Evamist

Use Evamist exactly as prescribed.

• Evamist is for skin use only.
• Apply Evamist at the same time each day.
• If you use sunscreen 1 hour after you use Evamist, it may reduce the amount of Evamist absorbed by your skin.
• The estrogen in Evamist spray can transfer from the area of skin where it was sprayed to other people or pets. Do not allow other people, especially children to come into contact with the area of your skin where you have sprayed Evamist.
• If another person accidentally touches the area of your skin where you have sprayed Evamist, that area of their skin should be washed with soap and water right away.
• Do not let pets lick or touch your arm where you have sprayed Evamist, especially small pets. Evamist may harm them. Cover your skin with clothing where you have sprayed Evamist if you think a pet could come in contact with that area of your skin.
  • If a pet accidentally comes in contact with the area of your skin where you have sprayed Evamist, the area of the pet’s skin should be washed with soap and water right away.
• Young children who are accidentally exposed to estrogen through contact with women using Evamist may show signs and symptoms of puberty that are not expected. Signs and symptoms in children of exposure to Evamist may include:

• breast budding or breast lumps
• other signs of abnormal sexual development

If a child shows signs and symptoms of accidental exposure to Evamist:

• have the child checked right away by their healthcare provider.
• stop using Evamist and call your healthcare provider right away.
• talk to your healthcare provider about the correct use of Evamist when around children.

Talk to your healthcare provider about other treatments for your menopause symptoms if accidental exposure to Evamist cannot be avoided.

You and your healthcare provider should talk regularly (for example, every 3 to 6 months) about the dose you are taking and whether you still need treatment with Evamist.

Your pharmacist can provide more information about estradiol topical.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. 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 drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 7.01. Revision date: 6/13/2012.

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In the U.S.

• Alora
• Cenestin
• Climara
• Divigel
• Elestrin
• Emcyt
• Enjuvia
• Esclim
• Estinyl
• EstroGel
• Evamist
• Femtrace
• Gynodiol
• Menest
• Menostar
• Minivelle
• Ogen .625
• Ogen 1.25
• Ogen 2.5
• Premarin
• Vivelle
• Vivelle-Dot

In Canada

• Estraderm
• Estradot Transdermal
• Estradot Transdermal Therapeutic System
• Estradot Transdermal Therapeutic System
• Estrogel
• Oesclim
• Rhoxal-Estradiol Derm 50
• Rhoxal-Estradiol Derm 75
• Roxal-Estradiol Derm 100
• Vivelle 100 Mcg
• Vivelle 25 Mcg

Available Dosage Forms:

• Tablet
• Cream
• Patch, Extended Release
• Gel/Jelly
• Spray
• Emulsion
• Tablet, Enteric Coated
• Capsule

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Use of this medicine before puberty is not recommended. Growth of bones can be stopped early. Girls and boys may develop growth of breasts. Girls may have vaginal changes, including vaginal bleeding.

This medicine may be used to start puberty in teenagers with some types of delayed puberty.

Geriatric

Elderly people are especially sensitive to the effects of estrogens. This may increase the chance of side effects during treatment, especially stroke, invasive breast cancer, and memory problems.

Pregnancy

Estrogens are not recommended for use during pregnancy or right after giving birth. Becoming pregnant or maintaining a pregnancy is not likely to occur around the time of menopause.

Certain estrogens have been shown to cause serious birth defects in humans and animals. Some daughters of women who took diethylstilbestrol (DES) during pregnancy have developed reproductive (genital) tract problems and, rarely, cancer of the vagina or cervix (opening to the uterus) when they reached childbearing age. Some sons of women who took DES during pregnancy have developed urinary-genital tract problems.

Breast Feeding

Use of this medicine is not recommended in nursing mothers. Estrogens pass into the breast milk and their possible effect on the baby is not known.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking any of these medicines, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using medicines in this class with any of the following medicines is not recommended. Your doctor may decide not to treat you with a medication in this class or change some of the other medicines you take.

• Dasabuvir
• Ombitasvir
• Paritaprevir
• Ritonavir
• Tranexamic Acid

Using medicines in this class with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Anagrelide
• Aprepitant
• Boceprevir
• Bosentan
• Bupropion
• Carbamazepine
• Ceritinib
• Conivaptan
• Dabrafenib
• Darunavir
• Dasabuvir
• Dexamethasone
• Donepezil
• Eliglustat
• Enzalutamide
• Fosphenytoin
• Griseofulvin
• Idelalisib
• Isotretinoin
• Lesinurad
• Lixisenatide
• Lumacaftor
• Mitotane
• Modafinil
• Netupitant
• Oxcarbazepine
• Paclitaxel
• Paclitaxel Protein-Bound
• Phenytoin
• Piperaquine
• Pitolisant
• Pixantrone
• Prednisone
• Rifabutin
• Rifampin
• St John's Wort
• Sugammadex
• Theophylline
• Tizanidine
• Topiramate
• Valproic Acid

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of medicines in this class. Make sure you tell your doctor if you have any other medical problems, especially:

For all patients

• Asthma or
• Calcium, too much or too little in blood or
• Diabetes or
• Epilepsy or seizures or
• Heart problems or
• Kidney problems or
• Liver tumors, benign or
• Lupus erythematosus, systemic or
• Migraine headaches—Estrogens may worsen these conditions.

• Blood clotting problems, or history of during previous estrogen therapy—Estrogens usually are not used until blood clotting problems stop; using estrogens is not a problem for most patients without a history of blood clotting problems due to estrogen use.

• Breast cancer or
• Bone cancer or
• Cancer of the uterus or
• Fibroid tumors of the uterus—Estrogens may interfere with the treatment of breast or bone cancer or worsen cancer of the uterus when these conditions are present.

• Bulging eyes or
• Double vision or
• Migraine headache or
• Vision changes, sudden onset including or
• Vision loss, partial or complete—Estrogens may cause these problems. Tell your doctor if you have had any of these problems, especially while taking estrogen or oral contraceptives (“birth control pills”).

• Changes in genital or vaginal bleeding of unknown causes—Use of estrogens may delay diagnosis or worsen condition. The reason for the bleeding should be determined before estrogens are used.

• Endometriosis or
• Gallbladder disease or gallstones, or history of or
• High cholesterol or triglycerides, or history of or
• Liver disease, or history of or
• Pancreatitis (inflammation of pancreas) or
• Porphyria—Estrogens may worsen these conditions. Although estrogens can improve blood cholesterol, they can worsen blood triglycerides for some people.

• Hypothyroid (too little thyroid hormone)—Dose of thyroid medicine may need to be increased.

For males treated for breast or prostate cancer:

• Blood clots or
• Heart or circulation disease or
• Stroke—Males with these medical problems may be more likely to have clotting problems while taking estrogens; the high doses of estrogens used to treat male breast or prostate cancer have been shown to increase the chances of heart attack, phlebitis (inflamed veins) caused by a blood clot, or blood clots in the lungs.

Women rarely have severe side effects from taking estrogens to replace estrogen. Discuss these possible effects with your doctor:

The prolonged use of estrogens has been reported to increase the risk of endometrial cancer (cancer of the lining of the uterus) in women after menopause. This risk seems to increase as the dose and the length of use increase. When estrogens are used in low doses for less than 1 year, there is less risk. The risk is also reduced if a progestin (another female hormone) is added to, or replaces part of, your estrogen dose. If the uterus has been removed by surgery (total hysterectomy), there is no risk of endometrial cancer.

Although the incidence is low, the use of estrogens may increase you chance of getting cancer of the breast. Breast cancer has been reported in men taking estrogens.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

The following side effects may be caused by blood clots, which could lead to stroke, heart attack, or death. These side effects occur rarely, and, when they do occur, they occur in men treated for cancer using high doses of estrogens.

Check with your doctor immediately if any of the following side effects occur:

More common

• Breast pain (in females and males)
• fast heartbeat
• fever
• hives
• hoarseness
• increased breast size (in females and males)
• irritation of the skin
• itching of the skin
• joint pain, stiffness, or swelling
• rash
• redness of the skin
• shortness of breath
• swelling of the eyelids, face, lips, hands, or feet
• swelling of the feet and lower legs
• tightness in the chest
• troubled breathing or swallowing
• weight gain (rapid)
• wheezing

Less common or rare

• Changes in vaginal bleeding (spotting, breakthrough bleeding, prolonged or heavier bleeding, or complete stoppage of bleeding)
• chest pain
• chills
• cough
• heavy non-menstrual vaginal bleeding
• lumps in, or discharge from, breast (in females and males)
• pains in the stomach, side, or abdomen
• yellow eyes or skin

Rare - for males being treated for breast or prostate cancer only

• Headache (sudden or severe)
• loss of coordination (sudden)
• loss of vision or change of vision (sudden)
• pains in the chest, groin, or leg, especially in the calf of leg
• shortness of breath (sudden and unexplained)
• slurring of speech (sudden)
• weakness or numbness in the arm or leg

Incidence not known

• Abdominal or stomach bloating
• abdominal or stomach cramps
• acid or sour stomach
• anxiety
• backache
• belching
• blindness
• blistering, peeling, or loosening of the skin
• blue-yellow color blindness
• blurred vision
• change in vaginal discharge
• changes in skin color
• changes in vision
• chest discomfort
• clay-colored stools
• clear or bloody discharge from nipple
• confusion
• constipation
• convulsions
• dark urine
• decrease in the amount of urine
• decreased vision
• depression
• diarrhea
• difficulty with breathing
• difficulty with speaking
• dimpling of the breast skin
• dizziness
• double vision
• dry mouth
• eye pain
• fainting
• fluid-filled skin blisters
• full feeling in upper abdomen or stomach
• full or bloated feeling or pressure in the stomach
• headache
• heartburn
• inability to move the arms, legs, or facial muscles
• inability to speak
• incoherent speech
• increased urination
• indigestion
• inverted nipple
• irregular heartbeats
• light-colored stools
• lightheadedness
• loss of appetite
• loss of bladder control
• lump under the arm
• metallic taste
• migraine headache
• mood or mental changes
• muscle cramps in the hands, arms, feet, legs, or face
• muscle pain
• muscle spasm or jerking of all extremities
• muscle weakness
• nausea
• noisy breathing
• numbness or tingling of the hands, feet, or face
• pain in the ankles or knees
• pain or discomfort in the arms, jaw, back or neck
• pain or feeling of pressure in the pelvis
• pain, tenderness, swelling of the foot or leg
• painful or tender cysts in the breasts
• painful, red lumps under the skin, mostly on the legs
• pains in the chest, groin, or legs, especially calves of the legs
• partial or complete loss of vision in the eye
• pelvic pain
• persistent crusting or scaling of nipple
• pinpoint red or purple spots on the skin
• prominent superficial veins over affected area
• red, irritated eyes
• redness or swelling of the breast
• sensitivity to the sun
• severe headaches of sudden onset
• skin thinness
• skin warmth
• slow speech
• sore on the skin of the breast that does not heal
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• stomach discomfort, upset, or pain
• sudden loss of consciousness
• sudden loss of coordination
• sudden onset of shortness of breath for no apparent reason
• sudden onset of slurred speech
• sudden vision changes
• swelling of the abdominal or stomach area
• swelling of the fingers or hands
• thirst
• tremor
• unpleasant breath odor
• unusual tiredness or weakness
• vomiting
• vomiting of blood
• weight loss

Some side effects 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:

More common

• Abnormal growth filled with fluid or semisolid material
• accidental injury
• bladder pain
• bloated full feeling
• bloody or cloudy urine
• body aches or pain
• coating or white patches on tongue
• congestion
• cough producing mucus
• decrease in amount of urine
• difficult, burning, or painful urination
• discouragement
• dryness of the throat
• ear congestion or pain
• excess air or gas in the stomach or intestines
• fear
• feeling of warmth
• feeling sad or empty
• frequent urge to urinate
• general feeling of discomfort or illness
• headache, severe and throbbing
• increased clear or white vaginal discharge
• irritability
• itching of the vaginal, rectal or genital areas
• lack of appetite
• lack or loss of strength
• loss of interest or pleasure
• mild dizziness
• neck pain
• nervousness
• pain
• pain during sexual intercourse
• painful or difficult urination
• pain or tenderness around the eyes and cheekbones
• passing gas
• redness of the face, neck, arms, and occasionally, upper chest
• runny nose
• skin irritation or redness where skin patch was worn
• shivering
• sleeplessness
• sneezing
• sore mouth or tongue
• stuffy nose
• sudden sweating
• tender, swollen glands in the neck
• thick, white vaginal discharge with no odor or with a mild odor
• tiredness
• trouble concentrating
• trouble sleeping
• unable to sleep
• voice changes

Less common

• Blemishes on the skin
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• burning or stinging of the skin
• diarrhea (mild)
• difficulty with moving
• dizziness (mild)
• increased hair growth, especially on the face
• lower abdominal or stomach pain or pressure
• mood or mental changes
• muscle stiffness
• painful cold sores or blisters on the lips, nose, eyes, or genitals
• pimples
• pounding in the ears
• problems in wearing contact lenses
• slow heartbeat
• tooth or gum pain
• unusual decrease in sexual desire (in males)
• unusual increase in sexual desire (in females)
• white or brownish vaginal discharge

Incidence not known

• Abnormal turning out of cervix
• changes in appetite
• dull ache or feeling of pressure or heaviness in the legs
• flushed, dry skin
• fruit-like breath odor
• increased hunger
• irritability
• large amount of triglyceride in the blood
• leg cramps
• patchy brown or dark brown discoloration of the skin
• poor insight and judgment
• problems with memory or speech
• trouble recognizing objects
• trouble thinking and planning
• trouble walking
• twitching, uncontrolled movements of the tongue, lips, face, arms, or legs
• unexpected or excess milk flow from the breasts

Also, many women who are taking estrogens with a progestin (another female hormone) will start having monthly vaginal bleeding, similar to menstrual periods, again. This effect will continue for as long as the medicine is taken. However, monthly bleeding will not occur in women who have had the uterus removed by surgery (total hysterectomy).

This medicine may cause loss or thinning of the scalp hair in some people.

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Generally, when estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be considered to reduce the risk of endometrial cancer. A woman without a uterus does not need a progestin. In some cases, however, hysterectomized women with a history of endometriosis may need a progestin [see Warnings and Precautions (5.2, 5.15)].

Use of estrogen-alone, or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary.

Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause.

Evamist therapy should be initiated with one spray per day. Dosage adjustment should be guided by the clinical response.

Before applying the first dose from a new applicator, the pump should be primed by spraying 3 sprays with the cover on. The container should be held upright and vertical for spraying.

One, two or three sprays are applied each morning to adjacent, non-overlapping areas on the inner surface of the forearm, starting near the elbow. Sprays should be allowed to dry for approximately 2 minutes before covering the site with clothing. The site should not be washed for at least one hour. Application of Evamist to other skin surfaces has not been adequately studied. Evamist should not be applied to skin surfaces other than the forearm.

Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to estradiol from Evamist-treated skin. Women should cover the Evamist application site with clothing if another person may come into contact with that area of skin after the spray dries. Additional precautions to minimize unintentional secondary exposure are outlined in Patient Counseling Information [see Patient Counseling Information (17.2)] and in the Patient Information Leaflet at the end of the prescribing information.

Evamist is contraindicated in women with any of the following conditions:

• Undiagnosed abnormal genital bleeding • Known, suspected, or history of cancer of the breast (See Warnings and Precautions (5.2)) • Known or suspected estrogen-dependent neoplasia (See Warnings and Precautions (5.2)) • Active DVT, PE, or history of these conditions (See Warnings and Precautions (5.1)) • Active arterial thromboembolic disease (for example, stroke and MI), or history of these conditions (See Warnings and Precautions (5.1)) • Known anaphylactic reaction or angioedema with Evamist • Known liver impairment or disease (See Warnings and Precautions (5.10)) • Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders • Known or suspected pregnancy (See Warnings and Precautions (8.1))

No drug interaction studies have been conducted for Evamist.

Metabolic Interactions

In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4 such as St. John's wort (Hypericum perforatum) preparations, phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects.

1. Rossouw JE, et al. Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause. JAMA. 2007:297;1465-1477. 2. Hsia J, et al. Conjugated Equine Estrogens and Coronary Heart Disease. Arch Int Med. 2006;166:357–365. 3. Curb JD, et al. Venous Thrombosis and Conjugated Equine Estrogen in Women Without a Uterus. Arch Int Med. 2006;166:772-780. 4. Cushman M, et al. Estrogen Plus Progestin and Risk of Venous Thrombosis. JAMA. 2004:292;1573-1580. 5. Stefanick ML, et al. Effects of Conjugated Equine Estrogens on Breast Cancer and Mammography Screening in Postmenopausal Women with Hysterectomy. JAMA. 2006;295:1647-1657. 6. Chlebowski RT, et al. Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women. JAMA. 2003:289;3234-3253. 7. Anderson GL, et al. Effects of Estrogen Plus Progestin in Gynecologic Cancers and Associated Diagnostic Procedures. JAMA. 2003:290;1739-1748. 8. Shumaker SA, et al. Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women. JAMA. 2004:291;2947-2958. 9. Jackson RD, et al. Effects of Conjugated Equine Estrogen on Risk of Fractures and BMD in Postmenopausal Women with Hysterectomy: Results from the Women’s Health Initiative Randomized Trial. J Bone Miner Res. 2006:21;817-828. 10. Hendrix SL, et al. Effects of Conjugated Equine Estrogen on Stroke in the Women’s Health Initiative. Circulation. 2006:113;2425-2434.

NDC 0574-2067-00

FOR TOPICAL USE ONLY

Evamist®

(estradiol transdermal spray)

Each spray contains 1.53 mg of estradiol

PROFESSIONAL SAMPLE

NOT TO BE SOLD

0.27 fl oz (8.1 mL)

Rx Only

Evamist  estradiol spray

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0574-2067 Route of Administration TRANSDERMAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ESTRADIOL (ESTRADIOL) ESTRADIOL 1.53 mg

Inactive Ingredients Ingredient Name Strength OCTISALATE   ALCOHOL

Packaging # Item Code Package Description 1 NDC:0574-2067-27 56 SPRAY in 1 VIAL, MULTI-DOSE 2 NDC:0574-2067-00 56 SPRAY in 1 VIAL, MULTI-DOSE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022014 04/11/2015

Labeler - Paddock Laboratories, LLC (967694121)

Revised: 08/2017   Paddock Laboratories, LLC