Aotal

How is the drug helping you?  No   Yes

Aotal uses

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Campral
• Aotal reviews

1 INDICATIONS AND USAGE

Campral® is indicated for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. Treatment with Aotal should be part of a comprehensive management program that includes psychosocial support.

The efficacy of Aotal in promoting abstinence has not been demonstrated in subjects who have not undergone detoxification and not achieved alcohol abstinence prior to beginning Aotal treatment. The efficacy of Aotal in promoting abstinence from alcohol in polysubstance abusers has not been adequately assessed.

• Campral® is indicated for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation (, ). 1 14
• Treatment with Aotal should be part of a comprehensive management program that includes psychosocial support ( ). 1

2 DOSAGE AND ADMINISTRATION

The recommended dose of Aotal is two 333 mg tablets 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 in those patients who regularly eat three meals daily.

Treatment with Aotal 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. Aotal should be used as part of a comprehensive psychosocial treatment program.

• 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
• Aotal is contraindicated in patients with severe renal impairment (creatinine clearance of ≤30 mL/min) (,,,, ). 2.1 4.2 5.1 8.6 12.3

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 three times daily is recommended. Aotal is contraindicated in patients with severe renal impairment (creatinine clearance of ≤30 mL/min) [ and ]. see Contraindications ( ), Warnings and Precautions ( ), Use in Specific Populations ( ), 4.2 5.1 8.6 Clinical Pharmacology ( ) 12.3

3 DOSAGE FORMS AND STRENGTHS

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

Enteric-coated tablets, 333 mg ( ). 3

4 CONTRAINDICATIONS

• Aotal is contraindicated in patients who previously have exhibited hypersensitivity to Aotal or any of its components. 4.1
• Aotal is contraindicated in patients with severe renal impairment ( ). 4.2

4.1 Hypersensitivity to Aotal

Aotal is contraindicated in patients who previously have exhibited hypersensitivity to Aotal or any of its components.

4.2 Severe Renal Impairment

Aotal is contraindicated in patients with severe renal impairment (creatinine clearance of ≤30 mL/min) [ and ]. see Dosage and Administration ( ), Warnings and Precautions ( ), Use in Specific Populations ( ), 2.1 5.1 8.6 Clinical Pharmacology ( ) 12.3

5 WARNINGS AND PRECAUTIONS

• Dose reduction is required for patients with moderate renal impairment. 5.1
• Monitor patients for depression or suicidal ideation and prompt patients, families, and caregivers to report such symptoms to the health care provider ( ). 5.2

5.1 Renal Impairment

Treatment with Aotal in patients with moderate renal impairment (creatinine clearance of 30-50 mL/min) requires a dose reduction [ ]. Aotal is contraindicated in patients with severe renal impairment (creatinine clearance of ≤30 mL/min) [ and ]. see Dosage and Administration ( ) 2.1 see Dosage and Administration ( ), Contraindications ( ), Use in Specific Populations ( ), 2.1 4.2 8.6 Clinical Pharmacology ( ) 12.3

5.2 Suicidality and Depression

In controlled clinical trials of Aotal, adverse events of a suicidal nature were infrequent overall, but were more common in Campral-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 Campral-treated and placebo-treated patients. Although many of these events occurred in 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 of suicidality was identified. Alcohol-dependent patients, including those patients being treated with Aotal, should be monitored for the development of symptoms of depression or suicidal thinking. Families and caregivers of patients being treated with Aotal 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 Aotal does not eliminate or diminish withdrawal symptoms.

6 ADVERSE REACTIONS

Common adverse events that occurred in any Aotal treatment group at a rate of 3% or greater and greater than the placebo 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 and sweating. 6.1

. To report SUSPECTED ADVERSE REACTIONS, contact Forest Laboratories, Inc. at 1-800-678-1605, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

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 Aotal described elsewhere in labeling include suicidality and depression and acute kidney failure [s, and ]. ee Warnings and Precautions ( ) 5.2 Adverse Reactions ( ) 6.2

The adverse event data described below reflect the safety experience in over 7000 patients exposed to Aotal 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 with discontinuation 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 overall profile of adverse events was similar using either method. shows those events that occurred in any Aotal 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. Table 1

Concomitant Therapies

In clinical trials, the safety profile in subjects treated with Aotal 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 Aotal concomitantly with antidepressants more commonly reported both weight gain and weight loss, compared with patients taking either medication alone.

Other Events Observed During the Premarketing Evaluation of Aotal

Following is a list of terms that reflect treatment-emergent adverse events reported by patients treated with Aotal in 20 clinical trials (4461 patients treated with Aotal, 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 considered remote; 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 in controlled trials appear in this listing); infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients.

: headache, abdominal pain, back pain, infection, flu syndrome, chest pain, chills, suicide attempt; : fever, intentional overdose, malaise, allergic reaction, abscess, neck pain, hernia, intentional injury; : ascites, face edema, photosensitivity reaction, abdomen enlarged, sudden death. Body as a Whole – Frequent Infrequent Rare

: palpitation, syncope; : hypotension, tachycardia, hemorrhage, angina pectoris, migraine, varicose vein, myocardial infarct, phlebitis, postural hypotension; : heart failure, mesenteric arterial occlusion, cardiomyopathy, deep thrombophlebitis, shock. Cardiovascular System – Frequent Infrequent Rare

: vomiting, dyspepsia, constipation, increased appetite; : liver function tests abnormal, gastroenteritis, gastritis, dysphagia, eructation, gastrointestinal hemorrhage, pancreatitis, rectal hemorrhage, liver cirrhosis, esophagitis, hematemesis, nausea and vomiting, hepatitis; melena, stomach ulcer, cholecystitis, colitis, duodenal ulcer, mouth ulceration, carcinoma of liver. Digestive System – Frequent Infrequent Rare:

goiter, hypothyroidism. Endocrine System – Rare:

: anemia, ecchymosis, eosinophilia, lymphocytosis, thrombocytopenia; leukopenia, lymphadenopathy, monocytosis. Hemic and Lymphatic System – Infrequent Rare:

– peripheral edema, weight gain; : weight loss, hyperglycemia, SGOT increased, SGPT increased, gout, thirst, hyperuricemia, diabetes mellitus, avitaminosis, bilirubinemia; alkaline phosphatase increased, creatinine increased, hyponatremia, lactic dehydrogenase increased. Metabolic and Nutritional Disorders – Frequent Infrequent Rare:

– myalgia, arthralgia; : leg cramps; rheumatoid arthritis, myopathy. Musculoskeletal System – Frequent Infrequent Rare:

–somnolence, libido decreased, amnesia, thinking abnormal, tremor, vasodilatation, hypertension; : convulsion, confusion, libido increased, vertigo, withdrawal syndrome, apathy, suicidal ideation, neuralgia, hostility, agitation, neurosis, abnormal dreams, hallucinations, hypesthesia; : alcohol craving, psychosis, hyperkinesia, twitching, depersonalization, increased salivation, paranoid reaction, torticollis, encephalopathy, manic reaction. Nervous System – Frequent Infrequent Rare

: rhinitis, cough increased, dyspnea, pharyngitis, bronchitis; : asthma, epistaxis, pneumonia; laryngismus, pulmonary embolus. Respiratory System – Frequent Infrequent Rare:

: rash; : acne, eczema, alopecia, maculopapular rash, dry skin, urticaria, exfoliative dermatitis, vesiculobullous rash; psoriasis. Skin and Appendages – Frequent Infrequent Rare:

: abnormal vision, taste perversion; : tinnitus, amblyopia, deafness; ophthalmitis, diplopia, photophobia. Special Senses – Frequent Infrequent Rare:

: impotence; – metrorrhagia, urinary frequency, urinary tract infection, sexual function abnormal, urinary incontinence, vaginitis; kidney calculus, abnormal ejaculation, hematuria, menorrhagia, nocturia, polyuria, urinary urgency. Urogenital System – Frequent Infrequent Rare:

6.2 Postmarketing Experience

The following adverse reactions have been identified during post approval use of Aotal. 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 Aotal (acamprosate calcium)

The serious adverse event of acute kidney failure has been reported to be temporally associated with Aotal treatment in at least 3 patients and is not described elsewhere in the labeling.

7 DRUG INTERACTIONS

Acamprosate 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 Clinical Pharmacology ( ) 12.3

8 USE IN SPECIFIC POPULATIONS

• Pregnancy: Aotal 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 when Aotal 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

8.1 Pregnancy

Pregnancy Category C

Aotal has been shown to be teratogenic in rats when given in doses that are approximately equal to the human dose (on a mg/m basis) and in rabbits when given in doses that are approximately 3 times the human dose (on a mg/m basis). Aotal 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/m 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/m 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/m 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/m 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. Aotal should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Teratogenic effects: ^{2 2 2 2 2 2}

A study conducted in pregnant mice that were administered Aotal 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/m basis). No effects were observed at a dose of 320 mg/kg/day (approximately one-half the MRHD dose on a mg/m basis). Nonteratogenic effects: ^{2 2}

8.2 Labor and Delivery

The potential for Aotal 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 Aotal. 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 Aotal is administered to a nursing woman.

8.4 Pediatric Use

The safety and efficacy of Aotal 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 Aotal 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 and ]. [see Clinical Pharmacology, Adverse Reactions ( ), 12.3 6.1 Dosage and Administration ( ) 2.1

8.6 Renal Impairment

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

10 OVERDOSAGE

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

11 DESCRIPTION

Aotal (acamprosate calcium) is supplied in an enteric-coated tablet for oral administration. Aotal is a synthetic compound with a chemical structure similar to that of the endogenous amino acid homotaurine, which is a structural analogue of the amino acid neurotransmitter γ-aminobutyric acid and the amino acid neuromodulator taurine. Its chemical name is calcium acetylaminopropane sulfonate. Its chemical formula is C H N O S Ca and molecular weight is 400.48. Its structural formula is: _{10 20 2 8 2}

Aotal is a white, odorless or nearly odorless powder. It is freely soluble in water, and practically insoluble in absolute ethanol and dichloromethane.

Each Aotal tablet contains Aotal 333 mg, equivalent to 300 mg of acamprosate. Inactive ingredients in Aotal 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. ^®

Structural Formula

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. and 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. In vitro in vivo

12.2 Pharmacodynamics

Pharmacodynamic studies have shown that Aotal 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.

Aotal has negligible observable central nervous system activity in animals outside of its effects on alcohol dependence, exhibiting no anticonvulsant, antidepressant, or anxiolytic activity.

The administration of Aotal is not associated with the development of tolerance or dependence in animal studies. Aotal 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 Aotal abuse or dependence.

Aotal 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 Aotal after oral administration is about 11%. Steady-state plasma concentrations of acamprosate are reached within 5 days of dosing. Steady-state peak plasma concentrations after Aotal doses of 2 x 333 mg tablets three times daily average 350 ng/mL and occur at 3-8 hours post-dose. Coadministration of Aotal with food decreases bioavailability as measured by C and AUC, by approximately 42% and 23%, respectively. The food effect on absorption is not clinically significant and no adjustment of dose is necessary. _max

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 Aotal, the terminal half-life ranges from approximately 20-33 hours. Following oral administration of Aotal, the major route of excretion is via the kidneys as acamprosate.

Special Populations

Aotal does not exhibit any significant pharmacokinetic differences between male and female subjects. Gender:

The pharmacokinetics of Aotal 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 population compared to younger adults. Age:

The pharmacokinetics of Aotal have not been evaluated in a pediatric population. Pediatrics:

: Peak plasma concentrations after administration of a single dose of 2 x 333 mg Aotal tablets to patients with moderate 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 relationship between creatinine clearance values and total apparent plasma clearance, renal clearance and plasma half-life of acamprosate. A dose of 1 x 333 mg Aotal, three times daily, is recommended in patients with moderate renal impairment (creatinine clearance of 30-50 mL/min, [ ]. Renal Impairment see Use in Specific Populations ( ) 8.6

Aotal is contraindicated in patients with severe renal impairment (creatinine clearance of ≤30 mL/min) [ and ]. see Dosage and Administration ( ), Contraindications ( ), Warnings and Precautions ( ), 2.1 4.2 5.1 Use in Specific Populations ( ) 8.6

: Acamprosate is not metabolized by the liver and the pharmacokinetics of Aotal are not altered in patients with mild to moderate hepatic impairment (groups A and B of the Child-Pugh classification). No adjustment of dosage is recommended in such patients. Hepatic Impairment

: A cross-study comparison of Aotal at doses of 2 x 333 mg three times daily indicated similar pharmacokinetics between alcohol-dependent subjects and healthy subjects. Alcohol-dependent subjects

Drug-Drug Interactions

Acamprosate had no inducing potential on the cytochrome CYP1A2 and 3A4 systems, and inhibition studies suggest that acamprosate does not inhibit metabolism mediated by cytochrome CYP1A2, 2C9, 2C19, 2D6, 2E1, or 3A4. The pharmacokinetics of Aotal were unaffected when co-administered 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 Aotal. However, co-administration of Aotal with naltrexone led to a 33% increase in the C and a 25% increase in the AUC of acamprosate. No adjustment of dosage is recommended in such patients. in vitro in vivo _max

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Dietary administration of Aotal 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.

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

Aotal 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/m basis). In mice, Aotal 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/m basis) had no effect on fertility. ^{2 2}

14 CLINICAL STUDIES

The efficacy of Aotal 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 Aotal 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. Aotal proved superior to placebo in maintaining abstinence, as indicated by a greater percentage of subjects being assessed as continuously abstinent throughout treatment.

In a fourth study, the efficacy of Aotal was evaluated in alcoholics, including patients with a history of polysubstance abuse and patients who had not undergone detoxification and were not required to be abstinent at baseline. This study failed to demonstrate superiority of Aotal over placebo.

16 HOW SUPPLIED/STORAGE AND HANDLING

NDC:68151-4760-0 in a PACKAGE of 1 TABLET, DELAYED RELEASES

Storage and Handling

Store 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 Aotal.

Renal Impairment

A lower dose is recommended for patients with moderate renal impairment. Aotal is contraindicated in patients with severe renal impairment (creatine clearance of ≤30 mL/min) [ ]. see Dosage and Administration ( ), Contraindications ( ), Warnings and Precautions ( ) and Use in Specific Populations ( ) 2.1 4.2 5.1 8.6

Suicidality and Depression

Families and caregivers of patients being treated with Aotal 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 [ ]. see Warnings and Precautions ( ) 5.2

Alcohol Withdrawal

Use of Aotal 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 Aotal therapy as directed, even in the event of relapse and remind them to discuss any renewed drinking with their physicians.
• Advise patients that Aotal 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

Aotal

Aotal pharmaceutical active ingredients containing related brand and generic drugs:

• Acamprosate Calcium

Aotal available forms, composition, doses:

• Tablets, Film-Coated; Oral; Acamprosate Calcium 333 mg

Aotal destination | category:

• Human:
• Central nervous system agents

Aotal Anatomical Therapeutic Chemical codes:

• N07BB03 - Acamprosate

Aotal pharmaceutical companies:

• Merck

References

1. Dailymed."CAMPRAL (ACAMPROSATE CALCIUM) TABLET, DELAYED RELEASE [CARILION MATERIALS MANAGEMENT]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
2. "Acamprosate". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
3. "Acamprosate". http://www.drugbank.ca/drugs/DB0065... (accessed August 28, 2018).

Frequently asked Questions

Depending on the reaction of the Aotal after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Aotal not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

Review

Visitor reports

Visitor reviews

The information was verified by Dr. Rachana Salvi, MD Pharmacology