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Vagifem Side Effects

Generic Name: estradiol topical

Note: This page contains side effects data for the generic drug estradiol topical. It is possible that some of the dosage forms included below may not apply to the brand name Vagifem.

For the Consumer

Applies to estradiol topical: vaginal cream

Other dosage forms:

Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Breast pain or tenderness; headache; hair loss; mild nausea or vomiting; spotting or breakthrough bleeding; stomach cramps or bloating.

Seek medical attention right away if any of these SEVERE side effects occur while taking estradiol topical (the active ingredient contained in Vagifem)

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); back pain;breast discharge or lump in the breast; calf or leg pain or swelling; chest pain; coughing up blood; dark urine; depression; dizziness; fainting; fever; memory problems; mental or mood changes; muscle pain; one-sided weakness; painful or difficult urination; persistent or severe breast pain or tenderness; persistent or severe headache, nausea, or vomiting; severe stomach pain or swelling; slurred speech; sudden shortness of breath; sunburn-like rash; swelling of hands, legs, or feet; unusual vaginal bleeding, discharge, itching, or odor; vision changes; vomiting; weakness or numbness of an arm or leg; yellowing of the skin or eyes.

For Healthcare Professionals

Applies to estradiol topical: transdermal film extended release, vaginal cream, vaginal ring, vaginal tablet


The most commonly reported side effects were headache, leukorrhea, vaginitis, vaginal pain/discomfort, and vaginal hemorrhage.[Ref]


Common (1% to 10%): Hot flushes
Frequency not reported: Deep and superficial venous thrombosis, thrombophlebitis, myocardial infarction, stroke, increase in blood pressure, congestive heart disease[Ref]


Frequency not reported: Breast cancer, endometrial cancer, ovarian cancer[Ref]


Frequency not reported: Hypersensitivity, anaphylactoid/anaphylactic reactions[Ref]


Very common (10% or more): Infection (12%)
Common (1% to 10%): Allergy
Postmarketing reports: Toxic shock syndrome (fever, nausea, vomiting, diarrhea, muscle pain, dizziness, faintness, or a sunburn-rash on face and body)[Ref]


Very common (10% or more): Endometrial disorder (15%), breast pain (10%)
Common (1% to 10%): Urinary tract infection, leukorrhea, vaginitis, vaginal discomfort/pain, vaginal hemorrhage, asymptomatic genital bacterial growth, genital moniliasis, vulvovaginal mycotic infection, vulvovaginal pruritus, bladder discomfort
Frequency not reported: Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow, breakthrough bleeding, spotting, dysmenorrhea, increase in size of uterine leiomyomata, vaginal candidiasis, change in amount of cervical secretion, changes in cervical ectropion, application site reactions of vulvovaginal discomfort including burning and irritation, genital pruritus, endometrial hyperplasia, breast (tenderness, enlargement), nipple discharge, galactorrhea, fibrocystic breast changes
Postmarketing reports: Ring adherence to the vaginal wall, genital edema, vulval disorder, micturition frequency, urethral disorder, ovarian cancer, endometrial hyperplasia, endometrial cancer, breast cancer, vaginal erosion, vaginal ulceration[Ref]


Frequency not reported: Increase or decrease in weight, reduced carbohydrate tolerance, aggravation of porphyria, hypocalcemia, increased triglycerides
Postmarketing reports: Fluid retention[Ref]


Common (1% to 10%): Abdominal pain, nausea, diarrhea, lower abdominal pain, abdominal discomfort, anorectal discomfort, dyspepsia
Frequency not reported: Vomiting, abdominal cramps, bloating, cholestatic jaundice, increased incidence of gallbladder disease, pancreatitis
Postmarketing reports: Bowel obstruction, enlarged abdomen, bloating, enlargement of hepatic hemangiomas[Ref]


Frequency not reported: Increased thyroid-binding globulin (TBG) levels
Postmarketing reports: Estrogen increase[Ref]


Frequency not reported: Enlargement of hepatic hemangiomas[Ref]


Frequency not reported: Retinal vascular thrombosis, intolerance to contact lenses, steepening of corneal curvature
Postmarketing reports: Abnormal vision[Ref]


Common (1% to 10%): Flu-like symptoms, peripheral edema
Frequency not reported: Edema[Ref]


Common (1% to 10%): Insomnia
Uncommon (0.1% to 1%): Anxiety
Frequency not reported: Changes in libido
Postmarketing reports: Depression[Ref]

Nervous system

Very common (10% or more): Headache (13%)
Frequency not reported: Migraine, dizziness, chorea, nervousness, mood disturbances, irritability, exacerbation of epilepsy, dementia[Ref]


Common (1% to 10%): Hyperhidrosis
Frequency not reported: Chloasma or melasma, erythema multiforme, erythema nodosum, hemorrhagic eruption, loss of scalp hair, hirsutism, pruritus, rash, urticaria, angioedema, vascular purpura
Postmarketing reports: Pruritus ani, erythematous rash[Ref]


Common (1% to 10%): Upper respiratory tract infection, sinusitis, pharyngitis
Frequency not reported: Pulmonary embolism (venous thromboembolism or VTE), exacerbation of asthma[Ref]


Common (1% to 10%): Back pain, arthritis, arthralgia, skeletal pain
Frequency not reported: Leg cramps
Postmarketing reports: Arthropathy (including arthrosis)[Ref]


Frequency not reported: Local abrasion[Ref]


1. "Product Information. Estrace (estradiol)." Bristol-Myers Squibb, Princeton, NJ.

2. Cerner Multum, Inc. "Australian Product Information." O 0

3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

It is possible that some side effects of Vagifem may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.