WO2010007629A1

WO2010007629A1 - A kit comprising anti-emetic and oral contraceptive

Info

Publication number: WO2010007629A1
Application number: PCT/IN2009/000403
Authority: WO
Inventors: Sofia Mumtaz; Sheetal Kulkarni
Original assignee: Lupin Ltd
Current assignee: Lupin Ltd
Priority date: 2008-07-15
Filing date: 2009-07-15
Publication date: 2010-01-21
Anticipated expiration: 2011-01-15

Abstract

A kit for administration of emergency contraception comprising an oral contraceptive and an antiemetic, administered simultaneously or sequentially. A pharmaceutical combination comprising separate dosage forms, in a common package, of oral contraceptive and an anti-emetic useful in reducing nausea and vomiting associated with the administration of oral contraceptive. A kit for administration of emergency contraception comprising an oral contraceptive and an antiemetic wherein the antiemetic in immediate release formulation is administered prior to the administration of oral contraceptive.

Description

A KIT COMPRISING ANTI-EMETIC AND ORAL CONTRACEPTIVE

Field of the Invention

The present invention relates to a composition for co-administration of oral contraceptive, more specifically emergency contraceptive, and an antiemetic to reduce the incidence of nausea and vomiting associated with hormonal administration.

More particularly the present invention relates to a kit comprising an oral contraceptive formulation preferably levonorgestrel and an antiemetic preferably meclizine for simultaneous or sequential administration.

The present invention relates to the method of preparing oral contraceptive formulation comprising progestin and /or estrogen and an antiemetic.

Background of the Invention

The ovarian/menstrual cycle is a complex event characterized by an estrogen rich follicular phase and, after ovulation, a progesterone rich luteal phase. Each has duration of approximately 14 days resulting in an intermenstrual interval of about 28 days. The endometrial tissue responds to the changes in hormonal milieu.

The onset of menstruation is the beginning of a new menstrual cycle and is counted as day 1. During a span of about 5 to 7 days, the superficial layers of the endometrium, which grew and devefoped during the antecedent ovarian/menstrual cycle, are sloughed because demise of the corpus luteum in the non-fertile menstrual cycle is associated with a loss of progesterone secretion. Ovarian follicular maturation occurs progressively resulting in a rise in the circulating levels of estrogen, which in turn leads to new endometrial proliferation.

The dominant ovarian follicle undergoes ovulation at mid-cycle, generally between menstrual cycle days 12 to 16 and is converted from a predominantly estrogen source to a predominantly progesterone source (the corpus luteum). The increasing level of progesterone in the blood converts the proliferative endometrium to a secretory phase in which the tissue proliferation has promptly abated, leading to the formation of endometrial glands or organs. When the ovulated oocyte is viably fertilized and continues its progressive embryonic cleavage, the secretory endometrium and the conceptus can interact to bring about implantation (nidation), beginning about 6 to 8 days after fertilization.

If an ongoing pregnancy is to be established via implantation, the embryo will attach and burrow into the secretory endometrium and begin to produce human chorionic gonadotropin (HCG). The HCG in turn stimulates extended corpus luteum function, i.e. the progesterone production remains elevated, and menses does not occur in the fertile menstrual cycle. Pregnancy is then established. In the non-fertile menstrual cycle, the waning level of progesterone in the blood causes the endometrial tissue to be sloughed. This starts a subsequent menstrual cycle.

Because endometrial proliferation serves to prepare the uterus for an impending pregnancy, manipulation of hormones and of the uterine environment can provide contraception. For example, estrogens are known to decrease follicle stimulating hormone secretion by feedback inhibition.

Progestins can also provide contraception. Endogenous progesterone after estrogen is responsible for the progestational changes of the endometrium and the cyclic changes of cells and tissue in the cervix and the vagina. Administration of progestin makes the cervical mucus thick, tenacious and cellular which is believed to impede spermatozoal transport. Administration of progestin also inhibits luteinizing hormone secretion and blocks ovulation in humans. Several devices and pharmaceutical compositions are available for the prevention of undesirable conception in the case of regular and planned coitus. For example, condom, pessary, intrauterine devices as well as the different mono-or multi-phasic oral contraceptives. The most prevalent form of oral contraception is a pill that combines an estrogen and/or a progestin, a so-called combined oral contraceptive preparation.

Further sometimes unintentional pregnancies occur for any number of reasons. They can occur following sexual intercourse when neither party uses a contraceptive device or drug. However, this is by no means, the only reason for unintended pregnancies. Condoms are known to break; diaphragms to slip; and traditional contraceptive pills are, by their own admission, not 100 percent effective, even when taken properly. Moreover, when pills are missed, particularly with the newer, low- dose products, the risk of pregnancy increases substantially. In fact, each year in the U.S. alone, approximately 750,000 pregnancies occur to women using traditional oral contraceptive regimens. Of course, some of these pregnancies occur because the patient has failed to completely and dogmatically follow the prescribed pharmaceutical regimen.

Emergency contraceptive ("EC") pills are an available treatment for women who are concerned they may have become pregnant by their most recent unprotected sexual encounter. These pills are intended for administration within days, and preferably within hours after unprotected sex and often contain relatively high doses of for example, a progestin and/or an estrogen. Reports in the scientific literature describe other drugs, which may be effective for emergency contraception as well. Dosages and protocols will vary with the drug(s) used. However, in each case, the "pills" help to prevent pregnancy, i.e. either preventing a fertilized ovum from implanting in the lining of the uterus and/or depending on the timing of intercourse, preventing the sperm from fertilizing an egg. The most commonly used emergency contraceptive pill is one tablet of levonorgestrel 0.75mg taken orally as soon as possible within 72 hours after unprotected intercourse. The second tablet should be taken 12 hours after the first dose. Efficacy is better if levonorgestrel is taken as directed as soon as possible after unprotected intercourse. Further 1.5mg of levonorgestrel can also be administered at one time as an emergency contraceptive pill. But all such emergency contraceptive pills, which contain high doses of contraceptive hormone, are associated with high incidence of nausea and vomiting. Further if vomiting occurs within three hours of taking the tablet; then another tablet of emergency contraceptive pill should be taken immediately.

Norgestrel and levonorgestrel, namely/the D isomer of norgestrel have been used in combined preparations as contraceptives for a long time. Further the dose range of levonorgestrel, as emergency contraceptive pill is 1.5 mg in divided doses or 1.5mg in single dose.

Another common problem associated with oral contraceptives as well as an emergency contraceptive pill is the incidence of nausea, which occurs in a significant percentage of patients. Women may experience vomiting and nausea as major side effect due to contraceptive. It had been observed that about 23.1% of patient experience nausea and 5.6% vomiting when 0.75mg of levonorgestrel is administered. This is not only uncomfortable, but may also compromise the efficacy of the contraceptive as the associated vomiting may expel out the contraceptive pill. Certainly, a woman who has taken an emergency contraceptive pill and has had an adverse effect, is less likely to take the steps to assure efficacy, including taking more emergency contraceptive pills.

One prior art CN 1485093 discloses a combination of maxeran preparation and acyeterion. CA2354250 discloses a combination of dimenhydrinate salt with d-norgestrel. But it is known that dimenhydrinate has duration of 4-6 hours, and its use has been limited after development of meclizine, which doesn't have much drowsiness.

Therefore, there remains a need for an oral contraceptive formulation, which reduces the incidence of nausea, and vomiting associated with the administration of oral contraceptive and in turn increases the patient compliance. The present invention relates to the methods of co-administration and kit provided for coadministration of oral contraceptive and an antiemetic. The kits so provided have the advantage of promoting better patient compliance, which in turn can translate into better therapeutic efficacy. For a patient lifestyle standpoint the methods of the present invention would also be more convenient.

Further it has also been recommended in the current therapy that if vomiting occurs within three hours of taking the tablet, another tablet of emergency contraceptive pill should be taken immediately to prevent contraceptive failure. Thus the present invention also eliminates the need to administer second pill to substitute the expelled emergency contraceptive pill and alleviates patient anxiety related to contraceptive failure.

Objects of the Invention

The object of the present invention is to provide a kit for administration of emergency contraception comprising an oral contraceptive and an antiemetic, administered simultaneously or sequentially.

Another object of the present invention is a pharmaceutical combination comprising separate dosage forms, in a common package, of oral contraceptive and an antiemetic useful in reducing nausea and vomiting associated with the administration of oral contraceptive. Another object of the present invention is a kit containing a single day's dosage for emergency contraception medicine, said kit including a pill for reducing emesis to be administered prior to the administration of emergency contraception.

Another object of the present invention is a kit for administration of emergency contraception comprising an oral contraceptive and an antiemetic, administered simultaneously wherein the oral contraceptive is in delayed release formulation.

Another object of the present invention is a kit for administration of emergency contraception comprising an oral contraceptive and an antiemetic wherein the antiemetic in immediate release formulation is administered prior to the administration of oral contraceptive.

Detailed Description of Invention

The present invention provides an oral contraceptive formulation, which shows reduced incidence of nausea and vomiting, associated with oral contraceptives hormones. The oral contraceptive formulation of the present invention comprises an oral contraceptive and antiemetic. The oral contraceptive hormones used according to present invention are progestin and /or estrogen. The present invention is provided in the form of kit comprising oral contraceptive and an antiemetic for simultaneous or sequential administration.

The oral contraceptive, which may be used in the present invention, includes progestogen and /or estrogens.

A "delayed release dosage form" is one that releases a drug (or drugs) at a time other than promptly after administration. A "modified release dosage form" is one for which the drug release characteristics, time course and/or location are chosen to accomplish therapeutic or convenience objectives not offered by conventional dosage forms such as solutions, ointments, or promptly dissolving dosage forms. Delayed release and extended or controlled release dosage forms and their combinations are types of modified release dosage forms.

"Pulsed release" refers to an initial release of drug, followed by a period of substantially no release, and followed by one or more additional releases of drug separated by a period of substantially no release. This does not mean that there are no blood levels of drugs between periods of release.

"Sustained release" or "SR" means the therapeutic pharmaceutical composition is provided in a formulation such that the composition provides an initial therapeutic effect and also an ongoing or additional release of the therapeutic pharmaceutical composition or therapeutic effect over a desired period of time.

A kit of two or more agents means that the two or more agents are packaged to visually and/or tactilely indicate an appropriate sequence for administering the bioactive agents to a single patient

The kit of the present invention contains a combination of one or more pharmaceutical agent(s) comprising an oral contraceptive formulation and an antiemetic.

The kits are packaged to provide both an oral contraceptive and an antiemetic in a convenient form for administration. In one embodiment, the kit contains multiple solid oral dosage forms, such as tablets, chewable tablets, or capsules containing the active ingredient(s) in the same or different dosages. Provided, among other things, is a formulation or kit comprising pharmaceutically effective dosage of (a) an oral contraceptive (b) an antiemetic

The packaging material may be a box, bottle, pouch, blister package, strip package tray, or card. The kit typically may also include instructions for coordinating the administration of the oral contraceptive with the administration of antiemetic.

The package may comprise of two tablets of emergency contraceptive preferably a formulation of 0.75mg of levonorgestrel and an antiemetic arranged for sequential or simultaneous administration. Any other kit or package which includes a combination of oral contraceptive preferably emergency contraceptive and an antiemetic will be included within the scope of the invention.

Progestogens which may be used in the present invention include but are not limited to, for example, progesterone and its derivatives such as 17-hydroxy progesterone esters and 19-nor- 17-hydroxy progesterone esters, 17-alpha-ethinyl testosterone, 17-alpha-ethinyl-19-nortestosterone (norethindrone) and derivatives thereof, norethindrone acetate, norgestrel, norgestimate, desogestrel, levonorgestrel, medroxyprogesterone, dienogest. Other exemplary progestogens include demegestone, drospirenone, dyhyrogesterone, gestodene, medrogestone, medroxy progesterone and esters thereof. The most preferable progestogen for the present invention is levonorgestrel and the preferred dose is 1.5mg in single or divided doses.

Estrogens which may be used in the present invention include but are not limited to, for example, ethinyl estradiol, 17.beta.-estradiol, 17.beta.-estradiol-3-acetate, mestranol, conjugated estrogens, USP and estrone or salts thereof. Furthermore natural estrogens can be used, e.g., estrone, estradiol or estriol, and the esters thereof, inter alia estradiol valerate, 17-α-ethinylestradiol and estradiol valerate are preferred. The amount of estrogen used is described herein as that which is "equivalent" in estrogenic potency to an amount of ethinyl estradiol. The equivalent estrogenic potency of an estrogen to ethinyl estradiol may be readily determined by one of ordinary skill in the art.

Suitable antiemetic for the present invention includes dopamine antagonist, 5HT3 receptor antagonist, anticholinergics, antihistaminics, cannabinoids and other drugs, which have antiemetic effects. The dopamine antagonists include metoclopramide, droperidol, domperidone, perphenazine, prochlorperazine, promethazine, triflupromazine and the likes. 5HT3 antagonist includes ondansetron, granisetron, dolasetron, tropisetron, and the likes. Anticholinergic drugs used as antiemetics are hyoscine, scopolamine and the likes. Anti-histaminics as promethazine, meclizine, buclizine, and likes are used as antiemetic. The most preferable antiemetic is ondansetron, meclizine and the preferable dosage range is 1-100mg. Other antiemetics, which are used as OTC antiemetics such as cyclizine, dimenhydrinate, diphenhydramine, can also be combined together with levonorgestrel to prepare an OTC emergency contraceptive formulation.

According to the methods of the invention, the method of reducing nausea and vomiting associated with administration of oral contraceptives includes as combination of progestin and anti emetic or estrogen and antiemetic or a combination of progestin, estrogen and antiemetic. The preferable method of invention is kit comprising the combination of progestin and antiemetic. The preferred progestin is levonorgestrel. The preferred anti-emetic is meclizine or ondansetron. The formulation of the present invention comprises combination of an oral contraceptive and an antiemetic.

Preferably the present invention is in the form of kit comprising oral contraceptive in immediate release and an antiemetic for immediate release for sequential administration. The sequential administration would ensure that an antiemetic is taken at least 30 min prior to the administration of oral contraceptive. The release of antiemetic may be modified such that it has extended duration to provide immediate effect as well as effect when a second dose of emergency contraceptive is administered after 12 hours of first dose.

Another embodiment of the invention is in the form of kit comprising oral contraceptive in delayed release and an antiemetic in immediate release for simultaneous administration

Further pulsatile release will also be included within the scope of the invention. The release of antiemetic may be modified such that it has extended duration to provide immediate effect as well as effect when a second dose of emergency contraceptive is administered after 12 hours of first dose.

The present invention is in the form of kit, which comprise of an oral contraceptive and antiemetic. Preferably the oral contraceptive is an emergency contraceptive pill. Most preferably the emergency contraceptive is two tablets of 0.75mg of levonorgestrel or one tablets of 1.5mg of levonorgestrel. The antiemetic is to be taken at least 30 min prior to the administration of emergency contraceptive. Most preferably the antiemetic is ondansetron or meclizine.

Administration of antiemetic prior to the emergency contraceptive reduces nausea and vomiting associated with the administration of contraceptive formulation. The kit provides an additional benefit of ease of administration and increase in patient compliance. Further the emergency contraceptive 0.75mg of levonorgestrel is available as an OTC drug for above 17 yrs of age. Thus co-packaging of emergency contraceptive and antiemetic or kit comprising emergency contraceptive and antiemetic provides a convenient form for administration. The kit may typically include instructions for coordinating the administration of the pharmaceutical formulation.

The pharmaceutical formulations may be in any suitable dosage form, including forms which providing controlled release of the pharmaceutical agent, including immediate, sustained, modified, delayed or pulsed release formulations or a combination thereof.

The formulations of the present invention may comprise of excipients known in the art. The polymers may include hydrophilic and / or hydrophobic polymer as cellulose derivative as hydroxypropylmethyl cellulose, methyl cellulose, ethyl cellulose, polysaccharides, gums, the polymerized gelatin, cellulose butyrate phthalate, cellulose hydrogen phthalate, cellulose propionate phthalate, polyvinyl acetate phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropyl methylcellulose phthalate, hydroxypropylmethylcellulose acetate, dioxypropyl methylcellulose succinate, carboxymethyl ethylcellulose, hydroxypropyl methylcellulose acetate succinate, polymers and copolymers formed from acrylic acid, methacrylic acid, and/or esters thereof preferably formed from acrylic acid, methacrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate, ethyl methacrylate, and/or other vinyl monomers. Preferred enteric polymers are acrylic acid and methacrylic acid polymers and copolymers, particularly those that are commercially available under the trade names Eudragit® L and Eudragit® S, in which the ratio of free carboxyl to ester groups is about1 :1 and 1:2, respectively, and wherein each copolymer has a (weight average) molecular weight of abouti 35,000 Da.

The delayed release dosage units in any of the embodiments of the invention can be prepared, for example, by coating a drug or a drug-containing composition with a selected coating material or by using a delayed release polymer. The coating may contain a plasticizer to prevent the formation of pores and cracks. Suitable plasticizers include, but are not limited to, triethyl citrate (Citroflex 2), triacetin (glyceryl triacetate), acetyl triethyl citrate (Citroflec A2), Carbowax 400 (polyethylene glycol 400), diethyl phthalate, tributyl citrate, acetylated monoglycerides, glycerol, fatty acid esters, propylene glycol, and dibutyl phthalate. The coating can also contain other coating excipients such as detackifiers, antifoaming agents, lubricants (e.g., magnesium stearate), and stabilizers (e.g., hydroxypropylcellulose, acids and bases) to solubilize or disperse the coating material, and to improve coating performance and the coated product.

Alternatively, a delayed release dosage unit may be formulated by dispersing an active agent within a matrix of a suitable material such as a delayed coating material or other delayed release polymeric materials.

Other additives may be incorporated in the formulation, such as diluents, binders, lubricants, antioxidants, colorings, sweeteners, flavorings and acidulants, wetting agents, hydrophilizing agents such as sorbitol and cyclodextrins, osmotic agents or pore forming agents such as mannitol, pH correctors, stabilizing agents such as trehalose and mannitol, adsorbents, chelating and sequestering agents and gastro resistant film-coating excipients of the type including cellulose acetyl phthalate and polymethacrylates.

By way of example, there may be chosen any one of the following diluents or alternatively a combination thereof: calcium carbonate, calcium sulfate, sucrose, dextrin, dextrose, dicalciumphosphatedihydrate, kaolin, magnesium carbonate, magnesium oxide, maltodextrin, cellulose, microcrystalline cellulose, sorbitol, starches, pregelatinized starch, talc, tricalciumphosphate and lactose. Among the binders, there may be mentioned: gum arabic, gum tragacanth, guar gum, alginic acid, sodium alginate, sodiumcarboxymethylcellulose, dextrin, gelatin, hydroxyethylcellulose, hydroxypropylcellulose, liquid glucose, magnesium and aluminium silicate, maltodextrin, povidone, pregelatinized starch, starch and zein. The lubricants are glidants (such as anhydrous colloidal silica, magnesium trisilicate, magnesium silicate, cellulose, starch, talc or tricalcium phosphate) or alternatively antifriction adhering agents (such as calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated vegetable oils, paraffin, magnesium stearate, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, fumaric acid, stearic acid or zinc stearate and talc).

As examples of antioxidants, persons skilled in the art may select any of the following compounds: ascorbic acid, ascorbyl palmitate, fumaric acid, propyl gallate, sodium ascorbate and sodium metabisulfite, alpha-tocopherol, malic acid, BHA and BTH.

Preferred wetting agents are: sodium docusate and sodium lauryl sulfate which are anionic surfactants; benzalkonium chloride, benzethonium chloride and cetrimide which are cationic surfactants; glyceryl monooleate, fatty acid esters of polyoxyethylene sorbitan, polyvinyl alcohol) and sorbitans, which are nonionic surfactants.

Among the pH regulators, there are acidifying agents of the type including citric acid, hydrochloric acid, lactic acid, tartaric acid, as well as alkalinizing agents of the type including monoethanolamine, diethanolamine and triethanolamine, potassium citrate, sodium bicarbonate, sodium citrate dihydrate.

Examples of adsorbents are bentonite, anhydrous colloidal silica, kaolin, magnesium and aluminum silicate, microcrystalline cellulose and cellulose. As chelating and sequestering agents, there may be used citric acid monohydrate, edetic acid, disodium phosphate, monosodium phosphate, potassium citrate, tartaric acid and sodium citrate dihydrate.

The quantities of these additives are those normally used in the art.

The formulation of the present invention may be prepared by conventional techniques well known to those skilled in the art such as wet granulation, melt granulation, direct compression or dry compaction and/or slugging and the like. Oral contraceptive or antiemetic, along with or without directly compressible grade excipients or granulated together or separately by wet granulation or dry granulation with or without excipients. The granules are prepared by sifting, oral contraceptive or antiemetic and excipients through the desired mesh size sieve and then are mixed using a rapid mixer granulator or planetary mixer or mass mixer or ribbon mixer or fluid bed processor or any other suitable device. The blend can be granulated, such as by adding a solution of a binder whether alcoholic or hydro-alcoholic or aqueous in a low or high shear mixer, fluidized bed granulator and the like or by dry granulation. The granulate can be dried using a tray drier or fluid bed drier or rotary cone vacuum drier and the like. The sizing of the granules can be done using an oscillating granulator or comminuting mill or any other conventional equipment equipped with a suitable screen. Alternatively, granules or pellets or spheroids can be prepared by extrusion and spheronization, or roller compaction. Also the manufacture of granules of actives can be made by mixing the directly compressible excipients or by roller compaction. The blend so obtained can be compressed using a suitable device, such as a station rotary machine to form slugs, which are passed through a mill or fluid energy mill or ball mill or colloid mill or roller mill or hammer mill and the like, equipped with a suitable screen to obtain the milled slugs.

In another aspect of the invention, the smaller tablets (mini-tablets) can be made by compressing the granules using die-and-punch of various sizes and shapes. Optionally, the coating on the tablets can be applied by techniques known to one skilled in the art such as spray coating, dip coating, fluidized bed coating and the like. Further, the oral contraceptive formulation may also be prepared, by dissolving the oral contraceptive hormone in an organic solvent and then granulating the excipients with it.

The invention is illustrated by the following not limiting example:

Levonorgestrel Tablet

Procedure:

1) Dissolve required qty. of drug in required quantity of Methylene chloride. Stir it, until clear solution was obtained, then add povidone, followed by stirring until it forms a clear solution.

2) Starch and Lactose were sifted and granulated with above binder solution, dried and lubricated. Lubricated blend then compressed into tablets.

3) The tablet is optionally coated with the coating solution mentioned above.

Meclizine Hydrochloride Tablets

Procedure:

1) Meclizine Hydrochloride, DCP, Sucrose and PEG were sifted using a suitable sieve.

2) Starch paste is prepared.

3) Sifted materials of the step 1 was then granulated with the above starch paste followed by drying and sifting.

4) Sifted dried granules were then lubricated with Mg-stearate and compressed.

Other technologies known to those skilled in the art can be used in order to achieve similar results.

Claims

1. A kit for administration of emergency contraception comprising an oral contraceptive and an antiemetic, administered simultaneously or sequentially.

2. A kit of claim 1 wherein the kit reduces nausea and vomiting associated with the administration of emergency contraceptive.

3. A kit of claim 1 wherein the emergency contraceptive is progestin only pill or combination of estrogen and progestin.

4. A kit of claim 1 , wherein antiemetic is selected from dopamine antagonist, 5HT3 receptor antagonist, anticholinergics, antihistaminics, cannabinoids and other drugs.

5. A kit of claim 4, wherein antiemetic is meclizine.

6. A kit of claim 3, wherein the emergency contraceptive is levonorgestrel.

7. A pharmaceutical combination comprising separate dosage forms, in a common package, of oral contraceptive and an anti-emetic useful in reducing nausea and vomiting associated with the administration of oral contraceptive.

8. A kit of claim 7 wherein the emergency contraceptive is progestin only pill or combination of estrogen and progestin.

9. A kit of claim 7, wherein antiemetic is selected from dopamine antagonist, 5HT3 receptor antagonist, anticholinergics, antihistaminics, cannabinoids and other drugs.

10. A kit of claim 9, wherein antiemetic selected is meclizine.

11. A kit of claim 8 wherein the emergency contraceptive is levonorgestrel.

12. A kit containing a single day's dosage for emergency contraception medicine, said kit including a pill for reducing emesis to be administered prior to the administration of emergency contraception.

13. A kit of claim 12 wherein the emergency contraceptive is progestin only pill or combination of estrogen and progestin.

14. A kit of claim 12, wherein the pill for reducing emesis is selected from dopamine antagonist, 5HT3 receptor antagonist, anticholinergics, antihistaminics, cannabinoids and other drugs.

15. A kit of claim 14, wherein the pill for reducing emesis is meclizine.

16. A kit of claim 13 wherein the emergency contraceptive is levonorgestrel.

17. A kit for administration of emergency contraception comprising an oral contraceptive and an antiemetic, administered simultaneously wherein the oral contraceptive is in delayed release formulation.

18. A kit of claim 17 wherein the emergency contraceptive is progestin only pill or combination of estrogen and progestin.

19. A kit of claim 17, wherein antiemetic is selected from dopamine antagonist, 5HT3 receptor antagonist, anticholinergics, antihistamines, cannabinoids and other drugs.

20. A kit of claim 19, wherein antiemetic is meclizine.

21. A kit of claim 18 wherein the emergency contraceptive is levonorgestrel.

22. A kit for administration of emergency contraception comprising an oral contraceptive and an antiemetic wherein the antiemetic in immediate release formulation is administered prior to the administration of oral contraceptive.

23. A kit of claim 22 wherein the emergency contraceptive is progestin only pill or combination of estrogen and progestin.

24. A kit of claim 22, wherein antiemetic is selected from dopamine antagonist, 5HT3 receptor antagonist, anticholinergics, antihistamines, cannabinoids and other drugs.

25. A kit of claim 24, wherein antiemetic is meclizine.

26. A kit of claim 23 wherein the emergency contraceptive is levonorgestrel.