Acamprosate: a new medication for alcohol use disorders
Substance Abuse Treatment Breaking News for the T reatment Field Acamprosate: A New Medication for Alcohol Use Disorders What is acamprosate?
glutamate and gamma-aminobutyric acid (GABA) neurotransmitter systems. Although acamprosate's
Acamprosate (calcium acetyl homotaurinate) is a
mechanism of action has not been clearly established,
new prescription medication to help people who
it may work by reducing symptoms of postacute
are alcohol dependent. Acamprosate is the third
(protracted) withdrawal, such as insomnia, anxiety,
medication, after disulfiram (Antabuse®) and
naltrexone (ReVia®), to receive U.S. Food and Drug Administration (FDA) approval for postwithdrawal
How does acamprosate's
maintenance of alcohol abstinence. It is the first new medication approved for this purpose in a
activity compare with that of
decade. FDA approved acamprosate in July 2004.
other medications used to treat
It became available in the United States in January
2005, under the trade name Campral® Delayed-
Acamprosate differs in significant ways from
Release Tablets. Acamprosate has been used for
disulfiram and naltrexone, the other two agents
nearly 20 years in Europe, where it has been found
approved by FDA for alcohol abstinence mainte
to be safe and effective for treating alcohol
dependence (Mann et al. 2004; Tempesta et al. 2000).
Disulfiram, used to treat alcohol dependence for decades, is an aversive medication that inhibits How does acamprosate work?
aldehyde dehydrogenase and leads to increased levels of acetaldehyde. When a person taking disul
Chronic, heavy use of alcohol affects several
firam drinks alcohol, the increased acetaldehyde
neurotransmitter systems in the brain. These neuro
causes severe physical reactions such as facial
transmitter systems adapt to the chronic presence
flushing, nausea, vomiting, low blood pressure,
of alcohol. Once they have adapted, these systems
headache, and weakness. Disulfiram does not
are only in equilibrium with alcohol. When alcohol
reduce craving or normalize brain functioning,
use ceases, the systems become disregulated and
as acamprosate and naltrexone are believed to do.
enter a pathologic hyperexcitatory state. It is
Instead, disulfiram's effectiveness depends on the
thought that acamprosate helps modulate and
patient's reluctance to suffer the aversive effects
normalize brain activity, particularly in the
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Substance Abuse and Mental Health Services Administration Center for Substance Abuse Treatment
Substance Abuse Treatment Table 1: Comparison of Drugs Approved for Maintenance of Abstinence From Alcohol Medication Acamprosate (Campral) Disulfiram (Antabuse) Naltrexone (ReVia) Mechanism of Action
is ingested; reduces craving for alcohol
Patient Status immediately following acute with
acamprosate may benefit from continuing the medication
isoniazid, rifampin, diazepam, chlordiazepoxide, imipramine, desipramine, and oral hypoglycemics
liver toxicity, peripheral neuropathy, potential liver toxicity (especially at psychosis, and delirium
Contraindi- cations and Cautions
patients with depression only when potential benefits justify potential risk 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
Acamprosate has not been found to be associated with
receptors, leading to reductions in craving and in the
any significant drug (including alcohol) interactions and
reinforcing effects of alcohol. Unlike naltrexone,
does not affect the action of coadministered disulfiram,
acamprosate does not affect the action or subjective
diazepam, nordiazepam, imipramine, desipramine,
effects of alcohol (Brasser et al. 2004).
selective serotonin reuptake inhibitors, naltrexone, or naltrexol. No adjustment of dosage is recommended in
Patients with liver damage usually cannot use either
patients taking these other medications.
naltrexone or disulfiram. However, because acamprosate is not metabolized in the liver, patients with liver
Can acamprosate be used for detoxification?
Preliminary evidence suggests that treatment outcomes improve when acamprosate is combined with naltrexone
Research on the effectiveness of acamprosate in treating
or with disulfiram, particularly for patients who
the symptoms of acute withdrawal has been inconclu
responded poorly to therapy with any of these medica
sive, and FDA has not approved its use for this purpose.
tions alone (Besson et al. 1998; Kiefer and Wiedemann
However, patients who are already taking acamprosate
2003; Kiefer et al. 2003). Combination therapy also
and who relapse may be medically withdrawn from
has been found to be safe. No specific protocol for
alcohol without discontinuing acamprosate.
combination therapy has been established as yet, but the results of a large national study, sponsored by the
How safe is acamprosate?
National Institute on Alcohol Abuse and Alcoholism,
Acamprosate is not addicting and appears to have no
will be available soon. The study, Combining
potential for abuse; patients maintained on the drug
Medications and Behavioral Interventions (COMBINE),
have developed no known tolerance for or dependence
examines the effects of naltrexone and acamprosate
on it. It also carries little overdose risk. Even at over
and two psychosocial therapies, alone and in various
doses up to 56 grams (a normal daily dose is 2 grams),
acamprosate was generally well tolerated by patients (Thomson Healthcare, Inc. 2005).
Are there side effects or drug
Because acamprosate is not metabolized by the liver, it
interactions with acamprosate?
can be used by individuals with liver disease. Because
The most common side effects experienced by people
acamprosate is excreted primarily from the kidneys,
taking acamprosate are diarrhea, insomnia, anxiety,
patients with severe renal impairment (creatinine
muscle weakness, nausea, itchiness, and dizziness.
clearance <30 mL/min) should not use acamprosate.
Uncommon, but serious, side effects include depression
Those with moderate renal impairment (creatinine
and suicidal thoughts. Most side effects are usually mild
clearance 30-50 mL/min) may be able to take the
and transient, lessening or disappearing within the first
medication with dosage adjustments and careful
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Patients should be told to be cautious about driving
How can treatment providers
or operating heavy machinery until they know how
incorporate acamprosate into their
acamprosate will affect their ability to engage in these
activities and until they have adjusted to any effects of the drug.
Treatment program staff should be well educated about acamprosate and its effects and be able to educate clients
In clinical trials, suicidal events (suicidal ideation,
about the medication. Acamprosate is a prescription
attempted suicides, completed suicides), although rare,
medication, so treatment providers need to be able to
were more common in acamprosate-treated participants
provide the medication and medically monitor the
than in participants receiving placebo. Patients should
patient, either on site or through relationships with
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
Treatment providers should assess patients' clinical
signs and report their occurrence to the substance abuse
appropriateness for acamprosate. Patients who have been
treatment counselor or prescribing professional.
in treatment multiple times but have been unable to sustain abstinence or those for whom disulfiram or
Use of acamprosate during pregnancy has not been
naltrexone or both have not been effective may be
studied with humans. Animal studies of acamprosate
particularly appropriate candidates for acamprosate.
and pregnancy have found some potential fetal risk. The
However, given the medication's good safety profile,
potential risk of taking acamprosate during pregnancy
patients new to treatment also may be considered good
should be balanced with the potential benefits (consider
candidates for acamprosate therapy. A good candidate
ing the known adverse effects of alcohol, particularly
also is interested in trying the medication and willing
and able to take it regularly as prescribed.
The use of acamprosate by older adults or by children
Motivation is an important factor. Clinical trials found
has not been studied. Because of the higher risk of
that participants receiving acamprosate who were
diminished renal function among older adults, acam
motivated and committed to total abstinence at the start
prosate should be used with caution with this population.
of treatment had lower relapse risk than less motivated participants (FDA Psychopharmacologic Drugs Advisory
Campral Dosage and Timing
Committee 2002). Less motivated patients are those whose personal goals, for instance, allow for slips, con
• The recommended dosage of Campral is two
trolled drinking, other modified alcohol consumption,
333 mg tablets three times a day, with or without
or other substance abuse. Research has not documented
the effectiveness of acamprosate with patients who use
• Treatment with acamprosate should be initiated
multiple substances in addition to alcohol.
as soon as possible after alcohol withdrawal and should be maintained if the patient relapses.
Researchers also have looked at whether certain clinical
• Treatment duration at this dosage ranged from
characteristics (e.g., age of onset of alcohol use disorder,
level of craving, gender, family history of alcohol use)
• The manufacturer recommends treatment
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might predict which individuals are more likely than others to abstain from alcohol successfully on acamprosate.
What To Tell the Patient
This research did not find a relationship between patient
Treatment program staff can support patients
characteristics and successful acamprosate therapy (Verheul
taking acamprosate by educating them about the
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
• Informing them about the benefits and
• Informing them that it can take 5 to 8 days
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
• Stressing the importance of taking the
should assess the patient's medical appropriateness for therapy with acamprosate by conducting a medical
• Encouraging them to talk to their prescribing
examination, including laboratory tests to obtain baseline
professional about the duration of acamprosate
• Encouraging them to talk to their prescribing
Medications for alcohol use disorders do not replace
professional about other medications they are
counseling. Individuals taking acamprosate should be
expected to participate fully in a treatment program's
• Encouraging them to report side effects of the
activities, including attending 12-Step or mutual-help
drug and explaining that most of these resolve
group meetings. In addition, they may need ongoing
motivational counseling specifically geared to helping
• Encouraging women to inform all treatment
providers immediately if they become pregnant
Regular communication between treatment providers
during therapy, if they are trying to become
and the prescribing medical professional is essential. In
particular, treatment providers need to communicate
• Stressing the importance of continuing
information concerning the patient to the prescribing
counseling and 12-Step or mutual-help group
• Stressing the need for caution in driving or
• Reported or detected drinking or drug use episodes
operating heavy machinery until they are
• Patient concerns about side effects
certain that acamprosate has no adverse effects on their participation in these activities and
• Issues affecting the patient's safety (suicidal ideation,
reported or observed increase in levels of depression or anxiety, or significant physical complaints)
• Advising them to continue taking the
medication if a slip or relapse occurs and to
inform their counselor and prescribing professional immediately
• Expressed desire to stop taking the medication
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Treatment providers should encourage patients to talk
directly to their prescribing professionals about these and
other issues or questions they may have.
3857b1_01_Lipha.pdf [accessed June 8, 2005].
Kiefer, F.; Holger, J.; Tarnaske, T.; Helwig, H.; Briken, P.;
How long should an individual take
Holzbach, R.; Kampf, P.; Stracke, R.; Baehr, M.;
Naber, D.; and Wiedemann, K. Comparing and com
The manufacturer of acamprosate recommends that
bining naltrexone and acamprosate in relapse preven
acamprosate therapy be continued for 1 year (the effec
tion of alcoholism. Archives of General Psychiatry
tiveness and safety of the medication have not been
evaluated for periods of use longer than a year). Given
Kiefer, F., and Wiedemann, K. Combined therapy: What
that guideline, the length of time a particular patient takes
does acamprosate and naltrexone combination tell us?
acamprosate will be determined, ideally, with input from
Alcohol and Alcoholism 39(6):542-547, 2003.
the prescribing professional, the treatment provider, and the patient. Discontinuation of acamprosate may be con
Mann, K.; Lehert, P.; and Morgan, M.Y. The efficacy
sidered once a patient has achieved stable abstinence from
of acamprosate in the maintenance of abstinence in
alcohol, reports diminished craving, and has established
alcohol-dependent individuals: Results of a meta
a sound plan and support for ongoing recovery.
analysis. Alcohol Clinical and Experimental Research
Acamprosate therapy also may be discontinued if a
patient is not compliant with the medication regimen.
Tempesta, E.; Janiri, L.; Bignamini, A.; Chabac, S.; and
Acamprosate should not be discontinued just because
Potgieter, A. Acamprosate and relapse prevention
in the treatment of alcohol dependence: A placebo-controlled study. Alcohol and Alcoholism References
Besson, J.; Aeby, F.; Kasas, A.; Lehert, P.; and Potgieter,
Thomson Healthcare, Inc. Physicians' Desk Reference,
A. Combined efficacy of acamprosate and disulfiram
59th Edition. Montvale, NJ: Thomson PDR, 2005,
in the treatment of alcoholism: A controlled study.
Alcoholism: Clinical and Experimental Research 22(3):573-579, 1998.
Verheul, R.; Lehert, P.; Geerlings, P.J.; Koeter, M.W.;
and van den Brink, W. Predictors of acamprosate
Brasser, S.M.; McCaul, M.E.; and Houtsmuller, E.J.
efficacy: Results from a pooled analysis of seven
Alcohol effects during acamprosate treatment: A dose-
European trials including 1,485 alcohol-dependent
response study in humans. Alcoholism: Clinical and
patients. Psychopharmacology (Berl) 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,
Substance Abuse Treatment
Resources for Additional Selected Publications Information
Center for Substance Abuse Treatment. Naltrexone and Alcoholism Treatment. Treatment Improvement Protocol
Substance Abuse and Mental Health Services
(TIP) Series 28. DHHS Publication No. (SMA) 98-3206.
Rockville, MD: Substance Abuse and Mental Health
Services Administration, 1998 (available through
Rockville, MD 20857 Phone: 240-276-2130 (Office of Communications)
Miller, W.R. (ed.) COMBINE Monograph Series, Volume 1. Combined Behavioral Intervention Manual: A Clinical Research Guide for Therapists Treating People With National Clearinghouse for Alcohol and Drug Alcohol Abuse and Dependence. DHHS Publication
No. (NIH) 04-5288. Bethesda, MD: National Institute on
Alcohol Abuse and Alcoholism (NIAAA), 2004 (available
NIAAA. Helping Patients Who Drink Too Much: A Clinician's Guide, 2005 Edition. Bethesda, MD: NIAAA,
National Institute on Alcohol Abuse and
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 U.S. Food and Drug Administration (FDA) Clinicians Providing Pharmacotherapy as Part of the Treatment for Alcohol Dependence. DHHS Publication
No. (NIH) 04-5289. Bethesda, MD: NIAAA, 2004
Substance Abuse Treatment 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 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.
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Substance Abuse Treatment Advisory
DHHS Publication No. (SMA) 05-4114 NCADI Publication No. MS974
Acamprosate: A New Medication for Alcohol Use Disorders
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