Read this Patient Information before you start using DOTTI and each time you get a refill. 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 is the most important information I should know about****DOTTI (an estrogen hormone)?

• Using estrogen-alone increases your chance of getting cancer of the uterus (womb).
• Report any unusual vaginal bleeding right away while you are using DOTTI. 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.
• Do not use estrogen-alone to prevent heart disease, heart attacks, strokes, or dementia (decline in brain function).
• Using estrogen-alone may increase your chances of getting strokes or blood clots.
• Using estrogen-alone may increase your chance of getting dementia, based on a study of women 65 years of age and older.
• Do not use estrogens with progestogens to prevent heart disease, heart attacks, strokes, or dementia.
• Using estrogens with progestogens may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots.
• Using estrogens with progestogens may increase your chance of getting dementia, based on a study of women 65 years of age and older.
• Only one estrogen-alone product and dose have been shown to increase your chances of getting strokes, blood clots, and dementia. Only one estrogen with progestogen product and dose have been shown to increase your chances of getting heart attacks, strokes, breast cancer, blood clots, and dementia.

Because other products and doses have not been studied in the same way, it is not known how the use of DOTTI will affect your chances of these conditions. You and your healthcare provider should talk regularly about whether you still need treatment with DOTTI.

What is** DOTTI?**

****DOTTI is a prescription medicine patch (transdermal system) that contains the estrogen hormone estradiol. When applied to the skin, estradiol is absorbed through the skin into the bloodstream.

What is****DOTTI used for?

****DOTTI is used after menopause to:

*Reduce moderate to severe hot flashes

Estrogens are hormones made by a woman’s ovaries. The ovaries normally stop making estrogens when a woman is between 45 and 55 years old. This drop in body estrogen levels causes the “change of life” or menopause (the end of monthly menstrual periods). Sometimes, both ovaries are removed during an operation before natural menopause takes place. The sudden drop in estrogen levels causes “surgical menopause.”

When estrogen levels begin dropping, some women develop very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest or sudden intense feelings of heat and sweating (“hot flashes” or “hot flushes”). In some women the symptoms are mild, and they will not need to use estrogens. In other women, symptoms can be more severe.

*Treat moderate to severe menopausal changes in and around the vagina

You and your healthcare provider should talk regularly about whether you still need treatment with DOTTI to control these problems. If you use DOTTI only to treat your menopausal changes in and around your vagina, talk with your healthcare provider about whether a topical vaginal product would be better for you.

*Treat certain conditions in women before menopause if their ovaries do not produce enough estrogens naturally *Help reduce your chances of getting osteoporosis (thin weak bones)

Osteoporosis from menopause is a thinning of the bones that makes them weaker and easier to break. If you use DOTTI to prevent osteoporosis due to menopause, talk with your healthcare provider about whether a different treatment or medicine without estrogens might be better for you.

You and your healthcare provider should talk regularly about whether you should continue treatment with DOTTI.

Who should not use** DOTTI? Do not start using****DOTTI if you:**

*have 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.

*have been diagnosed with a bleeding disorder *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 (womb). If you have or have had cancer, talk with your healthcare provider about whether you should use DOTTI.

*had a stroke or heart attack *currently have or have had blood clots *currently have or have had liver problems *are allergic to DOTTI or any of the ingredients in it

See the list of ingredients in DOTTI at the end of this leaflet.

Before you use** DOTTI, tell your healthcare provider about all of your medical conditions, including 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.

*have any other medical conditions that may become worse while you are using DOTTI

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, angioedema (swelling of face and tongue); problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood.

*are going to have surgery or will be on bed rest

Your healthcare provider will let you know if you need to stop using DOTTI.

*are pregnant or think you may be pregnant.

DOTTI is not for pregnant women.

*are breastfeeding

The hormone in DOTTI can pass into your breast milk.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines may affect how DOTTI works. DOTTI may also affect how your other medicines work. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get new medicine.

How should I use** DOTTI?**

******For detailed instructions, see the step-by-step instructions for using **DOTTI at the end of this Patient Information.

• Use DOTTI exactly as your healthcare provider tells you to use it.
• DOTTI is for skin use only.
• Change your DOTTI patch 2 times a week or every 3 to 4 days.
• Apply your DOTTI patch to a clean, dry area on your lower abdomen. This area must be clean, dry, and free of powder, oil or lotion for your patch to stick to your skin.
• Apply your DOTTI patch to a different area of your abdomen each time. Do not use the same application site 2 times in the same week.
• Do not apply DOTTI to your breasts.
• If you forget to apply a new DOTTI patch, apply a new patch as soon as possible.
• You and your healthcare provider should talk regularly (every 3 to 6 months) about your dose and whether you still need treatment with DOTTI.

How to change****DOTTI

• When changing the patch, peel off the used patch slowly from the skin.
• After removal of DOTTI if any adhesive residue remains on your skin, allow the area to dry for 15 minutes. Then, gently rub the area with oil or lotion to remove the adhesive from your skin.
• Apply the new patch to a different area of your lower abdomen**.** This area must be clean, dry, cool and free of powder, oil, or lotion.

What are the possible side effects of** DOTTI?**

****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

• high blood pressure

• stroke

• high levels of fat (triglyceride) in your blood

• blood clots

• liver problems

• breast cancer

• changes in your thyroid hormone levels

• cancer of the lining of the uterus (womb)

• fluid retention

• cancer of the ovary

• cancer changes of endometriosis

• dementia

• enlargement of benign tumors of the uterus (“fibroids”)

• high or low blood calcium

• worsening of swelling of face and tongue (angioedema) in women with a history of angioedema

• gallbladder disease

• visual abnormalities

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
• swelling of face and tongue with or without red, itchy bumps

Common side effects of DOTTI include:

• headache

• nausea and vomiting

• breast pain

• hair loss

• irregular vaginal bleeding or spotting

• fluid retention

• painful periods

• vaginal yeast infection

• stomach or abdominal cramps, bloating

• redness and/or irritation at patch placement site

These are not all the possible side effects of DOTTI. For more information, ask your healthcare provider or pharmacist. Tell your healthcare provider if you have any side effects that bother you or do not go away.

You may report side effects to FDA at 1-800-FDA-1088. You may report side effects to Amneal Pharmaceuticals (1-877-835-5472).

What can I do to lower my chances of getting a serious side effect with** DOTTI?**

• Talk with your healthcare provider regularly about whether you should continue using DOTTI.
• If you have a uterus, talk to your healthcare provider about whether the addition of a progestogen is right for you. In general, the addition of a progestogen is recommended for a woman with a uterus to reduce the chance of getting cancer of the uterus (womb).
• See your healthcare provider right away if you get vaginal bleeding while using DOTTI.
• 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.

How should I store and throw away used****DOTTI patches?

• Store DOTTI at room temperature 68° to 77°F (20° to 25°C)
• Do not store DOTTI patches outside of their pouches. Apply immediately upon removal from the protective pouch.
• Used patches still contain estrogen. To throw away the patch, fold the sticky side of the patch together, place it in a sturdy child-proof container, and place this container in the trash. Used patches should not be flushed in the toilet.

Keep****DOTTI and all medicines out of the reach of children.

****General information about safe and effective use ofDOTTI

****Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use DOTTI for conditions for which it was not prescribed. Do not give DOTTI to other people, even if they have the same symptoms you have. It may harm them.

You can ask your healthcare provider or pharmacist for information about DOTTI that is written for health professionals. For more information, call the toll- free number Amneal Pharmaceuticals (1-877-835-5472).

What are the ingredients in** DOTTI?**

****Active ingredient: estradiol, USP

Inactive ingredients: a polyester and ethylene vinyl acetate copolymer film, acrylic and silicone adhesives, oleyl alcohol, NF, povidone, USP, dipropylene glycol and a polyester release liner.

Distributed by:

Amneal Pharmaceuticals LLC

Bridgewater, NJ 08807

Rev. 03-2022-02