Version July 2025
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs are contraindicated in women who are over 35 years of age and smoke.
Abnormal uterine bleeding, acute (off-label use):
Note: For use in hemodynamically stable patients without high risk for thrombosis (Ref). 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 4 tablets on day 2, then 3 tablets on day 3, then 2 tablets on day 4, then 1 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).
Acne vulgaris, inflammatory, moderate to severe (Tri Femynor, Tri-Estarylla, Tri-Linyah, Tri-Mili, Tri-Nymyo, Tri-Previfem, Tri-Sprintec, Tri-VyLibra):
Note: For patients ≥15 years of age who have reached menarche and desire oral contraception (Ref).
Oral: Refer to dosing for contraception.
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). Quick start method is preferred by some experts (Ref).
Day 1 start: Start on first day of menstrual cycle. Additional method of contraception not required (Ref).
Quick start: Start on the day the patient receives the prescription. 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 the onset of menses, use an additional method of contraception (nonhormonal) until 7 days of consecutive administration (Ref).
|
Current method |
Instructions for switching to ethinyl estradiol/norgestimate |
|---|---|
|
Oral contraceptive |
Start ethinyl estradiol/norgestimate on the day a new pack of the previous oral contraceptive would be started.
|
|
Implant |
Start ethinyl estradiol/norgestimate on the day of implant removal. |
|
Injection |
Start ethinyl estradiol/norgestimate on the day when the next injection would have been scheduled. |
|
IUD |
Start ethinyl estradiol/norgestimate on the day of removal of the IUD. If the IUD is not removed on the first day of the menstrual cycle, use an additional method of contraception for the first 7 days of consecutive administration. |
|
Transdermal system |
Start ethinyl estradiol/norgestimate on the day when the next application would be scheduled. |
|
Vaginal insert |
Start ethinyl estradiol/norgestimate on the day when the next insertion would be scheduled. |
|
Refer to prescribing information for product-specific information. Additional guidance is also available (see CDC [Curtis 2016a]). | |
|
Use after childbirth (not breastfeeding) |
Do not initiate estradiol/norgestimate during the first 4 weeks after delivery due to the increased risk of venous thromboembolism. If menstrual cycles have returned, follow instructions for patients not currently using a hormonal contraceptive. If postpartum menstrual cycles have not returned, consider the possibility of ovulation occurring prior to use. |
|
Use after first-trimester abortion or miscarriage |
Estradiol/norgestimate 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 estradiol/norgestimate 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. |
|
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 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 back-up (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 tablets are missed in a row during weeks 1, 2, or 3 |
Day 1 start: • Throw out the rest of the pack and start a new pack that same day. Sunday start: • Continue taking 1 tablet a day until Sunday, then throw out the rest of the pack and start a new pack that same day. Use back-up (nonhormonal) contraception until active tablets have been taken for 7 consecutive days after the missed tablets. |
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 (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.
Use is contraindicated in patients with hepatic impairment.
Females:
Acne vulgaris: Oral: Adolescents ≥15 years; refer to adult dosing for contraception; not to be used prior to menarche.
Contraception: Oral: Refer to adult dosing; not to be used prior to menarche.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution and monitor blood pressure closely.
Use is contraindicated in patients with hepatic impairment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Nausea (≤16%), vomiting (≤16%)
Genitourinary: Breakthrough bleeding (7% to 38%)
Nervous system: Headache (≤34%), migraine (≤34%)
1% to 10%:
Dermatologic: Acne vulgaris (5%), skin rash (3%)
Endocrine & metabolic: Menstrual disease (9%; including amenorrhea, dysmenorrhea, and premenstrual syndrome), weight changes (3%; including weight gain and weight loss)
Gastrointestinal: Abdominal distention (3%), abdominal pain (≤9%), flatulence (3%), gastrointestinal pain (≤8%)
Genitourinary: Breast cyst (≤10%), breast hypertrophy (≤10%), breast swelling (≤10%), breast tenderness (≤10%), genital discharge (3% to 7%), mastalgia (≤10%), nipple discharge (≤10%), nipple pain (≤10%), vaginal infection (7% to 8%), vulvovaginal infection (4%)
Nervous system: Fatigue (2%), mood disorder (≤8%; including depression, emotional lability, irritability, and mood changes), nervousness (3%)
Frequency not defined:
Cardiovascular: Hypertension
Genitourinary: Abnormal uterine bleeding, cervical carcinoma (in situ), cervical dysplasia
Postmarketing:
Cardiovascular: Acute myocardial infarction, arterial thromboembolism, chest pain, palpitations, syncope, tachycardia, venous thromboembolism (including Budd-Chiari syndrome, deep vein thrombosis, hepatic vein thrombosis, and pulmonary embolism)
Dermatologic: Erythema nodosum, hyperhidrosis, night sweats, pruritus, skin photosensitivity, urticaria
Endocrine & metabolic: Dyslipidemia, hirsutism, hot flash
Gastrointestinal: Constipation, diarrhea, pancreatitis
Genitourinary: Breast neoplasm (benign), lactation insufficiency, malignant neoplasm of breast, ovarian cyst, urinary tract infection, vaginal dryness, vulvar dryness
Hepatic: Hepatic adenoma, hepatic focal nodular hyperplasia, hepatitis
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis and angioedema)
Nervous system: Anxiety, asthenia, cerebrovascular accident, dizziness, insomnia, paresthesia, seizure, vertigo
Neuromuscular & skeletal: Back pain, limb pain, muscle spasm, myalgia
Ophthalmic: Contact lens intolerance, dry eye syndrome, retinal thrombosis, visual impairment
Respiratory: Dyspnea
Breast cancer (current or a history of; may be hormonal-sensitive), hepatic tumors (benign or malignant) or hepatic disease, undiagnosed abnormal uterine bleeding; concomitant use of hepatitis C drug combinations containing ombitasvir/ritonavir, with or without dasabuvir.
Use is also contraindicated in patients at high risk of arterial or venous thrombotic diseases for example, patients with: Cerebrovascular disease, coronary artery disease, diabetes mellitus with vascular disease, DVT or PE (current or history of), hypercoagulopathies (inherited or acquired), hypertension (uncontrolled), headaches with focal neurological symptoms, migraine headaches with aura or migraine headaches if >35 years of age, thrombogenic valvular or rhythm diseases of the heart (eg, subacute bacterial endocarditis with valvular disease or atrial fibrillation), patients >35 years of age who smoke.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to ethinyl estradiol, norgestimate, or any component of the formulation; myocardial infarction (current or history of); persistent blood pressure ≥160 mm Hg systolic or ≥100 mm Hg diastolic; ocular lesions due to ophthalmic vascular disease including partial or complete loss of vision or defect in visual fields; steroid dependent jaundice, cholestatic jaundice or history of jaundice in pregnancy; pancreatitis associated with severe hypertriglyceridemia (current or history of); severe dyslipoproteinemia; prolonged immobilization or major surgery associated with an increased risk of postoperative thromboembolism; thrombophlebitis, thromboembolic disorders, or thrombophilic conditions (current or history of); prodromi of a thrombosis (eg, TIA, angina pectoris; current or history of); hereditary or acquired predisposition for venous or arterial thrombosis, such as 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); coadministration with ombitasvir, paritaprevir, ritonavir (with or without dasabuvir)
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 more than a few 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 slight 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 cholestasis of pregnancy or cholestasis with prior oral 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 thrombotic event occurs. The increased risk of venous thromboembolism (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. Older than 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 nonoral 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 history of depression; discontinue if serious depression recurs.
• Diabetes: May impair glucose tolerance; use caution in patients with diabetes or prediabetes. In general, use of combination oral 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 disease, 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 women 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. 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: Patients with systemic lupus erythematosus (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 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: Available evidence suggests efficacy of combination hormonal contraceptives may be decreased if BMI is ≥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]).
• Smoking: Cigarette smoking increases the risk of serious cardiovascular events from combination hormonal contraceptives use. This risk increases with age, particularly in patients >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: May contain FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions, including bronchial asthma, in susceptible individuals. Tartrazine sensitivity is frequently seen in in patients with aspirin hypersensitivity.
Other warnings/precautions:
• Appropriate use: When initiating a combination oral 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 events and patient preference (Ott 2014).
• 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
Tablet, Oral:
Estarylla: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 (indigo carm) aluminum lake, quinoline (d&c yellow #10) aluminum lake]
Femynor: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [DSC]
Mili: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 (indigo carm) aluminum lake]
Mono-Linyah: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #1 (brill blue) aluminum lake, fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40(allura red ac)aluminum lake, fd&c yellow #5 (tartrazine)aluminum lake]
Nymyo: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [DSC] [contains corn starch, fd&c blue #1 (brill blue) aluminum lake, fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40(allura red ac)aluminum lake, quinoline (d&c yellow #10) aluminum lake]
Previfem: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [DSC] [contains fd&c blue #2 (indigo carm) aluminum lake, quinoline (d&c yellow #10) aluminum lake]
Sprintec 28: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [contains corn starch, fd&c blue #2 (indigo carm) aluminum lake]
Tri Femynor: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [DSC]
Tri-Estarylla: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 (indigo carm) aluminum lake, quinoline (d&c yellow #10) aluminum lake]
Tri-Linyah: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #1 (brill blue) aluminum lake, fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40(allura red ac)aluminum lake, fd&c yellow #5 (tartrazine)aluminum lake]
Tri-Lo-Estarylla: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #1 (brill blue) aluminum lake, fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #5 (tartrazine)aluminum lake, fd&c yellow #6(sunset yellow)alumin lake]
Tri-Lo-Marzia: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 (indigo carm) aluminum lake]
Tri-Lo-Mili: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 (indigo carm) aluminum lake]
Tri-Lo-Sprintec: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 (indigo carm) aluminum lake]
Tri-Mili: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 (indigo carm) aluminum lake]
Tri-Nymyo: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [DSC] [contains corn starch, fd&c blue #1 (brill blue) aluminum lake, fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40(allura red ac)aluminum lake, quinoline (d&c yellow #10) aluminum lake]
Tri-Previfem: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [DSC] [contains fd&c blue #2 (indigo carm) aluminum lake, quinoline (d&c yellow #10) aluminum lake]
Tri-Sprintec: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains corn starch, fd&c blue #2 (indigotine,indigo carmine), fd&c red #40 (allura red ac dye), fd&c yellow #6 (sunset yellow)]
Tri-VyLibra: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 (indigo carm) aluminum lake]
Tri-VyLibra Lo: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 (indigo carm) aluminum lake]
VyLibra: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 (indigo carm) aluminum lake]
Generic: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [DSC], Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets, Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets]
Yes
Tablets (Estarylla Oral)
0.25-35 mg-mcg (per each): $1.15
Tablets (Mili Oral)
0.25-35 mg-mcg (per each): $1.15
Tablets (Mono-Linyah Oral)
0.25-35 mg-mcg (per each): $1.17
Tablets (Norgestim-Eth Estrad Triphasic Oral)
0.18/0.215/0.25 mg-35 mcg (per each): $1.40
Tablets (Norgestimate-Eth Estradiol Oral)
0.25-35 mg-mcg (per each): $1.15 - $1.30
Tablets (Sprintec 28 Oral)
0.25-35 mg-mcg (per each): $1.15
Tablets (Tri-Estarylla Oral)
0.18/0.215/0.25 mg-35 mcg (per each): $1.40
Tablets (Tri-Linyah Oral)
0.18/0.215/0.25 mg-35 mcg (per each): $1.40
Tablets (Tri-Lo-Estarylla Oral)
0.18/0.215/0.25 mg-25 mcg (per each): $2.20
Tablets (Tri-Lo-Marzia Oral)
0.18/0.215/0.25 mg-25 mcg (per each): $5.24
Tablets (Tri-Lo-Mili Oral)
0.18/0.215/0.25 mg-25 mcg (per each): $5.24
Tablets (Tri-Lo-Sprintec Oral)
0.18/0.215/0.25 mg-25 mcg (per each): $5.24
Tablets (Tri-Mili Oral)
0.18/0.215/0.25 mg-35 mcg (per each): $1.40
Tablets (Tri-Sprintec Oral)
0.18/0.215/0.25 mg-35 mcg (per each): $1.40
Tablets (Tri-VyLibra Lo Oral)
0.18/0.215/0.25 mg-25 mcg (per each): $4.73
Tablets (Tri-VyLibra Oral)
0.18/0.215/0.25 mg-35 mcg (per each): $1.40
Tablets (VyLibra Oral)
0.25-35 mg-mcg (per each): $1.17
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:
Tri-Cira Lo 21: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #1 (brill blue) aluminum lake, fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #5 (tartrazine)aluminum lake, fd&c yellow #6(sunset yellow)alumin lake]
Tri-Cira Lo 28: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #1 (brill blue) aluminum lake, fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #5 (tartrazine)aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, soybean lecithin]
TRI-Jordyna 21: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 (indigo carm) aluminum lake, quinoline yellow (d&c yellow #10)]
TRI-Jordyna 28: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 (indigo carm) aluminum lake, quinoline yellow (d&c yellow #10)]
Generic: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets
Oral: Administer at the same time each day at intervals not >24 hours.
According to the manufacturer, if severe diarrhea or vomiting occur 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).
Oral:
Contraception: Administer at the same time each day at intervals not >24 hours.
Combined hormonal contraceptives may be initiated at any time during the menstrual cycle if it is reasonably sure the woman is not pregnant. Back-up contraception should be used for 7 days unless contraception is initiated within the first 5 days of menstrual bleeding or the woman abstains from sexual intercourse. Combined hormonal contraceptives may be started immediately following or within 7 days of a first or second trimester abortion; back-up contraception is needed for 7 days unless contraception is started at the time of surgical abortion (Ref).
For the 21-tablet package, one dose is taken for 21 consecutive days, followed by 7 days off of the medication; a new course begins on the 8th day after the last tablet is taken.
For the 28-tablet package, one dose is taken daily without interruption
According to the manufacturer, if vomiting or diarrhea occurs, back-up contraceptive measures may be needed. Additional guidelines are available (Ref).
Acne: Ortho-TriCyclen, Tri-Estarylla, TriNessa, Tri Femynor, Tri-Linyah, Tri-Previfem, Tri-Sprintec, Tri-VyLibra: Females ≥15 years: Follow administration for contraception.
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Acne vulgaris, inflammatory, moderate to severe (Tri Femynor, Tri-Estarylla, Tri-Linyah, Tri-Mili, Tri-Nymyo, Tri-Previfem, Tri-Sprintec, Tri-VyLibra): Treatment of moderate acne vulgaris in patients ≥15 years of age only if the patient desires an oral contraceptive for birth control.
Limitations of use: For use only in patients who have reached menarche and have no contraindications to combination hormonal contraceptive use.
Contraception: 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.
Abnormal uterine bleeding, acute; Abnormal uterine bleeding, nonacute; Dysmenorrhea, primary and secondary to endometriosis; Hirsutism; Hyperlactation (hypergalactia); Menstrual suppression; Polycystic ovary syndrome in patients with hyperandrogenism and/or menstrual irregularities
Ortho-Cyclen may be confused with Ortho-Cept
Ortho Tri-Cyclen may be confused with Ortho Tri-Cyclen Lo
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (contraindicated in pregnancy) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
Vivelle: Brand name for ethinyl estradiol/norgestimate [Austria], but also a brand name for estradiol [US. (discontinued), Belgium]
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
Adalimumab: May decrease serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor
Ajmaline: Estrogen Derivatives may increase adverse/toxic effects of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor
Anastrozole: Estrogen Derivatives may decrease therapeutic effects of Anastrozole. Risk X: Avoid
Anthrax Immune Globulin (Human): Estrogen Derivatives may increase thrombogenic effects of Anthrax Immune Globulin (Human). Risk C: Monitor
Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Antihepaciviral Combination Products: Ethinyl Estradiol-Containing Products may increase hepatotoxic effects of Antihepaciviral Combination Products. Risk X: Avoid
Aprepitant: May decrease 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 increase thrombogenic effects 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
Atazanavir: May decrease serum concentration of Hormonal Contraceptives. Specifically, atazanavir/ritonavir may decrease concentrations of estrogens. Atazanavir may increase 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
Avapritinib: May increase serum concentration of Ethinyl Estradiol-Containing Products. Management: Use of an effective nonhormonal contraceptive or a hormonal contraceptive that does not contain estrogen is preferred. If an estrogen-containing contraceptive is required, use a formulation containing ethinyl estradiol 20 mcg or less, if possible. Risk D: Consider Therapy Modification
Bile Acid Sequestrants: May decrease 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 serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor
Brigatinib: May decrease 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 increase thrombogenic effects of C1 Inhibitors. Risk C: Monitor
Carfilzomib: Hormonal Contraceptives may increase thrombogenic effects 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 decrease therapeutic effects of Chenodiol. Risk C: Monitor
Chlorprothixene: Estrogen Derivatives may increase adverse/toxic effects of Chlorprothixene. Estrogen Derivatives may increase therapeutic effects of Chlorprothixene. Risk C: Monitor
Chlorprothixene: Progestins may increase therapeutic effects of Chlorprothixene. Progestins may increase adverse/toxic effects of Chlorprothixene. Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CloZAPine: CYP1A2 Inhibitors (Weak) may increase serum concentration of CloZAPine. Risk C: Monitor
Cobicistat: May decrease serum concentration of Hormonal Contraceptives. Specifically, cobicistat may decrease serum concentrations of estrogens. Cobicistat may increase 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 increase adverse/toxic effects of Hormonal Contraceptives. Risk C: Monitor
Corticosteroids (Systemic): Estrogen Derivatives may increase serum concentration of Corticosteroids (Systemic). Risk C: Monitor
Cosyntropin: Coadministration of Estrogen Derivatives and Cosyntropin may alter diagnostic results. 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 serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease 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 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 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 serum concentration of Hormonal Contraceptives. Risk C: Monitor
Dantrolene: Estrogen Derivatives may increase hepatotoxic effects of Dantrolene. Risk C: Monitor
Dasabuvir: Ethinyl Estradiol-Containing Products may increase hepatotoxic effects of Dasabuvir. Risk X: Avoid
Deferasirox: May decrease serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor
Efavirenz: May decrease 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
Elafibranor: May decrease serum concentration of Hormonal Contraceptives. Risk X: Avoid
Elagolix: Hormonal Contraceptives may decrease therapeutic effects of Elagolix. Specifically, estrogen-containing hormonal contraceptives may diminish the therapeutic effects of elagolix. Elagolix may decrease serum concentration of Hormonal Contraceptives. Specifically, concentrations of progestins may be decreased with elagolix therapy. Elagolix may increase 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 increase adverse/toxic effects of Elexacaftor, Tezacaftor, and Ivacaftor. Specifically, the risk for rash may be increased. Risk C: Monitor
Encorafenib: May decrease serum concentration of Hormonal Contraceptives. Risk X: Avoid
Etravirine: May decrease serum concentration of Hormonal Contraceptives. Specifically, progestin concentrations may decrease. Etravirine may increase serum concentration of Hormonal Contraceptives. Specifically, estrogen concentrations may increase. Risk C: Monitor
Exemestane: Estrogen Derivatives may decrease therapeutic effects of Exemestane. Risk X: Avoid
Exenatide: Hormonal Contraceptives may decrease therapeutic effects of Exenatide. Exenatide may decrease 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 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 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
Fezolinetant: CYP1A2 Inhibitors (Weak) may increase serum concentration of Fezolinetant. Risk X: Avoid
Flibanserin: Hormonal Contraceptives may increase serum concentration of Flibanserin. Risk C: Monitor
Fosaprepitant: May decrease 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 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 serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Glecaprevir and Pibrentasvir: Ethinyl Estradiol-Containing Products may increase hepatotoxic effects of Glecaprevir and Pibrentasvir. Glecaprevir and Pibrentasvir may increase serum concentration of Ethinyl Estradiol-Containing Products. Management: Use of glecaprevir/pibrentasvir and products containing 20 mcg of ethinyl estradiol or more is not recommended. Lower dose ethinyl estradiol-containing products may be used. Risk D: Consider Therapy Modification
Griseofulvin: May decrease 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 decrease therapeutic effects 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 decrease therapeutic effects of Guanethidine. Risk C: Monitor
Hemin: Estrogen Derivatives may decrease therapeutic effects of Hemin. Risk X: Avoid
Hyaluronidase: Estrogen Derivatives may decrease therapeutic effects of Hyaluronidase. Risk C: Monitor
Hydrocortisone (Systemic): Estrogen Derivatives may increase serum concentration of Hydrocortisone (Systemic). Estrogen Derivatives may decrease serum concentration of Hydrocortisone (Systemic). Risk C: Monitor
Immune Globulin: Estrogen Derivatives may increase thrombogenic effects of Immune Globulin. Management: Use the lowest dose of immune globulin and minimum infusion rate practicable during coadministration with estrogen derivatives. Risk D: Consider Therapy Modification
Indium 111 Capromab Pendetide: Coadministration of Estrogen Derivatives and Indium 111 Capromab Pendetide may alter diagnostic results. Risk X: Avoid
Interleukin-6 (IL-6) Inhibiting Therapies: May decrease serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor
Ivosidenib: May decrease 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 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 decrease therapeutic effects of Lactic Acid, Citric Acid, and Potassium Bitartrate. Risk X: Avoid
LamoTRIgine: Estrogen Derivatives (Contraceptive) may decrease 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 increase thrombogenic effects of Lenalidomide. Risk C: Monitor
Levomethadone: Hormonal Contraceptives may increase serum concentration of Levomethadone. Risk C: Monitor
Lixisenatide: Hormonal Contraceptives may decrease therapeutic effects of Lixisenatide. Lixisenatide may decrease 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 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 serum concentration of Hormonal Contraceptives. Management: Use with ethinyl estradiol/norethindrone is permitted. With other hormonal contraceptives, use a back-up (eg, condoms) or alternative (eg, IUD) method during coadministration, and to continue back-up contraception for 4 months after stopping mavacamten. Risk D: Consider Therapy Modification
Melatonin: Estrogen Derivatives may increase serum concentration of Melatonin. Risk C: Monitor
MetyraPONE: Coadministration of Estrogen Derivatives and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking estrogen derivatives. Risk D: Consider Therapy Modification
MetyraPONE: Coadministration of Progestins and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking progestins. Risk D: Consider Therapy Modification
MiFEPRIStone: May decrease therapeutic effects 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
Mirikizumab: May decrease serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor
Mitotane: May decrease 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
Mivacurium: Estrogen Derivatives may increase serum concentration of Mivacurium. Risk C: Monitor
Mobocertinib: May decrease serum concentration of Hormonal Contraceptives. Risk X: Avoid
Mycophenolate: May decrease 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
Nemolizumab: May decrease serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor
Nirmatrelvir and Ritonavir: May decrease serum concentration of Hormonal Contraceptives. Specifically, nirmatrelvir and ritonavir may decrease concentrations of estrogens. Nirmatrelvir and Ritonavir may increase 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 increase thrombogenic effects of Estrogen Derivatives. Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may increase serum concentration of Estrogen Derivatives. Risk C: Monitor
Octreotide: May decrease 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 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 serum concentration of Hormonal Contraceptives. Risk X: Avoid
Ospemifene: Estrogen Derivatives may increase adverse/toxic effects of Ospemifene. Risk X: Avoid
OXcarbazepine: May decrease 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
Pacritinib: May decrease serum concentration of Hormonal Contraceptives. Management: Avoid use of hormonal contraceptives with pacritinib, except for intrauterine systems containing levonorgestrel. If contraception is needed, use a nonhormonal contraceptive or an intrauterine system for at least 30 days after the last dose of pacritinib. Risk D: Consider Therapy Modification
Perampanel: May decrease serum concentration of Hormonal Contraceptives. Management: Patients should use an alternative, nonhormonal-based form of contraception during the concurrent use of perampanel and for 1 month after discontinuing perampanel. Risk D: Consider Therapy Modification
Pexidartinib: May decrease serum concentration of Hormonal Contraceptives. Risk X: Avoid
Pitolisant: May decrease 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 increase thrombogenic effects of Pomalidomide. Risk C: Monitor
Proguanil: Ethinyl Estradiol-Containing Products may decrease active metabolite exposure of Proguanil. Risk C: Monitor
Protease Inhibitors: May decrease serum concentration of Hormonal Contraceptives. Specifically, protease inhibitors may decrease concentrations of estrogens. Protease Inhibitors may increase 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 increase adverse/toxic effects of Raloxifene. Risk X: Avoid
Repotrectinib: May decrease serum concentration of Hormonal Contraceptives. Risk X: Avoid
Roflumilast-Containing Products: Ethinyl Estradiol-Containing Products may increase serum concentration of Roflumilast-Containing Products. Risk C: Monitor
ROPINIRole: Estrogen Derivatives may increase serum concentration of ROPINIRole. Risk C: Monitor
Selegiline: Ethinyl Estradiol-Containing Products may increase serum concentration of Selegiline. Risk C: Monitor
Succinylcholine: Estrogen Derivatives may increase serum concentration of Succinylcholine. Risk C: Monitor
Sugammadex: May decrease therapeutic effects 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
Suzetrigine: May decrease serum concentration of Hormonal Contraceptives. Management: Patients should use a nonhormonal contraceptive, an intrauterine system, or ethinyl estradiol and norethindrone or levonorgestrel for the duration of treatment with suzetrigine and for 28 days after stopping suzetrigine. Risk D: Consider Therapy Modification
Tacrolimus (Systemic): Estrogen Derivatives may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Taurursodiol: May decrease serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk X: Avoid
Tazemetostat: May decrease 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 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 THC/CBD buccal spray. Other forms of THC and CBD do not contain this warning. Risk D: Consider Therapy Modification
Thalidomide: Hormonal Contraceptives may increase thrombogenic effects of Thalidomide. Risk C: Monitor
Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase serum concentration of Theophylline Derivatives. Risk C: Monitor
Thyroid Products: Estrogen Derivatives may decrease therapeutic effects of Thyroid Products. Risk C: Monitor
Tirzepatide: May decrease 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 serum concentration of TiZANidine. Management: Avoid the use of tizanidine with weak CYP1A2 inhibitors when possible. If combined, monitor closely for increased tizanidine toxicities (eg, hypotension, bradycardia, drowsiness). Tizanidine dose reduction or discontinuation may be necessary. Risk D: Consider Therapy Modification
Tobacco (Smoked): May increase adverse/toxic effects 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 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
Tovorafenib: May decrease serum concentration of Hormonal Contraceptives. Management: Avoid concurrent use when possible. If combined use is unavoidable, use of an additional nonhormonal method of contraception is recommended during combined use and for 28 days after stopping tovorafenib. Risk D: Consider Therapy Modification
Tranexamic Acid: Hormonal Contraceptives may increase thrombogenic effects of Tranexamic Acid. Risk X: Avoid
Ulipristal: May decrease therapeutic effects of Progestins. Progestins may decrease therapeutic effects of Ulipristal. Risk X: Avoid
Ursodiol: Estrogen Derivatives may decrease therapeutic effects of Ursodiol. Risk C: Monitor
Ustekinumab: May decrease serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor
Vaborbactam: May decrease 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
Valproic Acid and Derivatives: Estrogen Derivatives may decrease serum concentration of Valproic Acid and Derivatives. Risk C: Monitor
Vedolizumab: May decrease serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor
Vitamin K Antagonists: Hormonal Contraceptives may increase serum concentration of Vitamin K Antagonists. Hormonal Contraceptives may decrease serum concentration of Vitamin K Antagonists. Risk C: Monitor
Vorasidenib: May decrease serum concentration of Hormonal Contraceptives. Management: Avoid combined use when possible, but if this combination cannot be avoided, use of an alternative, nonhormonal means of contraception is recommended during treatment with vorasidenib and for 3 months after the last dose. Risk D: Consider Therapy Modification
Voriconazole: Hormonal Contraceptives may increase serum concentration of Voriconazole. Voriconazole may increase serum concentration of Hormonal Contraceptives. Risk C: Monitor
Due to the increased risk of venous thromboembolism (VTE) postpartum, do not start 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.
All available forms of contraception, including combination hormonal contraceptives, can be considered for patients on gender-affirming testosterone therapy after evaluating the appropriateness of the method based on the patient's preferences and medical conditions (eg, risk for VTE) (Bonnington 2020; Krempasky 2020).
Combination oral contraceptives (COC) may be an option for menstrual suppression in patients who have reached menarche when few 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 use of combination hormonal contraceptives, when inadvertently used early in pregnancy, have not been associated 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 breastfeeding patients (CDC [Curtis 2016b]). Because estrogen containing contraceptives may reduce milk production, the manufacturer recommends 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 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]).
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 healthcare 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 1 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 patients 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 hyperlipidemia. Perform adequate diagnostic measures to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding.
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: Ethinyl estradiol (EE) and norgestimate (NGM): Rapid and well absorbed
Protein binding:
EE: >97% to albumin
Norelgestromin (NGMN): >97% to albumin
Norgestrel (NG): >97% to sex hormone-binding globulin (SHBG); SHBG capacity is affected by plasma ethinyl estradiol levels
Metabolism:
EE: Hepatic; forms metabolites
NGM: Hepatic; forms NGMN (major active metabolite) which is further metabolized to NG (active) and other metabolites
Half-life elimination:
EE: 10-16 hours
NGMN: 18-25 hours
NG: 38-45 hours
Time to peak, plasma: EE and NGM: ~2 hours
Excretion:
EE: Urine and feces
NGM: Urine (~47%) and feces (~37%) as metabolites
