Pharmacodynamics. The NuvaRing contains etonogestrel and ethinyl estradiol. Etonogestrel is a progestogen, a derivative of 19-nortestosterone, which has a high affinity for progesterone receptors in target organs. Ethinyl estradiol is an estrogen widely used in contraceptives. The contraceptive effect of NuvaRing is based on different mechanisms, the main one of which is inhibition of ovulation.
The Pearl Index for the NuvaRing ring is 0.765. In addition to protecting against pregnancy, NuvaRing regulates the menstrual cycle, reduces the severity of pain and the intensity of bleeding (which reduces the risk of developing iron deficiency anemia). There is evidence of a reduced risk of developing endometrial and ovarian cancer.
Pharmacokinetics.
Etonogestrel
Etonogestrel, released from the NuvaRing ring, is quickly absorbed by the vaginal mucosa. The maximum plasma concentration of etonogestrel (average 1700 pg/ml) is achieved approximately 1 week after insertion of the ring. Then after 3 weeks the concentration slowly decreases to 1400 pg/ml. Absolute bioavailability is 100% (which is higher than when using oral contraceptives). Etonogestrel combines with serum albumin and sex hormone binding globulin. The volume of distribution of etonogestrel is 2.3 l/kg body weight.
Etonogestrel is metabolized by hydroxylation and reduction to form sulfate and glucuronide conjugates. The rate of elimination of metabolites from blood plasma is on average 3.5 l/h. There was no interaction between etonogestrel and concomitantly taken ethinyl estradiol. The concentration of etonogestrel in the blood plasma decreases in 2 stages. The half-life at the last stage is about 29 hours. Etonogestrel and its metabolites are excreted in urine and bile in a ratio of 1.7:1. The half-life of metabolites is about 6 days.
Ethinyl estradiol
Ethinyl estradiol released from the NuvaRing ring is rapidly absorbed by the vaginal mucosa. The maximum concentration in blood plasma (about 35 pg/ml) is reached approximately on the 3rd day after insertion of the ring and decreases to 18 pg/ml after 3 weeks. The absolute bioavailability is 56%, which corresponds to the level of bioavailability of ethinyl estradiol when taken orally.
Ethinyl estradiol is metabolized by aromatic hydroxylation to form hydroxylated and methylated metabolites. These metabolites are present both in the free state and as conjugates of glucuronides and sulfates. Effective clearance is approximately 35 l/h. The level of ethinyl estradiol in the blood plasma decreases in 2 stages. The half-life at the last stage is characterized by significant individual differences with an average value of 34 hours. Ethinyl estradiol is not excreted unchanged. Ethinyl estradiol metabolites are excreted in urine and bile in a ratio of 1.3:1. The half-life of metabolites is 1.5 days.

Indications for use of the drug Nuvaring

Contraception.

Use of the drug Nuvaring

The NuvaRing ring is inserted into the vagina by the woman herself. The doctor should inform the woman how to insert and remove NuvaRing. To insert the ring, take a comfortable position: stand with your leg raised, sit down or lie down. Before insertion, the NuvaRing ring must be compressed and inserted into the vagina so that it fits well. The exact position of the ring in the vagina is not decisive for the contraceptive effect.
From the moment of insertion, the ring should remain in the vagina continuously for 3 weeks. If the ring is accidentally removed (for example, when removing a tampon), it should be rinsed with cold or cool (not hot) water and immediately reinserted into the vagina. NuvaRing should be removed after 3 weeks on the same day of the week when it was inserted. After a week's break, a new ring must be inserted. The NuvaRing can be removed by lifting it with your index finger or holding the ring between your index and middle fingers. Bleeding associated with discontinuation of the drug usually begins 2-3 days after NuvaRing is removed and may continue until the day the next ring is inserted.
Getting started
If hormonal contraceptives were not used during the previous menstrual cycle, NuvaRing must be administered between the 1st and 5th day of the cycle, but no later than the 5th day from the start of menstruation, even if the bleeding has not stopped yet. During the first 7 days of using NuvaRing, it is recommended to additionally use a condom.
Switching from combined oral contraceptives (COCs)
NuvaRing must be administered the next day after a break in taking the drug or after a period of taking placebo tablets in a COC course.
Switching from progestogen-only medications (mini-pill, implant, or injection) or from a progestogen-releasing intrauterine system
A woman taking the mini-pill can switch to NuvaRing any day. When using an implant or intrauterine system that releases progestogen, the transition occurs on the day of its removal, and when using injections, on the day of the next scheduled injection. In all of these cases, the woman should use an additional barrier method during the first 7 days.
After an abortion in the first trimester
You can start using the ring immediately after an abortion. There is no need for additional methods of contraception. If the use of NuvaRing immediately after an abortion is undesirable, you should follow the recommendations (see “If hormonal contraceptives were not used during the previous menstrual cycle”).
After childbirth or abortion in the second trimester
Women are recommended to start using the ring during the 4th week after childbirth or abortion in the second trimester. If the ring is used later, it is recommended to additionally use the barrier method during the first 7 days of using NuvaRing. If you have sexual intercourse during this period, before introducing NuvaRing, you must first rule out pregnancy or wait until the next menstruation.
Deviations from the recommended regime
The effectiveness of contraception and control of the menstrual cycle may be impaired if a woman does not adhere to the recommended regimen. To avoid a decrease in the effectiveness of contraception if the regimen is violated, the following recommendations should be followed.
When extending the break in using the ring
If you miss a ring replacement, a new ring should be inserted as soon as possible and a barrier method of contraception (condom) should be additionally used for the first 7 days. If you had sexual intercourse during the break from using the ring, the risk of pregnancy should be assessed. The longer the break, the higher the risk of pregnancy.
If there is a temporary absence of a ring in the vagina
The NuvaRing ring must remain in the vagina continuously for 3 weeks. Accidental removal and absence of a ring in the vagina for ≤3 hours does not affect the effectiveness of contraception. The ring should be reinserted as quickly as possible, no later than after 3 hours. The absence of the ring in the vagina for 3 hours reduces the effectiveness of contraception. You should insert the ring as soon as possible and use a barrier method of contraception (condom) for 7 days from the time the ring is inserted into the vagina. If the first of these 7 days falls on the 3rd week of using the ring, NuvaRing should be used for longer than 3 weeks. Then the ring should be removed and a new one inserted after a week's break.
If the ring is removed for a period of 3 hours during the 1st week of using the ring, the risk of pregnancy should be weighed.
As the period of use of the ring increases
The maximum period of use of NuvaRing without loss of contraceptive effectiveness is 4 weeks. You should take a week's break from using the ring and then insert a new one. Keeping NuvaRing in the vagina for 4 weeks reduces the effectiveness of contraception, and pregnancy should be ruled out before inserting a new ring.
If the recommended regimen is violated and menstruation is delayed during the next break in using the ring, pregnancy should be ruled out before introducing a new ring.
Change in timing or delay of menstruation
To delay menstruation, a new ring should be inserted without a week's break. The new ring should also be used for 3 weeks. During this period, a woman may experience light or thick bleeding. In the future, after the usual one-week break from using the ring, regular use of NuvaRing should be resumed.
Changing the period of menstruation, moving it to another day of the week that does not coincide with the planned day of insertion of the ring, should be done by shortening the next break by the required number of days. The shorter the previous break, the higher the risk of no menstruation, or the appearance of thick or light bleeding during the next break.

Contraindications to the use of the drug Nuvaring

Venous thrombosis with/without pulmonary embolism currently or in history; arterial thrombosis (cerebrovascular accident, myocardial infarction) or precursors of thrombosis (angina pectoris or transient ischemic cerebrovascular accident) currently or in history; predisposition to venous or arterial thrombosis with or without the inclusion of hereditary disorders such as activated protein C resistance (APC), antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant). migraine with focal neurological symptoms; diabetes mellitus with vascular complications; pancreatitis or previous pancreatitis, which is accompanied by hypertriglyceridemia; severe liver disease (until liver function indicators return to normal values); liver tumor (benign or malignant; present or in history); hormone-dependent malignant tumors (diagnosed or suspected); vaginal bleeding of unknown etiology; diagnosed or probable pregnancy; breastfeeding period; hypersensitivity to any component of the drug.
Use with caution in diabetes mellitus; obesity (body mass index 30 kg/m2); AH (arterial hypertension); atrial fibrillation; heart valve diseases; dyslipoproteinemia; diseases of the liver and gall bladder; Crohn's disease and ulcerative colitis; sickle cell anemia; systemic lupus erythematosus; hemolytic uremic syndrome; epilepsy; smoking over the age of 35; prolonged immobilization; extensive surgical interventions; fibrocystic mastopathy; uterine fibroids; congenital hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndrome); chloasma (avoid sun exposure and ultraviolet radiation); any of the conditions in which the woman will not be able to properly insert or may lose the ring; cervical prolapse; cystocele or rectocele, severe or chronic constipation.

Side effects of the drug Nuvaring

Adverse drug reactions reported in women using NuvaRing® are listed in the table below. The most appropriate MedDRA term (version 11.0) to describe the specific adverse event is appended.

Systems and organs	Frequent ≥ 1/100	Uncommon ≤1/100, ≥1/1000	Post marketing (1)
Infections and infestations	Vaginal infection
The immune system			Increased sensitivity
Metabolism and eating disorders		Increased appetite
Mental disorders	Depression, decreased libido	Change of mood
The cardiovascular system		Bring blood to your face
Digestive system	Abdominal pain, nausea	Bloating, diarrhea, vomiting, constipation
Skin and subcutaneous tissues		Alopecia, eczema, itching, rashes	Hives
Musculoskeletal and connective tissue		Back pain, muscle cramps, pain in limbs
urinary system
Reproductive system and mammary gland	Soreness, itching of the female genitals, dysmenorrhea, pelvic pain, vaginal discharge	Amenorrhea, discomfort in the mammary glands, enlarged mammary glands, cervical polyp, coital bleeding, dyspareunia, cervical ectropia, fibrocystic mastopathy, menorrhagia, metrorrhagia, pelvic discomfort, premenstrual syndrome, contractions of the uterine muscles, burning pain in the vagina, unpleasant vaginal odor, vaginal pain, vulvovaginal discomfort, vulvovaginal dryness.	Diseases of the genital organ in men2
General and administration site disorders		Fatigue, irritability, discomfort, swelling, foreign body sensation
	Weight gain	Hypertension
Injuries and procedural complications	Discomfort while using the ring, loss of the vaginal contraceptive ring	Complication when using a contraceptive ring, ring breakage

1) List of adverse events based on spontaneous report. It is impossible to determine the exact frequency.
2) Diseases of the genital organ in men (including reports of local reactions).

Special instructions for the use of the drug Nuvaring

Special warnings and special precautions.
If any of the following conditions/risk factors occur, the benefits or risks of continued use of NuvaRing should be considered for each individual woman and discussed with the patient before she decides to use this drug. In case of exacerbation, intensification or first manifestations of any of these conditions, a woman should consult a doctor. The doctor determines the need to use the drug NuvaRing. All data given below are based on epidemiological data obtained from the use of combined oral contraceptives. There are no epidemiological data obtained from the vaginal method of using hormones, but warnings are considered acceptable when using the drug NuvaRing.

1. Circulatory disorders

• Epidemiological studies suggest an association between COC use and an increased risk of arterial and venous thrombosis and thromboembolic diseases such as myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism. These phenomena occur rarely.
• Women using any combined oral contraceptives increases the risk of developing venous thromboembolism (VTE) compared to those not taking COCs. There is a particularly high risk of developing venous thromboembolism in the first year of using COCs. This increased risk is less than the pregnancy-associated risk of VTE, which is estimated to be 6 per 10,000 pregnancies. VTE is fatal in 1-2% of cases.
  It is unknown how NuvaRing affects the risk of VTE compared to other combined hormonal contraceptives.
• Very rarely, thrombosis has been reported to occur in other blood vessels, such as the hepatic, mesenteric, renal, cerebral or retinal veins and arteries, in women using COCs. There is no general consensus on whether these cases are related to the use of COCs.
• Symptoms of venous or arterial thrombotic cases may include: uncharacteristic unilateral lower extremity pain and/or swelling; sudden severe pain in the chest, regardless of whether it radiates to the left arm; sudden dyspnea; sudden attack of coughing; any unusual, severe, prolonged headache; sudden partial or complete loss of vision; diplopia; slurred speech or aphasia; vertigo; collapse with or without focal epileptic seizure; weakness or severe numbness on one side or part of the body; impaired coordination of movements; symptoms of an “acute” abdomen.
• The risk of venous thromboembolism increases due to:
  age;
  family history (presence of venous or arterial thromboembolism in siblings or parents at a relatively early age). If there is a suspicion of a hereditary predisposition, the woman should be referred for consultation with a specialist before making a decision about the use of COCs;
  prolonged immobilization, significant surgical interventions, various surgical interventions on the lower extremities or severe injuries. In these cases, it is recommended to stop taking the drug (in case of planned surgery, at least four weeks in advance) and not to resume it for two weeks after complete remobilization;
  obesity (body mass index more than 30 kg/m2);
  also in the presence of superficial thrombophlebitis and varicose veins. There is no consensus on the possible role of these conditions in the etiology of venous thrombosis.
• The risk of arterial thromboembolism increases due to:
  - age;
  - smoking (the more a person smokes and the older he is, the greater the risk, especially in women over 35 years old);
  - dislipoproteinemia;
  - obesity (body mass index ≤30 kg/m2);
  - AH (arterial hypertension);
  - migraine;
  - heart valve diseases;
  - atrial fibrillation;
  - a burdened family history (for example, arterial thrombosis in a brother/sister or parents at a relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding to use hormonal contraception.
• Biochemical factors that may indicate hereditary or acquired predisposition to venous or arterial thrombosis include activated protein C (APC) resistance, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant) .
• Other medical conditions that have been associated with adverse circulatory effects include diabetes mellitus, SLE, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease and ulcerative colitis), and sickle cell disease.
• The increased risk of thromboembolism in the postpartum period should be considered (see section "Use during pregnancy or lactation").
• An increase in the frequency or intensity of migraine while taking COCs (which may precede cerebrovascular accident) may be a reason for immediate discontinuation of COC use.

2. Tumors

• The highest risk factor for developing cervical cancer is persistent infection with the human papillomavirus (HPV). Epidemiological studies have suggested that long-term use of COCs may contribute to an increased risk of cervical cancer, but the extent to which this is related to confounding effects, such as increased frequency of cervical screening and variation in sexual behavior, including barrier contraceptive use and causal associations, is unclear. It is unknown how this effect relates to NuvaRing.
• A meta-analysis of 54 epidemiological studies found that there was a small increase in the relative risk (RR = 1.24) of developing breast cancer in diagnosed women who were currently using COCs. The high risk gradually decreases over 10 years after stopping the use of COCs. Because breast cancer rarely occurs in women under 40 years of age, the number of breast cancer diagnoses among current or former COC users is small compared with the overall risk of developing breast cancer. Breast cancer diagnosed in women is generally less advanced clinically than cancer diagnosed in people who have never used COCs. The pattern of increased risk observed may be due to the early diagnosis of breast cancer in women who used COCs, the biological effects of COCs, or a combination of both factors.
• Benign liver tumors and very rarely malignant liver tumors have been rarely reported in women who use COCs. In isolated cases, these tumors caused intra-abdominal bleeding that threatened life. Therefore, liver tumor should be considered in the differential diagnosis if women who use NuvaRing experience severe upper abdominal pain, liver enlargement, or signs of intra-abdominal bleeding.

3. Other states

• When using COCs in women with hypertriglyceridemia or a family history of it, there may be a risk of developing pancreatitis.
• Although slight increases in blood pressure have been reported in many women taking hormonal contraceptives, clinically significant increases are rare. The exact relationship between the use of hormonal contraceptives and hypertension (arterial hypertension) has not been established. However, if persistent clinically significant hypertension (arterial hypertension) develops while using NuvaRing, the doctor should stop using the ring for a while and treat the hypertension (arterial hypertension). The use of the drug NuvaRing can be resumed if blood pressure levels are achieved with the help of antihypertensive therapy.
• The occurrence or worsening of the following conditions has been reported during pregnancy and the use of hormonal contraceptives, but the evidence for an association with their use is inconclusive: jaundice and/or pruritus associated with cholestasis; formation of gallstones; porphyria; SCV ; hemolytic uremic syndrome; chorea; herpes during pregnancy; hearing loss associated with otosclerosis; hereditary angioedema.
• Acute or chronic liver dysfunction may require discontinuation of the drug NuvaRing until liver function tests normalize. Recurrence of cholestatic jaundice and/or pruritus associated with cholestasis that first occurred during pregnancy or previous use of sex steroids requires discontinuation of ring use.
• Estrogens and progestogens can affect peripheral insulin resistance and impaired glucose tolerance, and there is no need to change the treatment regimen of diabetic patients who use hormonal contraception. However, women with diabetes should be closely monitored while using NuvaRing, especially in the first months of use.
• Worsening of Crohn's disease and ulcerative colitis has been reported in association with the use of hormonal contraceptives.
• Chloasma may occur periodically, especially in women with a history of chloasma during pregnancy. Women who are prone to chloasma are advised to avoid exposure to the sun or exposure to ultraviolet radiation while taking NuvaRing.

If a woman has any of the following conditions, she may not be able to insert the NuvaRing correctly or may lose the ring: cervical prolapse, cystocele and/or rectocele, severe or chronic constipation.
Very rarely, NuvaRing has been reported to be accidentally inserted into the urethra and possibly end up in the bladder. Therefore, the possibility of ring misplacement should be considered in the differential diagnosis if symptoms of cystitis occur.
While using the drug NuvaRing, women may sometimes experience vaginitis. There is no evidence that the effectiveness of the drug NuvaRing is affected by the treatment of vaginitis or that the use of the drug NuvaRing affects the effectiveness of the treatment of vaginitis (see Section Interaction with other drugs and other types of interactions.).
Very rarely, it was reported that the ring grew into the vaginal mucosa, which required the intervention of a specialist doctor.
Medical supervision
Before using or resuming the use of NuvaRing, it is necessary to consult a doctor with a thorough collection of anamnestic data and a medical examination. In the future, the doctor’s examination should be repeated at least once a year with blood pressure measurement, examination of the mammary glands, abdominal and pelvic organs, cytological examination of the cervix and relevant laboratory tests.
The patient should be informed that the use of NuvaRing does not protect against HIV infection (AIDS) and other sexually transmitted diseases.
Reduced efficiency
The effectiveness of NuvaRing may decrease if the regimen is not followed or if certain medications are taken simultaneously.
Deterioration of menstrual cycle control
While using the drug NuvaRing, (minor or heavy) bleeding may be observed. If irregular bleeding occurs after previous regular cycles while using NuvaRing in accordance with the recommended regimen, non-hormonal causes should be considered and adequate diagnostics should be instituted to rule out pregnancy or malignancy, which may include curettage.
Some women may not experience any bleeding during a break from using the ring. If NuvaRing was used in accordance with the recommendations given in the “Method of administration and dosage” section, then the possibility of pregnancy is low. However, if NuvaRing was used without following such recommendations before the first case of absence of bleeding during the period without using the ring, or if there were no bleedings twice in a row, pregnancy should be excluded before continuing to use the drug NuvaRing.
Ring damage
In very rare cases, the NuvaRing ring has been reported to come loose during use (see Section Interactions with other medicinal products or other types of interactions). Since the core of the NuvaRing drug is solid, its contents remain intact and will not significantly affect the release of hormones. If the ring becomes disconnected, it may fall out. If NuvaRing is damaged, the woman should throw away the ring and replace it with a new one.
Removal
NuvaRing may reportedly be removed if the ring is not inserted correctly, when removing a tampon, during coitus, or in cases of severe and chronic constipation. Therefore, a woman is recommended to regularly check for the presence of NuvaRing in the vagina. If NuvaRing is accidentally removed, the woman should follow the instructions.
The effect of ethinyl estradiol and etonogestrel on men
The extent and possible pharmacological effects of ethinyl estradiol and etonogestrel on sexual partners through absorption through the mucous membrane of the male genital organ have not been studied.
Use of the drug during pregnancy or breastfeeding
Pregnancy is a contraindication for the use of NuvaRing. If pregnancy occurs, the ring should be removed.
Estrogens can reduce the amount and change the composition of breast milk. It is not recommended to use NuvaRing during breastfeeding (until the baby is completely weaned).
NuvaRing does not affect concentration or the ability to drive.

Drug interactions Nuvaring

Interactions between hormonal contraceptives and other medications may cause irregular bleeding and/or a lack of contraceptive effect.
Hepatic metabolism: Interactions may occur with drugs that induce microsomal enzymes that can lead to increased metabolism of sex hormones (eg, phenytoin, phenobarbital, primidone, carbamazepine, rifampicin, oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and preparations containing St. John's wort ).
Women taking any of these drugs should temporarily use a barrier method of contraception in addition to using NuvaRing or choose another method of contraception. When using drugs that induce microsomal enzymes, a barrier method of contraception should be used during the course of using such drugs and for another 28 days after stopping their use.
If the course of concomitant drug therapy exceeds the 3 weeks during which the ring is used, the next one should be administered immediately, without the usual one-week break.
The contraceptive effect of the drug may also be reduced when taking certain antibiotics at the same time, for example, penicillins and teracyclines. The mechanism of this effect has not been identified. In pharmacokinetic interaction studies, oral administration of amoxicillin (875 mg, twice daily) or doxycycline (200 mg on the first day, followed by 100 mg daily) for 10 days of NuvaRing did not significantly affect the pharmacokinetics of etonogestrel and ethinyl estradiol (EE). ). Women taking antibiotics (except amoxilin and doxycycline) should use a barrier method of contraception for up to 7 days after stopping. If concomitant drug use exceeds 3 weeks of the ring cycle, a new ring must be inserted immediately without taking the usual break before using the next ring.
According to pharmacokinetic data, intravaginally administered antimycotic agents and spermicides do not affect the contraceptive effectiveness and safety of the drug NuvaRing. During concomitant use of antimycotic suppositories, the risk of ring dislocation may be slightly higher.
Hormonal contraceptives may affect the metabolism of other drugs. Accordingly, the concentration in blood plasma and tissues can either increase (for example, cyclosporine) or decrease (for example, lamotrigine).
Directions for use of concomitant medications should be followed to identify potential interactions.
The use of contraceptive steroids may affect the results of some laboratory tests, including biochemical indicators of liver, thyroid, adrenal and kidney function, plasma protein levels (for example, levels of corticosteroid binding globulin and sex hormone binding globulin), lipid fractions and lipoproteins, indicators of carbohydrate metabolism, coagulation and fibrinolysis. Such changes usually remain within normal laboratory values.
Interaction with tampons.
Pharmacokinetic data show that the use of tampons does not affect the systemic absorption of hormones released by NuvaRing. In rare cases, NuvaRing may be removed when the tampon is removed.

Nuvaring drug overdose, symptoms and treatment

No serious or dangerous complications have been reported from overdose. In case of an overdose, nausea, vomiting may occur, and in young women, bleeding from the vagina. There is no antidote. Treatment in case of overdose is symptomatic.

Storage conditions for the drug Nuvaring

In original packaging at a temperature of 2-8 °C.

List of pharmacies where you can buy Nuvaring:

• Saint Petersburg

Nuvaring - a new description of the drug, you can see the pharmacological action, indications for use, Nuvaring. Reviews about Nuvaring -

Hormonal contraceptive for intravaginal use.
Drug: NuvaRing®
Active substance of the drug: ethinylestradiol, etonogestrel
ATX coding: G02BB01
KFG: Hormonal contraceptive for intravaginal administration
Registration number: P No. 015428/01
Registration date: 12/25/03
Owner reg. cert.: ORGANON N.V. (Netherlands)

Nuvaring release form, drug packaging and composition.

The vaginal ring is smooth, transparent, colorless or almost colorless, without major visible damage, with a transparent or almost transparent area at the junction.
Vaginal ring
1 ring
ethinylestradiol
2.7 mg
etonogestrel
11.7 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.

The description of the drug NuvaRing is based on the officially approved instructions for use.

Pharmacological action of Nuvaring

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 NuvaRing 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 of the drug.

Etonogestrel

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

Etonogestrel binds to serum albumin and sex hormone binding globulin (SHBG). Vd of etonogestrel 2.3 l/kg.

Metabolism

Etonogestrel is metabolized by hydroxylation and reduction to form sulfate and glucuronide conjugates. Serum clearance is about 3.5 l/h.

Removal

The decrease in serum etonogestrel concentrations 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 about 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 for use:

Contraception.

Dosage and method of administration of the drug.

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.

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.

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.

Switching from progestin-only contraception (mini-pill, implant, or injectable contraception) or progestogen-releasing intrauterine device (IUD)

NuvaRing should be administered on any day (if the patient took mini-pills), on the day of removal of the implant or IUD, and with injectable contraception - on the day when the next injection is necessary. 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 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.

After childbirth or abortion performed in the second trimester of pregnancy

Use of NuvaRing should begin 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 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 EFFECTS of NuvaRing

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, decreased libido.

From the endocrine system: increase or decrease in body weight.

From the reproductive system: vaginal discharge (“leucorrhoea”), vaginitis, cervicitis, pain, tension and enlargement of the mammary glands, dysmenorrhea.

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 NuvaRing

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 valve disease, dyslipoproteinemia, liver or gallbladder diseases, Crohn's disease or ulcerative colitis, sickle cell anemia, SLE, 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 during pregnancy and lactation.

The use of NuvaRing is contraindicated during pregnancy, suspected pregnancy and lactation.

Special instructions for the use of Nuvaring.

Before prescribing NuvaRing, you should collect a detailed medical history of the patient and 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, Sydenham's chorea (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.

Drug overdose:

Cases of overdose are unknown.

Expected symptoms: nausea, vomiting, vaginal bleeding.

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

Interaction of Nuvaring with other drugs.

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 unknown.

No direct interactions have been observed between etonogestrel and co-administered ethinyl estradiol.

Terms of sale in pharmacies.

The drug NuvaRing is available with a prescription.

Terms of storage conditions for the drug Nuvaring.

NuvaRing should be stored out of the reach of children at a temperature of 2° to 8°C. Shelf life: 3 years.

Description:

A modern combined hormonal contraceptive (ring) for intravaginal administration.

Manufacturer:

ORGANON (Netherlands)

Composition and release form

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

Active ingredients: ethinyl estradiol 2.7 mg, etonogestrel 11.7 mg. Excipients: ethylene vinyl acetate copolymer (28% vinyl acetate), ethylene vinyl acetate copolymer (9% vinyl acetate), magnesium stearate.

pharmachologic effect

Combined hormonal contraceptive drug for intravaginal use. Contains etonogestrel, which is a progestogen, a derivative of 19-nortestosterone, and ethinyl estradiol, which is an estrogen. The main mechanism of contraceptive action of the drug NuvaRing is inhibition of ovulation. The progestin component (etonogestrel) inhibits the synthesis of LH and FSH by the pituitary gland and, thus, prevents follicle maturation (blocks ovulation).

The Pearl index, an indicator reflecting the frequency of pregnancy in 100 women during a year of contraception, when using the drug NuvaRing is 0.96. The use of the drug reduces the pain and intensity of menstrual-like bleeding, reduces the frequency of acyclic bleeding and the likelihood of developing iron deficiency conditions. In addition, there is evidence of a reduced risk of endometrial and ovarian cancer with the use of the drug. NuvaRing does not reduce bone mineral density.

Indications for use

Intravaginal contraception (prevention of unwanted pregnancy) in women.

Mode of application

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 the NuvaRing and may not completely stop until a new ring is installed.

Start using Nuvaring

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 free interval in taking combined hormonal contraceptives (pills or patch). 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. The duration of the interval in taking hormonal contraceptives should not exceed the recommended period.

Switching from progestin-only contraception (mini-pill, implant, or injectable contraception) or progestogen-releasing intrauterine device (IUD)

A woman taking the mini-pill can switch to using NuvaRing on any day (the ring is inserted on the day the implant or IUD is removed or on the day of the next injection). In all these cases, the woman should use a barrier method of contraception for 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, the woman is recommended an alternative method of 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 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 the drug NuvaRing.

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, you must follow the following recommendations.

Extending the break from using the ring

If you had sexual intercourse during a break from using the ring, pregnancy should be ruled out. The longer the 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.

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 this ring and choose one of two methods:
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.

Wait for bleeding associated with the cessation of the drug, 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.

To change the time of onset of menstrual bleeding

To delay (prevent) 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 rare cases, ring rupture has occurred when using NuvaRing. 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.

Ring falling out

NuvaRing has sometimes been reported to fall out of the vagina, for example, when it was inserted incorrectly, when a tampon was removed, during sexual intercourse, or due to 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.

Incorrect insertion of the ring

In very rare cases, women have inadvertently inserted NuvaRing into the urethra. When symptoms of cystitis appear, it is necessary to consider the possibility of incorrect insertion of the 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.

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 with your index finger or squeeze it between your index and middle fingers and pull it out of the vagina.

Side effect

The following side effects may occur when using Nuvaring:

System-organ class	Often (? 1/100)	Infrequently (< 1/100, ? 1/1000)	Rarely (< 1/1000)
Infections and infestations	Vaginal infection (candidiasis, vaginitis)	Cystitis, cervicitis, urinary tract infections
The immune system			Hypersensitivity
Metabolic disorders	Weight gain	Increased appetite
Mental disorders	Depression, decreased libido	Mood changes
From the nervous system	Headache, migraine	Dizziness
From the side of the organ of vision		Visual impairment
From the cardiovascular system		"Tides"
From the digestive system	Abdominal pain, nausea	Bloating, diarrhea, vomiting, constipation
From the skin		Alopecia, eczema, itchy skin	Skin rash
From the musculoskeletal system		Pain in the lumbar region, muscle spasms, pain in the limbs
From the urinary system		Dysuria, urgency, pollakiuria
From the reproductive system	Engorgement and tenderness of the mammary glands, genital itching in women, pelvic pain, vaginal discharge	Amenorrhea, cervical polyps, contact (during sexual intercourse) spotting (bleeding), dyspareunia, ectropion of the uterus, fibrocystic mastopathy, menorrhagia, metrorrhagia, premenstrual syndrome, dysmenorrhea, uterine spasm, burning sensation in the vagina, dryness of the vulva and mucous membrane vagina.	Local reactions on the part of the penis (sensation of a foreign body by the partner during sexual intercourse, irritation of the penis with increased sensitivity to the components of the drug)
	Vaginal ring prolapse	Rupture (damage) of the ring, fatigue, malaise, abdominal pain, swelling, sensation of a foreign body in the vagina

Contraindications for use

Venous thrombosis (including a history), including deep vein thrombosis, pulmonary embolism;
- arterial thrombosis (including a history), including stroke, transient cerebrovascular accidents, myocardial infarction and/or precursors of thrombosis, including angina pectoris, transient ischemic attack;
- heart defects with thrombogenic complications;
- changes in blood parameters indicating a predisposition to the development of venous or arterial thrombosis, including 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;
- arterial hypertension (systolic blood pressure? 160 mm Hg. or diastolic blood pressure? 100 mm Hg.);
- diabetes mellitus with vascular damage;
- pancreatitis incl. history, in combination with severe hypertriglyceridemia;
- severe liver diseases, until normalization of liver function indicators;
- liver tumors (including in history);
- hormone-dependent malignant tumors (for example, breast cancer), established, suspected or in history;
- bleeding from the vagina of unknown etiology;
- pregnancy (including suspected);
- lactation period;
- surgical interventions followed by long-term immobilization;
- smoking (15 or more cigarettes per day) in women 35 years of age and older;
- hypersensitivity to the components of the drug.

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

Venous or arterial thrombosis (in siblings and/or parents);
- obesity (body mass index more than 30 kg/m2);
- dislipoproteinemia;
- varicose veins (in combination with thrombophlebitis of the superficial veins);
- atrial fibrillation;
- diabetes;
- systemic lupus erythematosus;
- hemolytic-uremic syndrome;
- epilepsy;
- chronic inflammatory bowel diseases (Crohn's disease and ulcerative colitis);
- sickle cell anemia;
- congenital hyperbilirubinemia (Gilbert, Dubin-Johnson, Rotor syndromes);
- chloasma;
- uterine fibroids;
- fibrocystic mastopathy;
- conditions that make it difficult to use a vaginal ring: cervical prolapse, bladder hernia, rectal hernia, severe chronic constipation;
- adhesions in the vagina;
- smoking (less than 15 cigarettes per day) in women 35 years of age and older.

If the disease worsens, the condition worsens, or other risk factors appear, the woman should also consult a doctor and possibly discontinue the drug.

Although a cause-and-effect relationship has not been convincingly proven, caution should be exercised when prescribing NovaRing if the following conditions/diseases have previously developed or worsened during the use of any other hormonal contraceptives or previous pregnancy: jaundice and/or itching associated with cholestasis, formation of gallstones, porphyria, Sydenham's chorea, herpes of pregnancy, otosclerosis with hearing loss, (hereditary) angioedema.

Recurrence of cholestatic jaundice and/or cholestasis with itching, which was observed during pregnancy or previous use of sex hormones, is grounds for discontinuing the use of NuvaRing.

Use of NuvaRing during pregnancy and breastfeeding

The use of NuvaRing is contraindicated during pregnancy, suspected pregnancy and lactation. NuvaRing is contraindicated during breastfeeding. NuvaRing 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 milk.

Use for liver dysfunction

NuvaRing is contraindicated in severe liver diseases (until normalization of function indicators).

special instructions

Before prescribing or resuming the use of the drug NuvaRing, you should conduct a medical examination: analyze your medical history (including family history) and exclude pregnancy; measure blood pressure; conduct an examination of the mammary glands, pelvic organs, including cytological examination of smears from the cervix; conduct some laboratory tests to exclude contraindications and reduce the risk of possible side effects of the drug NuvaRing. The frequency and nature of medical examinations are carried out by a specialist, taking into account the individual characteristics of each woman, but at least once every 6 months.

The patient should read the instructions for use of the drug NuvaRing and follow all recommendations.

It should be kept in mind that NuvaRing does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Women aged 40 years and older, women with cervical intraepithelial neoplasia, as well as women who smoke at any age require additional consultation with a gynecologist before prescribing NuvaRing.

The effectiveness of the drug NuvaRing may decrease if the regimen is not followed.

While using NuvaRing, acyclic bleeding (spotting or sudden bleeding) may occur. If such bleeding is observed after regular cycles while using NuvaRing in accordance with the instructions, you should contact your gynecologist to conduct the necessary diagnostic tests, incl. to exclude a malignant tumor and pregnancy. A diagnostic curettage may be required.

Some women do not bleed after the ring is removed. If NuvaRing is used as directed, 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 in two cycles in a row, pregnancy must be excluded.

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 combined hormonal contraceptives further increases this risk, but the extent to which this is due to other factors remains unclear. The positive role of regular examinations of women by a gynecologist and the use of barrier methods of contraception are obvious. There is no information about an increased risk of developing cervical cancer in HPV-infected women using NuvaRing.

Studies have found a small increase in the relative risk (1.24) of developing breast cancer in women taking combined hormonal oral contraceptives, but this risk gradually decreases over 10 years after discontinuation of the drugs. Breast cancer is rare in women under 40 years of age, so the additional incidence of breast cancer in women who have received or continue to use combined oral contraceptives is small compared to the overall risk of developing breast cancer. There is evidence that women who have taken oral combined contraceptives have less breast cancer than women who have never used such medications. The possibility of the effect of the drug NuvaRing on the incidence of breast cancer is being studied.

In rare cases, benign liver tumors were observed in women taking combined oral contraceptives, and even more rarely, malignant ones. In some cases, these tumors led to the development of life-threatening bleeding into the abdominal cavity. If severe pain appears in the upper abdomen, liver enlargement, or signs of intra-abdominal bleeding in a woman using NuvaRing, a liver tumor should be excluded.

Although many women taking hormonal contraceptives experience a slight increase in blood pressure, clinically significant hypertension is rare. A direct connection between the use of hormonal contraceptives and the development of arterial hypertension has not been established. However, if, when using the drug NuvaRing, there is a constant increase in blood pressure, the patient should contact her gynecologist; in such cases, the ring should be removed, antihypertensive therapy should be prescribed and the issue of choosing the most acceptable method of contraception, incl. possible resumption of use of the drug NuvaRing.

Although estrogens and progestogens can influence peripheral insulin resistance and tissue tolerance to glucose, 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 NuvaRing, especially in the first months of contraception.

The use of contraceptive steroids may affect the results of certain laboratory tests, including biochemical indicators 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, carbohydrate metabolism parameters and indicators of coagulation and fibrinolysis. Indicators, as a rule, vary within normal values.

Serious surgery (including on the lower extremities) is a contraindication to the use of the drug. In case of planned surgery, it is recommended to stop using the drug at least 4 weeks in advance, and resume no earlier than 2 weeks after complete restoration of motor activity.

Women predisposed to the development of chloasma should avoid exposure to sunlight and ultraviolet radiation while using NuvaRing.

The extent of exposure and possible pharmacological effects of ethinyl estradiol and etonogestrel on the glans mucosa and skin of the penis have not been studied.

Impact on the ability to drive vehicles and operate machinery

Considering the pharmacodynamic properties of the drug NuvaRing, its effect on the ability to drive a car and use complex equipment is not expected.

Overdose

Serious consequences of an overdose of hormonal contraceptives have not been described. Suspected symptoms: nausea, vomiting, slight vaginal bleeding in young girls.

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

Drug interactions

Interactions between hormonal contraceptives and other drugs may lead to the development of acyclic bleeding and/or contraceptive failure. There may be an interaction with drugs that induce microsomal enzymes, which can lead to increased clearance of sex hormones.

The effectiveness of NovaRing may be reduced with simultaneous use of antiepileptic drugs (phenytoin, phenobarbital, primidone, carbamazepine, oxcarbazepine, topiramate, felbamate), anti-tuberculosis drugs (rifampicin), antimicrobial drugs (ampicillin, tetracycline, griseofulvin), possibly antiviral drugs (ritonavir) and medicines containing St. John's wort.

When treating any of the listed drugs, a woman should temporarily use a barrier method of contraception in combination with the drug NuvaRing or choose another method of contraception. When treating with drugs that induce liver enzymes, a barrier method (condom) should be used during treatment and for 28 days after discontinuation of such drugs.

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

During treatment with antibiotics (excluding amoxicillin and doxycycline), it is necessary to use a barrier method of contraception (condom) during treatment and for 7 days after their discontinuation. If concomitant therapy is to be continued after 3 weeks of ring use, the next ring should be administered immediately without the usual interval.

As a result of pharmacokinetic studies, no effect on the contraceptive effectiveness and safety of the drug NuvaRing when used simultaneously with antifungals and spermicides was identified. When combined with suppositories and antifungal agents, the risk of ring rupture increases slightly.

Hormonal contraceptives can cause disruption of the metabolism of other drugs. 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.

The use of tampons does not affect the effectiveness of NuvaRing. In rare cases, the ring may be accidentally removed when removing the tampon.

Storage conditions and periods

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

Latin name: NovaRing
ATX code: G02BB01
Active substance: Ethinyl estradiol
and etonogestrel
Manufacturer: Organon, Netherlands
Conditions for dispensing from a pharmacy: On prescription

Nuvaring is a new highly effective contraceptive drug of the latest generation, intended for intravaginal use.

Indications for use

The Nuvaring contraceptive ring is prescribed for contraceptive purposes.

Compound

The active ingredients of the vaginal ring are ethinyl estradiol together with etonogestrel, the dosages of the active components are 2.7 mg and 11.7 mg, respectively.

Additional components include:

• Magnesium stearate
• Ethylene and vinyl acetate copolymer.

Medicinal properties

Price from 989 to 3897 rub.

Synthetic hormones released by the ring when used vaginally have a contraceptive effect by blocking the onset of ovulation. Each of the hormones entering the body affects the functioning of the ovaries, preventing the maturation of the follicles. Etonogestrel is the progestogen component of the ring, which binds to specific progesterone receptors in the so-called target organs.

Ethinyl estradiol is an estrogen component; the action of this drug is associated with the occurrence of various processes, which are mainly aimed at suppressing ovulation.

The hormonal drug exhibits not only contraceptive properties, normalizes the menstrual cycle, reduces pain during the first days of menstrual-like discharge, reducing blood loss. Due to this effect, the risk of iron deficiency and anemia is reduced.

When using Nuvaring, the likelihood of ectopic pregnancy, the development of ovarian and endometrial cancer of the uterus is significantly reduced. At the same time, cystic formations in the ovaries, inflammatory processes in the pelvic organs, and benign neoplasms in the mammary glands are less often diagnosed.

Etonogestrel penetrates the vaginal walls, its highest concentration is observed after 7 days, precisely when it begins to act as a contraceptive. Moreover, its bioavailability is 100%, which is significantly higher than that of oral contraceptives. Metabolic processes occur in liver cells, excretion is carried out by the intestines and the renal system. The half-life of metabolic products is about 6 days.

Ethinyl estradiol is characterized by fairly high absorption rates. The highest level of the hormone is observed after 3 days. from the moment of installation of the hormonal ring. The bioavailability rate is 56%, which is almost the same as the oral use of hormones. Metabolism occurs in the intestines and kidneys, metabolites are eliminated within 36 hours.

Release form

The surface of the hormonal ring is smooth, transparent and completely colorless. There is a small transparent area in the connection area. Inside the moisture-resistant bag there is 1 Nuvaring hormonal ring. A pack may contain 1 or 3 packets (with 3 rings - Nuvaring 3) along with instructions.

Nuvaring: instructions for use

The ring must be inserted into the vagina for 21 days. After this period, it must be removed on the day of the week on which it was installed. After a week break (7 days), a new contraceptive is introduced. It is worth noting that after 2-3 days. after removing the Nuvaring ring, menstrual-like bleeding usually begins, which ends after the next intravaginal installation of the contraceptive. If this contraceptive is used for the first time, then you should pay attention to some features of its use:

• A hormonal contraceptive has not been used before - the Nuvaring ring is inserted in the first days of the cycle (best on the 1st day). If the installation occurred later than 1 day. cycle, it is recommended to use additional methods of contraception for the next seven days.
• If you have previously used hormonal contraceptive drugs, the ring should be introduced in the interval between taking COCs (seven-day withdrawal period). If COCs are used correctly and it is confirmed that the woman is not pregnant, the Nuvaring ring can be inserted on any day of the MC. You can go from Yarina using the same scheme.
• After taking the mini-pill, single-component progestin contraceptive pills, using hormonal intrauterine systems, injectable contraceptives, and implants, the ring is inserted according to certain rules. After progestin pills (mini-pills), you can insert a contraceptive drug any day, regardless of when the last pill was taken, whether the cycle after childbirth has improved or not. After removing the IUD, you will need to insert a contraceptive ring on the same day (according to the instructions). If you have previously used an injectable contraceptive, you will need to install the ring on the day when the hormone injection procedure is to be carried out. During the seven-day use of the ring, it is necessary to use a barrier method of protection against unwanted pregnancy.

Instructions for use after abortion

If an abortion is performed before 4 months of pregnancy, you will need to insert the rings immediately after this procedure or wait until the first menstruation (in this case, the contraceptive is administered on the 1st day of the cycle).

After termination of pregnancy during the second trimester or after delivery, a vaginal ring can be installed no earlier than a month (4 weeks) after natural childbirth (breastfeeding is stopped) or abortion.
If the use of a hormonal drug deviates from the standard regimen, the following recommendations should be followed:

• The break in using the hormonal ring exceeds 7 days. in the presence of unprotected sexual contacts: first of all, pregnancy is excluded and a contraceptive is immediately introduced, the next 7 days. It is preferable to use barrier methods of protection against unwanted pregnancy.
• Temporary removal of the hormonal ring: its stay outside the vagina is less than three hours, but the level of protection against pregnancy is not reduced. If the period of absence of a hormonal drug in the vagina was more than 3 hours in the first weeks of using this contraceptive, the ring must be inserted as soon as possible. In this case, the contraceptive effect may be reduced, and there is a need to take additional measures to prevent pregnancy. If the ring was removed for more than 3 hours in the third week, you must stop using this drug and insert a new one. The break in use should not last more than 7 days. You can also wait for menstruation; on the first day when menstruation begins, you can insert an intravaginal contraceptive. Use condoms for the next 7 days. is mandatory.
• Use of vaginal contraception for more than 4 weeks. requires further exclusion of pregnancy due to the fact that the contraceptive effect of the drug has significantly decreased. After pregnancy has been ruled out, you can use the drug according to the standard regimen.

How to delay menstruation

To postpone your period (the onset of bleeding) by a day or several days, you can administer a hormonal ring without the standard seven-day break. However, the possibility of bleeding should not be ruled out.

How to properly insert a ring into the vagina

Before inserting the ring, you need to squeeze it with your index finger and thumb and carefully place it inside the vagina.

If the ring accidentally falls out when using tampons, it is recommended to rinse the contraceptive under running warm water, then reinsert it. If necessary, you can check with your doctor: “What should I do if I pull out the tampon along with the ring?” It is worth noting that with a tampon a woman will not feel any discomfort. When using tampons, you need to be more careful to prevent the ring from falling out of the vagina.

To remove the ring, you should pick it up with your index finger, squeeze it slightly, and then pull it towards you. The used hormonal drug, which the woman removed from the vagina after 21 days, should be disposed of.

If a woman inserts the ring incorrectly, it is accidentally placed in the urethra, the likelihood of developing cystitis increases, and frequent urination may occur. In this case, the woman can become pregnant. Before you fight cystitis, it is worth finding out the true cause of its appearance. You will need to remove the ring as quickly as possible. As a result of subsequent correct administration, it must be securely fastened, frequent inflammatory processes of the genitourinary system, and in particular cystitis, after Nuvaring will no longer bother you, pain during urination will disappear.

Using a ring for fibroids

The presence of fibroids is not a contraindication to the use of this contraceptive; you can use the ring without harm to your own health. It is worth noting that fibroids do not grow during the use of the ring, as evidenced by ultrasound. Patients with fibroids are advised to consult with their doctor about the advisability of using the ring. If necessary, you can switch from Nuvaring to tablets. Whether it is possible to treat fibroids in this way and which contraceptives to give preference, check with your gynecologist. Cancellation of Nuvaring should be agreed with a specialist. Recovery of the cycle after hormone therapy will occur after six months.

Treatment of endometriosis

For endometriosis, the use of a hormonal ring may be indicated; when switching from other COCs (for example, if Yarina was previously prescribed), a significant improvement in the course of the disease is observed; during menstruation, a woman loses less blood. During the first month of use, the severity of pain decreases, which contributes to the gradual restoration of the endometrial layer of the uterus. After a woman switches to using the ring, her periods are painless. The drug acts gently, without disturbing the functioning of other organs and systems. Each of the active ingredients has a local therapeutic effect.

Use during pregnancy and pregnancy

Such contraceptives are not prescribed to this group of patients. The use of Nuvaring during lactation and pregnancy is contraindicated.

Contraindications

• Tendency to develop thrombosis and thromboembolism
• Conditions that indicate the development of thrombosis
• Current or previous severe migraine-like headaches with significant focal neurological symptoms
• Diabetes mellitus complicated by vascular lesions
• Pancreatitis with hypertriglyceridemia
• Serious liver disorders (including benign and malignant tumor processes)
• Presence of hormone-dependent neoplasms
• Bloody discharge from the internal genital organs of unknown origin
• Pregnancy, GW
• Excessive sensitivity to Nova Ring (main components).

Precautionary measures

If you have not previously used contraceptives of this type, you should undergo a medical examination to identify diseases that are a contraindication to the use of a hormonal ring. Control visits to the gynecologist should take place every 6 months.

It must be remembered that this contraceptive does not protect against AIDS and other infectious diseases that are sexually transmitted. When using a contraceptive, the risk of thrombosis increases significantly.

Possible symptoms include:

• Feeling of heat in the lower extremities, pain or severe swelling
• Hyperemia of certain areas of the skin
• Cough syndrome, developing shortness of breath with characteristic attacks
• Impaired vision clarity
• Intense and prolonged headaches
• Blurred speech
• Collapse
• Movement disorder
• Lethargy, decreased sensitivity of some part of the body
• Acute abdomen syndrome.

If possible blockage of blood vessels by blood clots cannot be ruled out, you must immediately stop taking the drug and seek medical help.

During contraceptive therapy (women used pills), the development of a tumor process in the liver tissue was diagnosed. The use of a vaginal ring does not exclude the development of such pathology, as with tablets.

During hormonal therapy, the risk of pancreatitis increases rapidly.

If you are prone to chloasma, you should avoid prolonged exposure to direct sunlight.

A worsening of ulcerative colitis, as well as Crohn's disease, cannot be ruled out.

Persons with diabetes need to remain under strict medical supervision during the first months of hormonal therapy.

If your period stops and a woman becomes pregnant, you should stop using the contraceptive immediately.

Cross-drug interactions

It is necessary to read the instructions for drugs such as oxcarbazepine, carbamazepine, topiramate, phenytoin, felbamate, rifampicin, as well as barbiturates and drugs based on St. John's wort. This is due to the fact that with combined use the risk of acyclic bleeding increases. It is necessary to use additional means of protection during treatment with such drugs for a month.

The use of antibiotics (for example, tetracycline or ampicillin) reduces the contraceptive effect of the hormonal drug. It is recommended to use a condom during antibiotic treatment. It is better to ask your gynecologist which antibiotics to use and what the consequences of taking them are.

When using antifungal suppositories intravaginally, the risk of damage to the hormonal ring or its rupture increases.

During hormone therapy, changes in the metabolism of other drugs may be observed, these include cyclosporine and lamotrigine.

Side effects

With long-term use of hormonal drugs, it is worth studying the instructions for the drugs, as multiple side effects may develop, in particular with Nuvaring the following cannot be ruled out:

• Excessive sensitivity
• Increased appetite and weight gain
• Decreased libido
• Sudden mood swings, depressive mood
• Migraine-like pain
• Impaired visual acuity
• Deterioration of the cardiovascular system, which is characterized by thromboembolism, changes in blood pressure, and the occurrence of so-called hot flashes
• Gastrointestinal disorders
• Rashes, acne formations and severe itching
• Soreness in the muscles, spine and limbs
• Dysuria, tendency to frequent urination, cystitis
• Lethargy, swelling
• Reproductive system: breast engorgement, the appearance of a genital node, the development of dysmenorrhea, heavy periods or their absence, bleeding of unknown etiology, discharge mixed with blood during sexual intercourse, a local burning sensation, pain inside the vagina.

Overdose

No serious consequences of overdose were detected.

Bleeding and indigestion cannot be ruled out.

Please note that there is a dedicated hotline to help women with various vaginal ring concerns. If side symptoms develop due to an overdose, you should call the hotline (the number is listed on the official page of the drug Nuvaring in Russia). Hotline operators will advise and give recommendations on what to do in a given situation.

Storage conditions and shelf life

The hormonal ring must be stored under strict temperature conditions (2-8 C) for 3 years.

Analogs

Bayer, Germany

Price from 759 to 3295 rub.

Yarina belongs to combined hormonal drugs, the dose is designed for one month. The tablets act comprehensively, exhibiting a contraceptive effect and antiandrogenic effect. The package can contain 21 or 28 tablets.

Pros:

• Eliminate the appearance of acne
• Normalize MC
• Easy to switch from other COCs.

Minuses:

• Produced by a foreign manufacturer, which is reflected in the price
• Has a negative effect on liver function
• Adverse reactions may occur during hormone therapy.

Catad_pgroup Local contraceptives

Indications for use
- Contraception
- Idiopathic menorrhagia
- Prevention of endometrial hyperplasia during HRT

INFORMATION IS PROVIDED STRICTLY
FOR HEALTH PROFESSIONALS

NuvaRing - official* instructions for use

*registered by the Ministry of Health of the Russian Federation (according to grls.rosminzdrav.ru)

INSTRUCTIONS
on the use of a medicinal product for medical use

Registration number:

Tradename:

NuvaRing ® (NuvaRing ®)

International nonproprietary name or generic name:

ethinyl estradiol + etonogestrel

Dosage form:

vaginal rings

Compound

1 vaginal ring contains:
active substances: etonogestrel – 11.7 mg, ethinyl estradiol – 2.7 mg;
Excipients: ethylene and vinyl acetate copolymer – 1677 mg, ethylene and vinyl acetate copolymer – 197 mg, magnesium stearate – 1.7 mg.

Description

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

Pharmacotherapeutic group:

combined contraceptive (estrogen + gestagen)

ATX code: G02BB01

Pharmacological properties

Pharmacodynamics

Mechanism of action
The drug NuvaRing ® is a hormonal combined contraceptive 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 incidence 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 the study 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 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 one year in 1000 women using the drug NuvaRing ® and COCs containing levonorgestrel / ethinyl estradiol (0.150/0.030 mg) showed a significant reduction in the frequency of breakthrough bleeding or spotting when using the drug NuvaRing ® compared with COOK. 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 a non-hormonal intrauterine device (n=31) did not reveal any effect on bone mineral density in women.

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

Pharmacokinetics

Etonogestrel

Suction
Etonogestrel, released from the NuvaRing ® vaginal ring, is rapidly absorbed through the vaginal mucosa. The maximum concentration of etonogestrel in blood plasma, approximately 1700 pg/ml, is achieved approximately 1 week after insertion of the ring. Plasma concentrations vary within 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 of use. Absolute bioavailability is about 100%, which exceeds the bioavailability of etonogestrel when taken orally. 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 plasma albumin and sex hormone binding globulin (SHBG). The apparent volume of distribution of etonogestrel is 2.3 L/kg.

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

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

Ethinyl estradiol

Suction
Ethinyl estradiol, released from the NuvaRing ® vaginal ring, is rapidly absorbed through the vaginal mucosa. The maximum plasma concentration of about 35 pg/ml is achieved 3 days after administration of the ring and decreases to 19 pg/ml after 1 week, to 18 pg/ml after 2 weeks and 18 pg/ml after 3 weeks of use. 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 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 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 in healthy women. Systemic exposure to ethinyl estradiol over the course of a month (AUC0-?) for the drug NuvaRing ® was statistically significantly lower than for the patch and COCs, and amounted to 10.9, 37.4 and 22.5 ng h/ml, respectively.

Distribution
Ethinyl estradiol binds nonspecifically to plasma albumin. The apparent volume of distribution is approximately 15 l/kg.

Metabolism
Ethinyl estradiol is metabolized by aromatic hydroxylation. During its biotransformation, a large number of hydroxylated and methylated metabolites are formed. They circulate freely or as sulfate and glucuronide conjugates. The apparent clearance is approximately 35 l/h.

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

Special patient groups

Children
The pharmacokinetics of 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.

Indications for use

Contraception.

Contraindications

The drug NuvaRing ® is contraindicated in the presence of any of the conditions listed below. If any of these conditions occur during the use of the drug NuvaRing ®, you should immediately stop using the drug.

• 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.
• Severe 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), hypertension, lesions of the valvular apparatus of the heart, atrial fibrillation, extended surgery, prolonged immobilization, extensive trauma, obesity (body weight >30 kg/m²), smoking in women over 35 years of age (see section “Special instructions”).
• Pancreatitis with severe hypertriglyceridemia, current or history.
• Severe liver diseases.
• Liver tumors (malignant or benign), including history.
• Known or suspected hormone-dependent malignant tumors (for example, genital or breast).
• Bleeding from the vagina of unknown etiology.
• Pregnancy, including suspected pregnancy.
• Hypersensitivity to any of the active or excipients of the drug NuvaRing ®.

Carefully

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 ® (see section “Special Instructions”). In case of exacerbation of diseases, deterioration of the condition, or the first occurrence of any of the conditions listed below, a woman should consult a doctor to decide on the possibility of further use of the drug NuvaRing ®.

The drug NuvaRing ® should be used with caution in the following cases:

• 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 family), smoking, obesity, dyslipoproteinemia, arterial hypertension, migraine without focal neurological symptoms, heart valve disease , 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 diseases;
• 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;
• (hereditary) angioedema;
• chronic inflammatory bowel diseases (Crohn's disease and ulcerative colitis);
• sickle cell anemia;
• chloasma;
• Conditions that may make it difficult to use a vaginal ring: cervical prolapse, bladder hernia, rectal hernia, severe chronic constipation.

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, as this will help to correctly calculate the date of conception and birth.

Pregnancy

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

Breastfeeding period

The use of NuvaRing ® during breastfeeding is not indicated. The composition of the drug can affect lactation, reduce the amount and change the composition of breast milk. Small amounts of contraceptive sex hormones and/or their metabolites may be excreted in milk, but there is no evidence of their negative impact on the health of children.

Directions for use and doses

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

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

The doctor should inform the woman how to insert and remove the NuvaRing ® vaginal ring. To insert the ring, the woman should choose a comfortable position, for example, standing, raising one leg, squatting or lying down. The NuvaRing ® vaginal ring should be squeezed and inserted into the vagina until the ring is in a comfortable position. The exact position of the ring in the vagina is not decisive for the contraceptive effect (Fig. 1-4).

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

The NuvaRing ® vaginal ring should be removed after 3 weeks on the same day of the week when the ring was inserted into the vagina. After a week's break, a new ring is inserted (for example, if the NuvaRing ® vaginal ring was installed on Wednesday at approximately 10:00 pm, it should be removed on Wednesday 3 weeks later at approximately 10:00 pm. A new ring is inserted on the next Wednesday). To remove the ring, you need to pick it up with your index finger or squeeze it with your index and middle fingers and pull it out of the vagina (Fig. 5). The used ring should be placed in a bag (keep out of the reach of children and pets) and discarded. Bleeding associated with the cessation of the action of the drug NuvaRing ® usually begins 2-3 days after removal of the NovaRing ® vaginal ring and may not completely stop until a new ring is installed.

How to start using the drug NuvaRing ®?

• No hormonal contraceptives were used in the previous cycle
  The drug NuvaRing ® should be administered on the first day of the cycle (i.e., on 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 combined hormonal contraceptives
  A woman should insert the NuvaRing ® vaginal ring on the last day of the usual interval between cycles when taking combined hormonal contraceptives (pills or patch).
  If a woman has taken a combined hormonal contraceptive correctly and regularly and is sure that she is not pregnant, she can switch to using a vaginal ring on any day of the cycle.
  In no case should you exceed the recommended hormone-free interval of the previous method.
• Switching from progestogen-only medications (mini-pills, progestin-only oral contraceptives, implants, injectables, or hormone-containing intrauterine systems (IUDs))
  A woman taking mini-pills or progestin-only oral contraceptives 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 a barrier method of contraception for the first 7 days after insertion of the ring.
• After an abortion in the first trimester
  A woman can insert the ring immediately after an abortion. In this case, she does not need additional contraceptives. If the use of the drug NuvaRing ® immediately after an abortion is undesirable, it is necessary to follow the recommendations given in the subsection “In the previous cycle, hormonal contraceptives were not used.” In the interval, the woman is recommended an alternative method of contraception.
• After childbirth or after an abortion in the second trimester
  A woman is advised to have the ring inserted no earlier than 4 weeks after giving birth (if she is not breastfeeding) or having a second trimester abortion. If the ring is installed at a later date, it is recommended to use an additional barrier method for the first 7 days. However, if sexual intercourse has already taken place, 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 a woman does not comply with the recommended regimen. To avoid a decrease in the contraceptive effect, the following recommendations must be followed.

• What to do if the break in using the ring is prolonged?
  If you had sexual intercourse during a break in using the ring, pregnancy should be ruled out. The longer the break, the higher the likelihood of pregnancy. If pregnancy is ruled out, the woman should insert a new ring into the vagina as quickly as possible. Over the next 7 days, an additional barrier method of contraception, such as a condom, should be used.
• What to do if the ring has been temporarily removed from the vagina?
  The ring must remain in the vagina continuously for 3 weeks. If the ring is accidentally removed, it should be washed with cold or slightly warm (not hot) water and immediately inserted into the vagina.
  • If the ring remains outside the vagina for less than 3 hours, its contraceptive effect is not reduced. The woman should insert the ring into the vagina as quickly as possible (no later than after 3 hours).
  • If the ring was outside the vagina for more than 3 hours during the first or second week of use, the contraceptive effect may be reduced. A woman should insert the ring into her vagina as quickly 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 outside the vagina for more than 3 hours in 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.
       Note: 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. However, spotting or bleeding in the middle of the cycle is possible.
    2. Wait for bleeding associated with the cessation of the drug, and insert a new ring no later than 7 days after removing the previous ring.
       Note: This option should be chosen only if the ring application regimen has not been violated during the first two weeks.
• What to do in case of prolonged 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. A woman can take a week's break from using the ring and then insert a new ring.
  If the NuvaRing ® vaginal ring remains in the vagina for more than 4 weeks, the contraceptive effect may worsen, so pregnancy must be excluded before inserting a new ring.
  If a woman does not adhere to the recommended regimen and bleeding does not occur after a week's break in using the ring, then pregnancy should be ruled out before introducing a new ring.
• How to shift or delay the onset of menstrual bleeding?
  To delay menstrual-like withdrawal bleeding, a woman can insert a new ring without a week's break. The next ring must be used for 3 weeks. This may cause spotting or bleeding. Then, after the usual one-week break, the woman returns to regular use of the drug NuvaRing ® .
  To postpone the onset of bleeding to another day of the week, a woman may be advised to take a shorter break from 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 the ring is removed and bleeding or spotting occurring during the use of the next ring.

Children

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

Side effect

When using the drug, side effects may occur, occurring with varying frequencies: often (?1/100), infrequently (<1/100, ?1/1 000), редко (<1/1 000, ?1/10 000).

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

Interaction with other drugs and other types of interactions

Interaction with other drugs

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

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

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

When treating with any of the listed drugs, you should temporarily use a barrier method of contraception (condom) in combination with the use of the drug NuvaRing ® or choose another method of contraception. During concomitant use of drugs that induce microsomal 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.

Antibiotics: 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 a day) or doxycycline (200 mg per day, and then 100 mg per day) for 10 days while using the drug NuvaRing ® had little effect on the pharmacokinetics of etonogestrel and ethinyl estradiol. When using antibiotics (excluding amoxicillin and doxycycline), you should use a barrier method of contraception (condom) during treatment and for 7 days after 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 the simultaneous use of antifungal agents and spermicides on the contraceptive effectiveness and safety of the drug NuvaRing ®. When combined with suppositories and antifungal drugs, the risk of ring rupture slightly increases.

Hormonal contraceptives may interfere with the metabolism of other drugs. Accordingly, their concentrations in plasma and tissues may increase (for example, cyclosporine) or decrease (for example, lamotrigine).

To exclude possible interactions, you should read the instructions for use of other drugs.

Laboratory 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; on the plasma concentration of transport proteins, for example, corticosteroid binding globulin (CBG) and SHBG; for lipid/lipoprotein fractions; on indicators of carbohydrate metabolism; as well as on indicators of blood clotting and fibrinolysis. Indicators, as a rule, vary within normal values.

Combined use with tampons

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 the tampon is removed (see the subsection “What to do if the ring has been temporarily removed from the vagina” in the “Dosage and Administration” section).

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 first occurrence of any of the conditions listed below, 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 COC use. 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. The increase in risk occurs to a lesser extent than in pregnancy, where the risk is 5-20 per 10,000 YL (pregnancy data are based on the actual duration of pregnancy in standard studies; based on the assumption that pregnancy lasts 9 months, the risk is 7 to 27 cases per 10,000 YL). 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 the drug NuvaRing ® is similar to that in women using COCs (for adjusted risk ratio, see the table below). A large prospective observational study, TASC (Transatlantic Active Study of the Cardiovascular Safety of NuvaRing ®), assessed the risk of VTE in women who started using NuvaRing ® or COCs, switched to NuvaRing ® or COCs from other contraceptives, or resumed using NuvaRing ® or COCs. use of the drug NuvaRing ® or COCs in a population of typical users. The women were followed for 24-48 months. The results showed a similar level of risk of developing VTE in women using the drug NuvaRing ® (incidence of 8.3 cases per 10,000 YL) and in women using COCs (incidence of 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 (US Food and Drug Administration) showed that the incidence of VTE in women who started using the drug NuvaRing ® was 11.4 cases per 10,000 YL, while in of women who started using COCs containing levonorgestrel, the incidence of VTE is 9.2 cases per 10,000 women.

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

Epidemiological study, population	Comparator(s)	Risk ratio (RR) (95% CI)
TASC (Dinger, 2012) Women who started using the drug (including again after a break) and switched from other means of contraception.	All available COCs during the study 1.	OR 2: 0.8 (0.5-1.5)
	Available COCs other than 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.	COCs available during the 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 Including low-dose COCs containing the following progestins: 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 Including low-dose COCs containing the following progestins: 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 on 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; "acute" 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 young 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;
• possibly thrombophlebitis of the superficial veins with varicose veins.

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

Risk factors for 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 (body mass index more than 30 kg/m²);
• increased blood pressure;
• 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 CHCs should be advised to consult a doctor if possible symptoms of thrombosis occur. If thrombosis is suspected or confirmed, CHC use 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 further increases this risk, but it is unclear how much of this is due to other factors, such as increased frequency of cervical smears and differences in sexual behavior, including the use of barrier contraceptives. It remains unclear how this effect is related to the use of the drug NuvaRing ®.

A meta-analysis of 54 epidemiological studies found a small increase (1.24) in the relative risk of breast cancer in women taking combined hormonal oral contraceptives. 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. The doctor should consider the possibility of a liver tumor in the differential diagnosis of diseases in a woman taking NuvaRing ® if symptoms include acute pain in the upper abdomen, liver enlargement, or signs of intra-abdominal bleeding.

Other states

• Women with hypertriglyceridemia or 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, when using the drug NuvaRing ®, there is a constant increase in blood pressure, you should contact your doctor to decide whether it is necessary to remove the vaginal ring and prescribe antihypertensive therapy. With adequate control of blood pressure using antihypertensive drugs, it is possible to resume use of the drug NuvaRing ®.
• During pregnancy and during the use of combined oral contraceptives, 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, (hereditary) angioedema.
• Acute or chronic liver diseases 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 hormones, 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 for use and follow all recommendations. The woman should be informed that NuvaRing ® does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Reduced efficiency

The effectiveness of the drug NuvaRing ® may decrease if the regimen is not followed or concomitant therapy is carried out.

Reduced cycle control

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 studies, including 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.

Ring damage

In rare cases, when using the drug NuvaRing ®, ring rupture was observed. The core of the drug NuvaRing ® 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 (see the recommendations in the subsection “What to do if the ring has been temporarily removed from the vagina” in the “Dosage and Administration” section). If the ring ruptures, a new ring must be inserted.

Ring falling out

Sometimes the NuvaRing ® vaginal ring may fall out of the vagina, for example, if it is inserted incorrectly, when a tampon is removed, during sexual intercourse, or due to severe or chronic constipation. In this regard, it is advisable for a woman to regularly check the presence of the NuvaRing ® vaginal ring in the vagina. If the NuvaRing ® vaginal ring falls out of the vagina, you must follow the recommendations of the subsection “What to do if the ring has been temporarily removed from the vagina” in the “Method of administration and dosage” section.

Impact on the ability to drive vehicles and operate machinery

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

Release form

Vaginal rings 0.015 mg + 0.120 mg/day. 1 ring is packed in a waterproof aluminum foil bag, coated on the inside with a layer of low-density polyethylene and on the outside with a layer of polyethylene terephthalate (PET). 1 or 3 packets per cardboard box with instructions for use.

Storage conditions

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

Best before date

3 years.
Do not use after the expiration date stated on the package.

Vacation conditions

On prescription.

Legal entity in whose name the registration certificate was issued

N.V. Organon, Netherlands

Manufacturer

Produced:
N.V. Organon, Netherlands

Release quality control:
N.V. Organon, Netherlands
N.V. Organon, Kloosterstraat 6, 5349 AB, Oss, the Netherlands
or
Organon (Ireland) Ltd., Ireland
Organon (Ireland) Ltd., P.O. Box 2857, Drynam Road, Swords, Co. Dublin, Ireland

Consumer complaints should be sent to:
MSD Pharmaceuticals LLC
st. Pavlovskaya, 7, building 1
Moscow, Russia, 115093