Acamprosate

Brand name: Campral®

Generic name: Acamprosate

Manufacturer ⁽³⁾: Forest Laboratories

Drug Class ^(1,3,4): Alcohol withdrawal agent, Psychotherapeutic agent, GABA Agonist/Glutamate Antagonist

Labeled uses: Maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. ^(1,3,4)

Unlabeled uses: None

Mechanism of Action: Acamprosate is an analog of homotaurine a GABA-ergic agonist.  It stimulates inhibitory GABA-ergic neurotransmission in the brain and antagonizes the effects of certain excitatory amino acids, such as glutamate. It is active at postsynaptic GABA(b) receptors, but not at GABA(a) receptors in vitro, decreases electrical excitability but does not change membrane potential. ^(1,3,4)

Pharmacokinetics ^(1,3,4):

Metabolism: Acamprosate does not appear to undergo metabolism. ^(1,3,4)

Elimination: Renal 6.5%, Feces Extensive ^(1,3,4)

Efficacy:  Baltieri DA, De Andrade AG.  Acamprosate in alcohol dependence: a randomized controlled efficacy study in a standard clinical setting. J Stud Alcohol. 2004 Jan;65(1):136-9.

This study was a double-blind, placebo-controlled study in which patients received acamprosate for 12 weeks following a 1 week 

detox period.  They then completed follow-up visits for similar amounts of time.  Using intent-to-treat analyses, the Kaplan-Meier 

survival curve showed an advantage in relapse rates for acamprosate over placebo (log-rank test, p = .02), and acamprosate was well 

tolerated.  This study was conducted over a 12-week period which could be a weakness considering that the recommended therapy with

 acamprosate is 12 months. Acamprosate seems to be an effective treatment for alcohol dependence in a Brazilian population. 

Whitworth AB, et al. Comparison of acamprosate and placebo in long-term treatment of alcohol dependence. Lancet. 1996 May 25;347(9013):1438-42.

This study was a multicenter, double blind, placebo controlled study where patients who were eligible were treated with Acamprosate at a 

dose of 1998 mg for patients >60 kg and 1332 mg for patients <60 kg.  The patients who were assigned to the placebo group took the same

 amount of pills that was appropriate for their weight.  They were treated for a total of 360 days and then were followed-up on days 450, 540,

 630, and 720.  Lab values were monitored and adverse effects were recorded.  This study had a large sample size and therefore should be 

able to be extrapolated to the general population easier.  The study also was a long-term treatment study that would possibly identify more 

adverse reactions.  The criteria used in the analysis of this study are conservative and may cause the data to be less applicable.  This study 

concluded that Acamprosate could be a safe and effective adjunct to psychosocial alcohol rehabilitation programs.

Poldrugo F.  Acamprosate treatment in a long-term community-based alcohol rehabilitation programme. Addiction. 1997 Nov;92(11):1537-46.

This study was a multicenter, double-blind, randomized control trial where participants were randomized to two parallel groups and treated

 with Acamprosate or placebo for 6 months and then followed-up for 6 months.  Patients over 60 kg were given 1998 mg of Acamprosate Daily 

and patients under 60 kg were given 1332 mg of Acamprosate daily.  This study only looked at 6 months of therapy with Acamprosate and the 

recommended therapy duration is 1 year.  This study concluded that Acamprosate could be useful in assisting patients with continuation of 

abstinence from alcohol who are dependent upon it.

Adverse Effects ^(1,3,4):  CNS:  Insomnia, Confusion

GI:  Diarrhea (most common), Nausea, Vomiting, and Abdominal Pain

GU:  Sexual Dysfunction including Impotence, Frigidity, Increased Libido or Decreased Libido

Dermatologic:  Pruritus (most common)

Drug Interactions:  The absorption of Tetracyclines, Quinolones, Levothyroxine, atenolol, Iron, Alendronate, Sodium Flouride and Zinc may be decreased by the calcium component of Acamprosate during concurrent administration. ^(1,4)  The absorption of Acamprosate can be decreased by food. ⁽²⁾

Dosage/Administration ^(1,3,4): Initiation of therapy should begin after alcohol detoxification has taken place and the patient has abstained from alcohol for 7 days and should not be interrupted if relapses occur.  Therapy duration should be 1 year.

Usual Dose:  Patients >60 kg should receive 1998 mg/day in 3       divided doses with meals

Patients <60 kg should receive 1333 mg/day in 3 divided doses with meals

Geriatric:  The manufacturer recommends not using Acamprosate due to insignificant clinical experience.

Pediatric:  The manufacturer recommends not using Acamprosate due to insignificant clinical experience.

Renal Impairment:  Acamprosate should not be used in patients with serum creatinine greater then 120 micromoles/liter.

Hepatic Impairment:  Acamprosate should not be used in patients who obtain a Child-Pugh classification C.

Conclusion:  The quality of life of an alcohol dependent patient is much lower than that of a healthy patient.  Acamprosate can provide an effective adjunct therapy to psychological support.  Acamprosate was shown to safely and effectively assist in alcohol abstinence.  Studies show that with Acamprosate the rates of continued abstinence from alcohol is increased significantly.

Recommended References:

1. MicroMedex DrugDex
2. Drug Facts and Comparisons
3. http://www.campral.com/Campral_pi.pdf
4. Lexi-Comp Drugs
5. Baltieri DA, De Andrade AG.  Acamprosate in alcohol dependence: a randomized controlled efficacy study in a standard clinical setting. J Stud Alcohol. 2004 Jan;65(1):136-9.
6. Poldrugo F.  Acamprosate treatment in a long-term community-based alcohol rehabilitation programme. Addiction. 1997 Nov;92(11):1537-46.
7. Whitworth AB, et al. Comparison of acamprosate and placebo in long-term treatment of alcohol dependence. Lancet. 1996 May 25;347(9013):1438-42.