Home > Medical Reference > Complementary Medicine

Ethinyl Estradiol and Desogestrel


Pronunciation

 (ETH in il es tra DYE ole & des oh JES trel)


U.S. Brand Names

 Apri®; Cyclessa®; Desogen®; Kariva™; Mircette®; Ortho-Cept®; Solia™; Velivet™


Synonyms

 Desogestrel and Ethinyl Estradiol; Ortho Cept


Generic Available

 Yes


Canadian Brand Names

 Marvelon®; Ortho-Cept®


Use

 Prevention of pregnancy


Use - Unlabeled/Investigational

 Treatment of hypermenorrhea (menorrhagia); pain associated with endometriosis; dysmenorrhea; dysfunctional uterine bleeding


Pregnancy Risk Factor

 X


Pregnancy Implications

 Pregnancy should be ruled out prior to treatment and discontinued if pregnancy occurs. In general, the use of combination hormonal contraceptives when inadvertently taken early in pregnancy have not been associated with teratogenic effects. Due to increased risk of thromboembolism postpartum, combination hormonal contraceptives should not be started earlier than 4-6 weeks following delivery. Hormonal contraceptives may be less effective in obese patients. An increase in oral contraceptive failure was noted in women with a BMI >27.3. Similar findings were noted in patients weighing 90 kg (198 lb) using the contraceptive patch.


Lactation

 Enters breast milk/not recommended (AAP rates "compatible")


Contraindications

 Hypersensitivity to ethinyl estradiol, etonogestrel, desogestrel, or any component of the formulation; history of or current thrombophlebitis or venous thromboembolic disorders (including DVT, PE); active or recent (within 1 year) arterial thromboembolic disease (eg, stroke, MI); cerebral vascular disease, coronary artery disease, valvular heart disease with complications, severe hypertension; diabetes mellitus with vascular involvement; severe headache with focal neurological symptoms; known or suspected breast carcinoma, endometrial cancer, estrogen-dependent neoplasms, undiagnosed abnormal genital bleeding; hepatic dysfunction or tumor, cholestatic jaundice of pregnancy, jaundice with prior combination hormonal contraceptive use; major surgery with prolonged immobilization; heavy smoking ( 15 cigarettes/day) in patients >35 years of age; pregnancy


Warnings/Precautions

 Combination hormonal contraceptives do not protect against HIV infection or other sexually-transmitted diseases. The risk of cardiovascular side effects increases in women who smoke cigarettes, especially those who are >35 years of age; women who use combination hormonal contraceptives should be strongly advised not to smoke. Combination hormonal contraceptives may lead to increased risk of myocardial infarction, use with caution in patients with risk factors for coronary artery disease. May increase the risk of thromboembolism. Combination hormonal contraceptives may have a dose-related risk of vascular disease, hypertension, and gallbladder disease. Women with hypertension should be encouraged to use another form of contraception. The use of combination hormonal contraceptives has been associated with a slight increase in frequency of breast cancer, however, studies are not consistent. Combination hormonal contraceptives may cause glucose intolerance. Retinal thrombosis has been reported (rarely). Use with caution in patients with renal disease, conditions that may be aggravated by fluid retention, depression, or history of migraine. Not for use prior to menarche.

The minimum dosage combination of estrogen/progestin that will effectively treat the individual patient should be used. New patients should be started on products containing <50 mcg of estrogen per tablet.


Adverse Reactions

 Frequency not defined.

Cardiovascular: Arterial thromboembolism, cerebral hemorrhage, cerebral thrombosis, edema, hypertension, mesenteric thrombosis, MI

Central nervous system: Depression, dizziness, headache, migraine, nervousness, premenstrual syndrome, stroke

Dermatologic: Acne, erythema multiforme, erythema nodosum, hirsutism, loss of scalp hair, melasma (may persist), rash (allergic)

Endocrine & metabolic: Amenorrhea, breakthrough bleeding, breast enlargement, breast secretion, breast tenderness, carbohydrate intolerance, lactation decreased (postpartum), glucose tolerance decreased, libido changes, menstrual flow changes, sex hormone-binding globulins (SHBG) increased, spotting, temporary infertility (following discontinuation), thyroid-binding globulin increased, triglycerides increased

Gastrointestinal: Abdominal cramps, appetite changes, bloating, cholestasis, colitis, gallbladder disease, jaundice, nausea, vomiting, weight gain/loss

Genitourinary: Cervical erosion changes, cervical secretion changes, cystitis-like syndrome, vaginal candidiasis, vaginitis

Hematologic: Antithrombin III decreased, folate levels decreased, hemolytic uremic syndrome, norepinephrine induced platelet aggregability increased, porphyria, prothrombin increased; factors VII, VIII, IX, and X increased

Hepatic: Benign liver tumors, Budd-Chiari syndrome, cholestatic jaundice, hepatic adenomas

Local: Thrombophlebitis

Ocular: Cataracts, change in corneal curvature (steepening), contact lens intolerance, optic neuritis, retinal thrombosis

Renal: Impaired renal function

Respiratory: Pulmonary thromboembolism

Miscellaneous: Hemorrhagic eruption


Overdosage/Toxicology

 Toxicity is unlikely following single exposures of excessive doses. May cause withdrawal bleeding in females. Any treatment following emesis and charcoal administration should be supportive and symptomatic.


Drug Interactions

Ethinyl estradiol: Substrate of CYP2C8/9 (minor), 3A4 (major), 3A5-7 (minor); Inhibits CYP1A2 (weak), 2B6 (weak), 2C19 (weak), 3A4 (weak)

Desogestrel: Substrate of CYP2C19 (major)

Acetaminophen: May increase plasma concentration of synthetic estrogens, possibly by inhibiting conjugation. Combination hormonal contraceptives may also decrease the plasma concentration of acetaminophen.

Acitretin: Interferes with the contraceptive effect of microdosed progestin-containing "minipill" preparations. The effect on other progestational contraceptives (eg, implants, injectables) is unknown.

Aminoglutethimide: May increase CYP metabolism of progestins leading to possible decrease in contraceptive effectiveness. Use of a nonhormonal contraceptive product is recommended.

Antibiotics (ampicillin, tetracycline): Pregnancy has been reported following concomitant use, however, pharmacokinetic studies have not shown consistent effects with these antibiotics on plasma concentrations of synthetic steroids. Use of a nonhormonal contraceptive product is recommended.

Anticoagulants: Combination hormonal contraceptives may increase or decrease the effects of coumarin derivatives. Combination hormonal contraceptives may also increase risk of thromboembolic disorders

Anticonvulsants (carbamazepine, felbamate, phenobarbital, phenytoin, topiramate): Increase the metabolism of ethinyl estradiol and/or some progestins, leading to possible decrease in contraceptive effectiveness. Use of a nonhormonal contraceptive product is recommended.

Ascorbic acid: Doses of ascorbic acid (vitamin C) 1 g/day have been reported to increase plasma concentration of synthetic estrogens by ~47%, possibly by inhibiting conjugation; clinical implications are unclear.

Atorvastatin: Atorvastatin increases the AUC for norethindrone and ethinyl estradiol.

Benzodiazepines: Combination hormonal contraceptives may decrease the clearance of some benzodiazepines (alprazolam, chlordiazepoxide, diazepam) and increase the clearance of others (lorazepam, oxazepam, temazepam)

Clofibric acid: Combination hormonal contraceptives may increase the clearance of clofibric acid.

Cyclosporine: Combination hormonal contraceptives may inhibit the metabolism of cyclosporine, leading to increased plasma concentrations; monitor cyclosporine.

CYP2C19 inducers: May decrease the levels/effects of desogestrel. Example inducers include aminoglutethimide, carbamazepine, phenytoin, and rifampin.

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of ethinyl estradiol. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.

Griseofulvin: Griseofulvin may induce the metabolism of combination hormonal contraceptives causing menstrual changes; pregnancies have been reported. Use of barrier form of contraception is suggested while on griseofulvin therapy.

Morphine: Combination hormonal contraceptives may increase the clearance of morphine.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs): Nevirapine may decrease plasma levels of combination hormonal contraceptives; use of a nonhormonal contraceptive product is recommended. No data for delavirdine; incomplete data for efavirenz.

Prednisolone: Ethinyl estradiol may inhibit the metabolism of prednisolone, leading to increased plasma concentrations.

Protease inhibitors: Amprenavir, lopinavir, nelfinavir, and ritonavir have been shown to decrease plasma levels of combination hormonal contraceptives; use of a nonhormonal contraceptive product is recommended. Indinavir has been shown to increase plasma levels of combination hormonal contraceptives. No data for saquinavir.

Repaglinide: Increased level of ethinyl estradiol when combined with levonorgestrel.

Rifampin: Rifampin increases the metabolism of ethinyl estradiol and some progestins (norethindrone) resulting in decreased contraceptive effectiveness and increased menstrual irregularities. Use of a nonhormonal contraceptive product is recommended.

Salicylic acid: Combination hormonal contraceptives may increase the clearance of salicylic acid.

Selegiline: Combination hormonal contraceptives may increase the serum concentration of selegiline.

Theophylline: Ethinyl estradiol may inhibit the metabolism of theophylline, leading to increased plasma concentrations.

Tricyclic antidepressants (amitriptyline, imipramine, nortriptyline): Metabolism may be inhibited by combination hormonal contraceptives, increasing plasma levels of antidepressant; use caution.

Troglitazone: Troglitazone decreases the serum concentration of ethinyl estradiol and norethindrone by ~30%, leading to possible reduction in contraceptive effectiveness.


Ethanol/Nutrition/Herb Interactions

Food: CNS effects of caffeine may be enhanced if combination hormonal contraceptives are used concurrently with caffeine. Grapefruit juice increases ethinyl estradiol concentrations and would be expected to increase progesterone serum levels as well; clinical implications are unclear.

Herb/Nutraceutical: St John's wort may decrease the effectiveness of combination hormonal contraceptives by inducing hepatic enzymes. Avoid dong quai and black cohosh (have estrogen activity). Avoid saw palmetto, red clover, ginseng.


Stability

 Store at controlled room temperature of 25°C (77°F).


Mechanism of Action

 Combination hormonal contraceptives inhibit ovulation via a negative feedback mechanism on the hypothalamus, which alters the normal pattern of gonadotropin secretion of a follicle-stimulating hormone (FSH) and luteinizing hormone by the anterior pituitary. The follicular phase FSH and midcycle surge of gonadotropins are inhibited. In addition, combination hormonal contraceptives produce alterations in the genital tract, including changes in the cervical mucus, rendering it unfavorable for sperm penetration even if ovulation occurs. Changes in the endometrium may also occur, producing an unfavorable environment for nidation. Combination hormonal contraceptive drugs may alter the tubal transport of the ova through the fallopian tubes. Progestational agents may also alter sperm fertility.


Pharmacodynamics/Kinetics

Desogestrel:

Absorption: Rapid and complete

Protein binding: Etonogestrel (active metabolite): 98%, primarily to sex hormone-binding globulin

Metabolism: Hepatic via CYP2C9 to active metabolite etonogestrel (3-keto-desogestrel); etonogestrel metabolized via CYP3A4

Half-life elimination: 37.1 hours

Excretion: Urine and feces (as metabolites)


Dosage

 Oral: Adults: Female: Contraception:

Schedule 1 (Sunday starter): Dose begins on first Sunday after onset of menstruation; if the menstrual period starts on Sunday, take first tablet that very same day. With a Sunday start, an additional method of contraception should be used until after the first 7 days of consecutive administration.

For 21-tablet package: Dosage is 1 tablet daily for 21 consecutive days, followed by 7 days off of the medication; a new course begins on the 8th day after the last tablet is taken.

For 28-tablet package: Dosage is 1 tablet daily without interruption.

Schedule 2 (Day 1 starter): Dose starts on first day of menstrual cycle taking 1 tablet daily.

For 21-tablet package: Dosage is 1 tablet daily for 21 consecutive days, followed by 7 days off of the medication; a new course begins on the 8th day after the last tablet is taken.

For 28-tablet package: Dosage is 1 tablet daily without interruption.

If all doses have been taken on schedule and one menstrual period is missed, continue dosing cycle. If two consecutive menstrual periods are missed, pregnancy test is required before new dosing cycle is started.

Missed doses monophasic formulations (refer to package insert for complete information):

One dose missed: Take as soon as remembered or take 2 tablets next day

Two consecutive doses missed in the first 2 weeks: Take 2 tablets as soon as remembered or 2 tablets next 2 days. An additional method of contraception should be used for 7 days after missed dose.

Two consecutive doses missed in week 3 or three consecutive doses missed at any time:

Schedule 1 (Sunday starter): Continue to take 1 tablet daily until Sunday, then discard the rest of the pack, and a new pack is started that same day.

Schedule 2 (Day 1 starter): Current pack should be discarded, and a new pack started that same day. An additional method of contraception should be used for 7 days after missed dose.

Missed doses biphasic/triphasic formulations (refer to package insert for complete information):

One dose missed: Take as soon as remembered or take 2 tablets next day.

Two consecutive doses missed in week 1 or week 2 of the pack: Take 2 tablets as soon as remembered and 2 tablets the next day. Resume taking 1 tablet daily until the pack is empty. An additional method of contraception should be used for 7 days after a missed dose.

Two consecutive doses missed in week 3 of the pack; an additional method of contraception must be used for 7 days after a missed dose :

Schedule 1 (Sunday starter): Take 1 tablet every day until Sunday. Discard the remaining pack and start a new pack of pills on the same day.

Schedule 2 (Day 1 starter): Discard the remaining pack and start a new pack the same day.

Three or more consecutive doses missed; an additional method of contraception must be used for 7 days after a missed dose :

Schedule 1 (Sunday starter): Take 1 tablet every day until Sunday; on Sunday, discard the pack and start a new pack.

Schedule 2 (Day 1 starter): Discard the remaining pack and begin new pack of tablets starting on the same day.

Dosage adjustment in renal impairment: Specific guidelines not available; Use with caution

Dosage adjustment in hepatic impairment: Contraindicated in patients with hepatic impairment


Administration

 Administer at the same time each day.


Monitoring Parameters

 Blood pressure, breast exam, Pap smear, and pregnancy; lipid profiles in patients being treated for hyperlipidemias


Dietary Considerations

 Should be taken at same time each day.


Patient Education

 Oral contraceptives do not protect against HIV infection or other sexually-transmitted diseases. Take exactly as directed by prescriber (see package insert). You are at risk of becoming pregnant if doses are missed. Detailed and complete information on dosing and missed doses can be found in the package insert. Be aware that some medications may reduce the effectiveness of oral contraceptives; an alternate form of contraception may be needed. Check all medicines (prescription and over-the-counter), herbal and alternative products with prescriber. It is important that you check your blood pressure monthly (same day each month) and that you have an annual physical assessment, Pap smear, and vision exam while taking this medication. Avoid smoking while taking this medication; smoking increases risk of adverse effects, including thromboembolic events and heart attacks. You may experience loss of appetite (small, frequent meals will help); or constipation (increased exercise, fluids, fruit, fiber, or stool softeners may help). If you have diabetes, use accurate serum glucose testing to identify any changes in glucose tolerance; notify prescriber of significant changes so antidiabetic medication can be adjusted if necessary. Report immediately pain or muscle soreness; warmth, swelling, pain, or redness in calves; shortness of breath; sudden loss of vision; unresolved leg/foot swelling; change in menstrual pattern (unusual bleeding, amenorrhea, breakthrough spotting); breast tenderness that does not go away; acute abdominal cramping; signs of vaginal infection (drainage, pain, itching); CNS changes (blurred vision, confusion, acute anxiety, or unresolved depression); or significant weight gain (>5 lb/week). Notify prescriber of changes in contact lens tolerance. Pregnancy/breast-feeding precautions: This medication should not be used during pregnancy. If you suspect you may become pregnant, contact prescriber immediately. Consult prescriber if breast-feeding.


Nursing Implications

 Women should inform their physicians if signs or symptoms of any of the following occur: Thromboembolic or thrombotic disorders including sudden severe headache or vomiting, disturbance of vision or speech, loss of vision, numbness or weakness in an extremity, sharp or crushing chest pain, calf pain, shortness of breath, severe abdominal pain or mass, mental depression or unusual bleeding. Women should be advised to read package insert for missed-dose instructions. Women should discontinue taking the medication if they suspect they are pregnant or become pregnant.


Cardiovascular Considerations

 It is important to recognize that oral contraceptives may induce or worsen hypertension. These problems are less severe with low-dose oral contraceptives. Furthermore, oral contraceptives may precipitate thromboembolic events, particularly in women who smoke. It is important that patients on long-term oral contraceptives undergo monitoring of blood pressure and avoid cigarette use.


Dental Health: Effects on Dental Treatment

 When prescribing antibiotics, patient must be warned to use additional methods of birth control if on oral contraceptives.


Dental Health: Vasoconstrictor/Local Anesthetic Precautions

 No information available to require special precautions


Mental Health: Effects on Mental Status

 may cause depression, migraine, dizziness, anxiety, headache, and stroke


Mental Health: Effects on Psychiatric Treatment

 Barbiturates decrease the effects of oral contraceptives; may increase the toxicity of the benzodiazepines and TCAs. Associated with an increased risk of developing dementia in postmenopausal women 65 years of age when treated with conjugated estrogen and medroxyprogesterone acetate.


Dosage Forms

 Tablet:

Low-dose formulation:

Kariva™:

Day 1-21: Ethinyl estradiol 0.02 mg and desogestrel 0.15 mg [21 white tablets]

Day 22-23: 2 inactive light green tablets

Day 24-28: Ethinyl estradiol 0.01 mg [5 light blue tablets] (28s)

Mircette®:

Day 1-21: Ethinyl estradiol 0.02 mg and desogestrel 0.15 mg [21 white tablets]

Day 22-23: 2 inactive green tablets

Day 24-28: Ethinyl estradiol 0.01 mg [5 yellow tablets] (28s)

Monophasic formulations:

Apri® 28: Ethinyl estradiol 0.03 mg and desogestrel 0.15 mg [21 rose tablets and 7 white inactive tablets] (28s)

Desogen®, Solia™: Ethinyl estradiol 0.03 mg and desogestrel 0.15 mg [21 white tablets and 7 green inactive tablets] (28s)

Ortho-Cept® 28: Ethinyl estradiol 0.03 mg and desogestrel 0.15 mg [21 orange tablets and 7 green inactive tablets] (28s)

Triphasic formulation:

Cyclessa®:

Day 1-7:Ethinyl estradiol 0.025 mg and desogestrel 0.1 mg [7 light yellow tablets]

Day 8-14: Ethinyl estradiol 0.025 mg and desogestrel 0.125 mg [7 orange tablets]

Day 14-21: Ethinyl estradiol 0.025 mg and desogestrel 0.15 mg [7 red tablets]

Day 21-28: 7 green inactive tablets (28s)

Velivet™:

Day 1-7: Ethinyl estradiol 0.025 mg and desogestrel 0.1 mg [7 beige tablets]

Day 8-14: Ethinyl estradiol 0.025 mg and desogestrel 0.125 mg [7 orange tablets]

Day 14-21: Ethinyl estradiol 0.025 mg and desogestrel 0.15 mg [7 pink tablets]

Day 21-28: 7 white inactive tablets (28s)


References

"American Academy of Pediatrics Committee on Drugs. The Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics , 2001, 108(3):776-89.

"An Open-Label, Multicenter, Noncomparative Safety and Efficacy Study of Mircette, a Low-Dose Estrogen-Progestin Oral Contraceptive. The Mircette Study Group," Am J Obstet Gynecol , 1998, 179(1):S2-8.

Burkman R, Schlesselman JJ, and Zieman M, "Safety Concerns and Health Benefits Associated With Oral Contraception," Am J Obstet Gynecol , 2004, 190(4 Suppl):5-22

"Guidelines for the Use of Antiretroviral Agents in HIV-infected Adults and Adolescents. Panel on Clinical Practices for Treatment of HIV Infection," August 13, 2001. Available at: http://www.aidsinfo.nih.gov. Accessed September 5, 2001.

Holt VL, Scholes D, Wicklund KG, et al, "Body Mass Index, Weight, and Oral Contraceptive Failure Risk," Obstet Gynecol , 2005, 105(1):46-52.

Orme ML, Back DJ, and Breckenridge AM, "Clinical Pharmacokinetics of Oral Contraceptive Steroids," Clin Pharmacokinet , 1983, 8(2):95-136.

Shenfield GM and Griffin JM, "Clinical Pharmacokinetics of Contraceptive Steroids. An Update," Clin Pharmacokinet , 1991, 20(1):15-37.


International Brand Names

 Marvelon® (CA); Ortho-Cept® (CA)


A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is the first of its kind, requiring compliance with 53 standards of quality and accountability, verified by independent audit. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial process . A.D.A.M. is also a founding member of Hi-Ethics (www.hiethics.com) and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2007 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.
adam.com