Acamprosate

Acamprosate affects chemicals in the brain that may be unbalanced in a person who is addicted to alcohol. Acamprosate works by restoring this chemical balance in the brain in an alcohol-dependent person who has recently quit drinking.

Acamprosate is used together with behavior modification and counseling support to help a person who has recently quit drinking alcohol continue to choose not to drink.

Acamprosate is not likely to be helpful if you have not already quit drinking or undergone detoxification. It may not help you if you are also addicted to other substances besides alcohol.

Acamprosate may also be used for purposes not listed in this medication guide.

You should not use acamprosate if you have severe kidney disease.

You should not use acamprosate if you are allergic to it, or if you have severe kidney disease.

Acamprosate will not treat or prevent alcohol withdrawal symptoms.

To make sure acamprosate is safe for you, tell your doctor if you have any type of kidney problem.

You may have thoughts about suicide while taking acamprosate. Your doctor will need to check your progress at regular visits. Your family or other caregivers should also be alert to changes in your mood or symptoms.

It is not known whether acamprosate will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

It is not known whether acamprosate passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe anxiety or depression;
• mood or behavior changes;
• thoughts about suicide or hurting yourself;
• swelling in your hands or feet; or
• pounding heartbeats or fluttering in your chest.

Common side effects may include:

• pain or weakness;
• loss of appetite, nausea, diarrhea, gas;
• dizziness, anxiety;
• itching or sweating;
• depressed mood;
• sleep problems (insomnia);
• dry mouth; or
• numbness or tingly feeling.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe anxiety or depression;

• mood or behavior changes;

• thoughts about suicide or hurting yourself;

• swelling in your hands or feet; or

• pounding heartbeats or fluttering in your chest.

Common side effects may include:

• pain or weakness;

• loss of appetite, nausea, diarrhea, gas;

• dizziness, anxiety;

• itching or sweating;

• depressed mood;

• sleep problems (insomnia);

• dry mouth; or

• numbness or tingly feeling.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Usual Adult Dose for Alcohol Dependence:

666 mg orally three times a day

Usual Geriatric Dose for Alcohol Dependence:

666 mg orally three times a day

Since geriatric patients may be more prone to a decrease in renal function, the manufacturer advises greater care in dose selection and close monitoring of renal function during therapy in this population.

Usual Pediatric Dose for Alcohol Dependence:

There are no data on the safety and efficacy of acamprosate in this population.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include:

• diarrhea

If you take too much acamprosate regularly for a long time, you may experience certain symptoms. Call your doctor if you experience any of these symptoms:

• loss of appetite
• upset stomach
• constipation
• extreme thirst
• tiredness
• muscle weakness
• restlessness
• confusion

Keep all appointments with your doctor and counselor or support group.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Use acamprosate as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food as you have been told by your doctor.
• Swallow whole. Do not chew, break, or crush.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• To gain the most benefit, do not miss doses.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Pregnancy

Teratogenic effects: Acamprosate calcium has been shown to be teratogenic in rats when given in doses that are approximately equal to the human dose (on a mg/m2 basis) and in rabbits when given in doses that are approximately 3 times the human dose (on a mg/m2 basis). Acamprosate calcium produced a dose-related increase in the number of fetuses with malformations in rats at oral doses of 300 mg/kg/day or greater (approximately equal to the maximum recommended human daily (MRHD) oral dose on a mg/m2 basis). The malformations included hydronephrosis, malformed iris, retinal dysplasia, and retroesophageal subclavian artery. No findings were observed at an oral dose of 50 mg/kg/day (approximately one-fifth the MRHD oral dose on a mg/m2 basis). An increased incidence of hydronephrosis was also noted in Burgundy Tawny rabbits at oral doses of 400 mg/kg/day or greater (approximately 3 times the MRHD oral dose on a mg/m2 basis). No developmental effects were observed in New Zealand white rabbits at oral doses up to 1000 mg/kg/day (approximately 8 times the MRHD oral dose on a mg/m2 basis). The findings in animals should be considered in relation to known adverse developmental effects of ethyl alcohol, which include the characteristics of fetal alcohol syndrome (craniofacial dysmorphism, intrauterine and postnatal growth retardation, retarded psychomotor and intellectual development) and milder forms of neurological and behavioral disorders in humans. There are no adequate and well controlled studies in pregnant women. Acamprosate calcium should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic effects: A study conducted in pregnant mice that were administered Acamprosate calcium by the oral route starting on Day 15 of gestation through the end of lactation on postnatal day 28 demonstrated an increased incidence of still-born fetuses at doses of 960 mg/kg/day or greater (approximately 2 times the MRHD oral dose on a mg/m2 basis). No effects were observed at a dose of 320 mg/kg/day (approximately one-half the MRHD dose on a mg/m2 basis).

Labor and Delivery

The potential for Acamprosate calcium to affect the duration of labor and delivery is unknown.

Nursing Mothers

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 calcium is administered to a nursing woman.

Pediatric Use

The safety and efficacy of Acamprosate calcium have not been established in the pediatric population.

Geriatric Use

Forty-one of the 4234 patients in double-blind, placebo-controlled, clinical trials of Acamprosate calcium were 65 years of age or older, while none were 75 years of age or over. There were too few patients in the ≥65 age group to evaluate any differences in safety or effectiveness for geriatric patients compared to younger patients.

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 [see Clinical Pharmacology (12.3), Adverse Reactions (6.1), and Dosage and Administration (2.1)].

Renal Impairment

Acamprosate calcium is contraindicated in patients with severe renal impairment (creatinine clearance of ≤30 mL/min) [see Dosage and Administration (2.1), Contraindications (4.2), Warnings and Precautions (5.1), and Clinical Pharmacology (12.3)].

Carcinogenesis, Mutagenesis, Impairment of Fertility

Dietary administration of Acamprosate calcium for 2 years to Sprague-Dawley rats at doses of 25, 100 and 400 mg/kg/day (up to 3 times the maximum recommended human daily (MRHD) oral dose on an AUC basis) and CD-1 mice at doses of 400, 1200 and 3600 mg/kg/day (up to 25 times the MRHD on an AUC basis) showed no evidence of increased tumor incidence.

Acamprosate calcium was negative in all genetic toxicology studies conducted. Acamprosate calcium demonstrated no evidence of genotoxicity in an in vitro bacterial reverse point mutation assay (Ames assay) or an in vitro mammalian cell gene mutation test using Chinese Hamster Lung V79 cells. No clastogenicity was observed in an in vitro chromosomal aberration assay in human lymphocytes and no chromosomal damage detected in an in vivo mouse micronucleus assay.

Acamprosate calcium had no effect on fertility after treatment for 70 days prior to mating in male rats and for 14 days prior to mating, throughout mating, gestation and lactation in female rats at doses up to 1000 mg/kg/day (approximately 4 times the MRHD oral dose on a mg/m2 basis). In mice, Acamprosate calcium administered orally for 60 days prior to mating and throughout gestation in females at doses up to 2400 mg/kg/day (approximately 5 times the MRHD oral dose on a mg/m2 basis) had no effect on fertility.

• GABA Agonist/Glutamate Antagonist

Hypersensitivity to acamprosate or any component of the formulation; severe renal impairment (CrCl ≤30 mL/minute)

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Acamprosate may be found in some form under the following brand names:

• Campral

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• other medical conditions you have
• how you respond to this medication
• your kidney function

The recommended dose of acamprosate (Campral) is two 333 mg tablets (each dose should total 666 mg) taken three times daily. A lower dose may be effective in some patients.

The recommended dose of acamprosate (Campral), for patients with moderate renal impairment, is one 333 mg tablet taken three times daily.

Dosage Forms & Strengths

tablet

• 333mg

Alcholism

Indicated for maintenance of alcohol abstinence in patients who are abstinent at treatment initiation

666 mg PO TID

Renal Impairment

CrCl 30-50 mL/min: 333 mg PO TID

CrCl <30 mL/min: Do not administer

Fragile X Syndrome (Orphan)

Orphan designation for treatment of fragile X syndrome

Orphan sponsor

• Confluence Pharmaceuticals, LLC; Box 528, 351 West 10th Street; Indianapolis, IN 46202

Safety and efficacy have not been established

Contraindications

Hypersensitivity

Severe renal impairment

Cautions

Does not diminish withdrawal symptoms

May impair ability to operate heavy machinery or drive

Efficacy not established in promoting abstinence in non-abstinent patients

Check for suicidal tendencies

Use as part of a conprehensive to treat alcohol dependence

Possibility of acute renal failure (ARF)

Acamprosate is contraindicated in patients with a creatinine clearance equal to or less than 30 mL/min.

Acamprosate therapy has not been reported to eliminate or diminish alcohol withdrawal symptoms.

Acamprosate has not been reported to cause a disulfiram type reaction as a result of ethanol ingestion.

There are no data on acamprosate causing alcohol aversion.

Acamprosate may impair the mental abilities necessary for potentially hazardous tasks such as driving or operating machinery.

Acamprosate should only be used in conjunction with a treatment program that includes counseling and support.

Patients undergoing treatment for alcohol dependence, whether they are taking acamprosate or not, should be monitored for the emergence of symptoms of depression and/or suicidal behavior. 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 physician.

The concomitant intake of alcohol and acamprosate does not affect the pharmacokinetics of either alcohol or acamprosate.

Safety and efficacy have not been established in pediatric patients (less than 18 years of age).