Indications and Usage
● Prevention of Pregnancy
● Postmenopausal Osteoporosis (PMO)
● Hypermenorrhea
● Endometriosis
Mechanism of Action
Levonorgestrel prevents pregnancy by interfering with ovulation, fertilization, and implantation. The levonorgestrel-only containing emergency contraceptive tablet is 89% effective if it is used according to prescribing information within 72 hours after intercourse. Levonorgestrel utilized as a component of hormonal therapy helps to prevent endometrial carcinoma associated with unopposed estrogen administration. Levonorgestrel binds to progesterone and androgen receptors and slows the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. This process results in the suppression of the normal physiological luteinizing hormone (LH) surge that precedes ovulation. It inhibits the rupture of follicles and viable egg release from the ovaries. Levonorgestrel has been proven to be more effective when administered before ovulation.
Absorption: Orally administered levonorgestrel is absorbed in the gastrointestinal trac The Cmax following one dose of 0.75 mg of oral levonorgestrel is reached within the hour after administration.
Protein binding: The protein binding of levonorgestrel ranges from 97.5-99%, and it is mainly bound to sex hormone-binding globulin (SHBG). Levonorgestrel is also bound to albumin.
Metabolism: After absorption of the oral emergency contraceptive preparation, levonorgestrel is conjugated and forms a large number of sulfate conjugates. In addition, glucuronide conjugates have been identified in the plasma.
Elimination: Approximately 45% of an oral levonorgestrel dose and its conjugated or sulfate metabolites are found to be excreted in the urine. Approximately 32% of an orally ingested dose is found excreted in feces, primarily in the form of glucuronide conjugates of levonorgestrel. The elimination half-life of a 0.75 mg dose of 1.5 mg of levonorgestrel ranges between 20-60 hours post-administration.
Ethinylestradiol is a synthetic estrogen that decreases luteinizing hormone to decrease endometrial vascularization, and decreases gonadotrophic hormone to prevent ovulation. It has a long duration of action as it is taken once daily, and a wide therapeutic index as overdoses are generally not associated with serious adverse effects. Combined oral contraceptives suppress ovulation by suppressing gonadotrophic hormone, thickening cervical mucus to prevent the travel of sperm, and preventing changes in the endometrium required for implantation of a fertilized egg. Ethinylestradiol decreases luteinizing hormone, decreasing vascularity in the endometrium. It also increases sex hormone binding globulin.
Absorption: A 30µg oral dose of ethinylestradiol reaches a Cmax of 74.1±35.6pg/mL, with a Tmax of 1.5±0.5h
Protein binding: Enthinylestradiol is 98.3-98.5% bound to albumin in serum8 but also exhibits binding to sex hormone binding globulin.
Metabolism: Drug undergoes glcouridination, sulfation and hydroxylation. Hydroxylated metabolites can be methylated by catechol-O-methyltransferase. The methoxy metabolites can in turn be sulfated or glucuronidated.
Elimination: Ethinylestradiol is 59.2% eliminated in the urine and bile, while 2-3% is eliminated in the feces. Over 90% of ethinylestradiol is eliminated as the unchanged parent drug. A 30µg oral dose has a half-life of 8.4±4.8h
Side Effects
Common side effects include nausea, vomiting, headache, abdominal cramps/bloating, breast tenderness, swelling of the ankles/feet (retaining fluid), or weight change may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly. Many women will not have regular periods while taking this medication.
Contraindication
The drug should not be used in following conditions:
● Breast cancer
● A condition with low thyroid hormone level
● Diabetes
● High cholesterol
● High amount of triglyceride in the blood
● Inherited disorder of continuing episodes of swelling
● Deficiency of anti-clotting agents
● Increased risk of blood clotting
● Heart attack
● Coronary artery disease
● Liver problems
● Migraine with aura
Interaction
Some products that may interact with this drug include: aromatase inhibitors (such as anastrozole, exemestane), ospemifene, tamoxifen, tizanidine, tranexamic acid, certain combination products used to treat chronic hepatitis C (ombitasvir/paritaprevir/ritonavir with or without dasabuvir).
Some drugs may cause hormonal birth control to work less well by decreasing the amount of birth control hormones in your body. This effect can result in pregnancy. Examples include griseofulvin, modafinil, rifamycins (such as rifampin, rifabutin), St. John's wort, drugs used to treat seizures (such as barbiturates, carbamazepine, felbamate, phenytoin, primidone, topiramate), HIV drugs (such as nelfinavir, nevirapine, ritonavir), among others.