NuvaRing
Encyclopedia
NuvaRing is the trade name for a combined hormonal contraceptive vaginal ring
manufactured by Merck
(formerly Schering-Plough
, formerly Organon
) that is available by prescription. It is a flexible plastic (ethylene-vinyl acetate
copolymer) ring that releases a low dose of a progestin
and estrogen
over three weeks.
NuvaRing was first approved in The Netherlands on February 14, 2001, then by all 14 other countries then in the European Union on June 12, 2001, and in the United States by the U.S. Food and Drug Administration (FDA) on October 3, 2001.
NuvaRing was first marketed in the United States in July 2002, followed by several European countries in late 2002.
In March 2007, Organon announced the market launch of NuvaRing in Australia, bringing the total number of countries where NuvaRing is available to 32. NuvaRing is currently used by approximately 1.5 million women worldwide.
. The break week with NuvaRing is comparable to the placebo week for combined oral contraceptive pills ("the Pill"), and the contraceptive effect is maintained during this period. Extended use regimens (seven-week, quarterly, or annual) involving back-to-back use of (2, 4, or 17) rings have been studied in clinical trials, but are not currently approved.
Insertion of the ring is comparable to insertion of other vaginal ring
s. The muscles of the vagina keep NuvaRing securely in place, even during exercise or sex. Women can check the contraceptive ring periodically with their finger. In rare instances, NuvaRing may fall out during sexual intercourse, while straining before or during a bowel movement, or while removing a tampon.
In the case of accidental expulsion, the manufacturer recommends rinsing the ring with cool water before reinserting. If this does not happen the way it is supposed to, the risk of pregnancy is increased. Contraceptive efficacy is reduced if the ring is removed, accidentally expelled, or left outside of the vagina for more than three hours. If left outside of the vagina for more than three hours, the device is to be rinsed and reinserted immediately. If this occurs, the manufacturer recommends that a backup method of contraception be used until the ring has been used continuously for a subsequent seven days.
Nuvaring should not be used while breastfeeding. The hormones may pass to the baby through the milk, and it may decrease milk production.
In two large studies, over a one year period, 15.1% of users discontinued NuvaRing because of adverse events. Device-related adverse events (foreign object sensation, sexual problems, or expulsion) were the most frequently reported adverse events that resulted in discontinuation (by 2.5% of users). Device-related adverse events were reported at least once during the one year study period by 4.4% of NuvaRing users.
The most common adverse events reported by 5 to 14% of the 2501 women who used NuvaRing in five clinical trials were: vaginitis
(14.1%), headache
(9.8%), upper respiratory tract infection
(8.0%), leukorrhea
(5.8%), sinusitis
(5.7%), nausea (5.2%), and weight gain (4.9%).
NuvaRing is weight neutral.
Additional side effect information is provided in the NuvaRing full prescribing information.
NuvaRing has the cardiovascular contraindications associated with combined oral contraceptives, such as stroke and heart attack. These risks have been shown to be much greater if combined with other risk factors such as smoking, recent surgery, a history of cardiovascular disease, or old age.
Beyond the risks associated with combined oral contraceptives, NuvaRing is contraindicated for a risk of blood clots that is specific to NuvaRing's class of contraceptives. NuvaRing contains the hormone etonogestrel
, the active metabolite
of the prodrug
desogestrel
. This makes the NuvaRing a third-generation contraceptive. Epidemiological studies have shown that oral contraceptives that contain desogestrel can increase the risk of blood clots (venous thrombosis
) by 1.5 to 2.4 times the risk of second-generation oral contraceptives. Second-generation oral contraceptives do not contain desogestrel
. Large scale studies of NuvaRing have not been done to determine if NuvaRing's risk is larger or smaller than oral contraceptives that contain desogestrel. Hormones are released continuously from NuvaRing, thus peak and total estrogen and progestin doses are significantly lower than with combined oral contraceptives, but what effect this has on the risk of blood clots has not been established.
To date, over 730 other lawsuits have been filed in state and federal court. The company denies the allegations and trials are scheduled for 2012. The plaintiffs allege multiple problems with the advertising of NuvaRing and the downplaying of its risks and deaths.
NuvaRing should not be used if a woman is pregnant. There is however no known harm to the woman, the course of her pregnancy, or the fetus if NuvaRing is accidentally used during pregnancy.
NuvaRing delivers 120 µg of etonogestrel
(a progestin
) and 15 µg of ethinyl estradiol (an estrogen
) each day of use.
Vaginal ring
Vaginal rings are polymeric drug delivery devices designed to provide controlled release of drugs for intravaginal administration over extended periods of time. The ring is inserted into the vagina and provides contraception protection...
manufactured by Merck
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
(formerly Schering-Plough
Schering-Plough
Schering-Plough Corporation was a United States-based pharmaceutical company. It was founded in 1851 by Ernst Christian Friedrich Schering as Schering AG in Germany. In 1971, the Schering Corporation merged with Plough to form Schering-Plough. On November 4, 2009 Merck & Co...
, formerly Organon
Organon International
Organon is a human pharmaceutical company headquartered in Oss, Netherlands. In November 2007 the company became a part of Schering-Plough Corporation, acquired Organon, active pharmaceutical ingredient producer Diosynth , and its veterinary pharmaceutical sister company Intervet from Akzo Nobel. ...
) that is available by prescription. It is a flexible plastic (ethylene-vinyl acetate
Ethylene-vinyl acetate
Ethylene vinyl acetate is the copolymer of ethylene and vinyl acetate. The weight percent vinyl acetate usually varies from 10 to 40%, with the remainder being ethylene....
copolymer) ring that releases a low dose of a progestin
Progestin
A progestin is a synthetic progestogen that has progestinic effects similar to progesterone. The two most common uses of progestins are for hormonal contraception , and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy...
and estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
over three weeks.
NuvaRing was first approved in The Netherlands on February 14, 2001, then by all 14 other countries then in the European Union on June 12, 2001, and in the United States by the U.S. Food and Drug Administration (FDA) on October 3, 2001.
NuvaRing was first marketed in the United States in July 2002, followed by several European countries in late 2002.
In March 2007, Organon announced the market launch of NuvaRing in Australia, bringing the total number of countries where NuvaRing is available to 32. NuvaRing is currently used by approximately 1.5 million women worldwide.
Use
The currently approved NuvaRing regimen specifies insertion of the ring into the vagina for a three-week period, then removal of the ring for one week, during which the user will experience a menstrual periodMenstruation
Menstruation is the shedding of the uterine lining . It occurs on a regular basis in sexually reproductive-age females of certain mammal species. This article focuses on human menstruation.-Overview:...
. The break week with NuvaRing is comparable to the placebo week for combined oral contraceptive pills ("the Pill"), and the contraceptive effect is maintained during this period. Extended use regimens (seven-week, quarterly, or annual) involving back-to-back use of (2, 4, or 17) rings have been studied in clinical trials, but are not currently approved.
Insertion of the ring is comparable to insertion of other vaginal ring
Vaginal ring
Vaginal rings are polymeric drug delivery devices designed to provide controlled release of drugs for intravaginal administration over extended periods of time. The ring is inserted into the vagina and provides contraception protection...
s. The muscles of the vagina keep NuvaRing securely in place, even during exercise or sex. Women can check the contraceptive ring periodically with their finger. In rare instances, NuvaRing may fall out during sexual intercourse, while straining before or during a bowel movement, or while removing a tampon.
In the case of accidental expulsion, the manufacturer recommends rinsing the ring with cool water before reinserting. If this does not happen the way it is supposed to, the risk of pregnancy is increased. Contraceptive efficacy is reduced if the ring is removed, accidentally expelled, or left outside of the vagina for more than three hours. If left outside of the vagina for more than three hours, the device is to be rinsed and reinserted immediately. If this occurs, the manufacturer recommends that a backup method of contraception be used until the ring has been used continuously for a subsequent seven days.
Nuvaring should not be used while breastfeeding. The hormones may pass to the baby through the milk, and it may decrease milk production.
Benefits
The benefits of the ring include:- once-a-month self-administered use offering convenience, ease of use and privacy (most users and most partners do not feel the ring, and of those who do, most do not object to it)
- lower estrogen exposure than with combined oral contraceptive pills or the contraceptive patchContraceptive patchA contraceptive patch is a transdermal patch applied to the skin that releases synthetic estrogen and progestin hormones to prevent pregnancy. They have been shown to be as effective as the combined oral contraceptive pill with perfect use, and the patch may be more effective in typical use.The...
Ortho Evra. - a low incidence of estrogenic side effects such as nauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and breast tendernessMastalgiaMastodynia, mastalgia or mammalgia are names for a medical symptom that means breast pain .Pain can range from minor discomfort to severely incapacitating pain... - a low incidence of irregular bleedingBreakthrough bleedingBreakthrough bleeding is an abnormal uterine bleeding that occurs between menstrual periods, especially due to irregular sloughing of the endometrium in women on combined oral contraceptives...
despite its lower estrogen dose - may lead to a shorter and lighter period
- may help clear acne
- can be attributed to a reduction of menstrual cramps and PMS
- provides protection against iron deficiency anemia, pelvic inflammatory disease, ovarian cysts, and endometrial and ovarian cancers
Side effects
The most common adverse events reported by 5 to 14% of the 2501 women who used NuvaRing in five clinical trials were: vaginitis
Vaginitis
Vaginitis is an inflammation of the vagina. It can result in discharge, itching and pain, and is often associated with an irritation or infection of the vulva. It is usually due to infection. The three main kinds of vaginitis are bacterial vaginosis , vaginal candidiasis, and trichomoniasis. A...
(14.1%), headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
(9.8%), upper respiratory tract infection
Upper respiratory tract infection
Upper respiratory tract infections are the illnesses caused by an acute infection which involves the upper respiratory tract: nose, sinuses, pharynx or larynx...
(8.0%), leukorrhea
Leukorrhea
Leukorrhea or leucorrhoea is a medical term that denotes a thick, whitish or yellowish vaginal discharge.There are many causes of leukorrhea, the usual one being estrogen imbalance...
(5.8%), sinusitis
Sinusitis
Sinusitis is inflammation of the paranasal sinuses, which may be due to infection, allergy, or autoimmune issues. Most cases are due to a viral infection and resolve over the course of 10 days...
(5.7%), nausea (5.2%), and weight gain (4.9%).
NuvaRing is weight neutral.
Additional side effect information is provided in the NuvaRing full prescribing information.
NuvaRing has the cardiovascular contraindications associated with combined oral contraceptives, such as stroke and heart attack. These risks have been shown to be much greater if combined with other risk factors such as smoking, recent surgery, a history of cardiovascular disease, or old age.
Beyond the risks associated with combined oral contraceptives, NuvaRing is contraindicated for a risk of blood clots that is specific to NuvaRing's class of contraceptives. NuvaRing contains the hormone etonogestrel
Etonogestrel
Etonogestrel is a progestin used in hormonal contraceptives, most notably the subdermal implant Implanon and the contraceptive vaginal ring NuvaRing....
, the active metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
of the prodrug
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
desogestrel
Desogestrel
Desogestrel is a molecule used in hormonal contraceptives.-Benefits:Third-generation oral contraceptives are suitable for use in patients with diabetes or lipid disorders because they have minimal impact on blood glucose levels and the lipid profile...
. This makes the NuvaRing a third-generation contraceptive. Epidemiological studies have shown that oral contraceptives that contain desogestrel can increase the risk of blood clots (venous thrombosis
Venous thrombosis
A venous thrombosis is a blood clot that forms within a vein. A venous thrombosis is a blood clot that forms within a vein. A venous thrombosis is a blood clot that forms within a vein. (Thrombosis is a medical term for blood clotting (Haemostasis) occurring in the wrong place, i.e...
) by 1.5 to 2.4 times the risk of second-generation oral contraceptives. Second-generation oral contraceptives do not contain desogestrel
Desogestrel
Desogestrel is a molecule used in hormonal contraceptives.-Benefits:Third-generation oral contraceptives are suitable for use in patients with diabetes or lipid disorders because they have minimal impact on blood glucose levels and the lipid profile...
. Large scale studies of NuvaRing have not been done to determine if NuvaRing's risk is larger or smaller than oral contraceptives that contain desogestrel. Hormones are released continuously from NuvaRing, thus peak and total estrogen and progestin doses are significantly lower than with combined oral contraceptives, but what effect this has on the risk of blood clots has not been established.
Lawsuit
In March 2008, a lawsuit was filed against the manufacturers, distributors, and marketers of NuvaRing. The plaintiff alleges these companies concealed the health risks associated with using the device, which is claimed to have caused the death of the plaintiff's wife.To date, over 730 other lawsuits have been filed in state and federal court. The company denies the allegations and trials are scheduled for 2012. The plaintiffs allege multiple problems with the advertising of NuvaRing and the downplaying of its risks and deaths.
Mechanism of action
Like all combined hormonal contraceptives, NuvaRing works primarily by preventing ovulation. A secondary mechanism of action is inhibition of sperm penetration by changes in the cervical mucus. Hormonal contraceptives also have effects on the endometrium that theoretically could affect implantation, however no scientific evidence indicates that prevention of implantation actually results from their use.NuvaRing should not be used if a woman is pregnant. There is however no known harm to the woman, the course of her pregnancy, or the fetus if NuvaRing is accidentally used during pregnancy.
NuvaRing delivers 120 µg of etonogestrel
Etonogestrel
Etonogestrel is a progestin used in hormonal contraceptives, most notably the subdermal implant Implanon and the contraceptive vaginal ring NuvaRing....
(a progestin
Progestin
A progestin is a synthetic progestogen that has progestinic effects similar to progesterone. The two most common uses of progestins are for hormonal contraception , and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy...
) and 15 µg of ethinyl estradiol (an estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
) each day of use.