Version May 2024
Cigarette smoking increases the risk of serious cardiovascular events from combined hormonal contraceptive use. This risk increases with age, particularly in women >35 years of age, and with the number of cigarettes smoked. For this reason, combination hormonal contraceptives are contraindicated in women who are >35 years of age and smoke.
Ethinyl estradiol and levonorgestrel is contraindicated in women with a BMI ≥30 kg/m2. Compared to women with a lower BMI, women with a BMI ≥30 kg/m2 had reduced effectiveness and may have a higher risk of venous thromboembolism events.
Abnormal uterine bleeding, acute (off-label use):
Note: For use in hemodynamically stable patients without high risk for thrombosis (Zacur 2023). Use active (hormonal) tablets from monophasic combinations containing at least 30 mcg of ethinyl estradiol; do not use multiphasic combinations or inactive (placebo) tablets (Ref). Concurrent use of an antiemetic may improve tolerability. After resolution of acute bleeding, transition to maintenance therapy (eg, monthly or extended cycle oral contraceptive regimen, levonorgestrel IUD) (Ref).
Oral: Multiple regimens have been described:
One tablet 3 times per day for 7 days, then taper as tolerated to maintain control of bleeding (Ref)
or
One tablet every 6 to 8 hours until cessation of bleeding (24 to 48 hours), then taper as tolerated to maintain control of bleeding (Ref)
or
Five tablets on day 1, then four tablets on day 2, then three tablets on day 3, then two tablets on day 4, then one tablet daily; continue 1 tablet daily for at least 1 week after acute bleeding subsides, then discontinue for 3 to 5 days to allow for a withdrawal bleed. The daily dose may be administered as a single dose or in divided doses to improve tolerability (Ref).
Abnormal uterine bleeding, nonacute (off-label use): Note: Not indicated for management of acute abnormal bleeding (ie, excessively heavy or prolonged bleeding that requires urgent evaluation). Product selection: Other hormonal contraceptive combinations available as preparations with shorter hormone-free intervals (ie, ≤4 hormone-free days per month) may reduce withdrawal bleeding and are preferred by some experts (Ref).
Oral: Refer to dosing for "Contraception" (Ref).
Contraception:
Oral: One tablet once daily in the order presented in the blister pack.
Patients not currently using a hormonal contraceptive: Note: If reasonably sure the patient is not pregnant, may be initiated at any time during the menstrual cycle (Ref); however, Sunday start is advised for extended cycle (ie, 91 day) regimens. For non-extended cycle regimens, quick start method is preferred by some experts (Ref).
Day 1 start: Start on first day of menstrual cycle. Additional method of contraception is not required (Ref).
Quick start: Start on the day the patient receives the prescription (Ref). If initiated >5 days after the onset of menses, use an additional method of contraception (nonhormonal) until 7 days of consecutive administration (Ref).
Sunday start: Start on first Sunday after onset of menstruation; if the menstrual period starts on Sunday, take first tablet on same day. If initiated >5 days after onset of menses, use an additional method of contraception (nonhormonal) until 7 days of consecutive administration (Ref).
|
Current method |
Instructions for switching to oral ethinyl estradiol/levonorgestrel |
|---|---|
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a Refer to prescribing information for product-specific information; information provided in the manufacturer's labeling for 13-week packages may vary. Additional guidance is also available (see CDC [Curtis 2016a]). | |
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Combined oral contraceptive (COC) |
Start ethinyl estradiol/levonorgestrel on the day a new pack of the previous COC would be started. |
|
Implant |
Start ethinyl estradiol/levonorgestrel on the day of implant removal. |
|
Injection |
Start ethinyl estradiol/levonorgestrel on the day the next injection would have been scheduled. |
|
Intrauterine device (IUD) |
Start ethinyl estradiol/levonorgestrel on the day of IUD removal. If ethinyl estradiol/levonorgestrel is not initiated on the first day of menses or the day of IUD removal, use an additional method of contraception (nonhormonal) for the first 7 days of consecutive administration. |
|
Progestin only pill |
Start ethinyl estradiol/levonorgestrel on the day after the last progestin tablet was taken. |
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Transdermal system |
Start ethinyl estradiol/levonorgestrel on the day when the next application would be scheduled. |
|
Vaginal ring |
Start on the day when the next insertion would be scheduled. |
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a Refer to prescribing information for product-specific information; information provided in the manufacturer's labeling for 13-week packages may vary. Additional guidance is also available (see CDC [Curtis 2016a]). | |
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Use after childbirth (not breastfeeding) |
Do not initiate ethinyl estradiol/levonorgestrel during the first 4 weeks after delivery due to the increased risk of thromboembolic disease. If postpartum menstrual cycles have returned, follow instructions for patients not currently using a hormonal contraceptive. If menstrual cycles have not returned, consider the possibility of ovulation occurring prior to use. |
|
Use after first trimester abortion or miscarriage |
Ethinyl estradiol/levonorgestrel can be started immediately. If not started within 5 days of a first trimester abortion or miscarriage, use an additional method of contraception (nonhormonal) for the first 7 days of consecutive administration. |
|
Use after second trimester abortion or miscarriage |
Do not initiate ethinyl estradiol/levonorgestrel until 4 weeks after second trimester abortion or miscarriage due to the increased risk of thromboembolic disease. When started, follow instructions for patients not currently using a hormonal contraceptive. |
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a Refer to prescribing information for product-specific information. Additional guidance is also available (see CDC [Curtis 2016a]). | |
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If 1 active tablet is missed in weeks 1, 2 or 3 |
Take the missed dose as soon as possible. Continue taking 1 tablet daily until pack is finished. |
|
If 2 active tablets are missed in week 1 or week 2 |
Take the 2 missed doses as soon as possible and take the next 2 active tablets the next day. Continue taking 1 tablet a day until the pack is finished. Use backup (nonhormonal) contraception until active tablets have been taken for 7 consecutive days after the missed tablets. |
|
If 2 active tablets are missed during week 3, or ≥3 active tablets are missed in a row during weeks 1, 2 or 3 |
Day 1 start:
Sunday start:
Use backup (nonhormonal) contraception until active tablets have been taken for 7 consecutive days after the missed tablets. |
|
a Refer to prescribing information for product-specific information. Additional guidance is also available (see CDC [Curtis 2016a]). | |
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If 1 active tablet is missed in days 1 through 84 |
Take the missed dose as soon as possible. Take the next tablet at the regular time. Then continue taking 1 tablet daily until pack is finished. |
|
If 2 consecutive active tablets are missed in days 1 through 84 |
Take the 2 missed doses as soon as possible and take the next 2 active tablets the next day. Continue taking 1 tablet a day until the pack is finished. Use backup (nonhormonal) contraception until active tablets have been taken for 7 consecutive days after the missed tablets. |
|
If ≥3 active tablets are missed in a row during days 1 through 84 |
Do not take missed tablets. Continue taking one tablet daily until 91-day course is finished. Use backup (nonhormonal) contraception until active tablets have been taken for 7 consecutive days after the missed tablets. |
|
If any tablets are missed on days 85 to 91 |
Throw away the missed tablets, continue taking remaining tablets until the pack is finished. Backup contraception is not needed. |
Transdermal: Note: Indicated for patients with BMI <30 kg/m2. Apply one new patch each week for 3 weeks (21 total days); followed by one week that is patch-free. Apply each patch on the same day each week ("patch change day") and wear only one patch at a time. Do not allow more than 7 days to pass during the patch-free interval.
Patients not currently using a hormonal contraceptive:
Apply 1 patch during the first 24 hours of menstruation. If the first patch is applied after the first 24 hours of menstruation, use an additional method of contraception (nonhormonal) until 7 days of consecutive administration . Examples of nonhormonal contraception include a condom and spermicide or a diaphragm and spermicide.
|
Current method |
Instructions for switching to transdermal ethinyl estradiol/levonorgestrel |
|---|---|
|
Combined oral contraceptive (COC) |
Complete current oral pill cycle and apply the first patch on the day the next pill cycle would be started. If there is no menstrual bleeding within 7 days of taking the last active tablet, ensure the patient is not pregnant prior to first application. If patch is applied later than 7 days after the last active pill, use an additional method of contraception (nonhormonal) until after the first 7 days of consecutive administration. |
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Implant |
Apply ethinyl estradiol/levonorgestrel on the day of implant removal. |
|
Injection |
Apply ethinyl estradiol/levonorgestrel on the day the next injection would have been scheduled. |
|
Intrauterine device (IUD) |
Apply ethinyl estradiol/levonorgestrel on the day of IUD removal. |
|
Progestin only pill |
Complete current oral pill cycle and apply the first patch on the day the next pill cycle would be started. |
|
Transdermal system |
Complete the current transdermal system cycle and apply the first ethinyl estradiol/levonorgestrel patch on the day when the next application would be scheduled. If there is no menstrual bleeding within 7 days of taking removing the last transdermal system, the patient can initiate the first patch application; however, assess pregnancy status. If patch is applied later than 7 days after the last transdermal system was removed, use an additional method of contraception (nonhormonal) until after the first 7 days of consecutive administration. |
|
Vaginal ring |
Complete current vaginal ring cycle and apply the first patch on the day the next vaginal ring would be inserted. If there is no menstrual bleeding within 7 days of removing the vaginal ring, ensure the patient is not pregnant prior to first application. If the patch is applied later than 7 days after the vaginal ring was removed, use an additional method of contraception (nonhormonal) until after the first 7 days of consecutive administration. |
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Use after childbirth (not breastfeeding) |
Do not initiate TRANSDERMAL ethinyl estradiol/levonorgestrel during the first 4 weeks after delivery due to the increased risk of venous thromboembolism. Rule out pregnancy prior to treatment if menstrual periods have not restarted. Use an additional method of contraception (nonhormonal) until after the first 7 days of consecutive administration. |
|
Use after first trimester abortion or miscarriage |
Ethinyl estradiol/levonorgestrel can be started immediately. If not started within 5 days of a first trimester abortion or miscarriage, use an additional method of contraception (nonhormonal) for the first 7 days of consecutive administration. |
|
Use after second trimester abortion or miscarriage |
Do not initiate ethinyl estradiol/levonorgestrel until 4 weeks after second trimester abortion or miscarriage due to the increased risk of venous thromboembolism. |
|
Forgetting to apply the patch at the start of cycle (week 1/day 1) |
Apply first patch as soon as remembering, using this day of the week as the new "patch change day" from this point on. An additional method of contraception (nonhormonal) must be used until after the first 7 days of consecutive administration. |
|
Forgetting to change patch in the middle of the cycle (week 2/day 8 or week 3/day 15) |
If <48 hours from normal "patch change day," apply new patch immediately. No backup contraception is needed. If ≥48 hours from normal "patch change day," apply a new patch and use this day of the week as the new "patch change day" from this point on. An additional method of contraception (nonhormonal) must be used until after the first 7 days of consecutive administration. |
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Forgetting to remove patch at end of cycle (week 4/day 22) |
Take off as soon as remembering, start new cycle on usual "patch change day." |
Emergency contraception (off-label use): Oral: One dose followed by a second dose 12 hours later. Each dose should contain a minimum of ethinyl estradiol 0.1 mg and levonorgestrel 0.5 mg. Although no longer available in a dedicated dosage form, available combination oral contraceptive pills can be used to achieve this dose. Begin treatment for emergency contraception as soon as possible; however, treatment is still moderately effective if used within 5 days after unprotected or inadequately protected intercourse. Although routine use of antiemetics is not recommended, pretreatment may be considered for specific patients (Ref).
Hyperlactation (off-label use): Oral: One tablet once daily using a preparation containing ethinyl estradiol 0.02 to 0.035 mg. Do not initiate treatment <6 weeks' postpartum; discontinue once milk production decreases (may significantly decrease within 7 days) (Ref).
Menstrual suppression (off-label use): Oral: One tablet once daily in the order presented in the blister pack, omitting placebo tablets, and continuing with a new pack of active tablets. May consider initiating as cyclic therapy for 3 to 6 months, then transitioning to extended cycles. Products containing ethinyl estradiol 0.02 mg generally have more breakthrough bleeding than those with higher doses (Ref).
Polycystic ovary syndrome in patients with hyperandrogenism and/or menstrual irregularities (off-label use): Oral: One tablet once daily in the order presented in the blister pack (Ref). Note: Use a preparation with the lowest effective dose of ethinyl estradiol (eg, 0.02 to 0.03 mg) (Ref). Refer to dosing for “Contraception” for additional dosing instructions if also used for the prevention of pregnancy.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution and monitor blood pressure closely.
Contraindicated in patients with hepatic impairment.
(For additional information see "Ethinyl estradiol and levonorgestrel: Pediatric drug information")
Contraception, oral:
Postmenarche patients: Oral: 1 tablet once daily. General dosing guidelines; refer to prescribing information for product-specific information:
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.
Schedule 2 (Day 1 starter): Dose starts on first day of menstrual cycle taking 1 tablet daily.
Contraception, topical (in females with BMI <30 kg/m2) :
Postmenarche patients: Topical:
Apply 1 patch during the first 24 hours of menstruation in patients not currently using hormonal contraception. Apply 1 new patch each week for 3 weeks (21 total days); followed by 1 week that is patch-free. Each patch should be applied on the same day each week ("patch change day") and only 1 patch should be worn at a time. No more than 7 days should pass during the patch-free interval. If the first patch is applied after the first 24 hours of menstruation, nonhormonal backup contraception is needed for the first 7 days of the first cycle. Examples of nonhormonal contraception include a condom and spermicide or a diaphragm and spermicide.
Switching from a different contraceptive:
Oral contraceptive, transdermal patch, or vaginal ring: Complete current cycle and apply the first patch on the day the next pill cycle would be started or ring would be inserted. If there is no menstrual bleeding within 7 days of taking the last active tablet or removing the last vaginal ring, the patient can initiate the first patch application; however, assess pregnancy status. If patch is applied later than 7 days after the last active pill or removal of the vaginal ring, an additional method of contraception (nonhormonal) should be used until after the first 7 days of consecutive administration.
Injection, IUD, implant, or progestin-only oral contraceptive: Apply the first patch on the day the next injection, IUD, implant, or pill cycle would normally start.
Emergency contraception:
Note: Ethinyl estradiol in combination with levonorgestrel is effective and recommended as an alternative method for the management of emergency contraception when other methods are not available. The use of other methods is preferred due to increased adverse effects and decreased efficacy observed with this combination (Ref).
Postmenarche patients: Oral: 1 dose followed by a second dose 12 hours later. Each dose should contain a minimum of ethinyl estradiol 100 mcg and levonorgestrel 0.5 mg. Note: Although no longer available in a dedicated dosage form, available combination oral contraceptive pills can be used to achieve this dose. Treatment for emergency contraception should begin as soon as possible; however, treatment is still moderately effective if used within 5 days after unprotected or inadequately protected intercourse. Although routine use of antiemetics is not recommended, pretreatment may be considered for specific patients (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution and monitor blood pressure closely.
Contraindicated in patients with hepatic impairment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Unless otherwise noted, reactions listed are based on reports for other agents in this same pharmacologic class (oral contraceptives) and may not be specifically reported for ethinyl estradiol/levonorgestrel.
1% to 10%:
Endocrine & metabolic: Weight gain (transdermal patch: 2%)
Gastrointestinal: Nausea (oral; transdermal: 4%)
Genitourinary: Dysmenorrhea (oral; transdermal: 2%)
Local: Application site reaction (transdermal: 6%)
Nervous system: Headache (oral; transdermal: 4%)
Frequency not defined:
Cardiovascular: Acute myocardial infarction, arterial thromboembolism, Budd-Chiari syndrome, cerebral thrombosis, cerebrovascular accident, deep vein thrombosis, edema, hypertension, local thrombophlebitis, mesenteric thrombosis, pulmonary embolism, retinal thrombosis, venous thromboembolism, venous thrombosis, worsening of varicose veins
Dermatologic: Acne vulgaris, allergic skin rash, chloasma, erythema multiforme, erythema nodosum, loss of scalp hair
Endocrine & metabolic: Amenorrhea, breast changes (including breast hypertrophy, breast secretion, breast tenderness, mastalgia), change in libido, change in menstrual flow, changes in serum lipids, decreased serum folate level, exacerbation of porphyria, fluid retention, hirsutism, impaired glucose tolerance/prediabetes, infrequent uterine bleeding, premenstrual syndrome, weight changes
Gastrointestinal: Abdominal cramps, abdominal pain, bloating, change in appetite, cholecystitis, cholelithiasis, colitis, gallbladder disease, pancreatitis, vomiting
Genitourinary: Abnormal cervical or vaginal Papanicolaou smear, breakthrough bleeding, cervical ectropion, cervical erosion, change in cervical secretions, cystitis-like syndrome, endocervical hyperplasia, ectopic pregnancy, infertility (temporary), lactation insufficiency (with use immediately postpartum), spotting, vulvovaginal candidiasis, vaginitis
Hematologic & oncologic: Hemolytic-uremic syndrome, hemorrhagic eruption, uterine fibroid enlargement
Hepatic: Cholestatic jaundice, hepatic adenoma, hepatic focal nodular hyperplasia, hepatic neoplasm (benign)
Hypersensitivity: Anaphylaxis (including angioedema, circulatory shock, respiratory collapse, urticaria), nonimmune anaphylaxis
Nervous system: Cerebral hemorrhage, depression, dizziness, exacerbation of tics, major depressive disorder, migraine, mood changes, nervousness, suicidal ideation
Neuromuscular & skeletal: Exacerbation of systemic lupus erythematosus
Ophthalmic: Cataract, change in corneal curvature (steepening), contact lens intolerance, optic neuritis (with or without partial or complete loss of vision)
Otic: Auditory disturbance
Renal: Renal insufficiency
Respiratory: Rhinitis
Hypersensitivity to ethinyl estradiol, levonorgestrel, or any component of the formulation; breast cancer (current or a history of; may be hormonal-sensitive); hepatic tumors, acute viral hepatitis or severe (decompensated) cirrhosis; hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir; liver disease; undiagnosed abnormal uterine bleeding; BMI ≥30 kg/m2 (patch only).
Patients at high risk of arterial or venous thrombotic diseases including: Cerebrovascular disease; coronary artery disease; diabetes mellitus with any of the following: age >35 years, duration >20 years, hypertension, vascular disease, or other end-organ damage; deep vein thrombosis or pulmonary embolism (current or history of); hypercoagulopathies (inherited or acquired); hypertension (uncontrolled); hypertension with vascular disease; migraine headaches with any of the following: age >35 years, aura, or focal neurological symptoms; thrombogenic valvular or rhythm diseases of the heart (eg, subacute bacterial endocarditis with valvular disease or atrial fibrillation); smoking if >35 years of age.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindication (not in the US labeling): Ocular lesions due to ophthalmic vascular disease including partial or complete loss of vision or defect in visual fields; severe dyslipoproteinemia; persistent blood pressure ≥160 mm Hg systolic and ≥100 mm Hg diastolic; myocardial infarction (current or history of); prodromi of a thrombosis (eg, transient ischemic attack, angina pectoris; current or history of); major surgery associated with an increased risk of postoperative thromboembolism; prolonged immobilization; steroid-dependent jaundice, cholestatic jaundice, history of jaundice of pregnancy; pancreatitis if associated with severe hypertriglyceridemia (current or history of); women with hereditary or acquired predisposition for arterial or venous thrombosis, for example: Factor V Leiden mutation and activated protein C (APC-) resistance, antithrombin-III-deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia (eg, due to MTHFR C677T, A1298 mutations), prothrombin mutation G20210A, and antiphospholipid-antibodies (anticardiolipin antibodies, lupus anticoagulant); hepatitis C drug combinations containing glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir; hereditary or acquired thrombophilias; abnormal liver function testing; estrogen-dependent tumors (current or history of); pregnancy (current or suspected).
Concerns related to adverse effects:
• Bleeding irregularities: Amenorrhea, spotting, and unscheduled bleeding may occur, primarily during the first 3 months of therapy. Evaluate unscheduled or breakthrough bleeding that persists or occurs after previously regular cycles to rule out malignancy or pregnancy. Amenorrhea or oligomenorrhea may occur after discontinuing combination hormonal contraceptives, especially when such a condition was preexistent.
• Cervical cancer: The use of combination hormonal contraceptives has been associated with a slightly increased risk of cervical cancer; however, studies are not consistent, and the risk may be related to the specific histologic type of cervical cancer, duration of contraceptive use and other factors (Asthana 2020; Gadducci 2020). Theoretically, use may affect prognosis of existing disease. Patients awaiting treatment for cervical cancer may use combination hormonal contraceptives (CDC [Curtis 2016b]).
• Chloasma: Combination hormonal contraceptives, as well as sun exposure and pregnancy, are triggers for chloasma. Avoid exposure to sun or UV radiation during therapy in patients with a susceptibility to chloasma or additional risk factors.
• Cholestasis: Risk of cholestasis may be increased with previous cholestatic jaundice of pregnancy or jaundice with prior hormonal contraceptive use.
• Hepatic adenomas or carcinomas: Use of combination hormonal contraceptives is associated with hepatic adenomas (rare); rupture may cause fatal intra-abdominal hemorrhage. Long-term use may be associated with an increased risk of hepatocellular carcinoma (rare).
• Lipid effects: Combination hormonal contraceptives may adversely affect lipid levels, including serum triglycerides. Patients with hypertriglyceridemia or a family history of hypertriglyceridemia may be at increased risk of pancreatitis when using combination hormonal contraceptives. Consider alternative contraception for patients with uncontrolled dyslipidemia.
• Retinal thrombosis: Discontinue if unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions occur and immediately evaluate for retinal thrombosis.
• Thromboembolic disorders: Discontinue use of combination hormonal contraceptives if an arterial or venous thromboembolic event (VTE) occurs. The increased risk of VTE associated with combination hormonal contraceptives is greatest during first year of use and less than the risk associated with pregnancy; some studies suggest this risk may be higher in preparations with third- or fourth-generation progestins and/or high-dose ethinyl estradiol. Patients with inherited thrombophilias (eg, protein C or S deficiency, factor V Leiden mutation, prothrombin mutation, antithrombin deficiency) may have increased risk of VTE. Age >35 years, hypertension, obesity, and tobacco use also increase the risk of thromboembolic events in patients taking combination hormonal contraceptives (Abou-Ismail 2020; ASRM 2017; CDC [Curtis 2016b]). Combination hormonal contraceptives may also increase the risk of arterial thrombosis (eg, myocardial infarction, stroke); do not use in patients with a history of stroke or ischemic heart disease (CDC [Curtis 2016b]).
Disease-related concerns:
• Bariatric surgery: Fertility is increased following bariatric surgery. All available forms of contraception can be considered following bariatric surgery, considering the patient's body weight and time since surgery. However, long-acting reversible non-oral contraceptives (eg, implants, intrauterine devices) may be preferred. Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy both have the potential to expedite transit through the small bowel. RYGB may not significantly alter the absorption of oral estrogen or progestogens (limited evidence following a single dose). However, gastric and small bowel transit is not well studied following chronic oral dosing, therefore contraceptive efficacy cannot be guaranteed. Oral contraceptives may be used in patients having adjustable gastric banding unless there is diarrhea or vomiting. Reliable contraception using oral contraceptives cannot be guaranteed following jejunoileal (JI) bypass, biliopancreatic diversion (BPD), single anastomosis duodeno-ilial bypass (SADI), or omega-loop gastric bypass. Discontinue estrogen-containing birth control at least 4 weeks prior to bariatric surgery and resume no earlier than 4 weeks after surgery to minimize risk of VTE (Ciangura 2019; Mechanick 2020; Moreira de Brito 2021; Shawe 2019).
• Breast cancer: Available studies have not shown a consistent association with combination hormonal contraceptives and breast cancer risk. Multiple studies have shown no association in current or ever users (current or past); other studies have shown a small increased risk in current users (higher risk in current users with longer durations of use) and recent users (<6 months since last use). In patients at risk for breast cancer due to family history or susceptibility genes (BRCA1, BRCA2), it is unclear if combination hormonal contraceptives increase the risk for breast cancer. However, breast cancer is a hormonal sensitive tumor and the prognosis for patients with a current or recent history of breast cancer may be worse with combination hormonal contraceptive use (CDC [Curtis 2016b]; SGO/ASRM [Chen 2019]).
• Cardiovascular disease: Use with caution in patients with risk factors for cardiovascular disease (eg, hypertension, low HDL, high LDL, high triglycerides, older age, diabetes, patients who smoke); use of combination hormonal contraceptives may increase the risk of cardiovascular disease (CDC [Curtis 2016b]).
• Depression: Use with caution in patients with a high risk of depression; discontinue if serious depression recurs.
• Diabetes: May impair glucose tolerance; use caution in patients with diabetes. In general, use of combination hormonal contraceptives has limited effects on daily insulin needs and no long-term effects on diabetes control in patients with nonvascular disease. Evaluate contraceptive use in patients with concomitant nephropathy, neuropathy, retinopathy, other vascular diseases, or diabetes >20 years' duration based on the severity of the condition (CDC [Curtis 2016b]).
• Endometrial cancer: The risk of endometrial cancer is decreased in patients using combination hormonal contraceptives. Patients awaiting treatment for endometrial cancer may use combination hormonal contraceptives (CDC [Curtis 2016b]).
• Gallbladder disease: Combination hormonal contraceptives may cause a small increased risk of gallbladder disease or may worsen existing gallbladder disease (CDC [Curtis 2016b]).
• Hepatic impairment: Contraceptive steroids may be poorly metabolized in patients with hepatic impairment. Discontinue if jaundice develops during therapy or if liver function becomes abnormal. Consider use of combination hormonal contraceptives in patients with mild (compensated) cirrhosis; do not use in patients with severe (decompensated) cirrhosis (CDC [Curtis 2016b]).
• Hepatitis: Initiation of combination hormonal contraceptives is not recommended in patients with acute viral hepatitis or during a flare. Continued use in patients with chronic hepatitis has not been shown to increase the rate or severity of cirrhotic fibrosis or hepatocellular carcinoma. Continued use in patients who are carriers has not been shown to trigger liver failure or severe hepatic dysfunction (CDC [Curtis 2016b]).
• Hereditary angioedema: Estrogens may induce or exacerbate symptoms in patients with hereditary angioedema.
• Hypertension: The risk of hypertension may be increased with age, dose, and duration of use. Do not use combination hormonal contraceptives in patients with hypertension and vascular disease, or persistent BP values ≥160 mm Hg systolic or ≥100 mm Hg diastolic. The risks of use may not outweigh the benefits of treatment in patients with less severe hypertension (140 to 159 mm Hg systolic or 90 to 99 mm Hg diastolic) or those with hypertension that is adequately controlled (CDC [Curtis 2016a]). Consider other risk factors for cardiovascular disease (eg, older age, smoking, diabetes) when prescribing contraceptives (CDC [Curtis 2016b]). Monitor BP in patients with well-controlled hypertension; discontinue therapy if BP rises significantly.
• Migraine: Evaluate new, recurrent, severe, or persistent headaches and discontinue use if indicated. Use of combination hormonal contraceptives may be considered in patients who have migraines without aura (including menstrual migraines) (CDC [Curtis 2016b]).
• Ovarian cancer: The risk of ovarian cancer is decreased in patients using combination hormonal contraceptives (CDC [Curtis 2016b]; SGO/ASRM [Chen 2019]). Oral contraceptives may be used to reduce the risk of ovarian cancer in at risk patients with BRCA1 and BRCA2 mutations who do not have a personal history of breast cancer (SGO/ASRM [Chen 2019]). Patients awaiting treatment for ovarian cancer may use combination hormonal contraceptives (CDC [Curtis 2016b]).
• Solid organ transplant: Use of combination hormonal contraceptives is not recommended in patients with complicated organ transplants; although data are limited, serious medical complications have been reported (eg, graft failure, rejection, cardiac allograft vasculopathy) requiring discontinuation of the contraceptive (CDC [Curtis 2016b]).
• Systemic lupus erythematosus (SLE): Patients with SLE are at an increased risk for heart disease, stroke, and VTE. Do not use combination hormonal contraceptives in patients with SLE who have positive (or unknown) antiphospholipid antibodies, due to an increased risk of arterial and venous thrombosis (CDC [Curtis 2016b]).
Concurrent drug therapy issues:
• Testosterone: All available forms of contraception can be considered for patients receiving gender-affirming testosterone therapy after evaluating patient preferences and medical conditions (Bonnington 2020; Krempasky 2020). However, it has been suggested to use contraceptive products containing lower daily doses of ethinyl estradiol (0.01 to 0.02 mg) to decrease the risk of possible adverse reactions when testosterone therapy is used with combination hormonal contraceptives (Bonnington 2020).
Special populations:
• Body weight: The patch is less effective in patients with a BMI ≥30 kg/m2 and may also be less effective in patients with a BMI ≥25 kg/m2 to <30 kg/m2. Available evidence suggests efficacy of oral combination hormonal contraceptives may be decreased if BMI ≥30 kg/m2; however, reductions in effectiveness are considered minimal and information is conflicting. In this population, use of combination hormonal contraceptives may increase the risk of VTE. In general, the benefits of combination hormonal contraceptives may outweigh the risks in patients who otherwise are eligible for this method (CDC [Curtis 2016b]). Consult product labeling.
• Smoking: Cigarette smoking increases the risk of serious cardiovascular events from combination hormonal contraceptive use. This risk increases with age, particularly in patients over 35 years of age, and with the number of cigarettes smoked.
• Surgery: Whenever possible, discontinue estrogens at least 4 weeks prior to and through 2 weeks following elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization.
Dosage form specific issues:
• Tartrazine: Some products may contain tartrazine, which may cause allergic reactions in certain individuals.
Other warnings/precautions:
• Appropriate use: When initiating a combination hormonal contraceptive, consider initiating with a monthly bleeding monophasic formulation containing ethinyl estradiol 0.03 to 0.035 mg plus a progestin and adjusting based on adverse reactions and patient preference (Ott 2014).
• Extended cycle regimen: Contraceptives with an extended cycle regimen provide more hormonal exposure per year than conventional monthly contraceptives.
• HIV infection protection: Combination hormonal contraceptives do not protect against HIV infection or other sexually transmitted diseases (CDC [Curtis 2016a]; CDC [Curtis 2016b]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Kit, Oral:
FaLessa: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [DSC] [contains fd&c blue #1 (brilliant blue), fd&c blue #2 (indigotine,indigo carmine), fd&c red #40(allura red ac)aluminum lake, fd&c yellow #5 (tartrazine)aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, soybean lecithin]
Patch Weekly, Transdermal:
Twirla: Ethinyl estradiol 30 mcg and levonorgestrel 120 mcg per day (1 ea)
Tablet, Oral:
Afirmelle: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 (indigo carm) aluminum lake]
Altavera: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets and 7 inactive tablets]
Amethia: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [84 tablets]; ethinyl estradiol 0.01 mg [7 tablets] [contains corn starch, fd&c blue #1 (brilliant blue)]
Amethia Lo: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [84 tablets]; ethinyl estradiol 0.01 mg [7 tablets] [DSC] [contains corn starch, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Amethyst: Ethinyl estradiol 0.02 mg and levonorgestrel 0.09 mg [28 tablets]
Ashlyna: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [84 tablets]; ethinyl estradiol 0.01 mg [7 tablets] [contains fd&c blue #1 (brill blue) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Aubra: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [DSC]
Aubra EQ: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 (indigo carm) aluminum lake]
Aviane: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets]
Ayuna: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake]
Balcoltra: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets] and ferrous bisglycinate 36.5 mg [7 tablets] [contains fd&c blue #1 (brilliant blue), fd&c red #40(allura red ac)aluminum lake, fd&c yellow #5 (tartrazine)aluminum lake, fd&c yellow #6 (sunset yellow), soybean lecithin]
Camrese: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [84 tablets]; ethinyl estradiol 0.01 mg [7 tablets] [contains fd&c blue #1 (brill blue) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Camrese Lo: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [84 tablets]; ethinyl estradiol 0.01 mg [7 tablets] [contains fd&c yellow #6(sunset yellow)alumin lake, polysorbate 80, quinoline (d&c yellow #10) aluminum lake]
Chateal: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets and 7 inactive tablets] [DSC] [contains fd&c blue #1 (brill blue) aluminum lake]
Chateal EQ: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake]
Daysee: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [84 tablets]; ethinyl estradiol 0.01 mg [7 tablets] [contains fd&c blue #1 (brilliant blue), fd&c yellow #6 (sunset yellow)]
Delyla: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets]
Dolishale: Ethinyl estradiol 0.02 mg and levonorgestrel 0.09 mg [28 tablets] [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40(allura red ac)aluminum lake, fd&c yellow #5 (tartrazine)aluminum lake, soybean lecithin]
Enpresse-28: Day 1-6: Ethinyl estradiol 0.03 mg and levonorgestrel 0.05 mg [6 tablets]; Day 7-11: Ethinyl estradiol 0.04 mg and levonorgestrel 0.075 mg [5 tablets]; Day 12-21: Ethinyl estradiol 0.03 mg and levonorgestrel 0.125 mg [10 tablets]; Day 22-28: 7 inactive tablets
Falmina: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [contains fd&c red #40(allura red ac)aluminum lake, fd&c yellow #5 (tartrazine)aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, soybean lecithin]
Fayosim: Day 1-42: Ethinyl estradiol 0.02 mg and levonorgestrel 0.15 mg [42 tablets]; Day 43-63: Ethinyl estradiol 0.025 mg and levonorgestrel 0.15 mg [21 tablets]; Day 64-84: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets]; Day 85-91: Ethinyl estradiol 0.01 mg [7 tablets] [DSC] [contains fd&c blue #1 (brill blue) aluminum lake, fd&c red #40(allura red ac)aluminum lake, fd&c yellow #6(sunset yellow)alumin lake]
Iclevia: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [84 tablets and 7 inactive tablets] [contains fd&c blue #2 (indigo carm) aluminum lake]
Introvale: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [84 tablets and 7 inactive tablets]
Jaimiess: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [84 tablets]; ethinyl estradiol 0.01 mg [7 tablets]
Jolessa: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [84 tablets and 7 inactive tablets] [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye)]
Joyeaux: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets] and ferrous bisglycinate 36.5 mg [7 tablets] [contains corn starch]
Kurvelo: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets and 7 inactive tablets] [contains fd&c yellow #6 (sunset yellow)]
Larissia: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [DSC]
Lessina: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [contains fd&c red #40(allura red ac)aluminum lake]
Levonest: Day 1-6: Ethinyl estradiol 0.03 mg and levonorgestrel 0.05 mg [6 tablets]; Day 7-11: Ethinyl estradiol 0.04 mg and levonorgestrel 0.075 mg [5 tablets]; Day 12-21: Ethinyl estradiol 0.03 mg and levonorgestrel 0.125 mg [10 tablets]; Day 22-28: 7 inactive tablets [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40(allura red ac)aluminum lake, fd&c yellow #5 (tartrazine)aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, soybean lecithin]
Levora 0.15/30 (28): Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets and 7 inactive tablets] [contains fd&c yellow #6(sunset yellow)alumin lake]
Lillow: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets and 7 inactive tablets] [DSC]
LoJaimiess: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [84 tablets]; ethinyl estradiol 0.01 mg [7 tablets]
LoSeasonique: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [84 tablets]; ethinyl estradiol 0.01 mg [7 tablets] [DSC] [contains fd&c yellow #6(sunset yellow)alumin lake, polysorbate 80, quinoline (d&c yellow #10) aluminum lake]
Lutera: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets]
Marlissa: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets and 7 inactive tablets] [contains fd&c yellow #6 (sunset yellow)]
Orsythia: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [DSC] [contains corn starch, fd&c red #40(allura red ac)aluminum lake, quinoline (d&c yellow #10) aluminum lake]
Portia-28: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets and 7 inactive tablets]
Quartette: Day 1-42: Ethinyl estradiol 0.02 mg and levonorgestrel 0.15 mg [42 tablets]; Day 43-63: Ethinyl estradiol 0.025 mg and levonorgestrel 0.15 mg [21 tablets]; Day 64-84: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets]; Day 85-91: Ethinyl estradiol 0.01 mg [7 tablets] [DSC] [contains fd&c blue #1 (brill blue) aluminum lake, fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Rivelsa: Day 1-42: Ethinyl estradiol 0.02 mg and levonorgestrel 0.15 mg [42 tablets]; Day 43-63: Ethinyl estradiol 0.025 mg and levonorgestrel 0.15 mg [21 tablets]; Day 64-84: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets]; Day 85-91: Ethinyl estradiol 0.01 mg [7 tablets] [contains fd&c blue #1 (brill blue) aluminum lake, fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Seasonique: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [84 tablets]; ethinyl estradiol 0.01 mg [7 tablets] [DSC] [contains fd&c blue #1 (brill blue) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Setlakin: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [84 tablets and 7 inactive tablets] [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40(allura red ac)aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, soybean lecithin]
Simpesse: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [84 tablets]; ethinyl estradiol 0.01 mg [7 tablets] [contains corn starch, fd&c blue #1 (brilliant blue)]
Sronyx: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets]
Trivora (28): Day 1-6: Ethinyl estradiol 0.03 mg and levonorgestrel 0.05 mg [6 tablets]; Day 7-11: Ethinyl estradiol 0.04 mg and levonorgestrel 0.075 mg [5 tablets]; Day 12-21: Ethinyl estradiol 0.03 mg and levonorgestrel 0.125 mg [10 tablets]; Day 22-28: 7 inactive tablets [contains corn starch]
Tyblume: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [contains corn starch, fd&c red #40 aluminum lake, fd&c yellow #10 aluminum lake]
Vienva: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [contains corn starch, fd&c red #40(allura red ac)aluminum lake, quinoline (d&c yellow #10) aluminum lake]
Generic: Day 1-42: Ethinyl estradiol 0.02 mg and levonorgestrel 0.15 mg [42 tablets]; Day 43-63: Ethinyl estradiol 0.025 mg and levonorgestrel 0.15 mg [21 tablets]; Day 64-84: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets]; Day 85-91: Ethinyl estradiol 0.01 mg [7 tablets], Day 1-6: Ethinyl estradiol 0.03 mg and levonorgestrel 0.05 mg [6 tablets]; Day 7-11: Ethinyl estradiol 0.04 mg and levonorgestrel 0.075 mg [5 tablets]; Day 12-21: Ethinyl estradiol 0.03 mg and levonorgestrel 0.125 mg [10 tablets]; Day 22-28: 7 inactive tablets, Ethinyl estradiol 0.02 mg and levonorgestrel 0.09 mg [28 tablets], Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets], Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets] and ferrous bisglycinate 36.5 mg [7 tablets], Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [84 tablets]; ethinyl estradiol 0.01 mg [7 tablets], Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets and 7 inactive tablets], Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [84 tablets and 7 inactive tablets], Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [84 tablets]; ethinyl estradiol 0.01 mg [7 tablets]
May be product dependent
Chewable (Tyblume Oral)
0.1-20 mg-mcg (per each): $0.94
Patch weekly (Twirla Transdermal)
120-30 mcg/24 hrs (per each): $81.83
Tablets (Afirmelle Oral)
0.1-20 mg-mcg (per each): $1.26
Tablets (Altavera Oral)
0.15-30 mg-mcg (per each): $1.10
Tablets (Amethia Oral)
0.15-0.03 &0.01 mg (per each): $2.95
Tablets (Amethyst Oral)
90-20 mcg (per each): $2.12
Tablets (Ashlyna Oral)
0.15-0.03 &0.01 mg (per each): $3.35
Tablets (Aubra EQ Oral)
0.1-20 mg-mcg (per each): $1.26
Tablets (Aviane Oral)
0.1-20 mg-mcg (per each): $1.26
Tablets (Ayuna Oral)
0.15-30 mg-mcg (per each): $1.10
Tablets (Balcoltra Oral)
0.1-20MG-MCG(21) (per each): $11.79
Tablets (Camrese Lo Oral)
0.1-0.02 & 0.01 mg (per each): $2.95
Tablets (Camrese Oral)
0.15-0.03 &0.01 mg (per each): $2.95
Tablets (Chateal EQ Oral)
0.15-30 mg-mcg (per each): $1.10
Tablets (Daysee Oral)
0.15-0.03 &0.01 mg (per each): $2.95
Tablets (Delyla Oral)
0.1-20 mg-mcg (per each): $1.26
Tablets (Dolishale Oral)
90-20 mcg (per each): $2.12
Tablets (Enpresse-28 Oral)
50-30/75-40/125-30 MCG (per each): $0.98
Tablets (Falmina Oral)
0.1-20 mg-mcg (per each): $1.26
Tablets (Iclevia Oral)
0.15-0.03 mg (per each): $1.77
Tablets (Introvale Oral)
0.15-0.03 mg (per each): $1.77
Tablets (Jaimiess Oral)
0.15-0.03 &0.01 mg (per each): $2.95
Tablets (Jolessa Oral)
0.15-0.03 mg (per each): $1.77
Tablets (Joyeaux Oral)
0.1-20MG-MCG(21) (per each): $10.73
Tablets (Kurvelo Oral)
0.15-30 mg-mcg (per each): $1.10
Tablets (Lessina Oral)
0.1-20 mg-mcg (per each): $1.25
Tablets (Levonest Oral)
50-30/75-40/125-30 MCG (per each): $0.98
Tablets (Levonorg-Eth Estrad Triphasic Oral)
50-30/75-40/125-30 MCG (per each): $0.98
Tablets (Levonorgest-Eth Est & Eth Est Oral)
42-21-21-7 days (per each): $4.57
Tablets (Levonorgest-Eth Estrad 91-Day Oral)
0.1-0.02 & 0.01 mg (per each): $2.95
0.15-0.03 mg (per each): $1.77
0.15-0.03 &0.01 mg (per each): $2.95
Tablets (Levonorgest-Eth Estradiol-Iron Oral)
0.1-20MG-MCG(21) (per each): $10.73
Tablets (Levonorgestrel-Ethinyl Estrad Oral)
0.1-20 mg-mcg (per each): $1.26
0.15-30 mg-mcg (per each): $1.10
90-20 mcg (per each): $2.12
Tablets (Levora 0.15/30 (28) Oral)
0.15-30 mg-mcg (per each): $1.10
Tablets (LoJaimiess Oral)
0.1-0.02 & 0.01 mg (per each): $2.95
Tablets (Lutera Oral)
0.1-20 mg-mcg (per each): $1.26
Tablets (Portia-28 Oral)
0.15-30 mg-mcg (per each): $1.10
Tablets (Rivelsa Oral)
42-21-21-7 days (per each): $4.57
Tablets (Setlakin Oral)
0.15-0.03 mg (per each): $1.77
Tablets (Simpesse Oral)
0.15-0.03 &0.01 mg (per each): $2.95
Tablets (Sronyx Oral)
0.1-20 mg-mcg (per each): $1.26
Tablets (Trivora (28) Oral)
50-30/75-40/125-30 MCG (per each): $0.98
Tablets (Vienva Oral)
0.1-20 mg-mcg (per each): $1.05
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Alesse 21: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets]
Alesse 28: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #1 (brill blue) aluminum lake]
Alysena 21: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [contains corn starch, fd&c red #40(allura red ac)aluminum lake]
Alysena 28: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [contains corn starch, fd&c red #40(allura red ac)aluminum lake]
Audrina 21: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [contains fd&c red #40 (allura red ac dye), fd&c yellow #6 (sunset yellow)]
Audrina 28: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [contains fd&c red #40 (allura red ac dye), fd&c yellow #6 (sunset yellow)]
Aviane: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #1 (brill blue) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Laylaa 21: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets]
Laylaa 28: Ethinyl estradiol 0.02 mg and levonorgestrel 0.1 mg [21 tablets and 7 inactive tablets] [contains corn starch]
Min Ovral 21: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets and 7 inactive tablets]
Min Ovral 28: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets and 7 inactive tablets]
Ovima 21: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets and 7 inactive tablets] [contains fd&c red #40(allura red ac)aluminum lake]
Ovima 28: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets and 7 inactive tablets] [contains fd&c red #40(allura red ac)aluminum lake]
Portia 21: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye), polysorbate 80]
Portia 28: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 (indigotine,indigo carmine), fd&c red #40 (allura red ac dye), polysorbate 80]
Seasonale: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [84 tablets and 7 inactive tablets] [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye)]
Seasonique: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [84 tablets]; ethinyl estradiol 0.01 mg [7 tablets] [contains fd&c blue #1 (brill blue) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Triquilar 21: Day 1-6: Ethinyl estradiol 0.03 mg and levonorgestrel 0.05 mg [6 tablets]; Day 7-11: Ethinyl estradiol 0.04 mg and levonorgestrel 0.075 mg [5 tablets]; Day 12-21: Ethinyl estradiol 0.03 mg and levonorgestrel 0.125 mg [10 tablets]; Day 22-28: 7 inactive tablets
Triquilar 28: Day 1-6: Ethinyl estradiol 0.03 mg and levonorgestrel 0.05 mg [6 tablets]; Day 7-11: Ethinyl estradiol 0.04 mg and levonorgestrel 0.075 mg [5 tablets]; Day 12-21: Ethinyl estradiol 0.03 mg and levonorgestrel 0.125 mg [10 tablets]; Day 22-28: 7 inactive tablets
Generic: Ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg [84 tablets and 7 inactive tablets]
Oral:
Contraception: Administer at the same time each day.
According to the manufacturer, if severe diarrhea or vomiting occurs within 3 to 4 hours after taking an active tablet, consider the dose to be missed; additional contraceptive measures are recommended. Additional guidelines are also available (Ref).
Emergency contraception: If vomiting occurs within 3 hours, take a second dose as soon as possible; consider use of an antiemetic (Ref).
Transdermal:
Apply new patches on the same day each week. Apply to clean, dry, intact, healthy skin on the abdomen, buttock, or upper torso. Avoid areas that will be rubbed by tight clothing. Do not apply to the breasts or to skin that is red, irritated, or cut. Alternate application sites; do not apply to the same place as the previous patch. Do not apply makeup, creams, lotions, powders, or other topical products to the skin where the patch will be placed. Remove and discard large section of liner while holding small section of liner. Avoid touching surface of patch. Apply patch to skin and remove the rest of the liner. Press patch down firmly onto skin using palm of the hand; apply pressure for 10 seconds. Run fingers over entire surface area to smooth out any wrinkles in the patch. When changing the patch each week, the new patch may be applied in the same anatomic area but should be applied to a new spot in that area. Do not use supplemental adhesives or wraps to hold patch into place. Do not cut, damage, or alter the size of the patch; contraceptive efficacy may be impaired.
Check the patch daily to ensure all edges are sticking. Prolonged exposure to water may decrease adherence of the patch; check for partial or complete detachment of the patch after activities such as bathing, showering, or swimming.
If a patch becomes partially or completely detached for <24 hours: Try to reapply to same place or replace with a new patch immediately. Do not reapply if patch is no longer sticky, if it is sticking to itself or another surface, or if it has material sticking to it.
If a patch becomes partially or completely detached for >24 hours (or time period is unknown): Apply a new patch and use this day of the week as the new "patch change day" from this point on. Use an additional method of contraception (nonhormonal) until after the first 7 days of consecutive administration.
Changing the "patch change day": The "patch change day" can be changed to an earlier day in the week by first completing the current 3-week cycle. Then, during the "patch-free interval," select an earlier day to start the new cycle. Shortening the patch free interval may increase the incidence of spotting or breakthrough bleeding. Do not allow >7 consecutive patch-free days.
Skin irritation: If patch is in an uncomfortable location, it can be removed and a new patch applied to a different location until the next "patch change day."
To dispose of patch, fold the sticky sides together and dispose in the trash within a child-resistant container. Do not flush down the toilet.
|
Scenario |
Results in new patch change day |
Start new cycle |
Backup contraception needed |
|---|---|---|---|
|
Did not apply patch on scheduled day 1/week 1 of new cycle (late patch-on day) |
Yes |
Yes |
Yes |
|
Patch detached <24 hours |
No |
No |
No |
|
Patch detached ≥24 hours or unsure of duration |
Yes |
Yes |
Yes |
|
<48 hours late for patch change day (day 8 or 15) |
No |
No |
No |
|
≥48 hours late for patch change (day 8 or 15) |
Yes |
Yes |
Yes |
|
Forgot to remove patch on day 22 |
No |
No |
No |
Oral:
Contraception: Administer at the same time each day. Combined hormonal contraceptives may be initiated at any time during the menstrual cycle if it is reasonably sure the patient is not pregnant. Backup contraception should be used for 7 days unless contraception is initiated within the first 5 days of menstrual bleeding or the patient abstains from sexual intercourse. Combined hormonal contraceptives may be started immediately following or within 7 days of a first or second trimester abortion; backup contraception is needed for 7 days unless contraception is started at the time of surgical abortion (Ref)
According to the manufacturer, if diarrhea or vomiting occur, backup contraceptive measures may be needed. Additional guidelines are available (Ref).
Missed or late doses (Ref):
If 1 dose is late (<24 hours since dose should have been taken) or if 1 dose is missed (24 to <48 hours since dose should have been taken): Take dose as soon as possible. Continue remaining doses at the usual time (even if that means 2 doses on the same day).
If ≥2 consecutive doses are missed (≥48 hours since dose should have been taken): Take the most recently missed dose as soon as possible and discard any other missed doses. Continue remaining doses at the usual time (even if that means taking 2 doses on the same day); use backup contraception until hormonal pills have been taken for 7 consecutive days. If doses were missed during the last week of hormonal (active) tablets (eg, days 15 to 21 of a 28-day pack), omit the hormone-free interval by finishing the current pack and starting a new pack. If unable to start a new pack immediately, backup contraception is needed until hormonal pills from a new pack have been taken for 7 consecutive days. Consider use of emergency contraception in some situations (refer to guidelines for details).
Also refer to prescribing information for product-specific information.
Emergency contraception: If vomiting occurs within 3 hours, a second dose should be taken as soon as possible; consider use of an antiemetic (Ref).
Topical:
New patches should be applied on the same day each week. Apply to clean, dry, intact, healthy skin on the abdomen, buttock, or upper torso. Avoid areas that will be rubbed by tight clothing. Do not apply to the breasts or to skin that is red, irritated, or cut. Alternate application sites; do not apply to the same place as the previous patch. Do not apply makeup, creams, lotions, powders, or other topical products to the skin where the patch will be placed. Remove and discard large section of liner while holding small section of liner. Avoid touching surface of patch. Apply patch to skin and remove the rest of the liner. Press patch down firmly onto skin using palm of the hand; apply pressure for 10 seconds. Run fingers over entire surface area to smooth out any wrinkles in the patch. When changing the patch each week, the new patch may be applied in the same anatomic area but should be applied to a new spot in that area. Do not use supplemental adhesives or wraps to hold patch into place. Do not cut, damage, or alter the size of the patch; contraceptive efficacy may be impaired.
The patch should be checked daily to ensure all edges are sticking. Prolonged exposure to water may decrease adherence of the patch; check for partial or complete detachment of the patch after activities such as bathing, showering, or swimming.
If a patch becomes partially or completely detached for <24 hours: Try to reapply to same place or replace with a new patch immediately. Do not reapply if patch is no longer sticky, if it is sticking to itself or another surface, or if it has material sticking to it.
If a patch becomes partially or completely detached for >24 hours (or time period is unknown): Apply a new patch and use this day of the week as the new "patch change day" from this point on. An additional method of contraception (nonhormonal) must be used until after the first 7 days of consecutive administration.
Forgetting to apply the patch at the start of cycle (week 1/day 1): Apply first patch as soon as remembering, using this day of the week as the new "patch change day" from this point on. An additional method of contraception (nonhormonal) must be used until after the first 7 days of consecutive administration.
Forgetting to change patch in the middle of the cycle (week 2/day 8 or week 3/day 15): If <48 hours from normal "patch change day," apply new patch immediately. No backup contraception is needed. If >48 hours from normal "patch change day," apply a new patch and use this day of the week as the new "patch change day" from this point on. An additional method of contraception (nonhormonal) must be used until after the first 7 days of consecutive administration.
Forgetting to remove patch at end of cycle (week 4/day 22): Take off as soon as remembering, start new cycle on usual "patch change day."
Changing the "patch change day": The "patch change day" can be changed to an earlier day in the week by first completing the current cycle. Then, during the "patch-free interval," select an earlier day to start the new cycle. Shortening the patch free interval may increase the incidence of spotting or breakthrough bleeding. Do not allow >7 consecutive patch-free days.
Skin irritation: If patch is in an uncomfortable location, it can be removed and a new patch applied to a different location until the next "patch change day."
To dispose of patch, fold the sticky sides together and dispose in the trash within a child-resistant container. Do not flush down the toilet.
Hazardous agent (NIOSH 2016 [group 2]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tablets or capsules (NIOSH 2016).
Contraception:
Oral: For the prevention of pregnancy.
Limitations of use: For use in patients who may become pregnant; not for use prior to menarche or post-menopause.
Patch: For the prevention of pregnancy in patients with a BMI <30 kg/m2.
Limitations of use: For use in patients who may become pregnant; not for use prior to menarche or post-menopause. The patch may be less effective in patients with a BMI ≥25 kg/m2 to <30 kg/m2. Use is contraindicated in patients with a BMI ≥30 kg/m2.
Abnormal uterine bleeding, acute; Abnormal uterine bleeding, nonacute; Acne; Dysmenorrhea, primary, and secondary to endometriosis; Emergency contraception; Hirsutism; Hyperlactation (hypergalactia); Menstrual suppression; Polycystic ovary syndrome in patients with hyperandrogenism and/or menstrual irregularities
Alesse may be confused with Alecensa.
Lutera may be confused with Lutathera.
Portia may be confused with Potiga.
Seasonale may be confused with seasonal allergies, Seasonique.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Adalimumab: May decrease the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy
Ajmaline: Estrogen Derivatives may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy
Anastrozole: Estrogen Derivatives may diminish the therapeutic effect of Anastrozole. Risk X: Avoid combination
Anthrax Immune Globulin (Human): Estrogen Derivatives may enhance the thrombogenic effect of Anthrax Immune Globulin (Human). Risk C: Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antihepaciviral Combination Products: Ethinyl Estradiol-Containing Products may enhance the hepatotoxic effect of Antihepaciviral Combination Products. Risk X: Avoid combination
Aprepitant: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration with aprepitant, and to continue back-up contraception for 28 days after discontinuing aprepitant to ensure contraceptive reliability. Risk D: Consider therapy modification
Asparaginase Products: Hormonal Contraceptives may enhance the thrombogenic effect of Asparaginase Products. Management: Consider discontinuing hormonal contraceptives and using an alternative contraceptive method in patients treated with asparaginase products. Risk D: Consider therapy modification
Asunaprevir: May decrease the serum concentration of Hormonal Contraceptives. Management: Use of a high-dose oral contraceptive (at least 30 mcg of ethinyl estradiol combined with norethindrone) is recommended when combined with asunaprevir. Consider an additional barrier method when other forms of contraception are used with asunaprevir. Risk D: Consider therapy modification
Atazanavir: May decrease the serum concentration of Hormonal Contraceptives. Specifically, atazanavir/ritonavir may decrease concentrations of estrogens. Atazanavir may increase the serum concentration of Hormonal Contraceptives. Specifically, atazanavir alone may increase concentrations of estrogens and atazanavir alone or boosted may increase concentrations of progestins. Management: Dose adjustment of hormonal contraceptives or use of alternative or additional nonhormonal contraceptive may be needed when combined with atazanavir. See full interact monograph for details. Atazanavir/cobicistat with drospirenone is contraindicated. Risk D: Consider therapy modification
Bile Acid Sequestrants: May decrease the serum concentration of Ethinyl Estradiol-Containing Products. Management: Administer ethinyl estradiol-containing products 4 hours prior to the administration of a bile acid sequestrant. Risk D: Consider therapy modification
Bimekizumab: May decrease the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy
Brigatinib: May decrease the serum concentration of Hormonal Contraceptives. Management: Use a non-hormonal contraceptive during brigatinib use and for at least 4 months after the last brigatinib dose. Males with partners of reproductive potential should use contraception during treatment with brigatinib and for 3 months after brigatinib use. Risk D: Consider therapy modification
C1 inhibitors: Estrogen Derivatives may enhance the thrombogenic effect of C1 inhibitors. Risk C: Monitor therapy
Carfilzomib: Hormonal Contraceptives may enhance the thrombogenic effect of Carfilzomib. Management: Consider alternative, non-hormonal methods of contraception in patients requiring therapy with carfilzomib, especially patients using carfilzomib in combination with dexamethasone, lenalidomide plus dexamethasone, or daratumumab plus dexamethasone. Risk D: Consider therapy modification
Chenodiol: Estrogen Derivatives may diminish the therapeutic effect of Chenodiol. Risk C: Monitor therapy
Chlorprothixene: Estrogen Derivatives may enhance the adverse/toxic effect of Chlorprothixene. Estrogen Derivatives may enhance the therapeutic effect of Chlorprothixene. Risk C: Monitor therapy
Chlorprothixene: Progestins may enhance the adverse/toxic effect of Chlorprothixene. Progestins may enhance the therapeutic effect of Chlorprothixene. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
Cobicistat: May decrease the serum concentration of Hormonal Contraceptives. Specifically, cobicistat may decrease serum concentrations of estrogens. Cobicistat may increase the serum concentration of Hormonal Contraceptives. Specifically, cobicistat may increase serum concentrations of progestins. Management: Use alternative or additional nonhormonal forms of contraception when estrogen-containing hormonal contraceptives are combined with cobicistat. Progestin-only contraceptives can be used without back up, but monitor for progestin toxicities. Risk D: Consider therapy modification
Colchicine: May enhance the adverse/toxic effect of Hormonal Contraceptives. Risk C: Monitor therapy
Corticosteroids (Systemic): Estrogen Derivatives may increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy
Cosyntropin: Estrogen Derivatives may diminish the diagnostic effect of Cosyntropin. Management: Discontinue estrogen containing drugs 4 to 6 weeks prior to cosyntropin (ACTH) testing. Risk D: Consider therapy modification
CycloSPORINE (Systemic): Ethinyl Estradiol-Containing Products may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a moderate CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a strong CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification
CYP3A4 Inducers (Weak): May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a weak CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Hormonal Contraceptives. Risk C: Monitor therapy
Dantrolene: Estrogen Derivatives may enhance the hepatotoxic effect of Dantrolene. Risk C: Monitor therapy
Dasabuvir: Ethinyl Estradiol-Containing Products may enhance the hepatotoxic effect of Dasabuvir. Risk X: Avoid combination
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy
Dehydroepiandrosterone: May enhance the adverse/toxic effect of Estrogen Derivatives. Risk X: Avoid combination
Efavirenz: May decrease the serum concentration of Hormonal Contraceptives. Management: Use a back-up method during coadministration, and to continue back-up contraception for 12 weeks after stopping efavirenz to ensure contraceptive reliability. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Risk D: Consider therapy modification
Elagolix: Hormonal Contraceptives may diminish the therapeutic effect of Elagolix. Specifically, estrogen-containing hormonal contraceptives may diminish the therapeutic effects of elagolix. Elagolix may decrease the serum concentration of Hormonal Contraceptives. Specifically, concentrations of progestins may be decreased with elagolix therapy. Elagolix may increase the serum concentration of Hormonal Contraceptives. Specifically, concentrations of ethinyl estradiol may be increased with elagolix therapy. Management: Use an alternative, nonhormonal contraceptive during treatment with elagolix and for at least 28 days following discontinuation of elagolix treatment. Use of elagolix 200 mg twice daily with an estrogen-containing hormonal contraceptive is not recommended Risk D: Consider therapy modification
Elexacaftor, Tezacaftor, and Ivacaftor: Hormonal Contraceptives may enhance the adverse/toxic effect of Elexacaftor, Tezacaftor, and Ivacaftor. Specifically, the risk for rash may be increased. Risk C: Monitor therapy
Encorafenib: May decrease the serum concentration of Hormonal Contraceptives. Risk X: Avoid combination
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk X: Avoid combination
Etravirine: May decrease the serum concentration of Hormonal Contraceptives. Specifically, progestin concentrations may decrease. Etravirine may increase the serum concentration of Hormonal Contraceptives. Specifically, estrogen concentrations may increase. Risk C: Monitor therapy
Exemestane: Estrogen Derivatives may diminish the therapeutic effect of Exemestane. Risk X: Avoid combination
Exenatide: Hormonal Contraceptives may diminish the therapeutic effect of Exenatide. Exenatide may decrease the serum concentration of Hormonal Contraceptives. Management: Administer oral hormonal contraceptives at least one hour prior to exenatide. Monitor blood glucose more frequently when patients treated with exenatide initiate therapy with a hormonal contraceptive. Increases in exenatide doses may be needed. Risk D: Consider therapy modification
Felbamate: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing felbamate to ensure contraceptive reliability. Risk D: Consider therapy modification
Ferric Maltol: May decrease the serum concentration of Ethinyl Estradiol-Containing Products. Management: Ferric maltol labeling recommends separating administration of ethinyl estradiol-containing products from ferric maltol by at least four hours to minimize the potential for any interaction. Risk D: Consider therapy modification
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fezolinetant: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination
Flibanserin: Hormonal Contraceptives may increase the serum concentration of Flibanserin. Risk C: Monitor therapy
Fosaprepitant: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration with fosaprepitant, and to continue back-up contraception for 28 days after discontinuing fosaprepitant to ensure contraceptive reliability. Risk D: Consider therapy modification
Fostemsavir: May increase the serum concentration of Ethinyl Estradiol-Containing Products. Management: Ethinyl estradiol daily dose should not exceed 30 mcg during coadministration with fostemsavir. Monitor patients closely for any evidence of a thromboembolism. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Glecaprevir and Pibrentasvir: Ethinyl Estradiol-Containing Products may enhance the hepatotoxic effect of Glecaprevir and Pibrentasvir. Glecaprevir and Pibrentasvir may increase the serum concentration of Ethinyl Estradiol-Containing Products. Management: Use of glecaprevir/pibrentasvir and products containing more than 20 mcg of ethinyl estradiol is not recommended. Lower dose ethinyl estradiol-containing products may be used. Risk D: Consider therapy modification
Griseofulvin: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing griseofulvin to ensure contraceptive reliability. Risk D: Consider therapy modification
Growth Hormone Analogs: Estrogen Derivatives may diminish the therapeutic effect of Growth Hormone Analogs. Management: Initiate somapacitan at 2 mg once weekly in patients receiving oral estrogens. Monitor for reduced efficacy of growth hormone analogs; increased doses may be required. Risk D: Consider therapy modification
Guanethidine: Estrogen Derivatives may diminish the therapeutic effect of Guanethidine. Risk C: Monitor therapy
Hemin: Estrogen Derivatives may diminish the therapeutic effect of Hemin. Risk X: Avoid combination
Hyaluronidase: Estrogen Derivatives may diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy
Hydrocortisone (Systemic): Estrogen Derivatives may increase the serum concentration of Hydrocortisone (Systemic). Estrogen Derivatives may decrease the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy
Immune Globulin: Estrogen Derivatives may enhance the thrombogenic effect of Immune Globulin. Risk C: Monitor therapy
Indium 111 Capromab Pendetide: Estrogen Derivatives may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: Avoid combination
Interleukin-6 (IL-6) Inhibiting Therapies: May decrease the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy
Ivosidenib: May decrease the serum concentration of Hormonal Contraceptives. Management: Consider alternative methods of contraception (ie, non-hormonal) in patients receiving ivosidenib. Risk D: Consider therapy modification
Ixazomib: May decrease the serum concentration of Hormonal Contraceptives. More specifically, use of ixazomib with dexamethasone may decrease the serum concentrations of hormonal contraceptives. Management: Patients of reproductive potential should use a non-hormonal contraceptive method during treatment with ixazomib and for at least 90 days after the last ixazomib dose. Risk D: Consider therapy modification
Lactic Acid, Citric Acid, and Potassium Bitartrate: Ethinyl Estradiol may diminish the therapeutic effect of Lactic Acid, Citric Acid, and Potassium Bitartrate. Risk X: Avoid combination
LamoTRIgine: Estrogen Derivatives (Contraceptive) may decrease the serum concentration of LamoTRIgine. Management: Larger doses of lamotrigine may be needed when combined with estrogens. Specific dosing recommendations vary based on other concomitant medications and which medication is being initiated or discontinued. See interaction monograph for details. Risk D: Consider therapy modification
Lenalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Lenalidomide. Risk C: Monitor therapy
Lixisenatide: Hormonal Contraceptives may diminish the therapeutic effect of Lixisenatide. Lixisenatide may decrease the serum concentration of Hormonal Contraceptives. Management: Administer oral hormonal contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. Additionally, monitor blood glucose more frequently when patients treated with lixisenatide initiate therapy with a hormonal contraceptive. Risk D: Consider therapy modification
Lomitapide: Estrogen Derivatives may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 40 mg/day. Risk D: Consider therapy modification
Mavacamten: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative contraceptive that is not sensitive to CYP3A4 induction or a back-up method during coadministration, and to continue back-up contraception for 4 months after stopping mavacamten to ensure contraceptive reliability. Risk D: Consider therapy modification
Melatonin: Estrogen Derivatives may increase the serum concentration of Melatonin. Risk C: Monitor therapy
MetyraPONE: Estrogen Derivatives may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking estrogen derivatives. Risk D: Consider therapy modification
MetyraPONE: Progestins may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking progestins. Risk D: Consider therapy modification
MiFEPRIStone: May diminish the therapeutic effect of Hormonal Contraceptives. Management: Nonhormonal contraception should be used during, and for 4 weeks following, mifepristone treatment for hyperglycemia due to Cushing syndrome. If used for pregnancy termination, hormonal contraceptives can be used after pregnancy expulsion is confirmed. Risk D: Consider therapy modification
Mitotane: May decrease the serum concentration of Hormonal Contraceptives. Management: Effective nonhormonal contraception is recommended for those of reproductive potential during treatment with mitotane as well as after discontinuation of mitotane for as long as mitotane plasma levels are detectable. Risk X: Avoid combination
Mivacurium: Estrogen Derivatives may increase the serum concentration of Mivacurium. Risk C: Monitor therapy
Mobocertinib: May decrease the serum concentration of Hormonal Contraceptives. Risk X: Avoid combination
Mycophenolate: May decrease the serum concentration of Hormonal Contraceptives. Management: Patients of childbearing potential who are taking hormonal contraceptives should use an additional form of barrier contraception during treatment with mycophenolate and for 6 weeks after mycophenolate discontinuation. Risk D: Consider therapy modification
Nirmatrelvir and Ritonavir: May decrease the serum concentration of Hormonal Contraceptives. Specifically, nirmatrelvir and ritonavir may decrease concentrations of estrogens. Nirmatrelvir and Ritonavir may increase the serum concentration of Hormonal Contraceptives. Specifically, nirmatrelvir and ritonavir may increase concentrations of progestins. Management: Use additional nonhormonal forms of contraception (back-up method) when estrogen-containing hormonal contraceptives are combined with nirmatrelvir/ritonavir. Progestin-only contraceptives can be used without back-up, but monitor for progestin toxicities. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the thrombogenic effect of Estrogen Derivatives. Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy
Octreotide: May decrease the serum concentration of Hormonal Contraceptives. Management: Women should use an alternative non-hormonal method of contraception or a back-up method when octreotide is combined with hormonal contraceptives. Risk D: Consider therapy modification
Olutasidenib: May decrease the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Management: Avoid use of olutasidenib with sensitive or narrow therapeutic index CYP3A4 substrates when possible. If concurrent use with olutasidenib is unavoidable, monitor closely for evidence of decreased concentrations of the CYP3A4 substrates. Risk D: Consider therapy modification
Omaveloxolone: May decrease the serum concentration of Hormonal Contraceptives. Risk X: Avoid combination
Ospemifene: Estrogen Derivatives may enhance the adverse/toxic effect of Ospemifene. Risk X: Avoid combination
OXcarbazepine: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing oxcarbazepine to ensure contraceptive reliability. Risk D: Consider therapy modification
Perampanel: May decrease the serum concentration of Levonorgestrel (Systemic). Management: Patients taking levonorgestrel-containing contraceptives should use an alternative, non-hormonal form of contraception during the concurrent use of perampanel and for 1 month after discontinuing perampanel. Risk D: Consider therapy modification
Pexidartinib: May decrease the serum concentration of Hormonal Contraceptives. Risk X: Avoid combination
Pitolisant: May decrease the serum concentration of Hormonal Contraceptives. Management: Patients using hormonal contraception should be advised to use an alternative non-hormonal contraceptive method during treatment with pitolisant and for at least 21 days after discontinuation of pitolisant treatment. Risk D: Consider therapy modification
Pomalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Pomalidomide. Risk C: Monitor therapy
Proguanil: Ethinyl Estradiol-Containing Products may decrease serum concentrations of the active metabolite(s) of Proguanil. Risk C: Monitor therapy
Protease Inhibitors: May decrease the serum concentration of Hormonal Contraceptives. Specifically, protease inhibitors may decrease concentrations of estrogens. Protease Inhibitors may increase the serum concentration of Hormonal Contraceptives. Specifically, protease inhibitors may increase concentrations of progestins. Management: Use alternative or additional nonhormonal forms of contraception when estrogen-containing hormonal contraceptives are combined with protease inhibitors. Progestin-only contraceptives can be used without back up, but monitor for progestin toxicities. Risk D: Consider therapy modification
Raloxifene: Estrogen Derivatives may enhance the adverse/toxic effect of Raloxifene. Risk X: Avoid combination
Repotrectinib: May decrease the serum concentration of Hormonal Contraceptives. Risk X: Avoid combination
Retinoic Acid Derivatives: May diminish the therapeutic effect of Progestins (Contraceptive). Retinoic Acid Derivatives may decrease the serum concentration of Progestins (Contraceptive). Management: Two forms of effective contraception should be used in patients receiving retinoic acid derivatives. Microdosed progesterone-only preparations (ie, minipills that do not contain estrogen) are considered an inadequate method of contraception. Risk D: Consider therapy modification
Roflumilast-Containing Products: Ethinyl Estradiol-Containing Products may increase serum concentrations of the active metabolite(s) of Roflumilast-Containing Products. Ethinyl Estradiol-Containing Products may increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
ROPINIRole: Estrogen Derivatives may increase the serum concentration of ROPINIRole. Risk C: Monitor therapy
Selegiline: Ethinyl Estradiol-Containing Products may increase the serum concentration of Selegiline. Risk C: Monitor therapy
Succinylcholine: Estrogen Derivatives may increase the serum concentration of Succinylcholine. Risk C: Monitor therapy
Sugammadex: May diminish the therapeutic effect of Hormonal Contraceptives. Management: Patients receiving any hormonal contraceptive (oral or non-oral) should use an additional, nonhormonal contraceptive method during and for 7 days following sugammadex treatment. Risk D: Consider therapy modification
Tacrolimus (Systemic): Estrogen Derivatives may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Taurursodiol: May decrease the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk X: Avoid combination
Tazemetostat: May decrease the serum concentration of Hormonal Contraceptives. Management: Individuals of childbearing potential should use a non-hormonal contraceptive method during treatment with tazemetostat and for 6 months after. Males with partners of childbearing potential should use contraception during treatment and for 3 months after. Risk D: Consider therapy modification
Tetrahydrocannabinol and Cannabidiol: May decrease the serum concentration of Hormonal Contraceptives. Management: Product labeling recommends that patients taking hormonal contraceptives should use an additional, non-hormonal contraceptive or reliable barrier method during treatment with tetrahydrocannabinol and cannabidiol buccal spray. Risk D: Consider therapy modification
Thalidomide: Hormonal Contraceptives may enhance the thrombogenic effect of Thalidomide. Risk C: Monitor therapy
Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Thyroid Products: Estrogen Derivatives may diminish the therapeutic effect of Thyroid Products. Risk C: Monitor therapy
Tirzepatide: May decrease the serum concentration of Hormonal Contraceptives. Management: Patients using oral hormonal contraceptives should switch to a non-oral contraceptive method, or add a barrier method of contraception, for 4 weeks after initiation of tirzepatide and for 4 weeks after each dose escalation of tirzepatide. Risk D: Consider therapy modification
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification
Tobacco (Smoked): May enhance the adverse/toxic effect of Estrogen Derivatives (Contraceptive). Specifically, the risk of serious cardiovascular events (eg, stroke, venous thromboembolism, myocardial infarction) may be increased. Management: Avoid cigarette smoking in patients who use estrogen containing contraceptives whenever possible. If combined, monitor for signs and symptoms of serious cardiovascular events (eg, stroke, venous thromboembolism, myocardial infarction). Risk D: Consider therapy modification
Topiramate: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing topiramate to ensure contraceptive reliability. Risk D: Consider therapy modification
Tranexamic Acid: Hormonal Contraceptives may enhance the thrombogenic effect of Tranexamic Acid. Risk X: Avoid combination
Ulipristal: May diminish the therapeutic effect of Progestins. Progestins may diminish the therapeutic effect of Ulipristal. Risk X: Avoid combination
Ursodiol: Estrogen Derivatives may diminish the therapeutic effect of Ursodiol. Risk C: Monitor therapy
Ustekinumab: May decrease the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy
Vaborbactam: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing meropenem/vaborbactam to ensure contraceptive reliability. Risk D: Consider therapy modification
Valproate Products: Estrogen Derivatives may decrease the serum concentration of Valproate Products. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Hormonal Contraceptives may increase the serum concentration of Vitamin K Antagonists. Hormonal Contraceptives may decrease the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Voriconazole: Hormonal Contraceptives may increase the serum concentration of Voriconazole. Voriconazole may increase the serum concentration of Hormonal Contraceptives. Risk C: Monitor therapy
Due to the increased risk of venous thromboembolism (VTE) postpartum, do not initiate combination hormonal contraceptives in any patient <21 days following delivery. The risk decreases to baseline by postpartum day 42. In patients who are between 21 and 42 days after delivery, consider risk factors for VTE (eg, age ≥35 years, previous VTE, thrombophilia, immobility, preeclampsia, transfusion at delivery, cesarean delivery, peripartum cardiomyopathy, BMI ≥30 kg/m2, postpartum hemorrhage, smoking) (CDC [Curtis 2016b]). The manufacturer does not recommend use until ≥4 weeks after delivery in patients who choose not to breastfeed due to the risk of VTE.
The levonorgestrel/ethinyl estradiol patch is contraindicated in patients with a BMI ≥30 kg/m2 because the efficacy is reduced and the risk of VTE may be greater compared to patients with a lower BMI. The patch may also be less effective in patients with a BMI ≥25 kg/m2 to <30 kg/m2.
When used for emergency contraception, a barrier contraceptive is recommended immediately following use. Any regular (nonemergency) contraceptive method can be started immediately after combined estrogen/progestogen emergency contraception; however, a barrier method (or abstinence from sexual intercourse) is also needed for 7 days (ACOG 2015; CDC [Curtis 2016a]).
All available forms of contraception, including combination hormonal contraceptives, can be considered for patients on gender-affirming testosterone therapy after evaluating patient preferences and medical conditions (eg, risk for VTE) (Bonnington 2020; Krempasky 2020).
Combination oral contraceptives (COCs) may be an option for menstrual suppression in patients who have reached menarche when fewer or no menses are desired (ACOG 2022; SOGC [Kirkham 2019]). Future fertility is not decreased. Base the decision to use a COC or other hormonal preparation on patient preference, their ability to use the method, method effectiveness, potential contraindications, drug interactions, and adverse events. Consider for patients requesting menstrual suppression, including (but not limited to) adolescents, athletes, persons with physical and/or cognitive disabilities, persons on gender-affirming hormone therapy, and persons with limited access to menstrual products or other challenges to hygiene management (ACOG 2022).
A COC is a preferred therapy for treating hyperandrogenism and/or menstrual irregularities associated with polycystic ovary syndrome. A specific formulation is not recommended; product selection should follow available criteria for use guidelines, using a lower dose estrogen product (Teede 2018).
Combination hormonal contraceptives are used to prevent pregnancy; discontinue treatment if pregnancy occurs. In general, the inadvertent use of combination hormonal contraceptives early in pregnancy has not been associated with adverse fetal or maternal effects (CDC [Curtis 2016b]).
Contraceptive steroids may be present in breast milk.
Adverse health outcomes, or consistent effects on infant growth or illness due to exogenous estrogens have not been reported following maternal use of combination hormonal contraceptives in patients who are breastfeeding (CDC [Curtis 2016b]). Because estrogen-containing contraceptives may reduce milk production, some manufacturers recommend the use of other forms of contraception until the child is weaned.
Due to the increased risk of venous thromboembolism (VTE) postpartum, do not start combination hormonal contraceptives in breastfeeding patients <21 days following delivery. The risk decreases to baseline by postpartum day 42. In patients who are between 21 and 42 days after delivery, consider risk factors for VTE (eg, age ≥35 years, previous VTE, thrombophilia, immobility, preeclampsia, transfusion at delivery, cesarean delivery, peripartum cardiomyopathy, BMI ≥30 kg/m2, postpartum hemorrhage, smoking). Evaluate the risks, benefits, and alternatives to combination hormonal contraception when initiating treatment in breastfeeding patients (CDC [Curtis 2016b]). The manufacturer does not recommend use until ≥4 weeks after delivery in patients who choose not to breastfeed due to the risk of VTE.
Combination oral contraceptives (COCs) are a recommended option for the treatment of persistent idiopathic hyperlactation (hypergalactia) in patients requiring medication therapy. Consider postpartum age, patient preferences, potential adverse drug reactions, and interactions prior to therapy. COCs containing ethinyl estradiol 0.02 to 0.035 mg are recommended. Do not initiate treatment <6 weeks postpartum; discontinue once milk production decreases (may significantly decrease within 7 days). If COC therapy is continued, monitoring of milk production is recommended (ABM [Johnson 2020]).
Contraception:
Assessment of pregnancy status (prior to therapy); personal or family history of thrombotic or thromboembolic disorders (prior to therapy); BP (prior to therapy and yearly); weight (optional; BMI at baseline may be helpful to monitor changes during therapy); assess potential health status changes at routine visits (CDC [Curtis 2016a]).
Determining if reasonably certain a person is not pregnant (CDC [Curtis 2016a]): If the patient has no signs or symptoms of pregnancy and meets any one of the following criteria, a health care provider can be reasonably certain the person is not pregnant:
• ≤7 days after the start of normal menses
• No sexual intercourse since last menses
• Correct and consistent use of reliable contraception
• ≤7 days after spontaneous or induced abortion
• <4 weeks postpartum
• <6 months postpartum, amenorrheic, and exclusively breastfeeding or ≥85% of feeds are breastfeeds.
If all doses have not been taken on schedule and one menstrual period is missed, consider the possibility of pregnancy. If 2 consecutive menstrual periods are missed, assess pregnancy status before a new dosing cycle is started.
Monitor patient for vision changes; BP; signs and symptoms of thromboembolic disorders; signs or symptoms of depression; glycemic control in patients with diabetes; lipid profiles in patients being treated for hyperlipidemias. Perform adequate diagnostic measures to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding.
Emergency contraception: Evaluate for pregnancy, spontaneous abortion or ectopic pregnancy if menses is delayed for ≥1 week following emergency contraception, or if lower abdominal pain or persistent irregular bleeding develops (ACOG 2015).
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.
Absorption:
Oral: Rapid.
Transdermal: Rapid; reaches plateau by 24 to 48 hours. Absorption is therapeutically equivalent when applied to abdomen, buttock, and upper torso (excluding breasts). Absorption may be decreased with heat exposure due to whirlpool or treadmill.
Distribution: Oral: Ethinyl estradiol: 4.3 L/kg; Levonorgestrel: 1.8 L/kg.
Protein binding:
Ethinyl estradiol: 95% to 97% to albumin.
Levonorgestrel: 97% to 99% primarily to sex hormone binding globulin (SHBG), lesser amounts to albumin.
Metabolism:
Oral: Undergoes first pass metabolism.
Transdermal: Avoids first pass metabolism.
Ethinyl estradiol: Hepatic via CYP3A4; forms metabolites.
Levonorgestrel: Forms conjugated in unconjugated metabolites
Bioavailability: Oral: Ethinyl estradiol: 38% to 48%; Levonorgestrel: 100%.
Half-life elimination:
Oral: Ethinyl estradiol: 12 to 23 hours; Levonorgestrel: 22 to 49 hours.
Transdermal: Ethinyl estradiol: ~21 hours; Levonorgestrel: ~42 hours.
Excretion:
Ethinyl estradiol: Urine and feces
Levonorgestrel: Urine (40% to 68%, parent drug and metabolites); feces (16% to 48% as metabolites)
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