

Switching from progestogen-only contraceptives (“mini-pills”, injectable forms, implants) or from an intrauterine device releasing a progestogen

From “mini-pills”, you can switch on any day (without a break), from an implant or intrauterine device – on the day of its removal, from an injectable form – on the day when the next injection is due. In all cases, it is necessary to use barrier methods of contraception during the first 7 days of taking Oralcon.

Use of Oralcon after a first-trimester abortion

The drug can be started immediately. If this rule is followed, the woman does not need additional contraceptive protection.

Use of Oralcon after childbirth or a second-trimester abortion

It is recommended to start taking the drug on day 21-28 after childbirth or a second-trimester abortion. If the drug is started later, it is necessary to use a barrier method of contraception during the first 7 days of taking Oralcon. However, if the woman had sexual intercourse before starting Oralcon, pregnancy must first be ruled out or the first menstruation must be awaited.

Missed dose of Oralcon

If the delay in taking the drug is less than 12 hours, the contraceptive effect is not reduced. The missed tablet should be taken as soon as possible, and the next tablet is taken at the usual time.

If the delay in taking the drug is more than 12 hours, the contraceptive effect is reduced. The more tablets are missed and the closer the miss is to the 7-day break, the higher the likelihood of pregnancy. In this case, it is necessary to remember

• Taking the drug should never be interrupted for more than 7 days;
• 7 days of continuous intake are required for adequate suppression of the hypothalamic-pituitary-ovarian system.

In case of a missed dose of more than 12 hours (i.e., the interval since the last tablet was taken is more than 36 hours), the following rules should be followed

• if the miss occurred in the 1st week take the last missed tablet as soon as possible (as soon as the woman remembers), even if this means taking 2 tablets at the same time. The next tablet is taken at the usual time. Additionally, a barrier method of contraception may be used for the next 7 days. If sexual intercourse occurred during the week preceding the missed tablet, the possibility of pregnancy should be considered.
• if the miss occurred in the 2nd week take the last missed tablet as soon as possible (as soon as the woman remembers), even if this means taking 2 tablets at the same time. The next tablet is taken at the usual time. If the tablets were taken correctly for the 7 days preceding the first missed tablet, there is no need for additional barrier contraceptive methods. Otherwise, or if 2 or more tablets are missed, it is necessary to additionally use a barrier method of contraception for 7 days.
• if the miss occurred in the 3rd week of taking the drug, the risk of reduced contraceptive effect is inevitable. If the tablets were taken correctly for the 7 days preceding the first missed tablet, there is no need for additional barrier contraceptive methods. You can use two rules

1) take the last missed tablet as soon as possible (as soon as the woman remembers), even if this means taking 2 tablets at the same time. The following tablets are taken at the usual time until they run out in this package. The tablets from the next package must be started immediately. Withdrawal bleeding is unlikely until the end of the second package, and spotting and breakthrough bleeding may be noted during tablet intake;

2) you can stop taking the tablets from the current package and take a 7-day break, including the day of the missed tablet, and then start taking tablets from a new package.

If a woman missed taking tablets and does not have withdrawal bleeding during the break, pregnancy must be ruled out.

Changing the day of onset of withdrawal bleeding

If it is necessary to delay the onset of withdrawal bleeding, you should start taking Oralcon tablets from a new package immediately after finishing the tablets in the previous package (without a break in intake). Tablets from this package should be taken for as long as the woman plans to postpone the onset of withdrawal bleeding, or until the tablets in the second package run out. While taking the drug from the second package, spotting or breakthrough uterine bleeding may occur. Resumption of Oralcon intake from a new package should be after the usual 7-day break. To shift the day of onset of withdrawal bleeding to another day of the week, the nearest break in tablet intake should be shortened by the required number of days. However, it must be remembered that the shorter the interval between tablet intakes, the higher the likelihood of the woman not having withdrawal bleeding, and subsequently, spotting and breakthrough bleeding while taking the second package of Oralcon (just as in the case of delaying the onset of withdrawal bleeding).

Recommendations for taking the drug in case of vomiting or diarrhea

If vomiting or diarrhea occurred within 4 hours after taking the drug, its absorption may have been incomplete, so in this case, additional barrier methods of contraception should be used. The rules for missed tablets should be followed.

For hormone-dependent functional disorders of the menstrual cycle, the dose and course of treatment are selected by the doctor individually in each specific case.

Adverse Reactions

Possible nausea, vomiting, headache, breast tenderness, weight gain, decreased libido and mood, voice coarsening, intermenstrual spotting, in some cases – eyelid edema, conjunctivitis, visual disturbances, discomfort when wearing contact lenses (these phenomena are temporary and disappear after discontinuation without any therapy).

With long-term use, very rarely, chloasma, hearing loss, generalized itching, jaundice, calf muscle cramps, and increased frequency of epileptic seizures may occur.

Rarely hypertriglyceridemia, hyperglycemia, decreased glucose tolerance, increased blood pressure, thrombosis and venous thromboembolism, skin rashes, changes in the nature of vaginal secretion, vaginal candidiasis, increased fatigue, diarrhea are noted.

Contraindications

The drug should not be used in the presence of any of the conditions/diseases listed below. If any of these conditions/diseases develop for the first time during use, the drug must be immediately discontinued

• Current or history of thrombosis (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);
• Multiple or pronounced risk factors for venous or arterial thrombosis;
• Current or history of migraine with focal neurological symptoms;
• Diabetes mellitus with vascular complications;
• Current or history of pancreatitis with severe hypertriglyceridemia;
• Hepatic insufficiency and severe liver diseases (until liver function tests normalize);
• 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;
• Lactation (breastfeeding) period;
• Lactose/fructose intolerance, lactase deficiency, sucrase/isomaltase deficiency, fructose intolerance, lactose intolerance, glucose-galactose malabsorption (due to the presence of lactose and sucrose in the composition);
• Hypersensitivity to the components of the drug.

With caution

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

• Risk factors for thrombosis and thromboembolism (smoking, thrombosis, myocardial infarction or cerebrovascular accident at a young age in any first-degree relatives, obesity; dyslipoproteinemia, arterial hypertension, migraine without focal neurological symptoms, valvular heart disease, cardiac arrhythmias, prolonged immobilization, major surgical interventions, major trauma);
• Other diseases in which peripheral circulation disorders may be noted; diabetes mellitus without vascular lesions; systemic lupus erythematosus; hemolytic-uremic syndrome; Crohn’s disease and ulcerative colitis; sickle cell anemia; as well as superficial phlebitis;
• Hypertriglyceridemia;
• Mild to moderate liver diseases, with normal liver function tests;
• Diseases that first appeared or worsened during pregnancy or during previous use of sex hormones (e.g., jaundice, cholestasis, gallbladder diseases, otosclerosis with hearing impairment, porphyria, herpes gestationis, Sydenham’s chorea).

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

Use in Pregnancy and Lactation

Oralcon is contraindicated during pregnancy and breastfeeding. If pregnancy is detected while taking Oralcon, it should be discontinued immediately. However, numerous epidemiological studies have not revealed any increased risk of developmental defects in children born to women who received sex hormones before pregnancy, or a teratogenic effect when sex hormones were taken inadvertently in early pregnancy.

The use of combined oral contraceptives may reduce the amount of breast milk and change its composition, therefore, as a rule, their use is contraindicated during breastfeeding. A small amount of sex hormones and/or their metabolites may be excreted in breast milk.

Use in Hepatic Impairment

Contraindicated in hepatic insufficiency and severe liver diseases (until liver function tests normalize), current or history of liver tumors (benign or malignant).

Use with caution in mild to moderate liver diseases (with normal liver function test results).

Special Precautions

If any of the conditions/diseases/risk factors listed below are currently present, the potential risk and expected benefit of using combined oral contraceptives 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 a doctor, who may decide to discontinue the drug.

Cardiovascular diseases

Epidemiological study results indicate an association between the use of combined oral contraceptives and an increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders) when taking combined oral contraceptives. These diseases are rare.

The risk of developing venous thromboembolism (VTE) is highest in the first year of taking such drugs. An increased risk is present after initial use of combined oral contraceptives or resumption of taking the same or different combined oral contraceptives (after a drug-free interval of 4 weeks or more).

Data from a large prospective study with 3 groups of female volunteers show that this increased risk is present primarily during the first 3 months.

The overall risk of VTE in women taking low-dose combined oral contraceptives (< 50 mcg ethinylestradiol) is 2-3 times higher than in non-pregnant women not taking combined contraceptives; however, this risk remains lower compared to the risk of VTE during pregnancy and childbirth.

VTE can be fatal (in 1-2% of cases). VTE, manifesting as deep vein thrombosis or pulmonary embolism, can occur with the use of any combined oral contraceptives.

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

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

• With age;
• In smokers (the risk increases with the number of cigarettes or with increasing age, especially in women over 35 years old);
• In the presence of a family history (e.g., venous or arterial thromboembolism ever in close relatives or parents at a relatively young age). In case of hereditary or acquired predisposition, a woman should be examined by an appropriate specialist to decide on the possibility of taking combined oral contraceptives;
• With obesity (body mass index more than 30 kg/m²);
• With dyslipoproteinemia;
• With arterial hypertension;
• With migraine;
• With heart valve diseases;
• With atrial fibrillation;
• With prolonged immobilization, major surgical intervention, any surgery on the lower limbs, or extensive trauma. In these situations, it is advisable to discontinue combined oral contraceptives (in the case of planned surgery, at least 4 weeks before it) and not to resume taking them until 2 weeks after the end of immobilization.

The question of the possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial. The increased risk of thromboembolism in the postpartum period should be taken into account.

Peripheral circulatory disorders can also be observed in 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 during the use of combined oral contraceptives (which may precede cerebrovascular disorders) may be grounds for immediate discontinuation of these drugs.

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 (<0.05 mg ethinylestradiol).

Tumors

The most significant risk factor for the development of cervical cancer is persistent human papillomavirus infection. There are reports of a slight increase in the risk of developing cervical cancer with long-term use of combined oral contraceptives. A connection with the use of combined oral contraceptives has not been proven.

Controversy remains regarding the extent to which these findings are related to screening for cervical pathology or to sexual behavior characteristics (less frequent use of barrier contraception methods).

A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of developing breast cancer diagnosed in women currently taking combined oral contraceptives (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 diagnosed breast cancer in women currently taking or recently taking combined oral contraceptives is insignificant relative to the overall risk of this disease. Its connection with the use of combined oral contraceptives has not been proven.

The observed increase in risk may also be a consequence of earlier diagnosis of breast cancer in women using combined oral contraceptives. In women who have ever taken combined oral contraceptives, cancer is detected at earlier stages than in women who have never used them.

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

Other conditions

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

Although a slight increase in blood pressure has been described in many women taking combined oral contraceptives, clinically significant increases have been rare. However, if a persistent, clinically significant increase in blood pressure develops during the use of combined oral contraceptives, these drugs should be discontinued and treatment for arterial hypertension should be initiated.

Use of combined oral contraceptives 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 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; herpes gestationis; hearing loss associated with otosclerosis. Cases of Crohn’s disease and ulcerative colitis during the use of combined oral contraceptives have also been described.

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

Acute or chronic liver function disorders may require discontinuation of combined oral contraceptives until liver function tests return to normal. Recurrent cholestatic jaundice, which developed for the first time during pregnancy or previous use of sex hormones, requires discontinuation of combined oral contraceptives.

Although combined oral contraceptives can affect insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in patients with diabetes using low-dose combined oral contraceptives (<50 mcg ethinylestradiol). However, women with diabetes should be carefully monitored while taking 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 sun exposure and ultraviolet radiation.

Effect on bleeding pattern

While taking combined oral contraceptives, irregular bleeding (spotting or breakthrough bleeding) may occur, 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 performed to rule out malignant neoplasms or pregnancy.

In some women, withdrawal bleeding may not occur during the tablet-free interval. If combined oral contraceptives were taken as directed, it is unlikely that the woman is pregnant. 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 the drug.

Effect on ability to drive vehicles and machinery

No effect.

Overdose

No cases of overdose have been reported. Possible symptoms of overdose: nausea, vomiting, vaginal spotting or metrorrhagia.

Treatment: There is no specific antidote; treatment is symptomatic.

Drug Interactions

Some medicines may reduce the effectiveness of the drug: antiepileptic drugs (including primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine, topiramate, felbamate), anti-tuberculosis drugs (including rifampicin, rifabutin), drugs for the treatment of HIV infection (including ritonavir, nevirapine); medicines based on St. John’s wort.

A decrease in contraceptive effectiveness may also be observed with simultaneous use with some antimicrobial drugs (ampicillin, rifampicin, chloramphenicol, neomycin, polymyxin B, sulfonamides, tetracyclines), which is associated with a change in the intestinal microflora.

When taking progestogen-estrogen drugs, adjustment of the dosage regimen of hypoglycemic drugs and indirect anticoagulants may be required.

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 – 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.