STARTER KIT FOR LOW DOSE ORAL CONTRACEPTIVES

Abstract: The present invention provides a contraceptive kit which helps to overcome or ameliorate the problem of breakthrough bleeding and spotting associated with lowest does (15-20 mu g EE) estrogen contraceptives.

Description: STARTER KIT FOR LOW DOSE ORAL CONTRACEPTIVES BACKGROUND OF THE INVENTION Since the introduction of oral contraceptives (OCs) over a quarter-century ago, research has been directed toward developing preparations that minimize the potential for side effects while maintaining efficacy and normal menstrual patterns. At the start of an OC regimen, women experience rates of breakthrough bleeding and spotting in the first OC cycle which are about two times higher than the normal rates which remain generally steady after the fourth OC cycle. This is due to the change in the histology of the endometrium over during the first three to four cycles that is due to the effect if a progestin in the OC. Several months of OC use produces a more secretory endometrium which is less prone to breakthrough bleeding. Breakthrough bleeding and spotting are the most common complaints from women starting to use OCs and is a common reason for discontinuing their use. Furthermore, breakthrough bleeding and spotting rates are higher with OCs containing amounts of estrogen less than about 30 micrograms (μg), particularly in the first several months of use. Using a constant dose of progestin, Endrikat et al., 1997 found that the break through bleeding/spotting rate for 30μg ethinyl estradiol (EE) OC as compared to 20μg EE OC was 68% in cycle 1 , 85% in cycle 2 and 67% in cycle 3. Similarly, Akerlund et al. (1993) found that the break through bleeding/spotting rate for 30μg EE OC as compared to 20μg EE OC was 77% in cycle 1 , 60% in cycle 2 and 67% in cycle 3. These results are consistent with the conversion to a secretory endometrium occurring more quickly with an OC containing higher EE doses. The present invention provides a contraceptive kit which helps to overcome or ameliorate the problem of breakthrough bleeding and spotting associated with starting oral contraception using the lowest dose (15-20 μg EE) estrogen contraceptives. DETAILED DESCRIPTION OF THE INVENTION In accordance with the present invention is provided an oral contraceptive starter kit comprising at least two cycle packs of oral contraceptives containing an estrogen and a progestin, said kit having a first cycle pack and a last cycle pack, the first cycle pack containing an effective dosage of estrogen and progestin greater than the last cycle pack. It is preferred that the last cycle pack provides the lowest amount of effective steroid dosage, and most preferably the lowest amount of estrogen. It is also preferred that the effective dosage of estrogen and progestin in the first cycle pack is greater than in subsequent cycle packs. Most preferably, the last cycle pack preferably provides no more than about 20 μg of estrogen per dosage unit. In a further embodiment, the effective dosage of estrogen and progestin in the penultimate cycle pack is greater than the effective dosage of estrogen and progestin in the last cycle pack. The starter kit provides a means to gradually decrease the dose of estrogen over a number of cycles, thereby decreasing incidences of breakthrough bleeding and spotting that are often associated the lose-dose estrogen contraceptives. Thus, a first cycle may contain as a daily dosage, for example, 30 μg of estrogen per dosage unit. A second cycle may contain 30μg of estrogen per dosage unit. A third cycle may contain 20 μg of estrogen per dosage unit. Following the completion of the starter kit, standard cycle packs of lowest dose estrogen OC may be used. Hormonal active ingredients useful as oral contraceptives are well known in the art. Generally oral contraceptives contain an estrogen and a progestin (steroids) and may be formulated as monophasic, biphasic or triphasic cycles. Suitable estrogens include 17-β estradiol, estrone, or a salt thereof, estriol, ethinylestradiol and mestranol. Ethyinylestradiol (EE) is the preferred estrogen. Suitable progestins include trimegestone, nomegestrol, dienogest, norgestrel, levonorgestrol, cyproterone acetate, 3-ketodesogestrel (or etonogestrel), desogestrel, gestodene, norethindrone, drospirenone, medroxy progesterone acetate, megestrol acetate, norgestimate, 17β deactyl norgestimate, osaterone, norethindrone acetate, lynestrenol, norethynodrel, and ethynodiol diacetate. Combination oral contraceptives (containing estrogen and progestins) are commercially available such as those sold under the tradenames Alesse®, Brevicon®, Demulen®, Desogen®, Estrostep®, Harmonet®, Levlen®, Levlite®, Levora®, Loestrin®, Loette®, LoOvral®, Micronor®, Minesse®, Minulet®, Mircette®, Modicon®, Necon®, Nordette®, Norinyl®, Ortho-cept®, Ortho-Cyclen®, Ortho- Novum®, Ortho-Tri-Cyclen®, Ovcon®, Ovral®, Ovrette®, Trilevlen®, Trimiron®, TriMinulet®, Tri-Norinyl®, Triphasil®, Trivora®, and Zovia®. Kits of the present invention may contain multiple cycles dosages of various combination oral contraceptive arranged to appropriately decrease the effective dosage of total steroid from the penultimate cycle pack to the last cycle pack. For instance, a kit of the present invention might combine as a first cycle Nordette®, as a second cycle Triphasil® and as a third cycle Alesse®. Alternatively, a kit of the present invention might combined first and second cycles of Nordette®, third and fourth cycles of Triphasil® and a fifth cycle of Alesse®. In another embodiment of the invention, the kit might present a first cycle of Levora®, a second cycle of Trilevora® or Trilevlen® and a third cycle of Levlite®. In yet another embodiment of the invention, a first cycle of Loestrin® 1.5/30, a second cycle of Estrostep® and a third cycle of Loestrin® 1/20 might be combined. Similarly, a first cycle of Ortho- Novum® 1/35, a second cycle of Ortho-Novum® 7/7/7 and a third cycle of an OC containing norethindrone and an EE dose of less than or equal to 30 μg are combined in a starter kit. More detailed examples of cycles and dosages are described in the Examples. Although not required, in some preferred embodiments of the present invention the progestin and estrogen should be the same as those used in previous cycles, although the dosages are varied throughout the cycles of the kit. Effective dosage of estrogen and progestin refers to the combined amount of estrogen and progestin. (steroids) in a daily dosage unit taking into account the potency of a given steroid. The effective dose of a given steroid can be determined by one skilled in the art. Cycle pack, as used herein, refers to an oral contraceptive pill pack generally containing from 21-25 consecutive days of active ingredient-containing dosage units and may also contain placebos for the remainder of the cycle (3 to 7 days), which are free of hormonal active ingredient. Dosage units in the form of tablets or capsules may also contain excipients such as binders, diluents, disintegrating agents and lubricating agents. Placebos of the cycle pack may contain non- hormonal active agents such as iron or folic acid. Each cycle preferably ranges in duration from 21-25 consecutive days of steroid, followed by non-contraceptive placebos for the remainder of each cycle (i.e. 3-7 days). The kit may contain daily dosages arranged in dispensers such as blister packs or dial pack dispensers. The starter kit may contain 2 or more single cycle dosage arrangements, or the cycles may be combined to form a multi-cycle dosage arrangement. The starter kit may also contain instructional materials, markings or arrangements which explain the use and order of the cycle packs. In multi-cycle dosage arrangements the cycles may be separated from one another spatially and/or by other markings. Alternatively, blister packs containing individual cycles may be separated by perforations in the base of the blister pack or other means suitable for separation. Examples The following examples are illustrative but are not meant to be limiting of the present invention. Each example describes regimens of combination oral contraceptives which can be used to decrease the incidence of break through bleeding and spotting associated with the lowest dose (15-20μg) estrogen contraceptives. Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Example 8 Example 9 Example 10 Example 11 Example 12

Claims: CLAIMS What is claimed is: 1. An oral contraceptive starter kit comprising at least two cycle packs of oral contraceptives containing an estrogen and a progestin, said kit having a first cycle pack and a last cycle pack, the first cycle pack containing an effective dosage of estrogen and progestin greater than the last cycle pack. 2. The starter kit according to claim 1 in which the last cycle pack provides a daily dosage of estrogen equivalent to about 20 μg ethyinylestradiol per dosage unit. 3. The starter kit according to claim 1 in which the effective dosage of estrogen and progestin in the first cycle pack is greater than in subsequent cycle packs. 4. The starter kit according to claim 1 in which the effective dosage of estrogen and progestin in the penultimate cycle pack is greater than the effective dosage of estrogen and progestin in the last cycle pack. 5. The starter kit according to claim 1 in which the last cycle pack contains the lowest effective dosage of estrogen and progestin. 6. The starter kit according to claim 1 wherein the cycle packs are packaged in individual units. 7. The starter kit according to claim 1 wherein multiple cycle packs are packaged together as a single unit. 8. The starter kit according to claim 1 further comprising written instructions describing the order of use of said cycle packs. 9. The starter kit according any of the preceding claims wherein the estrogen is ethinylestradiol. 10. The starter kit according to any of the preceding claims wherein the progestin is selected from the group consisting of trimegestone, nomegestrol, norgestrel, levonorgestrol, cyproterone acetate, 3-ketodesogestrel, desogestrel, gestodene, drospirenone, medroxy progesterone acetate, megestroi acetate, norgestimate, 17B deactyl norgestimate, osaterone, norethindrone, norethindrone acetate, lynestrenol, norethynodrel, and ethynodiol diacetate. 11. The starter kit according to any of the preceding claims wherein the estrogen is ethinylestradiol and the progestin is levonorgestrel. 12. The starter kit according to any of the preceding claims wherein the estrogen is ethinylestradiol and the progestin is norethindrone. 13. The starter kit according to any of the preceding claims wherein the estrogen is ethinylestradiol and the progestin is norethindrone acetate. 14. The starter kit according to any of the preceding claims wherein the estrogen is ethinylestradiol and the progestin is gestodene. 15. The starter kit according to any of the preceding claims wherein the estrogen is ethinylestradiol and the progestin is norgestimate.

Inventors: GRUBB GARY S, GRUBB, GARY, S.
Applicants: AMERICAN HOME PROD, AMERICAN HOME PRODUCTS CORPORATION
Application year: 2001
Main classification: A61K31
IPC codes: A61K31, A61P5, A61P15