Contraindications
Acamprosate is primarily removed by the kidneys and should not be given to people with severely impaired kidneys (creatinine clearance less than 30 mL/min). A dose reduction is suggested in those with moderately impaired kidneys (creatinine clearance between 30 mL/min and 50 mL/min). It is also contraindicated in those who have a strong allergic reaction to acamprosate calcium or any of its components. Adverse effects
The US label carries warnings about increases of suicidal behavior, major depressive disorder, and kidney failure.Adverse effects that caused people to stop taking the drug in clinical trials included diarrhea, nausea, depression, and anxiety.Potential adverse effects include headache, stomach pain, back pain, muscle pain, joint pain, chest pain, infections, flu-like symptoms, chills, heart palpitations, high blood pressure, fainting, vomiting, upset stomach, constipation, increased appetite, weight gain, edema, sleepiness, decreased sex drive, impotence, forgetfulness, abnormal thinking, abnormal vision, distorted sense of taste, tremors, runny nose, coughing, difficulty breathing, sore throat, bronchitis, and rashes. Pharmacology
Pharmacodynamics
The pharmacodynamics of acamprosate are complex and not fully understood; however, it is believed to act as an NMDA receptor antagonist and positive allosteric modulator of GABAA receptors.Its activity on those receptors is indirect, unlike that of most other agents used in this context. An inhibition of the GABA-B system is believed to cause indirect enhancement of GABAA receptors.
Acamprosate has been successfully used to control tinnitus, hyperacusis, ear pain, and inner ear pressure during alcohol use due to spasms of the tensor tympani muscle.In addition, alcohol also inhibits the activity of N-methyl-D-aspartate receptors (NMDARs). Chronic alcohol consumption leads to the overproduction (upregulation) of these receptors. Thereafter, sudden alcohol abstinence causes the excessive numbers of NMDARs to be more active than normal and to contribute to the symptoms of delirium tremens and excitotoxic neuronal death. Withdrawal from alcohol induces a surge in release of excitatory neurotransmitters like glutamate, which activates NMDARs. Acamprosate reduces this glutamate surge. The drug also protects cultured cells from excitotoxicity induced by ethanol withdrawal and from glutamate exposure combined with ethanol withdrawal.The substance also helps re-establish a standard sleep architecture by normalizing stage 3 and REM sleep phases, which is believed to be an important aspect of its pharmacological activity. Pharmacokinetics
Acamprosate is not metabolized by the human body. Acamprosates absolute bioavailability from oral administration is approximately 11%, and its bioavailability is decreased when taken with food. Following administration and absorption of acamprosate, it is excreted unchanged (i.e., as acamprosate) via the kidneys.Its absorption and elimination are very slow, with a Tmax of 6 hours and an elimination half life of over 30 hours. History
Acamprosate was developed by Lipha, a subsidiary of Merck KGaA.