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Contraceptive vaginal ring (Ethinyl estradiol and etonogestrel [Monthly]): Drug information

Contraceptive vaginal ring (Ethinyl estradiol and etonogestrel [Monthly]): Drug information
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For additional information see "Contraceptive vaginal ring (Ethinyl estradiol and etonogestrel [Monthly]): Patient drug information" and "Contraceptive vaginal ring (Ethinyl estradiol and etonogestrel [Monthly]): Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
ALERT: US Boxed Warning
Cigarette smoke 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 women over 35 years of age, and with the number of cigarettes smoked. For this reason, CHCs, including ethinyl estradiol/etonogestrel, should not be used by women who are over 35 years of age and smoke.

Brand Names: US
  • EluRyng;
  • EnilloRing;
  • Haloette;
  • NuvaRing
Brand Names: Canada
  • Haloette;
  • NuvaRing
Pharmacologic Category
  • Contraceptive;
  • Estrogen and Progestin Combination
Dosing: Adult
Contraception

Contraception: Vaginal: One ring, inserted vaginally and left in place continuously for 3 consecutive weeks, then removed for 1 week. A new ring is inserted 7 days after the last was removed (even if bleeding is not complete) and should be inserted at approximately the same time of day the ring was removed the previous week. Note: The ring may interfere with proper placement of certain barrier methods (eg, diaphragm, cervical cap, female condom); therefore, those barrier methods are not recommended for use as additional forms of contraception.

Initial dose: Patients with no hormonal contraceptive use in the past month should insert ring on the first day of menstrual cycle. May also insert on days 2 to 5 of the menstrual cycle but in this case, a barrier method of contraception (eg, male condom with spermicide) should be used for the following 7 days.

Initial dose, quick-start method: If reasonably sure the patient is not pregnant, may be initiated at any time during the menstrual cycle (Ref). Start on the day the patient receives the prescription (Ref). If initiated >5 days after the onset of menses, use an additional method of contraception (nonhormonal) until 7 days of consecutive administration (Ref).

Patients Switching from Another Contraceptive Method to the Ethinyl Estradiol/Etonogestrel Vaginal Ring

Current method

Instructions for switching to vaginal ring

a A barrier method of contraception (eg, male condom with spermicide) should be used for 7 days following ring insertion. Certain barrier methods (eg, diaphragm, cervical cap, female condom) may interfere with proper ring placement, and therefore, are not recommended for use as an additional form of contraception

Combined hormonal contraceptive (CHC)

Vaginal ring can be inserted on any day, but at the latest on the day following the usual hormone-free interval, if patient is using the hormonal method consistently and correctly, or if it is reasonably sure patient is not pregnant.

Implant

Insert vaginal ring on the same day of implant removala

Injection

Insert vaginal ring on the day the next injection would be givena

Intrauterine system (IUS)

Insert vaginal ring on day of IUS removala

Progestin only pill (POP)

May switch to vaginal ring on any day; insert the vaginal ring on the day after the last POPa

Use of Ethinyl Estradiol/Etonogestrel Vaginal Ring After Childbirth, Abortion, or Miscarriage

a Certain barrier methods (eg, diaphragm, cervical cap, female condom) may interfere with proper ring placement, and therefore, are not recommended for use as an additional form of contraception.

Use after childbirth

The vaginal ring should not be started <4 weeks after childbirth in patients who are not breastfeeding.

If postpartum menstrual cycles have not returned, assess pregnancy status before use. If not pregnant, a barrier method of contraception (eg, male condom with spermicide) should be used for 7 days following ring insertion.a

The manufacturer recommends other forms of contraception for patients who are breastfeeding.

Use after first trimester abortion or miscarriage

Vaginal ring can be inserted within the first 5 days of a complete first trimester abortion or miscarriage. If not inserted within 5 days, a barrier method of contraception (eg, male condom with spermicide) should be used for 7 days following ring insertion.a

Use after second trimester abortion or miscarriage

Vaginal ring should not be initiated <4 weeks after a second trimester abortion or miscarriage due to increased risk of thromboembolism.

Additional Ethinyl Estradiol/Etonogestrel Vaginal Ring Contraceptive Considerations

a Certain barrier methods (eg, diaphragm, cervical cap, female condom) may interfere with proper ring placement, and therefore, are not recommended for use as an additional form of contraception. Additional guidelines are available following delayed insertion/reinsertion of vaginal ring (CDC [Curtis 2016a]).

Inadvertent removal or expulsion

If the ring is accidentally removed from the vagina at any time during the 3-week period of use, it may be rinsed with cool or lukewarm water (not hot) and reinserted as soon as possible.

If the vaginal ring is not reinserted within 3 hours, contraceptive effectiveness will be decreased.

If the ring is accidently removed from the vagina for >3 continuous hours during weeks 1 and 2:

  • The ring should be reinserted as soon as possible and a barrier method of contraception (eg, male condom with spermicide) should be used for 7 days following ring insertion.a

If the ring is accidently removed from the vagina for >3 hours during week 3:

  • The ring should be discarded. A new ring may be inserted immediately, restarting a new 3-week cycle, OR a new ring may be inserted ≤7 days from the time the previous ring was removed or expelled (the second option should only be done if a vaginal ring was in continuous use for ≥7 days prior to the inadvertent expulsion/removal). With either option, a barrier method of contraception (eg, male condom with spermicide) should be used for 7 days following ring insertion.a

If the vaginal ring has been removed for >1 week or for an unknown period of time:

  • Pregnancy must be ruled out prior to restarting therapy. If not pregnant, a barrier method of contraception (eg, male condom with spermicide) should be used for 7 days following ring insertion.a

Prolonged vaginal ring insertion

If the vaginal ring has been left in place for up to 1 extra week (up to 4 weeks total), a new ring should be inserted following a 1-week (ring-free) interval. If the vaginal ring is left in place >4 weeks, pregnancy must be ruled out prior to insertion and a barrier method of contraception (eg, male condom with spermicide) should be used for 7 days following ring insertion.a

Prolonged ring-free interval

If the ring-free interval is >1 week, pregnancy must be ruled out prior to insertion and a barrier method of contraception (eg, male condom with spermicide) should be used for 7 days following ring insertion.a

Ring breakage

In the event the vaginal ring disconnects at the weld joint, discard and replace with a new ring.

Menstrual suppression

Menstrual suppression (off-label use): Vaginal: One ring, inserted vaginally and left in place continuously for 3 consecutive weeks, then a new ring is inserted (omitting the ring-free interval) (Ref).

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).

Dosing: Liver Impairment: Adult

Use is contraindicated.

Dosing: Pediatric

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

Contraception

Contraception: Postmenarche patients: One ring, inserted vaginally and left in place continuously for 3 consecutive weeks, then removed for 1 week. A new ring is inserted 7 days after the last was removed (even if bleeding is not complete) and should be inserted at approximately the same time of day the ring was removed the previous week. Patients with no hormonal contraceptive use in the past month should insert ring on the first day of menstrual cycle. May also insert on days 2 to 5 of the menstrual cycle but in this case, a barrier method of contraception (eg, male condom with spermicide) should be used for the following 7 days. Certain barrier methods (eg, diaphragm, cervical cap, female condom) may interfere with proper ring placement and, therefore, are not recommended for use as an additional form of contraception.

Patients Switching from Another Contraceptive Method to the Ethinyl Estradiol/Etonogestrel Vaginal Ring

Current method

Instructions for switching to vaginal ring

a A barrier method of contraception (eg, male condom with spermicide) should be used for 7 days following ring insertion. Certain barrier methods (eg, diaphragm, cervical cap, female condom) may interfere with proper ring placement and, therefore, are not recommended for use as an additional form of contraception.

Combined hormonal contraceptive (CHC)

Vaginal ring can be inserted on any day, but at the latest on the day following the usual hormone-free interval, if patient is using the hormonal method consistently and correctly, or if it is reasonably sure patient is not pregnant.

Implant

Insert vaginal ring on the same day of implant removal.a

Injection

Insert vaginal ring on the day the next injection would be given.a

Intrauterine system (IUS)

Insert vaginal ring on day of IUS removal.a

Progestin-only pill (POP)

May switch to vaginal ring on any day; insert the vaginal ring on the day after the last POP.a

Additional Ethinyl Estradiol/Etonogestrel Vaginal Ring Contraceptive Considerations

a Certain barrier methods (eg, diaphragm, cervical cap, female condom) may interfere with proper ring placement and, therefore, are not recommended for use as an additional form of contraception. Additional guidelines are available following delayed insertion/reinsertion of vaginal ring (CDC [Curtis 2016a]).

Inadvertent removal or expulsion

If the ring is accidentally removed from the vagina at any time during the 3-week period of use, it may be rinsed with cool or lukewarm water (not hot) and reinserted as soon as possible.

If the vaginal ring is not reinserted within 3 hours, contraceptive effectiveness will be decreased.

If the ring is accidently removed from the vagina for >3 continuous hours during weeks 1 and 2:

• The ring should be reinserted as soon as possible and a barrier method of contraception (eg, male condom with spermicide) should be used for 7 days following ring insertion. a

If the ring is accidently removed from the vagina for >3 hours during week 3:

• The ring should be discarded. A new ring may be inserted immediately, restarting a new 3-week cycle, OR a new ring may be inserted ≤7 days from the time the previous ring was removed or expelled (the second option should only be done if a vaginal ring was in continuous use for ≥7 days prior to the inadvertent expulsion/removal). With either option, a barrier method of contraception (eg, male condom with spermicide) should be used for 7 days following ring insertion. a

If the vaginal ring has been removed for >1 week or for an unknown period of time:

• Pregnancy must be ruled out prior to restarting therapy. If not pregnant, a barrier method of contraception (eg, male condom with spermicide) should be used for 7 days following ring insertion. a

Prolonged vaginal ring insertion

If the vaginal ring has been left in place for up to 1 extra week (up to 4 weeks total), a new ring should be inserted following a 1-week (ring-free) interval. If the vaginal ring is left in place >4 weeks, pregnancy must be ruled out prior to insertion and a barrier method of contraception (eg, male condom with spermicide) should be used for 7 days following ring insertion. a

Prolonged ring-free interval

If the ring-free interval is >1 week, pregnancy must be ruled out prior to insertion and a barrier method of contraception (eg, male condom with spermicide) should be used for 7 days following ring insertion. a

Ring breakage

In the event the vaginal ring disconnects at the weld joint, discard and replace with a new ring.

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

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

Dosing: Liver Impairment: Pediatric

Use is contraindicated.

Adverse Reactions

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

>10%:

Endocrine & metabolic: Intermenstrual bleeding (7% to 12%)

Genitourinary: Vaginitis (14%)

Nervous system: Headache (11%; including migraine)

1% to 10%:

Dermatologic: Acne vulgaris (2%)

Endocrine & metabolic: Amenorrhea (≤4%), decreased libido (2%), weight gain (5%)

Gastrointestinal: Abdominal pain (3%), nausea (≤6%), vomiting (≤6%)

Genitourinary: Breast tenderness (≤4%), dysmenorrhea (4%), female birth control device expulsion from genital tract (≤6%), mastalgia (≤4%), vaginal discharge (6%), vaginal discomfort (4%)

Nervous system: Foreign body sensation (≤6%; including device discomfort), mood changes (6%; including depression, depressed mood, and emotional lability)

Frequency not defined:

Cardiovascular: Deep vein thrombosis

Gastrointestinal: Cholelithiasis

Nervous system: Anxiety

Postmarketing:

Cardiovascular: Acute myocardial infarction, arterial thromboembolism, worsening of varicose veins

Dermatologic: Chloasma, urticaria

Endocrine & metabolic: Galactorrhea not associated with childbirth

Genitourinary: Cervical erosion (including vaginal erosion), penile disease (male partners of women using ring; including local reactions), vaginal disease (ring adherence to vaginal tissue), vaginal ulcer

Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction

Infection: Toxic shock syndrome

Nervous system: Cerebrovascular accident

Contraindications

Hypersensitivity, including anaphylaxis and angioedema, to ethinyl estradiol, etonogestrel, or any component of the formulation; breast cancer (current or a history of; may be hormone sensitive); hepatic tumors (benign or malignant) or hepatic disease; pregnancy; undiagnosed abnormal uterine bleeding; concurrent use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir.

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

Use is also contraindicated in patients at high risk of arterial or venous thrombotic diseases including: Cerebrovascular disease; coronary artery disease; diabetes mellitus with vascular disease; DVT or PE (current or history of); headaches with focal neurological symptoms; migraine headaches with aura or migraine headaches if >35 years of age; hypertension (uncontrolled); thrombogenic valvular or rhythm diseases of the heart (eg, subacute bacterial endocarditis with valvular disease, atrial fibrillation); patients >35 years of age who smoke; inherited or acquired hypercoagulopathies.

Canadian labeling: Additional contraindications (not in US labeling): Prodromi of a thrombosis (eg, angina pectoris or transient ischemic attack); genital cancer (current or a history of; hormonal-sensitive); severe dyslipoproteinemia; major surgery with prolonged immobilization; any ocular lesion from ophthalmic vascular disease such as partial or complete loss of vision or defect in visual fields; pancreatitis or history of pancreatitis with severe hypertriglyceridemia; persistent BP ≥160 mm Hg systolic or ≥100 mm Hg diastolic; predisposition for arterial or venous thrombosis, with or without hereditary involvement such as activated protein C (APC-) resistance (including Factor V Leiden), antithrombin-III-deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia, and antiphospholipid-antibodies (anticardiolipin antibodies, lupus anticoagulant); concurrent use with drug combinations containing glecaprevir/pibrentasvir.

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding irregularities: Amenorrhea, spotting, and unscheduled bleeding may occur, primarily during the first 3 months of therapy. Evaluate unscheduled or breakthrough bleeding that persists or occurs after previously regular cycles to rule out malignancy or pregnancy. Amenorrhea or oligomenorrhea may occur after discontinuing combination hormonal contraceptives, especially when such a condition was preexistent.

• Cervical cancer: The use of combination hormonal contraceptives has been associated with a slight increased risk of cervical cancer; however, studies are not consistent and the risk may be related to the specific histologic type of cervical cancer, duration of contraceptive use, and other factors (Asthana 2020; Gadducci 2020). Theoretically, use may affect prognosis of existing disease. Patients awaiting treatment for cervical cancer may use combination hormonal contraceptives (CDC [Curtis 2016b]).

• Chloasma: Combination hormonal contraceptives, as well as sun exposure and pregnancy, are triggers for chloasma. Avoid sun exposure or ultraviolet radiation during therapy in patients with a susceptibility to chloasma or additional risk factors.

• Cholestasis: Risk of cholestasis may be increased with previous 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 thrombosis.

• Thromboembolic disorders: Discontinue use of combination hormonal contraceptives if an arterial or venous thrombotic event occurs. The increased risk of venous thromboembolism (VTE) associated with combination hormonal contraceptives is greatest during first year of use and less than the risk associated with pregnancy; some studies suggest this risk may be higher in preparations with third- or fourth-generation progestins and/or high-dose ethinyl estradiol. Patients with inherited thrombophilias (eg, protein C or S deficiency, factor V Leiden mutation, prothrombin mutation, antithrombin deficiency) may have increased risk of VTE. Age >35 years, hypertension, obesity, and tobacco use also increase the risk of thromboembolic events in patients taking combination hormonal contraceptives (Abou-Ismail 2020; ASRM 2017; CDC [Curtis 2016b]). Combination hormonal contraceptives may also increase the risk of arterial thrombosis (eg, myocardial infarction, stroke); do not use in patients with a history of stroke or ischemic heart disease (CDC [Curtis 2016b]).

• Toxic shock syndrome: Has been reported (causal relationship has not been established); increased risk with tampon use.

Disease-related concerns:

• Angioedema: Estrogens may induce or exacerbate symptoms in patients with hereditary angioedema.

• 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-ileal bypass, or omega-loop gastric bypass. Discontinue estrogen-containing birth control at least 4 weeks prior to bariatric surgery and resume no earlier than 4 weeks after surgery to minimize risk of VTE (Ciangura 2019; Mechanick 2020; Moreira de Brito 2021; Shawe 2019).

• Breast cancer: Available studies have not shown a consistent association with combination hormonal contraceptives and breast cancer risk. Multiple studies have shown no association in current or past users; other studies have shown a small increased risk in current users (higher risk with longer duration of use) and recent users (<6 months since last use). In patients at risk for breast cancer due to family history or susceptibility genes (BRCA1, BRCA2), it is unclear if combination hormonal contraceptives increase the risk for breast cancer. However, breast cancer is a hormone-sensitive tumor and the prognosis for patients with a current or recent history of breast cancer may be worse with combination hormonal contraceptive use (CDC [Curtis 2016b]; SGO/ASRM [Chen 2019]).

• Cardiovascular disease: Use with caution in patients with risk factors for cardiovascular disease (eg, hypertension, low high-density lipoprotein, high low-density lipoprotein, high triglycerides, older age, diabetes, women who smoke); use of combination hormonal contraceptives may increase the risk of cardiovascular disease (CDC [Curtis 2016b]).

• Depression: Use with caution in patients with a history of depression; discontinue if serious depression recurs.

• Diabetes: May impair glucose tolerance; use caution in patients with diabetes or prediabetes. In general, use of combination oral contraceptives has limited effects on daily insulin needs and no long-term effects on diabetes control in patients with nonvascular disease. Evaluate contraceptive use in patients with concomitant nephropathy, neuropathy, retinopathy, other vascular diseases, or diabetes >20 years' duration based on the severity of the condition (CDC [Curtis 2016b]).

• Endometrial cancer: The risk of endometrial cancer is decreased in patients using combination hormonal contraceptives. Patients awaiting treatment for endometrial cancer may use combination hormonal contraceptives (CDC [Curtis 2016b]).

• Gallbladder disease: Combination hormonal contraceptives may have a small increased risk of gallbladder disease or worsen existing gallbladder disease (CDC [Curtis 2016b]).

• Hepatic impairment: Contraceptive steroids may be poorly metabolized in patients with hepatic impairment. Discontinue if jaundice develops during therapy or if liver function becomes abnormal. Consider use of combination hormonal contraceptives in patients with mild (compensated) cirrhosis; do not use in patients with severe (decompensated) cirrhosis (CDC [Curtis 2016b]).

• Hepatitis: Initiation of combination hormonal contraceptives is not recommended in patients with acute viral hepatitis or during a flare. Continued use in patients with chronic hepatitis has not been shown to increase the rate or severity of cirrhotic fibrosis or hepatocellular carcinoma. Continued use in patients who are carriers has not been shown to trigger liver failure or severe hepatic dysfunction (CDC [Curtis 2016b]).

• Hypertension: The risk of hypertension may be increased with age, dose, and duration of use. Do not use combination hormonal contraceptives in patients with hypertension and vascular disease, or persistent BP values ≥160 mm Hg systolic or ≥100 mm Hg diastolic. The risks of use may not outweigh the benefits of treatment in patients with less severe hypertension (140 to 159 mm Hg systolic or 90 to 99 mm Hg diastolic) or those with hypertension that is adequately controlled (CDC [Curtis 2016a]). Consider other risk factors for cardiovascular disease (eg, older age, smoking, diabetes) when prescribing contraceptives (CDC [Curtis 2016b]). Monitor BP in patients with well-controlled hypertension; discontinue therapy if BP rises significantly.

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

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

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

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

Concurrent drug therapy issues:

• Testosterone: All available forms of contraception can be considered for patients receiving gender-affirming testosterone therapy after evaluating patient preferences and medical conditions (Bonnington 2020; Krempasky 2020); however, it has been suggested to use contraceptive products containing lower daily doses of ethinyl estradiol (0.01 to 0.02 mg) to decrease the risk of possible adverse reactions when testosterone therapy is used with combination hormonal contraceptives (Bonnington 2020).

Special populations:

• Body weight: In a study using the vaginal ring, ethinyl estradiol serum concentrations were decreased in obese women (BMI 30 to 39.9 kg/m2; n=19) in comparison to women of normal weight (BMI 19 to 24.9 kg/m2; n=18; p=0.004); etonogestrel concentrations did not differ significantly. Bleeding and spotting were more frequent in the obese women. The study was not powered to evaluate contraceptive effectiveness (Westhoff 2012). Patients with a BMI ≥30 kg/m2 may have an increased risk of VTE. In general, the benefits of combination hormonal contraceptives may outweigh the risks in patients who otherwise are eligible for this method (CDC [Curtis 2016b]).

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

• Surgery: Whenever possible, discontinue estrogens at least 4 weeks prior to and through 2 weeks following major surgery or other surgeries known to have an increased risk of thromboembolism or during periods of prolonged immobilization.

Dosage form specific issues:

• Vaginal preparation: Vaginally administered combination hormonal contraceptive agents may have similar adverse effects to those associated with oral contraceptive products. In order to reduce some of the possible risks, the minimum dosage combination of estrogen/progestin that is effective for the individual patient should be used. May not be appropriate for use in patients with conditions that make the vagina susceptible to irritation or ulceration; vaginal/cervical erosion and ulceration has been reported. Ring breakage has been reported including with concomitant use of intravaginal products (eg, antibiotic, antifungal, lubricant) and may cause vaginal injury and associated pain, discomfort, and bleeding. The patients and their sexual partner may feel the ring in the vagina during intercourse. Ensure proper vaginal placement of the ring to avoid inadvertent urinary bladder insertion.

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. [DSC] = Discontinued product

Ring, Vaginal:

EluRyng: Ethinyl estradiol 0.015 mg and etonogestrel 0.12 mg per 24 hours (1 ea)

EnilloRing: Ethinyl estradiol 0.015 mg and etonogestrel 0.12 mg per 24 hours (1 ea) [latex free]

Haloette: Ethinyl estradiol 0.015 mg and etonogestrel 0.12 mg per 24 hours (1 ea)

NuvaRing: Ethinyl estradiol 0.015 mg and etonogestrel 0.12 mg per 24 hours (1 ea)

NuvaRing: Ethinyl estradiol 0.015 mg and etonogestrel 0.12 mg per 24 hours (1 ea [DSC]) [latex free]

Generic: Ethinyl estradiol 0.015 mg and etonogestrel 0.12 mg per 24 hours (1 ea)

Generic Equivalent Available: US

Yes

Pricing: US

Ring (EluRyng Vaginal)

0.12-0.015 mg/24 hrs (per each): $185.40

Ring (EnilloRing Vaginal)

0.12-0.015 mg/24 hrs (per each): $185.40

Ring (Etonogestrel-Ethinyl Estradiol Vaginal)

0.12-0.015 mg/24 hrs (per each): $183.45 - $185.40

Ring (Haloette Vaginal)

0.12-0.015 mg/24 hrs (per each): $185.40

Ring (NuvaRing Vaginal)

0.12-0.015 mg/24 hrs (per each): $195.16

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.

Dosage Forms: Canada

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

Ring, Vaginal:

Haloette: Ethinyl estradiol 0.015 mg and etonogestrel 0.12 mg per 24 hours (1 ea)

NuvaRing: Ethinyl estradiol 0.015 mg and etonogestrel 0.12 mg per 24 hours (1 ea)

Administration: Adult

Intravaginal: Wash hands and remove ring from protective pouch (keep pouch for later ring disposal). Press sides of ring together between thumb and index finger and insert folded ring into vagina. Specific placement is not required for ring to be effective, but ring should be inserted far enough into the vagina as to be comfortable. To remove, hook index finger around rim and pull out. Vaginal ring cannot be disposed of in the toilet; place used vaginal ring back into foil pouch and dispose of in trash. New rings should be inserted at approximately the same time of day the ring was removed the previous week. If the ring accidentally falls out, it may be rinsed with cool or warm (not hot) water and replaced; however, it must be replaced within 3 hours. Refer to dosing if ring is out of place for >3 hours. Regularly check for the presence of the ring in the vagina (eg, before and after intercourse). Tampons do not interfere with the effectiveness of the ring; caution should be used when removing tampon not to remove ring. The ring may interfere with proper placement of certain barrier methods (eg, diaphragm, cervical cap, female condom); therefore, those barrier methods are not recommended for use as additional forms of contraception. Ensure proper vaginal placement of the ring to avoid inadvertent urinary bladder insertion.

Administration: Pediatric

Intravaginal: Wash hands and remove ring from protective pouch (keep pouch for later ring disposal). Press sides of ring together between thumb and index finger and insert folded ring into vagina. Specific placement is not required for ring to be effective, but ring should be inserted far enough into the vagina as to be comfortable. To remove, hook index finger around rim and pull out. Vaginal ring cannot be disposed of in the toilet; place used vaginal ring back into foil pouch and dispose of in trash. New rings should be inserted at approximately the same time of day the ring was removed the previous week. If the ring accidentally falls out, it may be rinsed with cool or warm (not hot) water and replaced; however, it must be replaced within 3 hours. Refer to dosing if ring is out of place for >3 hours. Regularly check for the presence of the ring in the vagina (eg, before and after intercourse). Tampons do not interfere with the effectiveness of the ring; caution should be used when removing tampon not to remove ring. Certain barrier methods (eg, diaphragm, cervical cap, female condom) may interfere with proper ring placement and, therefore, are not recommended for use as a back-up method of contraception. Ensure proper vaginal placement of the ring to avoid inadvertent urinary bladder insertion.

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

Contraception: For the prevention of pregnancy.

Limitations of use: For use in patients who may become pregnant; not for use prior to menarche or postmenopause.

Use: Off-Label: Adult

Abnormal uterine bleeding (chronic [eg, heavy menstrual bleeding]); Dysmenorrhea, primary and secondary to endometriosis; Menstrual suppression

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

Due to the increased risk of venous thromboembolism (VTE) postpartum, do not initiate combination hormonal contraceptives in any patient <21 days following delivery. The risk decreases to baseline by postpartum day 42. In patients who are between 21 and 42 days after delivery, consider risk factors for VTE (eg, age ≥35 years, previous VTE, thrombophilia, immobility, preeclampsia, transfusion at delivery, cesarean delivery, peripartum cardiomyopathy, BMI ≥30 kg/m2, postpartum hemorrhage, smoking) (CDC [Curtis 2016b]). The manufacturer does not recommend use until ≥4 weeks after delivery in patients who choose not to breastfeed due to the risk of VTE. The manufacturer states that combination hormonal contraceptives should not be started until ≥4 weeks after delivery in patients who choose not to breastfeed, or ≥4 weeks after a second trimester abortion or miscarriage.

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 surgery (Bonnington 2020).

Combination hormonal contraceptives may be an option for menstrual suppression in patients who have reached menarche when fewer or no menses are desired (ACOG 2022; SOGC [Kirkham 2019]). Future fertility is not decreased. Base the decision to use a combination hormonal contraceptive or other hormonal preparation on patient preference, their ability to use the method, method effectiveness, potential contraindications, drug interactions, and adverse events. Consider for patients requesting menstrual suppression, including (but not limited to) adolescents, athletes, persons with physical and/or cognitive disabilities, persons on gender-affirming hormone therapy, and persons with limited access to menstrual products or other challenges to hygiene management (ACOG 2022).

Pregnancy Considerations

Use is contraindicated during pregnancy. Combination hormonal contraceptives are used to prevent pregnancy; discontinue treatment if pregnancy occurs. In general, the use of combination hormonal contraceptives, when inadvertently used early in pregnancy, have not been associated with adverse fetal or maternal effects (CDC [Curtis 2016b]).

Breastfeeding Considerations

Etonogestrel and ethinyl estradiol are present in breast milk.

Adverse health outcomes or consistent effects on infant growth or illness due to exogenous estrogens have not been reported following maternal use of combination hormonal contraceptives in breastfeeding patients (CDC [Curtis 2016b]). Estrogen-containing contraceptives may reduce milk production. The manufacturer recommends the use of other forms of contraception until the child is weaned.

Due to the increased risk of venous thromboembolism (VTE) postpartum, do not initiate combination hormonal contraceptives in patients <21 days following delivery. The risk decreases to baseline by postpartum day 42. In patients who are between 21 and 42 days after delivery, consider risk factors for VTE (eg, age ≥35 years, previous VTE, thrombophilia, immobility, preeclampsia, transfusion at delivery, cesarean delivery, peripartum cardiomyopathy, BMI ≥30 kg/m2, postpartum hemorrhage, smoking). Evaluate risks, benefits, and alternatives to combination hormonal contraception when initiating treatment in breastfeeding patients (CDC [Curtis 2016b]). The manufacturer does not recommend use until ≥4 weeks after delivery in patients who choose not to breastfeed due to the risk of VTE.

Monitoring Parameters

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

Determining if reasonably certain a person is not pregnant (CDC [Curtis 2016a]):

If the patient has no signs or symptoms of pregnancy and meets any one of the following criteria, a health care provider can be reasonably certain the person is not pregnant:

• ≤7 days after the start of normal menses

• No sexual intercourse since last menses

• Correct and consistent use of reliable contraception

• ≤7 days after spontaneous or induced abortion

• <4 weeks postpartum

• <6 months postpartum, amenorrheic, and exclusively breastfeeding or ≥85% of feeds are breastfeeds.

If vaginal ring was out of the vagina >3 hours, or the ring free interval was extended for >1 week, and 1 menstrual period is missed, the possibility of pregnancy should be considered. If the ring was used as directed and 2 consecutive menstrual periods are missed, assess pregnancy status before a new dosing cycle is started. In addition, assess pregnancy status if ring was in place >4 weeks.

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. Perform adequate diagnostic measures, including endometrial sampling, if indicated, to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding. In patients with persistent urinary symptoms, assess for inadvertent urinary bladder insertion if ring is not otherwise located.

Mechanism of Action

Combination hormonal contraceptives inhibit ovulation via a negative feedback mechanism on the hypothalamus, which alters the normal pattern of gonadotropin secretion of a follicle-stimulating hormone (FSH) and luteinizing hormone by the anterior pituitary. The follicular phase FSH and midcycle surge of gonadotropins are inhibited. In addition, combination hormonal contraceptives produce alterations in the genital tract, including changes in the cervical mucus, rendering it unfavorable for sperm penetration even if ovulation occurs. Changes in the endometrium may also occur, producing an unfavorable environment for nidation. Combination hormonal contraceptive drugs may alter the tubal transport of the ova through the fallopian tubes. Progestational agents may also alter sperm fertility (Rivera 1999).

Pharmacokinetics (Adult Data Unless Noted)

Duration: Serum levels (contraceptive effectiveness) decrease after 3 weeks of continuous use

Absorption: Ethinyl estradiol and etonogestrel: Rapid

Tampons do not interfere with absorption.

Protein binding:

Ethinyl estradiol: 98.5%, primarily to albumin

Etonogestrel: ~32% to sex hormone-binding globulin (SHBG) and ~66% to albumin; SHBG capacity is affected by plasma ethinyl estradiol levels

Metabolism:

Ethinyl estradiol: Hepatic via CYP3A4; forms metabolites (weak estrogenic activity)

Etonogestrel: Hepatic via CYP3A4; forms metabolites (activity not known)

Bioavailability: Vaginal: Ethinyl estradiol: ~56% Etonogestrel: ~100%

Half-life elimination: Ethinyl estradiol: 45 hours; Etonogestrel: 29 hours

Time to peak: Vaginal: Ethinyl estradiol: 59 hours; Etonogestrel: 200 hours

Excretion: Ethinyl estradiol and etonogestrel: Urine, bile, and feces

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Hepatic function impairment: Steroid hormones may be poorly metabolized in women with impaired liver function.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Nuvaring;
  • (AR) Argentina: Circlet | Ellering | Nuvaring;
  • (AT) Austria: Femloop | Ginoring | Myring | Nuvaring | Setlona | Solvetta;
  • (BE) Belgium: Circlet | Daniciah | Izzyring | Myloop | Nuvaring | Ringafema;
  • (BG) Bulgaria: Nuvaring;
  • (BR) Brazil: Nuvaring;
  • (CH) Switzerland: Circlet | Danisia | Femiring | Lina gynial | Myloop | Nuvaring | Ornibel;
  • (CL) Chile: Anilera | Circlet | Esmartia | Exelring | Myloop | Nuvaring;
  • (CO) Colombia: Circlet | Exelring | Nuvaring | Stania;
  • (CR) Costa Rica: Nuvaring;
  • (CZ) Czech Republic: Adaring | Circlet | Nuvaring | Ornibel | Teyla;
  • (DE) Germany: Circlet | Cyclelle | Ginoring | Mycirq | Nuvaring | Setlona | Veri aristo;
  • (DO) Dominican Republic: Nuvaring;
  • (EC) Ecuador: Exelring | Nuvaring;
  • (EE) Estonia: Nuvaring | Setlona;
  • (EG) Egypt: Nuvaring;
  • (ES) Spain: Circlet | Dolna | Femloop | Nuvaring | Ornibel | Ringo | Setlona;
  • (FI) Finland: Circlet | Nuvaring | Ornibel | Vagiprev | Vonamyl;
  • (FR) France: Ethinylestradiol/etonogestrel biogaran | Ethinylestradiol/etonogestrel zentiva | Etonogestrel/Ethinylestradiol mylan | Etoring | Nuvaring;
  • (GB) United Kingdom: Nuvaring | Syreniring;
  • (GR) Greece: Nuvaring;
  • (HK) Hong Kong: Nuvaring;
  • (HR) Croatia: Nuvaring;
  • (HU) Hungary: Femiring | Ladeering | Nuvaring | Ringinel;
  • (IE) Ireland: Nuvaring;
  • (IN) India: Nuvaring;
  • (IT) Italy: Circlet | Kirkos | Myprimose | Nelova | Nuvaring | Ornibel | Solvetta;
  • (JO) Jordan: Nuvaring;
  • (KW) Kuwait: Nuvaring;
  • (LB) Lebanon: Nuvaring;
  • (LT) Lithuania: Nuvaring | Ringafema;
  • (LU) Luxembourg: Circlet | Izzyring | Myloop | Nuvaring | Ringafema;
  • (LV) Latvia: Nuvaring | Ornique | Setlona;
  • (MA) Morocco: Nuvaring;
  • (MX) Mexico: Nuvaring;
  • (MY) Malaysia: Nuvaring;
  • (NL) Netherlands: Etonogestrel/ethinylestradiol abbott | Etonogestrel/Ethinylestradiol mylan | Etonogestrel/Ethinylestradiol Sandoz | Nuvaring | Ornibel;
  • (NO) Norway: Nuvaring | Ornibel;
  • (NZ) New Zealand: Nuvaring;
  • (PA) Panama: Oseogyn;
  • (PE) Peru: Exelring | Nuvaring;
  • (PL) Poland: Adaring | Circlet | Contraseton | Ginoring | Mirgi | Nuvaring | Polaring;
  • (PR) Puerto Rico: Eluryng | Enilloring | Etonogestrel and ethinyl estradiol | Etonogestrel/ethinyl estradiol | Haloette | Nuvaring;
  • (PT) Portugal: Anette | Circlet | Mystrelle | Nuvaring | Ornibel | Ringo;
  • (PY) Paraguay: Fioribella | Stania;
  • (QA) Qatar: Nuvaring;
  • (RU) Russian Federation: Novaring;
  • (SA) Saudi Arabia: Nuvaring;
  • (SE) Sweden: Nuvaring | Ornibel | Vagiprev;
  • (SG) Singapore: Nuvaring;
  • (SI) Slovenia: Setlona;
  • (SK) Slovakia: Nuvaring | Ornibel | Teyla;
  • (TH) Thailand: Nuvaring;
  • (TR) Turkey: Nuvaring;
  • (UA) Ukraine: Novaring;
  • (UY) Uruguay: Ellering;
  • (VE) Venezuela, Bolivarian Republic of: Myring;
  • (ZA) South Africa: Nuvaring
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