Norelgestromin
Norelgestromin, or norelgestromine, sold under the brand names Evra and Ortho Evra among others, is a progestin medication which is used as a method of birth control for women. The medication is available in combination with an estrogen and is not available alone. It is used as a patch that is applied to the skin.
Side effects of the combination of an estrogen and norelgestromin include menstrual irregularities, headaches, nausea, abdominal pain, breast tenderness, mood changes, and others. Norelgestromin is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. It has very weak androgenic activity and no other important hormonal activity.
Norelgestromin was introduced for medical use in 2002. It is sometimes referred to as a "third-generation" progestin. Norelgestromin is marketed widely throughout the world. It is available as a generic medication.
Medical uses
Norelgestromin is used in combination with ethinyl estradiol in contraceptive patches. These patches mediate their contraceptive effects by suppressing gonadotropin levels as well as by causing changes in the cervical mucus and endometrium that diminish the likelihood of pregnancy.Available forms
Norelgestromin is available only as a transdermal contraceptive patch in combination with ethinyl estradiol. The Ortho Evra patch is a 20 cm, once-weekly adhesive that contains 6.0 mg norelgestromin and 0.6 mg ethinyl estradiol and delivers 200 μg/day norelgestromin and 35 μg/day ethinyl estradiol.Side effects
Norelgestromin has mostly been studied in combination with an estrogen, so the side effects of norelgestromin specifically or on its own have not been well-defined. Side effects associated with the combination of ethinylestradiol and norelgestromin as a transdermal patch in premenopausal women, with greater than or equal to 2.5% incidence over 6 to 13 menstrual cycles, include breast symptoms, headaches, application site reactions, nausea, abdominal pain, dysmenorrhea, vaginal bleeding and menstrual disorders, mood, affect, and anxiety disorders, vomiting, diarrhea, vaginal yeast infections, dizziness, acne, migraine, weight gain, fatigue, and pruritus.Pharmacology
Pharmacodynamics
Norelgestromin is a progestogen. It is one of the active metabolites of norgestimate. Unlike many related progestins, norelgestromin reportedly has negligible androgenic activity. However, it produces levonorgestrel as an active metabolite to some extent, which does have some androgenic activity. Nonetheless, transdermally-administered norelgestromin does not counteract the increase in sex hormone-binding globulin levels produced by ethinyl estradiol.Pharmacokinetics
Upon application of a transdermal patch containing norelgestromin and ethinyl estradiol, plateau levels of both are reached by approximately 48 hours, and steady-state levels are reached within 2 weeks of application. Absorption following application to the buttock, upper outer arm, abdomen, and upper torso was assessed and, while absorption from the abdomen was slightly lower, it was considered to be therapeutically equivalent for the various areas. Mean levels of norelgestromin at steady-state ranged from 0.305 ng/mL to 1.53 ng/mL, with an average of about 0.725 ng/mL. The plasma protein binding of norelgestromin is 99%, and it is bound to albumin but not to sex hormone-binding globulin.The metabolism of norelgestromin takes place in the liver and is via transformation into levonorgestrel as well as hydroxylation and conjugation. However, because norelgestromin is used parenterally, first-pass metabolism in the liver and gastrointestinal tract that normally occurs with oral administration are avoided. The biological half-life of norelgestromin is 17 to 37 hours. The metabolites of norelgestromin, along with those of ethinyl estradiol, are eliminated in the urine and feces.