CALCIUM CARBIMIDE

Citrated calcium carbimide is a mixture of two parts citric acid to one part calcium carbimide; it slows the metabolism of Alcohol (ethanol) from acetaldehyde to acetate, so it is used in the treatment of Alcoholism. It is also known as calcium cyanamide. As an antidipsotropic—an antialcohol or alcohol-sensitizing medication, it has been used for treatment in Canada, the United Kingdom, and Europe since its introduction for clinical use in 1956. Its only therapeutic use is for the treatment of alcoholism. In Canada it is sold under the brand name Temposil. As of 2000, however, calcium carbimide is still not approved for use in the United States.

PHARMACOLOGY

The Pharmacokinetic data on the absorption metabolism and elimination of carbimide in humans are incomplete. Since nausea, headache, and vomiting occur because of the rapid absorption of carbimide, for treatment purposes it is formulated as a slow-release tablet. Peak plasma concentrations of carbimide following oral administration in experimental animals occur at 60 minutes; the drug is then metabolized at a relatively rapid rate so that half disappears about every 90 minutes (i.e., an apparent elimination half-life of 92.4 minutes). In humans, an alcohol challenge reaction will occur on an average of 12 to 24 hours after drinking.

Alcohol (ethanol) is normally metabolized first to acetaldehyde, which is then quickly metabolized further so that levels of acetaldehyde are ordinarily quite low in the body (acetaldehyde is toxic). Carbimide produces competitive inhibition of hepatic (liver) aldehyde-NAD oxidoreductase dehydrogenase (ALDH), the enzyme from the liver responsible for oxidation of acetaldehyde into acetate and water. Within two hours of taking carbimide by mouth, ALDH inhibition occurs. If alcohol is then ingested, blood acetaldehyde levels are increased; also mild facial flushing, rapid heartbeat, shortness of breath, and nausea occur with just one drink. As more is drunk, the severity of the reaction increases, with rising discomfort and apprehension. Severe reactions can pose a serious medical risk that requires immediate attention.

DOSAGE AND ADMINISTRATION

In Canada, Temposil is available as round, white 50-mg tablets engraved with the letters "LL" and "U13." The usual dosage is 50 or 100 mg every twelve hours. The drug should never be given to an intoxicated patient and preferably no sooner than 36 hours after the last drink.

Calcium carbimide should be used with caution in patients with asthma, coronary artery disease, or myocardial disease.

In the event of an overdose, the patient should be given pure (100%) oxygen by mask or antihistamines administered intravenously.

SIDE EFFECTS

Unlike disulfiram, carbimide does not have the potential side effect of liver damage. Carbimide, however, exerts antithyroid activity, which can be clinically significant in patients with preexisting hypothyroid disease. According to a 1999 Canadian monograph, other side effects of calcium carbimide include fatigue, skin rashes, ringing in the ears, mild depression, a need to urinate frequently, and impotence. The clinical significance of transient white blood cell increases remains unclear.

USE IN TREATMENT

The rationale for use of carbimide in alcoholism treatment is similar to that of disulfiram. The threat of an unpleasant reaction, which one may expect following drinking, is sufficient to deter drinking. For alcoholics in treatment who take a drink, the ensuing reaction is unpleasant enough to strengthen their overall conditioned aversion to alcohol. Their reduction of alcohol consumption during carbimide treatment is expected to result in general bodily improvement. A second approach involves the use of carbimide as part of a Relapse-Prevention treatment, whereby an individual might take it in anticipation of a high-risk situation. As of 2000, scientific evidence supporting the efficacy of carbimide in alcoholism treatment is inconclusive because of a lack of well-controlled clinical trials. No multicenter clinical trials have yet been performed.

(See also: Causes of Substance Abuse: Learning ; Disulfiram ; Treatment Types: Aversion Therapy )

BIBLIOGRAPHY

Medical Economics Company. (1999). Physicians' Desk Reference, (PDR), 53rd edition. Montvale, NJ: Author.

Peachey, J. E., & Annis, H. (1985). New strategies for using the alcohol-sensitizing drugs. In C. A. Naranjo & E. M. Sellers (Eds.). Research advances in new psychopharmacological treatments for alcholism (pp. 199-218). New York: Excerpta Medica.

Peachey, J.E. et al. (1989a). Calcium carbimide in alcoholism treatment. Part 1: A placebo-controlled, double-blind clinical trial of short-term efficacy. British Journal of Addiction, 84, 877-887.

Peachey, J.E. et al. (1989b). Calcium carbimide in alcoholism treatment. Part 2: Medical findings of a short-term, placebo-controlled, double-blind clinical trial. British Journal of Addiction, 84, 1359-1366.

John E. Peachey

Revised by Rebecca J. Frey