Nafarelin, sold under the brand name Synarel among others, is a

gonadotropin-releasing hormone agonist A gonadotropin-releasing hormone agonist (GnRH agonist) is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treatm ...

(GnRH agonist) medication which is used in the treatment of endometriosis and

early puberty In medicine, precocious puberty is puberty occurring at an unusually early age. In most cases, the process is normal in every aspect except the unusually early age and simply represents a variation of normal development. In a minority of childr ...

.https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019886s033s035lbl.pdf It is also used to treat

uterine fibroid Uterine fibroids, also known as uterine leiomyomas or fibroids, are benign smooth muscle tumors of the uterus. Most women with fibroids have no symptoms while others may have painful or heavy periods. If large enough, they may push on the bl ...

s, to control ovarian stimulation in ''in vitro'' fertilization (IVF), and as part of

transgender hormone therapy Transgender hormone therapy, also called hormone replacement therapy (HRT) or gender-affirming hormone therapy (GAHT), is a form of hormone therapy in which sex hormones and other hormonal medications are administered to transgender or gender non ...

. The medication is used as a

nasal spray Nasal sprays are used to deliver medications locally in the nasal cavities or systemically. They are used locally for conditions such as nasal congestion and allergic rhinitis. In some situations, the nasal delivery route is preferred for syst ...

two to three times per day.

Side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s of nafarelin are related to

sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effect ...

deprivation and include symptoms of low testosterone levels and low estrogen levels such as

hot flash Hot flashes (also known as hot flushes) are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and ...

es,

sexual dysfunction Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction a ...

, vaginal atrophy, and osteoporosis. Nafarelin is a

(GnRH agonist) and works by preventing the

production Production may refer to: Economics and business * Production (economics) * Production, the act of manufacturing goods * Production, in the outline of industrial organization, the act of making products (goods and services) * Production as a stati ...

s by the gonads. It can lower sex hormone levels by 95% in both sexes. Nafarelin is a

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

and an analogue of . Nafarelin was introduced for medical use in 1990. It is available widely throughout the world, including in North America,

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 subcontinent of Eurasia and it is located entirel ...

, and elsewhere throughout the world. The medication is one of only two medically used GnRH analogues that are available as nasal sprays, the other being buserelin.

Medical uses

Nafarelin is approved and used in the treatment of endometriosis and

precocious puberty In medicine, precocious puberty is puberty occurring at an unusually early age. In most cases, the process is normal in every aspect except the unusually early age and simply represents a variation of normal development. In a minority of childr ...

. It is also used in the treatment of

s. The medication is used to control ovarian stimulation in ''in vitro'' fertilization (IVF). Nafarelin is used as a

puberty blocker Puberty blockers, also called puberty inhibitors or hormone blockers, are medicines used to postpone puberty in children. The most commonly used puberty blockers are gonadotropin-releasing hormone (GnRH) agonists, which suppress the production ...

transgender youth Transgender youth are children or adolescents who do not identify with the sex they were assigned at birth. Because transgender youth are usually dependent on their parents for care, shelter, financial support, and other needs, transgender yo ...

and to suppress

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 ...

levels in

transgender women A trans woman or a transgender woman is a woman who was assigned male at birth. Trans women have a female gender identity, may experience gender dysphoria, and may transition; this process commonly includes hormone replacement therapy and ...

. Nafarelin can also be used to treat

hirsutism Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin ''hirsutus'' meaning "hairy". It usually refers to a "male" pattern of hair growth in a female that ...

and

polycystic ovary syndrome Polycystic ovary syndrome, or PCOS, is the most common endocrine disorder in women of reproductive age. The syndrome is named after the characteristic cysts which may form on the ovaries, though it is important to note that this is a sign and no ...

by lowering

gonadotropin Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates. This family includes the mammalian hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the placental/ chorioni ...

and

androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...

levels. It is effective in the treatment of

benign prostatic hyperplasia Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss o ...

Dosages

Nafarelin is used to treat precocious puberty at a dosage of 1,600 to 1,800 μg per day. The 1,600 μg/day dosage is achieved by two sprays (400 μg total) into each nostril in the morning (four sprays, 800 μg total) and two sprays (400 μg total) into each nostril in the evening (four sprays, 800 μg total). If 1,600 μg/day is insufficient for adequate pubertal suppression, the 1,800 μg/day dosage can be used instead. This is achieved by three sprays (600 μg total) into alternating nostrils three times per day (nine sprays per day total). When administering the sprays, the head should be tilted back slightly and 30 seconds should elapse between each spray. A bottle of nafarelin nasal spray (brand name Synarel) lasts for about 7 days at a dosage of 1,600 μg/day. Nafarelin is used to treat endometriosis at lower dosages of 400 to 800 μg per day. This is achieved by one or two sprays (200 or 400 μg total) into alternating nostrils once in the morning and once in the evening (two to four sprays per day total). A bottle of nafarelin nasal spray (brand name Synarel) lasts for about 30 days at a dosage of 400 μg/day.

Available forms

Nafarelin is available in the form of a 0.2%

for use one, two, or three times per day. Each bottle of nafarelin nasal spray (brand name Synarel) contains about 60 sprays delivering approximately 200 μg nafarelin in 100 μL solution per actuation. Nafarelin is not available for use by any other

route Route or routes may refer to: * Route (gridiron football), a path run by a wide receiver * route (command), a program used to configure the routing table * Route, County Antrim, an area in Northern Ireland * ''The Route'', a 2013 Ugandan film * Ro ...

s than intranasal administration.

Side effects

s of nafarelin are related to sex hormone deficiency and include

es, vaginal dryness, headaches,

mood changes A mood swing is an extreme or sudden change of mood. Such changes can play a positive part in promoting problem solving and in producing flexible forward planning, or be disruptive. When mood swings are severe, they may be categorized as par ...

, and

. Nafarelin causes erectile dysfunction in more than half of men with

treated with it. Some people may experience

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 ...

muscle pain Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another like ...

, reduced breast size, and nasal irritation. These side effects are reversible and should resolve after stopping the medication.DailyMed
Synarel – nafarelin acetate spray
/ref> There is a

case report In medicine, a case report is a detailed report of the symptoms, signs, diagnosis, treatment, and follow-up of an individual patient. Case reports may contain a demographic profile of the patient, but usually describe an unusual or novel occurrenc ...

of severe

hyperkalemia Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasi ...

during nafarelin therapy in a woman with uterine fibroids. The mechanism is unknown.

Pharmacology

Pharmacodynamics

Nafarelin is a

GnRH agonist A gonadotropin-releasing hormone agonist (GnRH agonist) is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treat ...

, or an agonist of the GnRH receptor, the

biological target A biological target is anything within a living organism to which some other entity (like an endogenous ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets ...

GnRH Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and releas ...

. It works by continuously activating the GnRH receptor, which results in profound desensitization of the receptor such that it becomes non-functional. As a result, nafarelin suppresses the GnRH-induced secretion of the

luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...

and follicle-stimulating hormone, from the

pituitary gland In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The ...

. This, in turn, results in profound suppression of gonadal

, as well as reversible suppression of

fertility Fertility is the capability to produce offspring through reproduction following the onset of sexual maturity. The fertility rate is the average number of children born by a female during her lifetime and is quantified demographically. Fertili ...

Pharmacokinetics

The

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...

of nafarelin with intranasal administration is 2.8% on average, with a range of 1.2 to 5.6%. The

plasma protein binding Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse or diffuse t ...

of nafarelin is 80%. It is

metabolized 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 cell ...

primarily by

peptidase A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the for ...

s and not by

cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

s. The

elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

of nafarelin is 2.5 to 3.0 hours by intranasal administration, whereas the half-life of nafarelin and its metabolites by subcutaneous injection is 85.5 hours. Nafarelin is eliminated 44 to 55% in

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. Cellular ...

and 18.5 to 44.2% in feces.

Chemistry

Nafarelin is a

GnRH analogue A GnRH modulator, or GnRH receptor modulator, also known as an LHRH modulator or LHRH receptor modulator, is a type of medication which modulates the GnRH receptor, the biological target of the hypothalamic hormone gonadotropin-releasing hormone ...

, or a synthetic analogue of GnRH. It is a

decapeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

and is also known as -D-(2-naphthyl)alanineGnRH. Nafarelin is marketed for medical use in both its

free base Free base (freebase, free-base) is the conjugate base ( deprotonated) form of an amine, as opposed to its conjugate acid ( protonated) form. The amine is often an alkaloid, such as nicotine, cocaine, morphine, and ephedrine, or derivatives ther ...

(nafarelin) and acetate

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quant ...

(nafarelin acetate) forms.

History

Nafarelin was introduced for medical use in 1990.

Society and culture

Generic names

''Nafarelin'' is the generic name of the drug and its and , while ''nafaréline'' is its and ''nafarelin acetate'' is its , , and . It is also known by its former developmental code name ''RS-94991'' or ''RS-94991-298''.

Brand names

The major brand names of nafarelin are Synarel and Synarela. It has also been marketed under a number of other brand names including Synrelin, Synrelina, Nafarelil 0.2%, and Nasanyl 0.2%.

Availability

Nafarelin is available 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 primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...

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 tot ...

, 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 European mainland, continental mainland. It comprises England, Scotlan ...

Ireland Ireland ( ; ga, Éire ; Ulster Scots dialect, Ulster-Scots: ) is an island in the Atlantic Ocean, North Atlantic Ocean, in Northwestern Europe, north-western Europe. It is separated from Great Britain to its east by the North Channel (Grea ...

, other

an countries, Australia,

Israel Israel (; he, יִשְׂרָאֵל, ; ar, إِسْرَائِيل, ), officially the State of Israel ( he, מְדִינַת יִשְׂרָאֵל, label=none, translit=Medīnat Yīsrāʾēl; ), is a country in Western Asia. It is situated ...

Argentina Argentina (), officially the Argentine Republic ( es, link=no, República Argentina), is a country in the southern half of South America. Argentina covers an area of , making it the second-largest country in South America after Brazil, th ...

Brazil Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...

Mexico Mexico (Spanish: México), officially the United Mexican States, is a country in the southern portion of North America. It is bordered to the north by the United States; to the south and west by the Pacific Ocean; to the southeast by Guatema ...

, and Japan.