Trigestrel (Tablets) Instructions for Use

Marketing Authorization Holder

Famy Care, Limited (India)

ATC Code

G03AB03 (Levonorgestrel and Ethinylestradiol)

Active Substances

Ethinylestradiol (Rec.INN registered by WHO)

Levonorgestrel (Rec.INN registered by WHO)

Dosage Form

Trigestrel

Coated tablets: 21 pcs. in a blister, 1 or 3 blisters in a pack, incl.: brown tab. 30 mcg+50 mcg: 6 pcs. in a blister, white tab. 40 mcg+75 mcg: 5 pcs. in a blister, yellow tab. 30 mcg+125 mcg: 10 pcs. in a blister

Dosage Form, Packaging, and Composition

Coated tablets, three types.

Brown, round, biconvex sugar-coated tablets; the core on cross-section is white or almost white (6 pcs. in a blister).

Excipients: granulated lactose (lactose – 81.5%, sucrose – 9.58%, corn starch – 8.92%, disodium edetate – 0.023%, methylparaben – 0.134%) – 58.42 mg, potassium polacrilin – 1 mg, magnesium stearate – 0.5 mg.

Sugar coating composition: ethylcellulose – 0.325 mg, purified talc – 10.71 mg, acacia gum – 1.77 mg, disodium edetate – 0.00585 mg, sucrose – 15.61 mg, microcrystalline cellulose – 0.22 mg, titanium dioxide – 0.019 mg, red iron oxide – 0.081 mg, macrogol 6000 (polyethylene glycol 6000) – 0.268 mg.

White, round, biconvex sugar-coated tablets; the core on cross-section is white or almost white (5 pcs. in a blister).

Excipients: granulated lactose (lactose – 81.5%, sucrose – 9.58%, corn starch – 8.92%, disodium edetate – 0.023%, methylparaben – 0.134%) – 58.384 mg, potassium polacrilin – 1 mg, magnesium stearate – 0.5 mg.

Sugar coating composition: 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.

Yellow, round, biconvex sugar-coated tablets; the core on cross-section is white or almost white (10 pcs. in a blister).

Excipients: granulated lactose (lactose – 81.5%, sucrose – 9.58%, corn starch – 8.92%, disodium edetate – 0.023%, methylparaben – 0.134%) – 58.344 mg, potassium polacrilin – 1 mg, magnesium stearate – 0.5 mg.

Sugar coating composition: ethylcellulose – 0.325 mg, purified talc – 10.71 mg, acacia gum – 1.77 mg, disodium edetate – 0.00585 mg, sucrose – 15.61 mg, microcrystalline cellulose – 0.22 mg, titanium dioxide – 0.019 mg, yellow iron oxide – 0.081 mg, macrogol 6000 (polyethylene glycol 6000) – 0.268 mg.

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

Clinical-Pharmacological Group

Three-phase oral contraceptive

Pharmacotherapeutic Group

Contraceptive agent (estrogen + progestagen)

Pharmacological Action

Trigestrel is a low-dose three-phase oral combined (estrogen+progestogen) contraceptive drug.

The contraceptive effect is carried out through several complementary mechanisms.

Under the influence of levonorgestrel, blockade of the release of releasing factors (luteinizing and follicle-stimulating hormones) from the hypothalamus occurs, suppressing the secretion of gonadotropic hormones by the pituitary gland, which leads to inhibition of the maturation and release of an egg ready for fertilization (ovulation).

Changes in the endometrium occur, preventing the implantation of a fertilized egg.

Ethinylestradiol increases the viscosity of the cervical secretion, as a result of which it becomes impenetrable to spermatozoa.

In addition to the contraceptive effect, Trigestrel reduces the frequency of painful menstrual-like bleeding and reduces the intensity of bleeding, which, in turn, reduces one of the risk factors for the development of iron deficiency anemia.

During the seven-day periods when the next break in taking the drug is due, uterine bleeding occurs. With correct use, the Pearl index (an indicator reflecting the frequency of pregnancy in 100 women during one 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 blood plasma, about 2 ng/ml, is reached in approximately 1 h. After a single oral dose of 0.125 mg of levonorgestrel together with 0.03 mg of ethinylestradiol (which corresponds to the highest content of levonorgestrel in the three-phase preparation), the C_max in serum, amounting to 4.3 ng/ml, was determined approximately 1 h later.

Distribution

Levonorgestrel binds to serum albumin and sex hormone-binding globulin (SHBG). Only 1.4% of the total serum concentration is in the free form, while 55% is specifically bound to SHBG and about 40% to albumin. As a result of ethinylestradiol-induced synthesis of the binding protein, the fraction bound to SHBG increases, while the fraction bound to albumin decreases. The apparent V_d of levonorgestrel is about 128 L after a single oral dose of 1 Trigestrel tablet containing the highest dose of levonorgestrel.

The pharmacokinetics of levonorgestrel are influenced by the concentration of SHBG in the blood serum, which increases approximately 2-fold during the 21-day course of taking Trigestrel. As a result of daily intake of the drug, the concentration of levonorgestrel in the serum increases approximately 2-fold, and the equilibrium concentration is reached in the second half of the course. V_d at steady state and clearance decrease to 52 L and 0.5 ml/min/kg, respectively.

Metabolism

Levonorgestrel is completely metabolized via the pathway of metabolism characteristic of sex hormones. After a single oral dose of the highest dose of levonorgestrel, the plasma clearance rate is approximately 1 ml/min/kg.

Excretion

The concentration of levonorgestrel in the blood serum decreases in a biphasic manner. T_1/2 in the terminal phase is about 22 h. Levonorgestrel is not excreted unchanged, but only as metabolites by the kidneys and through the intestines with a T_1/2 of about 24 h in a ratio of approximately 1:1.

Ethinylestradiol

Absorption

After oral administration, Ethinylestradiol is absorbed rapidly and completely. C_max in blood serum, equal to approximately 115 pg/ml, is reached in approximately 1.3 h. Ethinylestradiol is metabolized due to the first-pass effect through the liver, as a result, its bioavailability when taken orally averages about 45%, with significant interindividual variations within 20-65%.

Distribution

Ethinylestradiol is almost completely (98%) bound to albumin. Ethinylestradiol induces the synthesis of SHBG. The apparent V_d of ethinylestradiol is approximately 3-8 L/kg.

Equilibrium concentration is reached after 1 week.

Metabolism

Ethinylestradiol undergoes presystemic conjugation, both in the small intestinal mucosa and in the liver. The main metabolic pathway is aromatic hydroxylation. Plasma clearance is 2.3-7 ml/min/kg.

Excretion

The concentration of ethinylestradiol in the blood serum decreases biphasically; the first phase is characterized by a T_1/2 of about 1 h, the second – 10-20 h. It is not excreted unchanged from the body. Ethinylestradiol metabolites are excreted by the kidneys and liver in a ratio of 4:6, with a T_1/2 of about 24 h.

Indications

• Contraception.

ICD codes

Dosage Regimen

The tablets should be taken orally in the order indicated on the package, every day at approximately the same time, with a small amount of water. Take 1 tablet daily continuously for 21 days. The next pack is started after a 7-day break in taking the tablets, during which withdrawal bleeding usually occurs. The bleeding 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 Trigestrel

If no hormonal contraceptives were taken in the previous month

Trigestrel intake is started on the 1st day of the menstrual cycle (i.e., on the 1st day of menstrual bleeding). It is permissible to start intake 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 pack.

When switching from other combined oral contraceptives, vaginal ring, or contraceptive patch

It is preferable to start taking Trigestrel on the day after taking the last active tablet from the previous pack, 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 in a pack). Trigestrel intake 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 applied.

When switching from contraceptives containing only progestogens (“mini-pills”, injectable forms, implant) or from a progestogen-releasing intrauterine contraceptive

A woman can switch from “mini-pills” to Trigestrel on any day (without a break), from an implant or 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. If this condition is met, the woman does not need additional contraceptive protection.

After childbirth or a second-trimester abortion

It is recommended to start taking the drug on the 21st-28th day after childbirth or a second-trimester 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. However, if the woman has already been sexually active, before starting Trigestrel, pregnancy must be excluded or the first menstruation must be awaited.

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, as soon as she remembers; the next one is taken at the usual time.

If the delay in taking the tablets is more than 12 hours, contraceptive protection may be reduced. 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

• Drug intake should never be interrupted for more than 7 days;
• 7 days of continuous tablet intake are required to achieve adequate suppression of the hypothalamic-pituitary-ovarian regulation.

Accordingly, the following advice can be given

First week of drug intake

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 (e.g., a condom) must 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 drug intake

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 took the tablets correctly for the 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 (e.g., a condom) for 7 days.

Third week of drug intake

The risk of reduced reliability is inevitable due to the upcoming break in taking the tablets. The woman must strictly adhere to one of the following two options. In this case, if all tablets were taken correctly during the 7 days preceding the first missed tablet, there is no need to use additional contraceptive methods.

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 pack are finished. The intake of the drug from the next pack should be started immediately. Withdrawal bleeding is unlikely until the second pack is finished, but bleeding of varying intensity (from spotting to breakthrough) may be noted during tablet intake.

The woman can also interrupt taking the tablets from the current pack. Then she should take a break for 7 days, including the day of missing the tablet, and then start taking a new pack.

If a woman missed taking tablets and then does not have withdrawal bleeding during the break in taking the drug, pregnancy must be excluded.

Recommendations in case of vomiting and diarrhea

If a woman had vomiting or diarrhea within 4 hours after taking the tablets, absorption may be incomplete and additional contraceptive measures must be taken. In these cases, one should be guided by the recommendations for missed tablets.

Changing the day of onset of menstrual-like bleeding

In order to delay the onset of menstrual-like bleeding, the woman should continue taking the drug, using the last 10 tablets from another pack of Trigestrel, without taking a break in intake. Thus, the cycle can be extended for up to 10 days until the end of the second pack. While taking the drug from the second pack, the woman may experience spotting or breakthrough uterine bleeding. Regular intake of Trigestrel is then resumed after the usual 7-day break in taking the tablets.

In order to move the day of onset of menstrual-like bleeding to another day of the week, the woman should shorten the next break in taking the tablets by the desired number of days. The shorter the interval, the higher the risk that she will not have withdrawal bleeding and, subsequently, will have spotting or breakthrough bleeding while taking the second pack (just as in the case when she would like to delay the onset of menstrual-like bleeding).

Children and adolescents

Trigestrel is indicated for use only after menarche.

Adverse Reactions

When taking combined oral contraceptives, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. While taking combined oral contraceptives, other undesirable effects have been observed in women, the connection of which with taking the drugs has not been confirmed but has not been refuted either.

As with other combined oral contraceptives, in rare cases, thrombosis and thromboembolism, chloasma may develop.

Taking exogenous estrogens may cause or exacerbate symptoms of angioedema in women with hereditary angioedema.

Contraindications

Trigestrel should not be used in the presence of any of the conditions listed below. If any of these conditions develop for the first time while taking the drug, it must be discontinued immediately

• Thromboses (venous and arterial) and thromboembolism currently or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction), cerebrovascular disorders;
• Conditions preceding thrombosis (including transient ischemic attacks, angina pectoris) currently or in history;
• Multiple or pronounced risk factors for venous or arterial thrombosis (including valvular heart disease, cardiac arrhythmias, deep vein thrombophlebitis, diseases of the cerebral or coronary arteries); uncontrolled arterial hypertension;
• prolonged immobilization, major surgical procedures, surgical interventions on the lower limbs, extensive trauma;
• migraine with focal neurological symptoms currently or in history;
• diabetes mellitus with vascular complications;
• pancreatitis with severe hypertriglyceridemia currently or in history;
• hepatic insufficiency and severe liver diseases (until liver function tests return to normal);
• liver tumors (benign or malignant) currently or in history;
• known hormone-dependent malignant diseases (including of the genital organs or breasts) or suspicion thereof;
• vaginal bleeding of unknown origin;
• pregnancy or suspected pregnancy;
• lactation (breastfeeding) period;
• lactase deficiency, sucrase/isomaltase deficiency, fructose intolerance, lactose intolerance, glucose-galactose malabsorption;
• hypersensitivity to the components of the drug.

With caution

If any of the conditions/risk factors listed below are currently present, the potential risk and expected benefit of using combined oral contraceptives should be correlated 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 (body mass index greater than 30 kg/m²); dyslipoproteinemia, arterial hypertension, migraine without focal neurological symptoms);
• 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;
• liver diseases;
• 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 gestations, Sydenham’s chorea).

Use in Pregnancy and Lactation

Trigestrel is not prescribed during pregnancy and breastfeeding. If pregnancy is detected while taking Trigestrel, the drug should be discontinued immediately. Extensive 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 not recommended during lactation. A small amount of sex hormones and/or their metabolites may be excreted in breast milk, but there is no evidence of their negative impact on the infant’s health.

Use in Hepatic Impairment

Contraindicated in hepatic insufficiency and severe liver diseases (until liver function tests return to normal), in liver tumors (benign or malignant) currently or in history.

Pediatric Use

Trigestrel is indicated for use only after menarche.

Geriatric Use

Contraceptive drug, not used in the elderly.

Special Precautions

If any of the conditions/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 manifestation of any of these conditions or risk factors, the woman should consult her doctor, who may decide on the need to discontinue the drug.

Cardiovascular diseases

There are epidemiological data on an increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke) 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. The approximate incidence of VTE among women taking low-dose oral contraceptives (<0.05 mg ethinyl estradiol) is 4 per 10,000 women per year compared to 0.5-3 per 10,000 women per year in women not taking oral contraceptives. However, the incidence of VTE in pregnant women is higher than in women taking oral contraceptives and is 6 per 10,000 women per year.

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 a positive 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, the woman should be examined by an appropriate specialist to decide on the possibility of taking combined oral contraceptives;
• In the presence of obesity (body mass index greater than 30 kg/m²);
• With dyslipoproteinemia;
• With arterial hypertension;
• With migraine;
• With heart valve diseases;
• With atrial fibrillation;
• With prolonged immobilization, major surgery, any leg surgery, or extensive trauma. In these situations, it is advisable to stop using combined oral contraceptives (in the case of planned surgery, at least 4 weeks before it) and not 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 circulation disorders may also be noted 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 relevant conditions may reduce the associated risk. 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 ethinyl estradiol).

Tumors

The most significant risk factor for cervical cancer is persistent papillomavirus infection. There are reports of a slight increase in the risk of cervical cancer with long-term use of combined oral contraceptives. The connection with the use of combined oral contraceptives has not been proven. Controversy remains as to the extent to which these phenomena are related to cervical pathology screening or sexual behavior characteristics (less frequent use of barrier contraceptive methods).

A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of 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 the number of detected breast cancers 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 rare cases, the development of benign, and in extremely rare cases, malignant liver tumors has been observed during the use of combined oral contraceptives, 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 in the differential diagnosis.

Other conditions

In women with hypertriglyceridemia (including a family history), 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 while taking combined oral contraceptives, these drugs should be discontinued and treatment for arterial hypertension should be initiated. The use of combined oral contraceptives may 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; herpes gestations; 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 dysfunction 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 may 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 (<0.05 mg ethinyl estradiol). 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 exposure to the sun and ultraviolet radiation.

Laboratory tests

Taking combined oral contraceptives may affect the results of some laboratory tests, including indicators of liver, kidney, thyroid, adrenal function, the concentration of transport proteins in plasma, parameters of carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes usually do not go beyond normal limits.

Reduced efficacy

The effectiveness of combined oral contraceptive drugs may be reduced in the following cases: when tablets are missed, with vomiting and diarrhea, or as a result of drug interactions.

Effect on the menstrual cycle

While taking combined oral contraceptives, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. Therefore, the evaluation of any irregular bleeding should be carried out only after an adaptation period of approximately three 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.

Medical examinations

Before starting or resuming the use of Trigestrel, it is necessary to review the woman’s life history, family history, conduct 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 the cervical mucosa), and rule out pregnancy.

The scope of additional studies and the frequency of follow-up examinations is determined individually. Usually, follow-up examinations should be carried out at least once every 6 months.

The woman should be warned that hormonal contraceptives (including Trigestrel) do not protect against HIV infection and other sexually transmitted diseases.

Effect on the ability to drive vehicles and mechanisms

Not identified.

Overdose

No serious disorders from overdose have been reported.

Symptoms that may occur with overdose: nausea, vomiting, spotting or metrorrhagia.

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

Drug Interactions

Effect on hepatic metabolism: the use of drugs that induce hepatic microsomal enzymes may lead to an increase in the clearance of sex hormones. Such drugs include: phenytoin, barbiturates, primidone, carbamazepine, rifampicin; there are also suggestions regarding oxcarbazepine, topiramate, felbamate, griseofulvin and preparations containing St. John’s wort.

HIV protease inhibitors (e.g., ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g., nevirapine) and their combinations may also potentially affect hepatic metabolism.

Effect on enterohepatic recirculation: according to individual studies, some antibiotics (e.g., penicillins and tetracyclines) may reduce the enterohepatic recirculation of estrogens, thereby reducing the concentration of ethinyl estradiol.

While taking drugs that affect hepatic microsomal enzymes and for 28 days after their discontinuation, an additional barrier method of contraception should be used.

While taking antibiotics (such as penicillins and tetracyclines) and for 7 days after their discontinuation, an additional barrier method of contraception should be used. If the period of using the barrier method of contraception ends later than the tablets in the package, you should proceed to the next package of Trigestrel without the usual break in taking the tablets.

Oral combined contraceptives may affect the metabolism of other drugs, leading to an increase (e.g., cyclosporine) or decrease (e.g., lamotrigine) in their plasma and tissue concentrations.

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

Interaction of oral contraceptives with other drugs may lead to breakthrough bleeding and/or reduced contraceptive reliability.

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. Do not use after the expiration date.

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.