Brands, Medical Use, Clinical Data
- Contraceptives, Oral, Synthetic
- Contraceptive Agents, Female
- Insert (extended-release)
Brands / Synonyms
D-Norgestrel; Follistrel; Jadelle; Levlen; Levlen Ed; Levonorgestrel; Levonorgestrel Implants; Levonorgestrel [Usan:Ban:Inn]; Levonorgestrelum [Inn-Latin]; Levonova; Levora-21; Levora-28; Logynon Ed; Malloside; Microgest Ed; Microgyn; Microgynon 21; Microgynon 28; Microgynon 30 Ed; Microgynon Cd; Microlution; Microval; Minivlar 30; Mirena; Monofeme 28; Neogynon 21; Nordet; Nordette; Nordette 21; Nordette 28; NORPLANT; Norplant 2; Norplant Ii; Norplant System in Plastic Container; Ovral-Lo; Ovranette; Ovrette; Plan B; Preven; Rigevidon 21+7; Stediril 30; Tri-Levlen; Tri-Levlen 21; Triagynon; Triciclor; Trifeme 28; Trigoa; Trinordiol 21; Trinordiol 28; Triphasil; Triphasil 21; Triphasil 28; Triquilar Ed; Trivora
For the treatment of menopausal and postmenopausal disorders and alone or in combination with other hormones as an oral contraceptive.
L-Norgestrel is used as a female contraceptive. L-Norgestrel is a progestin or a synthetic form of the naturally occurring female sex hormone, progesterone. In a woman's normal menstrual cycle, an egg matures and is released from the ovaries (ovulation). The ovary then produces progesterone, preventing the release of further eggs and priming the lining of the womb for a possible pregnancy. If pregnancy occurs, progesterone levels in the body remain high, maintaining the womb lining. If pregnancy does not occur, progesterone levels in the body fall, resulting in a menstrual period. L-Norgestrel tricks the body processes into thinking that ovulation has already occurred, by maintaining high levels of the synthetic progesterone. This prevents the release of eggs from the ovaries.
Mechanism of Action
Binds to the progesterone and estrogen receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like L-Norgestrel will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge.
Levonorgestrel is not subjected to a "first-pass" effect and is virtually 100% bioavailable.
LD50>5000 mg/kg (orally in rats)
Biotrnasformation / Drug Metabolism
Combination oral contraceptives should not be used in women with any of the following conditions: - Thrombophlebitis or thromboembolic disorders - A past history of deep-vein thrombophlebitis or thromboembolic disorders - Cerebral-vascular or coronary-artery disease (current or history) - Thrombogenic valvulopathies - Thrombogenic rhythm disorders - Major surgery with prolonged immobilization - Diabetes with vascular involvement - Headaches with focal neurological symptoms - Uncontrolled hypertension Known or suspected carcinoma of the breast or personal history of breast cancer - Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia - Undiagnosed abnormal genital bleeding - Cholestatic jaundice of pregnancy or jaundice with prior pill use - Hepatic adenomas or carcinomas, or active liver disease, as long as liver function has not returned to normal - Known or suspected pregnancy - Hypersensitivity to any of the components of Lo/Ovral
Changes in contraceptive effectiveness associated with coadministration of other products: Contraceptive effectiveness may be reduced when hormonal contraceptives are coadministered with antibiotics, anticonvulsants, and other drugs that increase the metabolism of contraceptive steroids. This could result in unintended pregnancy or breakthrough bleeding. Examples include rifampin, rifabutin, barbiturates, primidone, phenylbutazone, phenytoin, dexamethasone, carbamazepine, felbamate, oxcarbazepine, topiramate, griseofulvin, and modafinil.
Several cases of contraceptive failure and breakthrough bleeding have been reported in the literature with concomitant administration of antibiotics such as ampicillin and other penicillins, and tetracyclines, possibly due to a decrease of enterohepatic recirculation of estrogens.
However, clinical pharmacology studies investigating drug interactions between combined oral contraceptives and these antibiotics have reported inconsistent results. Enterohepatic recirculation of estrogens may also be decreased by substances that reduce gut transit time.
Several of the anti-HIV protease inhibitors have been studied with coadministration of oral combination hormonal contraceptives; significant changes (increase and decrease) in the plasma levels of the estrogen and progestin have been noted in some cases. The safety and efficacy of oral contraceptive products may be affected with coadministration of anti-HIV protease inhibitors. Health-care professionals should refer to the label of the individual anti-HIV protease inhibitors for further drug-drug interaction information.
Herbal products containing St. John's Wort (Hypericum perforatum) may induce hepatic enzymes (cytochrome P 450) and p-glycoprotein transporter and may reduce the effectiveness of contraceptive steroids. This may also result in breakthrough bleeding.
During concomitant use of ethinyl estradiol containing products and substances that may lead to decreased plasma steroid hormone concentrations, it is recommended that a nonhormonal backup method of birth control be used in addition to the regular intake of Lo/Ovral. If the use of a substance which leads to decreased ethinyl estradiol plasma concentrations is required for a prolonged period of time, combination oral contraceptives should not be considered the primary contraceptive.
After discontinuation of substances that may lead to decreased ethinyl estradiol plasma concentrations, use of a nonhormonal back-up method of birth control is recommended for 7 days. Longer use of a back-up method is advisable after discontinuation of substances that have led to induction of hepatic microsomal enzymes, resulting in decreased ethinyl estradiol concentrations. It may take several weeks until enzyme induction has completely subsided, depending on dosage, duration of use, and rate of elimination of the inducing substance.
Increase in plasma levels associated with coadministered drugs: Coadministration of atorvastatin and certain oral contraceptives containing ethinyl estradiol increase AUC values for ethinyl estradiol by approximately 20%. The mechanism of this interaction is unknown. Ascorbic acid and acetaminophen increase the bioavailability of ethinyl estradiol since these drugs act as competitive inhibitors for sulfation of ethinyl estradiol in the gastrointestinal wall, a known pathway of elimination for ethinyl estradiol. CYP 3A4 inhibitors such as indinavir, itraconazole, ketoconazole, fluconazole, and troleandomycin may increase plasma hormone levels. Troleandomycin may also increase the risk of intrahepatic cholestasis during coadministration with combination oral contraceptives.
Changes in plasma levels of coadministered drugs: Combination hormonal contraceptives containing some synthetic estrogens (eg, ethinyl estradiol) may inhibit the metabolism of other compounds. Increased plasma concentrations of cyclosporin, prednisolone and other corticosteroids, and theophylline have been reported with concomitant administration of oral contraceptives. Decreased plasma concentrations of acetaminophen and increased clearance of temazepam, salicylic acid, morphine, and clofibric acid, due to induction of conjugation (particularly glucuronidation), have been noted when these drugs were administered with oral contraceptives.
Interactions With Laboratory Tests - Certain endocrine and liver-function tests and blood components may be affected by oral contraceptives:
a. Increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability.
b. Increased thyroid-binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 by column or by radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG; free T4 concentration is unaltered.
c. Other binding proteins may be elevated in serum ie, corticosteroid binding globulin (CBG), sex hormone-binding globulins (SHBG) leading to increased levels of total circulating corticosteroids and sex steroids respectively. Free or biologically active hormone concentrations are unchanged.
d. Triglycerides may be increased and levels of various other lipids and lipoproteins may be affected.
e. Glucose tolerance may be decreased.
f. Serum folate levels may be depressed by oral-contraceptive therapy. This may be of clinical significance if a woman becomes pregnant shortly after discontinuing oral contraceptives.