In a single-center, open-label study (COL1620-007US), 99 women (aged 28 - 47 years) with either partial (n = 84) or premature ovarian failure (n = 15) who were candidates to receive a donor oocyte transfer as an Assisted Reproductive Technology ("ART") procedure were randomized to receive either Crinone (Progesterone) 8% twice daily (n = 68) or intramuscular progesterone 100 mg daily (n = 31). The study was divided into three phases (Pilot, Donor Egg and Treatment). The first phase of the study consisted of a test Pilot Cycle to ensure that the administration of transdermal estradiol and progesterone would adequately prime the endometrium to receive the donor egg. The second phase was the Donor Egg Cycle during which a fertilized oocyte was implanted. Crinone (Progesterone) 8% was administered beginning the evening of Day 14 of the Pilot and Donor Egg cycles. Subjects with partial ovarian function also underwent a Pre-Pilot Cycle and a Pre-Donor Egg Cycle during which time they were administered only leuprolide acetate to suppress remaining ovarian function. The Pre-Pilot Cycle, Pilot Cycle, Pre-Donor Egg Cycle, and Donor Egg Cycle each lasted approximately 34 days. The third phase of the study consisted of a 10-week treatment period to maintain a pregnancy until placental autonomy was achieved.
Sixty-one women received Crinone (Progesterone) 8% as part of the Pilot Cycle to determine their endometrial response. Of the 55 evaluable endometrial biopsies in the Crinone (Progesterone) 8% group performed on Day 25 - 27, all were histologically "in-phase", consistent with luteal phase biopsy specimens of menstruating women at comparable time intervals. Fifty-four women who received Crinone (Progesterone) 8% and had a histologically "in-phase" biopsy received a donor oocyte transfer. Among these 54 Crinone (Progesterone) -treated women, clinical pregnancies (assessed about week 10 after transfer by clinical examination, ultrasound and/or ß-hCG levels) occurred in 26 women (48%). In these 26 women, 17 women (31%) delivered a total of 25 newborns, seven women (13%) had spontaneous abortions and two women (4%) had elective abortions.
In a second study (COL1620-F01), Crinone (Progesterone) 8% was used in luteal phase support of women with tubal or idiopathic infertility due to endometriosis and normal ovulatory cycles, undergoing in vitro fertilization ("IVF") procedures. All women received a GnRH analog to suppress endogenous progesterone, human menopausal gonadotropins, and human chorionic gonadotropin. In this multi-center, open-label study, 139 women (aged 22-38 years) received Crinone (Progesterone) 8% once daily beginning within 24 hours of embryo transfer and continuing through Day 30 post-transfer. Clinical pregnancies assessed at Day 90 post-transfer were seen in 36 (26%) of women. Thirty-two women (23%) delivered newborns and four women (3%) had spontaneous abortions. (See )
In three parallel, open-label studies (COL1620-004US, COL1620-005US, COL1620-009US), 127 women (aged 18 - 44) with hypothalamic amenorrhea or premature ovarian failure were randomized to receive either Crinone (Progesterone) 4% (n = 62) or Crinone (Progesterone) 8% (n = 65). All women were treated with either conjugated estrogens 0.625 mg daily (n = 100) or transdermal estradiol (delivering 50 mcg/day) twice weekly (n = 27).
Estrogen therapy was continuous for the entire three 28-day cycle studies. At Day 15 of the second cycle (six weeks after initiating estrogen replacement), women who demonstrated adequate response to estrogen therapy (by ultrasound) and who continued to be amenorrheic received Crinone (Progesterone) every other day for six doses (Day 15 through Day 25 of the cycle).
In cycle 2, Crinone (Progesterone) 4% induced bleeding in 79% of women and Crinone (Progesterone) 8% induced bleeding in 77% of women. In the third cycle, estrogen was continued and Crinone (Progesterone) was administered every other day beginning on Day 15 for six doses. On Day 24 an endometrial biopsy was performed. In 53 women who received Crinone (Progesterone) 4%, biopsy results were as follows: 7% proliferative, 40% late secretory, 19% mid secretory, 13% early secretory, 7% atrophic, 6% menstrual endometrium, 6% inactive endometrium and 2% negative endometrium. In 54 women who received Crinone (Progesterone) 8%, biopsy results were as follows: 44% late secretory, 19% mid secretory, 11% early secretory, 19% atrophic, 5% menstrual endometrium and 2% "oral contraceptive like" endometrium.
In a study of 61 women with ovarian failure undergoing a donor oocyte transfer procedure receiving Crinone (Progesterone) 8% twice daily, treatment-emergent adverse events occurring in 5% or more of the women are shown in Table 3.
In a second clinical study of 139 women using Crinone (Progesterone) 8% once daily for luteal phase support while undergoing an fertilization procedure, treatment-emergent adverse events reported in ≥ 5% of the women are shown in Table 4.
In three studies, 127 women with secondary amenorrhea received estrogen replacement therapy and Crinone (Progesterone) 4% or 8% every other day for six doses. Treatment emergent adverse events during estrogen and Crinone (Progesterone) treatment that occurred in 5% or more of women are shown in Table 5.
Additional adverse events reported in women at a frequency
Autonomic Nervous System
Body as a Whole
Central and Peripheral Nervous System
Gastro-Intestinal
Metabolic and Nutritional
Musculo-Skeletal System
Neoplasm
Platelet, Bleeding & Clotting
Psychiatric
Red Blood Cell
Reproductive, Female
Resistance Mechanism
Respiratory System
Skin and Appendages
Urinary System
Vision Disorders
Crinone (Progesterone) 4% is administered vaginally every other day up to a total of six doses. For women who fail to respond, a trial of Crinone (Progesterone) 8% every other day up to a total of six doses may be instituted.
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.
SEE Crinone (Progesterone) - HOW TO USE Crinone (Progesterone) .
Note: The PATIENT INFORMATION SHEET contains special instructions for using the applicator at altitudes above 2500 feet in order to avoid a partial release of Crinone (Progesterone) before vaginal insertion.
Please read this information carefully before you start to use Crinone (Progesterone) 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.
Crinone (Progesterone) is a specially formulated gel that you insert in your vagina. It contains the natural female hormone called progesterone. Crinone (Progesterone) 8% is used as part of a program for women who are undergoing fertility 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 (Progesterone) may be prescribed to provide the progesterone you need.
The progesterone in Crinone (Progesterone) will help prepare the lining of your uterus so that it is ready to receive and nourish a fertilized egg. If pregnancy occurs, Crinone (Progesterone) may be supplemented for 10-12 weeks until production of progesterone by the placenta is adequate.
Be alert for unusual signs and symptoms. If any of these warning signals (or any other unusual symptoms) happen while you are using Crinone (Progesterone) , call your doctor immediately:
You should also notify your doctor if you experience depression, worsening of your diabetic condition, or fluid retention.
In addition to the risks listed above, the following side effects have been reported with Crinone (Progesterone) 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
SIDE EFFECTS REPORTED AT A FREQUENCY RANGING FROM 1% TO 5%
SIDE EFFECTS REPORTED AT A FREQUENCY OF LESS THAN 1%
Crinone (Progesterone) has been formulated to be administered through the vagina. The moisturizing gel in Crinone (Progesterone) 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 (Progesterone) contains no irritating perfumes or dyes.
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 (Progesterone) 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 (Progesterone) . 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.
Crinone (Progesterone) 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 (Progesterone) , use it as soon as you remember, but do not use more than the recommended daily dose. Crinone (Progesterone) should not be used at the same time that you are using other vaginal therapy.
This leaflet provides the most important information about Crinone (Progesterone) . 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.
Crinone (Progesterone) 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 (Progesterone) after the expiration date which is printed on the box.
For all medical inquiries contact:WATSONMedical CommunicationsParsippany, NJ 07054800-272-5525
Distributed By:Watson Pharma, Inc.Parsippany, NJ 07054 USA
Manufactured By:Fleet Laboratories Ltd.Watford, Herts WD18 7JJ UK
Revised: December 2011
PATIENT INFORMATION
Please read this information carefully before you start to use Crinone (Progesterone) 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.
Crinone (Progesterone) 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.
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 (Progesterone) may be prescribed to provide the progesterone you need.
When you do not produce enough progesterone, menstrual irregularities can occur. Crinone (Progesterone) can provide you with the progesterone needed during a normal menstrual cycle.
Be alert for unusual signs and symptoms. If any of these warning signals (or any other unusual symptoms) happen while you are using Crinone (Progesterone) , call your doctor immediately:
You should also notify your doctor if you experience depression, worsening of your diabetic condition, or fluid retention.
In addition to the risks listed above, the following side effects have been reported in studies with Crinone (Progesterone) used for the treatment of menstrual irregularities due to progesterone deficiency. In these studies, women were treated with estrogen prior to and during Crinone (Progesterone) therapy. All side effects reported at a frequency of 5% or greater after Crinone (Progesterone) 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
SIDE EFFECTS REPORTED AT A FREQUENCY RANGING FROM 1% TO 5%
SIDE EFFECTS REPORTED AT A FREQUENCY OF LESS THAN 1%
Crinone (Progesterone) has been formulated to be administered through the vagina. The moisturizing gel in Crinone (Progesterone) 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 (Progesterone) contains no irritating perfumes or dyes.
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 (Progesterone) 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 (Progesterone) . 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.
Crinone (Progesterone) 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 (Progesterone) , use it as soon as you remember, but do not use more than the recommended daily dose. Crinone (Progesterone) should not be used at the same time that you are using other vaginal therapy.
This leaflet provides the most important information about Crinone (Progesterone) . 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.
Crinone (Progesterone) 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 (Progesterone) after the expiration date which is printed on the box.
For all medical inquiries contact:WATSONMedical CommunicationsParsippany, NJ 07054800-272-5525
Distributed By:Watson Pharma, Inc.Parsippany, NJ 07054 USA
Manufactured By:Fleet Laboratories Ltd.Watford, Herts WD18 7JJ UK
Revised: December 2011
