Levonorgestrel is a type of oral contraceptive used for emergency contraception after unprotected intercourse. Levonorgestrel is classified as a progesterone-based birth control pill.
ATC code: G03AC03
Drug class: Progestin
Dosage form: Coated tablet
Available doses: 0.75 and 1.5 mg
Brand: Ovosis®
Indications: Emergency contraception in the first three days after unprotected intercourse.
Mechanism of action
Levonorgestrel prevents pregnancy through several mechanisms, including:
- Thickening of cervical mucus, which prevents sperm from passing through the cervix and surviving.
- Inhibition of ovulation through negative feedback on the hypothalamus, which reduces the secretion of FSH and LH hormones.
- Changing the endometrial tissue and making it unsuitable for implantation
Pharmacokinetics
Absorption: Fast and complete
Time to peak effect: 2 hours
Protein binding: Up to 50% binds to albumin and up to 47% to SHBG (Sex Hormone Binding Globulin).
Metabolism: Hepatic by cytochrome 3A4 as inactive metabolite
Inactive metabolites: tetrahydronorgestrel, hydroxynorgestrel and its sulfate and glucuronide conjugates
Half-life: 30 to 46 hours
Excretion: 45% through urine and 32% through feces
Dosage
Levonorgestrel should be taken up to 72 hours after unprotected intercourse, although some sources report that these pills are still effective up to 5 days after intercourse, but the closer the pill is taken to the time of intercourse, the better its effectiveness. Therefore, taking the pill should not be delayed as much as possible.
If you prepare a 0.75 mg tablet, it can be used in two ways:
1- Taking both pills at the same time
2- Take one pill after intercourse and take the next pill 12 hours after taking the first pill.
If you are taking a 1.5 mg tablet, one tablet is taken after intercourse.
Dose adjustment
There is no need to adjust the dose in hepatic and renal insufficiency.
Contraindications for using levonorgestrel
It is contraindicated in pregnancy. It should also not be used as a routine contraceptive pill.
Warnings and precautions
Precautions related to side effects:
Irregular menstrual cycle: Spotting may occur after taking levonorgestrel. If bleeding does not occur within 7 days of the expected menstrual period, the possibility of pregnancy should be investigated.
Ectopic pregnancy: A previous history of ectopic pregnancy is not a contraindication to the use of levonorgestrel. In case of severe lower abdominal pain, the possibility of ectopic pregnancy should be investigated.
Precautions related to other items:
Overweight and obesity: The pharmacokinetics of oral levonorgestrel are affected by overweight and obesity, and its effectiveness may be reduced in women with a BMI greater than 30.
Protection against HIV: Levonorgestrel does not provide protection against transmission of HIV or other sexually transmitted diseases.
Side effects of levonorgestrel
Prevalence greater than 10 percent
Endocrine system: Menstrual irregularities (delayed periods 26%, heavy and heavy bleeding 14%, decreased blood volume 13%), breast tenderness 11%
Gastrointestinal: abdominal pain 18%, nausea 23%
Central nervous system: dizziness 11%, fatigue 17%, headache 17%
Prevalence 1 to 10 percent
Gastrointestinal: diarrhea 5%, vomiting 6%
Drug interactions
Levonorgestrel reduces the effects of the following drugs:
Anticoagulants, antidiabetic drugs, ulipristal, vitamin K antagonist
The effect of levonorgestrel is reduced by the following drugs:
Acitretin, aprepitant, barbiturates, bile acid sequestrants, bosentan, brigatinib, carbamazepine, cladribine, clobazam, moderate and strong CYP3A4 inducers, dabrafenib, darunavir, deferasirox, efavirenz, encorafenib, enzalutamide, ordafitinib, slicarbazepine, felbamate, griseofulvin, ivocidinib, ixazomib, lamotrigine, lesinurad, lixisenatide, lopinavir, lumacaftor and ivacaftor, meterleptin, mifepristone, mitotane, mycophenolate, nelfinavir, nintedanib, octreotide, oxcarbazepine, prampanel, pexidartinib, phenytoin, pitolisant, primidone, retinoic acid derivatives, rifamycin derivatives, saquinavir, sarilumab, Siltuximab, Sugammadex, Tazmetostat, Tetrahydrocannabinol and Cannabidiol, Tocilizumab, Topiramate, Ulipristal, and Tea Tree
Levonorgestrel increases the effects of the following drugs:
C1 inhibitors, alexacaftor/tezacaftor/ivacaftor, flibanserin, pomalidomide, selegiline, thalidomide, tranexamic acid, triazolam, voriconazole
The effect of levonorgestrel is increased by the following drugs:
Atazanavir, carfilzomib, cobicistat, lopinavir, meterleptin, mifepristone, tipranavir, voriconazole, and herbs with progestogenic properties
Levonorgestrel use during pregnancy and breastfeeding
Pregnancy: Should not be used.
Breastfeeding: Levonorgestrel is secreted into breast milk. Peak concentrations occur between 2 and 4 hours after tablet intake and decline rapidly after 12 hours. The half-life of levonorgestrel in breast milk is 26 hours, and based on studies, the concentration of the drug that reaches the infant through milk is very low and negligible.
