Levonorgestrel is a hormonal drug used in a number of birth control methods. In pill form, sold under the brand name Plan B , among others, is useful in 120 hours as an emergency birth control. It becomes less effective longer after sex and only works before pregnancy has occurred. It is also combined with estrogen to make combined oral contraceptive pills. In uterine contraceptives (IUDs), sold as Mirena , among others, is effective for the prevention of long-term pregnancy. The levonorgestrel implant form is also available in some countries.
Common side effects include nausea, breast tenderness, headache, and an irregular increase, decrease, or menstruation. When used as a form of emergency contraception, if pregnancy occurs, there is no evidence of its use to harm the baby. Safe to use during breastfeeding. Birth control containing levonorgestrel will not alter the risk of sexually transmitted infections. It is a progestin and has a similar effect to the hormone progesterone. It works primarily by preventing ovulation and closing the cervix to prevent sperm passage.
Levonorgestrel was discovered in 1963 and was introduced for medical purposes along with ethinylestradiol in 1970. This is a List of Essential Medicines of the World Health Organization, the most effective and safe medication needed in the health system. It is available as a generic drug. Wholesale costs in developing countries cost between 0.23 and 1.65 USD for the doses required for emergency birth control. In the United States it is on the table for all ages.
Video Levonorgestrel
Medical use
Birth control
At lower doses, levonorgestrel is used in monophasic and triphas formulations of combined oral contraceptive pills, with available monophasic doses ranging from 100-250 Ã,Âμg, and a triphasic dose of 50Ã,Âμg/75Ã,Âμg/125Ã,Âμg. This is combined with estrogen ethinylestradiol in this formulation.
At a very low daily dose of 30 Âμg, levonorgestrel is used in some progestogen-only POP formulations alone.
Levonorgestrel is an active ingredient in a number of intrauterine devices including Mirena and Skyla. It is also an active ingredient in KB implants, Norplant and Jadelle.
Emergency birth control
Levonorgestrel is used in emergency contraceptive pills (ECPs), both in Yuzpe combined regimens that include estrogen, and as a levonorgestrel-only method. The levonorgestrel-only method used levonorgestrel 1.5Ã, mg (as a single dose or two doses of 0.75 mg 12 h) taken within 3 days of unprotected sex, with one study showing that starting at 120 h (5 days) after intercourse can be effective.
The main mechanism of levonorgestrel action as an emergency progestogen only contraceptive pills, according to the International Federation of Gynecology and Obstetrics (FIGO), to prevent conception by inhibiting ovulation and thickening of cervical mucus. FIGO has stated that: "evidence review shows that LNG [levonorgestreol] ECPs can not prevent implantation of fertilized eggs The language of implantation should not be included in ECP LNG labeling products." In November 2013, the European Medicines Agency (EMA) approved a change to the label saying it could not prevent implantation of fertilized eggs.
Other studies still find the evidence unclear. While it is unlikely that emergency contraception affects implantation it is impossible to completely exclude the possibility of post-fertilization effects.
In November 2013, the EMA also approved the label change for HRA Pharma NorLevo said: "In clinical trials, contraceptive efficacy was reduced in women weighing 75 kg [165 lb] or more, and levonorgestrel was ineffective at women who weighed more than 80 kg [176 lb]. "In November 2013 and January 2014, the FDA and EMA said they reviewed whether weight gain and body mass index (BMI) reduced the effectiveness of emergency contraception.
Hormone therapy
Levonorgestrel is used in combination with estrogen in menopausal hormone therapy. It is used under the brand name Klimonorm as a combined oral tablet with estradiol valerate and under the brand name Climara Pro as a combined transdermal patch with estradiol.
Maps Levonorgestrel
Side effects
After intake of 1.5 mg of levonorgestrel in clinical trials, very common side effects (reported by 10% or more) include: itching, dizziness, headache, nausea, abdominal pain, uterine pain, delayed menstruation, heavy menstruation, bleeding uterus, and fatigue; common side effects (reported by 1% to 10%) include painful diarrhea, vomiting, and menstruation; these side effects usually disappear within 48 hours.
Interactions
When taken together with a drug inducing the C4T4 liver enzyme CYT3A4, levonorgestrel can be metabolized more rapidly and may have lower effectiveness.
Pharmacology
Pharmacodynamics
Levonorgestrel is a progestogen; namely, progesterone receptor agonist (PR), the primary biological target of progesterone of the progestogen hormone. It is also a weak agonist of the androgen receptor (AR), the main biological target of the hormone testosterone androgen hormone. Levonorgestrel has no other important hormonal activity, including no estrogenic activity, glucocorticoids, or antimineralocorticoids. Lack of significant mineralocorticoid or antimineralocorticoid activity with levonorgestrel regardless of the relatively high affinity for mineralocorticoid receptors by 75% of aldosterone. Because of its progestogenic activity, levonorgestrel has antigonadotropic effects, and is able to suppress fertility and sex hormone production of gonads in women and men.
Androgenic Activity
Levonorgestrel is a weak androgenic progestin and in women can cause androgenic side effects such as decreased levels of globulin hormone-binding globulin (SHBG), decreased HDL cholesterol, body weight and acne. In combination with powerful estrogens such as ethinylestradiol, however, all contraceptives containing androgenic progestin are negligible androgenic in clinical practice and can in fact be used to treat androgen-dependent conditions such as acne and hirsutism in women. This is because ethinylestradiol causes an increase in SHBG levels and thus lowers free testosterone and therefore bioactivity, acting as a functional antiandrogen. However, contraceptives containing less androgenic progestins increase SHBG levels to a relatively greater extent and may be more effective for these indications. Levonorgestrel is currently the most androgenic progestin that remains in use in contraception, and levonorgestrel-containing contraceptives may be less effective for androgen-dependent conditions relative to other less androgenic progestin.
In men, levonorgestrel causes a marked emphasis on testosterone levels that circulate secondary to its antigonadotropic effects. Because of this, and due to androgenic activity which is only weak and therefore insufficient for the purpose of androgen replacement in men, levonorgestrel has potent functional antiandrogenic effects in men, and is capable of producing associated side effects such as decreased libido and erectile dysfunction among others. In this regard, levonorgestrel has been combined with androgens such as testosterone or dihydrotestosterone when studied as a hormonal contraceptive in men.
Pharmacokinetics
The levonorgestrel bioavailability is about 95% (range 85 to 100%). The binding of levonorgestrel plasma protein is about 98%. It is 50% bound for albumin and 48% for SHBG. Levonorgestrel is metabolized in the liver, via reduction, hydroxylation, and conjugation (especially glucuronidation and sulfation). Oxidation occurs mainly in C2? and C16? position, while the reduction occurs in the A ring. 5? -Dihydrolevonorgestrel produced as levonorgestrel active metabolite by 5? -reductase. The half-life of levonorgestrel elimination is 24 to 32 hours, although values ​​as short as 8 hours and as many as 45 hours have been reported. Approximately 20 to 67% of single oral levonorgestrel dose is removed in the urine and 21 to 34% in the feces.
Chemistry
Levonorgestrel, also known as 17? -ethynyl-18-methyl-19-nortestosterone or as 17? -ethynyl-18-methylestr-4-en-17? -ol-3-one, are synthetic estrus steroids and derivatives of testosterone. Is this C13? or levorotatory stereoisomers and enantiopure forms of norgestrel, C13? or dextrorotatori isomer becomes inactive. Levonorgestrel is more specifically a norethisterone derivative (17? -ethynyl-19-nortestosterone) and is a parent compound of the gonane subgroup (18-methylestrane) of the 19-nestestone nonsestosterone family. Levonorgestrel acetate and levonorgestrel butanoate are C17? esters of levonorgestrel.
History
Norgestrel ( rac -13-ethyl-17? -ethynyl-19-nortestosterone), a racemic mixture containing levonorgestrel and dextronorgestrel, was discovered by Hughes and his colleagues in Wyeth in 1963 through structural modification of norethisterone 17? -ethynyl-19-nortestosterone). It was the first progestogen produced by total chemical synthesis. Norgestrel was introduced for medical use as a contraceptive pill with ethinylestradiol under the brand name Eugynon in Germany in 1966 and under the brand name Ovral in the United States in 1968, and as a progestogen under the brand name Ovrette in the United States in 1973. After its discovery, norgestrel was licensed by Wyeth to Schering AG, which separated the racemic mixture into two optical isomers and identified levonorgestrel (13? -ethyl-17? -ethynyl-19-nortestosterone) as the active component of the mixture. Levonorgestrel was first studied in humans in 1970, and was introduced for medical use in Germany as a contraceptive pill with ethinylestradiol under the brand name Neogynon in August 1970. A more widely used formulation, containing lower doses. etinilestradiol and levonorgestrel, introduced with the brand name Microgynon in 1973. In addition to the combined formulation, levonorgestrel was introduced as a progestogen-only pill under the brand name Microlut by 1972 and Microval in 1974. Many other formulations and brand names birth control pills containing levonorgestrel have also been marketed.
Levonorgestrel, taken alone in a single high dose, was first evaluated as an emergency contraceptive form in 1973. This was the second progestin evaluated for that purpose, after a quingestanol acetate study in 1970. In 1974, the Yuzpe regimen, which consisted of high doses a combination pill containing ethinylestradiol and norgestrel, is described as an emergency contraceptive method by A. Albert Yuzpe and colleagues, and sees broad interest. Levonorgestrel emergency contraception was introduced only with the brand name Postinor in 1978. Ho and Kwan published the first study comparing levonorgestrel alone and the Yuzpe regimen as an emergency contraceptive method in 1993 and found that they had the same effectiveness. but levonorgestrel itself is better tolerated. In relation to this, the Yuzpe regimen has largely been replaced as an emergency contraceptive method with only levonorgrestrel preparations. Levonorgestrel emergency contraceptives alone were approved in the United States under the brand name Plan B in 1999, and have also been widely marketed elsewhere around the world under other brand names such as Levonelle and NorLevo other than Postinor . In 2013, the Food and Drug Administration approved the Plan B One Step for free sale in the United States without a prescription or age restriction.
Levonorgestrel has also been introduced for use as a progestogen only intrauterine device under the brand name Mirena and Skyla , among others, as a progestogen-only prolapse implant just under the brand name Norplant and Jadelle , as a combination of oral tablets with estradiol valerate for menopausal hormone therapy under the brand name Klimonorm , and as a combined transdermal patch with estradiol for menopausal hormone therapy under brand name Climara Pro . Estrogen prodrugs from levonorgestrel such as levonorgestrel acetate and levonorgestrel butanoate have been developed and studied as other forms of birth control such as progestogen only injectable contraceptives and contraceptive vaginal ring, but have not been marketed for medical use.
Society and culture
Common names
Levonorgestrel is the generic name of the drug and INN , USAN , USP , BAN , DCIT , and JAN , while lÃÆ' Â © vonorgestrel is DCF . It is also known as d-norgestrel , d (-) - norgestrel , or D -norgestrel , as well with the developmental code name WY-5104 (Wyeth) and SH-90999 (Schering AG).
Brand name
Levonorgestrel is marketed on its own or in combination with estrogen (especially ethinylestradiol, estradiol, or estradiol valerate under many brand names worldwide, including Alesse, Altavera, Alysena, Amethia, Amethyst, Ashlyna, Aviane, Camrese, Chateal , Climara Pro, Daysee, Emerres, Enpresse, Erlibelle, Escapelle , Falmina, Introvale, Isteranda, Jadelle , Jaydess >, Jolessa, Klimonorm , Kurvelo, Kyleena, Lessina, Levina , Levodonna, Levonelle , Levonest, Levosert, Levora, Liletta Loette , Logynon , LoSeasonique , Lutera, Lybrel, Marlissa, Microgynon , Microlut >, Min -Ovral, Miranova , Mirena , My Way, Myzilra, More Options, Nordette , Norgeston, NorLevo, Norplant , Option 2, Orsythia, Ovima, Ovranette, Plan B , Plan B One Step , Portia, Postinor , Postinor-2 , Ramon na, Rigevidon , Quartet, Quasense, Seasonal Seasoniqu e , Skyla , Sronyx, Tri-Levlen, < i> Trinordiol , Triphasil, Triquilar , Tri-Regol , Trivora, and Upostelle, among many others. This formulation is used as emergency contraception, normal contraception, or menopausal hormone therapy for the treatment of menopausal symptoms.
As an emergency contraceptive, levonorgestrel is often called colloquial as "morning-after pill".
Availability
Levonorgestrel is widely marketed worldwide and available in almost every country.
Accessibility
Emergency contraceptives containing Levonorgestrel are freely available in some countries, such as the United States.
A policy update by 2015 requires all pharmacies, clinics and emergency departments administered by the Indian Health Service to have a One Step Plan in stock, to distribute it to any woman (or representative) who requests it without a prescription, age verification, registration or other requirements , to provide orientation training to all staff regarding the drug, to provide unbiased and medically accurate information on emergency contraception, and to make a person available at all times to distribute the pill in case the main staff object to providing it on a religious or moral basis.
Research
Levonorgestrel has been studied in combination with androgens such as testosterone and dihydrotestosterone as hormonal contraceptives for men.
References
External links
- Levonorgestrel in EncyclopÃÆ'Â|dia Britannica
- Product information of Levonelle producers from Schering
- Monograph for levonorgestrel - Drug Information Uk
- US. National Drug Library: Drug Information Portal - Levonorgestrel
Source of the article : Wikipedia
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