Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who uses Estring (Estradiol-vaginal). If you are concerned about side effects, discuss the risks and benefits of Estring (Estradiol-vaginal) with your doctor.

The following side effects have been reported by at least 1% of people using Estring (Estradiol-vaginal). Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• abdominal or back pain
• breast tenderness
• clear vaginal discharge (usually means the medicine is working)
• hair loss
• headache
• nausea
• spotty darkening of the skin
• trouble sleeping
• vaginal discomfort
• vomiting

Although most of the side effects listed below don't happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• breast lumps
• feeling of vaginal pressure
• fluid retention (e.g., swelling of the feet, ankles, or lower legs)
• itching of the vagina or genitals
• leg swelling
• pain, swelling, or tenderness in the abdomen
• signs of Depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
• signs of liver problems (e.g., nausea, vomiting, Diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
• stinging or redness of the genital area
• symptoms of high blood sugar (e.g., frequent urination, increased thirst, excessive eating, unexplained weight loss, poor wound healing, infections, fruity breath odour)
• thick, white vaginal discharge without odour or with a mild odour
• unusual or unexpected uterine bleeding or spotting
• vaginal burning or pain

Stop using the medication and seek immediate medical attention if any of the following occur:

• pain in the calves or chest, sudden shortness of breath, or coughing blood
• severe headache or vomiting, dizziness, seizures, faintness, changes in vision or speech, visual disturbances, weakness or numbness of the arms or legs
• symptoms of allergic reaction (e.g., itching, Hives, swelling, vaginal discomfort/irritation, difficulty breathing)
• symptoms of Toxic Shock Syndrome (e.g., Fever, nausea, vomiting, muscle pain, dizziness, faintness, and a sunburn-like rash on the face and body)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are using Estring (Estradiol-vaginal).

Each slightly opaque vaginal ring, made of a silicone elastomer sheath surrounding a whitish silicone elastomer core, contains 2 mg of estradiol, barium sulfate as a marker, and silicone fluid as a dispersing agent. The estradiol is released slowly as 7.5 µg per 24 hours.

Do not use Estring (Estradiol-vaginal) if you:

• are allergic to estradiol or any ingredients of Estring (Estradiol-vaginal)
• are breast-feeding
• are or may be pregnant
• have a history of known or suspected estrogen-dependent tumours, such as breast, endometrial, or Uterine Cancer
• have active liver disease
• have endometrial hyperplasia (thickening of the inner lining of the uterus)
• have or have had Blood Clots (such as deep vein thrombosis or a pulmonary Embolism) or active Thrombophlebitis (inflammation of the legs)
• have or have had Stroke, Heart Attack, or coronary heart disease
• have health conditions that increase the risk of blood clots (such as certain inherited blood clotting disorders)
• have partial or complete loss of vision from blood vessel disease of the eyes
• have porphyria
• have unusual vaginal bleeding that has not been checked by a doctor

There may be an interaction between the estradiol vaginal ring and any of the following:

• Amiodarone
• Anastrozole
• anticoagulants (e.g., Apixaban, dabigatran, Edoxaban, Rivaroxaban)
• Aprepitant
• "azole" antifungals (e.g., itraconazole, ketoconazole, Voriconazole)
• Bosentan
• cannabis
• blood pressure-lowering medications (e.g., diuretics, Propranolol, Enalapril, Diltiazem)
• Carvedilol
• Celecoxib
• Clozapine
• Cobicistat
• conivaptan
• corticosteroids (e.g., Dexamethasone, Hydrocortisone, Prednisone)
• Cyclosporine
• daclatasvir
• Dantrolene
• Deferasirox
• dehydroepiandrosterone
• diabetes medications (e.g., Canagliflozin, chlorpropamide, Glyburide, insulin, Metformin, Rosiglitazone, Saxagliptin)
• Dronedarone
• Enzalutamide
• Exemestane
• grapefruit juice
• Heparin
• HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., delavirdine, efavirenz, etravirine, nevirapine)
• HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir, saquinavir)
• hyaluronidase
• Lenalidomide
• low molecular weight heparins (e.g., Dalteparin, Enoxaparin, Tinzaparin)
• macrolide antibiotics (e.g., clarithromycin, erythromycin)
• mifepristone
• Modafinil
• nefazodone
• protein kinase inhibitors (e.g., Dabrafenib, imatinib, Nilotinib, Sunitinib)
• quinidine
• quinine
• rifabutin
• rifampin
• Ropinirole
• St. John's wort
• Sarilumab
• seizure medications (e.g., Carbamazepine, Lamotrigine, Phenobarbital, Phenytoin, primidone)
• siltuximab
• Teriflunomide
• thalidomide
• theophyllines (e.g., Aminophylline, Oxtriphylline, Theophylline)
• thyroid
• Tocilizumab
• Ursodiol
• Verapamil
• Vitamin C (ascorbic acid)
• Warfarin

Estradiol vaginal ring releases small amounts of estrogen locally in the vagina and drug interactions are less likely to occur with the vaginal ring than with estrogen medications taken by mouth.

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with Estring (Estradiol-vaginal). Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the Nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

Before you begin using a medication, be sure to inform your doctor of any medical conditions or Allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use Estring (Estradiol-vaginal).

Note the following important information about estrogen replacement therapy:

The Women's Health Initiative (WHI) study results indicated an increased risk of heart attack, stroke, Breast Cancer, blood clots in the lungs, and blood clots in the leg veins in postmenopausal women during 5 years of treatment with 0.625 mg conjugated equine estrogens and 2.5 mg medroxyprogesterone compared to women receiving sugar tablets. Other combinations of estrogen and progestins were not studied. However, until additional data are available, the risks should be assumed to be similar for other hormone replacement products. Therefore,

• estrogens with or without progestins should be used at the lowest dose that relieves your menopausal symptoms for the shortest time period possible, as directed by your doctor
• estrogens with or without progestins should not be used to prevent heart disease, heart attacks, or strokes

Blood clotting disorders: Estrogens with or without progestins are associated with an increased risk of blood clots in the lungs and legs. This risk also increases with age; a personal or family history of blood clots; smoking; and Obesity. The risk of blood clots is also increased if you are immobilized for prolonged periods and with major surgery. If possible, Estring (Estradiol-vaginal) should be stopped 4 weeks before major surgery. Talk about the risk of blood clots with your doctor.

Blood pressure: Women may experience increased blood pressure when using estrogen replacement therapy. Talk to your doctor about how often you should have your blood pressure checked.

Bone disease: If you have bone disease due to cancer or a metabolic condition causing too much calcium in your body, discuss with your doctor how Estring (Estradiol-vaginal) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Estring (Estradiol-vaginal), and whether any special monitoring is needed.

Breast and Ovarian Cancer: Studies indicate an increased risk of breast and ovarian cancer with the use of combined estrogen and progestin therapy. Women who have a history of breast cancer should not use estrogens. Women with a family history of breast cancer or women with a history of breast lumps, breast biopsies, or abnormal mammograms should be closely monitored by their doctor if they use estrogens. Women should have a mammogram before starting hormone replacement therapy. Women taking estrogens should have regular breast examinations and should be taught how to do a breast self-examination.

Dementia: Women over age 65 receiving combined estrogen and progestin replacement therapy may be at increased risk of developing dementia (loss of memory and intellectual function). If you are over 65, talk to your doctor about whether you should be tested for dementia.

Diabetes: If you have diabetes, your doctor should closely monitor your condition while you are taking Estring (Estradiol-vaginal), as it may affect blood sugar control.

Endometrial cancer: Medications containing estrogen increase the risk of cancer of the endometrium (lining of the uterus) in women who have had menopause. If you use any estrogen-containing medication, it is important to visit your doctor regularly and report any unusual vaginal bleeding right away.

Endometriosis: Estrogen replacement therapy can cause endometriosis to reappear or get worse. If you have or have had endometriosis, discuss with your doctor how Estring (Estradiol-vaginal) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Estring (Estradiol-vaginal), and whether any special monitoring is needed.

Fibroids: Estring (Estradiol-vaginal) may worsen fibroids by causing sudden enlargement, pain, or tenderness. If you notice these effects, contact your doctor.

Fluid retention: Estrogen may cause fluid retention, and worsen heart disease, high blood pressure, Kidney Disease, or Asthma. Talk to your doctor if you have any concerns. If you experience worsening of these conditions while using Estring (Estradiol-vaginal), contact your doctor.

Follow-up examinations: It is important to have a follow-up examination 3 to 6 months after starting Estring (Estradiol-vaginal) to assess the response to treatment. Examinations should be done at least once a year after the first one.

Gallbladder: Estring (Estradiol-vaginal) can aggravate gallbladder disease or increase the risk of developing it. If you have gallbladder disease, discuss with your doctor how Estring (Estradiol-vaginal) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Estring (Estradiol-vaginal), and whether any special monitoring is needed.

Heart disease and stroke: Studies indicate an increased risk of heart disease and stroke with estrogen (with or without progestin) for postmenopausal women. If you experience symptoms of a heart attack (chest pain, tightness or pressure, sweating, nausea, feeling of impending doom) or stroke (sudden dizziness, headache, loss of speech, changes in vision, weakness or numbness in the arms and legs) while taking Estring (Estradiol-vaginal), get immediate medical attention.

Liver disease:  If you have liver disease, discuss with your doctor how Estring (Estradiol-vaginal) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Estring (Estradiol-vaginal), and whether any special monitoring is needed. See your doctor as soon as possible if you develop signs of liver problems such as yellow eyes or skin, abdominal pain, dark urine, pale stools, or itchy skin.

Seizures: Estradiol may cause an increase in the frequency of seizures. If you have a history of Epilepsy or medical conditions that increase the risk of seizures, discuss with your doctor how Estring (Estradiol-vaginal) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Estring (Estradiol-vaginal), and whether any special monitoring is needed.

Thyroid disease: Estring (Estradiol-vaginal) may affect how thyroid hormone is used by the body. If you are taking thyroid hormone for an underactive thyroid gland, discuss with your doctor how Estring (Estradiol-vaginal) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Estring (Estradiol-vaginal), and whether any special monitoring is needed.

Vaginal infections: Vaginal infections should be treated by your doctor before starting Estring (Estradiol-vaginal). If a vaginal infection develops while using estradiol vaginal ring, remove the ring until the infection has cleared, and then re-insert it into the vagina.

X-ray procedures: Remove the vaginal ring before having any X-ray procedures of the lower abdominal tract. Be sure to tell all your doctors that you are using an estrogen vaginal ring.

Pregnancy: Estrogen vaginal ring must not be used during pregnancy. If you become pregnant while using Estring (Estradiol-vaginal), contact your doctor immediately.

Breast-feeding: Estring (Estradiol-vaginal) passes into breast milk. If you are a breast-feeding mother and are taking Estring (Estradiol-vaginal), it may affect your baby. Estring (Estradiol-vaginal) is not recommended for breast-feeding women.

Children: The safety and effectiveness of using Estring (Estradiol-vaginal) have not been established for children. Estring (Estradiol-vaginal) is not intended for use by children.