STEPS

New Drug Reviews

Acamprosate (Campral) for Treatment of Alcoholism

Am Fam Physician. 2006 Aug 15;74(4):645-646.

Synopsis

Acamprosate has been used in Europe for the treatment of alcohol dependency since 1989. In 2004 it became the third drug to receive approval from the U.S. Food and Drug Administration for this indication, following disulfiram (Antabuse) and naltrexone (ReVia). Acamprosate is a structural analogue of γ-aminobutyric acid (GABA). It is thought to decrease alcohol intake by affecting calcium channels and modifying transmission along GABA and glutamine pathways in the brain, which may result in decreased positive reinforcement of alcohol intake and decreased withdrawal cravings. However, the exact mechanism of action of acamprosate is unknown.

Name Starting dosage Dose form Approximate monthly cost*

Acamprosate (Campral)

Two capsules three times daily

333-mg enteric-coated capsule

$125.00 for 180 tablets


*—Average wholesale cost, based on Red Book, Montvale, N.J.: Medical Economics Data, 2005.

Name Starting dosage Dose form Approximate monthly cost*

Acamprosate (Campral)

Two capsules three times daily

333-mg enteric-coated capsule

$125.00 for 180 tablets


*—Average wholesale cost, based on Red Book, Montvale, N.J.: Medical Economics Data, 2005.

SAFETY

Multiple studies have established a good safety profile for acamprosate.1,2 There is no potential for abuse or dependence.1 An increased rate of adverse events related to suicide (i.e., suicidal ideation, suicide attempts, and completed suicides) was reported in patients taking acamprosate compared with those taking placebo (2.4 versus 0.8 percent, number needed to harm = 63). However, the rates of completed suicides, specifically, did not differ between the two groups.3 A few cases of acute renal failure also have occurred, and acamprosate is contraindicated in patients with severe renal impairment (i.e., creatinine clearance less than 30 mL per minute [0.50 mL per second]).1

Acamprosate is pregnancy category C. It is teratogenic in animals, but no studies have been performed on women who are pregnant.3 It is not known whether acamprosate is distributed in breast milk.3 One study4 found that acamprosate can be used safely in adolescents. Overdose has never been fatal, but chronic overdose can result in hypercalcemia.3

TOLERABILITY

Acamprosate is well tolerated. Approximately one half of all patients given acamprosate discontinue use within a year, but this rate is similar to that seen with placebo.2 Ten to 17 percent of patients experience diarrhea, which is dose-related and usually transient and is the most common side effect of acamprosate. Other side effects reported more often with acamprosate than with placebo treatment were dizziness, pruritus, and increased sexual desire. Infrequent adverse effects included insomnia, anxiety, depression, asthenia, nausea, vomiting, headache, drowsiness, dry mouth, paresthesias, and diaphoresis. The Agency for Healthcare Research and Quality concluded that there is good evidence acamprosate is reasonably well tolerated and without serious harms.5

EFFECTIVENESS

Most evidence supports the effectiveness of acamprosate in maintaining abstinence from alcohol.1,2,6 Acamprosate is intended for use in patients who are receiving some form of psychosocial support and have been abstinent from alcohol for at least a few days. Randomized controlled trials (RCTs) lasting three to 24 months have compared acamprosate with placebo in more than 4,000 patients.2,6 Twice as many patients receiving acamprosate remained abstinent from alcohol for one year than did patients receiving placebo (27 versus 13 percent, respectively).6 For approximately every eight patients who were treated with acamprosate instead of placebo, one additional patient remained abstinent for 12 months. In patients who did not remain abstinent, acamprosate still was associated with decreased alcohol consumption.2,6 These findings are in contrast with a more recent RCT7 that found no difference between acamprosate and placebo in maintaining abstinence during or after a 16-week treatment period.

In a study conducted in primary care offices,8 acamprosate treatment in addition to standard care resulted in fewer alcohol-related problems, higher cumulative abstinence, and improved quality of life. In this group of patients, drop-out rates were much lower (20 percent) than those reported in other studies.2,6,7

The evidence comparing acamprosate and naltrexone is unclear, with one study9 finding acamprosate to be as effective as naltrexone and another reporting it to be less effective.7 The combination of acamprosate and naltrexone is more effective than acamprosate alone but is not more effective than naltrexone alone.7,9 The combined use of acamprosate and disulfiram may be more effective than use of either drug alone.10

PRICE

A one-month supply of acamprosate (180 tablets) costs $125. This is lower than the cost of naltrexone ($205 for ReVia, $128 to $137 for generic) but higher than that for disulfiram ($42).

SIMPLICITY

The typical dosage is two tablets three times per day. Some studies used a lower dosage of four tablets total per day in patients with a body weight less than 132 lb (60 kg). The dosage should be reduced to one tablet three times per day in patients with moderate renal failure (i.e., creatinine clearance 30 to 50 mL per minute [0.50 to 0.83 mL per second]). Acamprosate does not need to be discontinued in the event of a relapse.

Bottom Line

Acamprosate is a safe and well-tolerated treatment for patients with alcoholism and it appears to improve the likelihood that patients will remain abstinent. Most evidence suggests it is as effective as naltrexone but with fewer adverse reactions, and that it may be more effective when used in combination with naltrexone or disulfiram. Acamprosate used in conjunction with psychosocial support should be considered as a first-line therapy for maintenance of abstinence from alcohol.

The Authors

KAM HUNTER, M.D., PH.D., is a faculty physician at MedPro Family Medicine, Maricopa Integrated Health System, Phoenix, Arizona.

RICKY OCHOA, M.D., is a resident physician at the Phoenix Baptist Hospital Family Medicine Residency, Phoenix, Arizona.

REFERENCES

1. Acamprosate (Campral) for alcoholism.. Med Lett Drugs Ther. 2005;47:1–3.

2. Bouza C, Angeles M, Munoz A, Amate JM. Efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence: a systematic review [published correction appears in Addiction 2005;100:573]. Addiction. 2004;99:811–28.

3. Campral (acamprosate calcium) delayed-release tablets [Product information]. St. Louis, Mo.: Forest Pharmaceuticals, 2004. Accessed March 24, 2006, at: http://www.frx.com/pi/campral_pi.pdf.

4. Niederhofer H, Staffen W. Acamprosate and its efficacy in treating alcohol dependent adolescents. Eur Child Adolesc Psychiatry. 2003;12:144–8.

5. Pharmacotherapy for alcohol dependence. Rockville, Md.: Agency for Health Care Policy and Research, 1999. Accessed March 24, 2006, at: http://www.ahrq.gov/clinic/epcsums/alcosumm.htm.

6. Mann K, Lehert P, Morgan MY. The efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals: results of a meta-analysis. Alcohol Clin Exp Res. 2004;28:51–63.

7. Anton RF, O’Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006;295:2003–17.

8. Kiritze-Topor P, Huas D, Rosenzweig C, Comete S, Paille F, Lehert P. A pragmatic trial of acamprosate in the treatment of alcohol dependence in primary care. Alcohol Alcohol. 2004;39:520–7.

9. Kiefer F, Jahn H, Tarnaske T, Helwig H, Briken P, Holzbach R, et al. Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study. Arch Gen Psychiatry. 2003;60:92–9.

10. Besson J, Aeby F, Kasas A, Lehert P, Potgieter A. Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism: a controlled study. Alcohol Clin Exp Res. 1998;22:573–9.

STEPS drug updates cover Safety, Tolerability, Effectiveness, Price, and Simplicity. Each update provides an independent review of a new medication by authors who have no financial association with the drug manufacturer.

The series coordinator is Allen F. Shaughnessy, Pharm.D., Tufts University Family Medicine Residency Program, Malden, Mass.


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