Estetrol and drospirenone: Drug information

(For additional information see "Estetrol and drospirenone: Pediatric drug information" and see "Estetrol and drospirenone: 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 combined 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, including drospirenone/estetrol, are contraindicated in females who are >35 years of age and smoke.

Brand Names: US

Nextstellis

Brand Names: Canada

Nextstellis

Pharmacologic Category

Contraceptive;
Estrogen and Progestin Combination

Dosing: Adult

Contraception

Contraception: Oral: 1 tablet once daily in the order presented on the blister pack. For patients not currently using a hormonal contraceptive, the first active tablet should be taken on the first day of the menstrual cycle (day 1 start). If drospirenone/estetrol is not initiated on the first day of menses, an additional method of contraception (nonhormonal) must be used for the first 7 days of consecutive administration.

**Patients Switching to Drospirenone/Estetrol From Another Contraceptive Method**
Current method	Instructions for switching to drospirenone/estetrol
^aCOC = combined oral contraceptive.
^b IUS = Intrauterine system.
COC^a	Start drospirenone/estetrol on the day a new pack of the previous COC would be started.
Implant	Start drospirenone/estetrol on the day of implant removal.
Injection	Start drospirenone/estetrol on the day the next injection would have been scheduled.
IUS^b	Start drospirenone/estetrol on the day of IUS removal. If drospirenone/estetrol is not initiated on the first day of menses or the day of IUS removal, an additional method of contraception (nonhormonal) must be used for the first 7 days of consecutive administration.
Progestin only pill	Start drospirenone/estetrol on the day after the last progestin tablet was taken.
Transdermal system	Start drospirenone/estetrol on the day when the next application would be scheduled.
Vaginal insert	Start drospirenone/estetrol on the day when the next insertion would be scheduled.

**Use of Drospirenone/Estetrol After Childbirth, Abortion, or Miscarriage**
Use after childbirth	Drospirenone/estetrol should not be started <4 weeks after childbirth in patients who delivered >20 weeks' gestation due to the increased risk of thromboembolism. If menstrual cycles have returned, follow instructions for patients not currently using a hormonal contraceptive. If menstrual cycles have not returned, assess pregnancy status. If not pregnant, an additional method of contraception (nonhormonal) should be used for the first 7 days of consecutive administration.
Use after abortion or miscarriage ≤14 weeks' gestation	Drospirenone/estetrol can be started within 7 days of a complete first-trimester abortion or miscarriage. A n additional method of contraception (nonhormonal) should be used for the first 7 days of consecutive administration. If therapy is started >7 days, follow instructions for patients not currently using a hormonal contraceptive.
Use after abortion or miscarriage >14 weeks' but ≤20 weeks' gestation	Drospirenone/estetrol can be started >4 weeks after delivery; however, consider the patients risk of thromboembolism. If menstrual cycles have returned, follow instructions for patients not currently using a hormonal contraceptive. If menstrual cycles have not returned, assess pregnancy status. If not pregnant, an additional method of contraception (nonhormonal) should be used for the first 7 days of consecutive administration.

**Missed Doses of Drospirenone/Estetrol**
If 1 active tablet is missed	Take the missed dose as soon as possible. Continue remaining doses at the usual time (even if that means 2 doses on the same day).
If ≥2 active tablets are missed in week 1 or week 2	Take 1 missed dose as soon as possible, take the tablet for the current day (even if that means 2 doses on the same day), and discard any other missed doses. Continue remaining doses at the usual time; use back-up (nonhormonal) contraception until active tablets have been taken for 7 consecutive days.
If 2 doses are missed during week 3	Take 1 missed dose as soon as possible, take the tablet for the current day (even if that means 2 doses on the same day), and discard any other missed doses. Finish the remaining active tablets and discard the inactive tablets. Start a new pack of tablets the next day. Use back-up (nonhormonal) contraception until active tablets have been taken for 7 consecutive days.
If ≥1 inactive tablet(s) missed	Skip the missed pill days and continue taking 1 tablet daily until the pack is finished.

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

Use is contraindicated in patients with renal impairment.

Dosing: Hepatic Impairment: Adult

Use is contraindicated in patients with hepatic impairment.

Dosing: Pediatric

(For additional information see "Estetrol and drospirenone: Pediatric drug information")

Contraception

Contraception: Postmenarche patients: Oral: One tablet once daily in the order presented on the blister pack. For patients not currently using a hormonal contraceptive, the first active tablet should be taken on the first day of the menstrual cycle (day 1 start). If drospirenone/estetrol is not initiated on the first day of menses, an additional method of contraception (nonhormonal) must be used for the first 7 days of consecutive administration.

**Patients Switching to Drospirenone/Estetrol From Another Contraceptive Method**
Current method	Instructions for switching to drospirenone/estetrol
^aCOC = combined oral contraceptive.
^b IUS = Intrauterine system.
COC^a	Start drospirenone/estetrol on the day a new pack of the previous COC would be started.
Implant	Start drospirenone/estetrol on the day of implant removal.
Injection	Start drospirenone/estetrol on the day the next injection would have been scheduled.
IUS^b	Start drospirenone/estetrol on the day of IUS removal. If drospirenone/estetrol is not initiated on the first day of menses or the day of IUS removal, an additional method of contraception (nonhormonal) must be used for the first 7 days of consecutive administration.
Progestin-only pill	Start drospirenone/estetrol on the day after the last progestin tablet was taken.
Transdermal system	Start drospirenone/estetrol on the day when the next application would be scheduled.
Vaginal insert	Start drospirenone/estetrol on the day when the next insertion would be scheduled.

**Missed Doses of Drospirenone/Estetrol**
If 1 active tablet is missed	Take the missed dose as soon as possible. Continue remaining doses at the usual time (even if that means 2 doses on the same day).
If ≥2 active tablets are missed in week 1 or week 2	Take 1 missed dose as soon as possible, take the tablet for the current day (even if that means 2 doses on the same day), and discard any other missed doses. Continue remaining doses at the usual time; use back-up (nonhormonal) contraception until active tablets have been taken for 7 consecutive days.
If 2 doses are missed during week 3	Take 1 missed dose as soon as possible, take the tablet for the current day (even if that means 2 doses on the same day), and discard any other missed doses. Finish the remaining active tablets and discard the inactive tablets. Start a new pack of tablets the next day. Use back-up (nonhormonal) contraception until active tablets have been taken for 7 consecutive days.
If ≥1 inactive tablet(s) missed	Skip the missed pill days and continue taking 1 tablet daily until the pack is finished.

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

Use is contraindicated in patients with renal impairment.

Dosing: Hepatic Impairment: Pediatric

Use is contraindicated in patients with hepatic impairment.

Adverse Reactions

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

>10%:

Genitourinary: Gynecological bleeding (10% to 11%; includes amenorrhea, menometrorrhagia, menorrhagia, metrorrhagia, oligomenorrhea, polymenorrhea)

Nervous system: Mood disorder (9% to 11%; includes adjustment disorder, affective disorder, disorientation, euphoria, generalized anxiety disorder, insomnia, panic disorder, sleep disorder, suicidal ideation)

1% to 10%:

Dermatologic: Acne vulgaris (3% to 4%)

Endocrine & metabolic: Breast changes (5%; includes anisomastia, breast cyst, breast edema, breast mass, fibrocystic breast disease, galactorrhea, mastoptosis), decreased libido (≤2%), loss of libido (≤2%), weight gain (3%)

Genitourinary: Dysmenorrhea (4%)

Nervous system: Depression (2%), headache (5% to 6%; including migraine)

<1%:

Cardiovascular: Thromboembolic complications

Endocrine & metabolic: Hyperkalemia

Contraindications

Hormonally sensitive malignancy (eg, breast cancer) (current or a history of), undiagnosed abnormal uterine bleeding, hepatic adenoma, hepatocellular carcinoma, acute hepatitis, severe (decompensated) cirrhosis, use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir (due to potential ALT elevations), adrenal insufficiency, kidney impairment.

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 thromboembolic events, for example, patients with: cerebrovascular disease, coronary artery disease, diabetes mellitus with hypertension, diabetes mellitus with end-organ damage, diabetes mellitus >20 years duration, deep vein thrombosis or pulmonary embolism (current or history of), hypercoagulopathies (inherited or acquired), hypertension (uncontrolled) or hypertension with vascular disease, migraine headaches with aura, thrombogenic valvular or rhythm diseases of the heart (eg, subacute bacterial endocarditis with valvular disease or atrial fibrillation), patients >35 years of age who smoke.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to drospirenone, estetrol, or any component of the formulation; steroid-dependent jaundice, cholestatic jaundice, or history of jaundice of pregnancy; any ocular lesion arising from ophthalmic vascular disease (eg, partial or complete loss of vision or defect in visual fields); pancreatitis associated with severe hypertriglyceridemia (current or a history of); hepatic impairment; known or suspected pregnancy.

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding irregularities: Amenorrhea, spotting, and unscheduled bleeding may occur, primarily during the first 4 months of therapy. Evaluate unscheduled or breakthrough bleeding that persists more than a few cycles to rule out malignancy or pregnancy. Amenorrhea or oligomenorrhea may occur after discontinuing combination hormonal contraceptives, especially when such a condition was preexistent.

• Cervical cancer: The use of combination hormonal contraceptives has been associated with a slight increased risk of cervical cancer; however, studies are not consistent and 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 (Handel 2014).

• 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.

• Hyperkalemia: Drospirenone has antimineralocorticoid activity that may lead to hyperkalemia. Use is contraindicated with conditions that predispose to hyperkalemia (eg, adrenal insufficiency, hepatic impairment, kidney impairment).

• 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.

• Retinal thrombosis: Discontinue if unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions occur and immediately evaluate for retinal thrombosis.

• Thromboembolic disorders: Discontinue use of combination hormonal contraceptives if an arterial or venous thromboembolic 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. More than 35 years of age, 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]).

Disease-related concerns:

• Bariatric surgery: Fertility is increased following bariatric surgery. All available forms of contraception can be considered following bariatric surgery, considering the patient's body weight and time since surgery; however, long-acting reversible nonoral contraceptives (eg, implants, intrauterine devices) may be preferred. Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy both have the potential to expedite transit through the small bowel. RYGB may not significantly alter the absorption of oral estrogen or progestins (limited evidence following a single dose); however, gastric and small bowel transit 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: 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 high-density lipoprotein, high low-density lipoproteins, 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: Discontinue if liver function becomes abnormal. Use of combination hormonal contraceptives may be considered in patients with mild (compensated) cirrhosis but should not be used 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. Continuation of 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]). The manufacturer recommends monitoring BP if hypertension is well-controlled; discontinue therapy if BP rises significantly.

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

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

• Solid organ transplant: Although data are limited, serious medical complications have been reported in patients with complicated organ transplants (eg, graft failure, rejection, cardiac allograft vasculopathy); use of combination hormonal contraceptives is not recommended in patients with complicated organ transplants (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, drospirenone may potentially interfere with testosterone therapy more than other progestins due to its antiandrogenic and antimineralocorticoid properties (Bonnington 2020).

Special populations:

• Body weight: The contraceptive efficacy has not been studied in patients with a BMI >35 kg/m². Available evidence suggests contraceptive 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]). Consult product labeling.

• Prolonged immobilization: Discontinue during periods of prolonged immobilization; risk of VTE is increased.

• 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.

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.

Tablet, Oral:

Nextstellis: Drospirenone 3 mg and estetrol 14.2 mg [24 active tablets and 4 inactive tablets] [contains corn starch]

Generic Equivalent Available: US

Pricing: US

Tablets (Nextstellis Oral)

3-14.2 mg (per each): $8.71

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

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

Tablet, Oral:

Nextstellis: Drospirenone 3 mg and estetrol 14.2 mg [24 active tablets and 4 inactive tablets] [contains corn starch]

Administration: Adult

Oral: Tablets should be administered orally at the same time each day, with or without food. Nextstellis is a 28-day packet containing 24 active tablets and 4 inactive (inert) tablets administered daily without interruption. If vomiting or acute diarrhea occurs within 3 to 4 hours of an active tablet, the new active tablet scheduled for the next day should be administered as soon as possible (within 12 hours of the usual time if possible). If ≥2 tablets are missed, follow directions for "missed doses."

Administration: Pediatric

Oral: Tablets should be administered orally at the same time each day, with or without food. Nextstellis is a 28-day packet containing 24 active tablets and 4 inactive (inert) tablets administered daily without interruption. If vomiting or acute diarrhea occurs within 3 to 4 hours of an active tablet, the new active tablet scheduled for the next day should be administered as soon as possible (within 12 hours of the usual time if possible). If ≥2 tablets are missed, see "Dosing: Pediatric" for further information (table) on "missed doses."

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 2]).

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 2016; 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. Drospirenone/estetrol may be less effective in patients with a BMI ≥30 kg/m². In patients with BMI ≥30 kg/m², decreasing effectiveness may be associated with increasing BMI.

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

Aliskiren: Drospirenone-Containing Products may enhance the hyperkalemic effect of Aliskiren. Risk C: Monitor therapy

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

Angiotensin II Receptor Blockers: Drospirenone-Containing Products may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Drospirenone-Containing Products may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

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

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

Antihepaciviral Combination Products: Estetrol 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

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

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

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: Estetrol 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

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

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

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

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

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

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

Heparin: Drospirenone-Containing Products may enhance the hyperkalemic effect of Heparin. Risk C: Monitor therapy

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Nonsteroidal Anti-Inflammatory Agents: Drospirenone-Containing Products may enhance the hyperkalemic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

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

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

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

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

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

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

Perampanel: May decrease the serum concentration of Hormonal Contraceptives. Management: Patients should use an alternative, nonhormonal-based form of contraception during the concurrent use of perampanel and for 1 month after discontinuing perampanel. Risk D: Consider therapy modification

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

Pitolisant: May decrease the serum concentration of Hormonal Contraceptives. Management: Patients using hormonal contraception should be advised to use an alternative non-hormonal contraceptive method during treatment with pitolisant and for at least 21 days after discontinuation of pitolisant treatment. Risk D: Consider therapy modification

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

Potassium Salts: Drospirenone-Containing Products may enhance the hyperkalemic effect of Potassium Salts. Risk C: Monitor therapy

Potassium-Sparing Diuretics: Drospirenone-Containing Products may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy

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

Retinoic Acid Derivatives: May diminish the therapeutic effect of Progestins (Contraceptive). Retinoic Acid Derivatives may decrease the serum concentration of Progestins (Contraceptive). Management: Two forms of effective contraception should be used in patients receiving retinoic acid derivatives. Microdosed progesterone-only preparations (ie, minipills that do not contain estrogen) are considered an inadequate method of contraception. Risk D: Consider therapy modification

ROPINIRole: Estrogen Derivatives may increase the serum concentration of ROPINIRole. 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

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

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

Drospirenone/estetrol may be less effective in patients with a BMI ≥30 kg/m².

The manufacturer states that drospirenone/estetrol should not be started until ≥4 weeks after delivery or ≥4 weeks after a second-trimester abortion or miscarriage.

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]).

When treatment is discontinued, ovulation was found to recur within 10 to 22 days following the last inactive tablet (Duijkers 2021).

All available forms of contraception, including combination hormonal contraceptives, can be considered for patients on gender-affirming testosterone therapy after evaluating the appropriateness of the method based on patient preferences and medical conditions (eg, risk for VTE) (Bonnington 2020; Krempasky 2020); however, drospirenone may potentially interfere with testosterone therapy more than other progestins due to its antiandrogenic and antimineralocorticoid properties (Bonnington 2020).

Pregnancy Considerations

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

Breastfeeding Considerations

Contraceptive hormones, including drospirenone, 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]). Because combination oral contraceptives may reduce milk production, the manufacturer recommends use of other forms of contraception until the child is weaned, when possible.

Due to the increased risk of venous thromboembolism (VTE) postpartum, combination hormonal contraceptives should not be started in breastfeeding patients <21 days following delivery. The risk decreases to baseline by postpartum day 42. Use of combination hormonal contraceptives in patients between 21 and 42 days after delivery should take into consideration the individual 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). The risks, benefits, and alternatives to combination hormonal contraception should be evaluated when initiating treatment in breastfeeding patients (CDC [Curtis 2016b]).

Monitoring Parameters

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

In patients with conditions requiring chronic therapy with medications that may increase potassium, monitor serum potassium during the first treatment cycle. Monitor serum potassium in patients at risk for hyperkalemia (eg, taking strong CYP3A4 inhibitors, those who develop medical conditions putting them at risk).

Consider the possibility of pregnancy if scheduled bleeding does not occur.

Monitor patient for vision changes; BP; signs and symptoms of thromboembolic disorders; signs or symptoms of depression; glycemic control in patients with diabetes; lipid profiles in patients being treated for hyperlipidemias. Adequate diagnostic measures should be performed to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding.

Mechanism of Action

Combination hormonal contraceptives prevent pregnancy by suppressing ovulation. Drospirenone is a spironolactone analogue with antimineralocorticoid and antiandrogenic activity. Estetrol is a synthetic analogue of a natural estrogen synthesized by the fetal liver and present only during pregnancy. It is not metabolized to estradiol or estriol (Grandi 2020).

Pharmacokinetics (Adult Data Unless Noted)

Protein binding: Drospirenone: 95% to 97%, primarily to albumin; Estetrol (E4): 46% to 50%.

Metabolism: Drospirenone: Hepatic via CYP3A4, forms 2 inactive metabolites; E4: Hepatic via phase 2 metabolism to glucuronide and sulphate conjugates (negligible activity), undergoes enterohepatic recycling.

Half-life elimination: Drospirenone: 34 hours; E4: 27 hours.

Time to peak: Drospirenone: 1 to 3 hours; E4: 0.5 to 2 hours.

Excretion: Drospirenone: Urine 38%, feces 44%; E4: Urine 69% (0% unchanged), feces 22% (100% unchanged).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Patients with a CrCl of 30 to 49 mL/minute on a low potassium diet using potassium-sparing drugs had serum drospirenone concentrations ~37% higher than patients with a CrCl 50 to 79 mL/minute. Mean potassium concentrations increased by up to 0.33 mEq/L in most patients who continued use of potassium-sparing drugs.

Hepatic function impairment: The mean drospirenone exposure in patients with moderate hepatic impairment is ~3 times higher than the exposure in patients with normal liver function.

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AR) Argentina: Nextstellis;
(AT) Austria: Drovelis;
(AU) Australia: Nextstellis;
(BE) Belgium: Drovelis | Lydisilka;
(BG) Bulgaria: Drovelis;
(CZ) Czech Republic: Drovelis;
(DE) Germany: Drovelis;
(ES) Spain: Drovelis;
(FI) Finland: Drovelis;
(FR) France: Drovelis;
(HU) Hungary: Drovelis;
(IE) Ireland: Drovelis;
(IT) Italy: Drovelis;
(LT) Lithuania: Drovelis;
(LU) Luxembourg: Drovelis | Lydisilka;
(LV) Latvia: Drovelis;
(NL) Netherlands: Drovelis;
(NO) Norway: Drovelis;
(PL) Poland: Drovelis;
(PT) Portugal: Drovelis;
(RO) Romania: Drovelis;
(SE) Sweden: Drovelis;
(SI) Slovenia: Drovelis;
(SK) Slovakia: Drovelis;
(ZA) South Africa: Estelle

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Topic 131362 Version 66.0

خرید پکیج

Estetrol and drospirenone: Drug information