One tablet contains
active ingredients: ethinylestradiol 0.03 mg, dienogest 2.0 mg,
excipients: lactose monohydrate, corn starch, maltodextrin, magnesium stearate,
shell composition: sucrose, liquid glucose, calcium carbonate, povidone K 25, macrogol 35000, titanium dioxide (E 171), carnauba wax.
After oral administration, dienogest is rapidly and almost completely absorbed, its maximum serum concentration of 51 ng / ml is reached after about 2.5 hours. Bioavailability in combination with ethinyl estradiol is approximately 96%.
Dienogest binds to serum albumin and does not bind to sex hormone-binding globulin (SHBG) and corticoid-binding globulin (CBG). In the free form is about 10% of the total concentration in the blood serum; about 90% – non-specifically associated with serum albumin. The induction of SHBG synthesis by ethinylestradiol does not affect the binding of dienogest to whey protein. The apparent volume of distribution for dienogest is approximately 37-45 L/kg.
Dienogest is metabolized predominantly by hydroxylation and conjugation to form inactive metabolites. These metabolites are rapidly excreted from the blood plasma, thus, no active metabolite is noted in the plasma, and only dienogest is found in an unchanged state. The total clearance is about 3.6 l / h after a single application.
A decrease in the level of dienogest in the blood serum occurs with an elimination half-life of 8.5–10.8 hours. Only a small part of dienogest is excreted by the kidneys in an unchanged state. Metabolites are excreted in the urine and bile in a ratio of about 3:1. The half-life of metabolites is approximately 14.4 hours.
The pharmacokinetics of dienogest is not affected by the level of SHBG in the blood serum. As a result of daily administration of the drug, the level of the substance in the serum increases by about 1.5 times.
After oral administration, ethinylestradiol is rapidly and completely absorbed. The maximum concentration in blood serum, equal to approximately 67 pg / ml, is reached in 1.5-4 hours. During absorption and first passage through the liver, ethinyl estradiol is metabolized, resulting in an average oral bioavailability of about 44%.
Ethinylestradiol is almost completely (approximately 98%), although non-specific, bound to albumin. Ethinylestradiol induces the synthesis of SHBG. The apparent volume of distribution of ethinylestradiol is 2.8 – 8.6 l / kg.
Ethinylestradiol undergoes presystemic conjugation both in the small intestine mucosa and in the liver. Ethinylestradiol is primarily metabolized by aromatic hydroxylation, producing various hydroxylated and methylated metabolites, both as free metabolites and as conjugates with glucuronic and sulfuric acids. The rate of clearance from blood plasma is 2.3 – 7 ml / min / kg.
The decrease in the concentration of ethinylestradiol in the blood serum is biphasic; the first phase is characterized by a half-life of about 1 hour, the second – 10-20 hours. It is not excreted from the body unchanged. Metabolites of ethinylestradiol are excreted in the urine and bile in a ratio of 4:6 with an elimination half-life of about 24 hours.
The state of equilibrium concentration is reached during the second half of the treatment cycle, when the serum level of the drug increases by about 2 times compared with the level when taking a single dose of the drug.
Janine® is a low-dose monophasic oral combined estrogen-progestogen contraceptive drug.
The contraceptive effect of Jeanine® is based on the interaction of various factors, the most important of which are the inhibition of ovulation and changes in the secretion of cervical mucus. In addition to its contraceptive effect, Janine® has a positive effect that should be considered when choosing a birth control method: the menstrual cycle becomes more regular, painful periods are less common, bleeding decreases, resulting in a reduced risk of iron deficiency anemia.
The progestogenic component of Jeanine® – dienogest is considered the only derivative of nortestosterone with antiandrogenic properties.
The presence of an antiandrogenic effect has been proven in clinical studies with the participation of a limited number of patients with the inflammatory form of acne vulgaris.
Dienogest has a positive effect on the lipid profile, while increasing the content of high-density lipoproteins.
There is also evidence of a reduced risk of endometrial cancer and ovaries. In addition, high-dose oral contraceptives (0.05 mg ethinyl estradiol) reduce the incidence of ovarian cysts, pelvic inflammatory disease, benign breast disease, and ectopic pregnancy. The extent to which these data relate to low-dose contraceptives requires further study.
Indications for use
– oral contraception
– moderate acne in women who need hormonal contraception
Dosage and administration
Jeanine® has a high contraceptive reliability. The “method failure” rate is no more than 1% per year. Contraceptive reliability may be reduced when pills are missed or taken incorrectly.
The tablets should be taken orally in the order indicated on the package, every day at about the same time, with a little water. Take one tablet per day continuously for 21 days. The next pack is started after a 7-day tablet break, during which withdrawal bleeding usually occurs. Bleeding usually starts 2-3 days after taking the last pill and may not end before starting a new pack.
How to start taking Janine®
In the absence of taking any hormonal contraceptives in the previous month
Janine® is started on the first day of the menstrual cycle (i.e. the first 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 necessary to additionally use a barrier method of contraception during the first 7 days of taking the tablets from the first package.
• when switching from combined hormonal contraceptives (combined oral contraceptive, vaginal ring, transdermal patch) It is preferable to start taking Janine the next day after taking the last hormone-containing 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 hormone-free tablet for drugs, containing 28 tablets per pack). When switching from a vaginal ring or transdermal patch, it is preferable to start taking Janine® on the day the ring or patch is removed, but in no case no later than the day the next ring or patch should have been applied.
• when switching from contraceptives containing only gestagens (“mini-pill”, injectable forms, implant) or from a progestogen-releasing intrauterine system (IUD).
A woman can switch from a mini-pill to Jeanine® on any day (without a break), from an implant or intrauterine contraceptive with a progestogen – on the day it is removed, from an injection form – from the day the next injection was to be made. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets.
• After an abortion in the first trimester of pregnancy
A woman can start taking the drug immediately. If this condition is met, the woman does not need additional contraceptive protection.
• After childbirth or abortion in the second trimester of pregnancy
It is recommended to start taking the drug on the 21-28th day after childbirth or abortion. If the reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets. However, if a woman has already lived a sexual life, pregnancy should be excluded before taking Janine®, or it is necessary to wait for the first menstruation.
Taking missed pills
If the delay in taking the drug was less than 12 hours, contraceptive protection is not reduced. The woman should immediately take the missed pill, the next pill is taken at the usual time.
If the delay in taking the tablets was more than 12 hours, contraceptive protection may be reduced. In this case, you can be guided by the following two basic rules:
• The drug should never be interrupted for more than 7 days.
• 7 days of continuous tablet intake are required to achieve adequate suppression of hypothalamic-pituitary-ovarian regulation.
Accordingly, the following advice can be given if the delay in taking the tablets was more than 12 hours (the interval from the moment of taking the last tablet is more than 36 hours):
• First week of taking the drug
The woman should immediately take the last missed pill (even if it means taking two pills at the same time). The next tablet is taken at the usual time. Additionally, a barrier method of contraception (such as a condom) must be used for the next 7 days. If sexual intercourse took place during the week before the tablet was missed, the reliability of the drug is reduced, so the possibility of pregnancy must be taken into account.
As the number of missed pills increases and the regular break period approaches, the chance of pregnancy increases.
• Second week of taking the drug
The woman must urgently take the last missed pill (even if it means taking two pills at the same time). The next tablet is taken at the usual time.
If the woman has taken the pills correctly in the 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as if you miss two or more tablets, you must additionally use barrier methods of contraception (for example, a condom) for 7 days.
• Third week of taking the drug
The risk of reduced reliability is inevitable due to the upcoming break in taking pills.
A woman must strictly adhere to one of the two following options. At the same time, there is no need to use additional contraceptive measures if the drug was taken correctly in the previous 7 days before missing the pill.
1. The woman should urgently take the last missed pill (even if it means taking two pills at the same time). She then continues to take her tablets at the usual time. The next pack should be started immediately after the completion of taking the tablets from the current pack, that is, without interruption in taking the pills. Withdrawal bleeding is unlikely until the second pack is finished, but spotting and breakthrough bleeding may occur while taking the tablets.
2. The woman may also stop taking the pills from the current package. Then she should take a break for 7 days, including the day she missed the pill, and then start taking a new pack.
If a woman misses a pill and then does not have withdrawal bleeding during the pill break, pregnancy should be ruled out.
Recommendations in case of vomiting and diarrhea
In severe gastrointestinal disorders, the absorption of the drug may be incomplete. In this case, additional contraceptive measures should be taken.
If a woman vomits within 3-4 hours after taking the pill, it is necessary to focus on the advice regarding skipping pills. If a woman does not want to change the normal regimen of taking the drug, she should take an additional tablet if necessary (or 2 tablets from another package).
Changing the start date of the menstrual cycle
In order to delay the onset of menstruation, a woman should continue taking the pills from the new Jeanine® pack immediately after all the pills from the previous one have been taken, without interruption in taking. Tablets from a new package can be taken for as long as the woman wishes (until the package runs out). While taking the drug from the second package, a woman may experience spotting or breakthrough uterine bleeding. Resume taking Janine® from a new pack after the usual 7-day break.
In order to move the day of the start of menstruation to another day of the week, a woman is advised to shorten the duration of the next break in taking pills by as many days as she wishes. The shorter the interval, the higher the risk that she will not have withdrawal bleeding, and subsequently spotting and breakthrough bleeding during the second pack (same as if she would like to delay the onset of her period).
Possible side effects
Often (≥1/100, <1/10)
– pain in the mammary glands, including discomfort and tension
Uncommon (≥1/1000, 1/100)
– vaginitis/vulvovaginitis, vaginal candidiasis or other fungal vulvovaginal infections
– increased appetite
– decreased mood
– dizziness, migraine
– arterial hypertension and hypotension
– abdominal pain, discomfort and feeling of “bursting” in the abdomen, nausea, vomiting, diarrhea
– rash, including patchy and acne, itching, including generalized, alopecia
– pathological withdrawal bleeding, including menorrhagia, hypomenorrhea, oligomenorrhea, intermenstrual bleeding (vaginal or uterine); dysmenorrhea, amenorrhea; discharge from the genital tract; breast enlargement, including breast discomfort and tenderness, breast swelling, ovarian cysts, pelvic pain
– fatigue, including malaise and asthenia
– changes in body weight (gain, decrease or unstable weight)
Rare (≥1/10,000, <1/1000)
– hypersensitivity reactions
– salpingo-oophoritis, mastitis, cervicitis, fungal infections, candidiasis, influenza, herpes of the oral mucosa, bronchitis, sinusitis, upper respiratory tract infections, viral infection, urinary tract infections, cystitis
– uterine leiomyoma, breast lipoma
– depression, mental disorders, insomnia, sleep disorders, aggression
– ischemic stroke, cerebrovascular disorders, dystonia
– dry eyes, eye irritation, blurred vision, oscillopsia
– sudden hearing loss, tinnitus, vertigo, hearing loss
– cardiovascular disorders, tachycardia
– thrombosis / embolism of the pulmonary artery, thrombophlebitis, diastolic
hypertension, orthostatic circulatory dysregulation, hot flashes
– phlebeurysm, changes in the veins, pain in the veins
– bronchial asthma, hyperventilation
– dyspepsia, gastritis, enteritis
– skin reactions and skin changes, including allergic dermatitis, atopic dermatitis / neurodermatitis, eczema, psoriasis
– hyperhidrosis, chloasma, pigmentation disorders / hyperpigmentation,
seborrhea, dandruff, hirsutism, orange skin symptom,
back pain, musculoskeletal discomfort, myalgia, pain in
– cervical dysplasia, adnexal cyst, adnexal pain, breast cyst, fibrocystic disease of the mammary glands, pain in the genitals associated with sexual intercourse
– galactorrhea, menstrual disorders
– pain behind the sternum, peripheral edema, influenza-like illness, inflammatory diseases, pyrexia, irritability
– elevated plasma triglycerides, hypercholesterolemia
– manifestation of an asymptomatic accessory mammary gland
With an unknown frequency (revealed only in the process of post-marketing observations)
– mood changes, decreased libido, increased libido
– contact lens intolerance
– urticaria, erythema nodosum, erythema multiforme
– secretions from the mammary glands
– fluid retention
The following serious side effects, described in the Precautions and Warnings section, have been reported in women using combined oral contraceptives:
– venous thromboembolic disorders
– arterial thromboembolic disorders
– cerebrovascular disorders, including stroke
– arterial hypertension
– Impaired glucose tolerance or effects of peripheral insulin resistance
– liver tumors (benign and malignant)
– liver dysfunction
– in women with hereditary angioedema, provoking or exacerbating the symptoms of the disease under the influence of exogenous estrogens
– the appearance or worsening of the following conditions, the relationship of which with the use of combined oral contraceptives has not been proven: jaundice and / or itching associated with cholestasis; the formation of stones in the gallbladder; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea; herpes of pregnant women; hearing loss associated with otosclerosis, Crohn’s disease and ulcerative colitis, cervical cancer
Jeanine should not be used in the presence of any of the conditions listed below. In the event of the development of any of these conditions, the drug should be immediately canceled.
– hypersensitivity to any of the components of the drug
– thrombosis (venous and arterial) and thromboembolism at present or in history (for example, deep vein thrombosis, pulmonary embolism, myocardial infarction) or cerebrovascular disorders
– conditions preceding thrombosis (for example, transient
ischemic attacks, angina pectoris) currently or in history
– the presence of multiple or pronounced risk factors for venous or arterial thrombosis
– migraine with a history of focal neurological symptoms
– diabetes mellitus with vascular complications
– severe liver disease (before normalization of liver tests)
Liver tumors (benign or malignant) at present or in history
– identified hormone-dependent malignant diseases (including genital organs or mammary glands) or suspicion of them
– vaginal bleeding of unknown origin
– pregnancy or suspected pregnancy
– hereditary fructose intolerance, Lapp-lactase deficiency, glucose-galactose malabsorption
Interaction with certain drugs (drugs that induce liver enzymes, some antibiotics) may lead to breakthrough bleeding and / or reduce the contraceptive effectiveness of Janine®. In while taking such drugs, a woman should additionally use a barrier method of contraception or choose another method of contraception. While taking drugs that affect microsomal enzymes, and within 28 days after their withdrawal, you should additionally use a barrier method of contraception. While taking antibiotics (with the exception of rifampicin and griseofulvin) and within 7 days after their withdrawal, you should additionally use a barrier method of contraception. If the period of using the barrier method of contraception from unwanted pregnancy ends later than the pills in the pack, you need to move on to the next pack of Janine® without the usual break in taking the pills.
Substances that interfere with the effectiveness of Jeanine® (liver enzyme inducers and antibiotics)
Drugs that reduce contraceptive effectiveness include drugs that induce liver enzymes (increase hepatic metabolism): phenytoin, barbiturates, primidone, carbamazepine and rifampicin; there are also suggestions for oxcarbazepine, topiramate, felbamate, ritonavir and griseofulvina and preparations containing St. John’s wort.
In addition, HIV proteases (eg, ritonavir) and non-nucleoside reverse transcriptase inhibitors (such as nevirapine), and combinations thereof, have the potential to interfere with hepatic metabolism.
Effect on enterohepatic circulation:
Contraceptive protection is reduced when taking certain antibiotics (such as penicillins and tetracyclines), since, according to some reports, they can reduce the intrahepatic circulation of estrogens, thereby lowering the concentration of ethinyl estradiol.
Dienogest is a substrate of the cytochrome P450 (CYP) 3A4 system.
Known inhibitors of the cytochrome CYP3A4 system such as antifungals (ketoconazole), cimetidine, verapamil, macrolides (erythromycin), diltiazem, antidepressants, and grapefruit juice may increase plasma levels of dienogest.
Effect of Janine® on other drugs
Janine may interfere with the metabolism of other drugs, resulting in an increase (eg, cyclosporine) or a decrease (eg, lamotrigine) in plasma and tissue concentrations.
Precautions and Warnings
If any of the conditions/risk factors listed below are currently present, then the potential risk and expected benefit of treatment with Jeanine® should be carefully weighed in each individual case and discussed with the woman before she decides to start taking the drug. In the event of an increase or first manifestation of any of these conditions or risk factors, a decision should be made to discontinue the drug.
Diseases of the cardiovascular system
The results of epidemiological studies indicate a relationship between the use of combined oral contraceptives and an increased risk of developing venous and arterial thrombosis and thromboembolic processes, such as myocardial infarction, deep vein thrombosis, pulmonary embolism and cerebrovascular disorders. These diseases are rare.
The risk of developing venous thromboembolism (VTE) is highest in the first year of taking oral contraceptives. An increased risk is present after the initial use of combined oral contraceptives or the resumption of use of the same or different combined oral contraceptives (after a break between doses of 4 weeks or more). Data from a large prospective study in 3 groups of patients show that this increased risk is predominantly present during the first 3 months.
The overall risk of venous thromboembolism in patients taking oral contraceptives with a low dose of estrogens (less than 50 mcg ethinyl estradiol) is 2-3 times higher than in women not using them in the absence of pregnancy, however, this risk remains lower compared to with the risk of VTE during pregnancy and childbirth.
VTE can be fatal (in 1-2% of cases).
VTE manifesting as deep vein thrombosis and/or pulmonary embolism can occur with any combined oral contraceptive.
In women taking combined oral contraceptives, extremely rare cases of thrombosis of other blood vessels, such as hepatic, mesenteric, renal, cerebral arteries and veins, as well as retinal vessels, have been described. There is no consensus regarding the relationship between the occurrence of these events and the use of combined oral contraceptives.
Symptoms of deep vein thrombosis include the following: unilateral swelling in the leg or along a vein in the leg, pain or discomfort in the leg only when standing or walking, localized fever in the affected limb, redness or discoloration of the skin on the leg.
Symptoms of pulmonary embolism are as follows: the sudden onset of unexplained shortness of breath or rapid breathing, a sudden attack of coughing, which may be accompanied by hemoptysis, severe chest pain, which may increase with deep breathing, anxiety, severe dizziness; fast or irregular heartbeat. Some of these symptoms (eg, “shortness of breath” and “cough”) are nonspecific and may therefore be misinterpreted as signs of more frequent and less severe disorders (eg, respiratory tract infections).
Arterial thromboembolism may include cerebrovascular disorders, vascular occlusion, or myocardial infarction.
Symptoms of cerebrovascular disorders may include sudden weakness or numbness of the face, upper and lower extremities, especially on one side of the body, sudden confusion, impaired speech, or difficulty with perception; sudden blurred vision in one or both eyes, sudden trouble walking, dizziness, loss of balance or coordination, sudden severe or prolonged headache with no apparent cause, loss of consciousness or fainting with or without seizures. Other signs of vascular occlusion may also be sudden pain, swelling, or mild cyanosis limbs, symptoms of “acute abdomen”.
Symptoms of a myocardial infarction include: pain, discomfort, pressure, heaviness, a feeling of constriction or fullness in the chest, in the arm or behind the sternum, a feeling of discomfort radiating to the back, cheekbones, larynx, arm, abdomen, a feeling of fullness or fullness in the stomach, a feeling of suffocation , cold sweat, nausea, vomiting or dizziness, severe weakness, anxiety, shortness of breath, rapid or irregular heartbeat.
Arterial thromboembolism can be fatal.
Risk of thrombosis (venous and/or arterial), thromboembolic or cerebrovascular disorders