NovaRing® (NuvaRing®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceEtonogestrel + EthinylestradiolEtonogestrel + Ethinylestradiol
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  • NovaRing®
    implant the vagina. 
    Organon, N.V.     Netherlands
    • Dosage form: & nbspVaginal rings
    Composition:

    1 ring vaginal contains:

    active substances: etonogestrel - 11.7 mg, these sawed estradiol - 2.7 mg; Excipients: ethylene and vinyl acetate copolymer [28% vinyl acetate] - 1677 mg, ethylene and vinyl acetate copolymer [9% vinyl acetate] 197 mg, magnesium stearate 1.7 mg.

    Description:Smooth, clear, colorless or almost colorless ring without large visible damage with a transparent or almost transparent area at the junction.
    Pharmacotherapeutic group:contraceptive combination (estrogen + progestogen)
    ATX: & nbsp

    G.02.B.B.01   Intravaginal ring with progestogen and estrogen

    Pharmacodynamics:

    Mechanism of action

    NovaRing® is a hormonal combination contraceptive that contains etonogestrel and ethinylestradol. Etonogestrel is a progestogen (a derivative of 19-nortestosterone), which binds with high affinity to the receptors of progesterone in target organs. Ethinyl estradol is an estrogen and is widely used for the manufacture of contraceptives.

    The contraceptive effect of NovaRing® is due to a combination of various factors, the most important of which is suppression of ovulation.

    Efficiency

    In clinical studies, it was found that the Pearl Index (an indicator of the rate of pregnancy in 100 women for 1 year of contraception) in women aged 18 to 40 years for drug NovaRing® was 0.96 (95% CI: 0.64 -1.39) and 0.64 (95% CI: 0,35-1,07) for statistical analysis of all randomized member (PT assay) and the analysis of the member studies completed according to their protocol (PP analysis), respectively. These values ​​were similar to the values ​​Pearl index obtained in comparative studies of combined oral contraceptives (COC) containing levonorgestrel / ethinyl estradiol (0.150 / 0.030 mg) or drospirenoi / ethinyl estradiol (3 / 0.30 mg).

    Against the background of the drug NovaRing® cycle becomes more regular, reduced pain and bleeding intensity mepstrualnopodobpogo, thereby reducing the incidence of iron deficiency states. There is evidence of a reduction in the risk of endometrial and ovarian cancer when the drug is used.

    Nature of bleeding

    Comparison of the characteristics of the nature of bleeding during one year in 1000 women,NovaRing® and COC containing levonorgestrel / ethinyl estradiol (0.150 / 0.030 mg) showed a significant reduction in the frequency of breakthrough bleeding or spotting bleeding with NovaRing® in comparison with the COC. In addition, the frequency of cases when bleeding occurred only during a break in the use of the drug was significantly higher among women using NovaRing®.

    Effect on bone mineral density

    A comparative two-year study of the effect of NovaRing®(n = 76) and nonhormonal intrauterine device (n = 31) did not reveal an effect on bone mineral density in women.

    Children

    The safety and efficacy of NovaRing® for girls under the age of 18 years have not been studied.

    Pharmacokinetics:

    Etonogestrel

    Suction

    Etonogestrel released from the vaginal ring of NovaRing® is rapidly absorbed through the mucous membrane of the vagina. The maximum concentration of etonogestrel in the blood plasma, about 1700 pg / ml, is reached approximately 1 week after the introduction of the ring. Plasma concentrations vary in a small range and slowly decrease to about 1600 pg / ml after 1 week, 1500 pg / ml after 2 weeks and 1400 pg / ml through 3 application pads.Absolute bioavailability is about 100%, which exceeds the bioavailability of oral etonogestrel. According to the results of measurements of the concentrations of etonogestrel in the cervical region and inside the uterus, the observed values ​​of the concentrations of etonogestrel were comparable in women using NovaRing® and women using oral contraceptives containing 0.150 mg of desogestrel and 0.020 mg of ethinylestradanol.

    Distribution

    Etonogestrel binds to blood plasma albumin and sex hormone binding globulin (SHBG). The apparent volume of ethonogestrel distribution is 2.3 l / kg.

    Metabolism

    Biotransformation of etonogestrel occurs by the known ways of metabolism of sex hormones. Apparent blood plasma clearance is about 3.5 l / h. Direct interaction with ethyl estradiol, taken concomitantly, was not detected.

    Excretion

    The concentration of etonogestrel in the blood plasma is reduced in two phases. In the terminal phase, the half-life period is approximately 29 hours. Etonogestrel and its metabolites are excreted by the kidneys and through the intestine with bile in a ratio of about 1.7: 1.The period of nerve elimination of metabolites is approximately 6 days.

    Ethinylestradiol

    Suction

    Ethinyl estradiol, released from the vaginal ring of NovaRing ®, quickly absorbed through the mucous membrane of the vagina. The maximum plasma concentration of about 35 pg / ml is achieved 3 days after the introduction of the ring and decreases to 19 pg / ml after 1 week, up to 18 pg / ml after 2 weeks and 18 pg / ml after 3 weeks of use. The absolute bioavailability is about 56% and is comparable to that of oral ethinyl estradiol. Based on the results of measurements of ethinyl estradiol concentrations in the cervical region and inside the uterus, the observed values ​​of ethinyl estradiol concentrations were comparable in women using NovaRing® and women using oral contraceptives containing 0.150 mg of desogsstrelet and 0.020 mg of ethinylestradiol. The concentration of ethinyl estradiol was studied in a comparative randomized trial of NovaRing ® (daily release of ethinylestradiol in the vagina 0.015 mg), transdermal patch (noregestromine / ethinyl estradiol, daily release of ethinylestradiol 0.020mg) and COC (lswonorgersl / ethinyl estradiol, daily release of ethinylestradiol 0.030 mg) during one cycle in healthy women. Systemic exposure to ethinyl estradiol within a month (AUCo-∞) for NovaRing ® was statistically significantly lower than that of the patch and COC, and was 10.9ng / ml compared to 37.4 and 22.5 ng h / ml in the patch and COC, respectively.

    Distribution

    Ethinyl estradiol binds non-specifically to plasma albumin. The apparent volume of distribution is about 15 l / kg.

    Metabolism

    Ethinyl estradiol is metabolized by aromatic hydroxylation. In the course of its b-transformation, a large number of hydroxylated and methylated metabolites are formed. They circulate in free form or in the form of sulfate and piccuronide conjugates. The apparent clearance is approximately 35 l / h.

    Excretion

    The concentration of ethinylestradiol in blood plasma is reduced in two phases. The period of elimination in the terminal phase varies widely; median is about 34 hours. Ethinylestradiol not output in unmodified form. Metabolites of ethinyl estradiol are excreted by the kidneys and through the intestine with bile in a ratio of 1.3: 1.The half-life of metabolites is about 1.5 days.

    Special patient groups

    Children

    Pharmacokinetics of NovaRing ® in healthy young girls under the age of 18 years, who have already experienced menstruation, has not been studied.

    Impaired renal function

    Influence of kidney diseases on the pharmacokinetics of NovaRing ® not studied.

    Impaired liver function

    The effect of liver disease on the pharmacokinetics of NovaRing ® not studied. However, in patients with impaired liver function, a deterioration in the metabolism of sex hormones is possible.

    Ethnic groups

    The pharmacokinetics of the drug in representatives of ethnic groups has not been specifically studied.

    Indications:Contraception.
    Contraindications:

    Iova Ring preparation ® is contraindicated in the presence of any of the conditions listed below. In the event of any of these conditions occurring during the period of application of NovaRing ® should immediately stop using the drug.

    - Thrombosis (arterial or venous) and thromboembolism now or in history (including deep vein thrombosis, pulmonary thromboembolism, myocardial infarction, cerebrovascular disorders).

    - The conditions preceding thrombosis (including trapsitic ischemic attacks, angina pectoris) are presently or in the anamnesis.

    - Predisposition to the development of venous or arterial thrombosis, including hereditary diseases: resistance to activated protein C, antithrombin deficiency III, Protein C deficiency, protein deficiency S, hyperhomocysteinemia and antiphospholipid antibodies (antibodies to cardioliin, lupus anticoagulant).

    - Extensive surgery with prolonged immobilization (see section "Special instructions").

    - Migraine with focal neurological symptoms at present or in the anamnesis.

    - Diabetes mellitus with vascular lesions.

    - Expressed or multiple risk factors of venous or arterial thrombosis: hereditary predisposition to thrombosis (thrombosis, infarction myocardial infarction or cerebrovascular accident at a young age in any of the immediate relatives), uncontrolled arterial hypertension, heart valve disease, atrial fibrillation, extensive surgery, prolonged immobilization, extensive trauma, obesity (body mass index> 30 kg / m2), smoking in women older than 35 years (see section "Special instructions").

    - Pancreatitis with severe hypertriglyceridemia is currently or in the anamnesis.

    - Severe liver disease.

    - Liver tumors (malignant or benign), including in the anamnesis.

    - Known or suspected hormone-dependent malignant tumors (eg, genital organs or breast cancer).

    - Bleeding from the vagina of an unclear etiology.

    - Pregnancy, including presumed.

    - Breastfeeding period.

    - Hypersensitivity to any of the active or auxiliary substances NovaRing ® .

    - Safety and efficacy of NovaRing ® for teenage girls under the age of 18 have not been studied.

    Carefully:

    In the presence of any of the following diseases, conditions or risk factors, one should evaluate the benefits of NovaRing ® and the possible risks for each individual woman even before she starts using NovaRing ® (see section "Special instructions"). In case of worsening of the disease, worsening of the condition or the appearance of any of the following conditions for the first time, a woman should consult a doctor to decide the possibility of further use of NovaRing ®.

    With caution NovaRing ® should be used in the following cases:

    - risk factors for thrombosis and thromboembolism: hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebral circulation disorder at a young age in any of the next of kin), smoking, obesity, dyslinoproteinemia, arterial hypertension, migraine without focal neurological symptoms, heart valve disease, cardiac rhythm disturbances, prolonged immobilization, serious surgical interventions;

    - thrombophlebitis of superficial veins;

    - dyslipoproteinemia;

    - valvular heart disease;

    - adequately controlled arterial hypertension;

    - diabetes mellitus without vascular complications;

    - acute or chronic liver disease;

    - jaundice and / or itching caused by lobsters;

    - cholelithiasis;

    - porphyria;

    - systemic lupus erythematosus;

    - hemolytic-uremic syndrome;

    - Sydenham's chorea (minor chorea);

    - loss of hearing due to otosclerosis;

    - (hereditary) angioedema;

    - chronic inflammatory bowel disease (Crohn's disease and ulcerative colitis);

    - sickle-cell anemia;

    - Chloasma;

    - conditions that can make it difficult to use the vaginal ring: cervical prolapse,a hernia of a bladder, a hernia of a rectum, severe chronic constipation.

    Pregnancy and lactation:

    NovaRing ® is intended to prevent pregnancy. If a woman wants to stop using the drug to conceive, it is recommended to wait for the recovery of the natural cycle to be conceived, as this will help to correctly calculate the date of conception and childbirth.

    Pregnancy

    Application NovaRing ® during pregnancy is contraindicated. In case of pregnancy, the ring should be removed. Extensive epidemiological studies have not revealed an increased risk of congenital malformations in children born to women taking COCs before pregnancy, as well as teratogenic effects in cases where women took COC early in pregnancy, knowing about it. Although the ego refers to all COCs, it is not known whether this also applies to NovaRing. A clinical study in a small group of women showed that, despite the fact that the drug NovaRing ® is introduced into the vagina, the concentration of contraceptive sex hormones inside the uterus with NovaRing is similar to that of COCs.Pregnancy outcomes in women using NovaRing® during a clinical trial are not described.

    Breastfeeding period

    Application NovaRing ® during the period of breastfeeding is contraindicated. The composition of the drug can affect lactation, reduce the amount and change the composition of breast milk. Small amounts of contraceptive sex hormones and / or their metabolites can be excreted with milk, but evidence of their negative impact on children's health is not obtained.

    Dosing and Administration:

    To achieve a contraceptive effect, PovaRing ® must be used according to the instructions.

    A woman can independently enter the vaginal ring of NovaRing ® in the vagina. The doctor should inform the woman how to insert and remove the vaginal ring of NovaRing ® . To insert a ring, a woman should choose a comfortable position, for example, standing, lifting one leg, squatting or lying down. The NovaRing vaginal ring should be compressed and inserted into the vagina until the ring is in a comfortable position. The exact position of the ring in the vagina ns is of decisive importance for the contraceptive effect (Figure 1-4).

    After the introduction (see subsection "How to start using NovaRing® ) the ring should be in the vagina permanently for 3 weeks. A woman should regularly check whether it remains in the vagina. If the ring was accidentally deleted, then follow the instructions in "What to do if the ring was temporarily removed from the vagina".

    Vaginal ring of NovaRing ® should be removed after 3 weeks on the same day of the pedal when the ring was inserted into the vagina. After a week break, a new ring is inserted (for example, if the vaginal ring of NovaRing ® was installed on Wednesday at about 22.00, then it should be removed on Wednesday in 3 weeks at about 22.00. Next Wednesday, a new ring is introduced). To remove the ring, it must be picked up by the index finger or squeezed the index and middle finger and pulled out of the vagina (Figure 5). The used ring should be placed in a bag (keep out of reach of children and pets) and discarded. Bleeding associated with the cessation of NovaRing ®, usually begins 2-3 days after the removal of the vaginal ring NovaRing ® and can not completely stop until the moment when a new ring is installed.

    How to start using Nova Ring®?

    - In the previous cycle hormonal contraceptives were not used

    NovaRing ® should be entered on the first day of the cycle (ie on the first day of menstruation). It is allowed to install the ring on the 2nd-5th days of the cycle, but in the first cycle in the first 7 days of NovaRing ® additional use of barrier methods of contraception is recommended.

    - Transition from combined hormonal contraceptives

    A woman should enter the vaginal ring of NovaRing ® the last day of the usual interval between cycles when combined hormonal contraceptives (tablets or patch)

    If a woman correctly and regularly took a combined hormonal contraceptive and is sure that she is not pregnant, she can switch to using the vaginal ring on any day of the cycle.

    In any case, the recommended non-hormonal interval of the previous method should be exceeded.

    - Transition from preparations containing only progestogen ("mini-drank". progestinal oral contraceptives, implants.injection forms or hormone-containing intrauterine devices - IUD)

    A woman who takes "mini-pili" or progestinal oral contraceptives may switch to NovaRing ® any day. The ring is inserted on the day of removal of the implant or IUD. If a woman received injections, the NovaRing® drug is started on the day that the next injection should be made. In all these cases, a woman should use the barrier method of contraception within the first 7 days after the introduction of the ring.

    - After abortion in the first three mestre of pregnancy

    A woman can enter the ring right after the abortion. In this case, she does not need additional contraceptives. If NovaRing ® after the abortion is undesirable, it is necessary to follow the recommendations given in the subsection "In the previous cycle, hormonal contraceptives were not used." In the interval, a woman is recommended an alternative method of contraception.

    - After childbirth or after abortion in the second trimester of pregnancy

    A woman is recommended to enter the ring not earlier than 4 weeks after childbirth (if she does not feed the pile) or abortion in the second trimester of pregnancy.If the ring is installed at a later date, an additional barrier method is recommended for the first 7 days. However, if sexual intercourse has already taken place, before pregnancy NovaRing® is used, it is necessary to exclude pregnancy or wait for the first menstruation.

    When resuming NovaRing®, an increased risk of venous thromboembolism (VTE) in the postpartum period should be taken into account (see section "Special instructions").

    Deviations from the recommended mode

    Contraceptive effect and cycle control may be impaired if the woman does not follow the recommended regimen. To avoid reducing the contraceptive effect, the following recommendations should be followed.

    - What to do in case of an elongation break and application of the ring?

    If during interruption in the application of the ring there were sexual contacts, pregnancy should be excluded. The longer the break, the higher the probability of pregnancy. With the exception of pregnancy, a woman should insert a new ring into the vagina as soon as possible. For the next 7 days, an additional barrier method of contraception, for example, a condom, should be used.

    - What to do, if the ring was temporarily removed from the vagina?

    The ring should be constantly in the vagina for 3 weeks. If the ring was accidentally removed, it should be rinsed with cold or slightly warm (not hot) water and immediately inserted into the vagina.

    - If the ring remained outside the vagina for less than 3 hours, then its contraceptive effect does not decrease. A woman should enter the ring as soon as possible into the vagina (no later than 3 hours).

    - If the ring was outside the vagina for more than 3 hours during the first or second week of use, the contraceptive effect may decrease. A woman should enter the ring as quickly as possible into the vagina. During the next 7 days, it is necessary to use the barrier method of contraception, for example, a condom. The longer the ring was outside the vagina and the closer this time to a 7-day break in the application of the ring, the higher the probability of pregnancy.

    - If the ring was outside the vagina for more than 3 hours in the third week of use, then the contraceptive effect may decrease. A woman should throw this ring and choose one of the following two methods.

    1. Immediately install a new ring.

    Note: A new ring can be applied for the next 3 weeks.In this case, there may be no bleeding associated with the cessation of the drug. However, "smearing" spotting or bleeding in the middle of the cycle is possible.

    2. Wait for the bleeding associated with the cessation of the drug, and introduce a new ring ns later than 7 days after the removal of the previous ring.

    Note: This option should be selected only if the mode of application of the ring during the first two weeks is not violated.

    - What should I do if I use extended rings?

    If the drug NovaRing® was applied no more than a maximum period of 4 weeks, then the contraceptive effect remains sufficient. A woman can make a week break in applying the ring, and then introduce a new ring.

    If the vaginal ring of NovaRing ® remained in the vagina for more than 4 weeks, the contraceptive effect may worsen, so before the introduction of a new ring, pregnancy should be excluded.

    If a woman does not follow the recommended scheme of application and after a week break in the application of the ring does not bleed, then before the introduction of a new ring, pregnancy should be excluded.

    - How to move or delay the onset of menstrual bleeding? To delay the menstrual bleeding "cancellation", a woman can introduce a new ring without a one-week break. The next ring should be used within 3 weeks. In this case, "smearing" bleeding or bleeding may occur. After a normal week-long break, the woman returns to the regular use of NovaRing ® .

    To transfer the onset of bleeding to another day of the week, a woman can be recommended to take a shorter break in applying the ring (for as many days as necessary). The shorter the break in the application of the ring, the higher the probability of no bleeding that occurs after removal of the ring, and the occurrence of bleeding or "smearing" bleeding during the application of the next ring.

    Children

    Safety and efficacy of NovaRing ® for teenage girls under the age of 18 have not been studied.

    Side effects:

    When using the drug, there may be side effects, occurring at different frequencies: often (> 1/100), infrequently (<1/100.> 1/1000), rarely (<1/1000,> 1/10000).

    System-Organ Class

    Often> 1/100

    Uncommon <1/100,> 1/1000

    Rarely <1/1000,> 1/10000

    Data post-mar

    ketingovogo application1

    Infectious and parasitic diseases

    Vaginal infection

    Cervicitis, cystitis, urinary tract infections



    Immune system disorders




    Hypersensitivity

    Disorders from the metabolism and nutrition


    Increased appetite



    Disorders of the psyche

    Depression, decreased libido

    Mood Change



    Disturbances from the nervous system

    Headache, migraine

    Dizziness, hypoesthesia



    Disturbances on the part of the organ of sight


    Visual impairment



    Vascular disorders


    "Tides"

    Venous thromboembolism2, arterial thromboembolism2


    Disorders from the gastrointestinal tract

    Abdominal pain, nausea

    Bloating, diarrhea, vomiting, constipation



    Disturbances from the skin and subcutaneous tissues

    Acne

    Alopecia, eczema, itchy skin, rash


    Hives

    Disturbances from musculoskeletal and connective tissue


    Back pain, muscle spasms, pain in the limbs



    Disorders from the kidneys and urinary tract


    Dysuria, imperative urge to urinate, pollakiuria



    Violations of the genitals and mammary gland

    Coarsening and soreness of the mammary glands, genital itching in women, painful menstrual-like bleeding, pain in the pelvic region, vaginal discharge

    Absence of menstrual-like bleeding, unpleasant sensations in the mammary glands, enlargement of the mammary glands, densities in the mammary glands, cervical polyps, contact (during sexual intercourse) bleeding (bleeding), painful sensations in sexual intercourse, ectropion of the cervix, fibrocystic mastopathy , profuse menstrual-like bleeding, acyclic bleeding, unpleasant sensations in the pelvic region, prsdmsnstrual-like syndrome, burning sensation in the vagina, a vaginal odor, painful sensation swelling in the vagina, discomfort and dryness of the vulva and mucous membrane of the vagina


    Local reactions in the partner, galactorrhea

    General disorders and disorders at the site of administration

    Discomfort with the use of the vaginal ring, loss of the vaginal ring

    Fatigability, irritability, malaise, swelling, foreign body sensation, difficulty in using contraceptive,rupture



    Impact on the results of laboratory and instrumental studies

    Weight gain

    Increased blood pressure



    2 Number of cases according to observational cohort studies:> 1 / 10000- <1/1000 women-years (LL).

    3 "Local partner reactions" include reports of "local reactions from the penis" (for example, pain, congestion, bruising and abrasions).

    Side effects that occurred when taking combined hormonal contraceptives are described in detail in the section "Special instructions": pancreatitis, cholecystitis, cerebrovascular disorders, benign and malignant tumors of the liver, chloasma, changes in insulin resistance.

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

    Overdose:Serious consequences of an overdose of hormonal contraceptives are not described. Possible symptoms include nausea, vomiting and small bleeding from the vagina in young girls. Antidotes do not exist. Treatment is symptomatic.
    Interaction:

    The interaction between hormonal contraceptives and other drugs can lead to the development of acyclic bleeding and / or inefficiency of contraception.

    In the literature, the following interactions with combined oral contraceptives in general are described.

    Hepatic metabolism: may interact with drugs that induce microsomal enzymes of the liver, which can lead to an increase in the clearance of sex hormones. Interactions have been established, for example, with phenytoin, barbiturates, primidon, carbamazepine, rifampicin, and possibly with oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin, and preparations containing St. John's Wort (Hypericum perforatum).

    When treating any of the listed products, you should temporarily use the barrier method of contraception (condom) in combination with the NovaRing drug or choose another method of contraception. During the concomitant use of drugs that induce microsomal enzymes, n, barrier methods of contraception should be used within 28 days after their withdrawal.

    If concomitant therapy should be continued after a 3-week application of the ring, the next ring should be injected immediately without the usual interval.

    Antibiotics: decrease in the effectiveness of oral contraceptives containing ethinyl estradiol, was noted with the concomitant administration of antibiotics, such as ampicillin and tetracyclines. The mechanism of this effect has not been studied. In the study of pharmacokinetic interactions, ingestion of amoxicillin (875 mg, 2 times a day) or doxycycline (200 mg per day, and then 100 mg per day) for 10 days during the application of NovaRing® had little effect on the pharmacokinetics of this hormone warmed a and ethinyl estradiol. When using antibiotics (excluding amoxicillin and doxycycline) should use the barrier method of contraception (condom) during treatment and within 7 days after the abolition of antibiotics. If concomitant therapy should be continued after a 3-week application of the ring, the next ring should be injected immediately without the usual interval. Pharmacokinetic studies did not reveal the effect of simultaneous use of antifungal agents and spasmicides on the contraceptive efficacy and safety of NovaRing®.With the combined use of suppositories with antifungal agents, the risk of ring rupture is slightly increased. Hormonal contraceptives can cause a metabolic disorder in other medicines. Accordingly, their concentrations in plasma and tissues may increase (eg, cyclosporine) or decrease (eg, lamotrigine).

    To avoid possible interactions, it is necessary to read the instructions for the use of other drugs.

    Laboratory research

    The use of contraceptive hormonal drugs can affect the results of certain laboratory tests, including biochemical indicators of liver, thyroid, adrenal and kidney function; on the plasma concentration of transport proteins, for example, corticosteroid-binding globulin (CSG) and GSHG; lipid / lipoprotein fractions; on the parameters of carbohydrate metabolism; as well as on blood coagulation and fibrinolysis. Indicators, as a rule, vary within the limits of normal values.

    Joint application with tampons

    Pharmacokinetic data show that the use of tampons does not affect the absorption of hormones released from the vaginal ring NovaRing ® . In rare cases, the ring can be accidentally removed by removing the tampon (see "What to do if the ring was temporarily removed from the vagina" in the "Application and Dose" section).

    Special instructions:

    If you have any of the following diseases, conditions or risk factors, you should evaluate the benefits of using NovaRing® and the possible risks for each individual woman before she starts using NovaRing®. In case of worsening of the disease, worsening of the condition or the appearance of any of the following conditions for the first time, a woman should consult a doctor to decide whether NovaRing can be used further.

    Circulatory disorders

    The use of combined hormonal contraceptives (KGC) may be associated with the development of venous thrombosis (deep vein thrombosis and pulmonary embolism) and arterial thrombosis, as well as associated complications, sometimes with a fatal outcome.

    The use of KGC increases the risk of VTE development in comparison with the risk of developing B'GE in patients who do not use COCs. The greatest risk of VTE development is observed in the first year of application of KGC.Data from a large prospective cohort study of the safety of the use of various COCs suggest that the greatest risk increase in women who do not use COCs is observed in the first 6 months after the initiation of COC use or the resumption of their use after a break (4 weeks or more). In non-pregnant women who do not use KGC, the risk of developing VTE is 1 to 5 cases per 10,000 LLS, while for women using KGC, the risk of developing VTE is from 3 to 12 cases per 100,000 persons. However, the risk rises to a lesser extent than in pregnancy, when it is 5-20 cases per 10,000 LIL (pregnancy data are based on the actual duration of pregnancy in studies, when calculated for the duration of pregnancy 9 months, the risk is from 7 to 27 cases per 100,000 LIL) . In women in the postpartum period, the risk of VTE development ranges from 40 to 65 cases per 10,000 LL. VTE leads to a lethal outcome in 1-2% of cases.

    Based on the results of the studies, the increased risk of developing VTE in women using NovaRing® is similar to that of women using COCs (see the table below for an adjusted risk ratio). In a large prospective observational study TASC (Transatlantic Active Safety Study of NovaRing4 for the cardiovascular system), an assessment of the risk of developing VTE in women who started using NovaRing® or KOC, switched to NovaRing® or KOC from other contraceptives or resumed NovaRing® or COC use in a population of typical users. Women were observed within 24-48 months. The results showed a similar level of risk for VTE in women using NovaRing ® (8.3 cases per 10000 LL), and in women using COC (9.2 cases per 10,000 LL). For women who use COC, in addition to desogestrel, Gestodene and drospirenone, the frequency of VTE development was 8.5 cases per 10,000 LL.

    Retrospective cohort study initiated by FDA (US Food and Drug Administration), found that the incidence of VTE in women who started using NovaRing® was 11.4 per 100,000 people, while women who started using COC containing levonorgestrel, the frequency of VTE development is 9.2 cases per 10,000 LL.

    Epidemiological

    Comparison drug (s)

    Ratio of risks

    research, populations


    (RR) (95% CI)

    TASC (Dinger, 2012)

    All available COCs on

    PR2: 0,8 (0,5-1,5)

    Women who started using

    throughout the study1.


    drug (including again after

    Available COCs, except

    PR2: 0,9 (0,4-2,0)

    break) and passed from other

    containing desogestrel,


    means of contraception.

    gestodene, drospirenone.


    "The study initiated by

    COCs available in the period

    PR1: 1,09(0.55-2.16)

    FDA " (Sydney, 2011)

    research3.


    Women who started using

    Levonorgestrel / 0.03 mg

    PR4: 0,96 (0,47-1,95)

    combined hormonal

    ethinylestradiol.


    Contraceptives (KGC) for the first time in



    study period.



    1AT Tom number of low-dose COOK, containing the following progestins: chloromadinone acetate, cyproterone acetate, desogestrel, dienogesg, drospirenone, ethynodiol diacetate, gestodene, levonorgestrel, norethindrone, norgestimate or porgestrel.

    2 Taking into account age, IM'G, duration of application, anamnesis of VTE.

    3 AT Tom number of low-dose COOK, containing the following progestins: norgestimate, norethindrone or levonorgestrel.

    4 Taking into account the age, place and year of inclusion in the study.

    There are extremely rare cases of thrombosis of other blood vessels.


    Risk assessment (risk ratio) of the development of B'GE in women using NovaRing®, compared with the risk of developing VTE in women using COCs (for example, arteries and veins of the liver, mesenteric vessels, kidneys, brain and retina) .

    Possible symptoms of venous or arterial thrombosis may be unilateral edema and / or pain in the lower extremity, local increase in temperature in the lower extremity, hyperemia or discoloration of the skin on the lower limb; sudden severe pain in the chest, possibly radiating to the left arm; a shortness of breath, a cough; any unusual, severe, prolonged headaches; sudden partial or complete loss of vision; double vision in the eyes; slurred speech or aphasia; dizziness; collapse, accompanied or not accompanied by focal epileptic seizure; sudden weakness or numbness of one side of the body or any part of the body; motor disorders; "sharp" abdomen. The risk of venous thromboembolism increases with the following risk factors:

    - age;

    - the presence of diseases in the family history (venous thrombosis and embolism in the brothers / sisters at any age or at parents at a young age). If you suspect a hereditary predisposition, before starting any hormonal contraceptives, a woman should be referred to a specialist for consultation;

    - prolonged immobilization, major surgical interventions, any surgical intervention on the lower limbs, or serious trauma. In such situations, it is recommended to stop the use of the drug (in the case of a scheduled operation for at least 4 weeks) with the subsequent resumption of application of ns earlier than 2 weeks after complete recovery of the motor activity (see also the section "Contraindications");

    - Obesity (body mass index more than 30 kg / m2);

    - possibly, thrombophlebitis of superficial veins with varicose veins.

    There is no consensus on the possible role of these conditions in the etiology of venous thrombosis.

    The risk of complications of arterial thromboembolism increases with the following risk factors:

    - age;

    - smoking (with intensive smoking and age, the risk increases even more, especially in women older than 35 years);

    - dyslipoproteinemia;

    - Obesity (body mass index more than 30 kg / m2);

    - increased blood pressure;

    - migraine;

    - valvular heart disease;

    - atrial fibrillation;

    - the presence of diseases in the family history (arterial thrombosis of brothers / sisters at any age or in parents at a relatively early age). If you suspect a genetic predisposition, before starting any hormonal contraceptives, the woman should be referred to a specialist for consultation. Biochemical factors that may indicate hereditary or acquired predisposition to venous or arterial thrombosis include resistance to activated protein C, hyperhomocysteinemia, anthrombin III deficiency, protein C deficiency, protein deficiency S, antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant).

    Other conditions that can lead to unwanted circulatory disorders include diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel diseases (eg, Crohn's disease or ulcerative colitis) and sickle cell anemia.

    It is necessary to take into account the increased risk of thromboembolism in the postpartum period.

    Increasing the frequency or severity of migraine (which may be a prodromal symptom of cerebral circulatory disorders) during use of hormonal contraceptives may cause immediate termination of hormonal contraceptives.

    Women using KGC should be advised to consult a doctor if there are possible symptoms of thrombosis. With suspected or confirmed thrombosis, it is necessary to stop the use of KGC. In this case, it is necessary to use effective means of contraception, since anticoagulants (kumariyy) have teratogsn and mm action.

    The risk of developing tumors

    The most important risk factor for developing cervical cancer is infection with the human papillomavirus (HPV). Epidemiological studies have shown that prolonged use of COCs lead to a further increase this risk, but it remains unclear to what extent this is due to other factors, such as more frequent cervical screening and sexual behavior, including the number of sexual partners and less frequent use of barrier contraceptives,and their causal relationship. It remains unclear how this effect is related to NovaRing.

    A meta-analysis of the results of 54 epidemiological studies revealed a slight increase (1.24) in the relative risk of breast cancer in women taking COCs. The risk gradually decreases within 10 years after the withdrawal of drugs. Breast cancer rarely develops in women under the age of 40, so the additional number of cases of breast cancer in women who take or take COC is small compared to the overall risk of developing breast cancer. Women who use COC are diagnosed with earlier clinical stages of breast cancer than women who have never used COCs. The increased risk of developing breast cancer may be due to the fact that women who have COCs are diagnosed with breast cancer at an earlier time and with biological effects of COC, or a combination of both.

    In rare cases, women who took COC experienced cases of benign, and even more rarely, malignant liver tumors. In some cases, these tumors led to the development of life-threatening bleeding into the abdominal cavity.The doctor should consider the possibility of a liver tumor in the differential diagnosis of diseases in a woman taking NovaRing ® . if the symptoms include acute pain in the upper abdomen, an enlarged liver, or signs of intra-abdominal bleeding.

    Other condition

    - In women with hypertriglyus and ceridemia or a corresponding family history, the risk of developing pancreatitis when taking hormonal contraceptives is increased.

    - Many women taking hormonal contraceptives have a slight increase in blood pressure, but clinically significant increases in blood pressure are rare. A direct link between the use of hormonal contraceptives and the development of hypertension is not established. If using NovaRing ® there is a constant increase in blood pressure, you need to contact your doctor to decide whether to remove the vaginal ring and prescribe antihypertensive therapy. With adequate control of blood pressure with the help of antihypertensive drugs, the use of NovaRing ® .

    - On the background of pregnancy and during the use of combined oral contraceptives, the following conditions were observed or worsened, although their relationship with contraceptive use was not completely established: jaundice and / or pruritus caused by cholestasis, gallstones, porphyria, systemic lupus erythematosus, hemolytic uremic syndrome, Sydenham's chorea (small chorea), herpes of pregnant women, hearing loss due to otosclerosis, (hereditary) angioedema.

    - Acute or chronic liver disease may serve as the basis for the cancellation of NovaRing before normalization of liver function. The recurrence of cholestagic jaundice, observed earlier in pregnancy or with the use of sex hormones, requires the cancellation of NovaRing ®.

    - Although estrogens and progestogens can influence peripheral insulin resistance and tissue tolerance to glucose, there is no evidence for the need for a change in hypoglycemic therapy when hormonal contraceptives are used. However, women with diabetes should be under constant medical supervision with NovaRing ®, especially in the first months of contraception.

    - There is evidence of worsening of Crohn's disease and ulcerative colitis with the use of hormonal contraceptives.

    - In rare cases, pigmentation of facial skin (chloasma) can occur, especially if it occurred earlier in pregnancy. Women, predisposed to the development of chloasma, during the application of NovaRing ® Avoid exposure to sunlight and ultraviolet radiation.

    - The following conditions may prevent the correct introduction of the ring or contribute to its loss: prolapse of the cervix, bladder hernia and / or hernia of the rectum, severe chronic constipation.

    - In very rare cases, women unintentionally injected the NovaRing vaginal ring ® in the urethra and, possibly, in the bladder. When there are symptoms of cystitis, you must consider the likelihood of improper insertion of the ring.

    - The cases of vaginitis during the application of NovaRing are described. ®. Evidence that the treatment of vaginitis affects the effectiveness of NovaRing®, as well as evidence of the effect of NovaRing ® on the effectiveness of vaginitis treatment, are absent.

    - We described very rare cases of difficult extraction of the ring, which required its extraction by a medical worker.

    Medical examination / consultation

    Before NovaRing® is prescribed or renewed, a medical history (including family) of a woman should be thoroughly reviewed and a gynecological examination should be performed to exclude pregnancy. It is necessary to measure blood pressure, conduct a survey of mammary glands, pelvic organs, including cytological examination of cervical smears and some laboratory studies, to eliminate contraindications and reduce the risk of possible side effects of the drug. The frequency and nature of medical examinations depend on the individual characteristics of each patient, but medical examinations are conducted less than once every 6 months. A woman should read the instructions for use and follow all recommendations. It is necessary to inform the woman that the NovaRing drug does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

    Decreased efficiency

    The effectiveness of NovaRing® may decrease if the treatment regimen is not followed or concomitant therapy is administered.

    Changes in the nature of menstruation

    During the application of NovaRing ® possibly the occurrence of acyclic bleeding ("smearing" bloody discharge or sudden bleeding). If such bleeding is observed after regular cycles against the background of the correct use of the NovaRing® drug, you should contact your doctor-gynecologist for the necessary diagnostic tests, including to eliminate organic pathology or pregnancy. Diagnostic curettage may be required.

    Some women have a bleeding after removal of the ring. If the drug NovaRing was used in accordance with the instructions, it is unlikely that a woman is pregnant. If the instructions are not followed and there is no bleeding after removing the ring, and if there is no bleeding for two consecutive cycles, pregnancy should be excluded.

    The effect of ethinylestradiol and etonogestrel on the sexual partner Possible pharmacological effects and the degree of exposure of ethinylestradiol and etonogestrel to genitalmale parger (due to absorption through the penis tissue) have not been investigated.

    Damage to the ring

    In rare cases, when using NovaRing®, a rupture of the ring was observed. The core of NovaRing ® is solid, so its contents remain intact, and the release of hormones does not change significantly. In the case of rupture of the ring, it usually falls out of the vagina (see the recommendations of "What to do if the ring was temporarily removed from the vagina" in the section "Dosing and Administration"). When the ring is broken, a new ring must be inserted.

    Fallout of the ring

    Sometimes there was a fall of the vaginal ring of NovaRing ® from the vagina, for example, if it is incorrectly inserted, when the tampon is removed, during intercourse or against a background of severe or chronic constipation. In connection with this, it is advisable for a woman to regularly check for the presence of the vaginal ring of NovaRing ® in the vagina. In the case of the fall of the vaginal ring, NovaRing ® from the vagina it is necessary to follow the recommendations of the section "What to do if the ring was temporarily removed from the vagina" in the section "Method of administration and dose".

    Effect on the ability to drive transp. cf. and fur:Based on information about the pharmacodynamic properties of NovaRing ® it can be expected that it does not affect the ability to drive vehicles and work with machinery.
    Form release / dosage:

    Vaginal rings are 0.015 mg + 0.120 mg / day.

    Packaging:

    1 ring is packed in a waterproof aluminum foil bag, covered from the inside with a layer of low density polyethylene, externally with a layer of polyethylene terephthalate (PET). For I or 3 packages in a cardboard box with instructions for use.

    Storage conditions:

    Store at a temperature of 2 to 8 ° C. Keep out of the reach of children.

    Shelf life:

    3 years. Do not use at the end of the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:П N015411 / 01
    Date of registration:27.01.2010
    The owner of the registration certificate:Organon, N.V.Organon, N.V. Netherlands
    Manufacturer: & nbsp
    Representation: & nbspMSD Pharmaceuticals Ltd.MSD Pharmaceuticals Ltd.
    Information update date: & nbsp01.10.2015
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