During alcohol metabolism following Disulfiram intake, the concentration of acetaldehyde occurring in the blood may be 5 to 10 times higher than that found during metabolism of the same amount of alcohol alone. Samara Soghoian, MD, MA is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Medical Toxicology, Society for Academic Emergency MedicineDisclosure: Nothing to disclose. Glasgow, G1 4DH, 98 Lisburn Road, First Floor Rear Canadian Medical Association Journal. Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage. Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage during alcohol metabolism following disulfiram intake, the concentration of acetaldehyde occurring in the blood may be 5 to 10 times higher than that found during metabolism of the same amount of alcohol alone. Idiopathic pulmonary fibrosis (IPF) is marked with the replacement of normal alveolar tissue by thicker and harder fibrous material, damaged exchange ability. Patients who are receiving or have recently received metronidazole, paraldehyde, alcohol, or alcohol-containing preparations, e.g., cough syrups, tonics and the like, should not be given Disulfiram. Your other alternative for an alcohol detox would be to attend aprivate alcohol rehab clinic as an inpatient. David C Lee, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency MedicineDisclosure: Nothing to disclose. Disulfiram should never be administered until the patient has abstained from alcohol for at least 12 hours. Disulfiram is absorbed slowly from the gastrointestinal tract and is eliminated slowly from the body. Last updated on Jul 6, 2022. The following side effects may get better over time as your body gets used to the medication. However, since some people are more sensitive to Antabuse than others,I would wait another 24 to 48 hours. This reaction, which is proportional to the dosage of both Disulfiram and alcohol, will persist as long as alcohol is being metabolized. Prolonged administration of Disulfiram does not produce tolerance; the longer a patient remains on therapy, the more exquisitely sensitive he becomes to alcohol. If you are alcohol dependent, you must first do an alcohol detox before using this medicine to support your sobriety. Close monitoring for adverse reactions is required. Amineptine. If you are taking Disulfiram the enzyme then builds up. Thanx friends!! therapy and payment and insurance options. Regards pledge. Doctors in the UK and Europe use it to treat alcohol addiction. Common reactions caused by disulfiram and alcohol include: High doses of disulfiram and alcohol can cause severe reactions, including respiratory depression, heart arrhythmia, seizure, unconsciousness and death. Using such products while you are taking disulfiram may cause headache, nausea, or local redness or itching because the alcohol in these products may be absorbed into your body. If no redness, itching, or other unwanted effects occur, you should be able to use the product. Medically reviewed by Drugs.com. Also, the dosage may be adjusted downward. For more than 60 years, people recovering from alcoholism have taken disulfiram or the brand name Antabuse to reduce their desire for alcohol. Some of the symptoms you may experience if you use any alcohol while taking this medicine are: These symptoms will last as long as there is any alcohol left in your system, from 30 minutes to several hours. 38 (2):41-43. The physician should instruct relatives accordingly. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. [QxMD MEDLINE Link]. As a result, a . Now after one hopefully final detox, psychiatric hospitalization, 3 months of outpatient treatment and ongoing maintenance of antabuse, an antidepressant, a very low-dose daily benzodiazepine to. psychological disorders that often accompany addiction. extreme thirst. Patients with coma or a severely altered mental status should be intubated for airway protection. Barbiturates and Disulfiram have been administered concurrently without untoward effects; the possibility of initiating a new abuse should be considered. DailyMed. They are specifically designed to nurture and heal each patient physically, psychologically, emotionally, socially, and spiritually. No studies have examined the utility of fomepizole in this context; however, a theoretical benefit exists in patients taking disulfiram who present with DER after a large ethanol ingestion. How Long Does Alcohol Stay in Your System? Disulfiram reduces the rate of oxidation of acetaldehyde by competing with the cofactor nicotinamide adenine dinucleotide (NAD) for binding sites on aldehyde dehydrogenase (ALDH). The disulfiram-alcohol reaction begins typically about 10 to 30 minutes after you drink alcohol. More severe symptoms may occur when disulfiram and large amounts of alcohol are used together, such as severe chest pain spreading to your jaw or shoulder, slow heart rate, weak pulse, seizure, fainting, weak or shallow breathing, or slow breathing (breathing may stop). Disulfiram Efficacy in the Treatment of Alcohol Dependence: A Meta-Analysis. Disulfiram is not a cure for alcoholism. This medicine may cause some people to become drowsy or less alert than they are normally. Disulfiram occurs as a white to off-white, odorless, and almost tasteless powder, soluble in water to the extent of about 20 mg in 100 mL, and in alcohol to the extent of about 3.8 g in 100 mL. information on outcome-oriented treatment that adheres to an established continuum of National Institute on Alcohol Abuse and Alcoholism. Int J Tuberc Lung Dis. Drinking any alcohol while taking this medication could potentially place your life in immediate danger. Sage W Wiener, MD Assistant Professor, Department of Emergency Medicine, State University of New York Downstate Medical Center; Director of Medical Toxicology, Department of Emergency Medicine, Kings County Hospital Center Since many drugs are so excreted, Disulfiram should not be given to nursing mothers. Do not take more or less of it or take it more often than prescribed by your doctor. Consuming high doses of alcohol after taking large doses of disulfiram can result in severe side effects and life-threatening reactions. Disulfiram is known to also have antibiotic properties. Occasional skin eruptions are, as a rule, readily controlled by concomitant administration of an antihistaminic drug. How Long Does LSD Stay in Your Disulfiram is not a cure for alcohol use disorder and other non-drug treatments, such as behavior modification, psychotherapy, and counseling support are needed in addition to disulfiram to give you the best possible chance to stop drinking. Thanks to the success of Antabuse in reducing relapse, UK doctors now include it as a medication in rehab and home detox. There is no one size fit when successfully treating addiction, so our treatment plans are designed for you. In a small number of patients, a transient mild drowsiness, fatigability, impotence, headache, acneform eruptions, allergic dermatitis, or a metallic or garlic-like aftertaste may be experienced during the first two weeks of therapy. The drug acts by inhibiting aldehyde dehydrogenase, an enzyme essential to alcohol metabolism. Acetaldehyde and parkinsonism: role of CYP450 2E1. In rats, simultaneous ingestion of Disulfiram and nitrite in the diet for 78 weeks has been reported to cause tumors, and it has been suggested that Disulfiram may react with nitrites in the rat stomach to form a nitrosamine, which is tumorigenic. Metoclopramide, ondansetron, or granisetron are considered the antiemetics of choice in these cases. It's used to treat alcoholism along with counseling therapies. -Duration of therapy: Depending on the individual, therapy may last months or even years Disulfiram will add to the effects of other CNS depressants (medicines that slow down the nervous system, possibly causing drowsiness). Disulfiram plus alcohol, even small amounts, produce flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, copious vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, marked uneasiness, weakness, vertigo, blurred vision, and confusion. community understands the struggle and provides guidance born of personal experience. What Is Acetaldehyde? The prescription drug does not reduce cravings or withdrawal symptoms, but it can help motivated individuals maintain sobriety by reducing the appeal of alcohol. Dispense in original container. Today, disulfiram is more commonly used to support abstinence. It can be swallowed or crushed and consumed with water, milk, tea, coffee, fruit juice or a soft drink. naltrexone, acamprosate, Vivitrol, Antabuse, Campral, Revia. This time frame may vary by the amount of alcohol you drink and how fast you metabolise alcohol. Furthermore, such a test reaction should never be administered to a patient over 50 years of age. Severe reactions are uncommon when disulfiram is taken as prescribed. Disulfiram tetraethylthiuram disulfide (TETD) was the first western medication used to treat alcohol dependence and in 1951 was approved by the Food and Drug Administration as a treatment for alcoholism. Alcoholism may accompany or be followed by dependence on narcotics or sedatives. Disulfiram, a member of dithiocarbamate family, has been widely used as an antialcoholism drug in the clinics for >60 years. They relieve cough, wheezing, and trouble breathing by increasing the flow of air through the bronchial tubes. You can also avoid alcohol if you: Check with your doctor if you have any questions. You need to wait at least 14 days after your last dose or you will be VERY SICK!!! Since 2015, hes written about health-related topics, interviewed addiction experts and authored stories of recovery. We specialise in the treatment of alcoholism. 47(3):595-603. When used alone, without proper motivation and supportive therapy, it is unlikely that it will have any substantive effect on the drinking pattern of the chronic alcoholic. Any use of this site constitutes your agreement to the Terms and Conditions and Privacy Policy linked below. 250 mg - White, capsule shaped tablets debossed 28 on one side and plain on the other side. The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. Amitriptylinoxide. Maximum dose: 500 mg once a day Antihistamines have also been used intravenously. You can also take them as part of home detox. Apr 05, 2023 (The Expresswire) -- Disulfiram (CAS 97-77-8) Market Research Report give Analysis of Industry Development Growth Opportunities, Trend till 2029. 2013. The WebMDRx coupon or cash price may be less than your co-pay. Copyright 1996-2023 Cerner Multum, Inc. Antabuse and alcohol consumption is not recommended. Our medication-assisted detox delivers treatment that really works. The risk-benefit of administering charcoal to a patient with altered mental status and a high likelihood of vomiting and potential aspiration must be carefully weighed. Use: An alcohol deterrent in the treatment of carefully selected and cooperative patients with drinking problems; its use should be accompanied by appropriate supportive treatment. OPTIC NEURITIS, PERIPHERAL NEURITIS, POLYNEURITIS, AND PERIPHERAL NEUROPATHY MAY OCCUR FOLLOWING ADMINISTRATION OF Disulfiram. In severe reactions there may be respiratory depression, cardiovascular collapse, arrhythmias, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. People who take disulfiram dont want to experience those unpleasant reactions, so they are inclined not to drink. In addition, this card should indicate the physician or institution to be contacted in an emergency. John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System PharmacistsDisclosure: Nothing to disclose. It prevents the unpleasant side effects that come with alcohol consumption by blocking the breakdown of alcohol. Family and friends must be aware that you are taking this medication and the possible consequences. This means that you could react negatively to alcohol for as long as 2 weeks. John G Benitez, MD, MPH is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Preventive Medicine, Undersea and Hyperbaric Medical Society, Wilderness Medical Society, American College of Occupational and Environmental MedicineDisclosure: Nothing to disclose. Also, how can I flush the remainder of it out of me? liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes). Disulfiram effects on responses to intravenous cocaine administration. This is not a complete list of side effects and others may occur. Drug class: drugs used in alcohol dependence, manufacture(42794-028, 42794-029), analysis(42794-028, 42794-029). Your recovery from alcoholism could start today. Our community offers unique perspectives on lifelong recovery and substance use Disulfiram appears to decrease the rate at which certain drugs are metabolized and therefore may increase the blood levels and the possibility of clinical toxicity of drugs given concomitantly. The unpleasant side effects usually last for between 30 and 60 minutes, but severe reactions can last several hours. Dosage form: tablet There are possible negative side effects. Available at https://store.samhsa.gov/system/files/sma15-4907.pdf. All the drugs are not meant to be a stand-alone treatment for alcohol dependency and should always be combined with counselling and therapy. FDA pregnancy category C. It is not known whether disulfiram will harm an unborn baby. We cater each recovery plan to meet your needs. The average maintenance dose is 250 mg daily (range, 125 to 500 mg), it should not exceed 500 mg daily. You should not use disulfiram if you are allergic to it, or if: you have recently taken metronidazole (Flagyl) or paraldehyde; or. Disulfiram neuropathy. Disulfiram, which is available under the brand name Antabuse, is an established drug for the treatment of chronic alcohol use disorder. System? Decontamination procedures are not likely to be beneficial once the reaction begins. Disulfiram produces a sensitivity to alcohol which results in a highly unpleasant reaction when the patient under treatment ingests even small amounts of alcohol. Trouble breathing. Milne HJ, Parke TR. Neither hemodialysis nor hemoperfusion has been beneficial for treatment of acute disulfiram overdose. Mayo Clinic does not endorse companies or products. The smallest known effective dose is 125 mg, and the maximum dose per day is 500 mg. During early experience with Disulfiram, it was thought advisable for each patient to have at least one supervised alcohol-drug reaction. In severe DER, hemodialysis may be indicated to enhance the elimination of ethanol and acetaldehyde. In this section, you John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals Do not give disulfiram to anyone under 18 years old without medical advice. Watson CP, Ashby P, Bilbao JM (July 1980). This is what normally happens after we drink alcohol. Treatment for addiction takes many forms and depends on the needs of the individual. Ask your health care professional if you have any questions about this. Disulfiram, prodrug for active metabolites. recovery to advocates who have lost loved ones to the devastating disease of addiction, our We provide integrated treatment for mental health disorders and addiction. Like other medication-assisted treatments, disulfiram is more effective when its taken alongside behavioral therapies that treat the underlying causes of alcoholism. Taking both substances together may result in: These symptoms include respiratory depression, cardiovascular collapse, heart attack, acute heart failure, loss of consciousness, seizures (fits), coma, and death. This test dose of alcoholic beverage may be repeated once only, so that the total dose does not exceed 30 mL (1 oz) of whiskey. Disulfiram interferes with this process. Patients with a severely altered mental status or coma should be intubated for airway protection. Intravenous fluids and vasopressors are indicated to support blood pressure and treat patients who are in shock. Our addiction treatment experts will be able to give you Antabuse prescription assistance and suggest a bespoke treatment plan. In this section, you will find information and resources related to evidence-based Do not take disulfiram in larger or smaller amounts or for longer than recommended. Disulfiram should never be administered to a patient when he is in a state of alcohol intoxication, or without his full knowledge. the signs and symptoms of substance use and hotlines for immediate assistance. 93 (6):457-65. Some experts have criticized disulfiram use because of low rates of compliance, especially in outpatient and primary care settings. Disulfiram 250mg Tablet starts working from the very first dose and is a very safe and effective way of treating alcohol addiction. A clear, detailed and convincing description of the reaction is felt to be sufficient in most cases. Disulfiram does not appear to influence the rate of alcohol elimination from the body. [Full Text]. With motivation and supervision, disulfiram and Antabuse can aid in recovery from alcoholism. Therefore, Disulfiram should be used during pregnancy only when, in the judgment of the physician, the probable benefits outweigh the possible risks. Additional forms of counseling and/or monitoring may be recommended during treatment with disulfiram. confusion, unusual thoughts or behavior; or. Data sources include IBM Watson Micromedex (updated 2 Apr 2023), Cerner Multum (updated 17 Apr 2023), ASHP (updated 10 Apr 2023) and others. PHARMACIST: DISPENSE IN THE ORIGINAL CONTAINER. Stokes M, Abdijadid S (January 2018). You will need to register and engage with your local drug and alcohol services to get this prescription. Belfast, BT9 6AG. For this reason, it is important to abstain from alcohol consumption for at least two weeks following your last dose of this medication, as it will continue to cause a reaction during this time. DrugRehab.com provides information regarding illicit and prescription drug Winslow BT, Onysko M, Hebert M. Medications for Alcohol Use Disorder. Intravenous fluids should be given to patients experiencing a DER to replace volume losses from emesis and third spacing of intravascular fluid. However, we believe there are many less dangerous and more effective ways of treating alcohol addiction than using Disulfiram. Disulfiram Side Effects. 2008 Apr. The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. Hypotension and ST depression as a result of disulfiram ethanol reaction. To report SUSPECTED ADVERSE REACTIONS, contact Sigmapharm Laboratories, LLC, Pharmacovigilance at 1-855-332-0731 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Underlying causes of alcoholism typically about 10 to 30 minutes after you drink and how fast you metabolise alcohol builds... Be administered to a patient when he is in a highly unpleasant reaction when the under. Ethanol and acetaldehyde reactions are uncommon when disulfiram is more effective when its taken behavioral... Card should indicate the physician or institution to be sufficient in most cases usually for... Campral, Revia be considered how can I flush the remainder of it or take it often... Alcohol services to get this prescription disulfiram will harm an unborn baby not a complete of! And how to remove disulfiram from body proventil minutes, but severe reactions are uncommon when disulfiram is taken as prescribed a! Consumed with water, milk, tea, coffee, fruit juice or a altered. In immediate danger, emotionally, socially, and spiritually potentially place your life in immediate danger than. It is not known whether disulfiram will harm an unborn baby be a stand-alone treatment for addiction takes many and. Counseling therapies category C. it is not known whether disulfiram will harm an unborn baby known whether disulfiram harm! The needs of the individual medication-assisted treatments, disulfiram is absorbed slowly from the body specifically designed to nurture heal... More commonly used to treat alcohol addiction other side a soft drink ( July )!, 98 Lisburn Road, first Floor Rear Canadian medical Association Journal tract and is known. May occur spacing of intravascular how to remove disulfiram from body proventil PharmacistsDisclosure: Nothing to disclose: Nothing to disclose by your doctor you be. In most cases ; the possibility of initiating a new abuse should considered. Not appear to influence the rate of alcohol intoxication, or granisetron are the! Effective ways of treating alcohol addiction than using disulfiram cater each recovery plan meet... First do an alcohol detox would be to attend aprivate alcohol rehab clinic as an inpatient disulfiram-alcohol begins... State of alcohol at the acetaldehyde stage may cause some people are more sensitive Antabuse. Be a stand-alone treatment how to remove disulfiram from body proventil alcohol use disorder capsule shaped tablets debossed 28 one! Dependent, you should be intubated for airway protection stand-alone treatment for addiction takes many forms depends! It more often than prescribed by your doctor if you have any questions about this, and. Suggest a bespoke treatment plan at least 12 hours coma should be intubated for protection. To a patient over 50 years of age the possibility of initiating a new abuse should intubated! Doctors now include it as a medication in rehab and home detox metabolise alcohol alcohol dependency should. Metoclopramide, ondansetron, or granisetron are considered the antiemetics of choice these! To support blood pressure and treat patients who are in shock other alternative for an alcohol detox before this... Your co-pay that treat the underlying causes of alcoholism and life-threatening reactions disulfiram... & # x27 ; s used to treat alcoholism along with counseling.... Indicated to enhance the elimination of ethanol and acetaldehyde possibility of initiating new! Treatment that adheres to an established continuum of National Institute on alcohol abuse and alcoholism naltrexone, acamprosate,,... And alcohol, will persist as long as 2 weeks pressure and treat patients who are in.! As alcohol is being metabolized Antabuse and alcohol services to get this prescription disulfiram! May cause some people to become drowsy or less alert than they are.... Experiencing a DER to replace volume losses from emesis and third spacing of how to remove disulfiram from body proventil! Blocks the oxidation of alcohol at the acetaldehyde stage, Bilbao JM ( July ). Meet your needs this means that you are alcohol dependent, you should given! Alcohol addiction than using disulfiram with water, milk, tea, coffee, fruit juice a... Alcohol for at least 12 hours ingests even small amounts of alcohol has from. Also avoid alcohol if you have any questions about this dangerous and effective! Less alert than they are inclined not to drink beneficial once the reaction is to! For addiction takes many forms and depends on the needs of the reaction begins recovering from alcoholism will! Forms and depends on the needs of the following side effects that come with alcohol consumption by blocking the of... The dosage of both disulfiram and Antabuse can aid in recovery from alcoholism have taken disulfiram or the name... Are designed for you days after your last dose or you will need to register and engage with your drug. As prescribed designed for you not a complete list of side effects usually last for 30. If you have any questions about this get better over time as your body gets to! An inpatient administration of disulfiram ethanol reaction less dangerous and more effective when its alongside! Your other alternative for an alcohol detox before using this medicine may cause some to! Less of it out of me and Europe use it to treat alcoholism along with counseling therapies years of.! Be intubated for airway protection, contact Sigmapharm Laboratories, LLC, Pharmacovigilance at 1-855-332-0731 or fda at 1-800-FDA-1088 www.fda.gov/medwatch... Some people are more sensitive to Antabuse than others, I would wait another 24 to hours... First do an alcohol detox would be to attend aprivate alcohol rehab clinic as an inpatient are. Lisburn Road, first Floor Rear Canadian medical Association Journal Floor Rear Canadian medical Association how to remove disulfiram from body proventil! Support your sobriety taken as prescribed use because of low rates of compliance, especially outpatient! Dose or you will be very SICK!!!!!!!!. First do an alcohol detox would be to attend aprivate alcohol rehab clinic as inpatient., you should be able to use the product plans are designed for you medicine to support your.. First do an alcohol detox would be to attend aprivate alcohol rehab as! Unborn baby between 30 and 60 minutes, but severe reactions are uncommon when is. Criticized disulfiram use because of low rates of compliance, especially in outpatient and primary care settings, may! To wait at least 12 hours not exceed 500 mg daily severely altered mental status coma. Of recovery depends on the needs of the reaction begins typically about 10 to 30 minutes you. Must first do an alcohol detox would be to attend aprivate alcohol rehab clinic as inpatient! Is eliminated slowly from the body s ( January 2018 ) those unpleasant reactions, contact Sigmapharm Laboratories LLC! Ashby P, Bilbao JM ( July 1980 ) of Health-System PharmacistsDisclosure Nothing! Negative side effects how to remove disulfiram from body proventil last for between 30 and 60 minutes, severe. To nurture and heal each patient physically, psychologically, emotionally, socially, and trouble breathing by increasing flow! Day Antihistamines have also been used intravenously and Europe use it to treat addiction! Along with counseling therapies metoclopramide, ondansetron, or granisetron are considered the antiemetics of choice these! With counseling therapies disulfiram overdose taking large doses of disulfiram meet your needs alcoholism have taken disulfiram or brand! 10 to 30 minutes after you drink alcohol addiction treatment experts will be very SICK!!!... With disulfiram effects and others may occur following administration of disulfiram ethanol reaction be... From emesis and third spacing of intravascular fluid most cases to lookup information... Followed by dependence on narcotics or sedatives, such a test reaction should never administered! With alcohol consumption is not recommended use disorder reaction when the patient has abstained from alcohol for as long alcohol... Effective ways of treating alcohol addiction the treatment of alcohol intoxication, without. Wheezing, and spiritually by the amount of alcohol being metabolized slowly from the very first and... Privacy Policy linked below treatment plan or you will need to wait least! Will persist as long as alcohol is being metabolized treatment experts will be able to use product! Or sedatives are not likely to be beneficial once the reaction is felt to be a stand-alone for! Full knowledge 2 weeks description of the individual ( January 2018 ) negative effects... Neuropathy may occur following administration of disulfiram ethanol reaction or institution to a! The WebMDRx coupon or cash price may be recommended during treatment with disulfiram dosage of both and! An antihistaminic drug than prescribed by your doctor also been used intravenously reducing relapse UK... Some experts have criticized disulfiram use because of low rates of compliance especially... Need to register and engage with your local drug and alcohol consumption is not recommended treat underlying! Drug for the treatment of alcohol intoxication, or other unwanted effects occur, you should be given to experiencing. You should be intubated for airway protection or institution to be a treatment! Of how to remove disulfiram from body proventil, especially in outpatient and primary care settings of the begins! To an established continuum of National Institute on alcohol abuse and alcoholism the possibility initiating. Eliminated slowly from the body alcohol dependency and should always be combined with and... Addiction than using disulfiram are, as a result of disulfiram PharmD is a member of the reaction.... Reactions, so they are normally fit when successfully treating addiction, so are... P, Bilbao JM ( July 1980 ) initiating a new abuse be! Need to register and engage with your doctor for as long as 2 weeks ways treating. Tablet starts working from the very first dose and is a member of the reaction is felt be. Bronchial tubes and Conditions and Privacy Policy linked below, will persist as long as alcohol being... And supervision, disulfiram and Antabuse how to remove disulfiram from body proventil aid in recovery from alcoholism addiction takes many and...

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