Indications
Prevention of pregnancy. Regulation of menstrual cycle.
Emergency contraception (some products). Treatment
of heavy menstrual bleeding in women who choose to
use intrauterine contraception as their method of contraception
(Mirena). Treatment of heavy menstrual
bleeding in women who choose to use an oral contraceptive
as their method of contraception (Natazia).
Treatment of premenstrual dysphoric disorder (Beyaz,
Yaz, Yasmin). Management of acne in women 14 yr
who desire contraception, have no health problems,
and have failed topical treatment. Increase folate levels
in women who desire oral contraception to reduce the
risk of neural tube defects in a pregnancy that occurs
while taking or shortly after discontinuing the product.
Action
Monophasic Oral Contraceptives: Provide a fixed
dosage of estrogen/progestin over a 21-day cycle. Ovulation
is inhibited by suppression of follicle-stimulating
hormone (FSH) and luteinizing hormone (LH). May alter
cervical mucus and the endometrial environment,
preventing penetration by sperm and implantation of
the egg. Biphasic Oral Contraceptives: Ovulation is
inhibited by suppression of FSH and LH. May alter cervical
mucus and the endometrial environment, preventing
penetration by sperm and implantation of the egg.
In addition, smaller dose of progestin in phase 1 allows
for proliferation of endometrium. Larger amount in
phase 2 allows for adequate secretory development.
Triphasic Oral Contraceptives: Ovulation is inhibited
by suppression of FSH and LH. May alter cervical
mucus and the endometrial environment, preventing
penetration by sperm and implantation of the egg. Varying
doses of estrogen/progestin may more closely
mimic natural hormonal fluctuations. Fourphasic
Oral Contraceptives: Ovulation is inhibited by suppression
of FSH and LH. May alter cervical mucus and
the endometrial environment, preventing penetration
by sperm and implantation of the egg. Doses of estrogen
decrease while doses of progestin increase over the
28-day cycle. Extended-cycle: Provides continuous
estrogen/progestin for 84 days (365 days for Lybrel),
then off for 7 days (low-dose estrogen-only tablet taken
during these 7 days with LoSeasonique and Seasonique),
resulting in 4 menstrual periods/year (no periods/
year for Lybrel). Progressive Estrogen: Contains
constant amount of progestin with 3 progressive doses
of estrogen. Progestin-Only Contraceptives/Contraceptive
Implant/Intrauterine Levonorgestrel/
Medroxyprogesterone Injection: Mechanism not
clearly known. May alter cervical mucus and the endometrial
environment, preventing penetration by sperm
and implantation of the egg. Ovulation may also be suppressed.
Emergency Contraceptive Pills (ECPs):
Inhibit ovulation/fertilization; may also alter tubal transport
of sperm/egg and prevent implantation. Vaginal
Ring, Transdermal Patch: Inhibits ovulation, decreases
sperm entry into uterus, decreases likelihood
of implantation. Anti-acne effect: Combination of estrogen/progestin may increase sex hormone binding
globulin (SHBG) resulting in decreased unbound testosterone,
which may be a cause of acne. Therapeutic
Effects: Prevention of pregnancy. Decreased severity
of acne. Decrease in menstrual blood loss.
Decrease in premenstrual disphoric disorder. Decrease
in vasomotor symptoms or symptoms of vulvar and
vaginal atrophy due to menopause. Increase in folate
levels and prevention of neural tube defects.
Pharmacokinetics
Absorption: Ethinyl estradiol—rapidly absorbed;
Norethindrone—65% absorbed; Desogesrtrel and levonorgestrel—
100% absorbed; Dienogest—91%
absorbed. Others are well absorbed after oral administration.
Slowly absorbed from implant, subcutaneous or
IM injection. Some absorption follows intrauterine implantation.
Distribution: Unknown.
Protein Binding: Ethinyl estradiol—97–98%;
Drospirenone—97%; Dienogest—90%; Ulipristal—
94%.
Metabolism and Excretion: Ethinyl estradiol
and norethindrone—undergo extensive first-pass hepatic
metabolism. Mestranol—is rapidly converted to
ethinyl estradol. Desogestrel—is rapidly metabolized
to 3-keto-desogestgrel, the active metabolite. Most
agents are metabolized by the liver.
Half-life: Ethinyl estradiol—6–20 hr; Levonorgestrel—
45 hr; Norethindrone—5–14 hr; Desogestrel
(metabolite)—38 20 hr; Drospirenone—30 hr;
Norgestimate (metabolite)—12–20 hr; Dienogest—
11 hr; others—unknown; Ulipristal—32 hr.
TIME/ACTION PROFILE (prevention of
pregnancy)
ROUTE ONSET PEAK DURATION
PO 1 mo 1 mo 1 mo†
Implant 1 mo 1 mo 5 yr
Intrauterine
system
1 mo 1 mo 5 yr
IM 1 mo 1 mo 3 mo
Subcut unknown 1 wk 3 mo
†Only during mo of taking contraceptive.
Contraindications/Precautions
Contraindicated in: Hypersensitivity; OB: Pregnancy;
History of cigarette smoking or age 35 yr (q
risk of cardiovascular or thromboembolic phenomenon);
History of thromboembolic disease (e.g., DVT,
PE, MI, stroke); Protein C, protein S, or antithrombin
deficiency or other thrombophilic disorder; Valvular
heart disease; Major surgery with extended periods of
immobility; Diabetes with vascular involvement; Headache
with focal neurological symptoms; Uncontrolled
hypertension; History of breast, endometrial, or estrogen-
dependent cancer; Abnormal genital bleeding;
Liver disease; Hypersensitivity to parabens (injectable
only); Drosperinone-containing products only—
Renal impairment, liver disease, or adrenal insufficiency
(qrisk of hyperkalemia); Intrauterine levonorgestrel
only—Intrauterine anomaly, postpartum endometriosis,
multiple sexual partners, pelvic
inflammatory disease, liver disease, genital actinomycosis,
immunosuppression, IV drug abuse, untreated genitourinary
infection, history of ectopic pregnancy; Lactation:
Avoid use;qrisk of uterine rupture with
intrauterine levonorgestrel.
Use Cautiously in: Presence of other cardiovascular
risk factors (obesity, hyperglycemia, hypertension);
History or family history of hypertriglyceridemia (qrisk
of pancreatitis); History of diabetes mellitus, bleeding
disorders, concurrent anticoagulant therapy or headaches;
History of hereditary angioedema; Pedi: Avoid
use before menarche.
Adverse Reactions/Side Effects
CNS: depression, headache. EENT: contact lens intolerance,
optic neuritis, retinal thrombosis. CV: THROMBOEMBOLISM
(risk is greatest during first 6 mo of therapy
or after restarting the same or different therapy),
edema, hypertension, Raynaud’s phenomenon, thrombophlebitis.
F and E: Drosperinone-containing
products only—hyperkalemia. GI: PANCREATITIS, abdominal
cramps, bloating, cholestatic jaundice, gallbladder
disease, liver tumors, nausea, vomiting. GU:
amenorrhea, breakthrough bleeding, dysmenorrhea,
spotting, Intrauterine levonorgestrel only—uterine
imbedment/uterine rupture. Derm: melasma, rash.
Endo: hyperglycemia. MS: Injectable medroxyprogesterone
only—bone loss. Misc: weight change.
Interactions
Drug-Drug: Oral contraceptive efficacy may bepby
penicillins, chloramphenicol, barbiturates,
chronic alcohol use, carbamazepine, oxcarbazepine,
bosentan, felbamate, systemic corticosteroids,
phenytoin, topiramate, primidone, modafinil,
rifampin, rifabutin, nelfinavir, ritonavir,
darunavir/ritonavir, fosamprenavir/ritonavir, lopinavir/
ritonavir, tipranavir/ritonavir, nevirapine,
colesevelam, or tetracyclines. CYP3A4 inducers,
including barbiturates, bosentan,
carbamazepine, oxcarbazepine, phenytoin, topiramate,
felbamate, rifampin maypeffectiveness of
ulipristal; avoid concomitant use. Mayqeffects/risk of
toxicity of some benzodiazepines, beta blockers,
corticosteroids, cyclosporine, tizanidine, theophylline,
and voriconazole.qrisk of hepatic toxicity
with dantrolene (estrogen only). Indinavir, atazanavir/
ritonavir, etravirine, itraconazole, ketoconazole,
fluconazole, voriconazole, rosuvastatin,
and atorvastatin mayqeffects/risk of toxicity.
Smokingqrisk of thromboembolic phenomena (estrogen
only). Mayplevels of acetaminophen, temazepam,
lamotrigine, lorazepam, oxazepam, or
morphine. Drosperinone-containing products
only—concurrent use with NSAIDs, potassium sparing diuretics, potassium supplements, ACE
inhibitors, aldosterone receptor antagonists, or
angiotensin II receptor antagonists may result in
hyperkalemia. Drosperinone-containing products
only—concurrent use with strong CYP3A4 inhibitors,
including ketoconazole, itraconazole, voriconazole,
protease inhibitors, or clarithromycin
mayqrisk of hyperkalemia; consider monitoring K
concentrations. Ulipristal mayqlevels of P-glycoprotein
substrates, including dabigatran and digoxin.
Drug-Natural Products: Concomitant use with St.
John’s wort maypcontraceptive efficacy and cause
breakthrough bleeding and irregular menses.
Drug-Food: Grapefruit juice mayqeffects/risk of
toxicity.
Route/Dosage
Monophasic Oral Contraceptives
PO (Adults): On 21-day regimen, take first tablet on
first Sunday after menses begins (take on Sunday if
menses begins on Sunday) for 21 days, then skip 7 days
and begin again. Regimen may also be started on first
day of menses, continue for 21 days, then skip 7 days
and begin again. Some regimens contain 7 placebo tablets,
so that 1 tablet is taken every day for 28 days.
Biphasic Oral Contraceptives
PO (Adults): Given in 2 phases. First phase is 10 days
of smaller amount of progestin. Second phase is larger
amount of progestin. Amount of estrogen remains constant
for same length of time (total of 21 days), then
skip 7 days and begin again. Some regimens contain 7
placebo tablets for 28-day regimen.
Triphasic Oral Contraceptives
PO (Adults): Progestin amount varies throughout 21-
day cycle. Estrogen component stays the same or may
vary. Some regimens contain 7 placebo tablets for 28-
day regimen.
Fourphasic Oral Contraceptives
PO (Adults): Given in 4 phases. First phase contains
higher amount of estrogen and no progestin. Second
and third phases contains lower amount of estrogen,
and increasing amounts of progestin. Fourth phase
contains low dose of estrogen only. Also contains 2 placebo
tablets to complete 28-day regimen.
Extended-Cycle Contraceptive
PO (Adults): Daysee, LoSeasonique, Quartette, Seasonale
and Seasonique. Start taking first active pill on
first Sunday after menses begins (if first day is Sunday,
begin then), continue for 84 days of active pill, followed
by 7 days of placebo tablets (low-dose estrogen tablets
for Daysee, LoSeasonique, Quartette, and Seasonique),
then resume 84/7 cycle again. For Lybrel, begin taking
the first pill during the first day of the menstrual cycle
and start the next pack the day after the previous pack
ends.
Progestin-Only Oral Contraceptives
PO (Adults): Start on first day of menses. Taken daily
and continuously.
Progressive Estrogen Oral Contraceptives
PO (Adults): Estrogen amount increases q 7 days
throughout 21-day cycle. Progestin component stays
the same. Some regimens contain 7 placebo tablets for
28-day regimen.
Emergency Contraceptive
PO (Adults and Adolescents): Plan B—1 tablet
within 72 hr of unprotected intercourse followed by 1
more tablet 12 hr later; Lo/Ovral—4 white tablets
within 72 hr of unprotected intercourse followed by 4
more white tablets 12 hr later; Levlen, Nordette—4
light orange tablets within 72 hr of unprotected intercourse
followed by 4 more light orange tablets 12 hr
later; Triphasil, Tri-Levlen—4 yellow tablets within
72 hr of unprotected intercourse followed by 4 more
yellow tablets 12 hr later; Ulipristal—1 tablet as soon
as possible within 120 hr (5 days) after unprotected intercourse
or known/suspected contraceptive failure.
Injectable Contraceptive
medroxyprogesterone (Depo-Provera)
IM (Adults): 150 mg within first 5 days of menses or
within 5 days postpartum, if not breast feeding. If breast
feeding, give 6 wk postpartum; repeat q 3 mo.
medroxyprogesterone (Depo-Sub Q Provera
104)
Subcut (Adults): 104 mg within first 5 days of menses
or within 5 days postpartum, if not breast feeding. If
breast feeding, give 6 wk postpartum; repeat q 12–14
wk.
Intrauterine Contraceptive
Intrauterine (Adults): Insert one device into uterine
cavity within 7 days of menses or immediately after 1st
trimester abortion. Kyleena and Mirena should be removed
or replaced after 5 yr. Liletta and Skyla should
be removed or replaced after 3 yr.
Vaginal Ring Contraceptive
Vag (Adults): One ring inserted on or prior to day 5 of
menstrual cycle. Ring is left in place for 3 wk, then removed
for 1 wk, then a new ring is inserted.
Transdermal Patch
Transdermal (Adults): Patch is applied on day 1 of
menstrual cycle (or convenient day in first week),
changed weekly thereafter for 3 wk. Week 4 is patchfree.
Cycle is then repeated.
Acne
PO (Adults): Ortho Tri-Cyclen—Take daily for 21
days, off for 7 days.
Availability
Combination Estrogen/Progestin Oral
Contraceptives (generic available)
Oral contraceptive tablets: Usually in monthly packs
with enough (21) active tablets to complete a 28-day
cycle. Some contain 7 inert tablets to complete the cycle
with or without supplemental iron, Beyaz and Safyral
—contain 0.451 mg of levomefolate calcium/tablet.
Extended-Cycle Contraceptive
Tablets: LoSeasonique—active tablets containing
0.02 mg ethinyl estradiol, 0.1 mg levonorgestrel, and 7
tablets containing 0.01 mg ethinyl estradiol; Quartette—
42 tablets containing 0.02 mg ethinyl estradiol
and 0.15 mg levonorgestrel, 21 tablets containing
0.025 mg ethinyl estradiol and 0.15 mg levonorgestrel,
21 tablets containing 0.03 mg ethinyl estradiol and 0.15
mg levonorgestrel, and 7 tablets containing 0.01 mg
ethinyl estradiol; Seasonale—84 active tablets containing
0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel
and 7 inactive tablets; Daysee and Seasonique—
active tablets containing 0.03 mg ethinyl
estradiol, 0.15 mg levonorgestrel, and 7 tablets containing
0.01 mg ethinyl estradiol; Lybrel—28 active
tablets containing 0.09 mg levonorgestrel and 0.02 mg
ethinyl estradiol.
Levonorgestrel (generic available)
Emergency contraceptives: 2 tablets containing 0.75
mg levonorgestrel (Plan B). Implant: Rod contains 68
mg etonogestrel. Intrauterine system (Kyleena):
contains 19.5 mg levonorgestrel (releases 9 mcg/day).
Intrauterine system (Liletta): contains 52 mg levonorgestrel
(releases 15.6 mcg/day). Intrauterine system
(Mirena): contains 52 mg levonorgestrel (releases
20 mcg/day). Intrauterine system (Skyla):
contains 13.5 mg levonorgestrel (releases 14 mcg/
day).
Ulipristal
Tablets: 30 mg.
Medroxyprogesterone (generic available)
Injectable IM: 150 mg/mL. Injectable Subcutaneous:
104 mg/0.65 mL (in pre-filled syringes).
Vaginal Ring Contraceptive
Ring: delivers 0.015 mg ethinyl estradiol and 0.120 mg
etonogestrel/day.
Transdermal Patch
Patch (Xulane): contains 0.53 mg ethinyl estradiol
and 4.86 mg of norelgestromin; releases 35 mcg ethinyl
estradiol/150 mcg norelgestromin per 24 hr.
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