CAMPRAL- acamprosate calcium tablet
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 the amino acid neurotransmitter γ-aminobutyric acid and the amino acid neuromodulator taurine. Its chemical name is calcium acetylaminopropane sulfonate. Its chemical formula is C10 H20 CaN2 O8 S2 and molecular weight is 400.48.
Acamprosate calcium is a white, odorless or nearly odorless powder. It is freely soluble in water, and practically insoluble in absolute ethanol 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 L30D or equivalent. Sulfites were used in the synthesis of the drug substance and traces of residual sulfites may be present in the drug product.
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 vitroin vivo 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.
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 Campral should be part of a comprehensive management program that includes psychosocial support.
Dosage and administration
The 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 in those patients who regularly eat three meals daily.
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. Campral is contraindicated in patients with severe renal impairment (creatinine clearance of ≤30 mL/min).
- Campral is contraindicated in patients who previously have exhibited hypersensitivity to acamprosate calcium or any of its components.
- Campral is contraindicated in patients with severe renal impairment (creatinine clearance of ≤30 mL/min)
Warnings and precautions
Renal Impairment: Treatment with Campral in patients with moderate renal impairment (creatinine clearance of 30-50 mL/min) requires a dose reduction. Campral is contraindicated in patients with severe renal impairment (creatinine clearance of ≤30 mL/min).
Suicidal ideation: Monitor patients for depression or suicidal ideation and prompt patients, families, and caregivers to report such symptoms to the health care provider
Alcohol Withdrawal: Use of Campral does not eliminate or diminish withdrawal symptoms.
Common adverse 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 are: accidental injury, asthenia, pain, anorexia, diarrhea, flatulence, nausea, anxiety, depression, dizziness, dry mouth, insomnia, paresthesia, pruritus and sweating.
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.
Use in specific populations
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/m basis) and in rabbits when given in doses that are approximately 3 times the human dose (on a mg/m basis).
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 Campral is administered to a nursing woman.
Pediatric Use: The safety and efficacy of Campral have not been established in the pediatric population.
Geriatric use: 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.
In 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 symptomatic and supportive.