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Vagifem Side Effects

Generic Name: estradiol topical

Note: This document contains side effect information about estradiol topical. Some of the dosage forms listed on this page may not apply to the brand name Vagifem.

For the Consumer

Applies to estradiol topical: vaginal cream, vaginal ring, vaginal tablet

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of gallbladder problems like pain in the upper right belly area, right shoulder area, or between the shoulder blades; change in stools; dark urine or yellow skin or eyes; or fever with chills.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Chest pain or pressure.
  • Shortness of breath.
  • Coughing up blood.
  • Swelling, warmth, numbness, change of color, or pain in a leg or arm.
  • Very bad headache.
  • Very bad dizziness or passing out.
  • Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
  • Very upset stomach or throwing up.
  • Very bad belly pain.
  • Pelvic pain or pressure.
  • Very bad vaginal irritation.
  • Vaginal itching or discharge.
  • Vaginal bleeding that is not normal.
  • A lump in the breast, breast soreness, or nipple discharge.
  • Breast pain.
  • Low mood (depression).
  • Mood changes.
  • Memory problems or loss.
  • Bulging eyes.
  • Change in how contact lenses feel in the eyes.
  • Change in eyesight.
  • Loss of eyesight.
  • Swelling.

What are some other side effects of this drug?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Headache.
  • Hair loss.
  • Breast soreness.
  • Upset stomach or throwing up.
  • Cramps.
  • Bloating.
  • Vaginal bleeding or spotting.
  • Vaginal irritation.
  • This drug may cause dark patches of skin on your face. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at

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)." Warner Chilcott Laboratories, Rockaway, NJ.

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

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

Some side effects of Vagifem may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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.