Endometrin

IMPORTANT: For Vaginal Use Only.

Read the patient information that comes with Endometrin before you start to use it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or treatment. Your doctor may do a physical exam before prescribing Endometrin.

What is Endometrin?

Endometrin is a vaginal insert that contains the hormone progesterone. Endometrin is for women who need extra progesterone while undergoing treatment in an Assisted Reproductive Technology (ART) program.

Progesterone is one of the hormones essential for helping you to become and to stay pregnant. If you are undergoing ART treatment, your doctor may prescribe Endometrin to provide the progesterone your body needs.

Who should not use Endometrin?

Do not use Endometrin if you:

• Are allergic to anything in Endometrin. See the end of this leaflet for a complete list of ingredients.
• Have unusual vaginal bleeding that has not been evaluated by a doctor.
• Currently have or have had liver problems.
• Have or have had blood clots in the legs, lungs, eyes, or elsewhere in your body.

Endometrin may not be right for you. Before starting Endometrin, tell your doctor about all your health problems.

Tell your doctor about all the medicines you take including prescription and nonprescription medicines, vaginal products, vitamins, herbal supplements.

Some medicines may affect Endometrin.

Know what medicines you take. Keep a list of your medicines to show to the doctor and pharmacist.

How should I use Endometrin?

• Use Endometrin exactly as prescribed. The usual dose of Endometrin is one insert placed in your vagina 2 to 3 times a day for up to a total of 10 weeks, unless your healthcare provider advises otherwise.
• Place an Endometrin insert in your vagina with the disposable applicator provided.

Follow the steps below:

1. Unwrap the applicator.
2. Put one insert in the space provided at the end of the applicator. The insert should fit snugly and not fall out.
3. Place applicator with the insert into the vagina while you are standing, sitting, or when lying on your back with your knees bent. Gently place the thin end of the applicator well into the vagina.
4. Push the plunger to release the insert.
5. Remove the applicator and throw it away in the trash.

Other information for using Endometrin

• If you forget a dose of Endometrin, take the dose as soon as you remember, but do not use more than your daily dose.
• Call your doctor if you use too much Endometrin.
• Do not use any other vaginal products when you are using Endometrin.

What are the possible side effects of Endometrin?

Common side effects seen with ART and Endometrin included pelvic pain after surgery, abdominal pain, nausea, and swollen ovaries (ovarian hyperstimulation syndrome).

Other reported side effects included abdominal bloating, headache, urinary infections, uterine cramping, constipation, vomiting, tiredness, and vaginal bleeding.

Vaginal products with progesterone may also cause vaginal irritation, burning, and discharge.

Serious Risks of Progesterone

Progesterone can increase your chance of getting blood clots. Blood clots can be serious and lead to death.

Serious blood clots include those in the:

• legs (thrombophlebitis)
• lungs (pulmonary embolus)
• eyes (blindness)
• heart (heart attack)
• brain (stroke)

Call your doctor or get medical help right away if you have:

• persistent pain in the lower leg (calf)
• sudden shortness of breath
• coughing up blood
• sudden blindness, partial or complete
• severe chest pain
• sudden, severe headache, vomiting, dizziness, or fainting
• weakness in an arm or leg, or trouble speaking
• yellowing of the skin and/or white of the eyes indicating possible liver problem

Other risks of progesterone use include:

• headache
• breast tenderness
• bloating or fluid retention
• mood swings and depression
• irritability
• drowsiness

Call your doctor immediately if you have abnormal vaginal bleeding.

These are not all the side effects with Endometrin. Ask your doctor or pharmacist for more information.

How should I store Endometrin?

• Store Endometrin at room temperature, 20 - 25°C (68 - 77°F); excursions permitted between 15 - 30°C (59 - 86°F)
• Do not use Endometrin after the expiration date that is printed on the carton.
• Keep Endometrin and all medicines out of the reach of children.

General information about Endometrin

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use Endometrin for a condition for which it was not prescribed. Do not give Endometrin to other women, even if they have the same condition as you do. It may harm them.

This leaflet summarizes the most important information about Endometrin. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Endometrin that was written for healthcare professionals. For more information call Ferring Pharmaceuticals at 1-(888)-FERRING or 1- (888)-337-7464.

What are the ingredients in Endometrin?

Active Ingredient: progesterone

Inactive Ingredients: lactose monohydrate, polyvinylpyrrolidone, adipic acid, sodium bicarbonate, sodium lauryl sulfate, magnesium stearate, pregelatinized starch, and colloidal silicon dioxide

Endometrin is a prescription medication used to promote embryo implantation and pregnancy in conjunction with fertility treatments in women. Endometrin belongs to a group of drugs called progestins. These work to promote embryo implantation and pregnancy in women by preparing the uterus for embryo implantation and maintaining a suitable uterine environment once pregnancy is achieved.

This medication comes in vaginal insert form and is typically inserted into the vagina 2 to 3 times daily for up to 10 weeks of treatment.

Common side effects of Endometrin include abdominal pain, nausea, and ovarian hyperstimulation syndrome.

Endometrin can can also cause drowsiness. Do not drive or operate heavy machinery until you know how Endometrin affects you.

Endometrin is part of the drug class:

• Pregnen 4 derivatives

Before taking Endometrin, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• Are allergic to Endometrin or to any of its ingredients
• Have liver disease
• Have breast cancer
• Have active arterial or venous thromboembolism or severe thrombophlebitis
• Have a known missed abortion or ectopic pregnancy
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Call your doctor if you miss more than one dose.

Do not use another vaginal medicine within 6 hours before or after using progesterone vaginal gel. Use only vaginal products that your doctor has recommended.

Avoid using vaginal yeast treatments unless your doctor tells you to.

This medicine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Chest pain or pressure.
• Shortness of breath.
• Coughing up blood.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Swelling, warmth, numbness, change of color, or pain in a leg or arm.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• Trouble walking.
• Very bad headache.
• Very upset stomach or throwing up.
• Very bad dizziness or passing out.
• Bulging eyes.
• Change in eyesight.
• Loss of eyesight.
• A lump in the breast, breast soreness, or nipple discharge.
• Breast pain.
• Vaginal itching or discharge.
• Vaginal bleeding that is not normal.
• Pain when passing urine.
• Passing urine more often.
• Low mood (depression).
• Mood changes.
• Memory problems or loss.
• Seizures.
• Flushing.
• A fast heartbeat.
• A heartbeat that does not feel normal.
• Pelvic pain.

Endometrin is contraindicated in individuals with any of the following conditions:

• Previous allergic reactions to progesterone or any of the ingredients of Endometrin [see Description (11)]
• Undiagnosed vaginal bleeding
• Known missed abortion or ectopic pregnancy
• Liver disease
• Known or suspected malignancy of the breast or genital organs
• Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events

Carcinogenesis, Mutagenesis, Impairment of Fertility

Nonclinical toxicity studies to determine the potential of Endometrin to cause carcinogenicity or mutagenicity have not been performed. The effect of Endometrin on fertility has not been evaluated in animals.

Luteal Supplementation During Assisted Reproductive Treatment Study

A randomized, open-label, active-controlled study evaluated the efficacy of 10 weeks of treatment with two different daily dosing regimens of Endometrin (100 mg twice daily and 100 mg three times daily) for support of implantation and early pregnancy in infertile women participating in an Assisted Reproductive Technology treatment program. Efficacy was assessed on the endpoint of ongoing pregnancies, defined as the presence of at least one fetal heartbeat seen on ultrasound at 6 weeks post-embryo transfer. The study randomized to Endometrin 808 infertile women (74.9% White; 10.3% Hispanic, 5.4% Black, 5% Asian, and 4.6% Other) between 19 and 42 years of age (mean age 33) who had a body mass index <34 kg/m2 at screening.

The ongoing pregnancy rates for subjects treated with both dosing regimens of Endometrin were non-inferior (lower bounds of the 95% confidence interval of the difference between Endometrin and the active comparator excluded a difference greater than 10%) to the ongoing pregnancy rate for subjects treated with the active comparator. The results of this study are shown in Table 3.

Subjects participating in the study were stratified at randomization by age and ovarian reserve (as measured by serum FSH levels). The ongoing pregnancy rates for these subgroups are shown in Table 4.

In subjects under the age of 35 or with serum FSH levels less than 10 IU/L, results from both dosing regimens were non-inferior to the results from the comparator with respect to ongoing pregnancy rates. In women age 35 and older and in women with serum FSH levels between 10 and 15 IU/L, the results with respect to ongoing pregnancy rates for both dosing regimens of Endometrin did not reach the criteria for non-inferiority.

Subjects who became pregnant received study medication for a total of 10 weeks. Patients over 34 kg/m2 were not studied. The efficacy of Endometrin in this patient group is unknown.

Get emergency medical help if you have signs of an allergic reaction to Endometrin: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• unusual vaginal bleeding;

• pain or burning when you urinate;

• symptoms of depression (sleep problems, weakness, mood changes);

• a breast lump;

• sudden vision problems, severe headache or pain behind your eyes;

• heart attack symptoms - chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;

• liver problems - nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• signs of a stroke - sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with speech or balance;

• signs of a blood clot in the lung - chest pain, sudden cough, wheezing, rapid breathing, coughing up blood; or

• signs of a blood clot in your leg - pain, swelling, warmth, or redness in one or both legs.

Common Endometrin side effects may include:

• dizziness, confusion, drowsiness, tiredness;

• headache, mood changes, feeling nervous or irritable;

• stomach pain, nausea, diarrhea, constipation;

• bloating, swelling in your hands or feet;

• breast pain, swelling, or tenderness;

• cramps, pelvic pain; or

• vaginal itching, burning, or discharge.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Other drugs may interact with progesterone vaginal, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.