Prochieve 8% gel

Absorption

Due to the sustained release properties of Prochieve, progesterone absorption is prolonged with an absorption half-life of approximately 25-50 hours, and an elimination half-life of 5-20 minutes. Therefore, the pharmacokinetics of Prochieve are rate-limited by absorption rather than by elimination.

The bioavailability of progesterone in Prochieve was determined relative to progesterone administered intramuscularly. In a single dose crossover study, 20 healthy, estrogenized postmenopausal women received 45 mg or 90 mg progesterone vaginally in Prochieve 4% or Prochieve 8%, or 45 mg or 90 mg progesterone intramuscularly. The pharmacokinetic parameters (mean ± standard deviation) are shown in Table 1.

The multiple dose pharmacokinetics of Prochieve 4% and Prochieve 8% administered every other day and Prochieve 8% administered daily or twice daily for 12 days were studied in 10 healthy, estrogenized postmenopausal women in two separate studies. Steady state was achieved within the first 24 hours after initiation of treatment. The pharmacokinetic parameters (mean ± standard deviation) after the last administration of Prochieve 4% or 8% derived from these studies are shown in Table 2.

Distribution

Progesterone is extensively bound to serum proteins (~96-99%), primarily to serum albumin and corticosteroid binding globulin.

Metabolism

The major urinary metabolite of oral progesterone is 5(beta)-pregnan-3(alpha), 20(alpha)-diol glucuronide which is present in plasma in the conjugated form only. Plasma metabolites also include 5(beta)-pregnan-3(alpha)-ol-20-one (5(beta)-pregnanolone) and 5(alpha)-pregnan-3(alpha)-ol-20-one (5(alpha)-pregnanolone).

Excretion

Progesterone undergoes both biliary and renal elimination. Following an injection of labeled progesterone, 50-60% of the excretion of progesterone metabolites occurs via the kidney; approximately 10% occurs via the bile and feces, the second major excretory pathway. Overall recovery of labeled material accounts for 70% of an administered dose, with the remainder of the dose not characterized with respect to elimination. Only a small portion of unchanged progesterone is excreted in the bile.

Assisted Reproductive Technology

Prochieve 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

Prochieve 4% is indicated for the treatment of secondary amenorrhea. Prochieve 8% is indicated for use in women who have failed to respond to treatment with Prochieve 4%.

Prochieve should not be used in individuals with any of the following conditions:

1. Known sensitivity to Prochieve (progesterone or any of the other ingredients)
2. Undiagnosed vaginal bleeding
3. Liver dysfunction or disease
4. Known or suspected malignancy of the breast or genital organs
5. Missed abortion
6. Active thrombophlebitis or thromboembolic disorders, or a history of hormone-associated thrombophlebitis or thromboembolic disorders

There have been no reports of overdosage with Prochieve. In the case of overdosage, however, discontinue Prochieve, treat the patient symptomatically, and institute supportive measures.

As with all prescription drugs, this medicine should be kept out of the reach of children.

Assisted Reproductive Technology

Prochieve 8% is administered vaginally at a dose of 90 mg once daily in women who require progesterone supplementation. Prochieve 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 10-12 weeks.

Secondary Amenorrhea

Prochieve 4% is administered vaginally every other day up to a total of six doses. For women who fail to respond, a trial of Prochieve 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 Prochieve PATIENT INFORMATION SHEET - HOW TO USE Prochieve. 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 Prochieve before vaginal insertion.

Prochieve is available in the following strengths:

4% gel (45 mg) in a single use, one piece, disposable, white polyethylene vaginal applicator with a twist-off top. Each applicator contains 1.45 g of gel and delivers 1.125 g of gel.

NDC-55056-0406-1 - 6 Single-use prefilled applicators.

8% gel (90 mg) in a single use, one piece, disposable, white polyethylene vaginal applicator with a twist-off top. Each applicator contains 1.45 g of gel and delivers 1.125 g of gel.

NDC-55056-0806-1 - 6 Single-use prefilled applicators.

NDC-55056-0818-1 - 18 Single-use prefilled applicators

Each applicator is wrapped and sealed in a foil overwrap.

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).

Rx only.

U.S. Patent Numbers 4,615,697 and 5,543,150.

Manufactured for:   Columbia Laboratories, Inc. Livingston, NJ 07039

Manufactured by:   Fleet Laboratories Ltd., Watford, United Kingdom

40905010002                                                     Revised February 2004

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