NovaRing vaginal rings 0.015mg+0.120mg/day, 3pcs

Composition

Active ingredients:

Etonogestrel – 11.7 mg;

Ethinyl Estradiol – 2.7 mg.

Auxiliary substances:

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

Pharmacological action

Pharmacodynamics

NuvaRing® is a hormonal combination contraceptive containing etonogestrel and ethinyl estradiol. Etonogestrel is a progestogen (a 19-nortestosterone derivative) that binds with high affinity to progesterone receptors in target organs. Ethinyl Estradiol is an estrogen and is widely used in the production of contraceptives.

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

Efficiency

In clinical trials, it was found that the Pearl index (a measure that reflects the frequency of pregnancy in 100 women during 1 year of contraception) in women aged 18 to 40 years for NuvaRing® was 0.96 (95% CI: 0.64-1.39) and 0.64 (95% CI: 0.35-1.07) in statistical analysis of all randomized participants (ITT analysis) and analysis of study participants who completed them according to the protocol (PP analysis), respectively. These values were similar to the Perl index values obtained in comparative studies of combined oral contraceptives (COCs) containing levonorgestrel /ethinyl estradiol (0.150 / 0.030 mg) or drospirenone/ethinyl estradiol (3/0.30 mg).

When using NuvaRing®, the cycle becomes more regular, the soreness and intensity of menstrual-like bleeding decreases, which helps to reduce the frequency of iron deficiency conditions. There is evidence of a reduced risk of endometrial and ovarian cancer with the use of the drug.

Nature of bleeding

A comparison of the features of the nature of bleeding over one year in 1000 women who used NuvaRing® and COCs containing levonorgestrel / ethinyl estradiol (0.150 / 0.030 mg) showed a significant decrease in the frequency of “breakthrough” bleeding or spotting when using NuvaRing® compared to COCs. In addition, the frequency of cases where bleeding occurred only during a break in the use of the drug was significantly higher among women using NuvaRing®.

Effect on bone mineral density

A comparative two-year study of the effect of NuvaRing® (n=76) and a non-hormonal intrauterine device (n=31) did not reveal any effect on bone mineral density in women.

Children

The safety and efficacy of NuvaRing® for adolescent girls under 18 years of age has not been studied.

Pharmacokinetics

Etonogestrel

Suction

Etonogestrel, released from the vaginal ring of NuvaRing®, is rapidly absorbed through the vaginal mucosa. The maximum concentration of etonogestrel in blood plasma, which is about 1700 pg / ml, is reached approximately 1 week after use of the ring. Plasma concentrations vary over a small range and slowly decrease to approximately 1600 pg / ml after 1 week,1500 pg / ml after 2 weeks, and 1400 pg / ml after 3 weeks of use. Absolute bioavailability is about 100%, which exceeds the bioavailability of oral etonogestrel. According to the results of measurements of ethonogestrel concentrations in the cervix and inside the uterus in women using NuvaRing® and women using oral contraceptives containing 0.150 mg of desogestrel and 0.020 mg of ethinyl estradiol, the observed values of etonogestrel concentrations were comparable.

Distribution

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

Metabolism

Biotransformation of etonogestrel occurs by known pathways of sex hormone metabolism. The apparent plasma clearance is about 3.5 l/h. There was no direct interaction with ethinyl estradiol taken concomitantly.

Deduction

Plasma concentrations of etonogestrel decrease in two phases. In the terminal phase, the elimination half-life is approximately 29 hours. Etonogestrel and its metabolites are excreted by the kidneys and through the intestines with bile in a ratio of about 1.7: 1. The half-life of the metabolites is approximately 6 days.

Ethinyl Estradiol

Suction

Ethinyl Estradiol released from the vaginal ring of NuvaRing® is rapidly absorbed through the vaginal mucosa. The maximum concentration in blood plasma, which is about 35 pg / ml, is reached 3 days after use of the ring and decreases to 19 pg/ml after 1 week, to 18 pg/ml after 2 weeks and 18 pg/ml after 3 weeks of use. The absolute bioavailability is approximately 56% and is comparable to that of oral ethinyl estradiol. According to the results of measurements of ethinyl estradiol concentrations in the cervix and inside the uterus in women using NuvaRing® and women using oral contraceptives containing 0.150 mg of desogestrel and 0.020 mg of ethinyl estradiol, the observed values of ethinyl estradiol concentrations were comparable.

The concentration of ethinyl estradiol was studied in a comparative randomized trial of NuvaRing® (daily release of ethinyl estradiol in the vagina 0.015 mg), transdermal patch (norelgestromine / ethinyl estradiol; daily release of ethinyl estradiol 0.020 mg) and COCs (levonorgestrel / ethinyl estradiol; daily release of ethinyl estradiol 0.030 mg) during one cycle in healthy women. Systemic exposure to ethinyl estradiol for a month (AUC 0 -∞) for NuvaRing® was statistically significantly lower than for the patch and COCs, and amounted to 10.9,37.4 and 22.5 ng * h/ml, 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. During its biotransformation, a large number of hydroxylated and methylated metabolites are formed. They circulate in free form or in the form of sulfate and glucuronide conjugates. The apparent ground clearance is approximately 35 l/h.

Deduction

Plasma concentrations of ethinyl estradiol decrease in two phases. The half-life in the terminal phase varies widely; the median is about 34 hours. Ethinyl estradiol is not excreted unchanged. Metabolites of ethinyl estradiol are excreted by the kidneys and through the intestines with bile in a ratio of 1.3: 1. The half-life of metabolites is about 1.5 days.

Special patient groups

Children

The pharmacokinetics of NuvaRing® in healthy adolescent girls under 18 years of age who have already started menstruating have not been studied.

Impaired renal function

The effect of renal disease on the pharmacokinetics of NuvaRing has not been studied.

Impaired liver function

The effect of liver disease on the pharmacokinetics of NuvaRing has not been studied. However, in patients with impaired liver function, it is possible to worsen the metabolism of sex hormones.

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

Indications

Contraception.

Use during pregnancy and lactation

NuvaRing® is intended to prevent pregnancy. If a woman wants to stop using the drug in order to get pregnant, it is recommended to wait until the natural cycle is restored for conception, as this will help to correctly calculate the date of conception and delivery.

Pregnancy

The use of NuvaRing during pregnancy is contraindicated. In case of pregnancy, the ring should be removed. Extensive epidemiological studies have not found an increased risk of developing birth defects in children born to women who took COCs before pregnancy, as well as teratogenic effects in cases where women took COCs in the early stages of pregnancy without knowing about it. Although this applies to all COCs, it is not known whether this also applies to NuvaRing®. A clinical study in a small group of women showed that, despite the fact that NuvaRing® is administered into the vagina, the concentrations of contraceptive sex hormones inside the uterus when using NuvaRing® are similar to those when using COCs. Pregnancy outcomes in women treated with NuvaRing® during the clinical trial are not described.

Breast-feeding period

The use of NuvaRing® during breastfeeding is not indicated. 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 in milk, but there is no evidence of their negative effects on the health of children.

Children

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

Contraindications

NuvaRing® is contraindicated in the presence of any of the following conditions. If any of these conditions occur while NuvaRing is being used, the drug should be discontinued immediately.

• Thrombosis (arterial or venous) and thromboembolism at present or in the anamnesis (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);
• Conditions that precede thrombosis (including transient ischemic attacks, angina pectoris) at the present time or in the anamnesis;
• Predisposition to the development of venous or arterial thrombosis, including hereditary diseases: resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid antibodies (cardiolipin antibodies, lupus anticoagulant);
• Migraine with focal neurological symptoms at present or in the anamnesis;
• Diabetes mellitus with vascular damage;
• Expressed or multiple risk factors for venous or arterial thrombosis: a hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the next of kin), hypertension, valvular lesions of the heart, atrial fibrillation, advanced surgery, prolonged immobilization, extensive trauma, obesity (body weight >30 kg/m 2), Smoking in women older than 35 years (see “Special instructions”);
• Pancreatitis with severe hypertriglyceridemia at present or in the anamnesis.
• Severe liver diseases;
• Liver tumors (malignant or benign), including in the anamnesis;
• Known or suspected hormone-dependent malignancies (such as those of the genitals or breast).
• Bleeding from the vagina of unclear etiology;
• Pregnancy, including suspected pregnancy.
• Hypersensitivity to any of the active or auxiliary substances of NuvaRing®.

Caution: If you have any of the following diseases, conditions, or risk factors, you should evaluate the benefits of using NuvaRing® and the possible risks for each individual woman before she starts using NuvaRing®. In the event of an exacerbation of the disease, deterioration of the condition, or the first occurrence of any of the following conditions, a woman should consult a doctor to decide whether to continue using NuvaRing®. NuvaRing® should be used with caution in the following cases:: risk factors for developing thrombosis and thromboembolism: hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age in one of the closest relatives), smoking, obesity, dyslipoproteinemia, arterial hypertension, migraine without focal neurological symptoms, heart valve diseases, heart rhythm disorders, prolonged immobilization, serious surgery; superficial vein thrombophlebitis; dyslipoproteinemia; valvular heart disease; adequately controlled arterial hypertension; diabetes mellitus without vascular complications; acute or chronic liver diseases; jaundice and/or pruritus caused by cholestasis; cholelithiasis; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; Sydenham’s chorea (small chorea); hearing loss due to otosclerosis; (hereditary) angioedema; chronic inflammatory diseases bowel diseases (Crohn’s disease and ulcerative colitis); sickle cell anemia; chloasma; conditions that can make it difficult to use a vaginal ring: prolapse of the cervix, herniated bladder, herniated rectum, severe chronic constipation.

Side effects

When using the drug, side effects may occur with varying frequency:

• frequently ( ≥ 1/100);
• infrequently (< 1/100, ≥ 1/1,000);
• rarely (

Infectious and parasitic diseases: often ≥1/100-vaginal infection; infrequently

Immune system disorders: post-marketing use data 1-hypersensitivity.

Metabolic and nutritional disorders: infrequent

Mental disorders: often ≥ 1/100-depression, decreased libido; infrequently

Nervous system disorders: often ≥ 1/100 – headache, migraine; infrequently

Visual disturbances: infrequent

Vascular disorders: infrequently < 1/100, ≥ 1/1 000-Hot flashes; rarely < 1/1 000, ≥ 1/10 000-venous thromboembolism3.

Gastrointestinal disorders: often ≥ 1/100 – abdominal pain, nausea;  infrequently

Skin and subcutaneous tissue disorders: often ≥ 1/100-acne; infrequently

Musculoskeletal and connective tissue disorders: infrequent

Renal and urinary tract disorders: infrequent

Genital and breast disorders:  often ≥ 1/100 – breast engorgement and soreness, genital pruritus in women, painful menstrual-like bleeding, pelvic pain, vaginal discharge;  rarely < 1/100, ≥ 1/1 000 – no menstrualnopodobnoe bleeding, discomfort in the mammary glands, breast enlargement, seals in the mammary glands, cervical polyps, contact (during intercourse) spotting (bleeding), pain during intercourse, ectropion of the cervix, fibrocystic mastopathy, abundant menstrualnopodobnoe bleeding, acyclic bleeding, discomfort in the pelvis, premenstrually syndrome, burning sensation in the vagina, the smell from the vagina, pain in the vagina, discomfort and dryness of the vulva and vaginal mucosa; data post-marketing use 1 – local reaction partner 2.

General disorders and disorders at the injection site: often ≥ 1/100 – discomfort when using the vaginal ring, loss of the vaginal ring; infrequently

Influence on the results of laboratory and instrumental studies:  often ≥ 1/100 – weight gain; infrequently

1 – the list of side effects is based on data obtained from spontaneous reports. It is not possible to determine the exact frequency.

2 – “local partner reactions” include reports of “local penile reactions” (such as pain, flushing, bruising, and abrasions).

3-observational cohort study data: ≥ 1/10 000 –

Interaction

Interaction with other medicinal products

Interactions between hormonal contraceptives and other medications can lead to acyclic bleeding and / or ineffective contraception. The following interactions with combined oral contraceptives in general are described in the literature.

Hepatic metabolism: interactions with drugs that induce microsomal liver enzymes may occur, which may lead to increased clearance of sex hormones. Interactions have been established, for example, with phenytoin, barbiturates, primidone, carbamazepine, rifampicin, as well as, possibly, with oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and preparations containing St. John’s wort (Hypericum perforatum).

When treating any of these drugs, you should temporarily use a barrier method of contraception (condom) in combination with the use of NuvaRing® or choose another method of contraception. Barrier methods of contraception should be used during concomitant use of drugs that induce microsomal enzymes, and within 28 days after their withdrawal.

If concomitant therapy should be continued after 3 weeks of ring use, then the next ring should be administered immediately without the usual interval.

Antibiotics: A decrease in the effectiveness of oral contraceptives containing ethinyl estradiol was observed with concomitant use of antibiotics, such as ampicillin and tetracyclines. The mechanism of this effect has not been studied. In a pharmacokinetic interaction study, oral use of amoxicillin (875 mg, twice daily) or doxycycline (200 mg daily, followed by 100 mg daily) for 10 days during NuvaRing® use had little effect on the pharmacokinetics of etonogestrel and ethinyl estradiol. When using antibiotics (excluding amoxicillin and doxycycline), you should use a barrier method of contraception (condom) during treatment and for 7 days after the withdrawal of antibiotics. If concomitant therapy should be continued after 3 weeks of ring use, then the next ring should be administered immediately without the usual interval. Pharmacokinetic studies did not reveal the effect of simultaneous use of antifungal agents and spermicides on the contraceptive efficacy and safety of NuvaRing®. With the combined use of suppositories with antifungal drugs, the risk of ring rupture slightly increases. Hormonal contraceptives can disrupt the metabolism of other medications.Accordingly, their concentrations in plasma and tissues may increase (for example, cyclosporine) or decrease (for example, lamotrigine). To exclude possible interactions, you should read the instructions for use of other drugs.

Laboratory tests

The use of contraceptive hormonal drugs may affect the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function; plasma concentrations of transport proteins, such as corticosteroid-binding globulin (CSG) and SHBG; lipid/lipoprotein fractions; carbohydrate metabolism; and blood clotting and fibrinolysis. Indicators usually vary within normal values.

Concomitant use with tampons

Pharmacokinetic data show that the use of tampons does not affect the absorption of hormones released from the vaginal ring of NuvaRing®. In rare cases, the ring may be accidentally removed when the tampon is removed (see the section “What to do if the ring was temporarily removed from the vagina” in the section “Dosage and use”).

How to take, course of use and dosage

To achieve a contraceptive effect, NuvaRing® should be used according to the instructions.

A woman can insert the NuvaRing® vaginal ring into her vagina on her own.

The doctor should inform the woman how to insert and remove the NuvaRing vaginal ring. To insert the ring, a woman should choose a comfortable position, for example, standing, lifting one leg, squatting or lying down. The NuvaRing® vaginal ring should be squeezed and inserted into the vagina until the ring is comfortably positioned. The exact position of the ring in the vagina is not crucial for the contraceptive effect.

After use (see the section “How to start using NuvaRing®”), the ring should be kept in the vagina continuously for 3 weeks. It is advisable for a woman to regularly check whether it remains in the vagina. If the ring was accidentally removed, follow the instructions in “What to do if the ring was temporarily removed from the vagina”.

The NuvaRing ® vaginal ring should be removed after 3 weeks on the same day of the week when the ring was inserted into the vagina. After a week-long break, a new ring is inserted (for example, if the NuvaRing ® vaginal ring was installed on Wednesday at approximately 22.00, then it should be removed on Wednesday after 3 weeks at approximately 22.00. Next Wednesday, a new ring is introduced). To remove the ring, you need to pick it up with your index finger or squeeze it with your index and middle fingers and pull it out of the vagina. The used ring should be placed in a bag (keep out of the reach of children and pets) and discarded. Bleeding associated with discontinuation of NuvaRing® usually begins 2-3 days after removal of the NuvaRing® vaginal ring and may not completely stop until a new ring is installed.

How do I start using NuvaRing?

In the previous cycle, hormonal contraceptives were not used

NuvaRing should be administered on the first day of the cycle (i. e., 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 using NuvaRing®, additional use of barrier methods of contraception is recommended.

Switching from combined hormonal contraceptives

A woman should receive a NuvaRing vaginal ring on the last day of the usual interval between cycles when taking combined hormonal contraceptives (tablets or patches).

If a woman has taken a combined hormonal contraceptive correctly and regularly and is sure that she is not pregnant, she can switch to using a vaginal ring on any day of the cycle. In no case should you exceed the recommended hormone-free interval of the previous method.

Switching from progestogen-only medications (mini-pills, progestin oral contraceptives, implants, injectable forms, or hormone-containing intrauterine devices – IUDs))

A woman taking mini-pills or progestin oral contraceptives can switch to NuvaRing® on any given day. The ring is inserted on the day of removal of the implant or IUD. If a woman has received injections, then the use of NuvaRing® begins on the day when the next injection should have been made. In all these cases, the woman should use a barrier method of contraception for the first 7 days after the introduction of the ring.

After an abortion in the first trimester

, a woman can insert a ring immediately after the abortion. In this case, she does not need additional contraceptives. If the use of NuvaRing® immediately after an abortion is undesirable, follow the recommendations given in the subsection “No hormonal contraceptives were used in the previous cycle”. In the interval, the woman is recommended an alternative method of contraception.

After giving birth or after an abortion in the second trimester

, a woman is recommended to enter the ring no earlier than 4 weeks after giving birth (if she is not breastfeeding) or an abortion in the second trimester. If the ring is installed at a later date, it is recommended to use an additional barrier method within the first 7 days. However, if sexual contact has already taken place, then before using NuvaRing®, it is necessary to exclude pregnancy or wait for the first menstruation.

Deviations from the recommended mode

The contraceptive effect and cycle control may be disrupted if a woman does not follow the recommended regimen. To avoid reducing the contraceptive effect, you should follow the following recommendations.

What should I do if the break in the use of the ring is prolonged?

If during the break in the use of the ring there were sexual contacts, pregnancy should be excluded. The longer the break, the higher the chance of pregnancy. If pregnancy is excluded, a woman should insert a new ring into the vagina as soon as possible. During the next 7 days, an additional barrier method of contraception, such as a condom, should be used.

What should I do if the ring was temporarily removed from my vagina?

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

• If the ring was left out of the vagina for less than 3 hours, then its contraceptive effect is not reduced. A woman should insert the ring into her vagina as soon as possible (no later than 3 hours).
• If the ring has been out of the vagina for more than 3 hours during the first or second week of use, the contraceptive effect may decrease. A woman should insert the ring into her vagina as quickly as possible. During the next 7 days, you must use a barrier method of contraception, such as a condom. The longer the ring was out of the vagina and the closer this period is to the 7-day break in the use of the ring, the higher the probability of pregnancy.
• If the ring was out of the vagina for more than 3 hours in the third week of use, the contraceptive effect may decrease. A woman should discard this ring and choose one of the following two methods.

What should I do if the ring is used for an extended period of time?

If the drug NuvaRing® was used for no more than a maximum period of 4 weeks, then the contraceptive effect remains sufficient. A woman can take a one-week break from applying the ring, and then introduce a new ring.

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

If a woman does not adhere to the recommended regimen of use and after a one-week break in the use of the ring, bleeding does not occur, then pregnancy should be excluded before introducing a new ring.

How to move or delay the onset of menstrual-like bleeding?

To delay menstrual-like withdrawal bleeding, a woman can insert a new ring without a week’s break. The next ring must be applied within 3 weeks. In this case, spotting or bleeding may occur. Then, after the usual one-week break, the woman returns to regular use of NuvaRing®.

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

Overdose

Serious consequences of an overdose of hormonal contraceptives are not described.

Symptoms: Possible symptoms include nausea, vomiting, and slight vaginal bleeding in young girls.

Treatment: There are no antidotes. Treatment is symptomatic.

Special instructions

If you have any of the following diseases, conditions, or risk factors, you should evaluate the benefits of using NuvaRing® and the possible risks for each individual woman before she starts using NuvaRing®. In the event of an exacerbation of the disease, deterioration of the condition, or the first occurrence of any of the following conditions, a woman should consult a doctor to decide whether to continue using NuvaRing®.

Circulatory disorders

The use of hormonal contraceptives can be associated with the development of venous thrombosis (deep vein thrombosis and pulmonary embolism) and arterial thrombosis, as well as related complications, sometimes fatal.

The use of any COCs increases the risk of venous thromboembolism (VTE) compared to the risk of VTE in patients who do not use COCs. The greatest risk of developing VTE is observed in the first year of using COCs. Data from a large prospective cohort study of the safety of using various COCs suggest that the greatest increase in risk, compared with the risk level in women who do not use COCs, is observed in the first 6 months after starting COCs or resuming their use after a break (4 weeks or more). In non-pregnant women who do not use oral contraceptives, the risk of developing VTE is between 1 and 5 cases per 10,000 women-years (VL). Women who use oral contraceptives have a risk of developing VTE of 3 to 9 cases per 10,000 VL. The increase in risk occurs to a lesser extent than in pregnancy, when the risk is 5-20 cases per 10,000 VL (pregnancy data are based on the actual duration of pregnancy in standard studies; based on the position that pregnancy lasts 9 months, the risk is from 7 to 27 cases per 10,000 VL). In women in the postpartum period, the risk of developing VTE is from 40 to 65 cases per 10,000 VL. VTE is fatal in 1-2% of cases.

According to the results of studies, the increased risk of VTE in women using NuvaRing® is similar to that in women using COCs (see the table below for the adjusted risk ratio). The large prospective observational study TASC (Transatlantic Active Cardiovascular Safety Study) evaluated the risk of developing VTE in women who started using NuvaRing® or COCs, switched to NuvaRing® or COCs from other contraceptives, or resumed using NuvaRing® or COCs, in a population of typical users. Women were followed up for 24-48 months. The results showed a similar level of risk of VTE in women using NuvaRing® (frequency of 8.3 cases per 10,000 VL) and in women using COCs (frequency of 9.2 cases per 10,000 VL). For women using COCs other than those containing desogestrel, gestodene, and drospirenone, the incidence of VTE was 8.5 cases per 10,000 VL.

A retrospective cohort study initiated by the FDA (US Food and Drug use) found that the incidence of VTE in women who started using NuvaRing ® is 11.4 cases per 10,000 VL, while in women who started using COCs containing levonorgestrel, the incidence of VTE is 9.2 cases per 10,000 VL.

Assessment of the risk (risk ratio) of VTE in women using NuvaRing® compared to the risk of VTE in women using COCs

Epidemiological study, population:

Comparison drug (s):

Risk ratio (RR) (95% CI):

1 – Including low-dose COCs containing the following progestins: chlormadinone acetate, ciproterone acetate, desogestrel, dienogest, drospirenone, ethinodiol diacetate, gestoden, levonorgestrel, norethindrone, norgestimate or norgestrel.

2 – Based on age, BMI, duration of use, and history of VTE.

3-Including low-dose COCs containing the following progestins: norgestimate, norethindrone, or levonorgestrel.

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

Extremely rare cases of thrombosis of other blood vessels (for example, the arteries and veins of the liver, mesenteric vessels, kidneys, brain and retina) are known when using COCs. It is not known whether these cases are related to the use of COCs.

Possible symptoms of venous or arterial thrombosis may include unilateral swelling and/or pain in the lower limb, local fever in the lower limb, hyperemia or discoloration of the skin on the lower limb; sudden severe chest pain, possibly radiating to the left arm; an attack of shortness of breath, coughing; any unusual, severe, prolonged headaches; sudden partial or complete loss of vision; double vision; slurred speech or aphasia; dizziness; collapse, accompanied or not accompanied by accompanied by a focal epileptic seizure; sudden weakness or pronounced numbness of one side of the body or any part of the body; motor disorders; “sharp” stomach.

Risk factors for venous thrombosis and embolism:

• Age;
• The presence of a family history of diseases (venous thrombosis and embolism in siblings at any age or in parents at a young age). If a hereditary predisposition is suspected, a woman should be referred to a specialist for consultation before using any hormonal contraceptives.
• Prolonged immobilization, major surgery, any lower limb surgery, or serious injury. In such situations, it is recommended to stop using the drug (in the case of elective surgery for at least 4 weeks), followed by resumption of use no earlier than 2 weeks after full recovery of motor activity;
• Obesity (body mass index more than 30 kg / m2);
• Probably, thrombophlebitis of the superficial veins with varicose veins.

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

Risk factors for complications of arterial thromboembolism:

• Age;
• Smoking (with heavy smoking and with age, the risk increases even more significantly, especially in women over 35 years of age);
• Dyslipoproteinemia;
• Obesity (body mass index more than 30 kg / m2);
• Increased blood pressure;
• Migraines.
• Heart valve disease;
• Atrial fibrillation;
• The presence of diseases in the family history (arterial thrombosis in siblings at any age or in parents at a relatively early age). If a hereditary predisposition is suspected, a woman should be referred to a specialist for consultation before using any hormonal contraceptives. Biochemical factors that may indicate a hereditary or acquired predisposition to venous or arterial thrombosis include resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, phospholipid antibodies (cardiolipin antibodies, lupus anticoagulant).

Other conditions that can lead to undesirable circulatory disorders include diabetes mellitus, systemic lupus erythematosus, hemolytic-uremic syndrome, and chronic inflammatory bowel diseases (such as Crohn’s disease or ulcerative colitis), as well as sickle cell anemia.

It is necessary to take into account the increased risk of developing thromboembolism in the postpartum period. An increase in the frequency or severity of migraines (which may be a prodromal symptom of cerebral circulatory disorders) during the use of hormonal contraceptives may cause immediate discontinuation of hormonal contraceptives.

Women using KGC should be advised to consult a doctor if possible symptoms of thrombosis occur. In case of suspected or confirmed thrombosis, the use of KGK should be discontinued. At the same time, it is necessary to use effective contraceptives, since anticoagulants (coumarins) have a teratogenic effect.

Risk of developing tumors

The most important risk factor for cervical cancer is infection with the human papillomavirus (HPV). Epidemiological studies have shown that long-term use of COCs leads to an additional increase in the degree of such risk, but it remains unclear how much this is due to other factors, such as more frequent cervical smear tests and differences in sexual behavior, including the use of barrier contraceptives. It remains unclear how this effect is related to the use of NuvaRing®.

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 combined hormonal oral contraceptives. The risk gradually decreases within 10 years after drug withdrawal.Breast cancer rarely develops in women under the age of 40, so the additional number of breast cancer cases in women who take or have taken COCs is small compared to the overall risk of developing breast cancer. Breast cancer diagnosed in women who use COCs is clinically less pronounced than cancer diagnosed in women who have never used COCs. The increased risk of developing breast cancer may be due to the fact that women taking COCs are diagnosed with breast cancer at an earlier time, as well as the biological effects of COCs, or a combination of both of these factors.

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

Other states:

• Women with hypertriglyceridemia or an appropriate family history have an increased risk of developing pancreatitis when taking hormonal contraceptives.
• Many women taking hormonal contraceptives experience 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 arterial hypertension has not been established. If there is a persistent increase in blood pressure during the use of NuvaRing®, you should consult your doctor to decide whether to remove the vaginal ring and prescribe antihypertensive therapy. If blood pressure is adequately controlled with antihypertensive medications, it is possible to resume the use of NuvaRing®.
• During pregnancy and during the use of combined oral contraceptives, the following conditions were observed to develop or worsen, although their relationship with contraceptive use was not definitively established: jaundice and / or pruritus caused by cholestasis, gallstone formation, 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 diseases may lead to discontinuation of NuvaRing® before normalization of liver function indicators. Relapse of cholestatic jaundice previously observed during pregnancy or with the use of sex hormone preparations requires discontinuation of NuvaRing®.
• Although estrogens and progestogens can affect peripheral insulin resistance and tissue tolerance to glucose, there is no evidence to support the need to change hypoglycemic therapy with the use of hormonal contraceptives. However, women with diabetes should be under constant medical supervision when using NuvaRing®, especially during the first months of contraception.
• There is evidence of worsening of the course of Crohn’s disease and ulcerative colitis with the use of hormonal contraceptives.
• In rare cases, pigmentation of the facial skin (chloasma) may occur, especially if it occurred earlier during pregnancy. Women who are predisposed to developing chloasma should avoid exposure to sunlight and ultraviolet radiation while using NuvaRing®.
• The following conditions may prevent proper insertion of the ring or contribute to its loss: prolapse of the cervix, a herniated bladder and / or a herniated rectum, severe chronic constipation.
• In very rare cases, women have inadvertently inserted a NuvaRing® vaginal ring into the urethra and possibly into the bladder. If symptoms of cystitis occur, the possibility of incorrect ring insertion should be taken into account.
• Cases of vaginitis during the use of NuvaRing®are described. There is no evidence that treatment of vaginitis affects the effectiveness of NuvaRing®, as well as evidence of the effect of NuvaRing® on the effectiveness of treatment of vaginitis.
• Very rare cases of difficult extraction of the ring, which required its removal by a medical professional, are described.

Medical examination/consultation

Before prescribing NuvaRing® or resuming its use, you should carefully read the medical history (including family history) of the woman and conduct a gynecological examination to exclude pregnancy. It is necessary to measure blood pressure, conduct a breast and pelvic examination, including cytological examination of cervical smears and some laboratory tests, to exclude 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 carried out at least once every 6 months. A woman should read the instructions for use and follow all recommendations. The woman should be informed that NuvaRing® does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Reduced efficiency

The effectiveness of NuvaRing® may decrease if the regimen of use is not followed or concomitant therapy is performed.

Reduced cycle control

Acyclic bleeding (spotting or sudden bleeding) may occur during the use of NuvaRing®. If such bleeding is observed after regular cycles against the background of proper use of NuvaRing®, you should consult your attending gynecologist to conduct the necessary diagnostic tests, including to exclude organic pathology or pregnancy. Diagnostic curettage may be required.

Some women do not bleed after the ring is removed. If NuvaRing® has been used in accordance with the instructions, it is unlikely that the woman is pregnant. If the recommendations of the instructions are not followed and there is no bleeding after removing the ring, as well as if there is no bleeding for two consecutive cycles, pregnancy should be excluded.

Effects of ethinyl estradiol and etonogestrel on the sexual partner

Possible pharmacological effects and extent of exposure to ethinyl estradiol and etonogestrel on male sexual partners (due to absorption through penile tissues) not investigated.

Ring Damage

In rare cases, ring rupture has been observed with NuvaRing. The core of NuvaRing® is solid, so its contents remain intact, and the release of hormones does not change significantly. If the ring breaks, it usually falls out of the vagina (see the recommendations in the section “What to do if the ring was temporarily removed from the vagina” in the section “Dosage and use”). If the ring breaks, a new ring must be inserted.

Ring Dropout

NuvaRing® vaginal ring has sometimes been observed to fall out of the vagina, for example, when it is inserted incorrectly, when a tampon is removed, during sexual intercourse, or against the background of severe or chronic constipation. In this regard, it is advisable for a woman to regularly check for the presence of a vaginal ring NuvaRing® in the vagina. If the NuvaRing® vaginal ring falls out of the vagina, follow the recommendations in the section ” What to do if the ring was temporarily removed from the vagina “in the section”Dosage and use”.

Influence on the ability to drive vehicles and other mechanisms that require increased concentration of attention

Based on information about the pharmacodynamic properties of NuvaRing®, it can be expected that it does not affect the ability to drive vehicles and work with mechanisms.

Form of production

The ring is vaginal.

Storage conditions

At a temperature of 2-8 °C.

Shelf

life is 3 years.

Active ingredient

Ethinyl Estradiol, Etonogestrel

Conditions of release from pharmacies

By prescription

Dosage form

transdermal system

Purpose

For women of childbearing age, For adults

Indications

Contraception