Pharmacokinetics

Effects On Vasomotor Symptoms

A randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy of 12-week treatment with three different daily doses of Elestrin® for the treatment of vasomotor symptoms in 484 postmenopausal women between 28 and 74 years of age (mean 54 years; 83-88% Caucasian per group) who had at least 60 moderate-to-severe hot flushes per week at baseline. Subjects applied placebo, Elestrin® 0.87 g (0.52 mg estradiol), 1.7 g (1.04 mg estradiol), or 2.6 g (1.56 mg estradiol) once daily to the upper arm. Reduction in both the frequency and severity of moderate-to-severe hot flushes was statistically significant for the Elestrin® 1.7 g/day dose compared to placebo at week 4. Statistically significant reductions in both the frequency and severity of moderate-to-severe hot flushes when compared to placebo were delayed for the Elestrin® 0.87 g/day dose to week 5. Both the 0.87 g/day and 1.7 g/day doses were statistically significant compared to placebo at week 12. The reductions in frequency and severity are shown in Table 2.

TABLE 2 - Mean Change From Baselinea in the Number and Severity of Hot Flushes after Elestrin® Treatment

Evaluation		Placebo (N=137)	Elestrin® 0.87 g/day (N=136)	Elestrin® 1.7 g/day (N=142)
a Differences from baseline based on LS means derived from the ANCOVA model with factors for baseline, treatment, site, and treatment-by-baseline interaction.
b Unadjusted means and standard deviations, based on the first 14 days of the Screening Period.
c Severity score: 1=mild, 2=moderate, 3=severe.
SD: standard deviation
#P= ns, *P<0.01, **P<0.001, ***P<0.0001 for treatment comparison with placebo (Dunnett's test).
Number of Daily Hot Flushes
Baseline (Mean ± SD)b		13.5 ± 4.5	13.3± 4.6	13.1 ± 6.5
Mean Change:	Week 4	-5.1	-6.5#	-8.0***
	Week 5	-5.1	-7.5*	-8.8***
	Week 12	-5.4	-8.5***	-10.0***
Daily Hot Flush Severityc
Baseline (Mean ± SD)b		2.4 ± 0.3	2.4 ± 0.3	2.4 ± 0.3
Mean Change:	Week 4	-0.2	-0.5#	-0.7***
	Week 5	-0.2	-0.5*	-0.8***
	Week 12	-0.3	-0.8***	-1.2***

Women's Health Initiative Studies

The Women's Health Initiative (WHI) enrolled approximately 27,000 predominantly healthy postmenopausal women to assess the risks and benefits of either the use of oral conjugated estrogens (CE 0.625 mg) alone per day or in combination with medroxyprogesterone acetate (MPA 2.5 mg) per day compared to placebo in the prevention of certain chronic diseases. The primary endpoint was the incidence of coronary heart disease (CHD) (nonfatal myocardial infarction (MI), silent MI and CHD death), with invasive breast cancer as the primary adverse outcome studied. A "global index" included the earliest occurrence of CHD, invasive breast cancer, stroke, pulmonary embolism (PE), endometrial cancer (only in the estrogen plus progestin substudy), colorectal cancer, hip fracture, or death due to other cause. The study did not evaluate the effects of CE or CE/MPA on menopausal symptoms.

The estrogen alone substudy was stopped early because an increased risk of stroke was observed. Results of the estrogen alone substudy, which included 10,739 women (average age of 63 years, range 50 to 79; 75.3% White, 15.1% Black, 6.1% Hispanic, 3.6% Other), after an average follow-up of 6.8 years are presented in Table 3.

TABLE 3 - RELATIVE AND ABSOLUTE RISK SEEN IN THE ESTROGEN-ALONE SUBSTUDY OF WHIa

Event	Relative Risk CE vs. Placebo (95% nCIb)	Placebo n = 5,429	CE n = 5,310
		Absolute Risk per 10,000 Women-Years
a Adapted from JAMA. 2004;291:1701-1712.
b Nominal confidence intervals unadjusted for multiple looks and multiple comparisons.
c Results are based on centrally adjudicated data for an average follow-up of 7.1 years.
d Results are based on an average follow-up of 6.8 years.
e Not included in Global Index.
f All deaths, except from breast or colorectal cancer, definite/probable CHD, PE or cerebrovascular disease.
g A subset of the events was combined in a "global index," defined as the earliest occurrence of CHD events, invasive breast cancer, stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, or death due to other causes.
CHD eventsc	0.95 (0.79-1.16)	56	53
Non-fatal MI c	0.91 (0.73-1.14)	43	40
CHD death c	1.01 (0.71-1.43)	16	16
Invasive breast cancerc	0.80 (0.62-1.04)	34	28
Stroked	1.39 (1.10-1.77)	32	44
Deep vein thrombosisc,e	1.47 (1.06-2.06)	15	23
Pulmonary embolismc	1.37 (0.90-2.07)	10	14
Colorectal cancerd	1.08 (0.75-1.55)	16	17
Hip fractured	0.61 (0.41-0.91)	17	11
Vertebral fracturesd,e	0.62 (0.42-0.93)	17	11
Total fracturesd,e	0.70 (0.63-0.79)	195	139
Death due to other causesd,f	1.08 (0.88-1.32)	50	53
Overall mortalityd,e	1.04 (0.88-1.22)	78	81
Global indexd,g	1.01 (0.91-1.12)	190	192

For those outcomes included in the WHI "global index," that reached statistical significance, the absolute excess risk per 10,000 women-years in the group treated with CE 0.625 mg alone were 12 more strokes, while the absolute risk reduction per 10,000 women-years was 6 fewer hip fractures. The absolute excess risk of events included in the "global index" was a nonsignificant 2 events per 10,000 women-years. There was no difference between the groups in terms of all-cause mortality. (See BOXED WARNINGS, WARNINGS, and PRECAUTIONS.)

The CE/MPA substudy was also stopped early because, according to predefined stopping rule, the increased risk of breast cancer and cardiovascular events exceeded the specified benefits included in the "global index." Results of the CE/MPA substudy, which included 16,608 women (average age of 63 years, range 50 to 79; 83.9% White, 6.8% Black, 5.4% Hispanic, 3.9% Other) after an average follow-up of 5.6 years, are presented in Table 4:

TABLE 4 - Relative and Absolute Risk Seen in the CE/MPA Substudy of WHI at an Average of 5.6 Yearsa

a   Results are based on centrally adjudicated data. Mortality data was not part of the adjudicated data; however, data at 5.2 years of follow-up showed no difference between the groups in terms of all-cause mortality (RR 0.98, 95% nCI 0.82-1.18).
b   Nominal confidence intervals unadjusted for multiple looks and multiple comparisons.
c   Includes metastatic and non-metastatic breast cancer with the exception of in situ breast cancer.
Eventc	Relative Risk CE/MPA vs. Placebo (95% nCIb)	Placebo n = 8,102	CE/MPA n = 8,506
		Absolute Risk per 10,000 Women-Years
CHD events	1.24 (1.00-1.54)	33	39
Non-fatal MI	1.28 (1.00-1.63)	25	31
CHD death	1.10 (0.70-1.75)	8	8
Invasive breast cancerc	1.24 (1.01-1.54)	33	41
All Stroke	1.31 (1.02-1.68)	24	31
Ischemic Stroke	1.44 (1.09-1.90)	18	26
Deep vein thrombosis	1.95 (1.43-2.67)	13	26
Pulmonary embolism	2.13 (1.45-3.11)	8	18
Invasive Colorectal cancer	0.56 (0.38-0.81)	16	9
Endometrial cancer	0.81 (0.48-1.36)	7	6
Cervical cancer	1.44 (0.47-4.42)	1	2
Hip fracture	0.67 (0.47-0.96)	16	11
Vertebral fractures	0.65 (0.46-0.92)	17	11
Lower arm/wrist fractures	0.71 (0.59-0.85)	62	44
Total fractures	0.76 (0.69-0.83)	199	152

For those outcomes included in the WHI "global index" that reached statistical significance after 5.6 years of follow-up, the absolute excess risks per 10,000 women-years in the group treated with CE/MPA were 6 more CHD events, 7 more strokes, 10 more PEs, and 8 more invasive breast cancers, while the absolute risk reductions per 10,000 women-years were 7 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the "global index" was 19 per 10,000 women-years (RR 1.15, 95% nCI 1.03-1.28). (See BOXED WARNINGS, WARNINGS, and PRECAUTIONS.)

Women's Health Initiative Memory Study

The estrogen-alone Women's Health Initiative Memory Study (WHIMS), a substudy of the WHI, enrolled 2,947 predominantly healthy postmenopausal women 65 years of age and older (45% were aged 65 to 69 years, 36% were 70 to 74 years, and 19% were 75 years of age and older) to evaluate the effects of conjugated estrogens (CE 0.625 mg) on the incidence of probable dementia (primary outcome) compared with placebo.

After an average follow-up of 5.2 years, 28 women in the CE-alone group (37 per 10,000 women-years) and 19 in the placebo group (25 per 10,000 women-years) were diagnosed with probable dementia. The relative risk of probable dementia in the CE-alone group was 1.49 (95% confidence interval [CI], 0.83-2.66) compared to placebo. It is unknown whether these findings apply to younger postmenopausal women. (See BOXED WARNINGS, WARNINGS, Dementia, and PRECAUTIONS, Geriatric Use.)

The CE/MPA WHIMS substudy enrolled 4,532 predominantly healthy postmenopausal women 65 years of age and older (47% were age 65 to 69 years, 35% were 70 to 74 years, and 18% were 75 years of age and older) to evaluate the effects of conjugated estrogens (CE 0.625 mg) plus medroxyprogesterone acetate (MPA 2.5 mg) on the incidence of probable dementia (primary outcome) compared with placebo.

After an average follow-up of 4 years, 40 women in the CE/MPA group (45 per 10,000 women-years) and 21 in the placebo group (22 per 10,000 women-years) were diagnosed with probable dementia. The relative risk of probable dementia in the hormone therapy group was 2.05 (95% CI, 1.21-3.48) compared to placebo.

When data from the two populations were pooled as planned in the WHIMS protocol, the reported overall relative risk for probable dementia was 1.76 (95% CI, 1.19-2.60). Differences between groups became apparent in the first year of treatment. It is unknown whether these findings apply to younger postmenopausal women. (See BOXED WARNING and WARNINGS, Dementia, and PRECAUTIONS, Geriatric Use.)

1. Cardiovascular disorders

Estrogen-alone therapy has been associated with an increased risk of stroke and deep vein thrombosis (DVT).

Estrogen plus progestin therapy has been associated with an increased risk of myocardial infarction as well as stroke, venous thrombosis and pulmonary embolism. Should any of these events occur or be suspected, estrogens should be discontinued immediately.

Risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or VTE (e.g., personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately.

2. Malignant neoplasms

3. Dementia

In the estrogen-alone WHIMS, a substudy of WHI, a population of 2,947 hysterectomized women aged 65 to 79 years was randomized to CE (0.625 mg daily) or placebo. In the estrogen plus progestin WHIMS, a population of 4,532 postmenopausal women aged 65 to 79 years was randomized to CE/MPA (0.625 mg/2.5 mg daily) or placebo.

In the estrogen-alone substudy, after an average follow-up of 5.2 years, 28 women in the estrogen-alone group and 19 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for estrogen alone versus placebo was 1.49 (95% CI, 0.83-2.66). The absolute risk of probable dementia for estrogen-alone versus placebo was 37 versus 25 cases per 10,000 women-years. It is unknown whether these findings apply to younger postmenopausal women. (See CLINICAL STUDIES and PRECAUTIONS, Geriatric Use.)

In the estrogen plus progestin substudy, after an average follow-up of 4 years, 40 women in the estrogen plus progestin group and 21 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for estrogen plus progestin versus placebo was 2.05 (95% CI, 1.21-3.48). The absolute risk of probable dementia for CE/MPA versus placebo was 45 versus 22 cases per 10,000 women-years. (See CLINICAL STUDIES and PRECAUTIONS, Geriatric Use.)

When data from the two populations were pooled as planned in the WHIMS protocol, the reported overall relative risk for probable dementia was 1.76 (95% CI, 1.19-2.60). Since both substudies were conducted in women 65 to 79 years, it is unknown whether these findings apply to younger postmenopausal women. (See BOXED WARNINGS and PRECAUTIONS, Geriatric Use.)

4. Gallbladder disease

A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.

5. Hypercalcemia

Estrogen administration may lead to severe hypercalcemia in patients with breast cancer and bone metastases. If hypercalcemia occurs, use of the drug should be stopped and appropriate measures taken to reduce the serum calcium level.

6. Visual abnormalities

Retinal vascular thrombosis has been reported in patients receiving estrogens. Discontinue medication pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, estrogens should be permanently discontinued.

A. General

B. Information for Patients

Physicians are advised to discuss the Patient Information leaflet with patients for whom they prescribe Elestrin®.

C. Laboratory Tests

Estrogen administration should be initiated at the lowest dose approved for the treatment of postmenopausal moderate to severe vasomotor symptoms and then guided by clinical response rather than by serum hormone levels (e.g., estradiol, FSH).

D. Drug/Laboratory Test Interactions

1.

Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of anti-factor Xa and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity.

2.

Increased thyroid binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels as measured by protein-bound iodine (PBI), T4 levels (by column or by radioimmunoassay) or T3 levels by radioimmunoassay. T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Patients on thyroid replacement therapy may require higher doses of thyroid hormone.

3.

Other binding proteins may be elevated in serum (i.e., corticosteroid binding globulin [CBG], SHBG), leading to increased total circulating corticosteroids and sex steroids, respectively. Free hormone concentrations may be decreased. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).

4.

Increased plasma HDL and HDL2 cholesterol subfraction concentrations, reduced LDL cholesterol concentration, increased triglycerides levels.

5.

Impaired glucose tolerance.

6.

Reduced response to metyrapone test.

E. Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term continuous administration of estrogen, with or without progestin, in women with or without a uterus, has shown an increased risk of endometrial cancer, breast cancer, and ovarian cancer. (See BOXED WARNINGS, WARNINGS and PRECAUTIONS.)

Long-term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver.

F. Pregnancy

Estrogen products, including Elestrin, should not be used during pregnancy. (See CONTRAINDICATIONS.)

G. Nursing Mothers

Estrogen administration to nursing mothers has been shown to decrease the quantity and quality of the milk. Detectable amounts of estrogens have been identified in the milk of mothers receiving this drug. Caution should be exercised when estrogen products, including Elestrin, are administered to a nursing woman.

H. Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

I. Geriatric Use

Clinical studies of Elestrin® did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Of the total number of subjects in the estrogen-alone substudy of the WHI study, 46% (n = 4,943) were 65 years and older, while 7.1% (n = 767) were 75 years and older. There was a higher relative risk (CE versus placebo) of stroke in women less than 75 years of age compared to women 75 years and older.

In the estrogen-alone substudy of the WHIMS, a population of 2,947 hysterectomized women, aged 65 to 79 years, was randomized to estrogen alone (CE 0.625 mg) or placebo. After an average follow-up of 5.2 years, the relative risk (CE versus placebo) of probable dementia was 1.49 (95% CI, 0.83-2.66). The absolute risk of developing probable dementia with estrogen alone was 37 versus 25 cases per 10,000 women-years.

Of the total number of subjects in the CE/MPA substudy of the WHI, 44% (n = 7,320) were 65 years and older, while 6.6% (n = 1,095) were 75 years and older. There was a higher relative risk (CE/MPA versus placebo) of non-fatal stroke and invasive breast cancer in women 75 and older compared to women less than 75 years of age. In women greater than 75, the increased risk of non-fatal stroke and invasive breast cancer observed in the estrogen plus progestin combination group compared to the placebo group was 75 versus 24 per 10,000 women-years and 52 versus 12 per 10,000 women years, respectively.

In the estrogen plus progestin substudy of WHIMS, a population of 4,532 postmenopausal women, aged 65 to 70 years, was randomized to conjugated estrogens (CE 0.625 mg) plus medroxyprogesterone acetate (MPA 2.5 mg) or placebo. In the estrogen plus progestin group, after an average follow-up of 4 years, the relative risk (CE/MPA versus placebo) of probable dementia was 2.05 (95% CI, 1.21-3.48). The absolute risk of developing probable dementia with CE/MPA was 45 versus 22 per 10,000 women-years.

When data from the two populations were pooled as planned in the WHIMS protocol, the reported overall relative risk for probable dementia was 1.76 (95% CI, 1.19-2.60). Since both substudies were conducted in women aged 65 to 79 years, it is unknown whether these findings apply to younger postmenopausal women. (See BOXED WARNINGS and WARNINGS, Dementia.)

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

What is Elestrin?

Elestrin® is a medicine in a colorless gel that contains an estrogen hormone (estradiol) which is absorbed through the skin into the bloodstream.

What is Elestrin® used for?

Elestrin® 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 to 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 the estrogen levels begin dropping, some women develop very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden strong feelings of heat and sweating ("hot flashes" or "hot flushes"). In some women, the symptoms are mild, and they will not need estrogens. In other women, symptoms can be more severe. You and your healthcare provider should talk regularly about whether you still need treatment with Elestrin®.

Who should not use Elestrin®?

Do not start using Elestrin® 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 had cancer, talk with your healthcare provider about whether you should use Elestrin®.

•

Had a stroke or heart attack in the past year

•

Currently have or have had blood clots

•

Currently have or have had liver problems

•

Are allergic to Elestrin® or any of its ingredients
See below for a list of ingredients in Elestrin®

•

Think you may be pregnant

Tell your healthcare provider:

•

If you are breastfeeding
The hormone in Elestrin® can pass into your milk.

•

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), migraine, endometriosis, lupus, or 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 Elestrin® works. Elestrin® 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 Elestrin®.

What are the ingredients in Elestrin®?

Active ingredient: estradiol.

Inactive ingredients: purified water, ethanol, propylene glycol, diethylene glycol monoethyl ether, carbomer 940, triethanolamine, and edetate disodium.

How should I use Elestrin®?

1.

Start at the lowest dose and talk to your healthcare provider about how well that dose is working for you.

2.

Elestrin® should be used at the lowest dose possible for your treatment and 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 taking and whether you still need treatment with Elestrin®.

Elestrin® comes in a metered-dose pump container. One actuation of Elestrin® is released each time the pump is depressed (pressed down).

Use Elestrin® exactly how your healthcare provider tells you.

The Elestrin® pump container holds enough of the medicine to let you prime the pump before you use it the first time. To prime, actuate the pump until gel is dispensed. Discard the first actuation that produces gel as this will not contain a full actuation. The pump is now primed and ready to use. Use the pump a total of 30 times (30 actuations) as prescribed by your healthcare provider. After you have initially primed the pump and have used a total of 30 actuations of Elestrin®, you will need to throw the pump container away and use a new one. The correct amount of medicine in each actuation cannot be assured after 30 actuations have been used, even though the pump container is not completely empty.

Important things to remember when using Elestrin®

     Wash your hands with soap and water after applying the gel to reduce the chance that the
     medicine will be spread from your hands to other people.
     Allow the gel to dry for five minutes or more before dressing. Try to keep the area dry for as long as possible.
     Do not allow others to come in contact with the area of skin where you applied the gel for at least two hours after you apply Elestrin®.
     Always place the cap over the top of the pump after each use.
     Never apply Elestrin® to the breast. Never apply Elestrin® in or around the vagina.
     Do not allow others to apply the gel for you.
     Do not apply sunscreen to the area where the gel was applied for at least 25 minutes.
     Do not apply sunscreen to the area where the gel was applied for 7 or more consecutive days.
     Avoid fire, flame or smoking until the gel has dried. Elestrin® contains alcohol. Alcohol based gels are flammable.

It is important that you read and follow the detailed "Patient Instructions for Use" at the end of this leaflet on how to use the Elestrin® pump and apply the dose.

What should I do if someone else is exposed to Elestrin?

If someone else is exposed to Elestrin® by direct contact with the gel, that person should wash the area of contact with soap and water as soon as possible. The longer the gel is in contact with the skin before washing, the greater is the chance that the other person will absorb some of the estrogen hormone. This is especially important for men and children.

What should I do if I get Elestrin® in my eyes?

If you get Elestrin® in your eyes, rinse your eyes right away with warm clean water to flush out any Elestrin®. Seek medical attention if needed.

What should I do if I miss a dose?

If you miss a dose, do not double the dose on the next day to catch up. If your next dose is less than 12 hours away, it is best just to wait and apply your normal dose the next day. If it is more than 12 hours until the next dose, apply the dose you missed and resume your normal dosing the next day.

What are the possible side effects of estrogens?

Less common but serious side effects include:

•

Breast cancer

•

Cancer of the uterus

•

Stroke

•

Heart attack

•

Blood clots

•

Dementia

•

Gallbladder disease

•

Ovarian cancer

These are some of the warning signs of serious side effects:

•

Breast lumps

•

Unusual vaginal bleeding

•

Dizziness and faintness

•

Changes in speech

•

Severe headaches

•

Chest pain

•

Shortness of breath

•

Pains in your legs

•

Changes in vision

•

Vomiting

Call your healthcare provider right away if you get any of these warning signs, or any other unusual symptom that concerns you.

Common side effects include:

•

Headache

•

Breast pain

•

Irregular vaginal bleeding or spotting

•

Stomach/abdominal cramps, bloating

•

Nausea and vomiting

•

Hair loss

Other side effects include:

•

High blood pressure

•

Liver problems

•

High blood sugar

•

Fluid retention

•

Enlargement of benign tumors of the uterus ("fibroids")

•

Vaginal yeast infection

These are not all the possible side effects of Elestrin®. For more information, ask your healthcare provider or pharmacist.

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

Talk with your healthcare provider regularly about whether you should continue using Elestrin®. If you have a uterus, talk to your healthcare provider about whether the addition of a progestin is right for you. In general, the addition of a progestin is recommended for women 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 Elestrin®. Have a 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 a higher chance for getting heart disease. Ask your healthcare provider for ways to lower your chances of getting heart disease.

Have an annual gynecologic exam

General information about safe and effective use of Elestrin®

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

KEEP OUT OF REACH OF CHILDREN; THE PUMP CONTAINER IS NOT CHILD-RESISTANT.

This leaflet provides a summary of the most important information about Elestrin®. If you would like more information, talk with your healthcare provider or pharmacist. You can ask for information about Elestrin® that is written for health professionals. You can get more information by calling 1-800-890-3098 (toll free).

Patient Instructions for Use.

1. Remove the cap.

2. Prime the pump before using the pump for the first time.

•

To prime, actuate the pump until gel is dispensed. Discard the first actuation that produces gel as this will not contain a full actuation. The pump is now primed and ready to use.

•

Throw away the unused gel by placing it in the trash to avoid another person or pet from accidental contact with the gel, or eating or drinking it.

•

After priming, the pump is ready to use.
One complete actuation will dispense the same amount of Elestrin® each time.
After each daily dose, replace the cap before you put it away.

3. Apply Elestrin®.

•

Dry skin completely before applying Elestrin®.
You should apply your daily actuation(s) of gel to clean, dry, unbroken skin. If you take a bath or shower or use a sauna, apply Elestrin® after your bath, shower, or sauna. If you go swimming, try to leave as much time as possible, at least 2 hours, between applying your Elestrin® actuation(s) and going into the water.

•

Apply Elestrin® at the same time and the same locations each day.

Figure 1
To apply the dose, hold the pump with the tip facing the application area of the arm. For each actuation needed, press the pump firmly and fully with a continuous motion without hesitation.

Figure 2
Gently spread the gel using only 2 fingers. Spread and gently rub in the gel over the entire area of your upper arm and shoulder area, as illustrated.

4. Wash your hands with soap and water.

Elestrin® should not be used after the date printed on the container (expiration date).

Elestrin® is a trademark of Azur Pharma International II Limited

Distributed by:

1818 Market Street, Suite 2350, Philadelphia, PA 19103 • www.azurpharma.com • www.elestrin.com

Manufactured by:
DPT Laboratories, Ltd.
San Antonio, TX 78215

U.S. Pat. No. 7,198,801 and U.S. Pat. No. 7,470,433

©2010 Azur Pharma International II Limited

129450-6010

ELESp-10-01

Rev. 07/10