Applies to drospirenone / estetrol: oral tablet.

Serious side effects

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

• Absent, missed, or irregular menstrual periods
• anger
• anxiety
• breast discomfort, enlargement, fullness, pain, soreness, swelling, or tenderness
• chest pain or discomfort
• confusion about identity, place, and time
• cramps
• difficulty in speaking
• discouragement
• dizziness or lightheadedness
• double vision
• dry mouth
• fainting
• fast or pounding heartbeat
• feeling sad or empty
• headache
• headache, severe and throbbing
• heavy bleeding
• heavy non menstrual vaginal bleeding
• inability to move the arms, legs, or facial muscles
• inability to speak
• irregular heartbeat
• irritability
• lack of appetite
• longer or heavier menstrual periods
• loss of interest or pleasure
• lower stomach cramps or pain
• nausea
• nervousness
• nipple pain
• normal menstrual bleeding occurring earlier, possibly lasting longer than expected
• pain, redness, or swelling in the arm or leg
• pain in the chest, groin, or legs, especially the calves
• pain or discomfort in the arms, jaw, back, or neck
• painful or tender cysts or lumps in the breasts
• pelvic discomfort or pain
• restlessness
• shaking
• slurred speech
• stopping of menstrual bleeding
• sudden, severe weakness or numbness in the arm or leg
• sudden loss of coordination
• sweating
• thoughts of killing oneself changes in behavior
• tiredness
• trouble breathing
• trouble concentrating
• trouble sleeping
• unexpected or excess milk flow from the breasts
• unusually heavy or unexpected menstrual bleeding
• vaginal bleeding or spotting
• vision changes
• vomiting

Other side effects

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

• Blemishes on the skin
• decreased interest in sexual intercourse
• loss in sexual ability, desire, drive, or performance
• pimples
• weight increased

For Healthcare Professionals

Applies to drospirenone / estetrol: oral tablet.

General

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

Cardiovascular

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

Dermatologic

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

Endocrine

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)

Gastrointestinal

Common (1% to 10%): Nausea

Genitourinary

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.

Metabolic

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.

Oncologic

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.

Psychiatric

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)

Other

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

Frequency not reported: Abortion, ectopic pregnancy