Acamprosate

181.21014

181.21

278-667-4

N4K14YGM3J

DTXSID3044259

N07BB03|N - Nervous system

2924199090

91.8

-1.1

Solid

1.336g/cm3

1.491

1.88e+01 g/L

1.8X10-8 mm Hg at 25 deg C (est)

Henry's Law constant = 7.4X10-15 atm-cu m/mol at 25 °C (est)

pKa = 0.27 (sulfonic acid group) (est)

White, odorless or nearly odorless powder; freely soluble in water; practically insoluble in absolute ethanol and dichloromethane /Acamprosate calcium/|Hydroxyl radical reaction rate constant = 1.3X10-11 cu cm/molecule-sec at 25 °C (est)

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl acamprosate calcium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Acamprosate Calcium/

In all reported cases of acute overdosage with acamprosate (total reported doses of up to 56 grams of acamprosate calcium), the only symptom that could be reasonably associated with acamprosate was diarrhea.

Acamprosate therapy has not been associated with serum enzyme elevations over and above rates that occur with placebo therapy. Despite widescale use in alcohol treatment programs, there have yet to be published reports of clinically apparent acute liver injury attributed to acamprosate therapy.

Coadministration /with naltrexone/ increases Cmax 33% and AUC 25% of acamprosate...|Acamprosate had no inducing potential on the cytochrome CYP1A2 and 3A4 systems, and in vitro inhibition studies suggest that acamprosate does not inhibit in vivo metabolism mediated by cytochrome CYP1A2, 2C9, 2C19, 2D6, 2E1, or 3A4. The pharmacokinetics of /acamprosate/ were unaffected when coadministered with alcohol, disulfiram or diazepam. Similarly, the pharmacokinetics of ethanol, diazepam and nordiazepam, imipramine and desipramine, naltrexone and 6-beta naltrexol were unaffected following co-administration with /acamprosate/.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Non detectable

Acamprosate's production and use as a drug for maintaining abstinence from alcohol(1) may result in its release to the environment through various waste streams.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that acamprosate is expected to have very high mobility in soil(SRC). The estimated pKa of acamprosate is 0.27 (sulfonic acid)(3), indicating that this compound will exist primarily as an anion in the environment. Volatilization of acamprosate from moist soil surfaces is not expected to be an important fate process(SRC) because anions do not volatilize. Acamprosate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.8X10-8 mm Hg(SRC), determined from a fragment constant method(4). Biodegradation data for acamprosate were not available(SRC, 2005).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that acamprosate is not expected to adsorb to suspended solids and sediment(SRC). The pKa of acamprosate is 0.27 (sulfonic acid)(3), indicating that this compound will exist primarily as an anion in the environment. Volatilization from water surfaces is not expected(SRC) since anions do not volatilize. According to a classification scheme(4), an estimated BCF of 3(SRC), from an estimated log Kow of -2.9(5) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data for acamprosate were not available(SRC, 2005).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), acamprosate, which has an estimated vapor pressure of 1.8X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase acamprosate may be removed from the air by wet or dry deposition(SRC). Acamprosate does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Acamprosate is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Acamprosate does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated for acamprosate(SRC), using an estimated log Kow of -2.9(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of acamprosate can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that acamprosate is expected to have very high mobility in soil. The estimated pKa of acamprosate is 0.27 (sulfonic acid)(3), indicating that this compound will exist primarily as an anion in the environment and anions generally do not adsorb to soil as strongly as their neutral counterparts(4).

The estimated pKa of acamprosate is 0.27 (sulfonic acid)(1), indicating that this compound will exist primarily as an anion in the environment. Acamprosate is expected to be essentially nonvolatile from moist soil and water surfaces since anions do not volatilize. Acamprosate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.8X10-8 mm Hg(SRC), determined from a fragment constant method(2).

While data specific to acamprosate were not located(SRC, 2006), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

It is not known whether acamprosate is distributed into breast milk. However, acamprosate is distributed into the milk of lactating rats.

Occupational exposure to acamprosate may occur through inhalation and dermal contact with this compound at workplaces where acamprosate is produced or used. Exposure to acamprosate among the general population may be limited to those administered this substance as a drug. (SRC)

For the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation|FDA Label

Acamprosate is a synthetic amino acid and a neurotransmitter analogue that is used as an alcohol deterrent in management of alcohol dependence and abuse. Acamprosate has not been linked to serum enzyme elevations during therapy and has not been linked to cases of clinically apparent liver injury.

Substance Abuse Treatment Agents

Alcohol Deterrents|Acamprosate is indicated for the maintenance of sobriety in patients with alcohol dependence who are abstinent at treatment initiation. Acamprosate treatment should be part of a comprehensive management program including psychosocial support. /Included in US product labeling/

FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./|Patients sensitive to sulfites may be sensitive to acamprosate also. Sulfites were used in the synthesis and traces of residual sulfites may be present.|Acamprosate is contraindicated in patients with severe renal impairment (creatinine clearance

The administration of acamprosate calcium is not associated with the development of tolerance or dependence in animal studies. ... /acamprosate/ did not produce any evidence of withdrawal symptoms in patients in clinical trials at therapeutic doses. Post marketing data, collected retrospectively outside the U.S., have provided no evidence of /acamprosate/ abuse or dependence.

Pharmacodynamic studies have shown that acamprosate calcium reduces alcohol intake in alcohol-dependent animals in a dose-dependent manner and that this effect appears to be specific to alcohol and the mechanisms of alcohol dependence. Acamprosate calcium has negligible observable central nervous system (CNS) activity in animals outside of its effects on alcohol dependence, exhibiting no anticonvulsant, antidepressant, or anxiolytic activity.

Substances interfering with the metabolism of ethyl alcohol, causing unpleasant side effects thought to discourage the drinking of alcoholic beverages. Alcohol deterrents are used in the treatment of alcoholism. (See all compounds classified as Alcohol Deterrents.)

The absolute bioavailability of acamprosate after oral administration is about 11%. The food effect on absorption is not clinically significant and no adjustment of dose is necessary.|Following oral administration of CAMPRAL®, the major route of excretion is via the kidneys as acamprosate.|72 to 109 L|Protein binding: Negligible.|Volume of distribution (VolD): 72 to 109 liters (approximately 1 L/kg) following intravenous administration.|The absolute bioavailability following oral administration is about 11%. Food decreases bioavailability as measured by Cmax and AUC, 42% and 23% respectively. The effect of food on absorption is not clinically significant.|Elimination: Via the kidneys as unchanged drug.|For more Absorption, Distribution and Excretion (Complete) data for ACAMPROSATE (8 total), please visit the HSDB record page.

Acamprosate does not undergo metabolism.

20 - 33 hours|Terminal: 20 to 33 hours following oral dosing of 2 x 333 mg.

The mechanism of action of acamprosate in maintenance of alcohol abstinence is not completely understood. Chronic alcohol exposure is hypothesized to alter the normal balance between neuronal excitation and inhibition. in vitro and in vivo studies in animals have provided evidence to suggest acamprosate may interact with glutamate and GABA neurotransmitter systems centrally, and has led to the hypothesis that acamprosate restores this balance. It seems to inhibit NMDA receptors while activating GABA receptors.|... Chronic alcohol exposure is hypothesized to alter the normal balance between neuronal excitation and inhibition. In vitro and in vivo studies in animals have provided evidence to suggest acamprosate may interact with glutamate and GABA neurotransmitter systems centrally, and has led to the hypothesis that acamprosate restores this balance. Pharmacodynamic studies have shown that acamprosate calcium reduces alcohol intake in alcohol-dependent animals in a dose-dependent manner and that this effect appears to be specific to alcohol and the mechanisms of alcohol dependence. Acamprosate calcium has negligible observable central nervous system (CNS) activity in animals outside of its effects on alcohol dependence, exhibiting no anticonvulsant, antidepressant, or anxiolytic activity.

/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/HUMAN EXPOSURE STUDIES/ 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, no consistent pattern of relationship between the clinical course of recovery from alcoholism and the emergence of suicidality was identified.|/HUMAN EXPOSURE STUDIES/ In all reported cases of acute overdosage with /acamprosate/ (total reported doses of up to 56 grams of acamprosate calcium), the only symptom that could be reasonably associated with /acamprosate/ was diarrhea. Hypercalcemia has not been reported in cases of acute overdose. A risk of hypercalcemia should be considered in chronic overdosage only. Treatment of overdose should be symptomatic and supportive.

acamprosate

Campral: 333 mg tablets are enteric-coated.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients