Usage
- Acamprosate is prescribed for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. It is used as part of a comprehensive psychosocial treatment program.
- Pharmacological Classification: Acamprosate is classified as a homotaurine analogue and affects glutamatergic N-methyl-D-aspartate (NMDA) receptors and gamma-aminobutyric acid (GABA) neurotransmission. It’s sometimes categorized as an anti-craving medication or within a broader category of medications for substance use disorders.
Alternate Names
- International Nonproprietary Name (INN): Acamprosate Calcium
- Brand Name: Campral
How It Works
- Pharmacodynamics: Acamprosate is thought to restore the balance between neuronal excitation and inhibition altered by chronic alcohol exposure primarily by interacting with the glutamatergic and GABAergic systems in the brain. This suggests it may reduce the intensity of protracted withdrawal symptoms, including craving.
- Pharmacokinetics:
- Absorption: Oral absorption is slow, variable and incomplete (about 11%). Food can further reduce absorption.
- Metabolism: Acamprosate is not extensively metabolized.
- Elimination: Primarily eliminated unchanged by the kidneys. The elimination half-life is approximately 20-33 hours.
- Mode of Action: Acamprosate’s precise mechanism isn’t fully understood. It is believed to modulate glutamatergic and GABAergic neurotransmission, potentially by antagonizing NMDA receptors and stimulating GABAergic activity. It may also interact with calcium channels. No direct binding to specific receptors has been definitively demonstrated.
- Elimination Pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
- Standard Dose: 666 mg (two 333 mg tablets) three times a day with meals for patients weighing 60 kg or more.
- For patients weighing less than 60 kg: 666 mg in the morning, 333 mg at midday, and 333 mg at night.
Children:
- Not recommended for use in children under 18 years of age.
Special Cases:
- Elderly Patients: Not recommended for patients over 65 years. Dose reduction may be necessary due to age-related decline in renal function.
- Patients with Renal Impairment:
- Moderate renal impairment (creatinine clearance 30-50 mL/min): Initial dose 333 mg three times a day, maintenance dose can be titrated up to a maximum of 666mg three times a day.
- Severe renal impairment (CrCl <30 mL/min): Contraindicated.
- Patients with Hepatic Dysfunction:
- No dosage adjustment required for mild to moderate impairment.
- Severe hepatic impairment (Child-Pugh C): Contraindicated.
- Patients with Comorbid Conditions: Caution is advised in patients with depression and suicidal ideation due to the complex relationship between alcohol dependence, depression and suicidality. Careful monitoring for mood changes is essential.
Clinical Use Cases
Acamprosate is specifically indicated for maintaining abstinence from alcohol in patients with alcohol dependence. It’s not indicated for other clinical use cases like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose modifications are necessary for renal impairment. See special cases section for details.
Side Effects
Common Side Effects
- Diarrhea
- Nausea
- Vomiting
- Flatulence
- Abdominal pain
- Dry mouth
- Insomnia
- Headache
- Dizziness
- Depression
- Anxiety
- Asthenia (Weakness or lack of energy)
- Pruritus
- Decreased libido
- Impotence
Rare but Serious Side Effects
- Suicidal thoughts or behavior
- Severe allergic reactions (including anaphylaxis)
Long-Term Effects
Long-term effects are not well-established, however continued alcohol use can negatively impact health outcomes. Patients should be monitored for depression and suicidal ideation throughout treatment.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include severe allergic reactions and suicidal ideation. These warrant immediate intervention.
Contraindications
- Hypersensitivity to acamprosate or its components
- Severe renal impairment (CrCl < 30 mL/min)
- Severe hepatic impairment (Child-Pugh Class C)
- Breastfeeding
Drug Interactions
- No clinically significant drug interactions have been definitively identified.
- Coadministration with naltrexone may increase acamprosate exposure but typically doesn’t require a dose adjustment.
- Food decreases absorption but doesn’t generally require dose modification.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category C (US FDA). Although animal studies suggest a teratogenic potential, limited human data is available. Use only if the benefit outweighs the risk to the fetus.
- Breastfeeding: Acamprosate is likely excreted in breast milk. Breastfeeding is contraindicated.
Drug Profile Summary
- Mechanism of Action: Modulates glutamatergic NMDA and GABA neurotransmission, reducing alcohol cravings.
- Side Effects: Diarrhea, nausea, insomnia, anxiety, depression.
- Contraindications: Severe renal/hepatic impairment, hypersensitivity, breastfeeding.
- Drug Interactions: No significant interactions have been documented, although naltrexone may increase exposure.
- Pregnancy & Breastfeeding: Category C, contraindicated during breastfeeding.
- Dosage: 666 mg TID for adults over 60 kg, adjustments based on renal function and weight.
- Monitoring Parameters: Renal function, liver function tests, mental status including suicidal ideation.
Popular Combinations
- Naltrexone: Combination therapy might be more effective than monotherapy for some individuals.
Precautions
- Monitor renal and liver function, particularly at treatment initiation.
- Closely monitor for signs of depression and suicidality.
- Pregnancy: Assess risks and benefits carefully before use.
- Children and elderly: Not recommended.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Acamprosate?
A: 666 mg TID for adults over 60 kg, with dose reductions based on renal function and weight. Not recommended for children or the elderly.
Q2: How does Acamprosate work?
A: It modulates glutamatergic and GABAergic neurotransmission, reducing cravings and helping maintain abstinence.
Q3: What are the common side effects of Acamprosate?
A: Diarrhea, nausea, insomnia, headache, anxiety, depression.
Q4: Is Acamprosate safe during pregnancy?
A: Category C, use only if the potential benefit outweighs the risk.
Q5: Can Acamprosate be used with other medications for alcohol dependence?
A: Yes, acamprosate can be used with naltrexone, and it has not shown significant interactions with other drugs, though always check for potential issues.
Q6: What are the contraindications for Acamprosate?
A: Severe renal/hepatic impairment, hypersensitivity, breastfeeding.
Q7: How long should treatment with Acamprosate continue?
A: Treatment is typically recommended for one year.
Q8: Does Acamprosate interact with alcohol?
A: Acamprosate does not have a direct adverse reaction with alcohol. However, consuming alcohol while on Acamprosate might diminish the effectiveness of treatment.
Q9: Can Acamprosate prevent alcohol withdrawal symptoms?
A: No, it’s designed for maintaining abstinence after detoxification, not managing withdrawal.
Q10: What should patients be monitored for during Acamprosate therapy?
A: Monitor renal and hepatic function, as well as mental status changes, particularly depression and suicidal thoughts.
