Applies to dienogest / estradiol: oral tablet.

Serious side effects

Along with its needed effects, dienogest/estradiol 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 dienogest / estradiol:

More common

• Breast pain, discomfort, or tenderness
• headache, severe and throbbing
• irregular menstrual periods
• nausea
• normal menstrual bleeding occurring earlier, possibly lasting longer than expected
• vomiting

Rare

• Abdominal or stomach pain
• chills
• clay-colored stools
• dark urine
• difficulty with breathing
• dizziness
• fever
• headache
• itching
• loss of appetite
• pain in the chest, groin, or legs, especially the calves
• rash
• slurred speech
• sudden loss of coordination
• sudden, severe weakness or numbness in the arm or leg
• sudden, unexplained shortness of breath
• unpleasant breath odor
• unusual tiredness or weakness
• vision changes
• vomiting of blood
• yellow eyes or skin

Incidence not known

• Abdominal or stomach bloating
• anxiety
• blood in the stool
• chest pain or discomfort
• decrease in the amount of urine
• fainting
• hives
• irritation
• itching of the vagina or genitals
• joint pain, stiffness, or swelling
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• noisy, rattling breathing
• pain in the ankles or knees
• pain or discomfort in the arms, jaw, back, or neck
• pain, redness, or swelling in the arm or leg
• painful, red lumps under the skin, mostly on the legs
• pelvic pain
• pounding in the ears
• redness of the skin
• shortness of breath
• slow or fast heartbeat
• stomach or pelvic discomfort, aching, or heaviness
• sweating
• swelling of the eyelids, face, lips, hands, lower legs, or feet
• thick, white vaginal discharge with mild or no odor
• tightness in the chest
• troubled breathing at rest
• troubled breathing or swallowing
• upper right abdominal or stomach pain
• weight gain
• wheezing

Other side effects

Some side effects of dienogest / estradiol 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
• increased weight
• pimples

Incidence not known

• Patchy brown or dark brown discoloration of the skin

For Healthcare Professionals

Applies to dienogest / estradiol: oral tablet.

Cardiovascular

Common (1% to 10%): Blood pressure changes (including blood pressure increased and blood pressure decreased)

Uncommon (0.1% to 1%): Hypertension, myocardial infarction, palpitations, phlebitis superficialis, vein pain

Rare (less than 0.1%): Hypotension, bleeding varicose vein, venous thromboembolism (VTE), arterial thromboembolism (ATE)

Frequency not reported: Deep vein thrombosis

Postmarketing reports: Venous and arterial thromboembolic events (including pulmonary emboli, deep vein thrombosis, cerebral thrombosis, myocardial infarction, and stroke)^[Ref]

Hepatic

Common (1% to 10%): Liver enzymes increased (including alanine aminotransferase increased, aspartate aminotransferase increased, and gamma-glutamyltransferase increased)

Uncommon (0.1% to 1%): Cholecystitis chronic

Rare (less than 0.1%): Focal nodular hyperplasia of the liver, chronic acalculous cholecystitis

Frequency not reported: Acute cholecystitis

Postmarketing reports: Gallbladder disease, hepatitis^[Ref]

Genitourinary

Common (1% to 10%): Amenorrhea, breast pain/discomfort/tenderness (including nipple disorder and nipple pain), dysmenorrhea, intracyclic bleeding (metrorrhagia), menstrual disorders (menstruation irregular, menorrhagia, vaginal hemorrhage, dysfunctional uterine bleeding, genital hemorrhage, abnormal withdrawal bleeding, uterine hemorrhage), genital discharge

Uncommon (0.1% to 1%): Urinary tract pain, breast discharge, breast enlargement, breast mass, cervical dysplasia, dyspareunia, cervical polyp, cervix erythema, fibrocystic breast disease, ovarian cyst, pelvic pain, premenstrual syndrome, vulvovaginal dryness, smear cervix abnormal, fibrocystic breast disease, uterine spasm, uterine/vaginal bleeding including spotting, vaginal discharge, vulvovaginal dryness

Rare (less than 0.1%): Breast cyst, coital bleeding, galactorrhea, hypomenorrhea, menstruation delayed, ovarian cyst ruptured, vaginal odor, vulvovaginal burning sensation, vulvovaginal discomfort^[Ref]

Gastrointestinal

Common (1% to 10%): Nausea or vomiting, abdominal pain (including abdominal distension)

Uncommon (0.1% to 1%): Diarrhea, constipation, dry mouth

Rare (less than 0.1%): Dyspepsia, gastroesophageal reflux disease

Postmarketing reports: Gastrointestinal symptoms^[Ref]

Nervous system

Nervous Very common (10% or more): Headache (12.7%)

Common (1% to 10%): Tension headaches

Uncommon (0.1% to 1%): Dizziness, migraine (including migraine with and without aura)

Rare (less than 0.1%): Disturbance in attention, paresthesia, vertigo^[Ref]

Dermatologic

Common (1% to 10%): Acne

Uncommon (0.1% to 1%): Alopecia, pruritus (including pruritus generalized and rash pruritic), rash (including rash macular), hirsutism, hyperhidrosis, rash

Rare (less than 0.1%): Chloasma, dermatitis, neurodermatitis, pigmentation disorder, seborrhea, skin disorder (including skin tightness)

Postmarketing reports: Chloasma, angioedema, erythema nodosum, erythema multiforme^[Ref]

General

The most common adverse events were irregular uterine bleeding, nausea, breast tenderness, and headache.^[Ref]

Hematologic

Rare (less than 0.1%): Lymphadenopathy^[Ref]

Hypersensitivity

Rare (less than 0.1%): Allergic skin reaction (including dermatitis allergic and urticaria)

Postmarketing reports: Hypersensitivity^[Ref]

Immunologic

Common (1% to 10%): Vulvovaginal mycotic infection (including vaginal candidiasis)

Uncommon (0.1% to 1%): Fungal infection, vaginal infection

Rare (less than 0.1%): Candidiasis, herpes simplex, presumed ocular histoplasmosis syndrome, tinea versicolor, urinary tract infection, vaginitis bacterial, vulvovaginal mycotic infection, pelvic inflammatory disease^[Ref]

Metabolic

Uncommon (0.1% to 1%): Increased appetite, fluid retention

Rare (less than 0.1%): Hypertriglyceridemia^[Ref]

Musculoskeletal

Uncommon (0.1% to 1%): Muscle spasms, pain in jaw

Rare (less than 0.1%): Back pain^[Ref]

Ocular

Uncommon (0.1% to 1%): Dry eye, eye swelling

Rare (less than 0.1%): Contact lens intolerance^[Ref]

Oncologic

Uncommon (0.1% to 1%): Breast cancer in situ, uterine leiomyoma

Rare (less than 0.1%): Benign breast neoplasm^[Ref]

Other

Common (1% to 10%): Increased weight, fatigue

Uncommon (0.1% to 1%): Edema, weight decreased, peripheral edema, pyrexia

Rare (less than 0.1%): Hot flush, sensation of heaviness, malaise, chest pain

Postmarketing reports: Vulvovaginal candidiasis^[Ref]

Psychiatric

Common (1% to 10%): Mood changes (depression, mood swings, depressed mood, mood altered, affect lability, dysthymic disorder, crying), emotional disorder, insomnia, libido decreased

Uncommon (0.1% to 1%): Libido increased, nervousness, restlessness, sleep disorder, stress, irritability, nightmare

Rare (less than 0.1%): Aggression^[Ref]

Respiratory

Uncommon (0.1% to 1%): Asthma, dyspnea, epistaxis^[Ref]