Yuvafem

• If you have an allergy to estradiol or any other part of Yuvafem (estradiol vaginal tablets).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have had any of these health problems: Bleeding disorder, blood clots, a higher risk of having a blood clot, breast cancer, liver problems or liver tumor, heart attack, stroke, or a tumor where estrogen makes it grow.
• If you have unexplained vaginal bleeding.
• If you are pregnant or may be pregnant. Do not take this medicine if you are pregnant.
• If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with Yuvafem.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take Yuvafem. This includes your doctors, nurses, pharmacists, and dentists.
• If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
• Be sure to have regular breast exams and gynecology check-ups. Your doctor will tell you how often to have these. You will also need to do breast self-exams as your doctor has told you. Talk with your doctor.
• High blood pressure has happened with drugs like this one. Have your blood pressure checked as you have been told by your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• Do not smoke. Smoking raises the chance of heart disease. Talk with your doctor.
• Limit your drinking of alcohol.
• If you drink grapefruit juice or eat grapefruit often, talk with your doctor.
• This medicine may raise the chance of blood clots, a stroke, or a heart attack. Talk with the doctor.
• Talk with your doctor if you will need to be still for long periods of time like long trips, bedrest after surgery, or illness. Not moving for long periods may raise your chance of blood clots.
• If you are 65 or older, use Yuvafem with care. You could have more side effects.
• This medicine is not approved for use in children. Talk with the doctor.

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 medicine 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 http://www.fda.gov/medwatch.

1.1 Treatment of Atrophic Vaginitis due to Menopause

.

Yuvafem should not be used in women with any of the following conditions:

• Undiagnosed abnormal genital bleeding
• Known, suspected, or history of breast cancer
• Known or suspected estrogen-dependent neoplasia
• Active DVT, PE, or history of these conditions
• Active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions
• Known anaphylactic reaction or angioedema to Yuvafem
• Known liver impairment or disease
• Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
• Known or suspected pregnancy

8.1 Pregnancy

Yuvafem should not be used during pregnancy [see Contraindications (4)]. There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins as an oral contraceptive inadvertently during early pregnancy.

8.3 Nursing Mothers

Yuvafem should not be used during lactation. Estrogen administration to nursing women has been shown to decrease the quantity and quality of the breast milk. Detectable amounts of estrogens have been identified in the breast milk of women receiving estrogen therapy. Caution should be exercised when Yuvafem is administered to a nursing woman.

8.4 Pediatric Use

Yuvafem is not indicated in children. Clinical studies have not been conducted in the pediatric population.

8.5 Geriatric Use

There have not been sufficient numbers of geriatric women involved in clinical studies utilizing Yuvafem to determine whether those over 65 years of age differ from younger subjects in their response to Yuvafem.

The Women’s Health Initiative Studies

In the WHI estrogen-alone substudy (daily CE [0.625 mg]-alone versus placebo), there was a higher relative risk of stroke in women greater than 65 years of age [see Clinical Studies (14.2)].

In the WHI estrogen plus progestin substudy (daily CE [0.625 mg] plus MPA [2.5 mg] versus placebo), there was a higher relative risk of nonfatal stroke and invasive breast cancer in women greater than 65 years of age [see Clinical Studies (14.2)].

The Women’s Health Initiative Memory Study

In the WHIMS ancillary studies of postmenopausal women 65 to 79 years of age, there was an increased risk of developing probable dementia in women receiving estrogen-alone or estrogen plus progestin when compared to placebo [see Warnings and Precautions (5.4) and Clinical Studies (14.3)].

Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women8[see Warnings and Precautions (5.4) and Clinical Studies (14.3)].

8.6 Renal Impairment

The effect of renal impairment on the pharmacokinetics of Yuvafem has not been studied.

8.7 Hepatic Impairment

The effect of hepatic impairment on the pharmacokinetics of Yuvafem has not been studied.

Yuvafem® (estradiol vaginal inserts)                 

Read this PATIENT INFORMATION before you start using Yuvafem and read what you get each time you refill your Yuvafem prescription. There may be new information. This information does not take the place of talking to your healthcare provider about your menopausal symptoms or your treatment.

What are Yuvafem?

Yuvafem are a medicine that contains estradiol (an estrogen hormone) in a vaginal tablet.

What are Yuvafem used for?

Estradiol vaginal inserts are used after menopause to:

• Treat menopausal changes in and around the vagina

  You and your healthcare provider should talk regularly about whether you still need treatment with Yuvafem to control these problems.

  Who should not use Yuvafem?

  Do not start using Yuvafem if you:

• Have unusual vaginal bleeding
• Currently have or have had certain cancers

• Estrogens may increase the chances of getting certain types of cancers, including cancer of the breast or uterus. If you have or have had cancer, talk with your healthcare provider about whether you should use Yuvafem.

• Had a stroke or heart attack
• Currently have or have had blood clots
• Currently have or have had liver problems
• Have been diagnosed with a bleeding disorder
• Are allergic to Yuvafem or any of its ingredients

• See the list of ingredients in Yuvafem at the end of this leaflet.

• Think you may be pregnant

  Tell your healthcare provider:

• If you have any unusual vaginal bleeding

  Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.

• About all of your medical problems

  Your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma (wheezing), epilepsy (seizures), diabetes, migraine, endometriosis, lupus, problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood.

• About all the medicines you take

  This includes prescription and nonprescription medicines, vitamins and herbal supplements. Some medicines may affect how Yuvafem work. Yuvafem may also affect how your other medicines work.

• If you are going to have surgery or will be on bed rest

  You may need to stop using Yuvafem.

• If you are breast feeding

  The hormone in Yuvafem can pass into your breast milk.

  How should I useYuvafem?

  Yuvafem is a tablet that you place in your vagina with an applicator.

• Take the dose recommended by your healthcare provider and talk to him or her about how well that dose is working for you
• Estrogens should be used at the lowest dose possible for your treatment only as long as needed

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

Step 1: Tear off a single applicator.

Step 2: Separate the plastic wrap and remove the applicator from the plastic wrap as shown in Figure A. If after opening the package you see that the tablet has come out of the applicator but has not fallen out of the package, carefully put it back into the applicator for insertion. Please keep your hands clean and dry while handling the tablet.

Figure A

Step 3: Hold the applicator so that the finger of one hand can press the applicator plunger as shown in Figure B.

Figure B

Step 4: Next select the best position for vaginal insertion of Yuvafem that is most comfortable for you. See suggested reclining Figure C or standing Figure D position illustrated below:

Figure C

Figure D

Step 5: Using the other hand, guide the applicator gently and comfortably through the vaginal opening (see Figures C and D above). If prior to insertion the tablet falls out of the applicator, throw the tablet and applicator away and use a new tablet-filled applicator.

Step 6: The applicator should be inserted (without forcing) as far as comfortably possible, or until half of the applicator is inside your vagina, whichever is less.

Step 7: Once the tablet-filled applicator has been inserted, gently press the plunger until the plunger is fully depressed. This will eject the tablet inside your vagina where it will dissolve slowly over several hours.

Step 8: After depressing the plunger, gently remove the applicator and dispose of it the same way you would a plastic tampon applicator. The applicator is of no further use and should be discarded properly. Insertion may be done at any time of the day. It is advisable to use the same time daily for all applications of Yuvafem. If you have any questions, please consult your healthcare provider or pharmacist.

Dosage

Yuvafem therapy consists of the following dosing regimen:

One (1) Yuvafem inserted vaginally once daily for the first two (2) weeks, then one (1) tablet inserted twice weekly (for example Tuesday and Friday) for as long as you use estradiol vaginal inserts.

What are the possible side effects of Yuvafem?

Yuvafem is only used in the vagina; however, the risks associated with oral estrogens should be taken into account.

Side effects are grouped by how serious they are and how often they happen when you are treated.

Serious but less common side effects include:

• Heart attack
• Stroke
• Blood clots
• Dementia
• Breast cancer
• Cancer of the lining of the uterus (womb)
• Cancer of the ovary
• High blood pressure
• High blood sugar
• Gallbladder disease
• Liver problems
• Enlargement of benign tumors of the uterus (“fibroids”)

Call your healthcare provider right away if you get any of the following warning signs or any other unusual symptoms that concern you:

• New breast lumps
• Unusual vaginal bleeding
• Changes in vision or speech
• Sudden new severe headaches
• Severe pains in your chest or legs with or without shortness of breath, weakness and fatigue

Less serious, but common, side effects include:

• Headache
• Breast pain
• Irregular vaginal bleeding or spotting
• Stomach or abdominal cramps, bloating
• Nausea and vomiting
• Hair loss
• Fluid retention
• Vaginal yeast infection

These are not all the possible side effects of Yuvafem. For more information, ask your healthcare provider or pharmacist for advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What can I do to lower my chances of a serious side effect with Yuvafem?

• Talk with your healthcare provider regularly about whether you should continue using Yuvafem.
• If you have a uterus, talk with your healthcare provider about whether the addition of a progestin is right for you.

• The addition of a progestin is generally recommended for a woman with a uterus to reduce the chance of getting cancer of the uterus. See your healthcare provider right away if you get vaginal bleeding while using Yuvafem.

• Have a pelvic exam, breast exam and mammogram (breast X-ray) every year unless your healthcare provider tells you something else.
• If members of your family have had breast cancer or if you have ever had breast lumps or an abnormal mammogram, you may need to have breast exams more often.
• If you have high blood pressure, high cholesterol (fat in the blood), diabetes, are overweight, or if you use tobacco, you may have higher chances for getting heart disease.

• Ask your healthcare provider for ways to lower your chances for getting heart disease.

General information about the safe and effective use of Yuvafem.

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use Yuvafem for conditions for which it was not prescribed. Do not give Yuvafem to other people, even if they have the same symptoms you have. It may harm them.

Keep Yuvafem out of the reach of children.

This leaflet provides a summary of the most important information about Yuvafem. If you would like more information, talk with your healthcare provider or pharmacist. You can ask for information about Yuvafem that is written for health professionals. You can get more information by calling the toll free number 1-855-361-3993.

What are the ingredients in Yuvafem?

Yuvafem (estradiol vaginal tablets) are small, white, film-coated tablets containing estradiol. Each tablet also contains corn starch, hypromellose, lactose monohydrate and magnesium stearate. The film coating contains hypromellose and polyethylene glycol.

Each Yuvafem tablet is contained in a disposable applicator, packaged in a blister pack. Cartons contain 8 or 18 applicators with inset tablets.

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].

Do not refrigerate.

Manufactured for:
AvKARE, Inc.
Pulaski, TN 38478

Mfg. Rev. 08-2016-00  AV 10/16

AvKARE             
NDC 42291-962-18
Yuvafem®
(estradiol vaginal inserts, USP)
10 mcg
3 Blister packs each containing 6 vaginal tablets (with disposable applicators)
18 Vaginal Tablets
(with disposable applicators)
Rx only

Contents:
18 vaginal tablets with disposable applicators.
Each tablet contains: estradiol, USP 10 mcg; corn starch, hypromellose, lactose monohydrate and magnesium stearate.
The film coating contains hypromellose and polyethylene glycol.

Dosage:
One (1) Yuvafem Tablet inserted vaginally once per day for two weeks, then one (1) tablet inserted twice weekly (for example, Tuesday and Friday).

Each tablet is contained in a disposable single-use applicator.
Please read the Patient Package Insert for complete product information.

Dispenser:
This carton contains information intended for the patient.
This information is to be provided to the patient with each package dispensed.

Keep out of reach of children.

This package is not child-resistant.

Store at 20° to 25° (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [ see USP Controlled Room Temperature].

Do not refrigerate.

Manufactured for:
AvKARE, Inc.
Pulaski, TN 38478

Mfg. Rev. 08-2016-00     AV 10/16

N3 42291 96218 7

Lot No.
Exp. Date:

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