U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Substance Abuse and Mental Health Services Administration 

Center for Substance Abuse Treatment 

www.samhsa.gov 

Substance Abuse Treatment

ADVISORY 
 

Breaking News for the Treatment Field 

Fall 2005
 

Volume 4
 

Issue 1
 

Acamprosate: A New Medication 

for Alcohol Use Disorders 

What is acamprosate? 

Acamprosate (calcium acetyl homotaurinate) is a 

new prescription medication to help people who 

are alcohol dependent. Acamprosate is the third 

medication, after disulfiram (Antabuse®) and 

naltrexone (ReVia®), to receive U.S. Food and Drug 

Administration (FDA) approval for postwithdrawal 

maintenance of alcohol abstinence. It is the first 

new medication approved for this purpose in a 

decade. FDA approved acamprosate in July 2004. 

It became available in the United States in January 

2005, under the trade name Campral® DelayedRelease Tablets. Acamprosate has been used for 

nearly 20 years in Europe, where it has been found 

to be safe and effective for treating alcohol 

dependence (Mann et al. 2004; Tempesta et al. 

2000). 

How does acamprosate work? 

Chronic, heavy use of alcohol affects several 

neurotransmitter systems in the brain. These neurotransmitter systems adapt to the chronic presence 

of alcohol. Once they have adapted, these systems 

are only in equilibrium with alcohol. When alcohol 

use ceases, the systems become disregulated and 

enter a pathologic hyperexcitatory state. It is 

thought that acamprosate helps modulate and 

normalize brain activity, particularly in the 

glutamate and gamma-aminobutyric acid (GABA) 

neurotransmitter systems. Although acamprosate’s 

mechanism of action has not been clearly established, 

it may work by reducing symptoms of postacute 

(protracted) withdrawal, such as insomnia, anxiety, 

and restlessness. 

How does acamprosate’s 

activity compare with that of

other medications used to treat 

alcohol dependence? 

Acamprosate differs in significant ways from 

disulfiram and naltrexone, the other two agents 

approved by FDA for alcohol abstinence maintenance (table 1). 

Disulfiram, used to treat alcohol dependence for 

decades, is an aversive medication that inhibits 

aldehyde dehydrogenase and leads to increased 

levels of acetaldehyde. When a person taking disulfiram drinks alcohol, the increased acetaldehyde 

causes severe physical reactions such as facial 

flushing, nausea, vomiting, low blood pressure, 

headache, and weakness. Disulfiram does not 

reduce craving or normalize brain functioning, 

as acamprosate and naltrexone are believed to do. 

Instead, disulfiram’s effectiveness depends on the 

patient’s reluctance to suffer the aversive effects 

of drinking when on disulfiram. 
Fall 2005, Volume 4, Issue 1 

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Table 1: Comparison of Drugs Approved for Maintenance of Abstinence From Alcohol 

Medication Acamprosate (Campral) Disulfiram (Antabuse) Naltrexone (ReVia) 

Mechanism 

of Action 

Is not completely understood; 

appears to modulate/normalize 

alcohol-disrupted brain activity, 

particularly in the GABA and glutamate neurotransmitter systems; 

does not cause sickness if alcohol 

is ingested; reduces craving for 

alcohol 

Inhibits aldehyde dehydrogenase 

causing sickness (e.g., flushing, 

nausea, headache, sweating, weakness, increased blood pressure) 

when alcohol is ingested; does not 

reduce craving 

Blocks brain opioid receptors; 

eliminates euphoria associated with 

alcohol use; makes alcohol use less 

rewarding; does not cause sickness if 

alcohol is ingested; reduces craving 

Optimal 

Patient Status 

Abstinence at treatment initiation, 

immediately following acute withdrawal; commitment to recovery 

Patients who relapse while taking 

acamprosate may benefit from 

continuing the medication 

Abstinence at treatment initiation 

and during ongoing administration; 

commitment to recovery 

Abstinence at treatment initiation 

Patients who relapse while taking 

naltrexone may benefit from 

continuing the medication 

Examples 

of Drugs 

Causing 

Interactions 

None known Metronidazole (Flagyl®); paraldehyde; medications containing 

alcohol; and phenytoin, warfarin, 

isoniazid, rifampin, diazepam, 

chlordiazepoxide, imipramine, desipramine, and oral hypoglycemics 

Opioid-containing medications, 

thioridazine, yohimbine, and oral 

hypoglycemics 

Side Effects Most common: diarrhea and 

intestional cramps, itchiness, 

dizziness, muscle weakness, 

headache, flatulence, nausea, 

anxiety, and insomnia 

Less common, but more serious: 

depression and suicide risk 

Most common: disulfiram-alcohol 

reaction (can be serious) 

Common but usually mild and selflimiting: drowsiness, metallic taste, 

headache, impotence, and acne 

Less common, but more serious: 

liver toxicity, peripheral neuropathy, 

psychosis, and delirium 

Most common: opioid withdrawal 

symptoms (insomnia, nausea, vomiting, anxiety, headache, abdominal 

pain, muscle aches, rash, dizziness, 

fatigue, constipation, and chills) 

Less common, but more serious: 

potential liver toxicity (especially at 

high doses) and suicidal ideation 

Contraindications and 

Cautions 

Hypersensitivity to the drug; 

severe renal (kidney) impairment 

(creatinine clearance <30 mL/min) 

Dosage may be modified for moderate renal impairment (creatinine 

clearance 30–50 mL/min) 

Use with older adults or with 

patients with depression only 

when potential benefits justify 

potential risk 

FDA pregnancy category C* 

Hypersensitivity to the drug, 

significant liver disease, alcohol 

still in system, psychosis, coronary 

artery disease, paraldehyde use, 

diabetes, and severe metronidazole 

use 

FDA pregnancy category C* 

Hypersensitivity to the drug, any 

use of narcotic analgesics, liver 

disease, and acute opioid withdrawal 

FDA pregnancy category C* 

*FDA pregnancy category C: Animal studies have indicated potential fetal risk OR have not been conducted and no or insufficient 

human studies have been done. The drug should be used with pregnant or lactating women only when potential benefits justify 

potential risk to the fetus or infant. 

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Naltrexone (an opioid antagonist) blocks opioid 

receptors, leading to reductions in craving and in the 

reinforcing effects of alcohol. Unlike naltrexone, 

acamprosate does not affect the action or subjective 

effects of alcohol (Brasser et al. 2004). 

Patients with liver damage usually cannot use either 

naltrexone or disulfiram. However, because acamprosate 

is not metabolized in the liver, patients with liver 

damage can safely take the medication. 

Preliminary evidence suggests that treatment outcomes 

improve when acamprosate is combined with naltrexone 

or with disulfiram, particularly for patients who 

responded poorly to therapy with any of these medications alone (Besson et al. 1998; Kiefer and Wiedemann 

2003; Kiefer et al. 2003). Combination therapy also 

has been found to be safe. No specific protocol for 

combination therapy has been established as yet, but 

the results of a large national study, sponsored by the 

National Institute on Alcohol Abuse and Alcoholism, 

will be available soon. The study, Combining 

Medications and Behavioral Interventions (COMBINE), 

examines the effects of naltrexone and acamprosate 

and two psychosocial therapies, alone and in various 

combinations. 

Are there side effects or drug

interactions with acamprosate? 

The most common side effects experienced by people 

taking acamprosate are diarrhea, insomnia, anxiety, 

muscle weakness, nausea, itchiness, and dizziness. 

Uncommon, but serious, side effects include depression 

and suicidal thoughts. Most side effects are usually mild 

and transient, lessening or disappearing within the first 

few weeks of treatment. 

Acamprosate has not been found to be associated with 

any significant drug (including alcohol) interactions and 

does not affect the action of coadministered disulfiram, 

diazepam, nordiazepam, imipramine, desipramine, 

selective serotonin reuptake inhibitors, naltrexone, or 

naltrexol. No adjustment of dosage is recommended in 

patients taking these other medications. 

Can acamprosate be used for

detoxification? 

Research on the effectiveness of acamprosate in treating 

the symptoms of acute withdrawal has been inconclusive, and FDA has not approved its use for this purpose. 

However, patients who are already taking acamprosate 

and who relapse may be medically withdrawn from 

alcohol without discontinuing acamprosate. 

How safe is acamprosate? 

Acamprosate is not addicting and appears to have no 

potential for abuse; patients maintained on the drug 

have developed no known tolerance for or dependence 

on it. It also carries little overdose risk. Even at overdoses up to 56 grams (a normal daily dose is 2 grams), 

acamprosate was generally well tolerated by patients 

(Thomson Healthcare, Inc. 2005). 

Because acamprosate is not metabolized by the liver, it 

can be used by individuals with liver disease. Because 

acamprosate is excreted primarily from the kidneys, 

patients with severe renal impairment (creatinine 

clearance <30 mL/min) should not use acamprosate. 

Those with moderate renal impairment (creatinine 

clearance 30–50 mL/min) may be able to take the 

medication with dosage adjustments and careful 

monitoring. 

3 
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Patients should be told to be cautious about driving 

or operating heavy machinery until they know how 

acamprosate will affect their ability to engage in these 

activities and until they have adjusted to any effects 

of the drug. 

In clinical trials, suicidal events (suicidal ideation, 

attempted suicides, completed suicides), although rare, 

were more common in acamprosate-treated participants 

than in participants receiving placebo. Patients should 

be monitored for symptoms of depression or suicidal 

thinking. Families and caregivers should be informed 

of the need to monitor their family members for these 

signs and report their occurrence to the substance abuse 

treatment counselor or prescribing professional. 

Use of acamprosate during pregnancy has not been 

studied with humans. Animal studies of acamprosate 

and pregnancy have found some potential fetal risk. The 

potential risk of taking acamprosate during pregnancy 

should be balanced with the potential benefits (considering the known adverse effects of alcohol, particularly 

the risk of fetal alcohol syndrome). 

The use of acamprosate by older adults or by children 

has not been studied. Because of the higher risk of 

diminished renal function among older adults, acamprosate should be used with caution with this population. 

Campral Dosage and Timing 

•	 The recommended dosage of Campral is two 

333 mg tablets three times a day, with or without 

food. 

•	 Treatment with acamprosate should be initiated 

as soon as possible after alcohol withdrawal and 

should be maintained if the patient relapses. 

•	 Treatment duration at this dosage ranged from 

3 to 12 months in clinical trials.
 

•	 The manufacturer recommends treatment
 

duration of 1 year. 

How can treatment providers

incorporate acamprosate into their

programs? 

Treatment program staff should be well educated about 

acamprosate and its effects and be able to educate clients 

about the medication. Acamprosate is a prescription 

medication, so treatment providers need to be able to 

provide the medication and medically monitor the 

patient, either on site or through relationships with 

medical professionals in the community. 

Treatment providers should assess patients’ clinical 

appropriateness for acamprosate. Patients who have been 

in treatment multiple times but have been unable to 

sustain abstinence or those for whom disulfiram or 

naltrexone or both have not been effective may be 

particularly appropriate candidates for acamprosate. 

However, given the medication’s good safety profile, 

patients new to treatment also may be considered good 

candidates for acamprosate therapy. A good candidate 

also is interested in trying the medication and willing 

and able to take it regularly as prescribed. 

Motivation is an important factor. Clinical trials found 

that participants receiving acamprosate who were 

motivated and committed to total abstinence at the start 

of treatment had lower relapse risk than less motivated 

participants (FDA Psychopharmacologic Drugs Advisory 

Committee 2002). Less motivated patients are those 

whose personal goals, for instance, allow for slips, controlled drinking, other modified alcohol consumption, 

or other substance abuse. Research has not documented 

the effectiveness of acamprosate with patients who use 

multiple substances in addition to alcohol. 

Researchers also have looked at whether certain clinical 

characteristics (e.g., age of onset of alcohol use disorder, 

level of craving, gender, family history of alcohol use) 

4 
Acamprosate 

Substance Abuse Treatment 

ADVISORY .............................................................................. 
 

might predict which individuals are more likely than 

others to abstain from alcohol successfully on acamprosate. 

This research did not find a relationship between patient 

characteristics and successful acamprosate therapy (Verheul 

et al. 2005). Any patient who is found to be both medically 

and motivationally appropriate for acamprosate therapy 

and wants to try the medication should be given the 

opportunity. 

Once the treatment provider and patient decide that 

acamprosate may help, the client should be referred to a 

person who can prescribe it. The prescribing professional 

should assess the patient’s medical appropriateness for 

therapy with acamprosate by conducting a medical 

examination, including laboratory tests to obtain baseline 

readings of kidney function. 

Medications for alcohol use disorders do not replace 

counseling. Individuals taking acamprosate should be 

expected to participate fully in a treatment program’s 

activities, including attending 12-Step or mutual-help 

group meetings. In addition, they may need ongoing 

motivational counseling specifically geared to helping 

them comply with a drug regimen. 

Regular communication between treatment providers 

and the prescribing medical professional is essential. In 

particular, treatment providers need to communicate 

information concerning the patient to the prescribing 

professional such as 

•	 Reported or detected drinking or drug use episodes 

•	 Patient concerns about side effects 

•	 Issues affecting the patient’s safety (suicidal ideation, 

reported or observed increase in levels of depression or 

anxiety, or significant physical complaints) 

•	 Medication compliance issues 

•	 Expressed desire to stop taking the medication 

What To Tell the Patient 

Treatment program staff can support patients 

taking acamprosate by educating them about the 

drug, including 

•	 Informing them about the benefits and 

limitations of the medication 

•	 Informing them that it can take 5 to 8 days 

before acamprosate is fully effective 

•	 Stressing the importance of taking the 

medication as prescribed 

•	 Encouraging them to talk to their prescribing 

professional about the duration of acamprosate 

therapy 

•	 Encouraging them to talk to their prescribing 

professional about other medications they are 

taking 

•	 Encouraging them to report side effects of the 

drug and explaining that most of these resolve 

fairly quickly 

•	 Encouraging women to inform all treatment 

providers immediately if they become pregnant 

during therapy, if they are trying to become 

pregnant, or if they are breast-feeding 

•	 Stressing the importance of continuing 

counseling and 12-Step or mutual-help group 

participation 

•	 Stressing the need for caution in driving or 

operating heavy machinery until they are 

certain that acamprosate has no adverse effects 

on their participation in these activities and 

they have adjusted to the drug 

•	 Advising them to continue taking the 

medication if a slip or relapse occurs and to 

inform their counselor and prescribing 

professional immediately 

(continued on page 6) 

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ADVISORY .............................................................................. 
 

Treatment providers should encourage patients to talk 

directly to their prescribing professionals about these and 

other issues or questions they may have. 

How long should an individual take

acamprosate? 

The manufacturer of acamprosate recommends that 

acamprosate therapy be continued for 1 year (the effectiveness and safety of the medication have not been 

evaluated for periods of use longer than a year). Given 

that guideline, the length of time a particular patient takes 

acamprosate will be determined, ideally, with input from 

the prescribing professional, the treatment provider, and 

the patient. Discontinuation of acamprosate may be considered once a patient has achieved stable abstinence from 

alcohol, reports diminished craving, and has established 

a sound plan and support for ongoing recovery. 

Acamprosate therapy also may be discontinued if a 

patient is not compliant with the medication regimen. 

Acamprosate should not be discontinued just because 

a patient slips or relapses. 

References 

Besson, J.; Aeby, F.; Kasas, A.; Lehert, P.; and Potgieter, 

A. Combined efficacy of acamprosate and disulfiram 

in the treatment of alcoholism: A controlled study. 

Alcoholism: Clinical and Experimental Research 

22(3):573–579, 1998. 

Brasser, S.M.; McCaul, M.E.; and Houtsmuller, E.J. 

Alcohol effects during acamprosate treatment: A doseresponse study in humans. Alcoholism: Clinical and 

Experimental Research 28(7):1074–1083, 2004. 

FDA Psychopharmacologic Drugs Advisory Committee, 

May 10, 2002. Briefing Document for Acamprosate 

333 mg Tablets, April 3, 2002. Lipha Pharmaceuticals, 

Inc.: Darmstadt, Germany, 2002. 

www.fda.gov/ohrms/dockets/ac/02/Briefing/ 

3857b1_01_Lipha.pdf [accessed June 8, 2005]. 

Kiefer, F.; Holger, J.; Tarnaske, T.; Helwig, H.; Briken, P.; 

Holzbach, R.; Kampf, P.; Stracke, R.; Baehr, M.; 

Naber, D.; and Wiedemann, K. Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism. Archives of General Psychiatry 

60(1):92–99, 2003. 

Kiefer, F., and Wiedemann, K. Combined therapy: What 

does acamprosate and naltrexone combination tell us? 

Alcohol and Alcoholism 39(6):542–547, 2003. 

Mann, K.; Lehert, P.; and Morgan, M.Y. The efficacy 

of acamprosate in the maintenance of abstinence in 

alcohol-dependent individuals: Results of a metaanalysis. Alcohol Clinical and Experimental Research 

28(1):51–63, 2004. 

Tempesta, E.; Janiri, L.; Bignamini, A.; Chabac, S.; and 

Potgieter, A. Acamprosate and relapse prevention 

in the treatment of alcohol dependence: A placebocontrolled study. Alcohol and Alcoholism 

35(2):202–209, 2000. 

Thomson Healthcare, Inc. Physicians’ Desk Reference, 

59th Edition. Montvale, NJ: Thomson PDR, 2005, 

p. 3430. 

Verheul, R.; Lehert, P.; Geerlings, P.J.; Koeter, M.W.; 

and van den Brink, W. Predictors of acamprosate 

efficacy: Results from a pooled analysis of seven 

European trials including 1,485 alcohol-dependent 

patients. Psychopharmacology (Berl) 

178(2–3):167–173, 2005. 

6 
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ADVISORY .............................................................................. 
 

Resources for Additional 

Information 

Substance Abuse and Mental Health Services 

Administration (SAMHSA) 

1 Choke Cherry Road 

Room 8-1054 

Rockville, MD 20857 

Phone: 240-276-2130 (Office of Communications) 

Web: www.samhsa.gov 

National Clearinghouse for Alcohol and Drug 

Information (NCADI) 

Phone: 800-729-6686 

Español: 877-767-8432 

TDD: 800-487-4889 

Web: www.ncadi.samhsa.gov 

National Institute on Alcohol Abuse and 

Alcoholism (NIAAA) 

5635 Fishers Lane, MSC 9304 

Bethesda, MD 20892-9304 

Web: www.niaaa.nih.gov 

U.S. Food and Drug Administration (FDA) 

5600 Fishers Lane 

Rockville, MD 20857-0001 

Phone: 888-INFO-FDA (888-463-6332) 

Web: www.fda.gov 

Selected Publications 

Center for Substance Abuse Treatment. Naltrexone and 

Alcoholism Treatment. Treatment Improvement Protocol 

(TIP) Series 28. DHHS Publication No. (SMA) 98-3206. 

Rockville, MD: Substance Abuse and Mental Health 

Services Administration, 1998 (available through 

NCADI). 

Miller, W.R. (ed.) COMBINE Monograph Series, Volume 

1. Combined Behavioral Intervention Manual: A Clinical 

Research Guide for Therapists Treating People With 

Alcohol Abuse and Dependence. DHHS Publication 

No. (NIH) 04-5288. Bethesda, MD: National Institute on 

Alcohol Abuse and Alcoholism (NIAAA), 2004 (available 

through NIAAA). 

NIAAA. Helping Patients Who Drink Too Much: A 

Clinician’s Guide, 2005 Edition. Bethesda, MD: NIAAA, 

in development (will be available through NIAAA). 

Pettinati, H.M.; Weiss, R.D.; Miller, W.R.; Donovan, D.; 

Ernst, D.B.; and Rounsaville, B.J. COMBINE Monograph 

Series, Volume 2. Medical Management Treatment 

Manual: A Clinical Research Guide for Medically Trained 

Clinicians Providing Pharmacotherapy as Part of the 

Treatment for Alcohol Dependence. DHHS Publication 

No. (NIH) 04-5289. Bethesda, MD: NIAAA, 2004 

(available through NIAAA). 

7 
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Fall 2005, Volume 4, Issue 1 

Substance Abuse Treatment

ADVISORY .............................................................................. 
 

Substance Abuse Treatment Advisory 

Substance Abuse Treatment Advisory—published on an as-needed basis for treatment providers—was written and 

produced under contract number 270-04-7049 by the Knowledge Application Program (KAP), a Joint Venture of 

Johnson, Bassin & Shaw, Inc., and The CDM Group, Inc., for the Center for Substance Abuse Treatment (CSAT), 

Substance Abuse and Mental Health Services Administration (SAMHSA), U.S. Department of Health and Human 

Services (HHS). Christina Currier serves as the Government Project Officer for the Substance Abuse Treatment Advisory. 

The content of this publication does not necessarily reflect the views or policies of SAMHSA or HHS. 

Public Domain Notice: All material appearing in this report is in the public domain and may be reproduced or copied 

without permission; citation of the source is appreciated. However, this publication may not be reproduced or distributed 

for a fee without the specific, written authorization of the Office of Communications, SAMHSA, HHS. 

Electronic Access and Copies of Publication: This publication can be accessed electronically through the Internet at 

www.kap.samhsa.gov. Additional free print copies can be ordered from SAMHSA’s NCADI at 800-729-6686. 

Recommended Citation: Center for Substance Abuse Treatment. Acamprosate: A new medication for alcohol use 

disorders. Substance Abuse Treatment Advisory. Volume 4, Issue 1. Fall 2005. 

National Clearinghouse for Alcohol and Drug Information 

Substance Abuse and Mental Health Services Administration 

U.S. Department of Health and Human Services 

7079 Oakland Mills Road 

Columbia, MD 21046 

Substance Abuse Treatment Advisory 

Acamprosate: A New Medication for Alcohol Use Disorders 

DHHS Publication No. (SMA) 05–4114 

NCADI Publication No. MS974

Printed 2005