A First-Generation Antihistamine May Have Anti-HCV Properties: What is the Clinical Impact?

Preliminary evidence suggests that the first-generation antihistamines chlorcyclizine and hydroxyzine may fight HCV infection for pennies a day.

Preliminary evidence suggests that the first-generation antihistamines chlorcyclizine and hydroxyzine may fight HCV infection for pennies a day.

Recent in vitro data heralded in the popular press suggest that a first-generation antihistamine chlorcyclizine (CCZ) first approved in the 1960s may have anti-HCV properties, leading many patients to ask about the clinical relevance of this finding.

Closer examination of research reports indicate that these findings are from test tube studies—not high-quality human clinical trials. Researchers expect the drug to be useful as a lead compound for development of new therapies, but there are no immediate plans to commercialize CCZ as an anti-HCV treatment.

Interest in CCZ is mainly spurred by the high cost of novel direct-acting oral anti-HCV therapies, such as Sovaldi, Harvoni, Viekira Pak, and Olysio. A 12-week course of any of these products carries an average wholesale price ranging anywhere from $80,000 to more than $113,000. In contrast to these costs, CCZ is available for a few cents per tablet from multiple generic manufacturers.

Initial interest in CCZ resulted from researchers screening a total of 30,426 existing compounds for anti-HCV properties. This research uncovered a total of 49 existing drugs with anti-HCV properties. Of these, hydroxyzine and chlorcyclizine had the strongest effects, with nanomolar inhibitory concentrations against proteins that assist HCV virions in cell entry. Both drugs have a common structural elements. Specifically, the drugs both contain a benzhydrylpiperazine ring in common.

These in vitro effects were then validated in a mouse pharmacokinetic model. Not only did CCZ show anti-HCV effects, but it also distributed preferentially to liver tissue—a valuable property for a drug that targets a virus with hepatotoxic effects.

Over a period of 4 to 6 weeks, researchers administered daily doses of CCZ to mice implanted with human liver cells infected with genotype-1 HCV, confirming the favorable in vitro results.

According to NIH senior investigator T. Jake Liang, MD, “CCZ is a promising candidate for part of a treatment regimen for this potentially life-threatening disease,” but Liang cautioned patients not to self-treat with CCZ, despite its widespread availability.

“People should not take CCZ to treat their hepatitis C until it has been demonstrated that CCZ can be used safely and effectively for that purpose,” he said.

Despite this, researchers are cautiously optimistic about the drug’s outlook. According to NIH division research director Griffin P. Rodgers, MD, “[this drug] may eventually provide an affordable alternative to costly options, especially in low-resource communities where hepatitis C infection is widespread."


  • Chamoun-Emanuelli AM, Pécheur EI, Chen Z. Benzhydrylpiperazine compounds inhibit cholesterol-dependent cellular entry of hepatitis C virus. Antiviral Res. 2014;109:141-148.
  • He S, Lin B, Chu V, et al. Repurposing of the antihistamine chlorcyclizine and related compounds for treatment of hepatitis C virus infection. Sci Transl Med. 2015;7(282):282ra49.
  • National Institutes of Health. Allergy drug inhibits hepatitis C in mice. http://www.nih.gov/news/health/apr2015/niddk-08.htm. Accessed July 2015.