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Nextstellis Side Effects

Generic name: drospirenone / estetrol

Medically reviewed by Last updated on Nov 19, 2023.

Note: This document contains side effect information about drospirenone / estetrol. Some dosage forms listed on this page may not apply to the brand name Nextstellis.

Applies to drospirenone / estetrol: oral tablet.


Oral route (Tablet)

Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives (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 drospirenone and estetrol tablets, are contraindicated in women who are over 35 years of age and smoke.

Serious side effects of Nextstellis

Along with its needed effects, drospirenone / estetrol may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking drospirenone / estetrol:

Less common

Other side effects of Nextstellis

Some side effects of drospirenone / estetrol may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

For Healthcare Professionals

Applies to drospirenone / estetrol: oral tablet.


The more commonly reported adverse reactions have included bleeding irregularities, mood disturbances, headache, breast symptoms, dysmenorrhea, acne, weight gain, and decreased libido.[Ref]


Of the 2 prospective studies conducted with this drug in females 16 through 50 years old (n=3632), there was 1 reported VTE. This occurred in a female with a BMI less than 25 kg/m2 receiving this drug for 75 days.

Frequency not reported: Venous thromboembolism event (VTE), hypertension


Common (1% to 10%): Acne (includes acne and cystic acne)


Common (1% to 10%): Breast symptoms (includes anisomastia, breast cyst, breast discoloration, breast discomfort, breast disorder, breast engorgement, breast enlargement, breast mass, breast edema, breast pain, breast swelling, breast tenderness, fibrocystic breast disease, galactorrhea, gynecomastia, mastoptosis, nipple disorder, nipple pain)


Common (1% to 10%): Nausea


Very common (10% or more): Unscheduled bleeding (up to 30.3%); absence of scheduled bleeding (15.5%), bleeding irregularities 10.8% (includes abnormal withdrawal bleeding, amenorrhea, cervix hemorrhage uterine, coital bleeding, dysfunctional uterine bleeding, menometrorrhagia, menorrhagia, menstrual disorder, menstruation irregular, metrorrhagia, oligomenorrhea, polymenorrhea, uterine hemorrhage, vaginal hemorrhage)

Common (1% to 10%): Dysmenorrhea (includes adnexa uteri pain, dysmenorrhea, premenstrual cramps, pelvic discomfort, pelvic pain, uterine spasm), libido (lost/decreased)

During clinical trials, unscheduled bleeding (defined as bleeding or spotting occurring on Day 4 through Day 24 of a 28-day cycle) declined over time. During the first cycle, unscheduled bleeding was reported by 30.3% of patients compared to 17.4% at cycle 12. The mean number of unscheduled bleeding/spotting days per cycle also decreased with a mean of 0.4 bleeding days at cycle 1 and 0.2 bleeding days at cycle 12. The absence of scheduled bleeding remained constant from cycle one through cycle twelve.


Of the 2 prospective studies conducted with this drug in females 16 through 50 years old (n=3632), 7 women experienced hyperkalemia (1 discontinued due to elevated potassium levels). Most females who developed hyperkalemia had only mild potassium elevations and/or isolated increases that returned to normal while remaining on therapy.

Common (1% to 10%): Increased weight (includes weight increased, weight fluctuation, body mass index increased, weight loss poor, and obesity)

Frequency not reported: Hyperkalemia

Nervous system

Common (1% to 10%): Headache (includes headache, premenstrual headache, and tension headache)

Six subjects (0.17%) discontinued study participation due to new onset of migraine with aura; two subjects (0.05%) discontinued due to severe migraine.


Frequency not reported: Cervical cancer, breast cancer, intraepithelial neoplasia

Observational studies have reported an association with use of COCs for 5 years or more and increased cervical cancer and intraepithelial neoplasia compared to female who did not use oral hormonal contraceptives. Additionally, for females using COCs for 10 years or more, there were more cases compared to those who received COCs for 5 to 9 years. Limitations with this study included potential recall bias, differences in sexual behavior, and other factors such as data on Human Papilloma Virus infection.


In one of the clinical trials 36 (1.7%) women reported depression during therapy with this drug; 9 (0.3%) women stopped therapy due to symptoms of depression.

Common (1% to 10%): Mood disturbance (includes adjustment disorder, affective disorder, agitation, anger, anxiety, depressed mood, depression, depressive symptom, disorientation, emotional disorder, emotional distress, euphoric mood, generalized anxiety disorder, insomnia, irritability, mood altered, mood swings, nervousness, panic attack, panic disorder, performance fear, restlessness, sleep disorder, stress, suicidal ideation, tearfulness)


Very common (10% or more): Any treatment-related adverse reaction (27.1%)

Frequency not reported: Abortion, ectopic pregnancy


1. Product Information. Nextstellis (drospirenone-estetrol). Mayne Pharma. 2021.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.