home Consultations Nuvaring cures. Contraceptive ring "Novaring": instructions for use, reviews, photos

Nuvaring cures. Contraceptive ring "Novaring": instructions for use, reviews, photos

Combined hormonal contraceptive drug, containing etonogestrel and ethinyl estradiol.

Etonogestrel is a progestogen (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 the drug NuvaRing ® is due to a combination of various factors, the most important of which is the suppression of ovulation.

Efficiency

IN clinical studies it was found that the Pearl index (an indicator reflecting the frequency of pregnancy in 100 women during 1 year of contraception) in women aged 18 to 40 years for the drug NuvaRing ® 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 the analysis of study participants who completed them according to the protocol (PP analysis), respectively. These values were similar to the values of the Pearl indices obtained with comparative studies combined oral contraceptives (COCs) containing levonorgestrel/ethinyl estradiol (0.150/0.030 mg) or drospirenone/ethinyl estradiol (3/0.30 mg).

With the use of the drug NuvaRing ®, the cycle becomes more regular, the pain and intensity of menstrual-like bleeding decreases, which helps reduce the incidence of iron deficiency conditions. There is evidence of a reduction in the risk of endometrial and ovarian cancer with the use of the drug.

Nature of bleeding

A comparison of bleeding patterns over a one-year period in 1,000 women using NovaRing ® and COCs containing levonorgestrel/ethinyl estradiol (0.150/0.030 mg) showed a significant reduction in the incidence of breakthrough bleeding or spotting when using NovaRing ® 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 the drug NuvaRing ® .

Effect on bone mineral density

A comparative two-year study of the effect of the drug NuvaRing (n=76) and non-hormonal intrauterine device(n=31) showed no effect on mineral density bone tissue among women.

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

Pharmacokinetics

Etonogestrel

Suction

Etonogestrel released from vaginal ring NuvaRing ® is quickly absorbed through the vaginal mucosa. The etonogestrel plasma Cmax of approximately 1700 pg/ml is achieved approximately 1 week after ring administration. Plasma concentrations vary over a small range and decrease slowly to approximately 1600 pg/mL after 1 week, 1500 pg/mL after 2 weeks, and 1400 pg/mL after 3 weeks. Absolute bioavailability is about 100%, which exceeds the bioavailability at orally etonogestrel. Based on the results of measurements of etonogestrel concentrations in the cervix and inside the uterus in women using the drug 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 serum albumin and sex hormone binding globulin (SHBG). The apparent V d of etonogestrel is 2.3 l/kg.

Metabolism

Biotransformation of etonogestrel occurs through known pathways of sex hormone metabolism. Apparent plasma clearance is about 3.5 l/h. No direct interaction with ethinyl estradiol taken concomitantly has been identified.

Removal

The concentration of etonogestrel in the blood plasma decreases in two phases. In the terminal phase, T1/2 is about 29 hours. Etonogestrel and its metabolites are excreted by the kidneys and through the intestines with bile in a ratio of 1.7:1. Half life of metabolites is approximately 6 days.

Ethinyl estradiol

Suction

Ethinyl estradiol, released from the NuvaRing ® vaginal ring, is rapidly absorbed through the vaginal mucosa. Plasma Cmax of approximately 35 pg/ml is achieved 3 days after ring administration 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. Absolute bioavailability is approximately 56% and is comparable to that of oral ethinyl estradiol. Based on 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.

Ethinyl estradiol concentrations were studied in a comparative randomized study of NovaRing ® (daily vaginal release of ethinyl estradiol 0.015 mg), transdermal patch (norelgestromin/ethinyl estradiol; daily release of ethinyl estradiol 0.020 mg) and COC (levonorgestrel/ethinyl estradiol; daily release of ethinyl estradiol 0.030 mg) during one cycle y healthy women. Systemic exposure to ethinyl estradiol over a month (AUC 0-∞) for the drug NuvaRing ® was statistically significantly lower than for the patch and COC, and amounted to 10.9, 37.4 and 22.5 ngch/ml, respectively.

Distribution

Ethinyl estradiol binds to serum albumin. The apparent Vd is about 15 l/kg.

Metabolism

Ethinyl estradiol is metabolized by aromatic hydroxylation. During its biotransformation, it forms a large number of hydroxylated and methylated metabolites that circulate both in the free state and in the form of glucuronide and sulfate conjugates. The apparent clearance is approximately 3.5 l/h.

Removal

The concentration of ethinyl estradiol in the blood plasma decreases in two phases. T 1/2 in the terminal phase varies widely; the median is about 34 hours. Ethinyl estradiol is not excreted unchanged; its metabolites are excreted by the kidneys and through the intestines in a ratio of 1.3:1. Half life of metabolites is about 1.5 days.

Special patient groups

The pharmacokinetics of NovaRing ® in healthy adolescent girls under 18 years of age who have already menstruated have not been studied.

Renal dysfunction

The effect of kidney disease on the pharmacokinetics of NovaRing ® has not been studied.

Liver dysfunction

The effect of liver diseases on the pharmacokinetics of NovaRing ® has not been studied.

However, in patients with impaired liver function, the metabolism of sex hormones may deteriorate.

Ethnic groups

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

Release form

The vaginal ring is smooth, transparent, colorless or almost colorless, without large visible damage, with a transparent or almost transparent area at the junction.

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.

1 PC. - waterproof bags made of aluminum foil (1) - cardboard packs.
1 PC. - waterproof bags made of aluminum foil (3) - cardboard packs.

Dosage

NuvaRing ® is inserted into the vagina once every 4 weeks. The ring is in the vagina for 3 weeks and then removed on the same day of the week on which it was placed in the vagina; after a week's break, a new ring is inserted. For example: if the NuvaRing ® ring was installed on Wednesday at approximately 10:00 pm, then it should be removed on Wednesday 3 weeks later at approximately 10:00 pm; on the following Wednesday a new ring is inserted.

Bleeding associated with discontinuation of the drug usually begins 2-3 days after removal of NuvaRing ® and may not completely stop until a new ring is installed.

Hormonal contraceptives were not used in the previous menstrual cycle

NuvaRing ® should be administered on the first day of the cycle (i.e., the first day of menstruation). It is possible to install a ring on days 2-5 of the cycle, however, in the first cycle in the first 7 days of using the drug NuvaRing ®, additional use of barrier methods of contraception is recommended.

Switching from taking combined oral contraceptives

NuvaRing ® should be administered on the last day of the usual interval between cycles of combined hormonal contraceptives (pills or patches). If a woman has been taking the combined hormonal contraceptive correctly and regularly and is confident that she is not pregnant, she can switch to using a vaginal ring on any day of her cycle.

Switching from progestogen-only medications (mini-pills, progestin-only oral contraceptives, implants, injectables, or hormone-containing intrauterine systems (IUDs))

A woman taking the mini-pill can switch to using NuvaRing ® on any day. The ring is inserted on the day of removal of the implant or IUD. If a woman received injections, then use of the drug NuvaRing ® begins on the day when the next injection should have been given. In all these cases, the woman should use barrier method contraception during the first 7 days after insertion of the ring.

After an abortion performed in the first trimester of pregnancy

You can start using NuvaRing ® immediately after an abortion. In this case, there is no need for additional use of other contraceptives. If the use of NuvaRing ® immediately after an abortion is undesirable, the ring should be used in the same way as if hormonal contraceptives were not used in the previous cycle. In the interval, a woman is recommended alternative method contraception.

After childbirth or abortion performed in the second trimester of pregnancy

The use of NuvaRing ® should begin within the 4th week after childbirth (if the woman is not breastfeeding) or abortion in the second trimester. If the use of NuvaRing ® is started more than late dates, then additional use of barrier methods of contraception is necessary in the first 7 days of using NuvaRing ® . However, if sexual intercourse has already taken place during this period, then before using the drug NuvaRing ® it is necessary to exclude pregnancy or wait until the first menstruation.

The contraceptive effect and cycle control may be impaired if the patient does not comply with the recommended regimen. To avoid loss of contraceptive effect in case of deviation from the regimen, the following recommendations must be followed.

Extending the break from using the ring

If you had sexual intercourse during a break from using the ring, pregnancy should be ruled out. How longer break, the higher the likelihood of pregnancy. If pregnancy is ruled out, a new ring should be inserted into the vagina as quickly as possible. Over the next 7 days, an additional barrier method of contraception, such as a condom, can be used.

If the ring has been temporarily removed from the vagina

If the ring remains outside the vagina for less than 3 hours, the contraceptive effect will not decrease. The ring should be reinserted into the vagina as soon as possible (no later than after 3 hours).

If the ring was left outside the vagina for more than 3 hours during the first or second week of use, the contraceptive effect may be reduced. You should place the ring in your vagina as soon as possible. Over the next 7 days, you must use a barrier method of contraception, such as a condom. The longer the ring was outside the vagina and the closer this period is to the 7-day break in using the ring, the higher the likelihood of pregnancy.

If the ring was left outside the vagina for more than 3 hours during the third week of use, the contraceptive effect may be reduced. The woman should throw away the ring and choose one of the following two methods.

1. Immediately install a new ring. Please note that the 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's effect. However, spotting or bleeding in the middle of the cycle is possible.

2. Wait for bleeding associated with the cessation of the drug’s effect, and insert a new ring no later than 7 days after removing the previous ring. This option should only be chosen if the ring use regimen has not previously been violated during the first 2 weeks.

Extended use of the ring

If the drug NuvaRing ® was used for no more than a maximum period of 4 weeks, then the contraceptive effect remains sufficient. You can take a week's break from using the ring and then insert a new ring. If NuvaRing ® remains in the vagina for more than 4 weeks, the contraceptive effect may deteriorate, so pregnancy must be excluded before inserting a new ring.

How to shift or delay the onset of menstrual bleeding

To delay menstrual-like withdrawal bleeding, you can insert a new ring without a week's break. The next ring must be used within 3 weeks. This may cause bleeding or spotting. Then, after the usual one-week break, you should return to regular use of NuvaRing ®.

To postpone the onset of bleeding to another day of the week, it may be recommended to take a shorter break from using the ring (for as many days as necessary). The shorter the interval between ring use, the higher the likelihood that there will be no bleeding after ring removal, and no bleeding or spotting will occur when the next ring is used.

Ring damage

IN in rare cases When using NuvaRing ®, ring rupture was observed. The core of the NuvaRing ® ring is solid, so its contents remain intact, and the release of hormones does not change significantly. If the ring ruptures, it usually falls out of the vagina. If the ring ruptures, a new ring must be inserted (following the recommendations above "If the ring has been temporarily removed from the vagina").

Ring falling out

Sometimes NuvaRing ® fell out of the vagina, for example, when it was inserted incorrectly, when a tampon was 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 the presence of the NuvaRing ® ring in the vagina. If the ring falls out of the vagina, you should follow the recommendations above "If the ring has been temporarily removed from the vagina."

Rules for using NuvaRing ®

A woman can independently insert NuvaRing ® into the vagina. To insert the ring, a woman should choose the position that is most comfortable for her, for example, standing, raising one leg, squatting, or lying down. NuvaRing ® must be squeezed and inserted into the vagina until comfortable position rings. The exact position of NuvaRing ® in the vagina is not decisive for the contraceptive effect.

After insertion, the ring must remain in the vagina continuously for 3 weeks. If the ring was accidentally removed, it should be washed with warm (not hot) water and immediately inserted into the vagina.

To remove the ring, you can pick it up index finger or squeeze it between 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.

Overdose

Serious consequences of an overdose of hormonal contraceptives have not been described.

Expected symptoms: nausea, vomiting, minor vaginal bleeding in young girls.

Treatment: carried out symptomatic therapy. There are no antidotes.

Interaction

Interaction between hormonal contraceptives and other drugs can lead to the development acyclic bleeding and/or contraceptive failure.

The literature describes the following interactions with combined oral contraceptives in general.

Possible interaction with medicines, inducing microsomal liver enzymes, which can lead to increased clearance of sex hormones. Interactions have been established with the following drugs: phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and preparations containing St. John's wort.

When treating any of the listed drugs, you should temporarily use a barrier method of contraception (condom) in combination with the drug NuvaRing ® or choose another method of contraception. During concomitant use of drugs that cause the induction of microsomal liver enzymes, and for 28 days after their discontinuation, barrier methods of contraception should be used.

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

A decrease in the effectiveness of oral contraceptives containing ethinyl estradiol has been 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 administration of amoxicillin (875 mg 2 times / day) or doxycycline (200 mg / day, and then 100 mg / day) for 10 days while using the drug NuvaRing ® had a slight 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 stopping antibiotics. If concomitant therapy is to be continued after 3 weeks of ring use, the next ring should be administered immediately without the usual interval.

Pharmacokinetic studies did not reveal the effect of simultaneous use antifungal agents and spermicides on the contraceptive effectiveness and safety of the drug NuvaRing ®. When using suppositories in combination with antifungal drugs the risk of ring rupture increases slightly.

Hormonal contraceptives can cause metabolic disturbances in other medicines. Accordingly, their concentrations in plasma and tissues may increase (for example, cyclosporine) or decrease (for example, lamotrigine).

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

Pharmacokinetic data show that the use of tampons does not affect the absorption of hormones released from the NovaRing ® vaginal ring. In rare cases, the ring may be accidentally removed when removing the tampon.

Side effects

Frequency determination side effects: often (≥1/100), infrequently (<1/100, ≥1/1000), редко (<1/1000, ≥1/10 000).

Often	Infrequently	Rarely	Post-marketing data 1
Infections and infestations
Vaginal infection	Cervicitis, cystitis, urinary tract infections
From the immune system
			Hypersensitivity
Metabolism
Weight gain	Increased appetite
Mental disorders
Depression, decreased libido	Mood changes
From the nervous system
Headache, migraine	Dizziness, hypoesthesia
From the side of the organ of vision
	Visual impairment
From the cardiovascular system
	"Hot flashes", increased blood pressure	Venous thromboembolism 2
From the digestive system
Abdominal pain, nausea	Bloating, diarrhea, vomiting, constipation
From the skin
Acne	Alopecia, eczema, skin itching, rash		Hives
From the musculoskeletal system
	Back pain, muscle spasms, pain in limbs
From the urinary system
	Dysuria, urinary urgency, pollakiuria
From the genital organs and breast
Engorgement and tenderness of the mammary glands, genital itching in women, painful menstrual-like bleeding, pain in the pelvic area, vaginal discharge	Absence of menstrual-like bleeding, discomfort in the mammary glands, enlarged mammary glands, lumps in the mammary glands, cervical polyps, contact (during intercourse) spotting (bleeding), pain during intercourse, ectropion of the cervix, fibrocystic mastopathy , heavy menstrual-like bleeding, acyclic bleeding, discomfort in the pelvic area, premenstrual-like syndrome, burning sensation in the vagina, vaginal odor, pain in the vagina, discomfort and dryness of the vulva and vaginal mucosa		Local reactions in partner 3 galactorrhea
From the body as a whole
	Fatigue, irritability, malaise, swelling
Others
Discomfort when using the vaginal ring, loss of the vaginal ring	Difficulty using a contraceptive, rupture (damage) of the ring, sensation of a foreign body in the vagina

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

2 Observational cohort study data: ≥1/10,000 -<1/1000 женщин-лет.

3 Local reactions in the partner include reports of local reactions in the penis (eg, pain, flushing, bruising and abrasions).

Side effects that occurred when taking combined hormonal contraceptives: pancreatitis, cholecystitis, cerebrovascular disorders, benign and malignant liver tumors, chloasma, changes in insulin resistance.

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

Indications

Contraception.

Contraindications

thrombosis (arterial or venous) and thromboembolism currently or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);
conditions preceding thrombosis (including transient ischemic attacks, angina) currently or in history;
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 (anticardiolipin antibodies, lupus anticoagulant);
migraine with focal neurological symptoms currently or in history;
diabetes mellitus with vascular damage;
pronounced or multiple risk factors for venous or arterial thrombosis: hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age in one of the immediate family), arterial hypertension, lesions of the valvular apparatus of the heart, atrial fibrillation, extensive surgery, prolonged immobilization, extensive trauma, obesity (BMI>30 kg/m2), smoking in women over 35 years of age;
pancreatitis (including a history) in combination with severe hypertriglyceridemia;
severe liver disease;
liver tumors, malignant or benign (including history);
established or suspected hormone-dependent malignant tumors (for example, genital organs or breast);
vaginal bleeding of unknown etiology;
pregnancy (including suspected);
breastfeeding period;
hypersensitivity to any of the active or excipients of the drug NuvaRing ®.

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

If any of the above conditions occur, you should immediately stop using the drug.

The drug should be prescribed with caution if any of the following diseases, conditions or risk factors are present; in such cases, the doctor must carefully weigh the benefit-risk ratio of using the drug NuvaRing ®:

the presence of risk factors for the development of thrombosis and thromboembolism: hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age in one of the immediate relatives), smoking, obesity, dyslipoproteinemia, arterial hypertension, migraine without focal neurological symptoms, valve diseases heart, heart rhythm disturbances, prolonged immobilization, serious surgical interventions;
thrombophlebitis of superficial veins;
dyslipoproteinemia;
heart valve disease;
adequately controlled arterial hypertension;
diabetes mellitus without vascular complications;
acute or chronic liver dysfunction;
jaundice and/or itching caused by cholestasis;
cholelithiasis;
porphyria;
systemic lupus erythematosus;
hemolytic-uremic syndrome;
Sydenham's chorea (minor chorea);
hearing loss due to otosclerosis;
angioedema (hereditary) edema;
chronic inflammatory bowel diseases (Crohn's disease and ulcerative colitis);
sickle cell anemia;
chloasma;
conditions that make it difficult to use a vaginal ring: cervical prolapse, bladder hernia, rectal hernia, severe chronic constipation.

In case of exacerbation of diseases, deterioration of the condition, or the occurrence of any of the listed conditions, you should first consult a doctor to decide on the possibility of further use of the drug NuvaRing ® .

Features of application

Use during pregnancy and breastfeeding

The drug NuvaRing ® is intended to prevent pregnancy. If a woman wants to stop using the drug in order to become pregnant, it is recommended to wait for the restoration of the natural cycle to conceive, because this will help to correctly calculate the date of conception and birth.

The use of NuvaRing ® during pregnancy is contraindicated. If pregnancy occurs, the ring should be removed. Extensive epidemiological studies have not found an increased risk of birth defects in children born to women who took COCs before pregnancy, nor have there been teratogenic effects in cases where women took COCs in early pregnancy without knowing about it. Although this applies to all COCs, it is unknown whether this also applies to NuvaRing ® . A clinical study in a small group of women showed that, despite the fact that the drug NuvaRing ® is administered into the vagina, the concentrations of contraceptive hormones inside the uterus when using the drug NuvaRing ® are similar to those when using the COC. Pregnancy outcomes in women who used NuvaRing ® during a clinical trial have not been described.

The use of NuvaRing ® during 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 steroids and/or their metabolites may be excreted in breast milk, but there is no evidence of their negative effects on the health of children.

Use for liver dysfunction

Contraindicated in severe liver diseases (until normalization of function indicators).

Use in children

The safety and effectiveness of NuvaRing ® for adolescents under 18 years of age has not been studied.

special instructions

If any of the diseases, conditions or risk factors listed below are present, the benefits of using the drug NuvaRing ® and the possible risks for each individual woman should be assessed before she starts using the drug NuvaRing ® . In case of exacerbation of diseases, deterioration of the condition, or the occurrence of any of the conditions listed below for the first time, a woman should consult a doctor to decide on the possibility of further use of the drug NuvaRing ® .

Circulatory disorders

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

The use of any COC increases the risk of developing venous thromboembolism (VTE) compared to the risk of VTE in patients not using 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 various COCs suggest that the greatest increase in risk, compared with the risk in women not using COCs, is observed in the first 6 months after starting COC use or resuming their use after a break (4 weeks or more). . In nonpregnant women not using oral contraceptives, the risk of developing VTE is 1 to 5 per 10,000 woman-years (WY). In women using oral contraceptives, the risk of developing VTE ranges from 3 to 9 cases per 10,000 women. However, the risk increases to a lesser extent than during pregnancy, when it is 5-20 cases per 10,000 YL (pregnancy data are based on the actual duration of pregnancy in standard studies; when converted to a pregnancy duration of 9 months, the risk ranges from 7 to 27 cases per 10,000 JL). In postpartum women, the risk of developing VTE ranges from 40 to 65 cases per 10,000 women. VTE is fatal in 1-2% of cases.

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

A retrospective cohort study initiated by the FDA showed that the incidence of VTE in women who started using NuvaRing ® was 11.4 cases per 10,000 YL, while in women who started using COCs containing levonorgestrel, the incidence of VTE was 9.2 cases per 10,000 women. 10,000 JL.

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

Epidemiological study, population	Comparator(s)	Risk ratio (RR) (95% CI)
TAS (Dinger, 2012) Women who started using the drug (including again, after a break) and switched from other means of contraception.	All available PDAs during Study 1	OR 2: 0.8 (0.5-1.5)
	Available COCs, except those containing desogestrel, gestodene, drospirenone	OR 2: 0.9 (0.4-2.0)
"FDA Initiated Study" (Sydney, 2011) Women who started using combined hormonal contraceptives (CHCs) for the first time during the study period.	PDAs available during Study Period 3	OR 4: 1.09 (0.55-2.16)
	Levonorgestrel /0.03 mg ethinyl estradiol	OR 4: 0.96 (0.47-1.95)

1 Incl. low-dose COCs containing the following gestagens: chlormadinone acetate, cyproterone acetate, desogestrel, dienogest, drospirenone, ethynodiol diacetate, gestodene, levonorgestrel, norethindrone, norgestimate or norgestrel.

2 Taking into account age, BMI, duration of use, history of VTE.

3 Incl. low-dose COCs containing the following gestagens: norgestimate, norethindrone or levonorgestrel.

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

There are extremely rare cases of thrombosis of other blood vessels (for example, arteries and veins of the liver, mesenteric vessels, kidneys, brain and retina) with the use of COCs. It is unknown whether these cases are related to the use of COCs.

Possible symptoms of venous or arterial thrombosis may be unilateral swelling and/or pain in the lower extremity, local increase in temperature in the lower extremity, hyperemia or discoloration of the skin of the lower extremity; sudden severe chest pain, possibly radiating to the left arm; attack of shortness of breath, cough; 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 a focal epileptic seizure; sudden weakness or severe numbness on one side of the body or any part of the body; movement disorders; "sharp" stomach.

Risk factors for the development of venous thrombosis and embolism:

age;
presence of diseases in the family history (venous thrombosis and embolism in brothers/sisters at any age or in parents at a relatively early age). If a hereditary predisposition is suspected, before starting any hormonal contraceptives, the woman should be referred to a specialist for consultation;
prolonged immobilization, major surgery, any surgery on the lower extremities or serious trauma. In such situations, it is recommended to stop using the drug (in the case of a planned operation, at least 4 weeks in advance) with subsequent resumption of use no earlier than 2 weeks after complete restoration of motor activity;
for obesity (BMI more than 30 kg/m2);
possibly thrombophlebitis of the superficial veins and varicose veins.

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

Risk factors for the development of 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 (BMI more than 30 kg/m2);
arterial hypertension;
migraine;
heart valve disease;
atrial fibrillation;
presence of diseases in the family history (arterial thrombosis in brothers/sisters at any age or in parents at a relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for consultation before starting any hormonal contraceptives.

Biochemical factors that may indicate hereditary or acquired predisposition to venous or arterial thrombosis include activated protein C resistance, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

Other conditions that can cause unwanted circulatory problems include diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome and chronic inflammatory bowel disease (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 thromboembolism in the postpartum period.

An increase in the frequency or severity of migraine (which may be a prodromal symptom of cerebrovascular accidents) while using hormonal contraceptives may be a reason to immediately discontinue use of hormonal contraceptives.

Women using COCs should be advised to consult a doctor if possible symptoms of thrombosis appear. If thrombosis is suspected or confirmed, use of the COC should be discontinued. In this case, it is necessary to use effective contraception, since anticoagulants (coumarins) have a teratogenic effect.

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 long-term use of COCs leads to an additional increase in this risk, but it remains unclear to what extent this is due to other factors such as more frequent cervical smear examinations and differences in sexual behavior, including. use of barrier contraceptives. It remains unclear how this effect is related to the use of the drug NuvaRing ®.

A meta-analysis of the results of 54 epidemiological studies found a small increase (1.24) in the relative risk of developing breast cancer in women taking COCs. The risk gradually decreases over 10 years after stopping the drugs. Breast cancer rarely develops in women under 40 years of age, so the additional incidence of breast cancer 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 severe than cancer diagnosed in women who have never used COCs. The increased risk of breast cancer may be due to the earlier diagnosis of breast cancer in women taking COCs, the biological effects of COCs, or a combination of both.

In rare cases, cases of development of benign, and even more rarely, malignant liver tumors have been observed in women taking COCs. In some cases, these tumors led to the development of life-threatening bleeding into the abdominal cavity. A physician 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 a corresponding 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 connection between the use of hormonal contraceptives and the development of arterial hypertension has not been established. If a constant increase in blood pressure is observed when using the drug NuvaRing ®, it is necessary to contact your doctor to decide whether it is necessary to remove the vaginal ring and prescribe antihypertensive therapy. With adequate blood pressure control using antihypertensive drugs, it is possible to resume use of the drug NuvaRing ®.

During pregnancy and during the use of COCs, the development or worsening of the following conditions was noted, although their relationship with the use of contraceptives has not been definitively established: jaundice and/or itching caused by cholestasis, formation of gallstones, porphyria, systemic lupus erythematosus, hemolytic-uremic syndrome, Sydenham's chorea (minor chorea), herpes of pregnancy, hearing loss due to otosclerosis, angioedema (hereditary) edema.

Acute or chronic liver dysfunction may serve as a reason to discontinue the drug NuvaRing ® until liver function indicators normalize. Recurrence of cholestatic jaundice, previously observed during pregnancy or during the use of sex steroids, requires discontinuation of the drug NuvaRing ® .

Although estrogens and progestogens may influence peripheral insulin resistance and tissue glucose tolerance, there is no evidence to support the need to change hypoglycemic therapy during the use of hormonal contraceptives. However, women with diabetes should be under constant medical supervision when using the drug NuvaRing ® , especially in the first months of contraception.

There is evidence of a worsening 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 predisposed to the development of chloasma should avoid exposure to sunlight and ultraviolet radiation while using NuvaRing ®.

The following conditions may prevent the ring from being inserted correctly or may cause it to fall out: cervical prolapse, bladder and/or rectal hernia, severe chronic constipation.

In very rare cases, women have unintentionally inserted the NuvaRing ® vaginal ring into the urethra and possibly into the bladder. When symptoms of cystitis appear, it is necessary to consider the possibility of incorrect insertion of the ring.

Cases of vaginitis have been described during use of the drug NuvaRing ® . There is no evidence that treatment of vaginitis affects the effectiveness of the use of the drug NuvaRing ® , as well as evidence of the influence of the use of the drug NuvaRing ® on the effectiveness of treatment of vaginitis.

Very rare cases of difficult ring removal have been described that required removal by a medical professional.

Medical examination/consultation

Before prescribing the drug NuvaRing ® or resuming its use, you should carefully review the woman’s medical history (including family history) and conduct a gynecological examination to exclude pregnancy. It is necessary to measure blood pressure, conduct an examination of the mammary glands, pelvic organs, including a 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 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 the drug NuvaRing ® may decrease if the regimen is not followed or concomitant therapy is carried out.

Changes in the nature of menstruation

During use of the drug NuvaRing ®, acyclic bleeding (spotting or sudden bleeding) may occur. If such bleeding is observed after regular cycles while using the drug NuvaRing ® correctly, you should contact your gynecologist to conduct the necessary diagnostic tests, incl. to exclude organic pathology or pregnancy. A diagnostic curettage may be required.

Some women do not bleed after the ring is removed. If the drug NuvaRing ® was used according to 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 cycles in a row, pregnancy must be excluded.

Effects of ethinyl estradiol and etonogestrel on a sexual partner

The possible pharmacological effects and extent of exposure of ethinyl estradiol and etonogestrel to male sexual partners due to absorption through penile tissue have not been studied.

Laboratory research

The use of contraceptive hormonal drugs may affect the results of certain laboratory tests, including biochemical indicators of liver, thyroid, adrenal and kidney function, plasma concentrations of transport proteins (for example, corticosteroid binding globulin and sex hormone binding globulin), lipid/lipoprotein fractions, carbohydrate metabolism and indicators of coagulation and fibrinolysis. Indicators, as a rule, vary within normal values.

Impact on the ability to drive vehicles and operate machinery

Based on information about the pharmacodynamic properties of the drug NovaRing ®, it can be expected that it does not affect the ability to drive vehicles and operate machinery.

Ethinylestradiol
- etonogestrel

Composition and release form of the drug

Vaginal ring smooth, transparent, colorless or almost colorless, without major visible damage, with a transparent or almost transparent area at the junction.

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.

1 PC. - waterproof bags made of aluminum foil (1) - cardboard packs.
1 PC. - waterproof bags made of aluminum foil (3) - cardboard packs.

pharmachologic effect

A combined hormonal contraceptive drug containing etonogestrel and ethinyl estradiol.

Etonogestrel is a progestogen (a derivative of 19-nortestosterone) that binds with high affinity to receptors in target organs. Ethinyl estradiol is an estrogen and is widely used in the production of contraceptives.

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

In clinical studies, the Pearl index (an indicator reflecting the incidence of pregnancy in 100 women during 1 year of contraception) in women aged 18 to 40 years was found to be 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 the analysis of study participants who completed them according to the protocol (PP analysis), respectively. These values were similar to the Pearl 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).

With the use of the drug, the cycle becomes more regular, the pain and intensity of menstrual-like bleeding decreases, which helps reduce the incidence of iron deficiency conditions. There is evidence of a reduced risk of endometrial and ovarian cancer with the use of drugs containing this combination.

Pharmacokinetics

Ethinyl estradiol

Based on measurements of cervical and intrauterine ethinyl estradiol concentrations in women using and using oral contraceptives containing 0.150 mg desogestrel and 0.020 mg ethinyl estradiol, observed ethinyl estradiol concentrations were comparable.

Ethinyl estradiol binds to serum levels. The apparent Vd is about 15 l/kg.

Ethinyl estradiol is metabolized by aromatic hydroxylation. During its biotransformation, a large number of hydroxylated and methylated metabolites are formed, which circulate both in the free state and in the form of glucuronide and sulfate conjugates. The apparent clearance is approximately 3.5 l/h.

The concentration of ethinyl estradiol in the blood decreases in two phases. T 1/2 in the terminal phase varies widely; the median is about 34 hours. Ethinyl estradiol is not excreted unchanged; its metabolites are excreted by the kidneys and through the intestines in a ratio of 1.3:1. Half life of metabolites is about 1.5 days.

Etonogestrel

Based on the results of measurements of etonogestrel concentrations in the cervix and inside the uterus in women using the drug 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. Etonogestrel binds to serum albumin and sex hormone binding globulin (SHBG). The apparent V d of etonogestrel is 2.3 l/kg. Biotransformation of etonogestrel occurs through known pathways of sex hormone metabolism. Apparent plasma clearance is about 3.5 l/h. The concentration of etonogestrel in the blood plasma decreases in two phases. In the terminal phase, T1/2 is about 29 hours. Etonogestrel and its metabolites are excreted by the kidneys and through the intestines with bile in a ratio of 1.7:1. Half life of metabolites is approximately 6 days.

In patients with impaired liver function, the metabolism of sex hormones may deteriorate.

Indications

Contraception.

Contraindications

Thrombosis (arterial or venous) and thromboembolism currently or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders); conditions preceding thrombosis (including transient ischemic attacks, angina) currently or in history; 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 (anticardiolipin antibodies, lupus); migraine with focal neurological symptoms currently or in history; diabetes mellitus with vascular damage; pronounced or multiple risk factors for venous or arterial thrombosis: hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age in one of the immediate family), arterial hypertension, lesions of the valvular apparatus of the heart, atrial fibrillation, extensive surgery, prolonged immobilization, extensive trauma, obesity (BMI>30 kg/m2), smoking in women over 35 years of age; pancreatitis (including a history) in combination with severe hypertriglyceridemia; severe liver disease; liver tumors, malignant or benign (including history); established or suspected hormone-dependent malignant tumors (for example, genital organs or breast); vaginal bleeding of unknown etiology; pregnancy (including suspected); breastfeeding period; hypersensitivity to any of the active or excipients.

Carefully

The presence of risk factors for the development of thrombosis and thromboembolism: hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age in one of the immediate relatives), smoking, obesity, dyslipoproteinemia, arterial hypertension, migraine without focal neurological symptoms, valve diseases heart disease, rhythm disturbances, prolonged immobilization, serious surgical interventions; thrombophlebitis of superficial veins; dyslipoproteinemia; heart valve disease; adequately controlled arterial hypertension; diabetes mellitus without vascular complications; acute or chronic liver dysfunction; jaundice and/or itching caused by cholestasis; cholelithiasis; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; Sydenham's chorea (minor chorea); hearing loss due to otosclerosis; angioedema (hereditary) edema; chronic inflammatory bowel diseases (Crohn's disease and ulcerative colitis); sickle cell anemia; chloasma; conditions that make it difficult to use a vaginal ring: cervical prolapse, bladder hernia, rectal hernia, severe chronic constipation.

Dosage

This combination is used as part of a special dosage form for topical use.

Side effects

From the immune system: hypersensitivity.

Metabolism and nutrition: increased appetite, weight gain.

From the nervous system: headache, migraine, dizziness, hypoesthesia, depression, decreased libido, mood changes, fatigue, irritability.

From the urinary system: cervicitis, cystitis, urinary tract infections, dysuria, urinary urgency, pollakiuria isuria, urinary urgency, pollakiuria.

From the digestive system: abdominal pain, nausea, bloating, diarrhea, vomiting, constipation.

From the reproductive system: vaginal infection, engorgement and tenderness of the mammary glands, genital itching in women, painful menstrual-like bleeding, pain in the pelvic area, vaginal discharge, absence of menstrual-like bleeding, discomfort in the mammary glands, enlarged mammary glands, lumps in the mammary glands, cervical polyps uterus, contact (during sexual intercourse) spotting (bleeding), pain during intercourse, ectropion of the cervix, fibrocystic mastopathy, heavy menstrual-like bleeding, acyclic bleeding, discomfort in the pelvic area, premenstrual-like syndrome, burning sensation in the vagina, vaginal odor, pain in the vagina, discomfort and dryness of the vulva and vaginal mucosa.

From the musculoskeletal system: back pain, muscle spasms, pain in the limbs.

For the skin and skin: acne, alopecia, eczema, itchy skin, rash, urticaria.

From the side of the organ of vision: visual impairment.

From the cardiovascular system: external thromboembolism, hot flashes, increased blood pressure.

Other: discomfort when using the vaginal ring, loss of the vaginal ring, malaise, swelling, foreign body sensation, difficulty using a contraceptive, rupture (damage) of the ring.

Drug interactions

Interaction between hormonal contraceptives and other drugs may lead to the development of acyclic bleeding and/or contraceptive failure.

Possible interactions with medications inducing microsomal liver enzymes, which can lead to increased clearance of sex hormones. Interactions with the following drugs have been established: phenytoin, barbiturates, primidone, rifampicin, and possibly oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and preparations containing St. John's wort.

When treating any of the listed drugs, you should temporarily use a barrier method of contraception (condom) or choose another method of contraception. During concomitant use of drugs that cause induction of microsomal liver enzymes, and for 28 days after their cancellation, barrier methods of contraception should be used.

Decreased effectiveness of oral contraceptives containing ethinyl estradiol has been observed with concomitant use antibiotics such as ampicillin and tetracyclines. The mechanism of this effect has not been studied. In a pharmacokinetic interaction study, oral administration amoxicillin (875 mg 2 times/day) or doxycycline (200 mg/day, then 100 mg/day) within 10 days during use of the drug had a slight 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 stopping antibiotics. If concomitant therapy is to be continued after 3 weeks of ring use, the next ring should be administered immediately without the usual interval.

Hormonal contraceptives can cause disruption of the metabolism of other drugs. Accordingly, their concentrations in plasma and tissues may increase (eg, cyclosporine) or decrease (eg, lamotrigine).

special instructions

If any of the following diseases, conditions or risk factors are present, the benefits and possible risks for each individual woman should be assessed before she starts using the medicine. In case of exacerbation of diseases, deterioration of the condition, or the occurrence of any of the conditions listed below for the first time, a woman should consult a doctor.

Breast cancer diagnosed in women who use COCs is clinically less severe than cancer diagnosed in women who have never used COCs. The increased risk of breast cancer may be due to the earlier diagnosis of breast cancer in women taking COCs, the biological effects of COCs, or a combination of both.

In rare cases, cases of development of benign, and even more rarely, malignant liver tumors have been observed in women taking COCs. In some cases, these tumors led to the development of life-threatening bleeding into the abdominal cavity. A doctor should consider the possibility of a liver tumor in the differential diagnosis of a woman if symptoms include severe pain in the upper abdomen, an enlarged liver, or signs of intra-abdominal bleeding.

Women with hypertriglyceridemia or a corresponding 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 connection between the use of hormonal contraceptives and the development of arterial hypertension has not been established. If a constant increase in blood pressure is observed during use, you should consult your doctor to decide whether to remove the vaginal ring and prescribe antihypertensive therapy. With adequate blood pressure control, it is possible to resume use of the drug.

Acute or chronic liver dysfunction may warrant discontinuation until liver function tests normalize. Recurrence of cholestatic jaundice, previously observed during pregnancy or when using sex steroids, requires discontinuation of the drug.

Women with diabetes should be under constant medical supervision, especially in the first months of contraception.

There is evidence of a worsening 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 predisposed to developing chloasma should avoid exposure to sunlight and ultraviolet radiation.

During use, acyclic bleeding (spotting or sudden bleeding) may occur. If such bleeding is observed after regular cycles against the background of correct use, you should contact your gynecologist to conduct the necessary diagnostic tests, incl. to exclude organic pathology or pregnancy. A diagnostic curettage may be required.

Pregnancy and lactation

Contraindicated during pregnancy and lactation (breastfeeding).

For liver dysfunction

Contraindicated for severe liver diseases (until normalization of function indicators).

NuvaRing is a flexible contraceptive ring (diameter 54 mm, ring shell thickness 4 mm). In the form of a ring, you can see the ring only in the package, since when inserted into the vagina, it adapts to the individual contours of the woman’s body and occupies the optimal position. The ring is soft, it does not violate sexual harmony and does not reduce the sensitivity of partners. The ring does not interfere with playing sports, actively moving, swimming, running. Most women claim that NuvaRing is very convenient to use.

How Nuvaring works

Hormones (estrogen and progestogen) in microdoses, smaller than even in any microdosed birth control pill, are released daily from the ring directly into the uterus and ovaries, without penetrating into other organs. They prevent the egg from being released from the ovary and fertilization, so pregnancy is impossible.

Hormones begin to be released from the ring located in the vagina under the influence of body temperature. You should know that under various conditions, the temperature of the human body can fluctuate in the range from 34°C to 42°C. Fluctuations in this range do not affect the effectiveness of NuvaRing.

Rice. 1. The location of the NuvaRing ring in the vagina.

The shell of the ring is made of hypoallergenic material and consists of a complex system of membranes that allow the release of a strictly defined amount of hormones every day. Regardless of any individual characteristics of a woman, the dose of hormones released per day is always strictly the same (15 micrograms of estrogen and 120 micrograms of progestogen).

They enter the bloodstream through the vaginal mucosa. In this case, there is no primary passage through the liver and gastrointestinal tract. This allows you to achieve high efficiency (more than 99%). The ability to conceive is fully restored within a month after stopping the use of NuvaRing.

The main advantages of NovoRing are that you cannot gain weight, there is no effect on blood clotting (varicose veins of the lower extremities) and liver function. All these side effects, unfortunately, are present to one degree or another with birth control pills. Also, hormones from NuvaRing do not reduce the level of tissue testosterone, so the ring does not reduce libido and sensations during orgasm.

How to use NovoRing?

One hormonal ring is designed for one menstrual cycle. A woman inserts it into the vagina from the 1st to the 5th day of the menstrual cycle. NuvaRing is conveniently placed inside and remains in the vagina for 21 days (3 weeks); on day 22 the ring is removed. A week later, on day 8, a new one is introduced.

NuvaRing does not require any special position in the vagina. The flexible and elastic ring itself will take the optimal position, adapting to the individual contours of the woman’s body.

Do not forget to consult a gynecologist to assess the possibility of using this method of contraception. The doctor will teach you how to insert the ring correctly, and will also tell you about the scheme for switching from birth control pills to NuvaRing.

ATTENTION!!!
The NuvaRing hormonal ring does not protect against sexually transmitted diseases. Therefore, a prerequisite for its use is the presence of one permanent sexual partner, and the absence of both of you from sexually transmitted infections.

NuvaRing (vaginal rings. sachet N1) Netherlands N.V.Organon

Trade name: NuvaRing

International name: Etonogestrel + Ethinyl estradiol

Manufacturer: N.V.Organon

Country: Netherlands

Packaging: vaginal rings 1 pc., sachets (1) - cardboard packs

Registration number P N015411/01

Registration date 12/25/2003

Description (Vidal 2008):

NuvaRingR

Representation:

ORGANON ATX code: G02BB01

Registration Certificate Holder:

ethinylestradiol + etonogestrel

Release form, composition and packaging

The vaginal ring is smooth, transparent, colorless or almost colorless, without major visible damage, with a transparent or almost transparent area at the junction.

ethinylestradiol 2.7 mg

Excipients: ethylene vinyl acetate copolymer (28% vinyl acetate), ethylene vinyl acetate copolymer (9% vinyl acetate), magnesium stearate, purified water.

1 PC. - aluminum foil bag (1) - cardboard boxes.

Clinical and pharmacological group: Hormonal contraceptive for intravaginal administration

Registration No.:

# vaginal ring 11.7 mg+2.7 mg: 1 pc. - P No. 015411/01, 12/25/03 PPR

The description of the drug is based on the officially approved instructions for use and approved by the manufacturer for the 2006 edition.

pharmachologic effect

Hormonal contraceptive for intravaginal use containing estrogen - ethinyl estradiol and gestagen - etonogestrel. Etonogestrel, a 19-nortestosterone derivative, binds to progesterone receptors in target organs.

The contraceptive effect of the drug NuvaRing is based on various mechanisms, the most significant of which is inhibition of ovulation. The Pearl index of the drug NuvaRing is 0.765.

In addition to the contraceptive effect, the drug has a positive effect on the menstrual cycle. With its use, the cycle becomes more regular, menstruation is less painful, with less bleeding, which in turn can help reduce the frequency of iron deficiency conditions. In addition, there is evidence of a reduced risk of endometrial and ovarian cancer.

Pharmacokinetics

Suction

Etonogestrel released from NuvaRing is rapidly absorbed by the vaginal mucosa. The etonogestrel Cmax of approximately 1700 pg/ml is achieved approximately one week after ring insertion. Serum concentrations are subject to slight fluctuations and slowly reach a level of 1400 pg/ml after 3 weeks. Absolute bioavailability is about 100%.

Distribution

Metabolism

Removal

The decrease in serum etonogestrel concentration is biphasic. T1/2?-phase is about 29 hours. Etonogestrel and its metabolites are excreted in urine and bile in a ratio of 1.7:1. T1/2 of metabolites is about 6 days.

Ethinyl estradiol

Suction

Ethinyl estradiol released from NuvaRing is rapidly absorbed by the vaginal mucosa. Cmax is about 35 pg/ml, achieved by 3 days after insertion of the ring and decreases to 18 pg/ml after 3 weeks. Absolute bioavailability is approximately 56%, which is comparable to oral bioavailability.

Metabolism

Ethinyl estradiol is initially metabolized by aromatic hydroxylation to form a variety of hydroxylated and methylated metabolites, which are present both in the free state and as glucuronide and sulfate conjugates. Serum clearance is about 3.5 l/h.

Removal

The decrease in serum ethinyl estradiol concentration is biphasic. T1/2?-phase is characterized by large individual differences, and, on average, is about 34 hours. Ethinyl estradiol is not excreted unchanged; its metabolites are excreted in urine and bile in a ratio of 1.3:1. T1/2 of metabolites is about 1.5 days.

Indications

Contraception.

Dosage regimen

NuvaRing is inserted into the vagina once every 4 weeks. The ring is placed in the vagina for 3 weeks and then removed on the same day of the week on which it was placed in the vagina. After a week's break, a new ring is inserted. Bleeding associated with discontinuation of the drug usually begins 2-3 days after removal of the NuvaRing and may not completely stop until the next ring needs to be used.

If hormonal contraceptives were not used in the previous menstrual cycle, NuvaRing should be administered between the 1st and 5th day of the menstrual cycle, but no later than the 5th day of the cycle, even if the woman has not completed menstrual bleeding. During the first 7 days of the first cycle of NuvaRing use, additional use of barrier methods of contraception is recommended.

When switching from taking combined oral contraceptives, NuvaRing should be administered no later than the day following the interval in taking the drug. If the combined oral contraceptive also contains inactive tablets (placebo), then NuvaRing should be administered no later than the day following the taking of the last placebo tablet.

When switching from progestogen contraception (mini-pill, implant or injectable contraception) or progestogen-releasing intrauterine devices (IUD), NuvaRing should be administered on any day (if the patient took the mini-pill), the day after removal of the implant or IUD, and for injection contraception - on the day when the next injection is needed. In all these cases, an additional barrier method of contraception should be used during the first 7 days of using NuvaRing.

After an abortion performed in the first trimester of pregnancy, you can start using NuvaRing immediately after the abortion. In this case, there is no need for additional use of other contraceptives. If the use of NuvaRing immediately after an abortion is undesirable, then the ring should be used in the same way as if hormonal contraceptives were not used in the previous cycle.

After childbirth or an abortion performed in the second trimester of pregnancy, you should begin using NuvaRing within the 4th week after childbirth or abortion. If the use of NuvaRing is started at a later date, then additional use of barrier methods of contraception is necessary in the first 7 days of using NuvaRing. However, if sexual intercourse has already taken place during this period, you must first exclude pregnancy or wait until your first menstruation before starting to use NuvaRing.

The contraceptive effect and cycle control may be impaired if the patient violates the recommended regimen. To avoid loss of contraceptive effect in case of deviation from the regimen, you must follow the following recommendations:

If you are not using the ring for an extended period, you should place a new ring in your vagina as soon as possible. Additionally, over the next 7 days it is necessary to use a barrier method of contraception. If you had sexual intercourse during the break from using the ring, you should consider the possibility of pregnancy. The longer the break, the higher the risk of pregnancy.

If the ring was accidentally removed and remained outside the vagina for less than 3 hours, the contraceptive effect will not decrease. The ring should be reinserted into the vagina as soon as possible. If the ring is left outside the vagina for more than 3 hours, the contraceptive effect may be reduced. The ring should be placed in the vagina as soon as possible, after which it should remain in the vagina continuously for at least 7 days, and a barrier method of contraception should be additionally used during these 7 days. If the ring was outside the vagina for more than 3 hours during the third week of its use, then its use should be extended beyond the prescribed three weeks (until the end of 7 days after reinsertion of the ring). After this, the ring should be removed and a new one placed after a week's break. If removal of the ring from the vagina for a period of more than 3 hours occurs during the first week of using the ring, the possibility of pregnancy should be considered.

In case of prolonged use of the ring, but not longer than 4 weeks, the contraceptive effect is maintained. You can take a week's break and then place a new ring. If NuvaRing has been in the vagina for more than 4 weeks, the contraceptive effect may decrease, and pregnancy must be excluded before using a new NuvaRing ring.

If the patient does not adhere to the recommended regimen and then does not experience bleeding caused by ring removal during a week-long break from using the ring, pregnancy must be ruled out before using a new vaginal ring.

To delay the onset of menstruation, you can start using a new ring without a week's break. The next ring should also be used for 3 weeks. This may cause bleeding or spotting. Then, after the required one-week break, you should return to regular use of NuvaRing.

To shift the onset of menstruation to another day of the week from the day that falls according to the current scheme of using the ring, you can shorten the upcoming break in using the ring for as many days as necessary. The shorter the break in using the ring, the higher the likelihood of no bleeding occurring after ring removal, and the occurrence of untimely bleeding or spotting during the use of the next ring.

Rules for using NuvaRing

The patient can independently insert NuvaRing into the vagina. To insert the ring, a woman should choose the position that is most comfortable for her, for example, standing, raising one leg, squatting, or lying down. NuvaRing must be squeezed and inserted into the vagina until the ring is in a comfortable position. The exact position of NuvaRing in the vagina is not decisive for the contraceptive effect of the ring. After insertion, the ring must remain in the vagina continuously for 3 weeks. If it is accidentally removed (for example, when removing a tampon), the ring should be rinsed with warm water and immediately placed in the vagina. To remove the ring, you can pick it up with your index finger or squeeze it between your index and middle fingers and pull it out of the vagina.

Side effect

From the side of the central nervous system: headache, migraine, depression, emotional lability, dizziness, anxiety, feeling of fatigue.

From the digestive system: nausea, abdominal pain, diarrhea, vomiting.

From the endocrine system: decreased libido, pain, tension and enlargement of the mammary glands, dysmenorrhea, increase or decrease in body weight.

From the reproductive system: vaginal discharge (“leucorrhoea”), vaginitis, cervicitis.

From the urinary system: urinary tract infections (including cystitis).

Local reactions: loss of the ring, feeling of discomfort during sexual intercourse in women and men, sensation of a foreign body in the vagina.

Contraindications

Venous or arterial thrombosis/thromboembolism (including a history);

Risk factors for thrombosis (including history);

Migraine with focal neurological symptoms;

Diabetic angiopathy;

Pancreatitis (including a history) in combination with a high degree of hypertriglyceridemia (LDL concentration more than 500 mg/dL);

Severe liver diseases (until normalization of function indicators);

Liver tumors (benign or malignant, including history);

Hormone-dependent malignant tumors (established or suspected, for example, tumors of the genital organs or mammary glands);

Vaginal bleeding of unknown etiology;

Pregnancy or suspicion of it;

Lactation period;

Hypersensitivity to the components of the drug.

The drug should be prescribed with caution for diabetes mellitus, obesity (body mass index over 30 kg/m2), arterial hypertension, atrial fibrillation, heart defects, dyslipoproteinemia, liver or gallbladder diseases, Crohn's disease or ulcerative colitis, sickle cell anemia, systemic lupus erythematosus , hemolytic uremic syndrome, epilepsy, smoking in combination with age over 35 years, with prolonged immobilization, major surgical interventions, fibrocystic mastopathy, uterine fibroids, congenital hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndrome), chloasma (avoid exposure to ultraviolet rays), as well as conditions that make it difficult to use a vaginal ring (cervical prolapse, bladder hernia, rectal hernia, severe chronic constipation).

Use for liver dysfunction

Contraindicated in severe liver diseases (until normalization of function indicators).

special instructions

Before prescribing NuvaRing, you should collect a detailed medical history of the patient, as well as conduct a medical examination, taking into account contraindications and precautions. During the period of use of NuvaRing, the examination should be repeated at least once a year. The frequency and list of studies should be selected individually for each patient, but in any case, special attention should be paid to blood pressure control, examination of the mammary glands, abdominal and pelvic organs, including cytological examination of the cervix and relevant laboratory tests.

The effectiveness of NuvaRing may be reduced if the regimen is not followed or if other drugs are used concomitantly.

If it is necessary to use drugs that may affect the contraceptive effect of the ring while using NuvaRing, you should use a barrier method of contraception in addition to using NuvaRing or choose another method of contraception. When taking inducers of microsomal liver enzymes while using NuvaRing, you should use a barrier method of contraception during the course of taking concomitant medications and for 28 days after stopping them. When taking antibiotics simultaneously (excluding rifampicin and griseofulvin), the barrier method should be used for at least 7 days after stopping the course of antibacterial therapy. If the course of therapy with concomitant medications continues beyond 3 weeks of ring use, the next ring is placed immediately, without a week's break.

The use of contraceptive steroids may affect the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function, plasma levels of transport proteins (for example, corticosteroid binding globulin and sex hormone binding globulin), lipid/lipoprotein fractions, parameters carbohydrate metabolism and indicators of coagulation and fibrinolysis. Indicators, as a rule, vary within normal values.

During pregnancy or taking oral hormonal contraceptives, conditions such as gestational herpes, hearing loss, minor chorea, and porphyria may occur.

The patient should be informed that NuvaRing does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

While using NuvaRing, irregular bleeding may occur (minor discharge or sudden bleeding).

Some women do not experience any bleeding caused by ring removal while they are not using the ring. If NuvaRing is used as directed, it is unlikely that the woman will be pregnant. If you deviate from the recommended regimen and there is no bleeding from drug withdrawal, or if there is no bleeding 2 times in a row, pregnancy should be excluded.

The extent of exposure and possible pharmacological effects of ethinyl estradiol and etonogestrel on sexual partners through absorption through the skin of the penis have not been studied.

Overdose

Cases of overdose are unknown.

Suspected symptoms of overdose: nausea, vomiting, vaginal bleeding.

Treatment: carry out symptomatic therapy. There are no antidotes.

Drug interactions

Interactions between hormonal contraceptives and other medications may result in breakthrough bleeding and/or loss of contraceptive effect.

With simultaneous use of NuvaRing with drugs that induce microsomal liver enzymes (phenytoin, phenobarbital, primidone, carbamazepine, rifampicin, oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin, St. John's wort), the metabolism of sex hormones is increased and the contraceptive effect of NuvaRing is reduced.

The effectiveness of NuvaRing may also be reduced when taking certain antibiotics, such as penicillins and tetracyclines, at the same time. These drugs reduce the enterohepatic circulation of estrogens, resulting in decreased concentrations of ethinyl estradiol.

The effect on the contraceptive effect and safety of NuvaRing of antifungal drugs and spermicides prescribed intravaginally is not known. No direct interactions were observed between etonogestrel and co-administered ztinyl estradiol.

Storage conditions and periods

NuvaRing should be stored out of the reach of children at a temperature of 2° to 8°C.

Conditions for dispensing from pharmacies

NuvaRing is available with a prescription.

The NuvaRing ring is a hormonal drug that has a high contraceptive effect and does not cause negative consequences for the body. The instructions for use characterize it as a reliable method of protection.

It is not fussy to use, since it does not require the daily participation of a woman, acting independently. How exactly is this level of protection against unwanted conception achieved, and in what situations should it be preferred?

The Nuvaring ring, the instructions for use of which describe in detail the rules of use, is a highly effective new generation contraceptive. The artificial material from which the ring is made is also used for breast enlargement and in the manufacture of implants.

This is a translucent, almost colorless rim, 6 cm in diameter, which reliably protects the egg from fertilization by sperm and the onset of conception. The material from which the drug is made is hypoallergenic, so a negative reaction to it occurs extremely rarely.

Composition and principle of action

The instructions for the NuvaRing ring describe in detail the active substance and mechanism of action. Inside the ring are ethinyl estradiol and etonogestrel, which are released from their shell every day in strictly limited doses. Due to the fact that there are many vessels in the vagina, the active substance quickly penetrates the blood and begins to act.

Birth control pills work in the same way, when taken the substance is absorbed through the stomach, and not through the walls of the vagina.

NuvaRing has the following effects on the female body:

Suppresses the onset of ovulation.
Does not allow the hormonal system to function.
Promotes the formation of thick mucus in the cervix, preventing sperm from penetrating inside and fertilizing the egg.

These processes can be reversed if you stop removing the ring from the body and wait for the cycle to normalize.

Advantages of the method

In addition to the reliability of this type of contraception, the NuvaRing ring has other positive aspects:

Low doses of hormones that a woman receives daily while using the ring. According to researchers, it releases almost a third less ethinyl estradiol than oral contraceptives.
A woman does not need to think about taking contraceptives every day, since the drug works independently of her, releasing the required amount of the active substance.
With its help, it is easy to regulate your monthly cycle, namely, delay or bring forward the onset of menstrual bleeding.
Like any hormonal drug, NuvaRing has a beneficial effect on appearance - it improves skin, hair and nails, and helps reduce discomfort during menstruation and pain.

Disadvantages of the method

The main disadvantages of using a contraceptive ring are the presence of an impressive list of contraindications and side effects, as well as the need to strictly adhere to the regimen of using the drug.

But the disadvantages do not end there:

The NuvaRing cannot protect a woman from sexually transmitted diseases, such as AIDS and syphilis. The same can be said about all hormonal contraceptives.
Additionally, if a woman is susceptible to infection, the presence of a foreign object in the vagina can increase inflammation and increase the amount of discharge.
Due to the fact that the ring can move and even be removed from the vagina on its own, there is a need to periodically check its presence in order to prevent sperm from fertilizing the egg.
This method of contraception is psychologically unusual for women, and therefore often causes mistrust in its contraceptive properties.

Technique of use

You can use the NuvaRing ring only after fully reading the instructions and consulting with a gynecologist. You should not prescribe the use of this contraceptive yourself, as it is difficult to take into account all the nuances known only to a professional.

When the first period occurs, you can inject the drug into the vagina, and the procedure should be as follows:

To wash hands.
Take a comfortable position that allows access to the vagina and allows you to completely relax, for example, lie on the sofa.
Open the package and remove the ring from the aluminum wrapper.
Flatten it with two fingers and insert the ring deeply into the vagina, adhering to the back wall.

The whole process does not take much time and is very similar to inserting a tampon when menstruation occurs. There should not be any pain, therefore, if you feel discomfort, you should immediately remove the drug and consult a doctor. The elastic NuvaRing ring, if used correctly, should adhere to the walls of the vagina and secure itself to them.

After three weeks of use, the contraceptive should be removed. This needs to be done correctly, although there is nothing complicated in the process.

You need to again take a comfortable position and pick up the ring with your finger to carefully remove it from the body. This item can no longer be reused, so it can be disposed of. Next, the girl can expect bleeding, which should begin within the next 7 days. A new ring should be inserted 8 days after the previous one is removed.

Use if hormonal contraceptives were not used in the previous cycle

The NuvaRing ring can be administered already on the first day of the cycle at the initial signs of bleeding in order to protect yourself as much as possible from conception. If necessary, you can delay using the ring for 2-5 days if you turn to alternative methods of protection.

Switching from combined hormonal contraceptives

If desired, a woman can change the method of contraception and choose the NuvaRing ring instead of combined hormonal drugs. The instructions for use do not exclude this possibility if the woman followed the gynecologist’s instructions and did not miss taking pills.

Switching from drugs containing only progestogen

Mini-pills can also be easily replaced with NuvaRing. Moreover, the transition can be made on any day of the cycle by instantly replacing the implant or IUD with a ring. When using injections to prevent conception, you should not take breaks, but replace them after the final injection.

After this, it is better to use condoms for a week due to the possible decrease in the protective effect of the ring.

After an abortion in the first trimester

Using a NuvaRing ring after an early abortion, the instructions of which clearly describe this situation, does not require resorting to alternative methods of protection against conception. An exception may be medical indications, in which a woman is allowed to delay the insertion of the ring for up to 5 days.

After childbirth or after an abortion in the second trimester

More serious abortion, performed surgically for medical reasons, or childbirth requires a more delicate approach in further protection. NuvaRing should be used only after a month if the woman is not breastfeeding her newborn.

If you delay contraception and use the ring at a later date, you should use condoms to protect yourself as much as possible from conception. In addition, you need to make sure that you are not pregnant. It is necessary to continue using barrier methods of protection for 7 days after inserting the ring.

Use during pregnancy and breastfeeding

Due to the fact that the NuvaRing ring is a hormonal drug intended to prevent pregnancy, its use during this period is strictly prohibited. Although studies of the drug have not been conducted among women expecting to give birth, there is no need to risk the health of the baby.

In addition, once pregnancy has already occurred, there is no need for contraception. The same cannot be said about the lactation period, which is also not recommended to be combined with the use of hormonal contraceptives. This is due to the fact that the active substance contained in the ring can change the composition of breast milk or reduce its volume.

Break in use

Violation of the contraceptive regimen prescribed by the gynecologist can lead to conception. Before using the NuvaRing ring after a break, the instructions provided by the manufacturer advise you to make sure there is no pregnancy.

If fertilization of the egg has not occurred, the drug should be installed as soon as possible, while simultaneously using alternative methods of contraception. But a break does not always happen due to the fault of a woman who simply got lost in the dates.

The NuvaRing ring tends to involuntarily move into the vagina and even be removed from it. Then it is urgent to return it to its place. If the contraceptive was absent from the vagina for no more than 3 hours, then there is no need to be afraid of conception. Otherwise, it is better to play it safe and resort to condoms or other barrier methods.

Extended use

If NuvaRing was used longer than prescribed, but not longer than a month, then the contraceptive effect will remain sufficient to prevent conception. The woman needs to take the prescribed week break and use the following drug.

Scheme for using the NovaRing contraceptive ring.

After 4 weeks of use, the contraceptive effect of NuvaRing decreases, therefore, before inserting a new ring, you need to take a pregnancy test or consult a doctor to establish the fact that you are not pregnant.

Menstruation and bleeding during use

Bleeding during contraception with this hormonal drug is considered normal. Most often, menstruation begins immediately after the ring is removed and stops with the introduction of a new contraceptive. Less often, bleeding does not begin at all, and this is also not a deviation, provided that all recommendations are followed.

Repeated absence of menstruation requires the intervention of a gynecologist, as this may mean pregnancy. However, when using the NuvaRing ring, the instructions require strict monitoring of the body’s condition, since severe bleeding must be observed by the attending gynecologist.

Cancellation of NuvaRing

A woman can refuse contraception with NuvaRing at any time, since this process does not require special preparation. If necessary, the drug can be safely removed without waiting for 21 days of use.

Pregnancy after stopping the contraceptive ring

Refusal of hormonal contraception leads to the cessation of effects on the woman’s body, and NuvaRing is no exception. Conception can occur as early as 4-5 weeks after the contraceptive ring is removed.

Drug interactions

Parallel use of the NuvaRing ring with other medications may result in a decrease in contraceptive effect, as the instructions warn about.

Medicines that should not be combined with hormonal contraception:

Drugs that are excreted in large quantities by the liver, leading to hepatic metabolism. This refers to medications such as barbitures, carbamazepine, phenytoin, rifampicin, and some other medications containing St. John's wort. When undergoing therapy with these drugs, it is better to resort to alternative methods of contraception without removing the ring from the vagina.
Antibiotics also lead to a decrease in the contraceptive effect, as they have a great effect on the active substance of NuvaRing. When taking these drugs, with the exception of doxycycline and amoxicillin, you should use barrier contraceptives during treatment and for a week after the end of the course.

Protection using a hormonal ring can also affect the biochemical parameters of some organs and change the composition of the blood. If during contraception a woman needs to undergo a medical examination, the attending physician should be aware of the use of the NuvaRing ring.

Side effects

A negative reaction to the drug is extremely rare, but not completely excluded. Side effects that occur in connection with the use of the NuvaRing ring usually do not require emergency medical attention, since they go away on their own.

Side effects include:

Intoxication - nausea, diarrhea, and sometimes vomiting.
Dizziness, constant anxiety, changeable mood, pain in the head, as a result of the effect on the nervous system.
Weight gain, breast hardening, decreased libido.
Cystitis.
Minor discharge, vaginitis.

In addition, a woman may be bothered by the sensation of a foreign object in the vagina, as well as spontaneous removal of the ring.

Contraindications for use and use with caution

Not everyone is recommended to use the NuvaRing ring, since it has quite a lot of prohibitions and contraindications.

Hormone-dependent malignant tumors.
Vaginal bleeding that occurs for unknown reasons.
Blood disorders such as thrombosis or bleeding disorders.
Pregnancy and lactation.
Severe liver pathologies, including tumors.
Inflammatory processes in the vagina - vaginitis, colpitis.
Allergies to contraceptive components.

Careful use of the product is possible for:

varicose veins;
heart disease;
autoimmune diseases;
when the walls of the female genital organ droop or fall out;
cholelithiasis;
smoking.

It is necessary to stop using NuvaRing before the proposed surgery.

Conditions and shelf life

To ensure that the drug does not lose its contraceptive properties, it must be kept at 2-8 ° C, then the NuvaRing ring will not lose its properties for 3 years from the date of release. The best place for this would be a regular refrigerator compartment, where the required temperature is maintained.

In addition, the contraceptive ring should be protected from children's attention, since if it enters the body of a minor child, it can negatively affect the development of the baby. After the expiration date, it is strictly forbidden to use the drug for its intended purpose.

Where to buy and price

The NuvaRing ring is freely available, so you can find it at any pharmacy. A large selection of drugs is offered by online portals for the sale of medicines. This makes it possible to resort to the use of NuvaRing in the most remote corners of the country, thanks to well-established logistics and courier delivery. On average, the price of one ring ranges from 600 to 1000 rubles.

Packages of the NuvaRing ring containing 3 contraceptives will cost from 1300 to 1800 rubles.

Every woman will find her own positive aspects of this method of contraception, because the convenience and effectiveness of the NuvaRing ring are obvious. Before deciding to use a hormonal drug, you should study the instructions and also consult a gynecologist.

Video about the NuvaRing ring, its effectiveness and rules of use

Instructions for use of the NuvaRing ring:

Expert opinion about the Nuvaring ring: