Crinone

INDICATIONS AND USAGE Assisted Reproductive Technology Crinone 8% is indicated for progesterone supplementation or replacement as part of an Assisted Reproductive Technology ("ART") treatment for infertile women with progesterone deficiency. Secondary Amenorrhea Crinone 4% is indicated for the treatment of secondary amenorrhea. Crinone 8% is indicated for use in women who have failed to respond to treatment with Crinone 4%.

DOSAGE AND ADMINISTRATION Assisted Reproductive Technology Crinone 8% is administered vaginally at a dose of 90 mg once daily in women who require progesterone supplementation. Crinone 8% is administered vaginally at a dose of 90 mg twice daily in women with partial or complete ovarian failure who require progesterone replacement. If pregnancy occurs, treatment may be continued until placental autonomy is achieved, up to 10 to 12 weeks. Secondary Amenorrhea Crinone 4% is administered vaginally every other day up to a total of six doses. For women who fail to respond, a trial of Crinone 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.

CONTRAINDICATIONS Crinone should not be used in individuals with any of the following conditions: Known sensitivity to Crinone (progesterone or any of the other ingredients) Undiagnosed vaginal bleeding Liver dysfunction or disease Known or suspected malignancy of the breast or genital organs Missed abortion Active thrombophlebitis or thromboembolic disorders, or a history of hormone-associated thrombophlebitis or thromboembolic disorders

ADVERSE REACTIONS Assisted Reproductive Technology In a study of 61 women with ovarian failure undergoing a donor oocyte transfer procedure receiving Crinone 8% twice daily, treatment-emergent adverse events occurring in 5% or more of the women are shown in Table 3. TABLE 3 Treatment-Emergent Adverse Events in ≥ 5% of Women Receiving Crinone 8% Twice Daily Study COL1620-007US (n = 61) Body as a Whole Bloating 7% Cramps NOS 15% Pain 8% Central and Peripheral Nervous System Dizziness 5% Headache 13% Gastro-Intestinal System Nausea 7% Reproductive, Female Breast Pain 13% Moniliasis Genital 5% Vaginal Discharge 7% Skin and Appendages Pruritus Genital 5% In a second clinical study of 139 women using Crinone 8% once daily for luteal phase support while undergoing an in vitro fertilization procedure, treatment-emergent adverse events reported in ≥ 5% of the women are shown in Table 4. TABLE 4 Treatment-Emergent Adverse Events in ≥ 5% of Women Receiving Crinone 8% Once Daily Study COL1620-F01 (n = 139) Body as a Whole Abdominal Pain 12% Perineal Pain Female 17% Central and Peripheral Nervous System Headache 17% Gastro-Intestinal System Constipation 27% Diarrhea 8% Nausea 22% Vomiting 5% Musculo-Skeletal System Arthralgia 8% Psychiatric Depression 11% Libido Decreased 10% Nervousness 16% Somnolence 27% Reproductive, Female Breast Enlargement 40% Dyspareunia 6% Urinary System Nocturia 13% Secondary Amenorrhea In three studies, 127 women with secondary amenorrhea received estrogen replacement therapy and Crinone 4% or 8% every other day for six doses. Treatment-emergent adverse events during estrogen and Crinone treatment that occurred in 5% or more of women are shown in Table 5. TABLE 5 Treatment-Emergent Adverse Events in ≥ 5% of Women Receiving Estrogen Treatment and Crinone Every Other Day Studies COL1620-004US, COL1620-005US, COL1620-009US Estrogen + Crinone 4% n = 62 Estrogen + Crinone 8% n = 65 Body as a Whole Abdominal Pain 3 (5%) 6 (9%) Appetite Increased 3 (5%) 5 (8%) Bloating 8 (13%) 8 (12%) Cramps NOS 12 (19%) 17 (26%) Fatigue 13 (21%) 14 (22%) Central and Peripheral Nervous System Headache 12 (19%) 10 (15%) Gastro-Intestinal System Nausea 5 (8%) 4 (6%) Musculo-Skeletal System Back Pain 5 (8%) 2 (3%) Myalgia 5 (8%) 0 (0%) Psychiatric Depression 12 (19%) 10 (15%) Emotional Lability 14 (23%) 14 (22%) Sleep Disorder 11 (18%) 12 (18%) Reproductive, Female Vaginal Discharge 7 (11%) 2 (3%) Resistance Mechanism Upper Respiratory Tract Infection 3 (5%) 5 (8%) Skin and Appendages Pruritus Genital 1 (2%) 4 (6%)

Drug Interactions No drug interactions have been assessed with Crinone.

DESCRIPTION Crinone ® (progesterone gel) is a bioadhesive vaginal gel containing micronized progesterone in an emulsion system, which is contained in single use, polypropylene vaginal applicators. The carrier vehicle is an oil in water emulsion containing the water swellable, but insoluble polymer, polycarbophil. The progesterone is partially soluble in both the oil and water phase of the vehicle, with the majority of the progesterone existing as a suspension. Physically, Crinone has the appearance of a soft, white to off-white gel. The active ingredient, progesterone, is present in either a 4% or an 8% concentration (w/w). The chemical name for progesterone is pregn-4-ene-3,20-dione. It has an empirical formula of C 21 H 30 O 2 and a molecular weight of 314.5. The structural formula is: Progesterone exists in two polymorphic forms. Form 1, which is the form used in Crinone, exists as white orthorhombic prisms with a melting point of 127-131°C. Each applicator delivers 1.125 grams of Crinone gel containing either 45 mg (4% gel) or 90 mg (8% gel) of progesterone in a base containing glycerin, light mineral oil, polycarbophil, carbomer homopolymer Type B, hydrogenated palm oil glyceride, sorbic acid, purified water and may contain sodium hydroxide. The structural formula

OVERDOSAGE There have been no reports of overdosage with Crinone. In the case of overdosage, however, discontinue Crinone, treat the patient symptomatically, and institute supportive measures. As with all prescription drugs, this medicine should be kept out of the reach of children.

HOW SUPPLIED Crinone is available in the following strengths: 4% gel (45 mg) in a single use, disposable, white polypropylene vaginal applicator with a teal twist-off cap. Each applicator contains 1.3 g of gel and delivers 1.125 g of gel. NDC 0023-6150-04 : 6 Single-use prefilled applicators. 8% gel (90 mg) in a single use, disposable, white polypropylene vaginal applicator with a teal twist-off cap. Each applicator contains 1.3 g of gel and delivers 1.125 g of gel. NDC 0023-6151-08 : 15 Single-use prefilled applicators. Each applicator is wrapped and sealed in a foil overwrap. Store at 20-25oC (68-77oF). [See USP controlled room temperature.] Keep out of reach of children. Rx only For all medical inquiries contact: AbbVie Inc. 1-800-678-1605 Distributed by: AbbVie Inc. North Chicago, IL 60064 Content Updated: June 2017 © 2024 AbbVie. All rights reserved. CRINONE and its design are trademarks of Allergan Sales, LLC, an AbbVie company.