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

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

For abbreviations, symbols, and age group definitions used in Lexicomp (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

Therapeutic Category

Contraceptive;
Estrogen and Progestin Combination

Dosing: Pediatric

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: Hepatic 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.

Dosing: Adult

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

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: Hepatic 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.

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)

Generic Equivalent Available: US

Pricing: US

Ring (Annovera Vaginal)

0.013-0.15 mg/24 hrs (per each): $2,766.34

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: 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.

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.

Hazardous Drugs Handling Considerations

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 double gloving and a protective gown if health care workers administer (NIOSH 2016). Facilities may perform assessment of some (non-antineoplastic) hazardous drugs to determine if appropriate for alternative containment strategies and handling requirements; assess risk to determine appropriate containment strategy (USP-NF 2017).

Storage/Stability

Prior to dispensing, store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from direct sunlight. Do not refrigerate or freeze; avoid excessive heat.

Use

Prevention of pregnancy (FDA approved in females of reproductive potential)

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Adalimumab: May decrease the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

Ajmaline: Estrogen Derivatives may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy

Anastrozole: Estrogen Derivatives may diminish the therapeutic effect of Anastrozole. Risk X: Avoid combination

Anthrax Immune Globulin (Human): Estrogen Derivatives may enhance the thrombogenic effect of Anthrax Immune Globulin (Human). Risk C: Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Antihepaciviral Combination Products: Ethinyl Estradiol-Containing Products may enhance the hepatotoxic effect of Antihepaciviral Combination Products. Risk X: Avoid combination

Aprepitant: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration with aprepitant, and to continue back-up contraception for 28 days after discontinuing aprepitant to ensure contraceptive reliability. Risk D: Consider therapy modification

Asparaginase Products: Hormonal Contraceptives may enhance the thrombogenic effect of Asparaginase Products. Management: Consider discontinuing hormonal contraceptives and using an alternative contraceptive method in patients treated with asparaginase products. Risk D: Consider therapy modification

Asunaprevir: May decrease the serum concentration of Hormonal Contraceptives. Management: Use of a high-dose oral contraceptive (at least 30 mcg of ethinyl estradiol combined with norethindrone) is recommended when combined with asunaprevir. Consider an additional barrier method when other forms of contraception are used with asunaprevir. Risk D: Consider therapy modification

Atazanavir: May decrease the serum concentration of Hormonal Contraceptives. Specifically, atazanavir/ritonavir may decrease concentrations of estrogens. Atazanavir may increase the serum concentration of Hormonal Contraceptives. Specifically, atazanavir alone may increase concentrations of estrogens and atazanavir alone or boosted may increase concentrations of progestins. Management: Dose adjustment of hormonal contraceptives or use of alternative or additional nonhormonal contraceptive may be needed when combined with atazanavir. See full interact monograph for details. Atazanavir/cobicistat with drospirenone is contraindicated. Risk D: Consider therapy modification

Bile Acid Sequestrants: May decrease the serum concentration of Ethinyl Estradiol-Containing Products. Management: Administer ethinyl estradiol-containing products 4 hours prior to the administration of a bile acid sequestrant. Risk D: Consider therapy modification

Bimekizumab: May decrease the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

Brigatinib: May decrease the serum concentration of Hormonal Contraceptives. Management: Use a non-hormonal contraceptive during brigatinib use and for at least 4 months after the last brigatinib dose. Males with partners of reproductive potential should use contraception during treatment with brigatinib and for 3 months after brigatinib use. Risk D: Consider therapy modification

C1 inhibitors: Estrogen Derivatives may enhance the thrombogenic effect of C1 inhibitors. Risk C: Monitor therapy

Carfilzomib: Hormonal Contraceptives may enhance the thrombogenic effect of Carfilzomib. Management: Consider alternative, non-hormonal methods of contraception in patients requiring therapy with carfilzomib, especially patients using carfilzomib in combination with dexamethasone, lenalidomide plus dexamethasone, or daratumumab plus dexamethasone. Risk D: Consider therapy modification

Chenodiol: Estrogen Derivatives may diminish the therapeutic effect of Chenodiol. Risk C: Monitor therapy

Chlorprothixene: Estrogen Derivatives may enhance the adverse/toxic effect of Chlorprothixene. Estrogen Derivatives may enhance the therapeutic effect of Chlorprothixene. Risk C: Monitor therapy

Chlorprothixene: Progestins may enhance the adverse/toxic effect of Chlorprothixene. Progestins may enhance the therapeutic effect of Chlorprothixene. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

Cobicistat: May decrease the serum concentration of Hormonal Contraceptives. Specifically, cobicistat may decrease serum concentrations of estrogens. Cobicistat may increase the serum concentration of Hormonal Contraceptives. Specifically, cobicistat may increase serum concentrations of progestins. Management: Use alternative or additional nonhormonal forms of contraception when estrogen-containing hormonal contraceptives are combined with cobicistat. Progestin-only contraceptives can be used without back up, but monitor for progestin toxicities. Risk D: Consider therapy modification

Colchicine: May enhance the adverse/toxic effect of Hormonal Contraceptives. Risk C: Monitor therapy

Corticosteroids (Systemic): Estrogen Derivatives may increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy

Cosyntropin: Estrogen Derivatives may diminish the diagnostic effect of Cosyntropin. Management: Discontinue estrogen containing drugs 4 to 6 weeks prior to cosyntropin (ACTH) testing. Risk D: Consider therapy modification

CycloSPORINE (Systemic): Ethinyl Estradiol-Containing Products may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a moderate CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification

CYP3A4 Inducers (Strong): May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a strong CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification

CYP3A4 Inducers (Weak): May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a weak CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Hormonal Contraceptives. Risk C: Monitor therapy

Dantrolene: Estrogen Derivatives may enhance the hepatotoxic effect of Dantrolene. Risk C: Monitor therapy

Dasabuvir: Ethinyl Estradiol-Containing Products may enhance the hepatotoxic effect of Dasabuvir. Risk X: Avoid combination

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

Dehydroepiandrosterone: May enhance the adverse/toxic effect of Estrogen Derivatives. Risk X: Avoid combination

Efavirenz: May decrease the serum concentration of Hormonal Contraceptives. Management: Use a back-up method during coadministration, and to continue back-up contraception for 12 weeks after stopping efavirenz to ensure contraceptive reliability. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Risk D: Consider therapy modification

Elagolix: Hormonal Contraceptives may diminish the therapeutic effect of Elagolix. Specifically, estrogen-containing hormonal contraceptives may diminish the therapeutic effects of elagolix. Elagolix may decrease the serum concentration of Hormonal Contraceptives. Specifically, concentrations of progestins may be decreased with elagolix therapy. Elagolix may increase the serum concentration of Hormonal Contraceptives. Specifically, concentrations of ethinyl estradiol may be increased with elagolix therapy. Management: Use an alternative, nonhormonal contraceptive during treatment with elagolix and for at least 28 days following discontinuation of elagolix treatment. Use of elagolix 200 mg twice daily with an estrogen-containing hormonal contraceptive is not recommended Risk D: Consider therapy modification

Elexacaftor, Tezacaftor, and Ivacaftor: Hormonal Contraceptives may enhance the adverse/toxic effect of Elexacaftor, Tezacaftor, and Ivacaftor. Specifically, the risk for rash may be increased. Risk C: Monitor therapy

Encorafenib: May decrease the serum concentration of Hormonal Contraceptives. Risk X: Avoid combination

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk X: Avoid combination

Etravirine: May decrease the serum concentration of Hormonal Contraceptives. Specifically, progestin concentrations may decrease. Etravirine may increase the serum concentration of Hormonal Contraceptives. Specifically, estrogen concentrations may increase. Risk C: Monitor therapy

Exemestane: Estrogen Derivatives may diminish the therapeutic effect of Exemestane. Risk X: Avoid combination

Exenatide: Hormonal Contraceptives may diminish the therapeutic effect of Exenatide. Exenatide may decrease the serum concentration of Hormonal Contraceptives. Management: Administer oral hormonal contraceptives at least one hour prior to exenatide. Monitor blood glucose more frequently when patients treated with exenatide initiate therapy with a hormonal contraceptive. Increases in exenatide doses may be needed. Risk D: Consider therapy modification

Felbamate: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing felbamate to ensure contraceptive reliability. Risk D: Consider therapy modification

Ferric Maltol: May decrease the serum concentration of Ethinyl Estradiol-Containing Products. Management: Ferric maltol labeling recommends separating administration of ethinyl estradiol-containing products from ferric maltol by at least four hours to minimize the potential for any interaction. Risk D: Consider therapy modification

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fezolinetant: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination

Flibanserin: Hormonal Contraceptives may increase the serum concentration of Flibanserin. Risk C: Monitor therapy

Fosaprepitant: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration with fosaprepitant, and to continue back-up contraception for 28 days after discontinuing fosaprepitant to ensure contraceptive reliability. Risk D: Consider therapy modification

Fostemsavir: May increase the serum concentration of Ethinyl Estradiol-Containing Products. Management: Ethinyl estradiol daily dose should not exceed 30 mcg during coadministration with fostemsavir. Monitor patients closely for any evidence of a thromboembolism. Risk D: Consider therapy modification

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Glecaprevir and Pibrentasvir: Ethinyl Estradiol-Containing Products may enhance the hepatotoxic effect of Glecaprevir and Pibrentasvir. Glecaprevir and Pibrentasvir may increase the serum concentration of Ethinyl Estradiol-Containing Products. Management: Use of glecaprevir/pibrentasvir and products containing more than 20 mcg of ethinyl estradiol is not recommended. Lower dose ethinyl estradiol-containing products may be used. Risk D: Consider therapy modification

Griseofulvin: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing griseofulvin to ensure contraceptive reliability. Risk D: Consider therapy modification

Growth Hormone Analogs: Estrogen Derivatives may diminish the therapeutic effect of Growth Hormone Analogs. Management: Initiate somapacitan at 2 mg once weekly in patients receiving oral estrogens. Monitor for reduced efficacy of growth hormone analogs; increased doses may be required. Risk D: Consider therapy modification

Guanethidine: Estrogen Derivatives may diminish the therapeutic effect of Guanethidine. Risk C: Monitor therapy

Hemin: Estrogen Derivatives may diminish the therapeutic effect of Hemin. Risk X: Avoid combination

Hyaluronidase: Estrogen Derivatives may diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy

Hydrocortisone (Systemic): Estrogen Derivatives may increase the serum concentration of Hydrocortisone (Systemic). Estrogen Derivatives may decrease the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy

Immune Globulin: Estrogen Derivatives may enhance the thrombogenic effect of Immune Globulin. Risk C: Monitor therapy

Indium 111 Capromab Pendetide: Estrogen Derivatives may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: Avoid combination

Interleukin-6 (IL-6) Inhibiting Therapies: May decrease the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

Ivosidenib: May decrease the serum concentration of Hormonal Contraceptives. Management: Consider alternative methods of contraception (ie, non-hormonal) in patients receiving ivosidenib. Risk D: Consider therapy modification

Ixazomib: May decrease the serum concentration of Hormonal Contraceptives. More specifically, use of ixazomib with dexamethasone may decrease the serum concentrations of hormonal contraceptives. Management: Patients of reproductive potential should use a non-hormonal contraceptive method during treatment with ixazomib and for at least 90 days after the last ixazomib dose. Risk D: Consider therapy modification

Lactic Acid, Citric Acid, and Potassium Bitartrate: Ethinyl Estradiol may diminish the therapeutic effect of Lactic Acid, Citric Acid, and Potassium Bitartrate. Risk X: Avoid combination

LamoTRIgine: Estrogen Derivatives (Contraceptive) may decrease the serum concentration of LamoTRIgine. Management: Larger doses of lamotrigine may be needed when combined with estrogens. Specific dosing recommendations vary based on other concomitant medications and which medication is being initiated or discontinued. See interaction monograph for details. Risk D: Consider therapy modification

Lenalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Lenalidomide. Risk C: Monitor therapy

Lixisenatide: Hormonal Contraceptives may diminish the therapeutic effect of Lixisenatide. Lixisenatide may decrease the serum concentration of Hormonal Contraceptives. Management: Administer oral hormonal contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. Additionally, monitor blood glucose more frequently when patients treated with lixisenatide initiate therapy with a hormonal contraceptive. Risk D: Consider therapy modification

Lomitapide: Estrogen Derivatives may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 40 mg/day. Risk D: Consider therapy modification

Mavacamten: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative contraceptive that is not sensitive to CYP3A4 induction or a back-up method during coadministration, and to continue back-up contraception for 4 months after stopping mavacamten to ensure contraceptive reliability. Risk D: Consider therapy modification

Melatonin: Estrogen Derivatives may increase the serum concentration of Melatonin. Risk C: Monitor therapy

MetyraPONE: Estrogen Derivatives may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking estrogen derivatives. Risk D: Consider therapy modification

MetyraPONE: Progestins may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking progestins. Risk D: Consider therapy modification

MiFEPRIStone: May diminish the therapeutic effect of Hormonal Contraceptives. Management: Nonhormonal contraception should be used during, and for 4 weeks following, mifepristone treatment for hyperglycemia due to Cushing syndrome. If used for pregnancy termination, hormonal contraceptives can be used after pregnancy expulsion is confirmed. Risk D: Consider therapy modification

Mitotane: May decrease the serum concentration of Hormonal Contraceptives. Management: Effective nonhormonal contraception is recommended for those of reproductive potential during treatment with mitotane as well as after discontinuation of mitotane for as long as mitotane plasma levels are detectable. Risk X: Avoid combination

Mivacurium: Estrogen Derivatives may increase the serum concentration of Mivacurium. Risk C: Monitor therapy

Mobocertinib: May decrease the serum concentration of Hormonal Contraceptives. Risk X: Avoid combination

Mycophenolate: May decrease the serum concentration of Hormonal Contraceptives. Management: Patients of childbearing potential who are taking hormonal contraceptives should use an additional form of barrier contraception during treatment with mycophenolate and for 6 weeks after mycophenolate discontinuation. Risk D: Consider therapy modification

Nirmatrelvir and Ritonavir: May decrease the serum concentration of Hormonal Contraceptives. Specifically, nirmatrelvir and ritonavir may decrease concentrations of estrogens. Nirmatrelvir and Ritonavir may increase the serum concentration of Hormonal Contraceptives. Specifically, nirmatrelvir and ritonavir may increase concentrations of progestins. Management: Use additional nonhormonal forms of contraception (back-up method) when estrogen-containing hormonal contraceptives are combined with nirmatrelvir/ritonavir. Progestin-only contraceptives can be used without back-up, but monitor for progestin toxicities. Risk D: Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the thrombogenic effect of Estrogen Derivatives. Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy

Octreotide: May decrease the serum concentration of Hormonal Contraceptives. Management: Women should use an alternative non-hormonal method of contraception or a back-up method when octreotide is combined with hormonal contraceptives. Risk D: Consider therapy modification

Olutasidenib: May decrease the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Management: Avoid use of olutasidenib with sensitive or narrow therapeutic index CYP3A4 substrates when possible. If concurrent use with olutasidenib is unavoidable, monitor closely for evidence of decreased concentrations of the CYP3A4 substrates. Risk D: Consider therapy modification

Omaveloxolone: May decrease the serum concentration of Hormonal Contraceptives. Risk X: Avoid combination

Ospemifene: Estrogen Derivatives may enhance the adverse/toxic effect of Ospemifene. Risk X: Avoid combination

OXcarbazepine: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing oxcarbazepine to ensure contraceptive reliability. Risk D: Consider therapy modification

Perampanel: May decrease the serum concentration of 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

Proguanil: Ethinyl Estradiol-Containing Products may decrease serum concentrations of the active metabolite(s) of Proguanil. Risk C: Monitor therapy

Protease Inhibitors: May decrease the serum concentration of Hormonal Contraceptives. Specifically, protease inhibitors may decrease concentrations of estrogens. Protease Inhibitors may increase the serum concentration of Hormonal Contraceptives. Specifically, protease inhibitors may increase concentrations of progestins. Management: Use alternative or additional nonhormonal forms of contraception when estrogen-containing hormonal contraceptives are combined with protease inhibitors. Progestin-only contraceptives can be used without back up, but monitor for progestin toxicities. Risk D: Consider therapy modification

Raloxifene: Estrogen Derivatives may enhance the adverse/toxic effect of Raloxifene. Risk X: Avoid combination

Repotrectinib: May decrease the serum concentration of Hormonal Contraceptives. Risk X: Avoid combination

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

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]).

Monitoring Parameters

Assessment of pregnancy status (prior to therapy); blood pressure (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 (Curtis 2016a).

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

Monitor patient for vision changes; blood pressure; 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, including endometrial sampling, if indicated, should be performed to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding.

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 119751 Version 118.0

خرید پکیج

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