HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed
to use CAMPRAL safely and effectively. See fullprescribing information for CAMPRAL.
CAMPRAL® (acamprosate calcium) Delayed-Release
Tablets
Initial U.S. Approval: 2004----------------INDICATIONS AND USAGE------------------- Campral® is indicated for the maintenance of abstinencefrom alcohol in patients with alcohol dependence who are
abstinent at treatment initiation (1, 14).
 Treatment with Campral should be part of a comprehensive
management program that includes psychosocial support(1).
-------------DOSAGE AND ADMINISTRATION------------- Recommended dose: 666 mg (two 333 mg tablets) taken
three times daily (2).
 Dose reduction to one 333 mg tablet taken three times daily
for patients with moderate renal impairment (creatinine
clearance 30-50 mL/min) (2.1).
 Campral is contraindicated in patients with severe renal
impairment (creatinine clearance of ≤30 mL/min) (2.1, 4.2,
5.1, 8.6, 12.3).
------------DOSAGE FORMS AND STRENGTHS------------Enteric-coated tablets, 333 mg (3).

--------------WARNINGS AND PRECAUTIONS------------ Dose reduction is required for patients with moderate
renal impairment (5.1).
 Monitor patients for depression or suicidal ideation andprompt patients, families, and caregivers to report such
symptoms to the health care provider (5.2).
-----------------------ADVERSE REACTIONS-----------------Common adverse events that occurred in any Campral
treatment group at a rate of 3% or greater and greater than theplacebo group in controlled clinical trials with spontaneously
reported adverse events are: accidental injury, asthenia, pain,
anorexia, diarrhea, flatulence, nausea, anxiety, depression,dizziness, dry mouth, insomnia, paresthesia, pruritus andsweating (6.1).
To report SUSPECTED ADVERSE REACTIONS, contact
Forest Laboratories, Inc. at 1-800-678-1605, or FDA at 1800-FDA-1088 or www.fda.gov/medwatch.
---------------USE IN SPECIFIC POPULATIONS----------- Pregnancy: Campral should be used during pregnancy
only if the potential benefit justifies the potential risk to
the fetus (8.1).
 Nursing Mothers: Caution should be exercised whenCampral is administered to a nursing woman (8.3).
 Renal Impairment: Dose reduction required for moderate
renal impairment; contraindicated in severe renal
impairment (2.1, 4.2, 5.1, 8.6, 12.3)

See 17 for Patient Counseling Information.
---------------------CONTRAINDICATIONS-------------------- Campral is contraindicated in patients who previously
Revised: January 2012
have exhibited hypersensitivity to acamprosate calcium or
any of its components (4.1).
 Campral is contraindicated in patients with severe renal
impairment (4.2).
___________________________________________________________________________________________________________

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FULL PRESCRIBING INFORMATION: CONTENTS*
1
2
3
4

5

6

7
8

INDICATIONS AND USAGE
DOSAGE AND ADMINISTRATION
2.1 Dosage in Renal Impairment
DOSAGE FORMS AND STRENGTHSCONTRAINDICATIONS
4.1 Hypersensitivity to Acamprosate Calcium
4.2 Severe Renal Impairment
WARNINGS AND PRECAUTIONS
5.1 Renal Impairment
5.2 Suicidality and Depression
5.3 Alcohol Withdrawal
ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
DRUG INTERACTIONSUSE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Labor and Delivery
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment

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10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of
Fertility
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
17.1 Information for Patients* Sections or subsections omitted from the full prescribing
information are not listed.

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FULL PRESCRIBING INFORMATION
1

INDICATIONS AND USAGE

Campral® is indicated for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent attreatment initiation. Treatment with Campral should be part of a comprehensive management program that includes psychosocial
support.
The efficacy of Campral in promoting abstinence has not been demonstrated in subjects who have not undergone detoxification andnot achieved alcohol abstinence prior to beginning Campral treatment. The efficacy of Campral in promoting abstinence from alcoholin polysubstance abusers has not been adequately assessed.
2

DOSAGE AND ADMINISTRATIONThe recommended dose of 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.
Although dosing may be done without regard to meals, dosing with meals was employed during clinical trials and is suggested inthose patients who regularly eat three meals daily.
Treatment with Campral should be initiated as soon as possible after the period of alcohol withdrawal, when the patient has achieved
abstinence, and should be maintained if the patient relapses. Campral should be used as part of a comprehensive psychosocial
treatment program.
2.1 Dosage in Renal Impairment
For patients with moderate renal impairment (creatinine clearance of 30-50 mL/min), a starting dose of one 333 mg tablet taken threetimes daily is recommended. Campral is contraindicated in patients with severe renal impairment (creatinine clearance of ≤30
mL/min) [see Contraindications (4.2), Warnings and Precautions (5.1), Use in Specific Populations (8.6), and Clinical Pharmacology(12.3)].
3

DOSAGE FORMS AND STRENGTHS

Campral 333 mg tablets are enteric-coated, white, round, biconvex tablets, identified with “333” debossed on one side.
4

CONTRAINDICATIONS
4.1 Hypersensitivity to Acamprosate Calcium

Campral is contraindicated in patients who previously have exhibited hypersensitivity to acamprosate calcium or any of its
components.
4.2 Severe Renal Impairment
Campral is contraindicated in patients with severe renal impairment (creatinine clearance of ≤30 mL/min) [see Dosage andAdministration (2.1), Warnings and Precautions (5.1), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].
5

WARNINGS AND PRECAUTIONS
5.1 Renal Impairment

Treatment with Campral in patients with moderate renal impairment (creatinine clearance of 30-50 mL/min) requires a dose reduction[see Dosage and Administration (2.1)]. Campral is contraindicated in patients with severe renal impairment (creatinine clearance of≤30 mL/min) [see Dosage and Administration (2.1), Contraindications (4.2), Use in Specific Populations (8.6), and ClinicalPharmacology (12.3)].
5.2 Suicidality and Depression
In controlled clinical trials of Campral, adverse events of a suicidal nature (suicidal ideation, suicide attempts, completed suicides)
were infrequent overall, but were more common in Campral-treated patients than in patients treated with placebo (1.4% vs. 0.5% inCampral (acamprosate calcium) - draft-labeling-text-tracked
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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 thepooled 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 Campral-treated and placebo-treated patients. Although many of these events occurredin the context of alcohol relapse, and the interrelationship between alcohol dependence, depression and suicidality is well-recognized
and complex, no consistent pattern of relationship between the clinical course of recovery from alcoholism and the emergence ofsuicidality was identified. Alcohol-dependent patients, including those patients being treated with Campral, should be monitored forthe development of symptoms of depression or suicidal thinking. Families and caregivers of patients being treated with Campral
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 health care provider.
5.3 Alcohol Withdrawal
Use of Campral does not eliminate or diminish withdrawal symptoms.

6

ADVERSE REACTIONS
6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug
cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Clinically significant serious adverse reactions associated with Campral described elsewhere in labeling include suicidality anddepression and acute kidney failure [see Warnings and Precautions (5.2), and Adverse Reactions (6.2)].
The adverse event data described below reflect the safety experience in over 7000 patients exposed to Campral for up to one year,
including over 2000 Campral-exposed patients who participated in placebo-controlled trials.
Adverse Events Leading to Discontinuation
In placebo-controlled trials of 6 months or less, 8% of Campral-treated patients discontinued treatment due to an adverse event, as
compared to 6% of patients treated with placebo. In studies longer than 6 months, the discontinuation rate due to adverse events was
7% in both the placebo-treated and the Campral-treated patients. Only diarrhea was associated with the discontinuation of more than
1% of patients (2% of Campral-treated vs. 0.7% of placebo-treated patients). Other events, including nausea, depression, and anxiety,while accounting for discontinuation in less than 1% of patients, were nevertheless more commonly cited in association withdiscontinuation in Campral-treated patients than in placebo-treated patients.
Common Adverse Events Reported in Controlled Trials
Common adverse events were collected spontaneously in some controlled studies and using a checklist in other studies. The overallprofile of adverse events was similar using either method. Table 1 shows those events that occurred in any Campral treatment group at
a rate of 3% or greater and greater than the placebo group in controlled clinical trials with spontaneously reported adverse events. The
reported frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent
adverse event of the type listed, without regard to the causal relationship of the events to the drug.

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Table 1. Events Occurring at a Rate of at Least 3% and Greater than Placebo in any Campral Treatment Group inControlled Clinical Trials with Spontaneously Reported Adverse Events.

Body System/Preferred
Term
Number of patients in
Treatment Group
Number (%) of patientswith an AE
Body as a Whole
Accidental Injury*†
Asthenia
Pain
Digestive System
Anorexia
Diarrhea
Flatulence
NauseaNervous System
Anxiety††**Depression
Dizziness
Dry mouth
Insomnia
Paresthesia
Skin and Appendages
Pruritus
Sweating

Campral1332 mg/day
397
248 (62%)
121 (30%)
17 ( 4%)29 ( 7%)6 ( 2%)
85 (21%)20 ( 5%)39 (10%)4 ( 1%)
11 ( 3%)150 (38%)32 ( 8%)33 ( 8%)15 ( 4%)13 ( 3%)34 ( 9%)11 ( 3%)26 ( 7%)12 ( 3%)11 ( 3%)

Number of Patients (%) with Events
CampralCampralPooled2
1998 mg/day1
1539
2019
910 (59%)513 (33%)44 ( 3%)79 ( 5%)56 ( 4%)440 (29%)35 ( 2%)257 (17%)55 ( 4%)69 ( 4%)417 (27%)80 ( 5%)63 ( 4%)49 ( 3%)23 ( 1%)94 ( 6%)29 ( 2%)150 (10%)68 ( 4%)27 ( 2%)

Placebo1706

1231 (61%)

955 (56%)685 (34%)70 ( 3%)114 ( 6%)65 ( 3%)574 (28%)57 ( 3%)329 (16%)63 ( 3%)87 ( 4%)598 (30%)
118 ( 6%)102 ( 5%)67 ( 3%)36 ( 2%)137 ( 7%)40 ( 2%)187 ( 9%)82 ( 4%)40 ( 2%)517 (30%)52 ( 3%)93 ( 5%)55 ( 3%)344 (20%)44 ( 3%)166 (10%)28 ( 2%)58 ( 3%)500 (29%)
98 ( 6%)87 ( 5%)44 ( 3%)28 ( 2%)121 ( 7%)34 ( 2%)169 (10%)58 ( 3%)39 ( 2%)†*includes events coded as “fracture” by sponsor; ††**includes events coded as “nervousness” by sponsor
1
includes 258 patients treated with acamprosate calcium 2000 mg/day, using a different dosage strength andregimen.
2
includes all patients in the first two columns as well as 83 patients treated with acamprosate calcium 3000
mg/day, using a different dosage strength and regimen.
Concomitant Therapies
In clinical trials, the safety profile in subjects treated with Campral concomitantly with anxiolytics, hypnotics and sedatives (including
benzodiazepines), or non-opioid analgesics was similar to that of subjects taking placebo with these concomitant medications.
Patients taking Campral concomitantly with antidepressants more commonly reported both weight gain and weight loss, comparedwith patients taking either medication alone.
Other Events Observed During the Premarketing Evaluation of Campral
Following is a list of terms that reflect treatment-emergent adverse events reported by patients treated with Campral in 20 clinical
trials (4461 patients treated with Campral, 3526 of whom received the maximum recommended dose of 1998 mg/day for up to one
year in duration). This listing does not include those events already listed above; events for which a drug cause was consideredremote; event terms which were so general as to be uninformative; and events reported only once which were not likely to be acutely
life-threatening.
Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions:frequent adverse events are those occurring in at least 1/100 patients (only those not already listed in the summary of adverse events incontrolled trials appear in this listing); infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are thoseoccurring in fewer than 1/1000 patients.
Body as a Whole – Frequent: headache, abdominal pain, back pain, infection, flu syndrome, chest pain, chills, suicide attempt;
Infrequent: fever, intentional overdose, malaise, allergic reaction, abscess, neck pain, hernia, intentional injury; Rare: ascites, faceedema, photosensitivity reaction, abdomen enlarged, sudden death.
Cardiovascular System – Frequent: palpitation, syncope; Infrequent: hypotension, tachycardia, hemorrhage, angina pectoris,
migraine, varicose vein, myocardial infarct, phlebitis, postural hypotension; Rare: heart failure, mesenteric arterial occlusion,
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cardiomyopathy, deep thrombophlebitis, shock.
Digestive System – Frequent: vomiting, dyspepsia, constipation, increased appetite; Infrequent: liver function tests abnormal,
gastroenteritis, gastritis, dysphagia, eructation, gastrointestinal hemorrhage, pancreatitis, rectal hemorrhage, liver cirrhosis,
esophagitis, hematemesis, nausea and vomiting, hepatitis; Rare: melena, stomach ulcer, cholecystitis, colitis, duodenal ulcer, mouth
ulceration, carcinoma of liver.
Endocrine System – Rare: goiter, hypothyroidism.
Hemic and Lymphatic System – Infrequent:leukopenia, lymphadenopathy, monocytosis.

anemia, ecchymosis, eosinophilia, lymphocytosis, thrombocytopenia; Rare:

Metabolic and Nutritional Disorders – Frequent – peripheral edema, weight gain; Infrequent: weight loss, hyperglycemia, SGOT
increased, SGPT increased, gout, thirst, hyperuricemia, diabetes mellitus, avitaminosis, bilirubinemia; Rare: alkaline phosphataseincreased, creatinine increased, hyponatremia, lactic dehydrogenase increased.
Musculoskeletal System – Frequent – myalgia, arthralgia; Infrequent: leg cramps; Rare: rheumatoid arthritis, myopathy.
Nervous System – Frequent –somnolence, libido decreased, amnesia, thinking abnormal, tremor, vasodilatation, hypertension;
Infrequent: convulsion, confusion, libido increased, vertigo, withdrawal syndrome, apathy, suicidal ideation, neuralgia, hostility,
agitation, neurosis, abnormal dreams, hallucinations, hypesthesia; Rare: alcohol craving, psychosis, hyperkinesia, twitching,depersonalization, increased salivation, paranoid reaction, torticollis, encephalopathy, manic reaction.
Respiratory System – Frequent: rhinitis, cough increased, dyspnea, pharyngitis, bronchitis; Infrequent:pneumonia; Rare: laryngismus, pulmonary embolus.

asthma, epistaxis,

Skin and Appendages – Frequent: rash; Infrequent: acne, eczema, alopecia, maculopapular rash, dry skin, urticaria, exfoliative
dermatitis, vesiculobullous rash; Rare: psoriasis.
Special Senses – Frequent: abnormal vision, taste perversion; Infrequent: tinnitus, amblyopia, deafness; Rare: ophthalmitis,
diplopia, photophobia.
Urogenital System – Frequent: impotence; Infrequent – metrorrhagia, urinary frequency, urinary tract infection, sexual function
abnormal, urinary incontinence, vaginitis; Rare: kidney calculus, abnormal ejaculation, hematuria, menorrhagia, nocturia, polyuria,
urinary urgency.
6.2 Postmarketing Experience
The following adverse reactions have been identified during post approval use of Campral. Because these reactions are reported
voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal
relationship to drug exposure.
Serious Adverse Events Observed During the Non-US Postmarketing Evaluation of Campral (acamprosate calcium)
The serious adverse event of acute kidney failure has been reported to be temporally associated with Campral treatment in at least 3
patients and is not described elsewhere in the labeling.
7

DRUG INTERACTIONSAcamprosate does not affect the pharmacokinetics of alcohol. The pharmacokinetics of acamprosate are not affected by alcohol,
diazepam, or disulfiram, and clinically important interactions between naltrexone and acamprosate were not observed [see ClinicalPharmacology (12.3)].
8

USE IN SPECIFIC POPULATIONS
8.1 Pregnancy

Pregnancy Category C
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 wereCampral (acamprosate calcium) - draft-labeling-text-tracked
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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 ofhydronephrosis 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 ofneurological and behavioral disorders in humans. There are no adequate and well controlled studies in pregnant women. Campral
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 dosesof 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).
8.2 Labor and Delivery
The potential for Campral to affect the duration of labor and delivery is unknown.
8.3 Nursing Mothers
In animal studies, acamprosate was excreted in the milk of lactating rats dosed orally with acamprosate calcium. The concentration ofacamprosate 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 Campral is administered to a nursing woman.
8.4 Pediatric Use
The safety and efficacy of Campral have not been established in the pediatric population.
8.5 Geriatric Use
Forty-one of the 4234 patients in double-blind, placebo-controlled, clinical trials of Campral 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 effectivenessfor 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 patientswith 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 andAdministration (2.1)].
8.6 Renal Impairment
Campral is contraindicated in patients with severe renal impairment (creatinine clearance of ≤30 mL/min) [see Dosage andAdministration (2.1), Contraindications (4.2), Warnings and Precautions (5.1), and Clinical Pharmacology (12.3)].
10 OVERDOSAGEIn all reported cases of acute overdosage with Campral (total reported doses of up to 56 grams of acamprosate calcium), the only
symptom that could be reasonably associated with Campral 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 symptomaticand supportive.
11

DESCRIPTION

Campral (acamprosate calcium) is supplied in an enteric-coated tablet for oral administration. Acamprosate calcium is a synthetic
compound with a chemical structure similar to that of the endogenous amino acid homotaurine, which is a structural analogue of theamino acid neurotransmitter γ-aminobutyric acid and the amino acid neuromodulator taurine. Its chemical name is calcium
acetylaminopropane sulfonate. Its chemical formula is C10H20N2O8S2Ca and molecular weight is 400.48. Its structural formula is:Campral (acamprosate calcium) - draft-labeling-text-tracked
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O
C
H3C

NH

CH 2 _
CH 2
CH 2
SO3

NH

_
SO3

Ca2+
H3C
C

CH 2
CH 2

CH 2

O

Acamprosate calcium is a white, odorless or nearly odorless powder. It is freely soluble in water, and practically insoluble in absoluteethanol and dichloromethane.
Each Campral tablet contains acamprosate calcium 333 mg, equivalent to 300 mg of acamprosate. Inactive ingredients in Campral
tablets include: crospovidone, microcrystalline cellulose, magnesium silicate, sodium starch glycolate, colloidal anhydrous silica,magnesium stearate, talc, propylene glycol and Eudragit L 30 D or equivalent. Sulfites were used in the synthesis of the drug
substance and traces of residual sulfites may be present in the drug product.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
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.
12.2 Pharmacodynamics
Pharmacodynamic studies have shown that acamprosate calcium reduces alcohol intake in alcohol-dependent animals in a dosedependent 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.
The administration of acamprosate calcium is not associated with the development of tolerance or dependence in animal studies.
Campral 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 Campral abuse or dependence.
Campral is not known to cause alcohol aversion and does not cause a disulfiram-like reaction as a result of ethanol ingestion.
12.3 Pharmacokinetics
Absorption
The absolute bioavailability of Campral after oral administration is about 11%. Steady-state plasma concentrations of acamprosate arereached within 5 days of dosing. Steady-state peak plasma concentrations after Campral doses of 2 x 333 mg tablets three times daily
average 350 ng/mL and occur at 3-8 hours post-dose. Coadministration of Campral with food decreases bioavailability as measured
by Cmax and AUC, by approximately 42% and 23%, respectively. The food effect on absorption is not clinically significant and no
adjustment of dose is necessary.
Distribution
The volume of distribution for acamprosate following intravenous administration is estimated to be 72-109 liters (approximately 1
L/kg). Plasma protein binding of acamprosate is negligible.
Metabolism
Acamprosate does not undergo metabolism.
Elimination
After oral dosing of 2 x 333 mg of Campral, the terminal half-life ranges from approximately 20-33 hours. Following oral
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administration of Campral, the major route of excretion is via the kidneys as acamprosate.
Special Populations
Gender: Campral does not exhibit any significant pharmacokinetic differences between male and female subjects.
Age: The pharmacokinetics of Campral have not been evaluated in a geriatric population. However, since renal function diminishes in elderly
patients and acamprosate is excreted unchanged in urine, acamprosate plasma concentrations are likely to be higher in the elderly populationcompared to younger adults.
Pediatrics: The pharmacokinetics of Campral have not been evaluated in a pediatric population.
Renal Impairment: Peak plasma concentrations after administration of a single dose of 2 x 333 mg Campral tablets to patients withmoderate or severe renal impairment were about 2-fold and 4-fold higher, respectively, compared to healthy subjects. Similarly,
elimination half-life was about 1.8-fold and 2.6-fold longer, respectively, compared to healthy subjects. There is a linear relationshipbetween creatinine clearance values and total apparent plasma clearance, renal clearance and plasma half-life of acamprosate. A doseof 1 x 333 mg Campral, three times daily, is recommended in patients with moderate renal impairment (creatinine clearance of 30-50
mL/min, [see Use in Specific Populations (8.6)].
Campral is contraindicated in patients with severe renal impairment (creatinine clearance of ≤30 mL/min) [see Dosage andAdministration (2.1), Contraindications (4.2), Warnings and Precautions (5.1), and Use in Specific Populations (8.6)].
Hepatic Impairment: Acamprosate is not metabolized by the liver and the pharmacokinetics of Campral are not altered in patientswith mild to moderate hepatic impairment (groups A and B of the Child-Pugh classification). No adjustment of dosage isrecommended in such patients.
Alcohol-dependent subjects: A cross-study comparison of Campral at doses of 2 x 333 mg three times daily indicated similar
pharmacokinetics between alcohol-dependent subjects and healthy subjects.
Drug-Drug Interactions
Acamprosate had no inducing potential on the cytochrome CYP1A2 and 3A4 systems, and in vitro inhibition studies suggest thatacamprosate does not inhibit in vivo metabolism mediated by cytochrome CYP1A2, 2C9, 2C19, 2D6, 2E1, or 3A4. The
pharmacokinetics of Campral were unaffected when co-administered with alcohol, disulfiram or diazepam. Similarly, thepharmacokinetics of ethanol, diazepam and nordiazepam, imipramine and desipramine, naltrexone and 6-beta naltrexol were
unaffected following co-administration with Campral. However, co-administration of Campral with naltrexone led to a 33% increasein the Cmax and a 25% increase in the AUC of acamprosate. No adjustment of dosage is recommended in such patients.
13 NONCLINICAL TOXICOLOGY
13.1 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 doseon 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.
14 CLINICAL STUDIESThe efficacy of Campral in the maintenance of abstinence was supported by three clinical studies involving a total of 998 patients who
were administered at least one dose of Campral or placebo as an adjunct to psychosocial therapy. Each study was a double-blind,placebo-controlled trial in alcohol-dependent patients who had undergone inpatient detoxification and were abstinent from alcohol on
the day of randomization. Study durations ranged from 90 days to 360 days. Campral proved superior to placebo in maintaining
abstinence, as indicated by a greater percentage of subjects being assessed as continuously abstinent throughout treatment.
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In a fourth study, the efficacy of Campral was evaluated in alcoholics, including patients with a history of polysubstance abuse andpatients who had not undergone detoxification and were not required to be abstinent at baseline. This study failed to demonstratesuperiority of Campral over placebo.
16 HOW SUPPLIED/STORAGE AND HANDLING
Opaque HDPE bottles of 180

NDC #0456-3330-01

Storage and HandlingStore at 25ºC (77ºF); excursions permitted to 15º to 30ºC (59º to 86ºF).
17 PATIENT COUNSELING INFORMATION
17.1 Information for Patients
Physicians are advised to discuss the following issues with patients for whom they prescribe Campral.
Renal Impairment
A lower dose is recommended for patients with moderate renal impairment. Campral is contraindicated in patients with severe renal
impairment (creatinine clearance of ≤30 mL/min) [see Dosage and Administration (2.1), Contraindications (4.2), Warnings andPrecautions (5.1) and Use in Specific Populations (8.6)].
Suicidality and Depression
Families and caregivers of patients being treated with Campral should be alerted to the need to monitor patients for the emergence ofsymptoms of depression or suicidality, and to report such symptoms to the patient's health care provider [see Warnings andPrecautions (5.2)].
Alcohol Withdrawal
Use of Campral does not eliminate or diminish withdrawal symptoms [see Warnings and Precautions (5.3)].
Pregnancy and Breast Feeding
 Advise patients to notify their physician if they become pregnant or intend to become pregnant during therapy.
 Advise patients to notify their physician if they are breast-feeding.
Relapse to Drinking
 Advise patients to continue Campral therapy as directed, even in the event of relapse and remind them to discuss any renewed
drinking with their physicians.
 Advise patients that Campral has been shown to help maintain abstinence only when used as a part of a treatment program that
includes counseling and support.
Manufactured by:
Merck Santé s.a.s.
Subsidiary of Merck KGaA, Darmstadt, Germany
37, rue Saint-Romain
69008 LYON FRANCE
Manufactured for:
Forest Pharmaceuticals, Inc.
Subsidiary of Forest Laboratories, Inc.
St. Louis, MO 63045

Campral (acamprosate calcium) - draft-labeling-text-tracked
Reference ID: 3079232

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