ESTROGEN-PROGESTIN COMBINATIONS (CONTRACEPTIVES)
Oral
Monophasic: Apri, Alesse, Aviane, Demulen, Desogen, Lessina, Levlen, Levlite, Levora, Loestrin, Lo/Ovral, Low-Ogestrel, Microgestin, Modicon, Necon, Nordette, Norinyl, Nortrel, Ortho-Cept, Ortho-Cyclen, Ortho-Novum, Ogestrel, Ovcon, Ovral, Seasonale, Yasmin, Zovia
Biphasic: Jenest, Kariva, Mircette, Necon 10/11, Ortho-Novum 10/11
Triphasic: Estrostep, Ortho-Novum 7/7/7, Ortho Tri-Cyclen, Ortho Tri-Cyclen Lo, Tri-Levlen, Tri-Norinyl, Triphasil, Trivora
Postcoital Contraceptives: Plan B, Preven
Transdermal
Ortho Evra
Intravaginal
NuvaRing
Classifications: hormones and synthetic substitutes; estrogen-progestin combinations
Prototype: Estradiol, Norgestrel
Pregnancy Category: X

Availability

Combination oral contraceptives contain one of the following estrogens and one of the following progestins. Estrogen: Ethinyl estradiol 10 mcg, 20 mcg, 25 mcg, 30 mcg, 35 mcg, 40 mcg, 50 mcg; mestranol 50 mcg; Progestin: Desogestrel 0.15 mg; drospirenone 3 mg; ethynodiol diacetate 1 mg; levonorgestrel 0.05 mg, 0.075 mg, 0.1 mg, 0.125 mg, 0.15 mg, 0.25 mg, 0.75 mg; norethindrone 0.4 mg, 0.5 mg, 0.75 mg, 1 mg; norethindrone acetate 1 mg, 1.5 mg; norgestimate 0.18 mg, 0.215 mg, 0.25 mg; norgestrel 0.3 mg, 0.5 mg; Transdermal: Norelgestromin 6 mg/0.75 mg ethinyl estradiol patch; Vaginal: Etonorgestrel 11.7 mg/2.7 mg ethinyl estradiol vaginal insert

Actions

Three types of estrogen-progestin combinations are available: (1) monophasic, fixed dosage of estrogen-progestin throughout the cycle; (2) biphasic, amount of estrogen remains the same throughout cycle, less progestin in first half of cycle and increased progestin in second half; (3) triphasic, estrogen amount is the same or varies throughout cycle, progestin amount varies.

Therapeutic Effects

Fixed combination of estrogen and progestin produces contraception by preventing ovulation and rendering reproductive tract structures hostile to sperm penetration and zygote implantation.

Uses

To prevent conception and to treat hypermenorrhea and endometriosis; postcoital contraceptive or "morning after pill"; moderate acne in females 15 y (Tri-Cyclen).

Contraindications

Pregnancy (category X), lactation, missed abortion. Familial or personal history of or existence of breast or other estrogen-dependent neoplasm, recurrent chronic cystic mastitis, history of or existence of thrombophlebitis or thromboembolic disorders, cerebral vascular or coronary artery disease, MI, serious hepatic dysfunction, hepatic neoplasm, family history of hepatic porphyria, undiagnosed abnormal vaginal bleeding, women age 40 and over, adolescents with incomplete epiphyseal closure.

Cautious Use

History of depression, preexisting hypertension, or cardiac or renal disease; impaired liver function, history of migraine, convulsive disorders, or asthma; multiparous women with grossly irregular menses, diabetes, or familial history of diabetes; gallbladder disease, lupus erythematosus, rheumatic disease, varicosities, smokers.

Route & Dosage

Contraception
Adult: PO 1 active tablet daily for 21 d, then placebo tablet or no tablets for 7 d, repeat cycle Continuous regimen (Seasonale) 1 tablet daily x 84 consecutive days. Wait 7 d for withdrawal bleeding before starting next cycle Topical Apply one patch once weekly for 3 wk, then have 1 wk patch-free before repeating the cycle Intravaginal Insert 1 ring on or before day 5 of the cycle. Remove ring after 3 wk, followed by a 1/wk rest. Then insert new ring.

Postcoital Contraception (Plan B, Preven, Ovral)
Adult: PO Ovral, 2 tablets within 72 h of intercourse, then 2 tablets 12 h later; 1 (Plan B) or 2 (Preven) tablets within 72 h of unprotected intercourse, take second dose of 1 (Plan B) or 2 (Preven) tablets 12 h later

Administration

Adverse Effects (1%)

Body as a Whole: Paresthesias. CV: Malignant hypertension, thrombotic and thromboembolic disorders, mild to moderate increase in BP, increase in size of varicosities, edema. Endocrine: Estrogen excess (nausea, bloating, menstrual tension, cervical mucorrhea, polyposis, chloasma, hypertension, migraine headache, breast fullness or tenderness, edema); estrogen deficiency (hypomenorrhea, early or mid-cycle breakthrough bleeding, increased spotting); progestin excess (hypomenorrhea, breast regression, vaginal candidiasis, depression, fatigue, weight gain, increased appetite, acne, oily scalp, hair loss); progestin deficiency (late-cycle breakthrough bleeding, amenorrhea). GI: Nausea, cholelithiasis, gallbladder disease, cholestatic jaundice, benign hepatic adenomas; diarrhea, constipation, abdominal cramps. Metabolic: Decreased glucose tolerance, pyridoxine deficiency (see also diagnostic test interferences), acute intermittent porphyria. Skin: Rash (allergic), photosensitivity (photoallergy or phototoxicity), irritation from patch. Special Senses: Unexplained loss of vision, optic neuritis, proptosis, diplopia, change in corneal curvature (steepening), intolerance to contact lenses, retinal thrombosis, papilledema. Urogenital: Ureteral dilation, increased incidence of urinary tract infection, hemolytic uremia syndrome, renal failure, increased risk of congenital anomalies, decreased quality and quantity of breast milk, dysmenorrhea, increased size of preexisting uterine fibroids, menstrual disorders. Foreign body sensation, coital problems, device expulsion, vaginal discomfort, vaginitis, leukorrhea from ring.

Diagnostic Test Interference

oral contraceptives (OCs) increase BSP retention, prothrombin and coagulation factors II, VII, VIII, IX, X; platelet agregability, thyroid-binding globulin, PBI, T4: transcortin; corticosteroid, triglyceride and phospholipid levels; ceruloplasmin, aldosterone, amylase, transferrin; renin activity, vitamin A. OCs decrease antithrombin III, T3 resin uptake, serum folate, glucose tolerance, albumin, vitamin B12 and reduce the metyrapone test response.

Interactions

Drug: Aminocaproic acid may increase clotting factors, leading to hypercoagulable state; barbiturates, anticonvulsants, antibiotics, rifampin, antifungals reduce efficacy of OCs and increase incidence of breakthrough bleeding and risk of pregnancy. May decrease efficacy of lamotrigine.

Pharmacokinetics

Absorption: Oral: Readily absorbed from GI tract; readily absorbed from transdermal patch placed on abdomen, buttock, upper outer arm and upper torso (excluding breast). Vaginal insert: norgestrel 100% absorbed, ethinyl estradiol 56% absorbed. Peak: Patch: 48 h. Duration: Patch: 1 wk. Distribution: Widely distributed; crosses placenta; small amount distributed into breast milk. Metabolism: Metabolized in liver. Elimination: Excreted in urine and feces. Half-Life: 6–45 h oral. Following removal of the patch: norelgestromin 28 h, ethinyl estradiol 17 h; vaginal ring: norgestrel 29 h; ethinyl estradiol 45 h.

Nursing Implications

Assessment & Drug Effects

Patient & Family Education


Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug