Expiration date: 10/2025

Composition

Vaginal Rings 1 pc.

active substance:

11.7 mg etonogestrel

ethinyl estradiol 2.7 mg

Excipients: ethylene-vinyl acetate copolymer (28% vinyl acetate) - 1677 mg; ethylene-vinyl acetate copolymer (9% vinyl acetate) - 197 mg; magnesium stearate - 1.7 mg

The drug forms

Smooth, transparent, colorless or almost colorless ring without large visible lesions with transparent or almost transparent area at the junction.

pharmachologic effect

Mode of action - a contraceptive.

pharmacodynamics

Mechanism of action. The drug NuvaRing® - combined hormonal contraceptive containing ethinyl estradiol and etonogestrel. Progestagen is etonogestrel (a derivative of 19-nortestosterone) which has a high affinity for the progesterone receptors in target organs.

Ethinyl estradiol is the estrogen and is widely used for the production of contraceptives.

The contraceptive effect of the drug due to NuvaRing® combination of various factors, the most important of which is to suppress 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) for NuvaRing® drug in women aged 18 to 40 years was 0.96 (95% CI: 0.64 -1.39) and 0.64 (95% CI: 0,35-1,07) in the statistical analysis of all randomized participants (ITT-analysis) and analysis of research participants who completed them according to the protocol (PP-analysis), respectively. These values ??were similar to the values ??Pearl indices obtained in comparative studies of combined oral contraceptives (COCs) containing levonogrestrel / ethinyl estradiol (0.15 / 0.03 mg) and drospirenone / ethinyl estradiol (3 / 0.3 mg).

Against the background of the drug NuvaRing® cycle becomes more regular, decrease the intensity of pain and bleeding menstrualnopodobnoe, helping to reduce the incidence of iron deficiency states. There is evidence of a decrease in the risk of endometrial cancer and ovarian cancer during treatment with the drug.

The nature of bleeding. Compare features of nature bleeding for one year from 1000 women who used the drug NuvaRing® and COCs containing levonorgestrel / ethinyl estradiol (0.15 / 0.03 mg), showed a significant reduction in the incidence of breakthrough bleeding or spotting during the use of the drug as compared NuvaRing® with COCs. In addition, the frequency of cases when bleeding occurs only during a break in the use of the drug was significantly higher among women who used the drug NuvaRing®.

Effect on bone mineral density. Comparative 2-year study of the influence of the drug NuvaRing® (n = 76) and non-hormonal intrauterine device (n = 31) showed no effect on bone mineral density in women.

Children. The safety and efficacy of the drug NuvaRing® for teenagers under the age of 18 years have not been studied.

Pharmacokinetics

etonogestrel

Suction. Etonogestrel, released from vaginal rings NuvaRing® quickly absorbed through the vaginal mucosa. Cmax plasma levels of etonogestrel constituting about 1700 pg / ml, is reached after approximately one week after the administration of the ring. plasma concentrations vary in a small range and slowly declining to about 1600 pg / ml - 1 week, 1500 pg / ml - 2 weeks and 1400 pg / ml - after 3 weeks of application. The absolute bioavailability of approximately 100%, which exceeds the oral bioavailability of etonogestrel. According to the results of measurements of concentrations of etonogestrel in the cervical region and the inside of the uterus in women who use the drug NuvaRing®, and women using oral contraceptives containing desogestrel 0.15 mg and 0.02 mg of ethinyl estradiol, etonogestrel concentrations observed values ??were comparable.

Distribution. Etonogestrel bound to plasma albumin and blood globulin, sex hormone binding (SHBG). The apparent Vd of etonogestrel is 2.3 L / kg.

Metabolism. etonogestrel biotransformation occurs known routes of metabolism of sex hormones. Apparent clearance blood plasma is about 3.5 l / h. Direct interaction with ethinylestradiol, taken at the same time, it is not revealed.

Withdrawal. Concentration in blood plasma decreases etonogestrel in 2 phases. In the terminal phase of the T1 / 2 of approximately 29 hours of etonogestrel and its metabolites are excreted by the kidneys and the intestines through the bile in a ratio of about 1.7:. 1. T1 / 2 of metabolites is about 6 days.

Ethinylestradiol

Suction. Ethinyl estradiol released from vaginal rings NuvaRing® quickly absorbed through the vaginal mucosa. Cmax in plasma, comprising about 35 pg / ml, achieved after 3 days after injection and reduced to the ring 19 pg / ml - 1 week to 18 pg / ml - 3 weeks after application. The absolute bioavailability is about 56% and comparable to that after oral administration of ethinyl estradiol. According to the results of measurements of ethinyl estradiol concentrations in the cervical region and the inside of the uterus in women who use the drug NuvaRing®, and women using oral contraceptives containing desogestrel 0.15 mg and 0.02 mg of ethinyl estradiol, ethinyl estradiol concentrations observed values ??were comparable.

Concentration of ethinyl estradiol was studied in a comparative randomized study NuvaRing® drug (daily release of ethinyl estradiol into the vagina - 0,015 mg) transdermal patch (norelgestromin / ethinyl estradiol, ethinyl estradiol daily release - 0.02 mg) and COC (levonorgestrel / ethinyl estradiol, ethinyl estradiol daily release - 0 , 03 mg) during one cycle in healthy women. Systemic exposure over months ethinylestradiol (AUC0-?) for the preparation NuvaRing® was statistically significantly lower than that of the patch and KOC, and 10.9 ng · hr / mL compared to 37.4 and 22.5 ng · hr / ml in plaster and HEC respectively.

Distribution. Ethinylestradiol nonspecifically binds to plasma albumin. Apparent Vd is about 15 L / kg.

Metabolism. Ethinyl estradiol is metabolized by aromatic hydroxylation. During its biotransformation, a large number of hydroxylated and methylated metabolites. They circulate in the free form or in the form of sulfate and glucuronide conjugates. Apparent clearance is approximately 35 l / h.

Withdrawal. The concentration of ethinyl estradiol in blood plasma is reduced in phase 2. T1 / 2 in the terminal phase varies widely; the median is about 34 hours. Ethinylestradiol is not excreted unchanged. ethinylestradiol metabolites are excreted by the kidneys and the intestines through the bile in the ratio of 1.3: 1. T1 / 2 of metabolites is about 1.5 days.

Special patient groups

Children. NuvaRing® pharmacokinetics of the drug in healthy adolescent girls in the age of 18 who have already come menstruation, has not been studied.

Impaired renal function. Effect of renal disease on the pharmacokinetics of the drug has not been studied NuvaRing®.

Abnormal liver function. The impact of liver disease on the pharmacokinetics of the drug has not been studied NuvaRing®. However, in patients with impaired hepatic function may impair the metabolism of sex hormones.

Ethnic groups. The pharmacokinetics of the drug has not been studied specifically at ethnic groups.

Indications NuvaRing® drug

Contraception.

Contraindications

NuvaRing® drug is contraindicated in the presence of any of the conditions listed below. In the event of any of these conditions during treatment NuvaRing® should immediately stop using the product.

• hypersensitivity to any of the active substances or auxiliaries NuvaRing® drug;
  
• thrombosis (arterial or venous) and thromboembolism present or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular accident);
  
• state prior thrombosis (including transient ischemic attack, angina pectoris) now or in history;
  
• predisposition to venous or arterial thrombosis, including hereditary diseases: resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein deficit S, hyperhomocysteinemia and antiphospholipid antibodies (antibodies to cardiolipin, lupus anticoagulant);
  
• migraine with focal neurological symptoms now or in history;
  
• diabetes with vascular disease;
  
• expressed or multiple risk factors for venous or arterial thrombosis: a genetic predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the next of kin), hypertension, defeat valvular atrial fibrillation, advanced surgery, prolonged immobilisation, major trauma, obesity (body weight> 30 kg / m2), smoking in women over 35 years of age (see "Special instructions".);
  
• pancreatitis with severe hypertriglyceridemia now or in history;
  
• severe liver disease;
  
• liver tumors (benign or malignant), including: in history;
  
• known or suspected hormone-dependent cancers (eg genital tumors, or breast cancer);
  
• vaginal bleeding of unknown etiology;
  
• pregnancy, including prospective;
  
• breastfeeding;
  
• safety and efficacy of the drug NuvaRing® for teenage girls under the age of 18 years have not been studied.
  

Carefully

If any of the following diseases, conditions or risk factors should evaluate the usefulness of the drug NuvaRing® and the possible risks for each individual woman before she starts NuvaRing® use of the drug (see. "Special Instructions" section). In the case of aggravation of diseases, deterioration of, or the first time any of the following conditions a woman should see a doctor to decide on possible further application NuvaRing® drug.

With careful preparation NuvaRing® should be applied in the following cases:

• risk factors for thrombosis and thromboembolism: a genetic predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the next of kin), smoking, obesity, dislipoproteinemia, hypertension, migraine without focal neurological symptoms, heart valve disease , cardiac arrhythmias, prolonged immobilization, major surgery;
  
• thrombophlebitis of superficial veins;
  
• dislipoproteinemia;
  
• valvular disease;
  
• adequately controlled hypertension;
  
• diabetes without vascular complications;
  
• acute or chronic liver disease;
  
• Jaundice and / or itching caused by cholestasis;
  
• cholelithiasis;
  
• porphyria;
  
• systemic lupus erythematosus;
  
• hemolytic-uremic syndrome;
  
• Sydenham's chorea (chorea);
  
• hearing loss due to otosclerosis;
  
• (Hereditary) angioedema;
  
• chronic inflammatory bowel disease (Crohn's disease and ulcerative colitis);
  
• sickle cell anemia;
  
• chloasma;
  
• conditions that may hinder the use of the vaginal ring: cervical prolapse, hernia of the bladder, hernia of the rectum, severe chronic constipation.
  

Pregnancy and breast-feeding

NuvaRing® The drug is designed to prevent pregnancy. If a woman wants to terminate the application of the drug to get pregnant, it is recommended to wait for the conception of the restoration of the natural cycle, because it will help to calculate the date of conception and childbirth.

Application NuvaRing® drug during pregnancy is contraindicated. In case of pregnancy the ring should be removed. Extensive epidemiological studies have revealed no increased risk of birth defects in children born to women taking COCs before pregnancy, and teratogenic effects in cases where women have taken COCs in early pregnancy, not knowing about it. Although this applies to all COCs, it is unknown whether this also applies to NuvaRing® drug. A clinical trial in a small group of women found that, despite the fact that the drug NuvaRing® inserted into the vagina, the concentration of the contraceptive in the uterus hormones when applied NuvaRing® preparation are similar to those when using HEC. The outcome of pregnancy in women who used the drug NuvaRing® during clinical studies have not been described.

Application NuvaRing® drug during breast-feeding is contraindicated. The composition of the drug can interfere with lactation, reduce the amount and change the composition of breast milk. Small amounts of contraceptive hormones and / or metabolites thereof can be excreted with the milk, but the evidence of their negative impact on the health of children received.

Interaction

Interaction with other drugs

Interactions between hormonal contraceptives and other drugs may lead to the development of acyclic bleeding and / or ineffective contraception. The literature describes the following interactions with combined oral contraceptives in general.

Hepatic metabolism: interactions may occur with drugs that induce hepatic microsomal enzymes which may lead to an increase in clearance of sex hormones. Installed interaction, eg phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also with oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and preparations containing St. John's wort (Hypericum perforatum). In the treatment of any of these funds should temporarily use a barrier method of contraception (condoms) in combination with the drug NuvaRing® or choose another method of contraception. During concomitant drugs that induce microsomal enzymes, and within 28 days after their cancellation should use barrier methods of contraception.

If concomitant therapy should be continued after 3 weeks of use of the ring, the ring must enter the following immediately, without the usual interval.

Antibiotics: decrease the effectiveness of oral contraceptives containing ethinyl estradiol, indicated with concomitant antibiotics such as ampicillin and tetracyclines. The mechanism of this effect has not been studied. In a study of pharmacokinetic interactions intake of amoxicillin (875 mg 2 times daily) or doxycycline (200 mg / day, followed by 100 mg / day) for 10 days during use of the drug NuvaRing® significantly affect pharmacokinetics of etonogestrel and ethinyl estradiol. When using antibiotics (except amoxicillin and doxycycline) should use a barrier method of contraception (condoms) during treatment and during the 7 days after discontinuation of antibiotics.

If concomitant therapy should be continued after 3 weeks of use of the ring, the ring must enter the following immediately, without the usual interval.

Pharmacokinetic studies have not revealed the influence of the simultaneous application of anti-fungal agents and spermicides on the contraceptive efficacy and safety of the drug NuvaRing®. The combined application of suppositories with antifungal drugs significantly increased the risk of rupture of the ring. Hormonal contraceptives may cause violation of other drug metabolism. Accordingly, their concentration in the plasma and tissues may increase (e.g. cyclosporin) or decrease (eg lamotrigine).

To eliminate possible interactions should be familiar with the instructions for use of other drugs.

Other interactions

Laboratory research. The use of contraceptive steroids may influence the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney; transport to the plasma concentration of proteins, such as SHBG kortikosteroidsvyazyvayuschego globulin and plasma; fractionating lipids / lipoproteins; on carbohydrate metabolism; as well as indicators of blood coagulation and fibrinolysis. Indicators tend to vary in the range of normal values.

The combined use of tampons. Pharmacokinetic data indicate that the use of tampons has no effect on the absorption of the hormones released from vaginal rings NuvaRing®. In rare cases, the ring can be accidentally removed when removing a tampon (see. Subsection What to do if the ring was temporarily removed from the vagina in the "Dosage and Administration" section).

Dosing and Administration

Vaginally. In order to achieve a contraceptive effect NuvaRing® drug should be used according to instructions.

A woman can independently enter NuvaRing® vaginal ring into the vagina.

The physician should inform the woman how to enter and delete NuvaRing® vaginal ring (Fig. 1, 2).

For the introduction of a ring the woman should choose a comfortable position, such as standing up, lifting one leg, squatting, or lying down. NuvaRing® vaginal ring should be compressed and inserted into the vagina to a comfortable position of the ring. The exact position of the ring inside the vagina is not critical for the contraceptive effect (Fig. 3).

Methods of administration (see. Figure 4a, 4b, 4c).

1. With one hand to introduce the ring into the vagina with the other hand to dissolve labia (Fig. 4a), if necessary.

2. Push the ring into the vagina to a comfortable position of the ring (Fig. 4b).

3. Leave the ring in the vagina for 3 weeks (Figure 4c).

After the introduction (see. How to start the use of the drug NuvaRing®) ring must be in the vagina continuously for 3 weeks. Woman advisable to regularly check whether it remains in the vagina. If the ring is accidentally deleted, you must follow the instructions of sub-section What to do if the ring was temporarily removed from the vagina.

NuvaRing® vaginal ring must be removed after 3 weeks on the same day of the week, when the ring was introduced into the vagina. After a one week interval injected new ring (for example, if NuvaRing® vaginal ring has been found in the medium at about 22.00, it should be removed in the medium after 3 weeks at about 22.00. In a new ring is introduced next Wednesday). To remove the ring, it is necessary to pick up the index finger or compress the index and middle finger and pull out of the vagina (Fig. 5).

The used ring should be placed in a bag (to keep out of the reach of children and pets) and discarded. Bleeding associated with the discontinuation of the drug NuvaRing® usually starts 2-3 days after removal of the vaginal ring NuvaRing® and can not completely stop until the moment when it is established a new ring.

How to start the use of the drug NuvaRing®

In the previous cycle, hormonal contraceptives have not been applied. NuvaRing® drug should enter in the 1st day of the cycle (i.e., in the 1st day of menstruation). You can install the rings on the 2-5 th days of the cycle, but in the first cycle in the first 7 days of the drug NuvaRing® recommend the additional use of barrier methods of contraception.

The transition from a combined hormonal contraceptive (KGC). A woman should enter the vaginal ring NuvaRing® the last day of the usual interval between cycles to accept SCC (tablets or patches). If a woman is properly and regularly took the SCC and is confident that is not pregnant, she can go to the use of the vaginal ring on any day of the cycle. In no case should not exceed the recommended bezgormonalny interval of the previous method.

Go to products containing only a progestogen (mini-pill, progestin-only oral contraceptives, implants, injectable form or gormonosoderzhaschie intrauterine system - Navy). Women taking the mini-pill or progestin-only oral contraceptives can go to use the drug NuvaRing® any day. Ring is administered daily removal of the implant or the IUD. If a woman received injections, the use of the drug NuvaRing® begin on the day when the next injection should produce. In all these cases the woman should use a barrier method of contraception during the first 7 days after the administration of the ring.

After the abortion I trimester. A woman can enter the ring immediately after the abortion. In this case, it does not need any additional contraceptive. If the use of the drug NuvaRing® immediately after abortion is undesirable, it is necessary to implement the recommendations contained in the section In the previous cycle, hormonal contraceptives have not been applied. In the interval the woman recommend an alternative method of contraception.

After delivery or after abortion in the II trimester. Women are encouraged to enter the ring is not earlier than 4 weeks after the first birth (if she is not breastfeeding) or abortion in the II trimester. If the ring is installed at a later date, the recommended use of an additional barrier method for the first 7 days. However, if you have already taken place sex, it is necessary to exclude pregnancy or wait until the first menstrual period before applying NuvaRing® drug.

Deviations from the recommended mode

The contraceptive effect, and cycle control may be violated if a woman does not comply with the recommended mode. To avoid reducing the contraceptive effect, it is necessary to carry out the following recommendations.

What to do in case of a break elongation in the application of the ring. If, during a break in the application of the ring had sexual intercourse, pregnancy should be ruled. The longer the interval, the higher the probability of pregnancy. With the exclusion of pregnancy, women should be as soon as possible to enter a new ring in the vagina. In an additional barrier method can be used for the next 7 days, such as a condom.

What to do if the ring was temporarily removed from the vagina. The ring should remain in the vagina for 3 weeks. If the ring is accidentally deleted, it should be washed with cold or lukewarm (not hot) water and inserted into the vagina immediately.

• If the ring remains outside the vagina less than 3 hours, the contraceptive effect it is not reduced. A woman should be like a ring into the vagina (not later than 3 hours) can be entered quickly.
  
• If the ring is outside the vagina for more than 3 hours during the 1st or 2nd week of application, the contraceptive effect may be reduced. A woman should be like to enter the ring in the vagina as soon as possible. Over the next 7 days is necessary to use a barrier method of contraception, such as condoms. The longer the ring is outside the vagina and the closer this time for a 7-day break in the application of the ring, the greater the chance of pregnancy.
  
• If the ring is outside the vagina for more than 3 hours in the 3rd week of application, the contraceptive effect may be reduced. The woman should discard that ring and choose one of the following two methods:
  

1. Immediately establish a new ring (a new ring can be used for the next 3 weeks. In this case, there may be no bleeding associated with the cessation of the drug. However, possible blood spotting or bleeding in the middle of the cycle).
   
2. Wait for bleeding associated with the cessation of the drug, and enter a new ring no later than 7 days after the removal of the previous rings (this option should be selected only if the application mode of the ring for the first 2 weeks are not violated).
   

What to do in case of prolonged use of the ring. If NuvaRing® drug used no more than a maximum period of 4 weeks, then the contraceptive effect is sufficient. A woman can make a week break in the application of the ring, and then enter a new ring.

If the vaginal ring NuvaRing® left in the vagina for more than 4 weeks, the contraceptive effect may deteriorate, so before the introduction of the new ring is necessary to exclude pregnancy. If a woman does not adhere to the recommended scheme of application and after a week's break in the application of the ring no bleeding occurs, it is necessary to exclude pregnancy before the introduction of the new ring.

How to move or delay the onset of bleeding menstrualnopodobnoe. To delay menstrualnopodobnoe withdrawal bleeding, a woman can enter a new ring without a week's break. The next ring must be used within three weeks. This may have spotting or bleeding. Then, after a week's break normal woman returns to the regular use of the drug NuvaRing®.

To move the start of bleeding to another day of the week, a woman can be recommended to make a short break in the application of the ring (for as many days, as many as needed). The short break in the application of the ring, the higher the probability of absence of bleeding that occurs after removal of the ring, and the occurrence of bleeding or spotting during the application of the next ring.

Children

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

Overdose

Serious consequences of an overdose of hormonal contraceptives are not described. Possible symptoms include nausea, vomiting, and slight vaginal bleeding in young girls. There is no antidote. Treatment is symptomatic.

release Form

Vaginal rings, 0.015 mg + 0.12 mg / day. 1 ring packaged in a waterproof bag made of aluminum foil coated with a layer of LDPE on the inside, outside - a layer of polyethylene terephthalate (PET). By 1 or 3 pack packaged in a cardboard box.