NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
Center for Substance Abuse Treatment. Incorporating Alcohol Pharmacotherapies Into Medical Practice. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2009. (Treatment Improvement Protocol (TIP) Series, No. 49.)
Incorporating Alcohol Pharmacotherapies Into Medical Practice.
Show detailsAcamprosate At a Glance
Chemical name: Calcium acetyl homotaurinate.
Trade name: Campral® Delayed-Release Tablets.
U.S. distributor: Forest Pharmaceuticals (subsidiary of Forest Laboratories, Inc.), St. Louis, MO.
U.S. Food and Drug Administration approval to treat alcohol dependence: July 2004.
Dosage/How taken: Two 333 mg delayed-release tablets by mouth three times per day, with or without food (a lower dose may be effective with some patients and must be used with those with impaired renal function). Pills are swallowed whole, not crushed or broken.
How supplied: Opaque bottles or Dose Paks of 180 enteric-coated 333 mg tablets.
Storage: Keep out of reach of children; keep tightly closed in original container; store at room temperature, away from excess heat and moisture (not in the bathroom or near a sink); discard when outdated or no longer needed.
What Is Acamprosate?
Acamprosate was the third medication, after disulfiram and naltrexone, to receive U.S. Food and Drug Administration (FDA) approval for postwithdrawal maintenance of alcohol abstinence. Acamprosate's mechanism of action has not been clearly established, but it is thought that acamprosate helps modulate and normalize alcohol-related changes in brain activity, thereby reducing symptoms of postacute (protracted) withdrawal, such as disturbances in sleep and mood, that may trigger a relapse to drinking.
Brief History of Development
The French pharmaceutical company Laboratoires Meram began clinical development and testing of acamprosate in 1982. From 1982 to 1988, acamprosate was tested for safety and for efficacy as a treatment for alcohol dependence. Based on these studies, in 1989 Laboratoires Meram was granted marketing authorization for acamprosate in France under the trade name Aotal®. Since then, acamprosate has been extensively used and studied throughout Europe and, subsequently, in the United States.
Although acamprosate has been used in Europe for more than 20 years, it was not approved by FDA until July 2004. Acamprosate became available for use in the United States in January 2005, under the trade name Campral® Delayed-Release Tablets (Merck Santé, a subsidiary of Merck KGaA, Darmstadt, Germany). Campral is currently marketed in the United States by Forest Pharmaceuticals.
Pharmacology
Acamprosate's action in maintenance of alcohol abstinence is not completely understood, but evidence indicates that acamprosate interacts with the glutamate neurotransmitter system, reducing and normalizing the pathologic glutamatergic hyperactivity that occurs during protracted withdrawal from alcohol. It is hypothesized that this normalization leads to a reduction of common symptoms of protracted, or postacute, withdrawal such as insomnia, anxiety, and restlessness—symptoms that may contribute to a patient's return to alcohol use (reviewed by Litten, Fertig, Mattson, & Egli, 2005; Myrick & Anton, 2004; Thomson Healthcare, Inc., 2006). Chick, Lehert, and Landron (2003) have proposed that patients who returned to drinking while taking acamprosate drank less, and less frequently, than those taking placebo.
The bioavailability of acamprosate after oral administration is approximately 11 percent, and stable plasma concentrations are reached within 5 days of taking the medication. Acamprosate is not metabolized and is excreted primarily by the kidneys as acamprosate.
Why Use Acamprosate?
Efficacy
Considerable evidence supports the efficacy of acamprosate in the treatment of alcohol use disorders (AUDs). Numerous European trials have found acamprosate significantly more effective than placebo in reducing drinking days, increasing complete abstinence, and lengthening time to relapse. Evidence from U.S. studies has been mixed. The Combining Medications and Behavioral Interventions (COMBINE) study did not find acamprosate to be more effective than placebo (Anton et al., 2006). However, some analyses and reviews have concluded otherwise (although these analyses did not include data from the COMBINE study). A meta-analysis (an analysis of the outcome data of multiple individual studies) of European studies concluded that acamprosate is moderately effective in achieving and maintaining abstinence (Bouza, Magro, Muñoz, & Amate, 2004). This analysis of 12 studies found that acamprosate increased the continuous abstinence rate and doubled continuous abstinence duration compared with placebo. Similarly, a review of clinical trials by Mann (2004) concluded that acamprosate is more effective than placebo in the short and long term. Mason and colleagues (2006) found acamprosate to be superior to placebo only when controlling for patient characteristics associated with treatment efficacy. They also found acamprosate superior to placebo for a subgroup of patients motivated to achieve total abstinence.
Methodological differences between U.S. and European studies may account for differing results. These differences have included the following:
- Duration of pretreatment abstinence required
- Duration of treatment (European studies tended to be longer than U.S. studies)
- Concomitant medications allowed (European studies tended to be more flexible in allowing medications than U.S. studies)
- Nature and intensity of psychosocial treatment (U.S. studies tended to have more standardized and intensive psychosocial treatments)
- Outcome measures used
- Severity of participants' AUDs.
A thorough discussion of acamprosate efficacy studies is in this TIP's online literature review.
Safety
Acamprosate has a good safety profile:
- Patients maintained on acamprosate have not developed tolerance for or dependence on it, and it appears to have no potential for abuse.
- It carries virtually no overdose risk; even at overdoses up to 56 grams (a normal daily dose is 2 grams), acamprosate was generally well tolerated by patients (Thomson Healthcare, Inc., 2006).
- Most side effects are mild and transient, lessening or disappearing within the first few weeks of treatment (diarrhea tends to persist).
- Although there is a pharmacokinetic interaction by which acamprosate can increase naltrexone blood levels, there are no other clinically significant interactions between acamprosate and other medications (Johnson et al., 2003).
Acamprosate also has advantages over other medications for treating AUDs in some patients:
- Because acamprosate is not metabolized by the liver, it can be used safely even by patients with severe liver disease, unlike oral or injectable naltrexone or disulfiram.
- Because it does not affect endogenous or exogenous opioids, it can be used with patients receiving opioid maintenance therapy (reviewed by Myrick & Anton, 2004) or undergoing treatment with opioids for acute or chronic pain, unlike oral or injectable naltrexone.
- Because acamprosate does not interact with benzodiazepines or other medications used in medical detoxification, it can be continued safely if a patient returns to drinking and subsequently requires detoxification.
How Is Acamprosate Used?
Initiating Treatment With Acamprosate
Acamprosate is typically initiated 5 days following drinking cessation. However, acamprosate can be used safely with alcohol (and with benzodiazepines), and it can be started during medically supervised withdrawal. Acamprosate therapy should be maintained if a patient relapses to alcohol use. Acamprosate reaches full effectiveness in 5 to 8 days.
Before initiating treatment, healthcare practitioners should do the following:
- Conduct or refer patients for a thorough medical exam and assessment (as described in Chapter 6—Patient Management).
- Perform renal function tests (a standard panel for urea, electrolytes, and serum creatinine) to rule out severe renal impairment.
Side Effects, Contraindications, and Cautions
Exhibit 2-1 lists acamprosate's side effects. The most common side effect of acamprosate is diarrhea. This and other side effects are usually mild and resolve quickly. In some patients, diarrhea is severe and persistent. Patients should be instructed not to discontinue acamprosate if they experience side effects and to inform their prescribing professional.
Exhibit 2-1 Acamprosate Side Effects
| Most Common Side Effect | Less Common Side Effects |
|---|---|
| Diarrhea | Suicidal ideation (less common, but serious) Intestinal cramps Headache Flatulence Increased or decreased libido Insomnia Anxiety Muscle weakness Nausea Itchiness Dizziness |
Exhibit 2-2 lists acamprosate contraindications, and Exhibit 2-3 lists cautions.
Exhibit 2-2 Acamprosate Contraindications
| Patient Condition or Circumstance | Treatment Recommendation |
|---|---|
| Previous hypersensitivity to acamprosate or its components | Do not prescribe acamprosate |
| Severe renal impairment (creatinine clearance ≤30 mL/min) | Do not prescribe acamprosate |
Exhibit 2-3 Acamprosate Cautions
| Patient Condition or Circumstance | Treatment Recommendation |
|---|---|
| Moderate renal impairment (creatinine clearance 30–50 mL/min) | Reduce dosage to one 333 mg tablet daily |
| Pregnant or nursing women | Avoid using acamprosate unless potential benefits outweigh risks (Acamprosate is FDA pregnancy category C; it is unknown whether acamprosate is excreted in human milk.) |
| Age 65 or older | Because of a higher risk of diminished renal function in persons 65 or older, perform baseline and frequent renal function tests; acamprosate has not been evaluated for safety or efficacy in geriatric populations |
| Children or adolescents | Prescribe with caution; acamprosate has not been evaluated for safety or efficacy in pediatric or adolescent populations |
Patient Management
Ways for managing adverse reactions to acamprosate are listed in Exhibit 2-4.
Exhibit 2-4 Adverse Reactions to Acamprosate and Their Management
| Adverse Reaction | Management |
|---|---|
| Suicidal ideation, suicide attempts (very uncommon, but serious)* | Inform patients to contact the prescribing professional immediately Monitor patients for onset or worsening of depression Obtain a psychiatric consult and/or prescribe antidepressant medication as necessary Discontinue acamprosate |
| Severe and/or persistent diarrhea | Treat with Imodium® or Pepto-Bismol®
Recommend appropriate dietary changes Reduce acamprosate dosage or discontinue use if diarrhea remains intolerable after treatment |
- *
Suicidal ideation is closely linked with substance use disorders, with or without acamprosate use. More information about managing the risk can be found at the National Suicide Prevention Center's Web site (http://www
.sprc.org) and at the Suicide Prevention for Physicians Web site (http: //suicideandmentalhealthassociationinternational .org/preventionphy.html).
There is no evidence that acamprosate impairs renal function. Followup laboratory work is not necessary unless evidence of renal impairment exists at treatment initiation.
Patient Education
In addition to giving patients the general patient education guidelines discussed in Chapter 6, healthcare providers should ensure that patients taking acamprosate know the following:
- The benefits and limitations of acamprosate
- What to expect—
- Possible side effects
- Full effectiveness in 5–8 days
- For women of childbearing age, the importance of using an effective birth control method
- To continue taking acamprosate if a slip or relapse occurs and to inform their prescribing professional immediately
- To notify the prescribing professional immediately if they begin to have suicidal thoughts, if they begin to feel depressed, or if an existing depression worsens
- That tablets should not be crushed
- Not to take extra medication if a dose is missed and it is time to take the next dose.
Who Is Appropriate for Treatment With Acamprosate?
Research on patient-specific characteristics as predictors of acamprosate efficacy has not identified any particular characteristics (e.g., level of physiological dependence on alcohol, age of onset, gender) that predict acamprosate treatment outcomes (Verheul, Lehert, Geerlings, Koeter, & Van Den Brink, 2005). However, evidence exists that acamprosate is most effective for patients who, at treatment onset, are motivated for complete abstinence rather than decreased drinking (Mason et al., 2006).
As noted earlier, acamprosate does not affect endogenous or exogenous opioids, so it may be particularly appropriate for patients who are receiving opioid maintenance therapy (reviewed by Myrick & Anton, 2004), at risk of relapsing to opioid use, or undergoing treatment with opioids for pain. Because there are no clinically significant drug interactions with acamprosate, it can be a safe medication for patients who are coping with multiple medical issues and are taking many other medications.
Acamprosate must be taken three times per day. Extra support will be needed for patients with cognitive deficits or who otherwise might have trouble remembering and adhering to a schedule. Seven-day dosing pillboxes or blistercard packages that indicate the time of day for each dose may be useful.
Treatment Duration and Discontinuing Acamprosate
The effectiveness and safety of acamprosate have been evaluated for up to 1 year. The length of time a particular patient takes acamprosate will be determined, ideally, with input from the prescribing professional, the specialty treatment provider, and the patient. Discontinuation of acamprosate may be considered once a patient has achieved stable abstinence from alcohol, reports diminished craving, and has established a sound plan and support for ongoing recovery. Acamprosate therapy also may be discontinued if a patient is not adhering to the medication regimen. Acamprosate should not be discontinued just because a patient returns to alcohol use.
There is no withdrawal syndrome associated with discontinuing acamprosate, and it is not necessary to taper the dose.
Final Clinical Thoughts
Evidence from European studies and clinical experience suggest acamprosate can be an effective medication for the treatment of AUDs. Acamprosate has several attractive features, including its minimal side effects, lack of negative liver effects, and drug interaction profiles. For many patients, these features make it a worthwhile agent to try despite its small therapeutic effect. Hence, the clinician using medications to treat patients with alcohol dependence should be familiar with acamprosate and its use and may find it a useful medication for certain patients (e.g., those treated with opioid analgesics) or under certain circumstances (e.g., for a patient who is taking several other medications). The healthcare provider may also find it useful when combined with other alcohol treatment medications and with psychosocial support.
Because acamprosate must be taken three times per day, providers must pay particular attention to patient adherence. Providers can help patients adhere to the regimen by helping them develop ways to remember, such as wearing a “reminder” bracelet, setting a watch alarm, implementing a recovery-oriented ritual around taking the medication, or providing them with a special pillbox or blistercard pack.
- Chapter 2—Acamprosate - Incorporating Alcohol Pharmacotherapies Into Medical Pra...Chapter 2—Acamprosate - Incorporating Alcohol Pharmacotherapies Into Medical Practice
Your browsing activity is empty.
Activity recording is turned off.
See more...