Drug Interactions between Antabuse and black cohosh

GENERALLY AVOID: Due to a potentially high alcohol content, tincture formulations of black cohosh may produce severe reactions when coadministered with disulfiram. The mechanism is inhibition of aldehyde dehydrogenase (ALDH) by 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.

GENERALLY AVOID: Concomitant use of black cohosh (Cimicifuga racemosa rhizome) with other agents that are known to induce hepatotoxicity including disulfiram may theoretically increase the risk of liver injury. Black cohosh has been suspected in rare cases of liver toxicity ranging from abnormal liver function tests and jaundice to various forms of hepatitis and hepatic failure requiring transplantation. The onset has typically been within the first 3 months after initiation of black cohosh. Although approximately half of the cases resulted in hospitalization, most improved or resolved following discontinuation of the product. Many of the cases were not well documented with respect to the specific herbal formulation and dose used or timeframe of treatment in relation to onset of reaction, or they were complicated by multiple confounding factors. Some of the cases also involved products containing multiple herbal or other medicinal substances. Nevertheless, the European Medicines Agency (EMEA) and the Committee on Herbal Medicinal Products (HMPC) reviewed 42 such cases and released an assessment statement in 2006 indicating a potential connection between products containing Cimicifuga racemosa rhizome and human hepatotoxicity. The Medicines and Healthcare products Regulatory Agency (MHRA) in the U.K. also issued an assessment report supporting a causal association after reviewing data from over 40 cases received through their reporting system and similar systems in other countries, as well as in the published literature. Hepatotoxicity warnings are currently required on products containing black cohosh marketed in many European countries and Australia. With respect to disulfiram, cases of hepatotoxicity including hepatic failure resulting in transplantation or death have been reported. Severe and sometimes fatal hepatitis may develop even after many months of therapy. Both patients with or without prior history of hepatic impairment have been affected.

MANAGEMENT: The use of black cohosh tinctures in combination with disulfiram should be avoided. Until more information is available, patients should also consider avoiding the use of other products containing black cohosh if they are receiving treatment with disulfiram due to the potential for additive hepatotoxicity. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, light-colored stools, and jaundice.