indication

For treatment of moderate to severe vasomotor symptoms associated with the menopause, female hypogonadism, prostatic carcinoma-palliative therapy of advanced disease, breast cancer, as an oral contraceptive, and as emergency contraceptive.

pharmacology

Ethinyl estradiol is a synthetic derivative of the natural estrogen estradiol. It is one of two estrogens currently used in oral contraceptive pills. The other, mestranol, is converted to ethinyl estradiol before it is biologically active. Ethinyl estradiol and norethindrone are used together as an oral contraceptive agent.

mechanism of action

Estrogens diffuse into their target cells and interact with a protein receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. This cascade is initiated by initially binding to the estrogen receptors. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).

toxicity

Oral, mouse LD₅₀: 1737 mg/kg. Symptoms of overdose include nausea and vomiting, and withdrawal bleeding may occur in females.

biotransformation

Hepatic. Quantitatively, the major metabolic pathway for ethinyl estradiol, both in rats and in humans, is aromatic hydroxylation, as it is for the natural estrogens.

absorption

Rapid and complete absorption follows oral intake of ethinyl estradiol (bioavailability 43%).

half life

36 +/- 13 hours

drug interactions

Acenocoumarol: Increased thrombotic risk due to estrogen

Aminophylline: The contraceptive increases the effect and toxicity of theophylline

Amobarbital: This product may cause a slight decrease of contraceptive effect

Amoxicillin: This anti-infectious agent could decrease the effect of the oral contraceptive

Ampicillin: This anti-infectious agent could decrease the effect of the oral contraceptive

Amprenavir: Ritonavir could decrease the contraceptive efficacy

Anisindione: Increased thrombotic risk due to estrogen

Aprepitant: Aprepitant could decrease the effect of the oral contraceptive

Aprobarbital: This product may cause a slight decrease of contraceptive effect

Artemether: Artemether may decrease the effectiveness of ethinyl estradiol by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.

Azlocillin: This anti-infectious agent could decrease the effect of the oral contraceptive

Aztreonam: This anti-infectious agent could decrease the effect of the oral contraceptive

Bacampicillin: This anti-infectious agent could decrease the effect of the oral contraceptive

Bosentan: Bosentan may decrease the contraceptive effect of ethinyl estradiol. Hormonal contraception should not be relied on alone during concomitant therapy with bosentan.

Butabarbital: This product may cause a slight decrease of contraceptive effect

Butalbital: This product may cause a slight decrease of contraceptive effect

Butethal: This product may cause a slight decrease of contraceptive effect

Carbamazepine: Carbamazepine may decrease the contraceptive effect of ethinyl estradiol. Hormonal contraception should not be relied on alone during concomitant therapy with carbamazepine.

Clavulanate: This anti-infectious agent could decrease the effect of the oral contraceptive

Cloxacillin: This anti-infectious agent could decrease the effect of the oral contraceptive

Colesevelam: Bile Acid Sequestrants may decrease the serum concentration of Contraceptives (Estrogens). Administer estrogen-based oral contraceptives at least 1-4 hours prior to or 4-6 hours after administration of a bile acid sequestrant. Consider alternatives in order to avoid this combination when possible, due to the risk for impaired contraceptive effectiveness. Ethinyl estradiol patches and vaginal rings may also be somewhat impacted by this interaction, though the extent and significance of such an interaction is uncertain.

Cyclacillin: This anti-infectious agent could decrease the effect of the oral contraceptive

Cyclosporine: The contraceptive increases the effect and toxicity of cyclosporine

Demeclocycline: This anti-infectious agent could decrease the effect of the oral contraceptive

Dicloxacillin: This anti-infectious agent could decrease the effect of the oral contraceptive

Dicumarol: Increased thrombotic risk due to estrogen

Doxycycline: Doxycycline may decrease the contraceptive effect of ethinyl estradiol.

Dyphylline: The contraceptive increases the effect and toxicity of theophylline

Ethotoin: This product may cause a slight decrease of contraceptive effect

Etoricoxib: Etoricoxib may increase the levels of ethinyl estradiol.

Flucloxacillin: This anti-infectious agent could decrease the effect of the oral contraceptive

Fosphenytoin: This product may cause a slight decrease of contraceptive effect

Griseofulvin: This product may cause a slight decrease of contraceptive effect

Heptabarbital: This product may cause a slight decrease of contraceptive effect

Hetacillin: This anti-infectious agent could decrease the effect of the oral contraceptive

Hexobarbital: This product may cause a slight decrease of contraceptive effect

Ketoconazole: This anti-infectious agent could decrease the effect of the oral contraceptive

Lamotrigine: The oral contraceptive decreases the effect of lamotrigine

Mephenytoin: This product may cause a slight decrease of contraceptive effect

Methacycline: This anti-infectious agent could decrease the effect of the oral contraceptive

Methohexital: This product may cause a slight decrease of contraceptive effect

Methylphenobarbital: This product may cause a slight decrease of contraceptive effect

Meticillin: This anti-infectious agent could decrease the effect of the oral contraceptive

Mezlocillin: This anti-infectious agent could decrease the effect of the oral contraceptive

Minocycline: This anti-infectious agent could decrease the effect of the oral contraceptive

Modafinil: Modafinil may decrease the contraceptive effect of ethinyl estradiol. Hormonal contraception should not be solely relied on during concomitant therapy with modafinil.

Nafcillin: This anti-infectious agent could decrease the effect of the oral contraceptive

Nelfinavir: Ritonavir could decrease the contraceptive efficacy

Oxacillin: This anti-infectious agent could decrease the effect of the oral contraceptive

Oxcarbazepine: Oxcarbazepine may decrease the contraceptive effect of ethinyl estradiol. Hormonal contraception should not be solely relied upon during concomitant therapy with oxcarbazepine.

Oxtriphylline: The contraceptive increases the effect and toxicity of theophylline

Oxytetracycline: This anti-infectious agent could decrease the effect of the oral contraceptive

Pentobarbital: This product may cause a slight decrease of contraceptive effect

Phenobarbital: This product may cause a slight decrease of contraceptive effect

Phenytoin: This product may cause a slight decrease of contraceptive effect

Piperacillin: This anti-infectious agent could decrease the effect of the oral contraceptive

Pivampicillin: This anti-infectious agent could decrease the effect of the oral contraceptive

Prednisolone: The estrogenic agent, ethinyl estradiol, may increase the effect of the corticosteroid, prednisolone.

Prednisone: The estrogenic agent, ethinyl estradiol, may increase the effect of corticosteroid, prednisone.

Primidone: This product may cause a slight decrease of contraceptive effect

Raloxifene: Association not recommended

Rifabutin: Rifabutin may decrease the contraceptive effect of ethinyl estradiol. Hormonal contraception should not be solely relied on alone during concomitant therapy with rifabutin.

Rifampin: This product may cause a slight decrease of contraceptive effect

Rifapentine: This product may cause a slight decrease of contraceptive effect

Ritonavir: Ritonavir could decrease the contraceptive efficacy

Rolitetracycline: This anti-infectious agent could decrease the effect of the oral contraceptive

Secobarbital: This product may cause a slight decrease of contraceptive effect

St. John's Wort: St. John's Wort could reduce the contraceptive effect

Tacrolimus: Ethinyl estradiol may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Ethinyl estradiol therapy is initiated, discontinued or altered.

Talbutal: This product may cause a slight decrease of contraceptive effect

Tazobactam: This anti-infectious agent could decrease the effect of the oral contraceptive

Tetracycline: This anti-infectious agent could decrease the effect of the oral contraceptive

Theophylline: The contraceptive increases the effect and toxicity of theophylline

Thiopental: Thiopental may decrease the effect of Ethinyl estradiol. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.

Ticarcillin: This anti-infectious agent could decrease the effect of the oral contraceptive

Tipranavir: Tipranavir, co-administered with Ritonavir, decreases Ethinyl estradiol concentrations. Ethinyl estradiol may increase the adverse dermatological effects (i.e. skin rash) of Tipranavir. Use an alternate form of contraception or monitor for estrogen deficiency if Ethinyl estradiol is used for hormone replacement therapy.

Tizanidine: Ethinyl estradiol may increase the serum concentration of tizanidine. Monitor for changes in the therapeutic and adverse effects of tizanidine if ethinyl estradiol is initiated, discontinued or dose changed.

Topiramate: Topiramate may decrease the effect of the oral contraceptive, Ethinyl estradiol. An alternate form of contraception should be used during concomitant therapy.

Tretinoin: Oral Tretinoin may decrease the effect of the oral contraceptive, Ethinyl Estradiol. An alternate form of contraception should be used during concomitant therapy.

Troglitazone: Possible loss of contracepitve effect

Ursodeoxycholic acid: Estrogens decreases the effect of ursodiol

Warfarin: Ethinyl estradiol may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if ethinyl estradiol is initiated, discontinued or dose changed.