Campral

Agents Used In Alcohol Dependence

May be dosed without regard to meals; however, dosing with meals was used during clinical trials and may aide compliance in patients who regularly eat three meals daily.

Acamprosate delayed-release tablets should be swallowed whole. Tablets are enteric-coated; do not chew, crush or cut.

seizures / Delayed / 0.1-1.0
suicidal ideation / Delayed / 0.1-1.0
cirrhosis / Delayed / 0.1-1.0
GI bleeding / Delayed / 0.1-1.0
hematemesis / Delayed / 0.1-1.0
pancreatitis / Delayed / 0.1-1.0
exfoliative dermatitis / Delayed / 0.1-1.0
myocardial infarction / Delayed / 0.1-1.0
bronchospasm / Rapid / 0.1-1.0
hearing loss / Delayed / 0.1-1.0
torticollis / Delayed / 0-0.1
peptic ulcer / Delayed / 0-0.1
cholecystitis / Delayed / 0-0.1
cardiomyopathy / Delayed / 0-0.1
heart failure / Delayed / 0-0.1
pulmonary embolism / Delayed / 0-0.1
visual impairment / Early / 1.0
renal failure (unspecified) / Delayed / Incidence not known
bone fractures / Delayed / Incidence not known

depression / Delayed / 4.0-8.0
hyperesthesia / Delayed / 0.1-1.0
neuropathic pain / Delayed / 0.1-1.0
hostility / Early / 0.1-1.0
withdrawal / Early / 0.1-1.0
hallucinations / Early / 0.1-1.0
confusion / Early / 0.1-1.0
migraine / Early / 0.1-1.0
dysphagia / Delayed / 0.1-1.0
gastritis / Delayed / 0.1-1.0
esophagitis / Delayed / 0.1-1.0
elevated hepatic enzymes / Delayed / 0.1-1.0
vaginitis / Delayed / 0.1-1.0
urinary incontinence / Early / 0.1-1.0
atopic dermatitis / Delayed / 0.1-1.0
phlebitis / Rapid / 0.1-1.0
sinus tachycardia / Rapid / 0.1-1.0
hypotension / Rapid / 0.1-1.0
angina / Early / 0.1-1.0
orthostatic hypotension / Delayed / 0.1-1.0
anemia / Delayed / 0.1-1.0
eosinophilia / Delayed / 0.1-1.0
thrombocytopenia / Delayed / 0.1-1.0
lymphocytosis / Delayed / 0.1-1.0
diabetes mellitus / Delayed / 0.1-1.0
hyperuricemia / Delayed / 0.1-1.0
gout / Delayed / 0.1-1.0
hyperbilirubinemia / Delayed / 0.1-1.0
hyperglycemia / Delayed / 0.1-1.0
amblyopia / Delayed / 0.1-1.0
encephalopathy / Delayed / 0-0.1
psychosis / Early / 0-0.1
mania / Early / 0-0.1
hepatitis / Delayed / 0-0.1
oral ulceration / Delayed / 0-0.1
melena / Delayed / 0-0.1
colitis / Delayed / 0-0.1
nephrolithiasis / Delayed / 0-0.1
hematuria / Delayed / 0-0.1
ejaculation dysfunction / Delayed / 0-0.1
psoriasis / Delayed / 0-0.1
goiter / Delayed / 0-0.1
hypothyroidism / Delayed / 0-0.1
lymphadenopathy / Delayed / 0-0.1
leukopenia / Delayed / 0-0.1
hyponatremia / Delayed / 0-0.1
myopathy / Delayed / 0-0.1
photophobia / Early / 0-0.1
ascites / Delayed / 0-0.1
amnesia / Delayed / 1.0
constipation / Delayed / 1.0
impotence (erectile dysfunction) / Delayed / 1.0
hypertension / Early / 1.0
peripheral vasodilation / Rapid / 1.0
chest pain (unspecified) / Early / 1.0
palpitations / Early / 1.0
peripheral edema / Delayed / 1.0
dyspnea / Early / 1.0

diarrhea / Early / 10.0-17.0
insomnia / Early / 6.0-9.0
anxiety / Delayed / 5.0-8.0
asthenia / Delayed / 5.0-7.0
anorexia / Delayed / 2.0-5.0
dizziness / Early / 3.0-4.0
nausea / Early / 3.0-4.0
flatulence / Early / 1.0-4.0
pruritus / Rapid / 3.0-4.0
paresthesias / Delayed / 2.0-3.0
hyperhidrosis / Delayed / 2.0-3.0
agitation / Early / 0.1-1.0
vertigo / Early / 0.1-1.0
eructation / Early / 0.1-1.0
weight loss / Delayed / 0.1-1.0
increased urinary frequency / Early / 0.1-1.0
libido increase / Delayed / 0.1-1.0
maculopapular rash / Early / 0.1-1.0
urticaria / Rapid / 0.1-1.0
acne vulgaris / Delayed / 0.1-1.0
alopecia / Delayed / 0.1-1.0
xerosis / Delayed / 0.1-1.0
ecchymosis / Delayed / 0.1-1.0
muscle cramps / Delayed / 0.1-1.0
epistaxis / Delayed / 0.1-1.0
tinnitus / Delayed / 0.1-1.0
malaise / Early / 0.1-1.0
fever / Early / 0.1-1.0
paranoia / Early / 0-0.1
hyperkinesis / Delayed / 0-0.1
hypersalivation / Early / 0-0.1
polyuria / Early / 0-0.1
urinary urgency / Early / 0-0.1
nocturia / Early / 0-0.1
menorrhagia / Delayed / 0-0.1
photosensitivity / Delayed / 0-0.1
diplopia / Early / 0-0.1
headache / Early / 1.0
tremor / Early / 1.0
drowsiness / Early / 1.0
abdominal pain / Early / 1.0
appetite stimulation / Delayed / 1.0
dyspepsia / Early / 1.0
weight gain / Delayed / 1.0
vomiting / Early / 1.0
libido decrease / Delayed / 1.0
rash / Early / 1.0
syncope / Early / 1.0
arthralgia / Delayed / 1.0
myalgia / Early / 1.0
rhinitis / Early / 1.0
cough / Delayed / 1.0
pharyngitis / Delayed / 1.0
dysgeusia / Early / 1.0
chills / Rapid / 1.0
infection / Delayed / 0.1
back pain / Delayed / 1.0
influenza / Delayed / 1.0

Campral

Rx

Oral medication adjunct to maintain abstinence in ethanol-dependent patients following ethanol withdrawal.

666 mg PO 3 times daily in combination with naltrexone (50 mg PO once daily with food). In a double-blind placebo-controlled trial, 160 patients were randomized to receive naltrexone, acamprosate, naltrexone plus acamprosate, or placebo for 12 weeks. All therapies were significantly more efficacious than placebo with regard to the primary outcomes of time to first drink, time to relapse, and cumulative abstinence. The naltrexone group tended to have a better outcome of time to first drink and time to relapse when directly compared to acamprosate. The combination of naltrexone and acamprosate demonstrated significantly lower relapse rates than placebo and acamprosate but not naltrexone. Patients received psychotherapy and psychopathologic assessments weekly throughout the treatment phase of the study.

666 mg PO 3 times daily is the suggested dosage. A lower dose may be effective in some patients. Lower initial doses may be required in geriatric adults since renal function may be diminished. Alternative dosage regimens have been used. In one study, doses of 1332 mg/day PO (666 mg in the morning, 333 mg at mid-day, and 333 mg in the evening) were administered for patients 60 kg or less, and doses of 1998 mg/day PO (666 mg PO 3 times daily) were administered for patients more than 60 kg. Efficacy in promoting abstinence has not been demonstrated in patients who have not undergone detoxification or achieved alcohol abstinence; therefore, acamprosate is indicated only in patients who are abstinent at the time of treatment initiation. Maintain treatment even if the patient relapses. Pharmacotherapy should be used as a part of a comprehensive management program that includes psychosocial support and treatment.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

CrCl > 50 mL/min: No dosage adjustment necessary.
CrCl 30—50 mL/min: A starting dose of 333 mg PO three times daily is recommended.
CrCl < 30 mL/min: Use is contraindicated.

Bupropion; Naltrexone: (Minor) The administration of naltrexone with acamprosate results in an increase in acamprosate exposure (AUC) by 25% and in peak concentration (Cmax) by 33%. However, acamprosate dosage adjustments are not required.
Naltrexone: (Minor) The administration of naltrexone with acamprosate results in an increase in acamprosate exposure (AUC) by 25% and in peak concentration (Cmax) by 33%. However, acamprosate dosage adjustments are not required.

Acamprosate/Acamprosate Calcium/Campral Oral Tab DR: 333mg

Maximum dosage limit information is not available.

Maximum dosage limit information is not available.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Mechanism of Action: The mechanism of action of acamprosate in maintenance of alcohol abstinence is not completely understood. However, in vitro data suggests that acamprosate has affinity for type A and type B GABA receptors, however it has since been proposed that the drug lowers neuronal excitability; this action appears to be a centrally-mediated. Chronic alcohol consumption results in the up-regulation of N-methyl-D-aspartate (NMDA), an excitatory neurotransmitter of the glutamatergic system, to overcome the sedative effects of the potentiated GABAnergic system. This action allows the CNS to function more normally in a depressed state. This change in the neurotransmitter system results in anxiety, hyper-excitability and sleeplessness during alcohol withdrawal, causing the dependent patient to drink alcohol in order to relieve these symptoms. By reducing the postsynaptic efficacy of the excitatory receptors, acamprosate heightens the patients ability to remain abstinent during withdrawal. Animal studies note that the drug does not have anxiolytic, antidepressant, hypnotic, muscle relaxant, or psychotropic actions. Acamprosate reduces alcohol intake in alcohol-dependent animals in a dose-dependent manner; the effect is specific to alcohol and the mechanisms of alcohol dependence.

Acamprosate is administered orally. Protein binding of acamprosate is negligible and the volume of distribution is approximately 72 to 109 L (approximately 1 L/kg). Acamprosate does not undergo hepatic metabolism but is excreted as unchanged drug via the kidneys. The terminal half-life is approximately 20 to 33 hours. A linear relationship exists between creatinine clearance, total apparent plasma clearance and acamprosate half-life.
 
Affected Cytochrome P450 (CYP450) isoenzymes and drug transporters: None
Acamprosate had no inducing potential on CYP1A2 and CYP3A4, and acamprosate does not inhibit in vivo metabolism mediated by CYP1A2, 2C9, 2C19, 2D6, 2E1, or 3A4. The pharmacokinetic parameters of acamprosate were unaffected when administered with alcohol, disulfiram or diazepam. While co-administration of acamprosate calcium delayed-release tablets with naltrexone led to a 33% increase in the Cmax and a 25% increase acamprosate exposure (AUC), no adjustment of acamprosate dosage is recommended.

The absolute bioavailability of acamprosate is approximately 11% after oral administration. When taken with food, acamprosate peak concentration (Cmax) and exposure (AUC) are reduced by approximately 42% and 23%, respectively. However, no dosage adjustment is necessary and the drug may be given with meals.

Acamprosate is classified as FDA pregnancy risk category C.  While the manufacturer recommends use during pregnancy only if the benefits justify the potential risk to the fetus, in women with alcoholism the risk of administering acaprosate compared to the risk of continued alcohol consumption should be taken into consideration. Animal studies have shown the drug to be teratogenic at doses comparable to the human dose on a mg/m2 basis; non-teratogenic effects on gestation have also been reported. There are no adequate and well controlled studies in pregnant women.

Excretion of acamprosate in human milk and its potential effects on a nursing infant are unknown. Although data during breast-feeding are limited, its use may be considered in those women requiring the drug to avoid alcohol consumption. The manufacturer recommends caution when administering to lactating women. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.