Cilest (Tablets) Instructions for Use

Marketing Authorization Holder

Johnson & Johnson, LLC (Russia)

Manufactured By

Cilag, AG (Switzerland)

ATC Code

G03AA11 (Norgestimate and Ethinylestradiol)

Active Substances

Ethinylestradiol (Rec.INN registered by WHO)

Norgestimate (Rec.INN registered by WHO)

Dosage Form

Cilest

Tablets 250 mcg+35 mcg: 21 or 63 pcs.

Dosage Form, Packaging, and Composition

Tablets are blue, round, flat-cylindrical, with bevelled edges and the engraving “C250” on both sides.

Excipients: lactose, pregelatinized starch, magnesium stearate, dye FD & C Blue No.2 Lake 13%.

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

Cilest is a combined oral contraceptive, the action of which is due to central and peripheral mechanisms. By suppressing the release of gonadotropins, Cilest prevents the maturation of eggs in the ovaries and ovulation.

In addition, Cilest increases the viscosity of cervical mucus, which impedes the penetration of sperm into the uterus, and acts on the endometrial epithelium, reducing the likelihood of implantation.

Pharmacokinetics

When taken orally, Norgestimate is well absorbed both separately and in combination with ethinylestradiol. C_max in blood plasma is reached after 1-2 hours. Norgestimate is actively metabolized. The half-life is about 4 hours. Metabolites are slowly excreted from the body. After 2 weeks, about 50% of the active substance is excreted in the urine and about 40% in the feces.

Ethinylestradiol is rapidly and almost completely absorbed when taken orally. C_max in blood plasma is reached after 1-2 hours. Ethinylestradiol is only partially metabolized in the body. The half-life is 4.5 hours. Over 17% of the active substance is excreted unchanged in the urine and more than 10% is excreted in the feces. The metabolites are estradiol, estriol and, mainly, 2-hydroxy- and 16β-hydroxyethinylestradiol.

Indications

• Contraception in women.

ICD codes

Dosage Regimen

Orally. The use of Cilest should be started by taking one tablet of the drug on the first day of menstrual bleeding. After that, it is necessary to take one tablet daily for 20 days. This is followed by a seven-day break in taking the drug. Usually, a few days after the end of taking the tablets, menstrual-like bleeding occurs. The next cycle of taking Cilest should be started on the eighth day, i.e., seven days after stopping the tablets in the previous cycle. The first tablet of the new cycle should be taken regardless of whether the bleeding has stopped or is still continuing.

The blister pack of the drug has days of the week printed on it. To facilitate checking the regularity of tablet intake, it is recommended to start each new cycle with the tablet marked with the corresponding day of the week and then continue without interruptions for the entire intake cycle.

Contraceptive pills are most effective if taken at the same time of day, for example, in the morning. In case of missing the usual intake time, the tablet should be taken immediately. A deviation from the usual intake time of up to 12 hours provides reliable contraceptive action. The effectiveness of the drug decreases if the tablet intake is delayed by more than 12 hours. If more than 12 hours have passed since the usual intake time or more than one tablet has been missed, the drug intake should be resumed immediately, leaving the missed tablet in the pack. However, until the end of this cycle, additional means of protection against pregnancy should be used, such as a condom or vaginal contraceptive suppositories. In such situations, one should not rely on the “safe days” method or the “temperature” method of contraception.

After childbirth, taking Cilest should be started no earlier than 4 weeks after delivery, provided that the woman is not breastfeeding. After an abortion or miscarriage up to 20 weeks of pregnancy, taking the pills can be started immediately; in these cases, the use of additional contraceptive methods is not required.

After an induced or spontaneous abortion at a gestational age of more than 20 weeks, hormonal contraceptive agents can be started on the 21st day after the abortion or on the first day of the appearance of natural menstruation (whichever comes first). In these cases, during the first 7 days of the cycle, it is recommended to use additional local contraceptive means in addition to taking Cilest. In exceptional cases, if there are medical indications for providing immediate reliable contraception, taking Cilest can be started 1 week after the abortion. It must be taken into account that the risk of thromboembolic complications is increased when taken in the post-abortion period. If vomiting or diarrhea occurs, Cilest may lose its effectiveness, since 4 hours are required for the complete absorption of the tablet by the body. In this case, it is recommended to continue taking Cilest, supplementing its action with other contraceptive means until menstruation occurs.

Adverse Reactions

Cardiovascular system: arterial hypertension, myocardial infarction, cerebrovascular disorders, deep vein thrombosis, arterial thromboembolism, thromboembolism of pulmonary or other vessels, edema.

Tumors: benign and malignant liver tumors, cervical cancer and breast cancer.

Hepatobiliary system: cholestatic jaundice, Budd-Chiari syndrome, intrahepatic cholestasis, cholelithiasis.

Gastrointestinal tract: nausea, vomiting, abdominal pain, flatulence, colitis.

Genital organs: intermenstrual bleeding, spotting, amenorrhea, changes in the menstrual cycle, increase in the size of uterine fibroids, vaginal candidiasis, increased cervical secretion, cervical erosion, decreased libido, premenstrual syndrome, temporary infertility after discontinuation of the drug.

Breasts: tenderness and feeling of tension, galactorrhea, engorgement, enlargement, decreased lactation when taken immediately after childbirth.

Skin: erythema nodosum, skin rash, chloasma, erythema exudativum, acne, seborrhea, alopecia, hirsutism, facial pigmentation, hypertrichosis, pemphigoid (gestational herpes), melanoderma with a tendency to persist.

Organs of vision: cataract, lesions of the optic nerve, change in corneal curvature, discomfort when wearing contact lenses.

Central nervous system: headache, mood changes, irritability, depression, chorea.

Metabolism: fluid retention, changes in body weight (decrease or increase), decreased glucose tolerance, changes in appetite.

Kidneys: decreased renal function, hemolytic-uremic syndrome.

Other: dizziness, migraine.

If menstrual-like bleeding occurs, taking Cilest should be continued. If the bleeding does not stop, then an examination is necessary to rule out organic causes. Similar recommendations apply to spotting, which may appear irregularly over several cycles of taking Cilest or for the first time after prolonged use of the drug. If bleeding does not occur at the end of the drug intake cycle, it is necessary to rule out pregnancy before starting a new cycle of taking Cilest.

Contraindications

• Hypersensitivity to any of the components of the drug;
• Venous thrombosis, including in the medical history (including deep vein thrombosis, pulmonary embolism);
• Arterial thrombosis, including in the medical history (including acute cerebrovascular accident, myocardial infarction, retinal artery thrombosis) or precursors of thrombosis (including angina pectoris or transient ischemic attack);
• Presence of serious or multiple risk factors for arterial thrombosis;
• Arterial hypertension (persistent increase in blood pressure above 160/100 mm Hg);
• Diabetes mellitus with vascular damage;
• Hereditary dyslipoproteinemia;
• Hereditary predisposition to venous or arterial thrombosis, for example, antithrombin-III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia, presence of antiphospholipid antibodies (anticardiolipin antibodies, group of antibodies against negatively charged phospholipids);
• Migraine with aura;
• Confirmed or suspected breast cancer;
• Endometrial cancer or other confirmed or suspected estrogen-dependent neoplasms;
• Benign or malignant liver tumors;
• Genital bleeding of unknown etiology;
• Postmenopausal period;
• Age under 18 years;
• Postpartum period (4 weeks);
• Lactation period;
• Confirmed or suspected pregnancy;
• Cholestatic jaundice during pregnancy, including in the medical history;
• Sickle cell anemia;
• Hepatic insufficiency;
• Hemolytic anemia;
• Otosclerosis.

With caution

• Venous or arterial embolism in siblings or parents at a relatively young age;
• Prolonged immobilization or extensive surgical operation;
• Risk factors for coronary heart disease, such as smoking, hyperlipidemia, arterial hypertension or obesity;
• Arterial hypertension (persistent blood pressure levels 140-159/90-99 mm Hg);
• Superficial phlebitis and varicose veins;
• Heart valve lesions with complications (mitral stenosis with atrial fibrillation);
• Diabetes mellitus;
• Severe depression or a history of this disease;
• Systemic lupus erythematosus;
• Crohn’s disease;
• Ulcerative colitis;
• Hypertriglyceridemia, including in family history;
• Acute liver dysfunction during previous pregnancy or previous use of sex hormones;
• Menstrual cycle disorders;
• Renal dysfunction;
• Gallbladder diseases;
• Epilepsy;
• Uterine fibroids;
• Mastopathy;
• Tuberculosis.

Use in Pregnancy and Lactation

Cilest is contraindicated in pregnant women.

Epidemiological studies have not revealed an increased risk of birth defects in children whose mothers took oral contraceptives before pregnancy. Most modern studies have also not found teratogenic effects, in particular heart abnormalities and limb shortening, in the offspring of women who mistakenly took oral contraceptives during pregnancy.

Combined oral contraceptives can affect lactation, i.e., reduce the amount and change the composition of breast milk. In addition, a small part of contraceptive steroids and/or their metabolites can penetrate into breast milk. In this regard, Cilest is contraindicated during breastfeeding.

Use in Hepatic Impairment

With caution in renal dysfunction.

Use in Renal Impairment

With caution in acute liver dysfunction during previous pregnancy or previous use of sex hormones.

Pediatric Use

Contraindicated in children under 18 years of age.

Special Precautions

Laboratory tests

Oral contraceptives can cause changes in hormonal parameters and liver function indicators.

• Levels of prothrombin and factors II, VII, VIII, IX, X, XII and XIII increase; the level of antithrombin 3 decreases; platelet aggregation induced by norepinephrine is enhanced.

• The concentration of thyroxine-binding globulin increases, which causes an increase in the concentration of total thyroid hormone.

• The content of other binding proteins in the serum may increase.

• Levels of sex hormone-binding globulins increase, resulting in an increase in the concentration of sex hormones; it should be noted, however, that the levels of free or biologically active sex hormones decrease or do not change.

• Levels of high-density lipoprotein cholesterol (HDL-C) and total cholesterol may increase, levels of low-density lipoprotein cholesterol (LDL-C) may increase or decrease, while the LDL-C/HDL-C ratio may decrease, and triglyceride levels remain unchanged.

• Glucose tolerance may decrease.

• The use of oral contraceptives can cause a decrease in the concentration of serum folates. This change may be clinically important if a woman becomes pregnant shortly after discontinuing the oral contraceptive.

Oral contraceptives do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Before prescribing an oral contraceptive to a patient, it is recommended to collect a complete medical history and conduct a thorough physical examination. Examinations must be repeated periodically in accordance with the standards of quality gynecological care.

Before prescribing an oral contraceptive to a patient, it is necessary to find out which herbal remedies she is taking, as well as familiarize herself with the information in the leaflets for the drugs that the woman will take simultaneously with the oral contraceptive.

In the presence of undiagnosed, persistent or recurrent abnormal vaginal bleeding, a malignant tumor must be ruled out. After hepatitis, an oral contraceptive can be prescribed after 3 months (in severe cases after 6 months) after the normalization of the results of functional liver tests.

Thromboembolic and other vascular complications

It has been established that the use of oral contraceptives increases the risk of thromboembolic complications and thrombosis. Case-control studies have shown that the relative risk for women using oral contraceptives, compared to those who do not use these drugs, is 3:1 for the first episode of superficial vein thrombosis, 11:4 for deep vein thrombosis or pulmonary embolism and 6:1.5 for women with diseases predisposing to thromboembolic complications. Studies have shown that the relative risk is somewhat lower, approximately 3:1 for new cases and about 4.5:1 for new cases requiring hospitalization. The risk of thromboembolic complications associated with the use of oral contraceptives does not depend on the duration of use of these drugs and disappears after their discontinuation. In women using oral contraceptives, the relative risk of postoperative thromboembolic complications is increased by 2-4 times. The relative risk of venous thrombosis in women with diseases predisposing to this complication is 2 times higher than in women without such diseases. If possible, oral contraceptives should not be taken at least 4 weeks before and for 2 weeks after a planned surgery, which is associated with an increased risk of thromboembolism, as well as during prolonged immobilization and during the recovery period. In the early postpartum period, the risk of thromboembolic complications is also increased, and therefore women who decide not to breastfeed can start taking oral contraceptives no earlier than 3 weeks after delivery. After an artificial or spontaneous abortion that occurred at the 20th week of pregnancy or later, the use of hormonal contraceptives can be started either on the 21st day after the abortion or on the first day of the first spontaneous menstruation, whichever comes first.

The relative risk of arterial thrombosis (e.g., stroke, myocardial infarction) increases in the presence of other predisposing factors, such as smoking, arterial hypertension, hyperlipidemia, obesity, diabetes mellitus, history of preeclampsia and older age. These severe vascular complications were observed in women who took oral contraceptives with an estrogen content of 50 mcg or more. The risk of vascular complications is probably lower when using oral contraceptives containing lower doses of estrogen and progestogen, but this assumption has not yet received solid evidence.

The risk of serious cardiovascular side effects increases with age and in heavy smokers. This risk is very high in smoking women over 35 years of age. Women using oral contraceptives should be strongly advised to quit smoking.

An increase in blood pressure has been reported in women taking oral contraceptives. Studies have shown that with long-term use of estrogen at a dose of 50 mcg or more, the likelihood of increased blood pressure increases with age. In many women, blood pressure normalizes after discontinuation of oral contraceptives. No difference was found in the frequency of arterial hypertension in women who had taken oral contraceptives in the past and in women who had never taken such drugs. In women with arterial hypertension (persistent blood pressure level 140-159/90-99 mm Hg) before starting an oral contraceptive, blood pressure must be normalized. In case of a strong increase in blood pressure, the oral contraceptive must be discontinued.

There are reports of retinal thrombosis associated with the use of oral contraceptives. The use of oral contraceptives must be discontinued in case of unexplained transient, partial or complete loss of vision; appearance of a veil before the eyes or diplopia; papilledema or occurrence of retinal vascular changes. In such situations, appropriate diagnostic and therapeutic actions must be taken without delay.

Liver neoplasms

Benign and malignant liver tumors (adenomas and hepatocellular carcinoma) occur rarely. Case-control studies have shown that the risk of these tumors may increase with the use of oral contraceptives and depends on the duration of their use. Rupture of benign liver adenomas can cause death due to internal bleeding.

Cancers of the Reproductive Organs and Breast

The incidence of breast, endometrial, ovarian, and cervical cancer in women using oral contraceptives has been the subject of numerous epidemiological studies. Results are conflicting, however, data from most studies have shown that the use of oral contraceptives is not associated with an overall increase in the risk of breast cancer. Some authors have reported an increased relative risk of breast cancer, particularly in young women. It has been shown that this increased relative risk depends on the duration of oral contraceptive use.

A meta-analysis of the results of 54 epidemiological studies indicates that women who are currently using combined oral contraceptives or have used them in the preceding 10 years have a slightly increased risk of having breast cancer diagnosed. Based on these data, it is impossible to determine whether the increased risk is due to earlier diagnosis of breast cancer in women who have ever used oral contraceptives, the biological effects of hormonal contraceptives, or a combination of these two factors. This meta-analysis also suggests that the age at which women stop taking combined oral contraceptives is an important risk factor for breast cancer: the older the age, the more frequently breast cancer is diagnosed. The duration of oral contraceptive use plays a less important role.

Before prescribing an oral contraceptive to a woman, the possibility of an increased risk of breast cancer should be discussed with her, and this risk should be weighed against the benefits of combined oral contraceptives.

Some epidemiological studies have shown that long-term use of oral contraceptives is associated with an increased risk of cervical neoplasia. The association of these data with the use of combined oral contraceptives has not been proven. It should be noted, however, the uncertainty regarding the extent to which these data may be influenced by differences in sexual behavior and other factors.

Metabolic Effects

Oral contraceptives may reduce glucose tolerance. This effect has been shown to be directly dependent on the estrogen dose. In addition, progestogens can enhance insulin secretion and cause insulin resistance, and this effect is not the same for different progestogens. However, it should be noted that in women without diabetes mellitus, oral contraceptives are unlikely to affect fasting blood glucose levels. Given the above, the condition of women with impaired glucose tolerance or diabetes mellitus who are taking oral contraceptives should be carefully monitored. In a small percentage of women, persistent hypertriglyceridemia occurs while taking oral contraceptives. Changes in serum triglyceride and lipoprotein levels have been observed in women using oral contraceptives.

Headache

In case of onset or worsening of migraine, or the appearance of a new type of headache that is recurrent, persistent, or severe, it is necessary to discontinue the oral contraceptive and determine the cause of the headache.

Menstrual Irregularities

Women using oral contraceptives, especially during the first 3 months of use, may experience intermenstrual bleeding, spotting, and/or amenorrhea. Non-hormonal causes of such irregularities should be considered and, if necessary, appropriate diagnostic procedures should be performed to rule out malignancy or pregnancy.

Some women may experience amenorrhea or oligomenorrhea while taking an oral contraceptive, especially if these conditions were present before starting the contraceptive drug.

Chloasma

Chloasma may sometimes occur while taking oral contraceptives, particularly in women with a history of chloasma of pregnancy. Women prone to developing chloasma should avoid exposure to sunlight and ultraviolet radiation while using oral contraceptives. Chloasma often does not disappear completely.

Overdose

No serious cases of poisoning due to overdose of Cilest have been reported. Overdose may cause nausea, vomiting, and vaginal bleeding.

There is no specific antidote. In case of overdose, gastric lavage should be performed (within the first hour after drug intake) and symptomatic therapy should be administered.

Drug Interactions

Drugs that induce enzymes metabolizing estrogens (for example, estrogen-2-hydroxylase – coenzyme CYP3A4 of the cytochrome P-450 system) reduce the contraceptive effectiveness of hormonal drugs. It is also possible that induction of these same isoenzymes may lead to a decrease in the blood concentration of the progestogenic component of Cilest. Potentially clinically significant in this regard are medicinal products and herbal remedies that affect enzymes involved in the biological transformation of contraceptive steroid hormones (for example, St. John’s wort, barbiturates, carbamazepine, phenytoin, sulfonamides, pyrazolone derivatives, rifampicin).

Some protease inhibitors and some antiretroviral drugs have been shown to increase (e.g., indinavir) or decrease (e.g., ritonavir) the blood concentration of combined hormonal contraceptives. Another type of interaction involves disruption of the intrahepatic circulation of estrogens, resulting in accelerated excretion and decreased concentration of ethinylestradiol. When taken concomitantly with some antibiotics (e.g., ampicillin or tetracycline), insufficient breakdown of estrogen and fatty acid conjugates by intestinal bacteria is observed.

Storage Conditions

At a temperature between 15°C and 30°C (86°F). Keep out of reach of children.

Shelf Life

The shelf life is 2 years.

Dispensing Status

By prescription.

Important Safety Information

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