Yes

Contraceptive

Prevention of pregnancy; treatment of hypermenorrhea, endometriosis, female hypogonadism

X

Thrombophlebitis, undiagnosed vaginal bleeding, hypersensitivity to ethinyl estradiol or any component, known or suspected pregnancy, carcinoma of the breast, estrogen-dependent tumor

Use of any progestin during the first 4 months of pregnancy is not recommended; use with caution in patients with asthma, seizure disorders, migraine, cardiac, renal or hepatic impairment, cerebrovascular disorders or history of breast cancer, past and present thromboembolic disease, smokers >35 years of age. Products containing 50 mcg of estrogen should be used only when medically indicated (there is a dose-related risk of vascular disease).

>10%:

Cardiovascular: Peripheral edema

Endocrine & metabolic: Enlargement of breasts, breast tenderness

Gastrointestinal: Nausea, anorexia, bloating

1% to 10%:

Central nervous system: Headache

Endocrine & metabolic: Increased libido

Gastrointestinal: Vomiting, diarrhea

<1%: Hypertension, thromboembolism, stroke, myocardial infarction, edema, depression, dizziness, anxiety, chloasma, melasma, rash, decreased glucose tolerance, amenorrhea, alterations in frequency and flow of menses, increased triglycerides and LDL, GI distress, cholestatic jaundice, intolerance to contact lenses, increased susceptibility to Candida infection, breast tumors

Hormonal Balance in Oral Contraceptives:

Estrogen Excess: Nausea, bloating, cervical mucorrhea, polyposis, melasma, migraine headache, breast fullness or tenderness, edema, hypertension

Estrogen Deficiency: Early or midcycle breakthrough bleeding, increased spotting, hypomenorrhea

Progestin Excess: Increased appetite, weight gain, tiredness, fatigue, hypomenorrhea, acne, oily scalp*, hair loss, hirsutism*, depression, monilial vaginitis, breast regression

Progestin Deficiency: Late breakthrough bleeding, amenorrhea, hypermenorrhea

*Result of androgenic activity of progestins

Pharmacological effects of progestins used in oral contraceptives:

Norgestrel/levonorgestrel:

Progestin: Pronounced effect

Estrogen: No effect

Antiestrogen: Moderate effect

Androgen: Pronounced effect

Ethynodiol diacetate:

Progestin: Moderate effect

Estrogen: Slight effect*

Antiestrogen: Slight effect*

Androgen: Slight effect

Norethindrone acetate:

Progestin: Slight effect

Estrogen: Slight effect

Antiestrogen: Pronounced effect

Androgen: Slight effect

Norethindrone:

Progestin: Slight effect

Estrogen: Slight effect*

Antiestrogen +*

Androgen: Slight effect

Norethynodrel:

Progestin: Slight effect

Estrogen: Pronounced effect

Antiestrogen: No effect

Androgen: No effect

*Has estrogenic effect at low doses; may have antiestrogenic effect at higher doses.

Toxicity is unlikely following single exposures of excessive doses

Any treatment following emesis and charcoal administration should be supportive and symptomatic

Ethinyl estradiol is a CYP3A3/4 and 3A5-7 enzyme substrate; CYP1A2 enzyme inhibitor

Increased toxicity of acetaminophen, anticoagulants, benzodiazepines, caffeine, corticosteroids, metoprolol, theophylline, tricyclic antidepressants

Combination oral 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, oral 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. Oral contraceptive drugs may alter the tubal transport of the ova through the fallopian tubes. Progestational agents may also alter sperm fertility.

Ethinyl estradiol:

Absorption: Absorbed well from GI tract

Protein binding: 98%

Metabolism: Inactivated by liver

Half-life: 6-20 hours

Elimination: Bile and urine, enterohepatic recycling

Levonorgestrel:

Metabolism: Does not undergo first-pass effect; chiefly metabolized by reduction and conjugation

Bioavailability: Completely

Half-life, terminal: 11-45 hours

Time to peak: 0.5-2 hours

Oral: Adults: Female: Contraception:

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: An additional method of contraception must be used for 7 days after a missed dose.

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

Schedule 2 (Day 1 starter): Current pack should be discarded, and a new pack should be started that same day.

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.

Should be administered with food at same time each day

Decreased antithrombin III

Decreased serum folate concentration

Increased prothrombin and factors VII, VIII, IX, X

Increased platelet aggregability

Increased thyroid binding globulin

Increased total thyroid hormone (T₄)

Increased serum triglycerides/phospholipids

No information available to require special precautions

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

Inform your physician 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

If any doses are missed, alternative contraceptive methods should be used for the next 2 days or until 2 days into the new cycle

Discontinue taking the medication if you suspect you are pregnant or become pregnant

Inform your physician 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. If any doses are missed, alternative contraceptive methods should be used for the next 2 days or until 2 days into the new cycle. Discontinue taking the medication if you suspect you are pregnant or become pregnant.

Tablet:

Levlen®, Levora®, Nordette®: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg (21s, 28s)

Tri-Levlen®, Triphasil®: Phase 1 (6 brown tablets): Ethinyl estradiol 0.03 mg and levonorgestrel 0.05 mg; Phase 2 (5 white tablets): Ethinyl estradiol 0.04 mg and levonorgestrel 0.075 mg; Phase 3 (10 yellow tablets): Ethinyl estradiol 0.03 mg and levonorgestrel 0.125 mg (21s, 28s)

PREVEN™: Ethinyl estradiol 0.05 mg and levonorgestrel 0.25 mg (4 pills per kit along with a pregnancy test)