Contraceptive vaginal ring (Ethinyl estradiol and segesterone [Yearly]): Drug information

For additional information see "Contraceptive vaginal ring (Ethinyl estradiol and segesterone [Yearly]): Patient drug information" and "Contraceptive vaginal ring (Ethinyl estradiol and segesterone [Yearly]): Pediatric drug information"

For abbreviations, symbols, and age group definitions show table

ALERT: US Boxed Warning

Cigarette smoking and serious cardiovascular events

Cigarette smoking increases the risk of serious cardiovascular events from combination hormonal contraceptive (CHC) use. This risk increases with age, particularly in females >35 years of age, and with the number of cigarettes smoked. For this reason, CHCs should not be used by females who are >35 years of age and smoke.

Brand Names: US

Annovera

Pharmacologic Category

Contraceptive;
Estrogen and Progestin Combination

Dosing: Adult

Contraception

Contraception: Vaginal: Insert 1 ring vaginally. Following insertion, ring should remain in place for 21 continuous days (3 weeks), then removed for 7 days (1 week). This pattern (3 weeks in and 1 week out) is one cycle; one ring provides contraception for 13 cycles (1 year).

Patients not currently using a hormonal contraceptive: Insert between days 2 and 5 of menstrual cycle. Back-up barrier contraception should be used for the first 7 days of therapy if menstrual cycles are irregular or if start is >5 days from last menstrual bleeding.

**Patients Switching From Another Contraceptive Method to the Ethinyl Estradiol/Segesterone Acetate Vaginal Ring**
Current method	Instructions for switching to estradiol/segesterone acetate vaginal ring
^a CHC = combined hormonal contraceptive.
^b Examples of an additional back-up barrier method are male condoms or spermicide.
CHC^a	Insert at any time during the 28-day cycle. Back-up barrier contraception is not needed if CHC was used correctly and consistently and there are ≤7 hormone-free days prior to start.
Copper IUD	Follow instructions for patients not currently using a hormonal contraceptive.
Progestin-only pill	Insert at the time the next oral pill would be taken. Back-up barrier contraception^b should be used for the first 7 days of therapy.
Progestin-only injection	Insert at the time of the next scheduled injection. Back-up barrier contraception^b should be used for the first 7 days of therapy.
Progestin-only implant	Insert at the time the implant is removed. Back-up barrier contraception^b should be used for the first 7 days of therapy.
Progestin-only intrauterine system	Insert at the time the intrauterine system is removed. Back-up barrier contraception^b should be used for the first 7 days of therapy.

**Use of Ethinyl Estradiol/Segesterone Acetate After Childbirth, Abortion, or Miscarriage**
^aExamples of an additional back-up barrier method are male condoms or spermicide.
Use after childbirth (not breastfeeding)	Do not insert <4 weeks following childbirth due to increased risk of thromboembolism. When starting therapy ≥4 weeks postpartum in patients who have not yet had a menstrual cycle, back-up barrier contraception^a should be used for the first 7 days of therapy. Consider the possibility of ovulation and conception prior to initiation.
Use after first trimester abortion or miscarriage	Insert within 5 days following first trimester abortion or miscarriage; back-up barrier contraception is not needed. If insertion does not occur within 5 days, follow instructions for patients not currently using a hormonal contraceptive.
Use after second trimester abortion or miscarriage	Do not insert <4 weeks following second trimester abortion or miscarriage due to increased risk of thromboembolism.

**Additional Ethinyl Estradiol/Segesterone Acetate Vaginal Ring Contraceptive Considerations**
^a Examples of an additional back-up barrier method are male condoms or spermicide.
Deviation from recommended regimen	Any deviation from the recommended dosing cycle (3 weeks in and 1 week out is 1 cycle) that results in the ring being out of the vagina for >7 days requires back-up barrier contraception^a for 7 consecutive days.
Inadvertent removal or expulsion	If ring is accidently expelled during the 21 days of vaginal use and replaced within 2 hours, back-up contraception is not required. If ring is out of the vagina for >2 hours (or >2 cumulative hours if multiple expulsions occur), back-up barrier contraception^a should be used until the vaginal ring has been in place for 7 consecutive days. Use of combined hormonal contraceptives (containing estrogen) for emergency contraception is not recommended.
Prolonged vaginal-free interval	If vaginal-free interval is prolonged (ring has been removed for >7 days), back-up barrier contraception^a should be used until the vaginal ring has been in place for 7 consecutive days. Use of combined hormonal contraceptives (containing estrogen) for emergency contraception is not recommended.
Prolonged insertion	If ring is left in place for >21 days, remove for 7 days, then restart/resume a 21/7-day cycle

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use is not recommended.

Dosing: Liver Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Acute or chronic changes in liver function may require discontinuation until tests of hepatic function become normal and causation has been excluded. Use is contraindicated in patients with hepatic tumors, acute hepatitis, or severe (decompensated) cirrhosis.

Dosing: Pediatric

(For additional information see "Contraceptive vaginal ring (Ethinyl estradiol and segesterone [Yearly]): Pediatric drug information")

Contraception

Contraception: Postmenarche female: Intravaginal: Insert one ring vaginally. Following insertion, ring should remain in place for 21 continuous days (3 weeks), then removed for 7 days (1 week). The pattern of 3 weeks in and 1 week out is one cycle; one ring provides contraception for 13 cycles (1 year).

Initiation of therapy:

No hormonal contraceptive use in preceding cycle and after copper IUD removal: Insert ring between days 2 and 5 of regular menstrual bleeding. Back-up barrier contraception should be used for the first 7 days of therapy if menstrual cycles are irregular or if start is >5 days from last menstrual bleeding.

Switching from a combination hormonal contraceptive (CHC): Insert ring at any time during the 28-day cycle. Back-up barrier contraception is not needed if CHC was used correctly and consistently and there are ≤7 hormone free days prior to start.

Switching from a progestin only method (progestin only pill, injection, implant, or intrauterine system): Insert ring at the time of either: The next oral pill would be taken, the implant or intrauterine system is removed, or at the next scheduled injection. Back-up barrier contraception should be used for the first 7 days of therapy.

Following first trimester abortion or miscarriage: Insert ring within 5 days following a first trimester abortion or miscarriage; back-up barrier contraception is not needed. If insertion does not occur within 5 days, back-up barrier contraception should be used for the first 7 days of therapy.

Following second trimester abortion or miscarriage: Do not insert <4 weeks following second trimester abortion or miscarriage.

Following childbirth in non-breastfeeding individuals: Do not insert <4 weeks following childbirth. Back-up barrier contraception should be used for the first 7 days of therapy. Note: Breastfeeding individuals may begin therapy after weaning.

Additional contraception dosing considerations:

Any deviation from the recommended dosing cycle (3 weeks in and 1 week out is one cycle) that results in the ring being out of the vagina for >7 days requires back-up contraception.

Inadvertent removal or expulsion: If ring is accidently expelled during the 21 days of vaginal use and replaced within 2 hours, back-up contraception is not required. If ring is out of the vagina for >2 hours (or >2 cumulative hours if multiple expulsions occur), back-up contraception (male condom or spermicide) should be used until the vaginal ring has been in place for 7 consecutive days. Use of combined hormonal contraceptives (containing estrogen) used for emergency contraception are not recommended.

Prolonged vaginal free interval: If vaginal free interval is prolonged (ring has been removed for >7 days), back-up contraception (male condom or spermicide) should be used until the vaginal ring has been in place for 7 consecutive days. Use of combined hormonal contraceptives (containing estrogen) used for emergency contraception are not recommended.

Prolonged insertion: If ring is left in place for >21 days, remove for 7 days, then restart/resume a 21/7 day cycle.

Concomitant use with enzyme inducers (eg, aprepitant, barbiturates, bosentan, carbamazepine, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, rifabutin, furinamide, topiramate, St John's wort, certain protease inhibitors): Alternate methods of contraception are recommended, otherwise, back-up contraception should be used during therapy with the concomitant medication and for 28 days after the last dose of the enzyme inducer.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Segesterone acetate/ethinyl estradiol is not recommended in patients with renal impairment; has not been studied.

Dosing: Liver Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling (has not been studied). Acute or chronic changes in liver function may require discontinuation until tests of hepatic function become normal and causation has been excluded. Use is contraindicated in patients with hepatic tumors (benign or malignant), acute hepatitis, or severe (decompensated) cirrhosis.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Central nervous system: Headache (≤39%), migraine (≤39%)

Gastrointestinal: Nausea (≤25%), vomiting (≤25%), abdominal pain (≤13%), lower abdominal pain (≤13%), upper abdominal pain (≤13%)

Genitourinary: Vulvovaginal candidiasis (15%), dysmenorrhea (13%), vaginal discharge (12%)

1% to 10%:

Cardiovascular: Cerebral thrombosis (≥2%), deep vein thrombosis (≥2%), pulmonary embolism (≥2%)

Central nervous system: Psychiatric disturbance (≥2%)

Dermatologic: Genital pruritus (6%)

Endocrine & metabolic: Heavy menstrual bleeding (≤8%), menstrual disease (≤8%), amenorrhea (≤5%)

Gastrointestinal: Diarrhea (7%)

Genitourinary: Breakthrough bleeding (≤10%), breast tenderness (≤10%), cystitis (≤10%), genitourinary infection (≤10%), mastalgia (≤10%), spotting (≤10%), urinary tract infection (≤10%), spontaneous abortion (≥2%)

Hypersensitivity: Drug-induced hypersensitivity (≥2%)

Renal: Pyelonephritis (≤10%)

Contraindications

Hypersensitivity to segesterone, ethinyl estradiol, or any component of the formulation; breast cancer (current or a history of [may be hormonal-sensitive]), hepatic tumors (benign or malignant), acute hepatitis, severe (decompensated) cirrhosis, pregnancy, undiagnosed abnormal uterine bleeding; concomitant 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, for example, patients with: cerebrovascular disease, coronary artery disease, diabetes mellitus with hypertension or vascular disease (or other end organ damage), diabetes mellitus and >35 years of age, diabetes mellitus >20 years duration, deep vein thrombosis or pulmonary embolism (current or history of), hypercoagulopathies (inherited or acquired), headaches with focal neurological symptoms, migraine headaches with aura, migraine headaches if >35 years of age, hypertension (uncontrolled or with concomitant vascular disease), 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.

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding irregularities: Breakthrough or intracyclic bleeding and spotting may occur, especially during the first month of therapy. Persistent unscheduled bleeding or breakthrough bleeding following previously regular cycles during therapy warrants further evaluation to rule out malignancy or pregnancy. Amenorrhea may occur during therapy. In addition, 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. Patients with a susceptibility to chloasma or additional risk factors should avoid exposure to sun or ultraviolet radiation during therapy.

• 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 use if unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions occur and immediately evaluate for retinal vein 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) and should not be used in patients with a history of stroke or ischemic heart disease (CDC [Curtis 2016b]).

• Toxic shock syndrome: Has been reported following use of vaginal rings and in some cases, concomitant tampon use (causal relationship has not been established).

Disease-related concerns:

• Bariatric surgery: Fertility is increased following bariatric surgery. All available forms of contraception can be considered following bariatric surgery, considering the patient's body weight and time since surgery. However, long-acting reversible non-oral contraceptives (eg, implants, intrauterine devices) may be preferred. Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy both have the potential to expedite transit through the small bowel. RYGB may not significantly alter the absorption of oral estrogen or progestins (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 bypass, biliopancreatic diversion, single anastomosis duodeno-ilial bypass, or omega-loop gastric bypass. Estrogen-containing birth control should be stopped 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 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. However, use in patients with concomitant nephropathy, neuropathy, retinopathy, other vascular disease, or diabetes >20 years duration should be evaluated for contraceptive use 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. Use of combination hormonal contraceptives may be considered in patients with mild (compensated) 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 of combination hormonal contraceptives 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. Combination hormonal contraceptives should not be used 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]). Other risk factors for cardiovascular disease (eg, older age, smoking, diabetes) should be considered when prescribing contraceptives (CDC [Curtis 2016b]). Monitor BP in patients with well-controlled hypertension; discontinue therapy if BP rises significantly.

• Migraine: Evaluate new, recurrent, severe, or persistent headaches and discontinue use if indicated. Use of combination hormonal contraceptives may be considered in patients who have migraines without aura (including menstrual migraines) (CDC [Curtis 2016b]).

• Ovarian cancer: The risk of ovarian cancer is decreased in patients using combination hormonal contraceptives (CDC [Curtis 2016b]; SGO/ASRM [Chen 2019]). Oral contraceptives may be used to reduce the risk of ovarian cancer in at-risk patients with BRCA1 and BRCA2 mutations who do not have a personal history of breast cancer (SGO/ASRM [Chen 2019]). Patients awaiting treatment for ovarian cancer may use combination hormonal contraceptives (CDC [Curtis 2016b]).

• Solid organ transplant: Use of combination hormonal contraceptives is not recommended in patients with complicated organ transplants; although data are limited, serious medical complications have been reported (eg, graft failure, rejection, cardiac allograft vasculopathy) requiring discontinuation of the contraceptive (CDC [Curtis 2016b]).

• Systemic lupus erythematosus: Patients with systemic lupus erythematosus (SLE) are at an increased risk for heart disease, stroke, and VTE. Combination hormonal contraceptives should not be used in patients with SLE who have positive (or unknown) antiphospholipid antibodies, due to an increased risk of arterial and venous thrombosis (CDC [Curtis 2016b]).

Concurrent drug therapy issues:

• Testosterone: All available forms of contraception can be considered for patients receiving gender-affirming testosterone therapy after evaluating patient preferences and medical conditions (Bonnington 2020; Krempasky 2020). However, it has been suggested to use contraceptive products containing lower daily doses of ethinyl estradiol (10 to 20 mcg) to decrease the risk of possible adverse reactions when testosterone therapy is used with combination hormonal contraceptives (Bonnington 2020).

Special populations:

• Body weight: This product has not been adequately studied in patients with a BMI >29 kg/m². 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]). Clinical studies excluded females with a BMI >29 kg/m² after two VTEs occurred in females with a BMI >29 kg/m².

• Smoking: Cigarette smoking increases the risk of serious cardiovascular events from combination hormonal contraceptive use. This risk increases with age, particularly in patients >35 years of age, and with the number of cigarettes smoked.

• Surgical patients: Discontinue during periods of prolonged immobilization. Whenever possible, discontinue at least 4 weeks prior to and through 2 weeks following major surgery or other surgery associated with an increased risk of thromboembolism.

Dosage form specific issues:

• Vaginal ring: Use may not be appropriate in patients with conditions that may increase the risk of vaginal irritation or ulceration. Information related to concomitant use with diaphragms, cervical caps, and female condoms is not available. Water-based vaginal creams, suppositories, or lubricants may be used with the vaginal ring; oil-based (including silicone based) vaginal products should not be used. Use is compatible with male condoms made with natural rubber latex, polyisoprene, and polyurethane. Patients and their partners may be aware of the vaginal ring during intercourse.

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]).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Ring, Vaginal:

Annovera: Ethinyl estradiol 0.013 mg/day and segesterone acetate 0.15 mg/day [3-week duration] (1 ea)

Annovera: Ethinyl estradiol 0.013 mg/day and segesterone acetate 0.15 mg/day [3-week duration] (1 ea) [latex free]

Generic Equivalent Available: US

Pricing: US

Ring (Annovera Vaginal)

0.013-0.15 mg/24 hrs (per each): $2,904.66

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.

Administration: Adult

Intravaginal: Prior to each insertion, wash vaginal ring with mild soap and water, rinse and pat dry. Press sides of ring together and insert folded ring into vagina as far as possible, to a comfortable position completely inside the vagina and behind the pelvic bone. Note day of week and time of day, then remove at the same time/day of the week 3 weeks later. To remove, hook ring with finger and pull downward and forward. Wash ring with mild soap and lukewarm water, dry, and store in provided case until next insertion. Do not discard in toilet.

One vaginal ring can be used for 13 cycles (1 year) when used 3 weeks in and 1 week out per cycle.

Administration: Pediatric

Intravaginal: Prior to each insertion, wash vaginal ring with mild soap and water, rinse, and pat dry. Press sides of ring together and insert folded ring into vagina as far as possible, to a comfortable position completely inside the vagina and behind the pelvic bone. Note day of week and time of day, then remove at the same time and day 3 weeks later. To remove, hook ring with finger and pull downward and forward. Wash ring with mild soap and lukewarm water, dry, and store in provided case until next insertion. Do not discard in toilet. One vaginal ring can be used for 13 cycles (1 year) when used 3 weeks in and 1 week out per cycle.

Hazardous Drugs Handling Considerations

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.

Use: Labeled Indications

Contraceptive: 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. This product has not been adequately studied in patients with a BMI >29 kg/m².

Medication Safety Issues

High alert medication:

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).

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

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

Reproductive Considerations

Information related to concomitant use with diaphragms, cervical caps and female condoms is not available. Use is compatible with male condoms made with natural rubber latex, polyisoprene, and polyurethane. Fertility is expected to return within 6 months after discontinuing use.

Due to the increased risk of venous thromboembolism (VTE) postpartum, combination hormonal contraceptives should not be started in any patient <21 days following delivery. The risk decreases to baseline by postpartum day 42. Use of combination hormonal contraceptives in patients between 21 and 42 days after delivery should take into consideration the individual patient's risk factors for VTE (eg, ≥35 years of age, previous VTE, thrombophilia, immobility, preeclampsia, transfusion at delivery, cesarean delivery, peripartum cardiomyopathy, BMI ≥30 kg/m², postpartum hemorrhage, smoking) (CDC [Curtis 2016b]).

All available forms of contraception, including combination hormonal contraceptives, can be considered for patients on gender-affirming testosterone therapy after evaluating patient preferences and medical conditions (eg, risk for VTE) (Bonnington 2020; Krempasky 2020). Use of the vaginal ring may promote growth of breast tissue even after top (chest masculinization) surgery (Bonnington 2020).

This product has not been adequately studied in patients with a BMI >29 kg/m².

Pregnancy Considerations

Combination hormonal contraceptives are used to prevent pregnancy; treatment should be discontinued 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]).

Breastfeeding Considerations

Contraceptive steroids are present in breast milk.

Segesterone acetate has been detected in breast milk following use as a contraceptive implant, a dosage form that provided lower maternal serum levels than the vaginal ring. Adverse events were not observed in the infants. Segesterone acetate has low oral bioavailability, which would limit adverse events if exposure occurs to the infant via breast milk (Lähteenmäki 1990).

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 combination hormonal 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, combination hormonal contraceptives should not be started in patients <21 days following delivery. The risk decreases to baseline by postpartum day 42. Use of combination hormonal contraceptives in patients between 21 and 42 days after delivery should take into consideration the individual patients risk factors for VTE (eg, ≥35 years of age, previous VTE, thrombophilia, immobility, preeclampsia, transfusion at delivery, cesarean delivery, peripartum cardiomyopathy, BMI ≥30 kg/m², postpartum hemorrhage, smoking). The risks, benefits, and alternatives to combination hormonal contraception should be evaluated when initiating treatment in breastfeeding patients (CDC [Curtis 2016b]).

Monitoring Parameters

Assessment of pregnancy status (prior to therapy); BP (prior to therapy and yearly); personal or family history of thrombotic or thromboembolic disorders (prior to therapy); weight (optional; BMI at baseline may be helpful to monitor changes during therapy); assess potential health status changes at routine visits (CDC [Curtis 2016a]).

If not used on schedule and 1 menstrual period is missed, the possibility of pregnancy should be considered. If 2 consecutive menstrual periods are missed, assess pregnancy status before a new dosing cycle is started.

Monitor patient for vision changes; 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. Adequate diagnostic measures should be performed to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding.

Reference Range

Releases ethinyl estradiol ~0.013 mg and segesterone acetate ~0.15 mg daily over 3-week dosing interval.

Mechanism of Action

Combination hormonal contraceptives lower the risk of pregnancy primarily by suppressing ovulation.

Pharmacokinetics (Adult Data Unless Noted)

Onset: Effective on the day of insertion when inserted between days 2 and 5 of menstrual period

Distribution: Segesterone acetate: V_d 19.6 L/kg

Protein binding: Ethinyl estradiol: 98.5%; increases sex hormone binding globulin (SHBG); Segesterone acetate: 95% to human serum; negligible to SHBG

Metabolism: Ethinyl estradiol and segesterone acetate: Hepatic via CYP 3A4 to metabolites

Half-life elimination: Ethinyl estradiol: 15.1 ± 7.5 hours; Segesterone acetate: 4.5 ± 3.4 hours

Time to peak: Ethinyl estradiol and segesterone acetate: 2 hours (median) following cycle 1; peak concentrations decline over subsequent dosing cycles

Excretion: Ethinyl estradiol: Urine and feces

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Obesity: Systemic exposure (AUC _{0-21 day}) of ethinyl estradiol is decreased by 33% and systemic exposure of segesterone acetate is decreased by 16% in patients with a BMI >25 kg/m² when compared to patients with a BMI <25 kg/m²

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(PR) Puerto Rico: Annovera

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Topic 118741 Version 162.0

خرید پکیج

Contraceptive vaginal ring (Ethinyl estradiol and segesterone [Yearly]): Drug information