RxPRODUCT NEWS: PROFILE: Campral(acamprosate calcium)

Alcohol dependence affects morethan 14 million adults in theUnited States. Excessive drinkingmay cause many detrimental problems,such as cancer (primarily of the liver,throat, larynx), liver cirrhosis, braindamage, and fetal complications duringpregnancy. Four symptoms are used tocharacterize alcohol dependence: craving,loss of control, physical dependence,and tolerance. The first step inthe treatment of alcohol dependence isthe individual's acceptance of the condition.After admitting the problem,other treatment steps can begin.¹ Campralis an FDA-approved product fromForest Laboratories that helps maintainself-restraint from alcohol in peoplewho are sober at the beginning oftreatment.²

Pharmacology

The exact mechanism of action ofCampral is unknown. Alcohol dependenceis believed to change the regularbalance of neuronal excitation andinhibition. In vitro data suggest thatCampral has affinity for type A andtype B GABA receptors and that thedrug lowers neuronal excitabilitythrough the central nervous system.Campral is thought to restore the balanceof excitation and inhibitionwhen patients stop using alcohol.³

Clinical Trials

Campral was studied in a double-blind,multicenter, placebo-controlled,randomized study. A total of 455patients between the ages of 18 and 65years with chronic or episodic alcoholdependence were enrolled in this study.Patients were randomly assigned toeither placebo or Campral 1998 mg perday for body weight >60 kg or 1332 mgper day for body weight <60 kg for 360days. The results showed that Campralwas the superior agent in preventingrelapse, when compared with placebo.Study investigators also concluded thatCampral was not only effective, butalso a well-tolerated adjunct therapyhelpful in behavioral or psychosocialtreatment programs that involve alcohol-dependent patients.⁴

Another randomized, double-blind,placebo-controlled study was conductedto compare Campral with placebo,naltrexone with placebo, and a combinationof naltrexone and Campralwith placebo. A total of 160 patientswith alcoholism (according to Diagnosticand Statistical Manual of MentalDisorders, Fourth Edition,⁵ criteria foralcohol dependence) were enrolled inthe study. Patients were randomlyassigned to placebo, naltrexone 50 mgper day, Campral 1998 mg per day, ornaltrexone plus Campral dosed respectively,for 12 weeks. The resultsshowed the naltrexone, Campral, andcombination groups to be more effectivein preventing relapse, comparedwith placebo. Furthermore, the studyshowed that the naltrexone and Campralcombination was the most effectiveregarding time to first drink andtime to relapse, and that the combinationproduced lower relapse rates thanCampral alone and placebo but notlower than naltrexone.⁶

Safety

Overall, Campral is well tolerated.The most common side effects arediarrhea, nausea/vomiting, depression,and anxiety.³ Other less commonside effects include insomnia, asthenia,pruritus, dizziness, dry mouth,paresthesias, and diaphoresis. BecauseCampral can cause dizziness andmight impair judgment. Patientsshould be cautioned about operatingmachinery when taking the drug.Contraindications include patientswith sulfite hypersensitivity andsevere renal impairment or renal failure(creatinine clearance [CrCl] <30mL/min). Patients with moderaterenal impairment (CrCl 30-50mL/min) should initiate Campral therapyat a reduced dose.³ Additional cautionshould be taken with patientswho suffer from suicidal ideations, theelderly, and women who are breast-feeding.Campral is in pregnancy categoryC and should be avoided duringpregnancy.^2,3

Outlook

Campral is available in a 333-mgenteric-coated, delayed-release tablet.The recommended dose is 2 tablets 3times daily.² Studies have reported thatCampral has a safer adverse drug profilethan any medication strictly characterizedas an alcohol-dependenceagent. Furthermore, studies havefound that Campral is even moreeffective in combination with otheragents, such as naltrexone, or withbehavioral therapies and counseling.^2,3Campral gives health care practitionersanother safe and effective adjunctivetherapy option for the treatmentof alcohol dependence.

Drs. Faria and Soo are both senior researchpharmacists with the Investigational DrugService at Brigham and Women's Hospital,Boston, Mass. Dr. Faria also is a seniorhuman research specialist at PartnersHealthCare System. Mr. Barbat is a sixth-yearPharmD candidate at the MassachusettsCollege of Pharmacy and Health Sciencesand currently is at the Brigham andWomen's Hospital on a clinical clerkship.

For a list of references, send astamped, self-addressed envelope to:References Department, Attn. A. Stahl,Pharmacy Times, 241 Forsgate Drive,Jamesburg, NJ 08831; or send an e-mailrequest to: astahl@mwc.com.