Crinone 8%
(progesterone gel)

For Vaginal Use Only

FOR PROGESTERONE SUPPLEMENTATION OR REPLACEMENT AS PART OF AN ASSISTED REPRODUCTIVE TECHNOLOGY ("ART") TREATMENT FOR INFERTILE WOMEN WITH PROGESTERONE DEFICIENCY

Please read this information carefully before you start to use Crinone and each time your prescription is renewed, in case anything has changed. This leaflet does not take the place of discussions with your doctor. If you still have any questions, ask your doctor or health-care provider.

What Crinone is

Crinone is a specially formulated gel that you insert in your vagina. It contains the natural female hormone called progesterone. Crinone 8% is used as part of a program for women who are undergoing fertility treatment.

Understanding the role of Crinone in your infertility treatment

Progesterone is one of the hormones essential for maintaining a pregnancy. If you are undergoing ART treatment and your doctor has determined your body does not produce enough progesterone on its own, Crinone may be prescribed to provide the progesterone you need.

The progesterone in Crinone will help prepare the lining of your uterus so that it is ready to receive and nourish a fertilized egg. If pregnancy occurs, Crinone may be supplemented for 10-12 weeks until production of progesterone by the placenta is adequate.

When you should not use Crinone

• If you are allergic to progesterone, progesterone-like drugs, or any of the inactive ingredients in the gel (ask a pharmacist if you are not sure about the inactive ingredients in Crinone).
• If you have unusual vaginal bleeding which has not been evaluated by a doctor.
• If you have a liver disease.
• If you have known or suspected cancer of the breast or genital organs.
• If you have a miscarriage and your physician suspects some tissue is still in the uterus.
• If you have or have had blood clots in the legs, lungs, eyes, or elsewhere.

Risks of Crinone

• Risk to the fetus. Birth defects have been reported in the offspring of women who were using Crinone during early pregnancy. These included an abdominal wall defect and a cleft palate. A causal association has been neither confirmed nor refuted. You should check with your doctor about the risks to your unborn child of any medication used during pregnancy.
• Blood clots and related health problems. Blood clots have been reported with the use of estrogens and progestational drugs (alone or in combination). If blood clots do form in your bloodstream, they can cut off the blood supply to vital organs, causing serious problems. These problems may include a stroke (by cutting off blood to part of the brain), a heart attack (by cutting off blood to part of the heart), a pulmonary embolus (by cutting off blood to part of the lungs), or other problems. Any of these conditions may cause death or serious long-term disability. Call your doctor immediately if you suspect you have any of these conditions. He or she may advise you to stop using this drug.

PRECAUTIONS

Be alert for unusual signs and symptoms. If any of these warning signals (or any other unusual symptoms) happen while you are using Crinone, call your doctor immediately:

• Abnormal bleeding from the vagina.
• Pains in the calves or chest, a sudden shortness of breath or coughing blood indicating possible clots in the legs, heart, or lungs.
• Severe headache or vomiting, dizziness, faintness, or changes in vision or speech, weakness or numbness of an arm or leg indicating possible clots in the brain or eye.
• Breast lumps, which could be associated with fibrocystic disorders, fibroadenoma, or breast cancer. (Ask your doctor or health-care provider to show you how to examine your breasts monthly.)
• Yellowing of the skin and/or white of the eyes indicating possible liver problems.

You should also notify your doctor if you experience depression, worsening of your diabetic condition, or fluid retention.

Possible side effects of Crinone

In addition to the risks listed above, the following side effects have been reported with Crinone used either for progesterone supplementation or for replacement as part of an ART treatment for infertile women with progesterone deficiency. Consult your doctor if you experience any of the side effects mentioned below, or other side effects.

SIDE EFFECTS REPORTED AT A FREQUENCY OF 5% OR GREATER

• abdominal pain; perineal pain (the perineum is the area between the vagina and the rectum)
• headache
• constipation; diarrhea; nausea
• joint pain
• depression; decreased libido; nervousness; sleepiness*
• breast enlargement
• excessive urination at night

SIDE EFFECTS REPORTED AT A FREQUENCY RANGING FROM 1% TO 5%

• allergy; bloating; cramps; fatigue; pain
• dizziness*
• vomiting
• mood swings
• breast pain
• difficult or painful intercourse; genital itching; genital yeast infection; vaginal discharge
• urinary tract infection

SIDE EFFECTS REPORTED AT A FREQUENCY OF LESS THAN 1%

• fever; flu-like symptoms
• water retention^†
• gastrointestinal discomfort; gas; abdominal swelling
• back pain; leg pain
• insomnia
• sinusitis; upper respiratory tract infection
• asthma
• acne; itching
• painful or difficult urination; frequent urination

*If you experience dizziness or sleepiness, do not drive or operate machinery.
^†This may worsen some conditions such as asthma, epilepsy, migraine, heart disease, or kidney disease.

How Crinone works

Crinone has been formulated to be administered through the vagina. The moisturizing gel in Crinone forms a coating on the walls of the vagina which allows for absorption of progesterone through the vaginal tissue. Small, white globules may appear as a vaginal discharge possibly due to gel accumulation, even several days after usage. Crinone contains no irritating perfumes or dyes.

Other information

1. Your doctor has prescribed this drug for you and you alone. Do not give this drug to anyone else.
2. This medication was prescribed for your particular medical condition. Do not use it for another condition.
3. Keep this and all drugs out of the reach of children.

How to use Crinone

The dosage is one application of the 8% gel (90 mg of progesterone) vaginally, daily or twice daily as directed by your doctor. If you become pregnant, your doctor may decide to continue treatment for up to 10 to 12 weeks.

Crinone is to be applied directly from the specially designed sealed applicator into the vagina. The applicator is designed to deliver a premeasured dose of Crinone. A small amount of gel will be left in the tube after usage. Do not be concerned because you will still be receiving the appropriate, measured dosage.

1. Remove the applicator from the sealed wrapper. DO NOT remove the twist-off tab at this time. For use at altitudes above 2500 feet, see special instructions below.
2. Hold the applicator between the thumb and forefinger along the seam on the sides of the bulb. Shake down vigorously 3 to 4 times (like a thermometer) to ensure that the contents are at the thin end of the applicator.

3. Hold the applicator by the flat section of the bulb. Twist off the tab at the thin end and throw away. DO NOT squeeze the bulb while twisting the tab. This could force some gel to be released before it is inserted.

4. The applicator may be inserted into the vagina while you are in a sitting position or when lying on your back with your knees bent. Gently insert the thin end well into the vagina.

5. Squeeze the bulb of the applicator to deposit the gel into the vagina. Remove the applicator and throw it away in a waste container. Do not be concerned if a small amount of gel is left in the applicator. You will still be receiving the appropriate, measured dosage.

SPECIAL INSTRUCTIONS FOR USE AT ALTITUDES ABOVE 2500 FEET

1. Remove the applicator from the sealed wrapper. DO NOT remove the twist-off tab at this time. Hold the applicator on both sides of the bulb, as shown. Using a lancet or a stick pin, make a single puncture in the flat part of the bulb. This will relieve the difference in air pressure between the inside and outside of the applicator caused by high altitudes. It will not affect the amount of gel administered. You will still be receiving the appropriate measured dosage.

2. See Step 2 above.

3. See Step 3 above.

4. See Step 4 above.

5. Place your thumb or finger over the puncture that you made in the bulb of the applicator. Squeeze the bulb of the applicator to deposit the gel into the vagina. Remove the applicator and throw it away in a waste container. Do not be concerned if a small amount of gel is left in the applicator. You will still be receiving the appropriate, measured dosage.

Crinone coats the vaginal lining to provide long-lasting release of progesterone. Small, white globules may appear as a vaginal discharge possibly due to gel accumulation, even several days after usage. It is not unusual, but if you are concerned, discuss this with your doctor.

If you forget a dose of Crinone, use it as soon as you remember, but do not use more than the recommended daily dose. Crinone should not be used at the same time that you are using other vaginal therapy.

This leaflet provides the most important information about Crinone. If you want to read more, ask your doctor or pharmacist about the professional leaflet. You may need their help to understand some of the information.

How Supplied

Crinone is available as 8% gel (90 mg of progesterone).

Each box of the 8% gel contains fifteen single use, disposable vaginal applicators with a twist-off tab. Each applicator is wrapped and sealed in a foil overwrap.

Store at 20-25ºC (68-77ºF). [See USP controlled room temperature.]

Do not use Crinone after the expiration date which is printed on the box.

Keep out of reach of children.

PATIENT INFORMATION

Crinone 4% and Crinone 8%
(progesterone gel)

For Vaginal Use Only

FOR THE TREATMENT OF SECONDARY AMENORRHEA (ABSENCE OF MENSES IN WOMEN WHO HAVE PREVIOUSLY HAD A MENSTRUAL PERIOD)

Please read this information carefully before you start to use Crinone and each time your prescription is renewed, in case anything has changed. This leaflet does not take the place of discussions with your doctor. If you still have any questions, ask your doctor or health-care provider.

What Crinone is

Crinone is a specially formulated gel that you insert in your vagina. It contains the natural female hormone called progesterone. The 4% gel is used for women whose menstrual cycle has stopped. The 8% gel is to be used when the 4% gel has not worked.

Understanding the role of Crinone in the treatment of your menstrual irregularities

Progesterone is one of the hormones essential for regular menstrual periods. If your doctor has determined your body does not produce enough progesterone on its own, Crinone may be prescribed to provide the progesterone you need.

When you do not produce enough progesterone, menstrual irregularities can occur. Crinone can provide you with the progesterone needed during a normal menstrual cycle.

When you should not use Crinone

• If you are allergic to progesterone, progesterone-like drugs, or any of the inactive ingredients in the gel (ask a pharmacist if you are not sure about the inactive ingredients in Crinone).
• If you have unusual vaginal bleeding which has not been evaluated by a doctor.
• If you have a liver disease.
• If you have known or suspected cancer of the breast or genital organs.
• If you have a miscarriage and your physician suspects some tissue is still in the uterus.
• If you have or have had blood clots in the legs, lungs, eyes, or elsewhere. Risks of Crinone

Risk to the fetus.

• Birth defects have been reported in the offspring of women who were using Crinone during early pregnancy. These included an abdominal wall defect and a cleft palate. A causal association has been neither confirmed nor refuted. You should check with your doctor about the risks to your unborn child of any medication used during pregnancy.
• Blood clots and related health problems. Blood clots have been reported with the use of estrogens and progestational drugs (alone or in combination). If blood clots do form in your bloodstream, they can cut off the blood supply to vital organs, causing serious problems. These problems may include a stroke (by cutting off blood to part of the brain), a heart attack (by cutting off blood to part of the heart), a pulmonary embolus (by cutting off blood to part of the lungs), or other problems. Any of these conditions may cause death or serious long-term disability. Call your doctor immediately if you suspect you have any of these conditions. He or she may advise you to stop using this drug.

PRECAUTIONS

Be alert for unusual signs and symptoms. If any of these warning signals (or any other unusual symptoms) happen while you are using Crinone, call your doctor immediately:

• Abnormal bleeding from the vagina.
• Pains in the calves or chest, a sudden shortness of breath or coughing blood indicating possible clots in the legs, heart, or lungs.
• Severe headache or vomiting, dizziness, faintness, or changes in vision or speech, weakness or numbness of an arm or leg indicating possible clots in the brain or eye.
• Breast lumps, which could be associated with fibrocystic disorders, fibroadenoma, or breast cancer. (Ask your doctor or health-care provider to show you how to examine your breasts monthly.)
• Yellowing of the skin and/or white of the eyes indicating possible liver problems.

You should also notify your doctor if you experience depression, worsening of your diabetic condition, or fluid retention.

Possible side effects of Crinone

In addition to the risks listed above, the following side effects have been reported in studies with Crinone used for the treatment of menstrual irregularities due to progesterone deficiency. In these studies, women were treated with estrogen prior to and during Crinone therapy. All side effects reported at a frequency of 5% or greater after Crinone was added to estrogen therapy also were reported with estrogen therapy alone. Consult your doctor if you experience any of the side effects mentioned below, or other side effects.

SIDE EFFECTS REPORTED AT A FREQUENCY OF 5% OR GREATER

• abdominal pain; increased appetite; bloating; cramps; fatigue
• headache
• nausea
• back pain
• depression; mood swings; sleep disorder
• vaginal discharge
• upper respiratory tract infection

SIDE EFFECTS REPORTED AT A FREQUENCY RANGING FROM 1% TO 5%

• increased sweating
• allergy; flu-like symptoms; hot flushes; pain
• dizziness
• migraine; tremor
• gas; gastrointestinal discomfort
• thirst
• leg pain; muscle pain
• insomnia; nervousness; sleepiness*
• breast pain; painful menstruation
• infection; genital yeast infection
• acne; genital itching; rash; skin disorder
• frequent urination

SIDE EFFECTS REPORTED AT A FREQUENCY OF LESS THAN 1%

• dry mouth
• abnormal crying; allergic reaction; decreased appetite; dry eyes; swelling; face swelling; perineal pain (the perineum is the area between the vagina and the rectum); water retention^† weakness
• fainting
• abdominal swelling; gastritis; toothache
• joint pain; leg cramps; skeletal pain
• non-cancerous cyst
• bruising
• aggressive reaction; forgetfulness
• anemia
• premenstrual syndrome; vaginal dryness
• sore throat
• rapid, shallow breathing; shortness of breath; runny nose
• hives; itching; oily or dry scaly skin; skin discoloration
• bladder inflammation; painful or difficult urination
• "pink eye"

*If you experience dizziness or sleepiness, do not drive or operate machinery.
^†This may worsen some conditions such as asthma, epilepsy, migraine, heart disease, or kidney disease.

How Crinone works

Crinone has been formulated to be administered through the vagina. The moisturizing gel in Crinone forms a coating on the walls of the vagina which allows for absorption of progesterone through the vaginal tissue. Small, white globules may appear as a vaginal discharge possibly due to gel accumulation, even several days after usage. Crinone contains no irritating perfumes or dyes.

Other information

1. Your doctor has prescribed this drug for you and you alone. Do not give this drug to anyone else.
2. This medication was prescribed for your particular medical condition. Do not use it for another condition.
3. Keep this and all drugs out of the reach of children.

How to use Crinone

The dosage is one application of the 4% gel (45 mg of progesterone), vaginally, every other day as directed by your doctor, for a total of six doses. In some cases, your doctor may prescribe the 8% gel (90 mg of progesterone) every other day, for a total of six doses.

It is important to note that a dosage increase from the 4% gel can only be accomplished by using the 8% gel. Increasing the volume of gel administered does not increase the amount of progesterone absorbed.

Crinone is to be applied directly from the specially designed sealed applicator into the vagina. The applicator is designed to deliver a premeasured dose of Crinone. A small amount of gel will be left in the tube after usage. Do not be concerned because you will still be receiving the appropriate, measured dosage.

1. Remove the applicator from the sealed wrapper. DO NOT remove the twist-off tab at this time. For use at altitudes above 2500 feet, see special instructions below.

2. Hold the applicator between the thumb and forefinger along the seam on the sides of the bulb. Shake down vigorously 3 to 4 times (like a thermometer) to ensure that the contents are at the thin end of the applicator.

3. Hold the applicator by the flat section of the bulb. Twist off the tab at the thin end and throw away. DO NOT squeeze the bulb while twisting the tab. This could force some gel to be released before it is inserted.

Twist off completely - Do not pull off

4. The applicator may be inserted into the vagina while you are in a sitting position or when lying on your back with your knees bent. Gently insert the thin end well into the vagina.

5. Squeeze the bulb of the applicator to deposit the gel into the vagina. Remove the applicator and throw it away in a waste container. Do not be concerned if a small amount of gel is left in the applicator. You will still be receiving the appropriate, measured dosage.

SPECIAL INSTRUCTIONS FOR USE AT ALTITUDES ABOVE 2500 FEET

1. Remove the applicator from the sealed wrapper. DO NOT remove the twist-off tab at this time. Hold the applicator on both sides of the bulb, as shown. Using a lancet or a stick pin, make a single puncture in the flat part of the bulb. This will relieve the difference in air pressure between the inside and outside of the applicator caused by high altitudes. It will not affect the amount of gel administered. You will still be receiving the appropriate, measured dosage.

2. See Step 2 above.

3. See Step 3 above.

4. See Step 4 above.

5. Place your thumb or finger over the puncture that you made in the bulb of the applicator. Squeeze the bulb of the applicator to deposit the gel into the vagina. Remove the applicator and throw it away in a waste container. Do not be concerned if a small amount of gel is left in the applicator. You will still be receiving the appropriate, measured dosage.

Crinone coats the vaginal lining to provide long-lasting release of progesterone. Small, white globules may appear as a vaginal discharge possibly due to gel accumulation, even several days after usage. It is not unusual, but if you are concerned, discuss this with your doctor.

If you forget a dose of Crinone, use it as soon as you remember, but do not use more than the recommended daily dose. Crinone should not be used at the same time that you are using other vaginal therapy.

This leaflet provides the most important information about Crinone. If you want to read more, ask your doctor or pharmacist about the professional leaflet. You may need their help to understand some of the information.

How Supplied

Crinone is available in two strengths: 4% gel (45 mg of progesterone) and 8% gel (90 mg of progesterone).

Each box of the 4% gel contains six single use, disposable vaginal applicators with a twist-off tab. Each box of the 8% gel contains fifteen single use, disposable vaginal applicators with a twist-off tab. Each applicator is wrapped and sealed in a foil overwrap. Store at 20-25ºC (68-77ºF). [See USP controlled room temperature.]

Do not use Crinone after the expiration date which is printed on the box.

Keep out of reach of children.

Last reviewed on RxList: 1/3/2012
This monograph has been modified to include the generic and brand name in many instances.