Pharmacology Update

Acamprosate Calcium Tablets (Campral®)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The FDA has approved a new drug for the management of alcohol dependence. Acamprosate, which is available in most European countries, is manufactured by Merck Santé in Germany, and marketed in the United States by Forest Pharmaceuticals as Campral®.

Indications

Acamprosate is indicated for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. It should be used as part of a comprehensive management program that includes psychosocial support.1

Dosage

The recommended dose is two 333 mg tablets taken 3 times daily. It may be taken without regard to meals, but dosing with meals is recommended to improve compliance.1 Patients with moderate renal impairment (creatinine clearance 30-50 mg/min.) should take half the normal dose.1

Acamprosate is available in 333 mg enteric-coated tablets.

Potential Advantages

Acamprosate provides a drug with a different mechanism of action than naltrexone, for the management of abstinence. The former is believed to stabilize abstinence, while the latter decreases alcohol consumption.2 Acamprosate appears to be better tolerated than natrexone, and is the most widely validated pharmacotherapy for alcoholism.2,3

Potential Disadvantages

Acamprosate may be less effective than naltrexone in terms of the time to first drink, time to relapse, or preventing relapse into heavy drinking.4,5 The benefit of acamprosate is regarded as modest.6 It may not be effective in patients who have not undergone detoxification and are not abstinent.1 The most common adverse event related discontinuation of treatment was diarrhea (2% vs 0.7% for placebo).1

Comments

Acamprosate is believed to maintain abstinence by blocking negative craving in alcohol-dependent patients during abstinence.2 This is the result restoration of a normal N-methyl-D-aspartate (NMDA) receptor tone in glutamatergic systems.7 The approval of acamprosate was based primarily on 3 double-blind, placebo-controlled trials in patients who had undergone inpatient detoxification and were abstinent at the time of randomization. When used as part of a multidisciplinary approach, acamprosate showed better cumulative abstinence duration than placebo. In a comparative trial (n = 160), naltrexone showed a tendency for better outcomes in terms of time to relapse and to first drink.4 The combination was statistically better than acamprosate monotherapy, but not to naltrexone. The drug appears to be well tolerated, and the effect regarded as modest. The price of acamprosate was not available at the time of this review.

Clinical Implications

Currently, naltrexone is approved for treating alcoholism. It is an opioid receptor antagonist that is believed to reduce the positive-reinforcing pleasurable effects of alcohol, as well as craving.2 The effects of naltrexone and acamprosate appear to be somewhat additive.4 The evidence for efficacy appears to be more consistent with acamprosate than naltrexone.2 Relapse rate is high for alcoholics, as 50-60% of patient treated with naltrexone or acamprosate relapse within 12 weeks. Combination therapy with naltrexone and acamprosate seems logical, and warrants further study.

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Asst. Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.

References

1. Campral Product Information. Forest Pharmaceuticals. April 2004.

2. Mann K. CNS Drugs. 2004;18(8):485-504.

3. Mason BJ. Eur Neuropsychopharmacol. 2003;13(6):469-475.

4. Kiefer F, et al. Arch Gen Psychiatry. 2003;60:92-99.

5. Rubio G, et al. Alcohol Alcohol. 2001;36:419-25.

6. Verheul R, et al. Psychopharmacology (Berl). 2004; 19:(Epub).

7. Rammes G, et al. Neuropharmacology. 2001;40: 749-760.