US 20120022122A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0022122 A1 Tokunaga (43) Pub. Date: Jan. 26, 2012

(54) TREATMENT AND PREVENTION OF Publication Classification DELETERIOUS EFFECTS ASSOCATED (51) Int. Cl. WITH ALCOHOL CONSUMPTION A6II 3/426 (2006.01) A6IP 25/32 (2006.01) (76) Inventor: Richard Tokunaga, Honolulu, HI (52) U.S. Cl...... 514/370 (US) (57) ABSTRACT The present invention provides to methods and compositions (21) Appl. No.: 13/248,375 that treat or prevent deleterious effects associated with alco hol consumption including alcohol-induced flush reaction and hangover. The methods and compositions include famo (22) Filed: Sep. 29, 2011 tidine and optionally succinic acid. The present invention further demonstrates compositions that include famotidine Related U.S. Application Data are effective at treating symptoms associated with a flush reaction in Subjects that are not significantly responsive to (62) Division of application No. 12/323,098, filed on Nov. treatments with the H1 antagonist loratidine or the H2 antago 25, 2008, now Pat. No. 8,058,296. nist cimetidine.

Patent Application Publication Jan. 26, 2012 Sheet 1 of 2 US 2012/0022122 A1

FIG. 1

F.G. 2 Patent Application Publication Jan. 26, 2012 Sheet 2 of 2 US 2012/0022122 A1

FIG. 3A

FIG. 3B US 2012/0022122 A1 Jan. 26, 2012

TREATMENT AND PREVENTION OF contributes to hangover, which is often felt by many the DELETERIOUS EFFECTS ASSOCIATED morning after alcohol consumption. Common hangover WITH ALCOHOL CONSUMPTION effects include headache, nausea, dizziness, fatigue, thirst, tension, anxiety, paleness, tremorand perspiration. It is com CROSS REFERENCE TO RELATED monly believed that black coffee or further consumption of APPLICATIONS alcohol in the morning reduces the symptoms; however, the effectiveness varies across individuals. 0001. The present invention is a divisional of U.S. patent 0007 Accordingly, there remains a need to develop new application Ser. No. 12/323,098, filed Nov. 25, 2008 and is methods and compositions for the treatment and prevention herein incorporated by reference in its entirety. of deleterious effects associated with alcohol consumption. TECHNICAL FIELD OF THE INVENTION SUMMARY OF THE INVENTION 0002 The present invention relates to the prevention or 0008. The present invention addresses deficiencies in treatment of effects associated with alcohol consumption and methods and compositions for the treatment or prevention of more specifically to methods and compositions for the treat deleterious effects associated with alcohol consumption and ment or prevention of alcohol-induced flush reaction and provides related benefits. This is accomplished by the com hangover. positions and their administration as provided herein. 0009. In one aspect of the present invention a composition BACKGROUND OF THE INVENTION for the prevention or reduction of deleterious effects associ 0003 Metabolism of alcohol involves a two step enzy ated with alcohol consumption is provided including an effec matic reaction. First, alcohol is oxidized to acetaldehyde by tive amount of each of famotidine and succinic acid and a alcoholdehydrogenase. Second, the acetaldehyde is oxidized pharmaceutically acceptable carrier. The composition is to acetic acid by acetaldehyde dehydrogenase and glu effective at preventing or reducing alcohol-induced flush tathione. Acetic acid is then transported to the muscles and reaction and hangover. The composition is particularly useful adipose tissue where it is further broken down into carbon for Subjects that do not significantly respond to treatments dioxide and water. Thus, the rate at which alcohol is metabo such as the H1 receptor antagonist loratidine or the H2 recep lized to acetic acid depends in part upon the balance of both tor antagonist cemetidine. alcohol dehydrogenase and acetaldehyde dehydrogenase. 10010. In another aspect of the present invention, a method This balance is important because although alcohol is toxic to for preventing or reducing alcohol-induced flush reaction and the body, acetaldehyde is actually more toxic than alcohol. hangover in a human is provided including administering to 0004 Polymorphisms in the acetaldehyde dehydrogenase the human an effective amount of a composition including gene correlate significantly to particular populations, such as famotadine and succinic acid with a pharmaceutically accept those having Asian ancestry and even more significantly to able carrier prior to imbibing in alcohol. Famotidine may be those having Japanese ancestry. These polymorphisms fre provided as the sole histamine receptor antagonist. The quently result in slowed conversion of acetaldehyde to acetic method may be particularly desired for humans that do not acid. Accordingly, without significant slowing of alcohol significantly respond to loratidine and/or cemetidine. dehydrogenase activity, acetaldehyde begins to buildup in the 0011. In another aspect of the present invention a method body. Rapid accumulation of acetaldehyde causes redness in for the prevention or reducing alcohol-induced flush reaction the skin, primarily along the face and limbs. This condition is in a human is provided including administering to the human referred to as alcohol-induced flush reaction, also known as an effective amount of famotidine as a sole histamine receptor Asian flush. antagonist prior to imbibing in alcohol and optionally suc 0005. A combination treatment for controlling alcohol cinic acid. induced flush reaction is proposed in published U.S. patent 0012. In another aspect of the present invention a method application Ser. No. 11/009,559. Specifically, the authors for treating alcohol-induced flush reaction in a human is propose a combined treatment prior to imbibing in alcohol, provided including administering to a human in need thereof the treatment including administering both an H1 receptor an effective amount of famotidine and a pharmaceutically histamine antagonist and a H2 receptor histamine antagonist. acceptable carrier. The proposed H1 receptor antagonists include terfenadine, astemisole and fenoxifene. The proposed H2 receptor antago BRIEF DESCRIPTION OF THE DRAWINGS nists included cimetidine, famotidine, nizatidine and raniti dine. Such treatments do not address the conversion of alco 0013 FIG. 1 is a structural formula of famotidine. hol to acetic acid but instead propose to competitively 0014 FIG. 2 is a structural formula of succinic acid. antagonize H1 and H2 histadine receptors while in circula 0015 FIG. 3A is a structural formula of cimetidine. FIG. tion, which temporarily reduces the appearance of symptoms. 3B is a structural formula of loratidine. However, the proposed treatments suffer from two draw DETAILED DESCRIPTION OF THE INVENTION backs. First, many that suffer from alcohol-induced flush reaction do not respond to many of the proposed antagonists, 0016. The present invention provides methods and com which indicates the antagonists are not interchangeable. Sec positions for the treatment, prevention or amelioration of ond, in some instances temporarily masking symptoms may symptoms associated with consumption of alcohol. In some lead to increased alcohol consumption, which may intensify embodiments, the present invention treats, prevents or deleterious effects once temporary relief ends. reduces hangover. In some embodiments, the present inven 0006 Although alcohol-induced flush reaction is typically tion treats, prevents or reduces symptoms associated with associated with redness that occurs relatively shortly after alcohol-induced flush reaction. The objects of the present consumption of alcohol, the build up of acetaldehyde also invention are accomplished by providing an effective amount US 2012/00221 22 A1 Jan. 26, 2012

of famotidine, Succinic acid, or a combination thereof. which is a component in the citric acid cycle. Esters of Suc Administration preferably occurs prior to imbibing in alco cinic acid are referred to as alkyl Succinates. Succinic acid is hol; however, in some embodiments the treatment is provided commercially available as dietary Supplement. Though non after or during imbibing in alcohol. limiting, it is believed that the addition of succinic acid will 0017. The preferred composition and methods of the accelerate the decomposition of acetaldehyde. This is present invention provide a sole histamine receptor antago believed to be due at least in part to its role in the citric acid nist, famotidine. The term "sole histamine receptor antago cycle. nist” refers to the use of famotidine without inclusion of an 0023 The compositions provided herein, namely famoti dine and/or Succinic acid are administered in an effective additional H1 or H2 receptor antagonist. Famotidine is a amount. The term “effective amount’ as used herein refers to white to pale yellow crystalline compound that is freely the amount of each active ingredient, which provides a ben soluble in glacial acetic acid, slightly soluble in methanol, eficial effect. With respect to famotidine, an effect amount very slightly soluble in water, and practically insoluble in significantly reduces symptoms associated with alcohol-in ethanol. It has a molecular weight of 337.43; an empirical duced flush reaction, such as decreased redness that is easily formula of CHN.O.S., and its structural formula is pro observable compared to no treatment or in Some instances vided as FIG. 1. The chemical name for famotidine is N'- compared to treatment with cimetidine or loratidine. Prefer (aminosulfonyl)-3-(2diaminomethyleneamino)-4-thiaz ably, increased redness is not visually observed at the face, olylmethylthio)propanamidine. limbs or torso. With respect to succinic acid, the effective 0.018. Like cimetidine, famotidine is a member of com amount prevents or reduces one or more hangover symptoms. pounds referred to histamine H2 antagonists (also referred to The effective amount may vary depending on route of admin as histamine-2 blockers). H2 antagonists selectively block istration and between individuals. In some embodiments the histamine H2 receptors and not histamine H1 receptors. effective amount is less than 20 mg for each of famotidine and Famotidine is commercially available under the brand names Succinic acid. For instance, the present invention provides a PEPCID and MYLANTA and is believed to decrease the study wherein 10 mg of famotidine significantly prevents amount of acid the stomach produces. Famotidine is adver redness while imbibing in alcohol. The present invention tised as a treatment for ulcers in the stomach and intestines, includes 10 mg as an effective amount of famotidine in the Zollinger-Ellison syndrome, gastroesophageal reflux disease prevention or treatment of alcohol-induced flush reaction or (GERD), and other conditions associated with the presence of when used in combination with Succinic acid; however, lower acid in the espophagus, causing heatburn. Famotidine is com doses such as about 1 mg to nearly 10 mg are also encom mercially available in doses of 20 mg and 40 mg. passed by the present invention. Succinic acid may be pro 0019. The examples provided herein demonstrate a series vided any effective amount Such as between about 1 mg and of exemplary studies that demonstrate famotidine is effective about 500 mg. In some embodiments, succinic acid is pro as a preventative treatment against symptoms associated with vided in 10 mg. In other embodiments. Succinic acid is pro alcohol-induced flush reaction. In addition, the studies dem vided between 20 mg and 100 mg: 100 mg and 250 mg: 250 onstrate famotidine is highly effective at low dose; whereas mg and 500 mg; or 500 mg and 750 mg. In a preferred cimetidine (another H2 antagonist) was minimally effective embodiment 200 mg of succinic acid was effective at reduc evenata higher dose. Thus the treatment effects of famotidine ing or eliminating hangover when provided in combination are not believed to be associated with all H2 antagonists. with 10 mg of famotidine. 0020. Although famotidine is effective at reducing alco 0024. Although the methods of the present invention hol-induced flush reaction, when combined with succinic encompass any Suitable administration technique known in acid the composition is also effective at preventing or reduc the pharmaceutical arts, in the preferred embodiment, the ing hangover. Famotidine may provide instant, near term or compositions are administered orally. Oral administration temporary relief and Succinic acid may provide prolonged may involve providing famotidine and/or Succinic acid in any relief. Accordingly, in Some embodiments famotidine and Suitable form Such as pill, capsule, oral syrup and the like. Succinic acid are provided with a pharmaceutically effective Techniques for the formation of Such compositions are well carrier for the prevention or treatment of deleterious effects known in the pharmaceutical arts and can be found in a variety associated with alcohol consumption. The composition may of pharmaceutical textbooks and publications, such as Rem reduce immediate deleterious effects such as redness and may ington's Pharmaceutical Sciences (Mack Publishing Co., reduce or prevent hangover. Eaton, Pa.), the contents of which are herein incorporated by 0021 Hangovers are believed to be multi-causal. First, reference in its entirety. The compositions typically involve ethanol is a diuretic, which increases urine production, and mixing the active ingredient or a salt thereof in the presence of thus has a dehydrating effect. Dehydration leads to symptoms a Suitable carrier, also referred to as a pharmaceutically such as headache, dry mouth and lethargy. Second, NADH is acceptable carrier. Thus, the active ingredients may be mixed accumulated from the metabolism of alcohol from alcohol with diluents, excipients or other carriers used in the pharma dehydrogenase enzyme. Excess NADH can slow down glu ceutical arts. Further, active ingredients may be mixed with coneogenesis in the liver, which causes hypoglycemia. Third, solublizers, stabilizers, buffering agents, coloring agents, fla when ethanol is metabolized it is converted to acetaldehyde. Voring agents, emulsions and the like as performed and Acetaldehyde dehydrogenase breaks acetaldehyde into acetic known in pharmaceutical practice. acid. Acetylaldehyde is about 10 to 30 times more toxic than EXAMPLES ethanol. Example 1 0022. Succinic acid, also known as butanedioic acid or ethane-1,2-dicarboxylic acid, has the formula CHO and Prevention of Alcohol-Induced Flush Reaction in the structure of such is provided as FIG. 2. At room tempera Subjects Treated with Famotidine ture Succinic acid is a solid that forms colorless, odorless 0025. The following examples demonstrate the prevention crystals. The carboxylate anion is referred to as Succinate, or reduction of symptoms associated with alchohol-induced US 2012/00221 22 A1 Jan. 26, 2012

flush reaction. As control, each subject was tested without to imbibe any alcoholic beverage, CA orally self-adminis treatment. As a second control, each Subject was treated with tered 300 mg of cimetidine (TAGAMET) in tablet form. either loratidine (an H antagonist) or cimetidine (an H2 Subsequently/after drinking 2 alcoholic beverages over about antogonist). Cimetidine is shown as FIG.3A andloratidine is three hours time, CA still experienced a facial flushing reac shown as FIG. 3B. Each subject was also treated with famo tion and an increased heart rate as a result of his intake of tidine in a Subsequent study. The results are summarized in alcohol. Thus, the flushing blockade remained generally inef tables 1-4 that follow. fective with the use of cimetidine by itself. 0034) To examine potential treatment with famotidine, Subject 1: Patent LB Patient CA also underwent a protocol of medical treatment to 0026 Patient LB is a female, is 27 years old and weighs control alcohol-induced flushing. In accordance with the 115 lbs. She is not taking any medications presently. There is treatment protocol, about forty five (45) minutes before the no other medical history of consequence. next Social occasion when she was expecting (or intending) to 0027 Ms. LB drinks alcohol socially on occasion, usually imbibe mixed cocktails or any other alcoholic beverage, CA in the form of Vodka. After imbibing several glasses of Vodka, orally self-administered 10 mg of famotidine in chewable however, LB consistently finds that she has a flushing of the tablet form. Subsequently, after then drinking cocktails over a face and torso. Via her own history and symptoms, Patient LB time period of about 4 hours duration, CA experienced no is demonstrably susceptible to alcohol-induced flushing. flushing reactions of the face. Thus, the flushing blockade 0028. To examine potential treatment with loratidine (an never became ineffective over the duration of the social drink H1 histamine antagonist), Patient LB underwent a protocol of ing occasion. In addition, CA experienced no undesired side medical treatment to control alcohol-induced facial flushing. effects whatsoever; in particular, CA felt no drowsiness or In accordance with the treatment protocol, about forty five sedation over the entire duration of the flushing blockade and (45) minutes before the next social occasion when she was the Social drinking occasion. expecting (or intending) to imbibe any alcoholic beverage, 0035. The effects were slightly less aggressive when tak LB orally self-administered 20 mg of loratadine (CLAR ing cimetidine alone compared to no treatment but the present ITIN) in tablet form. Subsequently/after drinking 3 alcoholic study shows that the use of famotidine proved to be much beverages over about three to four hours time, LB experi more effective than cimetidine or no treatment. enced a facial flushing reaction and an increased heart rate as a result of her intake of alcohol. Thus, the flushing blockade Subject 3: Patient YT remained ineffective with the use of loratadine by itself. 0036 Patient YT is a female, is 61 years old and weighs 0029. To examine potential treatment with famotidine, 155 lbs. She is taking Ambien (by prescription) presently. She Patient LB again underwent a protocol of medical treatment has no other medical history of consequence. to control alcohol-induced flushing. In accordance with the treatment protocol, about forty five (45) minutes before the 0037 Ms. YT drinks alcohol socially on occasion, usually next Social occasion when she was expecting (orintending) to in the form of wine. By her own admission, YT typically imbibe Vodka or any other alcoholic beverage, LB orally drinks ten (10) or more glasses of wine per week. After self-administered 10 mg of famotidine in chewable tablet imbibing wine, however, YT consistently has headaches and form. Subsequently, after then drinking 2-3 glasses of Vodka has a marked flushing of the face and torso. Via her own over several hours time, LB experienced no flushing reac history and symptoms, Patient YT is clearly susceptible to tions, either of the face or of the torso. Thus, the flushing alcohol-induced flushing. blockade never became ineffective over the duration of the 0038. To examine potential treatment with loratadine, Social drinking occasion. In addition, LB experienced no Patient YT underwent a protocol of medical treatment to undesired side-effects whatsoever; in particular, LB felt no control alcohol-induced facial flushing. In accordance with drowsiness or sedation over the entire duration of the flushing the treatment protocol, about forty five (45) minutes before blockade and the Social drinking occasion. the next Social occasion when she was expecting (or intend 0030 Thus, famotidine but not loratidine provided an ing) to imbibe any alcoholic beverage, YT orally self-admin effective preventative treatment against alchohol-induced istered 20 mg of loratadine (CLARITIN) in tablet form. Sub flush reaction for Patient LB. sequently/after drinking 3 alcoholic beverages over about three to four hours time, YT experienced a facial flushing Subject 2: Patient CA reaction and an increased heart rate as a result of her intake of alcohol. Thus, the flushing blockade remained ineffective 0031. Patient CA is a male, is 29 years old and weighs 165 with the use of loratadine by itself. lbs. He is taking no medication presently and also has no prior 0039. To examine potential treatment with famotidine, medical history of consequence. Patient YT underwent a protocol of medical treatment to 0032. Mr. CA drinks alcohol socially, usually in the form control alcohol-induced flushing. In accordance with the of mixed cocktails known as 'Vodka/RedBull', after imbib treatment protocol, about forty five (45) minutes before the ing several alcoholic cocktails; however, CA routinely finds next Social occasion when she was expecting (or intending) to that he has undergone a marked flushing of the face. Via his imbibe wine or any other alcoholic beverage, YT orally self own history and symptoms, Patient CA is demonstrably sus administered 10 mg of famotidine in chewable tablet form. ceptible to alcohol-induced flushing. Subsequently, after then drinking multiple glasses of wine 0033. To examine potential treatment with cimetidine, over four (4) hours time, YT experienced no flushing reac Patient CAthen underwent a protocol of medical treatment to tions of the face or of the torso. In addition, YT experienced control alcohol-induced facial flushing. In accordance with no undesired side-effects whatsoever; in particular, YT felt no the treatment protocol, about forty five (45) minutes before drowsiness or sedation over the entire duration of the flushing the next Social occasion when he was expecting (orintending) blockade and the Social drinking occasion. US 2012/00221 22 A1 Jan. 26, 2012

0040 Thus, famotidine but not loratidine provided an tered 20 mg of loratadine (CLARITIN) in tablet form. Sub effective treatment in the prevention of alchohol-induced sequently/after drinking 1 alcoholic beverage overa one hour flush reaction for Patient YT. time, CJR experienced a facial flushing reaction and an increased heart rate as a result of his intake of alcohol. Thus, Subject 4: Patient MC the flushing blockade remained ineffective with the use of 0041. Patient MC is a female, is 24 years old and weighs loratadine by itself. 110 lbs. She is taking birth control medication. She has no 0049. To examine potential treatment with famotidine, other medical history of consequence. Patient CJR underwent a protocol of medical treatment to 0042. Ms. MC drinks alcohol socially on occasion, usually control alcohol-induced flushing. In accordance with the in the form of beer and tequila. After imbibing several glasses treatment protocol, about forty five (45) minutes before the of beer or alcohol, however, MC routinely finds that a flushing next Social occasion when he was expecting (or intending) to of the face results and nausea. Via her own history and Symp imbibe any alcoholic beverage, CJR orally self-administered toms, Patient MC is susceptible to alcohol-induced facial 10 mg of famotidine in chewable tablet form. Subsequently, flushing. after drinking 5 alcoholic beverages over about five hours 0043. To examine potential treatment with cimetidine, time, CJR experienced neither a facial flushing reaction nor Patient MC underwent a protocol of medical treatment to any nasal congestion. Thus, the flushing blockade remained control alcohol-induced facial flushing. In accordance with effective over the five hours time of his social drinking occa the treatment protocol, about forty five (45) minutes before sion. In addition, CJR experienced no undesired side-effects the next Social occasion when she was expecting (or intend whatsoever; in particular, CJR felt no drowsiness or sedation ing) to imbibe any alcoholic beverage, MC orally self-admin over the duration of the flushing blockade. istered 300 mg of cimetidine (TAGAMET) in tablet form. 0050. However, on this occasion, CJR chose to continue Subsequently/after drinking 2 alcoholic beverages over about his consumption of alcoholic beverages beyond six drinks a two hours time, MC still experienced a facial flushing reac and for an extended period of time greater than six hours. The tion, increased heart rate, as well as a headache as result of his duration of effective facial flushing blockade did not extend intake of alcohol. Thus, the flushing blockade remained gen beyond the initial five hours time period; and CJR showed erally ineffective with the use of cimetidine by itself. specific symptoms as a result of him continuing intake of 0044) To examine potential treatment with famotidine, alcohol, including facial flushing, an increased heart rate, and Patient MC underwent a protocol of medical treatment to nasal congestion. control alcohol-induced facial flushing. In accordance with 0051. Thus, famotidine but not loratidine provided an the treatment protocol, about forty five (45) minutes before effective treatment in the prevention of alchohol-induced the next Social occasion when she was expecting (or intend flush reaction for Patient CJR and the protective effect of ing) to imbibe beer or any other alcoholic beverage, MC famotidine dissipated after a period of about five hours. orally self-administered 10 mg of famotidine in chewable tablet form Then Subsequently, in spite of drinking 2 ounces TABLE 1 of tequila and 5 glasses of beer over more than six (6) hours drinking time, MC nevertheless experienced no facial flush Initial Measurements No Treatment & No Alcohol ing reaction. Thus, the flushing blockade never became inef Subject Initials Sex Weight (lbs) Temp (F.) Heart rate fective over the more than six hour duration of MC's social 1 LB F 115 97.4 74 drinking. In addition, MC experienced no undesired side 2 CA M 16S 98.1 84 effects whatsoever; in particular, MC felt no drowsiness or 3 YT F 145 97.7 78 sedation over the entire duration of the flushing blockade and 4 MC F 110 96.5 72 the Social drinking occasion. 5 CJR M 185 97.1 81 0045. In summary, the effects were slightly less aggressive when taking cimetidine alone when compared to no treatment but the present study shows that the use of famotidine proved TABLE 2 to be much more effective than cimetidine to preventalchohol induced flushing for Patent MC. Control Measurements Alcohol Exposure without Treatment Subject Initials Sex Treatment Temp (F.) Heart rate Subject 5: Patient CJR 1 LB F None 97.1 89 0046 Patient CJR is a male, is 30 years old and weighs 185 2 CA M None 98.0 97 lbs. He has no other medical history of consequence. 3 YT F None 97.5 93 4 MC F None 97.1 87 0047 Mr. CJR drinks alcohol socially on occasion, but 5 CJR M None 96.9 91 without preference as to alcoholic form. After imbibing only a few alcoholic drinks, however, CJR consistently finds that he has a flushing of the face and also experiences nasal con gestion. Via his own history and symptoms, Patient CJR is TABLE 3 demonstrably susceptible to alcohol-induced flushing. Control Treatment (Loratidine or Cimetidine) with Alcohol 0048. To examine potential treatment with loratidine, Patient CJR underwent a protocol of medical treatment to Subject Initials Sex Treatment Temp (F.) Heart rate control alcohol-induced facial flushing. In accordance with 1 LB F Loratidine 97.1 89 the treatment protocol, about forty five (45) minutes before 2 CA M Cimetidine 98.0 97 the next Social occasion when he was expecting (orintending) 3 YT F Loratidine 97.5 93 to imbibe any alcoholic beverage, CJR orally self-adminis US 2012/00221 22 A1 Jan. 26, 2012

tially of a therapeutically effective amount of famotidine and TABLE 3-continued Succinic acid in a therapeutically acceptable carrier. 2. The composition according to claim 1, wherein the Control Treatment (Loratidine or Cimetidine) with Alcohol therapeutically effective amount of famotidine is at least 10 Subject Initials Sex Treatment Temp (F.) Heart rate ng. 3. The composition according to claim 2, wherein the 4 MC F Cimetidine 97.1 87 therapeutically effective amount of famotidine is at least 20 5 CJR M Loratidine 96.9 91 ng. 4. The composition according to claim 1, wherein the therapeutically effective amount of Succinic acid is from 1 mg TABLE 4 to 500 mg. 5. The composition according to claim 4, wherein the Famotidine Treatment with Alcohol therapeutically effective amount of succinic acid is 200 mg. Subject Initials Sex Treatment Temp (F.) Heart rate 6. The composition according to claim 1, wherein the therapeutically effective amount of famotidine is at least 10 1 LB F Famotidine 97.3 77 mg and the therapeutically effective amount of Succinic acid 2 CA M Famotidine 98.2 82 3 YT F Famotidine 97.4 84 is 200 mg. 4 MC F Famotidine 97.1 78 7. The composition according to claim 1, wherein the car 5 CJR M Famotidine 97.3 83 rier is suitable for oral administration to the subject. 8. A composition for the treatment of alcohol induced flush reaction and hangover in a subject that is not effectively Example 2 treated by administration of a sole histamine receptor antago nist of loratidine or cemetidine, the composition consisting Prevention of Alcohol Flush Reaction and Hangover essentially of a therapeutically effective amount of famoti by Administration of Famotidine and Succinic Acid dine and Succinic acid in a therapeutically acceptable carrier. 0.052 To test whether both alcohol flush reaction and 9. The composition according to claim 8, wherein the hangover could be prevented, four subjects susceptible to therapeutically effective amount of famotidine is at least 10 both alcohol flush reaction and hangover were given a com ng. bination of famotidine and succinic acid prior to imbibing in 10. The composition according to claim 9, wherein the alcohol. Previous studies with famotidine alone did not therapeutically effective amount of famotidine is at least 20 appear to significantly reduce or eliminate symptoms associ ng. ated with hangover. Each subject was given 10 mg famotidine 11. The composition according to claim 8, wherein the and 200 mg. Succinic acid prior to imbibing in alcohol. After therapeutically effective amount of Succinic acid is from 1 mg wards each ingested sufficient alcohol that would ordinarily to 500 mg. result in both flush reaction and hangover. None of the four 12. The composition according to claim 11, wherein the tested individuals indicated flush symptoms or symptoms therapeutically effective amount is 200 mg. associated with hangover. Thus, the results show the combi 13. The composition according to claim 8, wherein the nation of both famotidine and Succinic acid prevents alcohol therapeutically effective amount of famotidine is at least 10 flush reaction and hangover. mg and the therapeutically effective amount of Succinic acid 0053. The present invention is not to be restricted in scope is 200 mg. not limited in form except by the claims attached hereto. 14. The composition according to claim 8, wherein the What is claimed is: carrier is suitable for oral administration to the subject. 1. A composition for the treatment of alcohol induced flush reaction and hangover in a human Subject, consisting essen c c c c c