Drug Interactions between Cymbalta and Zefazone

GENERALLY AVOID: Use of duloxetine in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Duloxetine alone can increase serum transaminase levels. In clinical trials, 0.3% of patients discontinued duloxetine due to liver transaminase elevations. The median time to detection was about two months. Three duloxetine-treated patients had liver injury as manifested by transaminase and bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, which may have contributed to the abnormalities observed. Duloxetine does not appear to enhance the central nervous system effects of alcohol. When duloxetine and ethanol were administered several hours apart so that peak concentrations of each would coincide, duloxetine did not increase the impairment of mental and motor skills caused by alcohol.

MANAGEMENT: Due to the risk of liver injury, patients prescribed duloxetine should be counseled to avoid excessive use of alcohol. Duloxetine should generally not be prescribed to patients with substantial alcohol use.

GENERALLY AVOID: Some cephalosporins may occasionally induce a disulfiram-like reaction when coadministered with alcohol. The interaction has been reported for cefamandole, cefoperazone, cefotetan, and moxalactam. These agents contain an N-methylthiotetrazole (NMTT) side chain that may inhibit aldehyde dehydrogenase (ALDH) similar to disulfiram. Following ingestion of alcohol, inhibition of ALDH results in increased concentration of acetaldehyde, the accumulation of which produces an unpleasant physiologic response referred to as the 'disulfiram reaction'. Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion. Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmias, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. Cefonicid contains a structurally similar side chain but did not produce elevations in blood acetaldehyde or a disulfiram reaction to ethanol in 15 healthy volunteers given single and multiple one gram doses of the drug.

MANAGEMENT: Patients receiving cephalosporins with the NMTT side chain should avoid the concomitant use of alcohol and alcohol-containing products.