Version May 2024
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, combination oral contraceptives should not be used by women who are over 35 years of age and smoke.
Acne vulgaris, premenstrual dysphoric disorder (for patients eligible for and desiring oral contraception): (Beyaz, Rajani): Refer to dosing for contraception.
Contraception, folate supplementation: Oral: 1 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 (CDC [Curtis 2016a]).
Day 1 start: Dose starts on first day of menstrual cycle. An additional method of contraception is not required (CDC [Curtis 2016a]).
Quick start: Start on the day the patient receives the prescription (Brahmi 2013; Lopez 2012; Stechna 2013; Westhoff 2007). If initiated >5 days after the onset of menses, use an additional method of contraception (nonhormonal) until 7 days of consecutive administration (CDC [Curtis 2016a]).
Sunday start: Start on the first Sunday after the onset of menstruation; if the menstrual period starts on Sunday, take first tablet that very same day. If initiated >5 days after the onset of menses, use an additional method of contraception (nonhormonal) until 7 days of consecutive administration (CDC [Curtis 2016a]).
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Current method |
Instructions for switching to ethinyl estradiol/drospirenone/levomefolate |
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Contraceptive, oral |
Start ethinyl estradiol/drospirenone/levomefolate on the day a new pack of the previous oral contraceptive would be started. |
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Implant or intrauterine system (IUS) |
Start ethinyl estradiol/drospirenone/levomefolate on the day of implant or IUS removal. |
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Injection |
Start ethinyl estradiol/drospirenone/levomefolate on the day the next injection would have been scheduled. |
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Transdermal system |
Start ethinyl estradiol/drospirenone/levomefolate on the day the next application would be scheduled. |
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Vaginal ring |
Start ethinyl estradiol/drospirenone/levomefolate on the day the next insertion would be scheduled. |
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a CDC (Curtis 2016a). | |
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Use after childbirth (not breastfeeding) |
Ethinyl estradiol/drospirenone/levomefolate should not be initiated <4 weeks after delivery due to the increased risk of venous thromboembolism. If postpartum menstrual cycles have not returned, evaluate for possible pregnancy; use an additional method of contraception (nonhormonal) until 7 days of consecutive administration. |
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Use after second trimester abortion |
Ethinyl estradiol/drospirenone/levomefolate should not be initiated <4 weeks after a second trimester abortion due to the increased risk of venous thromboembolism. If menstrual cycles have not returned, evaluate for possible pregnancy; use an additional method of contraception (nonhormonal) for the first 7 days of consecutive administration. |
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Use after spontaneous or induced abortiona |
Combination hormonal contraceptives can be started within 7 days of a complete first trimester or second trimester abortion. Use an additional method of contraception (nonhormonal) for the first 7 days of consecutive administration. |
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Use after surgical abortiona |
Combination hormonal contraceptives can be started the time of a surgical abortion. If not started at the time of surgical abortion, use a n additional method of contraception (nonhormonal) for the first 7 days of consecutive administration. |
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If 1 active (hormonal) tablet is missed |
Take the missed dose as soon as possible. Continue remaining doses at the usual time (even if that means 2 doses on the same day). |
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If 2 consecutive active (hormonal) tablets are missed in weeks 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 hormonal (active) tablets have been taken for 7 consecutive days. |
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If 2 consecutive active (hormonal) tablets are missed during week 3 or 4 or if ≥3 consecutive active (hormonal) tablets are missed during any week |
Day 1 start: • Throw out the rest of the pack and start a new pack the same day Sunday start: • Keep taking 1 tablet every day until Sunday. On Sunday, throw out the rest of the pack and start a new pack on Sunday. Use back-up (nonhormonal) contraception until active (hormonal) tablets have been taken for 7 consecutive days. Consider the possibility of pregnancy if 2 consecutive menstrual periods are missed. |
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If any inactive (nonhormonal) tablets are missed in week 4 |
Throw away any missed tablets. Keep taking 1 tablet every day until the pack is finished. |
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If patient is unsure about what to do about missing tablets |
Use back-up (nonhormonal) contraception. Contact health care provider and continue taking 1 active (hormonal) tablet daily unless directed to do otherwise. |
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) (ABM [Johnson 2020]).
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 (ACOG 2022).
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 (Teede 2018; manufacturer's labeling). Note: Use a preparation with the lowest effective dose of ethinyl estradiol (eg, 0.02 to 0.03 mg) (Teede 2018). 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.
Contraindicated in patients with renal dysfunction.
Contraindicated in patients with hepatic disease.
Acne vulgaris: Females: Adolescents ≥14 years: Oral: Refer to adult dosing.
Contraception, Folate supplementation, PMDD: Females: Oral: Refer to adult dosing; not to be used prior to menarche.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not always defined. Percentages reported with Beyaz. For additional adverse events and postmarketing reports, refer to the Ethinyl Estradiol and Drospirenone (Yasmin, Yaz) monograph.
Central nervous system: Headache (≤6% to 13%), migraine (≤6% to 13%), fatigue (4%), irritability (3%), emotional lability (2%)
Endocrine & metabolic: Menstrual disease (4% to 25%, including menorrhagia, spotting, uterine hemorrhage, vaginal hemorrhage), decreased libido (3%), weight gain (3%)
Gastrointestinal: Nausea (≤4% to 16%), vomiting (≤4% to 16%)
Genitourinary: Breast tenderness (≤3% to 11%), mastalgia (≤3% to 11%), cervical carcinoma (stage 0), cervical dysplasia
Adrenal insufficiency, breast cancer (current or a history of; may be hormonal-sensitive), hepatic tumors (benign or malignant) or hepatic disease, renal impairment, undiagnosed abnormal uterine bleeding; use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Use is also contraindicated in patients at high risk of arterial or venous thrombotic diseases including: Cerebrovascular disease, coronary artery disease, diabetes mellitus with vascular disease, deep vein thrombosis or pulmonary embolism (current or history of), hypercoagulopathies (inherited or acquired), headaches with focal neurological symptoms, hypertension (uncontrolled), 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.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to ethinyl estradiol, drospirenone, levomefolate, or any component of the formulation; myocardial infarction (current or history of); persist blood pressure ≥160 mm Hg systolic or ≥100 mm Hg diastolic; steroid-dependent jaundice, cholestatic jaundice, or history of jaundice during pregnancy; any ocular lesion arising from ophthalmic vascular disease (such as partial or complete loss of vision or visual field defect); 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; pancreatitis associated with severe hypertriglyceridemia (current or history of); severe dyslipoproteinemia; women with hereditary or acquired predisposition for arterial or venous thrombosis, for example: Factor V Leiden mutation, 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 paritaprevir, ritonavir, ombitasvir (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 sun exposure or ultraviolet 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 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).
• Hyperkalemia: Drospirenone has antimineralocorticoid activity that may lead to hyperkalemia. Use is contraindicated in patients with conditions which predispose to hyperkalemia (eg, renal insufficiency, hepatic dysfunction, adrenal insufficiency); use caution with medications that may increase serum potassium.
• 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 (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 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 progestins (limited evidence following a single dose). However, gastric and small bowel transit are 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 resumed 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 past users; other studies have shown a small increased risk in current users (higher risk with longer duration 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 hormone-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 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 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 blood pressure 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: Discontinue use in patients with new headaches that are recurrent, severe, or persistent. 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, drospirenone may potentially interfere with testosterone therapy more than other progestins due to its anti-androgenic and anti-mineralocorticoid properties (Bonnington 2020).
Special populations:
• Body weight: Available evidence suggests efficacy of 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]).
• 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 major surgery or other surgeries known to have an increased risk of thromboembolism or during periods of prolonged immobilization.
Other warnings/precautions:
• 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.
Tablet, Oral:
Beyaz: Ethinyl estradiol 0.02 mg, drospirenone 3 mg, and levomefolate calcium 0.451 mg [24 tablets] and levomefolate calcium 0.451 mg [4 tablets]
Safyral: Ethinyl estradiol 0.03 mg, drospirenone 3 mg, and levomefolate calcium 0.451 mg [21 tablets] and levomefolate calcium 0.451 mg [7 tablets]
Tydemy: Ethinyl estradiol 0.03 mg, drospirenone 3 mg, and levomefolate calcium 0.451 mg [21 tablets] and levomefolate calcium 0.451 mg [7 tablets] [contains corn starch]
Generic: Ethinyl estradiol 0.02 mg, drospirenone 3 mg, and levomefolate calcium 0.451 mg [24 tablets] and levomefolate calcium 0.451 mg [4 tablets], Ethinyl estradiol 0.03 mg, drospirenone 3 mg, and levomefolate calcium 0.451 mg [21 tablets] and levomefolate calcium 0.451 mg [7 tablets]
Yes
Tablets (Beyaz Oral)
3-0.02-0.451 mg (per each): $10.40
Tablets (Drospiren-Eth Estrad-Levomefol Oral)
3-0.02-0.451 mg (per each): $5.50 - $6.05
3-0.03-0.451 mg (per each): $6.65
Tablets (Safyral Oral)
3-0.03-0.451 mg (per each): $8.56
Tablets (Tydemy Oral)
3-0.03-0.451 mg (per each): $7.71
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:
YAZ Plus: Ethinyl estradiol 0.02 mg, drospirenone 3 mg, and levomefolate calcium 0.451 mg [24 tablets] and levomefolate calcium 0.451 mg [4 tablets]
Oral: Dose should be taken at the same time each day, either after the evening meal or at bedtime. May be administered with or without food.
According to the manufacturer, if severe diarrhea or vomiting occurs within 3 to 4 hours after taking an active tablet, consider the dose missed; back-up contraceptive measures may be needed. Additional guidelines are available (CDC [Curtis 2016a]).
Oral: Dose should be taken at the same time each day, either after the evening meal or at bedtime. May be administered with or without food.
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 (Curtis 2016a).
According to the manufacturer, if severe vomiting or diarrhea occurs, additional contraception (nonhormonal) should be used. If vomiting occurs within 3 to 4 hours of dosing, consider the dose to be missed. Additional guidelines are available (Curtis 2016a).
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).
Acne vulgaris (Beyaz, Rajani only): Treatment of moderate acne vulgaris in patients 14 years and older who have achieved menarche and who desire 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.
Folate supplementation: To increase folate concentrations in patients choosing an oral contraceptive as their method of contraception, in order to reduce the risk of neural tube defects in pregnancies conceived during therapy or soon after treatment is discontinued.
Premenstrual dysphoric disorder (Beyaz, Rajani only): Treatment of symptoms of premenstrual dysphoric disorder (PMDD) in patients who choose to use an oral contraceptive for contraception.
Limitations of use: The effectiveness of use for more than 3 menstrual cycles has not been evaluated. Has not been evaluated for the treatment of premenstrual syndrome (PMS).
Dysmenorrhea, primary and secondary to endometriosis; Hirsutism; Hyperlactation (hypergalactia); Menstrual suppression; Polycystic ovary syndrome in patients with hyperandrogenism and/or menstrual irregularities
Beyaz may be confused with Yaz
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
Aliskiren: Drospirenone-Containing Products may enhance the hyperkalemic effect of Aliskiren. Risk C: Monitor therapy
Anastrozole: Estrogen Derivatives may diminish the therapeutic effect of Anastrozole. Risk X: Avoid combination
Angiotensin II Receptor Blockers: Drospirenone-Containing Products may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Angiotensin-Converting Enzyme Inhibitors: Drospirenone-Containing Products may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
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
Heparin: Drospirenone-Containing Products may enhance the hyperkalemic effect of Heparin. Risk C: Monitor therapy
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: Drospirenone-Containing Products may enhance the hyperkalemic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
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 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 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
Potassium Salts: Drospirenone-Containing Products may enhance the hyperkalemic effect of Potassium Salts. Risk C: Monitor therapy
Potassium-Sparing Diuretics: Drospirenone-Containing Products may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. 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
Raltitrexed: Levomefolate may diminish the therapeutic effect of Raltitrexed. 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
The manufacturer states that combination hormonal contraceptives should not be started until ≥4 weeks after delivery in patients who choose not to breastfeed, or ≥4 weeks after a second trimester abortion or miscarriage.
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.
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 (Bonnington 2020; Krempasky 2020). However, drospirenone may potentially interfere with testosterone therapy more than other progestins due to its anti-androgenic and anti-mineralocorticoid properties (Bonnington 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 if pregnancy occurs. In general, the use of combination hormonal contraceptives, when inadvertently used early in pregnancy, have not been associated with adverse fetal or maternal effects (CDC [Curtis 2016b]).
The addition of levomefolate in this product is intended to decrease the risk of neural tube defects if pregnancy inadvertently occurs during therapy or shortly after discontinuation.
Drospirenone is present in breast milk. Refer to Drospirenone/Ethinyl Estradiol monograph for additional information. An increase in folate concentrations in breast milk is not expected.
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]).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Because combination hormonal contraceptives may reduce milk production, the manufacturer recommends use of other forms of contraception until the child is weaned when possible.
Due to the increased risk of venous thromboembolism (VTE) postpartum, do not initiate combination hormonal contraceptives in 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]).
Consider other sources of folic acid and ensure supplementation continues once therapy is discontinued. The RDA for folate in females 14 to 50 years of age is 400 mcg/day of dietary folate equivalents (IOM 1998). The USPSTF recommends that all patients who may become pregnant take a supplement containing folic acid 400 to 800 mcg/day in order to decrease the risk of neural tube defects (USPSTF 2017).
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]). In patients with conditions requiring chronic therapy with medications that may increase potassium, monitor serum potassium during the first treatment cycle. Consider monitoring serum potassium in high-risk patients taking strong CYP3A4 inhibitors.
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 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 measure to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding.
Combination oral contraceptives inhibit ovulation via a negative feedback mechanism on the hypothalamus, which alters the normal pattern of gonadotropin secretion of a follicle-stimulating hormone (FSH) and luteinizing hormone by the anterior pituitary. The follicular phase FSH and midcycle surge of gonadotropins are inhibited. In addition, oral contraceptives produce alterations in the genital tract, including changes in the cervical mucus, rendering it unfavorable for sperm penetration even if ovulation occurs. Changes in the endometrium may also occur, producing an unfavorable environment for nidation. Oral contraceptive drugs may alter the tubal transport of the ova through the fallopian tubes. Progestational agents may also alter sperm fertility. Drospirenone is a spironolactone analogue with antimineralocorticoid and antiandrogenic activity.
Distribution: Drospirenone: ~4 L/kg; Ethinyl estradiol: ~4-5 L/kg
Protein binding: Drospirenone: Serum proteins (excluding sex hormone-binding globulin and corticosteroid-binding globulin): ~97%; Ethinyl estradiol: ~99%
Metabolism: Drospirenone: To inactive metabolites, minor metabolism hepatically via CYP3A4; Ethinyl estradiol: Hepatic via CYP3A4; forms metabolites; undergoes first-pass metabolism and enterohepatic circulation
Bioavailability: Drospirenone: ~76%; Ethinyl estradiol: ~40%
Half-life elimination: Terminal: Drospirenone: ~31 hours; Ethinyl estradiol: ~24 hours; levomefolate calcium: ~4-5 hours
Time to peak: Drospirenone, ethinyl estradiol: 1-2 hours; Levomefolate calcium: 0.5-1.5 hours
Excretion: Drospirenone, ethinyl estradiol, levomefolate calcium: Urine and feces
Altered kidney function: Serum drospirenone concentrations are increased on average 37% in patients with a CrCl of 30 to 49 mL/minute.
Hepatic function impairment: The mean drospirenone exposure is 3 times greater in patients with moderate hepatic impairment.
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