Norelgestromin, or norelgestromine, sold under the brand names Evra and Ortho Evra among others, is a

progestin A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a ''synthetic'' progestogen. Pro ...

medication which is used as a method of

birth control Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent unwanted pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth contr ...

for women.Drugs.com
Norelgestromin/Ethinyl Estradiol Patch
/ref> The medication is available in combination with an

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...

and is not available alone. It is used as a patch that is applied to the skin. Side effects of the combination of an estrogen and norelgestromin include menstrual irregularities,

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...

abdominal pain Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a m ...

, breast tenderness, mood changes, and others. Norelgestromin is a progestin, or a

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic ...

progestogen Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the bod ...

, and hence is an

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ag ...

of the progesterone receptor, the biological target of progestogens like

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the majo ...

. It has very weak androgenic activity and no other important hormonal activity. Norelgestromin was introduced for medical use in 2002. It is sometimes referred to as a "third-generation" progestin. Norelgestromin is marketed widely throughout the world. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ...

Medical uses

Norelgestromin is used in combination with ethinyl estradiol in

contraceptive patch A contraceptive patch, also known as "the patch", is a transdermal patch applied to the skin that releases synthetic oestrogen and progestogen hormones to prevent pregnancy. They have been shown to be as effective as the combined oral contr ...

es. These patches mediate their contraceptive effects by suppressing gonadotropin levels as well as by causing changes in the

cervical mucus The cervix or cervix uteri (Latin, 'neck of the uterus') is the lower part of the uterus (womb) in the human female reproductive system. The cervix is usually 2 to 3 cm long (~1 inch) and roughly cylindrical in shape, which changes during ...

and

endometrium The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional layer ...

that diminish the likelihood of

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

Available forms

Norelgestromin is available only as a transdermal contraceptive patch in combination with ethinyl estradiol. The Ortho Evra patch is a 20 cm, once-weekly adhesive that contains 6.0 mg norelgestromin and 0.75 mg ethinyl estradiol and delivers 150 µg/day norelgestromin and 35 µg/day ethinyl estradiol.

Contraindications

Side effects

Norelgestromin has mostly been studied in combination with an estrogen, so the side effects of norelgestromin specifically or on its own have not been well-defined. Side effects associated with the combination of ethinylestradiol and norelgestromin as a transdermal patch in premenopausal women, with greater than or equal to 2.5% incidence over 6 to 13

menstrual cycle The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs ...

s, include breast symptoms (including discomfort,

engorgement Breast engorgement occurs in the mammary glands due to expansion and pressure exerted by the synthesis and storage of breast milk. It is also a main factor in altering the ability of the infant to latch-on. Engorgement changes the shape and cu ...

, and/or

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

; 22.4%),

s (21.0%),

application site reaction Application site reactions are reactions to medical treatments which occur at the site of application. An example is skin reactions to transdermal patches. See also * Injection site reaction * Skin lesion * List of cutaneous conditions Many ...

s (17.1%),

(16.6%),

(8.1%),

dysmenorrhea Dysmenorrhea, also known as period pain, painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in th ...

(7.8%), vaginal bleeding and menstrual disorders (6.4%), mood, affect, and

anxiety disorder Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause phy ...

s (6.3%),

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenter ...

(5.1%),

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

(4.2%),

vaginal yeast infection Vaginal yeast infection, also known as candidal vulvovaginitis and vaginal thrush, is excessive growth of yeast in the vagina that results in irritation. The most common symptom is vaginal itching, which may be severe. Other symptoms include bu ...

s (3.9%),

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

(3.3%),

acne Acne, also known as ''acne vulgaris'', is a long-term skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and ...

(2.9%),

migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

(2.7%), weight gain (2.7%),

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

(2.6%), and pruritus (2.5%).

Overdose

Interactions

Pharmacology

Pharmacodynamics

Norelgestromin is a

. It is one of the

active metabolite An active metabolite is an active form of a drug after it has been processed by the body. Metabolites of drugs An active metabolite results when a drug is metabolized by the body into a modified form which continues to produce effects in the body ...

s of norgestimate. Unlike many related progestins, norelgestromin reportedly has negligible androgenic activity. However, it produces

levonorgestrel Levonorgestrel is a hormonal medication which is used in a number of birth control methods. It is combined with an estrogen to make combination birth control pills. As an emergency birth control, sold under the brand name Plan B One-Step amon ...

as an active metabolite to some extent, which does have some androgenic activity. Nonetheless, transdermally-administered norelgestromin does not counteract the increase in sex hormone-binding globulin levels produced by ethinyl estradiol.

Pharmacokinetics

Upon application of a transdermal patch containing norelgestromin and ethinyl estradiol, plateau levels of both are reached by approximately 48 hours, and steady-state levels are reached within 2 weeks of application. Absorption following application to the buttock, upper outer arm, abdomen, and upper torso was assessed and, while absorption from the abdomen was slightly lower, it was considered to be therapeutically equivalent for the various areas. Mean levels of norelgestromin at steady-state ranged from 0.305 ng/mL to 1.53 ng/mL, with an average of about 0.725 ng/mL. The plasma protein binding of norelgestromin is 99%, and it is bound to

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Album ...

but not to sex hormone-binding globulin. The

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run ...

of norelgestromin takes place in the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...

and is via transformation into

(conversion of the C3 oxime into a

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double b ...

) as well as

hydroxylation In chemistry, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemical process that introduces a hydroxyl group () into an organic compound. *(ii) the ''degree of hydroxylation'' refers to the number of OH groups in a ...

and

conjugation Conjugation or conjugate may refer to: Linguistics *Grammatical conjugation, the modification of a verb from its basic form * Emotive conjugation or Russell's conjugation, the use of loaded language Mathematics *Complex conjugation, the change ...

.https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021180s043lbl.pdf However, because norelgestromin is used

parenteral A route of administration in pharmacology and toxicology is the way by which a drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance is applied. ...

ly, first-pass metabolism in the liver and

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

that normally occurs with

oral administration Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are ...

are avoided. The biological half-life of norelgestromin is 17 to 37 hours. The

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

s of norelgestromin, along with those of ethinyl estradiol, are eliminated in the

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellul ...

and

feces Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a rela ...

Chemistry

Norelgestromin, also known as 17α-ethynyl-18-methyl-19-nortestosterone 3-oxime or as 17α-ethynyl-18-methylestr-4-en-17β-ol-3-one 3-oxime, is a

estrane Estrane is a C18 steroid derivative, with a gonane core. ''Estrenes'' are estrane derivatives that contain a double bond, with an example being nandrolone. ''Estratrienes'' (estrins) are estrane derivatives that contain three double bonds, for i ...

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...

and a

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...

. It is a

racemic mixture In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...

of ''E'' and ''Z'' isomers, which have approximately the same activity. Norelgestromin is more specifically a derivative of

norethisterone Norethisterone, also known as norethindrone and sold under many brand names, is a progestin medication used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication is available in b ...

(17α-ethynyl-19-nortestosterone) and is a member of the

gonane Gonane is a chemical compound with formula , whose molecule can be described as three molecules or entities of cyclohexane and one of cyclopentane, fused in a particular way. More specifically, the molecule can be described as that of cycloh ...

(18-methylestrane) subgroup of the

19-nortestosterone Nandrolone, also known as 19-nortestosterone, is an androgen and anabolic steroid (AAS) which is used in the form of esters such as nandrolone decanoate (brand name Deca-Durabolin) and nandrolone phenylpropionate (brand name Durabolin). Nandrolon ...

family of progestins. It is the C3 oxime derivative of

and the C17β deacetyl derivative of norgestimate and is also known as levonorgestrel 3-oxime and as 17β-deacetylnorgestimate. A related progestin is norethisterone acetate oxime (17α-ethynyl-19-nortestosterone 3-oxime 17β-acetate).

History

Norelgestromin was introduced for medical use in 2002.

Society and culture

Generic names

''Norelgestromin'' is the generic name of the drug and its , , and . The combined ethinyl estradiol and norelgestromin contraceptive patch is also known by its developmental code name ''RWJ-10553''.

Brand names

Norelgestromin is marketed under the brand names Evra, Ortho Evra, Xulane, and others, all in combination with ethinylestradiol.

Availability

Norelgestromin is marketed widely throughout the world, including in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...

Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by to ...

, the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and ...

Ireland Ireland ( ; ga, Éire ; Ulster-Scots: ) is an island in the North Atlantic Ocean, in north-western Europe. It is separated from Great Britain to its east by the North Channel, the Irish Sea, and St George's Channel. Ireland is the s ...

, elsewhere throughout

Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...

South Africa South Africa, officially the Republic of South Africa (RSA), is the southernmost country in Africa. It is bounded to the south by of coastline that stretch along the South Atlantic and Indian Oceans; to the north by the neighbouring coun ...

Latin America Latin America or * french: Amérique Latine, link=no * ht, Amerik Latin, link=no * pt, América Latina, link=no, name=a, sometimes referred to as LatAm is a large cultural region in the Americas where Romance languages — languages derived ...

Asia Asia (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an are ...

, and elsewhere in the world. It is not listed as being marketed in

Australia Australia, officially the Commonwealth of Australia, is a sovereign country comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands. With an area of , Australia is the largest country by ...

New Zealand New Zealand ( mi, Aotearoa ) is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and over 700 smaller islands. It is the sixth-largest island coun ...

Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the n ...

South Korea South Korea, officially the Republic of Korea (ROK), is a country in East Asia, constituting the southern part of the Korea, Korean Peninsula and sharing a Korean Demilitarized Zone, land border with North Korea. Its western border is formed ...

China China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's List of countries and dependencies by population, most populous country, with a Population of China, population exceeding 1.4 billion, slig ...

India India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the List of countries and dependencies by area, seventh-largest country by area, the List of countries and dependencies by population, second-most populous ...

, or certain other countries.

Research

A transdermal

gel A gel is a semi-solid that can have properties ranging from soft and weak to hard and tough. Gels are defined as a substantially dilute cross-linked system, which exhibits no flow when in the steady-state, although the liquid phase may still di ...

formulation of norgelstromin and ethinyl estradiol was under development by Antares Pharma for use as a method of birth control with the code name AP-1081 but development was discontinued.

References

External links

Ethinylestradiol/norelgestromin transdermal - AdisInsight
{{Navboxes , title =

Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms ...

, titlestyle = background:#ccccff , list1 = {{Androgen receptor modulators {{Progesterone receptor modulators {{Xenobiotic-sensing receptor modulators Tertiary alcohols Ethynyl compounds Androgens and anabolic steroids Estranes Hormonal contraception Human drug metabolites Progestogens Steroid oximes Ketoximes