Learn a Drug a Day - Acamprosate

Today's drug is acamprosate.
What is acamprosate indicated for?
INDICATIONS : 

• It is indicated for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. Treatment with acamprosate should be part of a comprehensive management program that includes psychosocial support.
• The efficacy of acamprosate in promoting abstinence has not been demonstrated in subjects who have not undergone detoxification and not achieved alcohol abstinence prior to beginning acamprosate treatment. The efficacy of Campral in promoting abstinence from alcohol in polysubstance abusers has not been adequately assessed.

How does acamprosate work?

MECHANISMS OF ACTION : 

• The mechanism of action of acamprosate in maintenance of alcohol abstinence is not completely understood.
• In vitro and in vivo studies in animals have provided evidence to suggest acamprosate affects the balance of GABA and glutamate neurotransmitters by decreasing glutamergic transmission and modulation of neuronal hyperexcitability.

How is acamprosate being used?

ROUTE OF ADMINISTRATION : 

• It is taken orally as tablets. 
• It should be taken with food. (Take at meal times.)
• Treatment with acamprosate should be initiated as soon as possible after the period of alcohol withdrawal, when the patient has achieved abstinence, and should be maintained if the patient relapses. 
• It should be used as part of a comprehensive psychosocial treatment program.

Is there any contraindication?

CONTRAINDICATIONS : 

• It is contraindicated in patients who previously have exhibited hypersensitivity to acamprosate.
• It is also contraindicated in patients with severe renal impairment (creatinine clearance of ≤ 30 mL/min). 

Are there any possible side effects?

SIDE EFFECTS : 

Most common possible side effects : 

• diarrhea and intestional cramps
• itchiness 
• dizziness
• muscle weakness 
• headache
• flatulence
• nausea 
• anxiety
• insomnia 

Less common, but more serious side effects: 

• depression and suicide risk

What precautions are necessary?

PRECAUTIONS : 

(i) Suicidality and Depression

• In controlled clinical trials of acamprosate, adverse events of a suicidal nature (suicidal ideation, suicide attempts, completed suicides) were infrequent overall, but were more common in  acamprosate-treated patients than in patients treated with placebo (1.4% vs. 0.5% in studies of 6 months or less; 2.4% vs. 0.8% in year-long studies). \
• Completed suicides occurred in 3 of 2272 (0.13%) patients in the pooled acamprosate group from all controlled studies and 2 of 1962 patients (0.10%) in the placebo group. 
• Adverse events coded as “depression” were reported at similar rates in  acamprosate-treated and placebo-treated patients.
•  Although many of these events occurred in the context of alcohol relapse, and the interrelationship between alcohol dependence, depression and suicidality is well-recognized and complex, no consistent pattern of relationship between the clinical course of recovery from alcoholism and the emergence of suicidality was identified. 
• Alcohol-dependent patients, including those patients being treated with acamprosate, should be monitored for the development of symptoms of depression or suicidal thinking. 
• Families and caregivers of patients being treated with  acamprosate should be alerted to the need to monitor patients for the emergence of symptoms of depression or suicidality, and to report such symptoms to the patient's health care provider.

(ii) Alcohol Withdrawal

• Use of acamprosate does not eliminate or diminish withdrawal symptoms.

DRUG INTERACTIONS : 

• The concomitant intake of alcohol and acamprosate does not affect the pharmacokinetics of either alcohol or acamprosate. 
• Pharmacokinetic studies indicate that administration of disulfiram or diazepam does not affect the pharmacokinetics of acamprosate. 
• Co-administration of naltrexone with acamprosate produced a 25% increase in AUC (area under curve) and a 33% increase in the Cmax of acamprosate.  No adjustment of dosage is recommended in such patients.  The pharmacokinetics of naltrexone and its  major metabolite 6-beta-naltrexol were unaffected following co-administration with  acamprosate. 
• In clinical trials, the safety profile in subjects treated with acamprosate concomitantly with anxiolytics, hypnotics and sedatives (including benzodiazepines), or non-opioid  analgesics was similar to that of subjects taking placebo with these concomitant medications.  Patients taking acamprosate  concomitantly with antidepressants more commonly reported both weight gain and weight loss, compared with patients taking either medication alone. 

Pregnancy and breastfeeding:  

• There are no adequate and well controlled studies in pregnant women. Acamprosate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
• In animal studies, acamprosate was excreted in the milk of lactating rats dosed orally with acamprosate calcium. The concentration of acamprosate in milk compared to blood was 1.3:1. It is not known whether acamprosate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when acamprosate is administered to a nursing woman.

1. Acamprosate by FOREST PHARMACEUTICALS, Inc.  

2. Acamprosate by RxList.

3. Acamprosate by MIMS Malaysia.