Levonorgestrel (oral): Difference between revisions

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|drugClass=emergency [[contraceptive]]
|drugClass=emergency [[contraceptive]]
|indicationType=prophylaxis
|indicationType=prophylaxis
|indication=pregnancy following unprotected intercourse or a known or suspected contraceptive failure. To obtain optimal efficacy, the tablet should be taken as soon as possible within 72 hours of intercourse.
|indication=pregnancy following unprotected intercourse or a known or suspected contraceptive failure. To obtain optimal efficacy, the tablet should be taken as soon as possible within 72 hours of intercourse
|adverseReactions=[[menstrual bleeding]], [[nausea]], [[lower abdominal pain]], [[fatigue]], [[headache]], and [[dizziness]].
|adverseReactions=[[menstrual bleeding]], [[nausea]], [[lower abdominal pain]], [[fatigue]], [[headache]], and [[dizziness]]
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b>
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b>
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)
Line 92: Line 92:
|useInRenalImpair=No formal studies were conducted to evaluate the effect of renal disease on the disposition of levonorgestrel tablet.
|useInRenalImpair=No formal studies were conducted to evaluate the effect of renal disease on the disposition of levonorgestrel tablet.
|useInHepaticImpair=No formal studies were conducted to evaluate the effect of hepatic disease on the disposition of levonorgestrel tablet.
|useInHepaticImpair=No formal studies were conducted to evaluate the effect of hepatic disease on the disposition of levonorgestrel tablet.
|overdose=There are no data on overdosage of levonorgestrel tablet, although the common adverse event of nausea and associated vomiting may be anticipated.
|drugBox={{Drugbox2
| Watchedfields = changed
| verifiedrevid = 462091161
| IUPAC_name = (8R,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-17-hydroxy-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydrocyclopenta[''a'']phenanthren-3-one
| image = Levonorgestrel.svg
| width = 220px
| image2 = Levonorgestrel3D.png
| width2 = 220px
<!--Clinical data-->
| tradename = Norplant
| Drugs.com = {{drugs.com|monograph|progestins-etonogestrel-levonorgestrel-norethindrone}}
| MedlinePlus = a610021
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category = X
| legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
| legal_UK = <!-- GSL / P / POM / CD -->
| legal_US = <!-- OTC / Rx-only -->
| legal_status =  Rx-OTC
| routes_of_administration = [[Implant (medicine)|Implant]]; insert (extended-release); oral
<!--Pharmacokinetic data-->
| bioavailability = ~100%
| protein_bound = 55%
| metabolism = [[Liver|Hepatic]] via [[CYP3A4]]{{Citation needed|date=April 2014}}
| elimination_half-life = 36 ± 13 hours
| excretion = [[Kidney|Renal]]: 45%; [[Feces|Fecal]]:32%
<!--Identifiers-->
| CASNo_Ref = {{cascite}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 797-63-7
| ATC_prefix = G03
| ATC_suffix = AC03
| ATC_supplemental =  {{ATC|G03|AD01}}
| PubChem = 13109
| IUPHAR_ligand = 2881
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00367
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 12560
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 5W7SIA7YZW
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00950
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 6443
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1389
<!--Chemical data-->
| C=21 | H=28 | O=2
| molecular_weight = 312.446 g/mol
| smiles = [H][C@]12CCC(=O)C=C1CC[C@]1([H])[C@]2([H])CC[C@@]2(CC)[C@@]1([H])CC[C@@]2(O)C#C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C21H28O2/c1-3-20-11-9-17-16-8-6-15(22)13-14(16)5-7-18(17)19(20)10-12-21(20,23)4-2/h2,13,16-19,23H,3,5-12H2,1H3/t16-,17+,18+,19-,20-,21-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = WWYNJERNGUHSAO-XUDSTZEESA-N
}}
|mechAction=Emergency contraceptive pills are not effective if a woman is already pregnant. Levonorgestrel is believed to act as an emergency contraceptive principally by preventing [[ovulation]] or [[fertilization]] (by altering tubal transport of sperm and/or ova). In addition, it may inhibit [[implantation]] (by altering the [[endometrium]]). It is not effective once the process of [[implantation]] has begun.
|structure=The inactive ingredients present are colloidal silicon dioxide, corn starch, FD&C Yellow #6, lactose monohydrate,  magnesium stearate, povidone.
Levonorgestrel has a molecular weight of 312.45, and the following structural and molecular formulas:
|PK======Absorption=====
Following a single dose administration of levonorgestrel 1.5 mg in 30 women under fasting conditions, maximum plasma concentrations of levonorgestrel of 19.1 ng/mL were reached at 1.7 hours.
|alcohol=Alcohol-Levonorgestrel interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
|alcohol=Alcohol-Levonorgestrel interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
}}
}}

Revision as of 15:21, 12 January 2015

Levonorgestrel (oral)
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]

Disclaimer

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Overview

Levonorgestrel (oral) is an emergency contraceptive that is FDA approved for the prophylaxis of pregnancy following unprotected intercourse or a known or suspected contraceptive failure. To obtain optimal efficacy, the tablet should be taken as soon as possible within 72 hours of intercourse. Common adverse reactions include menstrual bleeding, nausea, lower abdominal pain, fatigue, headache, and dizziness.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Emergency Contraceptive
  • Dosage: Taken orally as soon as possible within 72 hours after unprotected intercourse or a known or suspected contraceptive failure. Efficacy is better if the tablet is taken as soon as possible after unprotected intercourse. Each round tablet containing 1.5 mg of levonorgestrel.
Menorrhagia
  • Dosage: Disposed as an IUD which releases 20 micrograms/day.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Levonorgestrel in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Levonorgestrel in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Levonorgestrel (oral) FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Levonorgestrel in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Levonorgestrel in pediatric patients.

Contraindications

Contraindicated for use in the case of known or suspected pregnancy.

Warnings

Ectopic Pregnancy

Ectopic pregnancies account for approximately 2% of all reported pregnancies. Up to 10% of pregnancies reported in clinical studies of routine use of progestin-only contraceptives are ectopic.

A history of ectopic pregnancy is not a contraindication to use of this emergency contraceptive method. Healthcare providers, however, should consider the possibility of an ectopic pregnancy in women who become pregnant or complain of lower abdominal pain after taking Levonorgestrel. A follow-up physical or pelvic examination is recommended if there is any doubt concerning the general health or pregnancy status of any woman after taking Next Choice One DoseTM.

Existing Pregnancy

Levonorgestrel is not effective in terminating an existing pregnancy.

Effect on Menses

Some women may experience spotting a few days after taking Levonorgestrel. Menstrual bleeding patterns are often irregular among women using progestin-only oral contraceptives and women using levonorgestrel for postcoital and emergency contraception.

If there is a delay in the onset of expected menses beyond 1 week, consider the possibility of pregnancy.

STI/HIV

Levonorgestrel does not protect against HIV infection (AIDS) or other sexually transmitted infections (STIs).

Physical Examination and Follow-up

A physical examination is not required prior to prescribing Next Choice One DoseTM. A follow-up physical or pelvic examination is recommended if there is any doubt concerning the general health or pregnancy status of any woman after taking Levonorgestrel.

Fertility Following Discontinuation

A rapid return of fertility is likely following treatment with Levonorgestrel for emergency contraception; therefore, routine contraception should be continued or initiated as soon as possible following use of Next Choice One DoseTM to ensure ongoing prevention of pregnancy.

Presence of FD&C Yellow

Levonorgestrel contains FD&C Yellow #6 as a color additive.

Adverse Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Levonorgestrel tablet was studied in a randomized, double-blinded multicenter clinical trial. In this study, all women who had received at least one dose of study medication were included in the safety analysis: 1,379 women in the levonorgestrel tablet group (1 dose of 1.5 mg levonorgestrel), and 1,377 women in the levonorgestrel tablets group (2 doses of 0.75 mg levonorgestrel taken 12 hours apart). The mean age of women given levonorgestrel tablet was 27 years. The racial demographic of those enrolled was 54% Chinese, 12% Other Asian or Black, and 34% were Caucasian in each treatment group. 1.6% of women in the levonorgestrel tablet group and 1.4% in levonorgestrel tablets group were lost to follow-up.

The most common adverse events (>10%) in the clinical trial for women receiving levonorgestrel tablet included heavier menstrual bleeding (30.9%), nausea (13.7%), lower abdominal pain (13.3%), fatigue (13.3%), and headache (10.3%). Table 1 lists those adverse events that were reported in > 4% of levonorgestrel tablet users.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of levonorgestrel tablets (2 doses of 0.75 mg levonorgestrel taken 12 hours apart). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal Disorders
General Disorders and Administration Site Conditions
Nervous System Disorders
Reproductive System and Breast Disorders

Drug Interactions

Drugs or herbal products that induce enzymes, including CYP3A4, that metabolize progestins may decrease the plasma concentrations of progestins, and may decrease the effectiveness of progestin-only pills. Some drugs or herbal products that may decrease the effectiveness of progestin-only pills include:

Significant changes (increase or decrease) in the plasma levels of the progestin have been noted in some cases of coadministration with HIV protease inhibitors or with non-nucleoside reverse transcriptase inhibitors.

Consult the labeling of all concurrently used drugs to obtain further information about interactions with progestin-only pills or the potential for enzyme alterations.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): X Many studies have found no harmful effects on fetal development associated with long-term use of contraceptive doses of oral progestins. The few studies of infant growth and development that have been conducted with progestin-only pills have not demonstrated significant adverse effects.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Levonorgestrel (oral) in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Levonorgestrel (oral) during labor and delivery.

Nursing Mothers

In general, no adverse effects of progestin-only pills have been found on breastfeeding performance or on the health, growth, or development of the infant. However, isolated post-marketing cases of decreased milk production have been reported. Small amounts of progestins pass into the breast milk of nursing mothers taking progestin-only pills for long-term contraception, resulting in detectable steroid levels in infant plasma.

Pediatric Use

Safety and efficacy of progestin-only pills for long-term contraception have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents less than 17 years and for users 17 years and older. Use of Next Choice One DoseTM emergency contraception before menarche is not indicated.

Geriatic Use

This product is not intended for use in postmenopausal women.

Gender

There is no FDA guidance on the use of Levonorgestrel (oral) with respect to specific gender populations.

Race

No formal studies have evaluated the effect of race. However, clinical trials demonstrated a higher pregnancy rate in Chinese women with both levonorgestrel tablets (2 doses of 0.75 mg levonorgestrel taken 12 hours apart) and the Yuzpe regimen (another form of emergency contraception). There was a non-statistically significant increased rate of pregnancy among Chinese women in the levonorgestrel tablet trial. The reason for this apparent increase in the pregnancy rate with emergency contraceptives in Chinese women is unknown.

Renal Impairment

No formal studies were conducted to evaluate the effect of renal disease on the disposition of levonorgestrel tablet.

Hepatic Impairment

No formal studies were conducted to evaluate the effect of hepatic disease on the disposition of levonorgestrel tablet.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Levonorgestrel (oral) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Levonorgestrel (oral) in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Levonorgestrel (oral) Administration in the drug label.

Monitoring

There is limited information regarding Levonorgestrel (oral) Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Levonorgestrel (oral) and IV administrations.

Overdosage

There are no data on overdosage of levonorgestrel tablet, although the common adverse event of nausea and associated vomiting may be anticipated.

Pharmacology

Template:Px
Template:Px
Levonorgestrel (oral)
Systematic (IUPAC) name
(8R,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-17-hydroxy-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-one
Identifiers
CAS number 797-63-7
ATC code G03AC03 G03AD01 (WHO)
PubChem 13109
DrugBank DB00367
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 312.446 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability ~100%
Protein binding 55%
Metabolism Hepatic via CYP3A4[citation needed]
Half life 36 ± 13 hours
Excretion Renal: 45%; Fecal:32%
Therapeutic considerations
Pregnancy cat.

X

Legal status

Rx-OTC

Routes Implant; insert (extended-release); oral

Mechanism of Action

Emergency contraceptive pills are not effective if a woman is already pregnant. Levonorgestrel is believed to act as an emergency contraceptive principally by preventing ovulation or fertilization (by altering tubal transport of sperm and/or ova). In addition, it may inhibit implantation (by altering the endometrium). It is not effective once the process of implantation has begun.

Structure

The inactive ingredients present are colloidal silicon dioxide, corn starch, FD&C Yellow #6, lactose monohydrate, magnesium stearate, povidone.

Levonorgestrel has a molecular weight of 312.45, and the following structural and molecular formulas:

Pharmacodynamics

There is limited information regarding Levonorgestrel (oral) Pharmacodynamics in the drug label.

Pharmacokinetics

Absorption

Following a single dose administration of levonorgestrel 1.5 mg in 30 women under fasting conditions, maximum plasma concentrations of levonorgestrel of 19.1 ng/mL were reached at 1.7 hours.

Nonclinical Toxicology

There is limited information regarding Levonorgestrel (oral) Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Levonorgestrel (oral) Clinical Studies in the drug label.

How Supplied

There is limited information regarding Levonorgestrel (oral) How Supplied in the drug label.

Storage

There is limited information regarding Levonorgestrel (oral) Storage in the drug label.

Images

Drug Images

{{#ask: Page Name::Levonorgestrel (oral) |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Levonorgestrel (oral) |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Levonorgestrel (oral) Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Levonorgestrel interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Levonorgestrel (oral) Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Levonorgestrel (oral) Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Levonorgestrel (oral)
Clinical data
Pregnancy
category
  • X
Routes of
administration
Implant; insert (extended-release); oral
ATC code
Pharmacokinetic data
Bioavailability~100%
Protein binding55%
MetabolismHepatic
Elimination half-life36 ± 13 hours
ExcretionRenal: 45%; Fecal:32%
Identifiers
CAS Number
PubChem CID
DrugBank
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC21H28O2
Molar mass312.446 g/mol

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List of terms related to Levonorgestrel (oral)

Levonorgestrel (or l-norgestrel or D-norgestrel) is a synthetic progestogen used as an active ingredient in some hormonal contraceptives.

Chemistry

Chemically, it is a hormonally active levorotatory enantiomer of the racemic mixture norgestrel. It is a gonane progestin derived from 19-nortestosterone.[1]

Its in vitro relative binding affinities at human steroid hormone receptors are: 323% that of progesterone at the progesterone receptor, 58% that of testosterone at the androgen receptor, 17% that of aldosterone at the mineralocorticoid receptor, 7.5% that of cortisol at the glucocorticoid receptor, and <0.02% that of estradiol at the estrogen receptor.[2]

Usage

Oral contraceptives

At low doses, levonorgestrel is used in monophasic and triphasic formulations of combined oral contraceptive pills, with available monophasic doses ranging from 100-250 µg, and triphasic doses of 50 µg/75 µg/125 µg.

At very low daily dose of 30 µg, levonorgestrel is used in some progestogen only pill formulations.

Emergency contraception

Levonorgestrel is used in emergency contraceptive pills (ECPs), both in a combined Yuzpe regimen which includes estrogen, and as a levonorgestrel-only method. The levonorgestrel-only method uses levonorgestrel 1500 μg (as a single dose or as two 750 μg doses 12 hours apart) taken within 3 days of unprotected sex. There are many brand names of levonorgestrel-only ECPs, including: Plan B, Levonelle, NorLevo, Postinor-2, and 72-HOURS.[3]

IUD

Levonorgestrel is the active ingredient in Mirena.

Contraceptive implants

Levonorgestrel is the active ingredient in Norplant and Jadelle.

References

  1. Edgren RA, Stanczyk FZ (1999). "Nomenclature of the gonane progestins". Contraception. 60 (6): 313. PMID 10715364.
  2. Sitruk-Ware R (2006). "New progestagens for contraceptive use". Hum Reprod Update. 12 (2): 169–78. PMID 16291771.
  3. Trussell, James; Cleland, Kelly (2007-04-10). "Emergency Contraceptive Pills Worldwide". Princeton University. Retrieved 2007-05-28.

External links

Template:Sex hormones de:Levonorgestrel nl:Levonorgestrel

Template:WikiDoc Sources