Brands, Medical Use, Clinical Data
Drug Category
Dosage Forms
Brands / Synonyms
Alesse; Alpha-Norgestrel; Component of Lo/Ovral; Component of Ovral; D-Norgestrel; DL-Norgestrel; Follistrel; Jadelle; LD Norgestrel; Ld Norgestrel [French]; Levlen; Levlen Ed; Levonorgestrel; Levonorgestrel Implants; Levonorgestrel [Usan:Ban:Inn]; Levonorgestrelum [Inn-Latin]; Levonova; Levora-21; Levora-28; LO Ovral; Lo/Ovral; Logynon; Logynon Ed; LOW-Ogestrel; Methylnorethindrone; Microgest Ed; Microgyn; Microgynon; Microgynon 21; Microgynon 28; Microgynon 30 Ed; Microgynon Cd; Microlut; Microlution; Microval; Minivlar 30; Mirena; Monofeme 28; Monovar; Neogest; Neogynon 21; NOG; Nordet; Nordette; Nordette 21; Nordette 28; Norgeston; Norgestrel [Progestins]; Norgestrel [Usan:Ban:Inn:Jan]; Norgestrelum [Inn-Latin]; Norplant; Norplant 2; Norplant II; Norplant System in Plastic Container; Ovral; Ovral-Lo; Ovran; Ovranette; Ovrette; Plan B; Postinor; Preven; Rigevidon 21+7; Stediril; Stediril 30; Tetragynon; Tri-Levlen; Tri-Levlen 21; Triagynon; Triciclor; Trifeme 28; Trigoa; Trinordiol; Trinordiol 21; Trinordiol 28; Triphasil; Triphasil 21; Triphasil 28; Triquilar Ed; Trivora
Indications
Used as an oral contraceptive to prevent pregnancy
Pharmacology
Norgestrel is used as a female contraceptive. 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. 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
Norgestrel 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 Norgestrel will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge.
Absorption
65%
Toxicity
Nausea, vomiting, and drowsiness/fatigue; Withdrawal bleeding; LD50=mg/kg (orally in rat)
Biotrnasformation / Drug Metabolism
Hepatic
Contraindications
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
Drug Interactions
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.
The prescribing information of concomitant medications should be consulted to identify potential
interactions.
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.
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