An over-the-counter allergy drug may be repurposed to treat patients with hepatitis C, researchers show. Chlorcyclizine, which costs about $0.50 a tablet, could offer a low-cost alternative or addition to treatment for patients with hepatitis C virus (HCV) infection.
Direct-acting antiviral therapies can cure hepatitis C, but their high cost—which can reach $84,000 for a 12-week course of treatment—currently prohibits widespread use, particularly in Asian and African countries where the disease is endemic.
To search for a cheaper alternative, Shanshan He et al used an innovative cell-based high-throughput screening strategy to analyze a library of drugs approved by the US Food and Drug Administration. He et al report in the April 8 issue of Science Translational Medicine that chlorcyclizine HCl, an antihistamine that relieves allergy symptoms, prevents HCV from entering human liver cells.
Chlorcyclizine significantly inhibited HCV infection of human hepatoma cells and primary human hepatocytes. The drug worked by blocking an early stage of HCV infection—probably entry of the virus into the cells.
He et al showed that the drug specifically blocked HCV infection, compared with 13 other viruses, including the hepatitis B virus. Furthermore, they found that the in vitro antiviral effect of chlorcyclizine synergized with that of other anti-HCV drugs, including ribavirin, interferon, telaprevir, boceprevir, sofosbuvir, daclatasvir, and cyclosporin A, without significant cytotoxicity. Chlorcyclizine might therefore be used in combination therapy for hepatitis C.
In mice, chlorcyclizine localized to the liver. The drug significantly inhibited infection of engrafted human hepatocytes, blocking HCV genotypes 1b and 2a over a time course of 4 and 6 weeks, respectively. There was no evidence of resistance—a problem commonly encountered with current hepatitis C drugs.
The authors state that because of the drug’s established clinical safety profile as an allergy medication, affordability, and simple chemical structure for optimization, chlorcyclizine is a promising candidate for “drug repurposing and further development as an effective and accessible agent for treatment of HCV infection.”
“Although hepatitis C is curable, there is an unmet need for effective and affordable medication,” said lead author T. Jake Liang (National Institute of Diabetes and Digestive and Kidney Diseases) in a press release from the NIH. He added that chlorcyclizine is “a promising candidate for part of a treatment regimen for this potentially life-threatening disease.”
Liang told HealthDay ‘”this drug complements the existing hepatitis C drugs and can be used in combination with them.”
Anton Simeonov, acting scientific director of NIH’s National Center for Advancing Translational Sciences, said that identifying already approved drugs from the US government’s pharmaceutical collection could offer a faster route to identify treatments for all diseases.
He et al will next study how the drug affects people. “People should not take chlorcyclizine to treat their hepatitis C until it has been demonstrated that it can be used safely and effectively for that purpose,” cautions Liang.
NIDDK Director Griffin P. Rodgers said that chlorcyclizine may eventually provide an affordable alternative to costly options, especially in low-resource communities where hepatitis C infection is widespread.”
About 3.2 million Americans have hepatitis C, according to the Centers for Disease Control and Prevention. A recent study put the cost of getting the new drugs to patients at $65 billion over just 5 years.
For now, “only those with more advanced liver disease are obtaining access, due to high drug costs and restrictive policies of many public and private insurance carriers,” Joseph Lim, director of the viral hepatitis program at Yale University School of Medicine, told HealthDay.
Chlorcyclizine has been around for decades but is not widely used.
Liang told HealthDay that the drug could be used in all kinds of patients with hepatitis C patients, and prevent re-infection in patients who undergo liver transplantation.
HealthDay wrote that the research is in its earliest stages, and a number of challenges remain. For one thing, “we would have to use the currently accepted dosing for any clinical trial, because the drug at high doses may have significant side effects, such as drowsiness,” Liang said. “It is possible that the current dosing may not be active against hepatitis C in people.”
In addition, Liang said, scientists might have to modify the drug to minimize its antihistamine effect. “This effort will require additional pharmacological research and development,” Liang said. Drowsiness and dry mouth are common side effects of older hay fever drugs.