Epilepsy drug can induce skin disorders in Asians

By Alison Hsiao  /  Staff reporter, with CNA

Tue, Nov 26, 2013 - Page 4

Severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are not merely medical conditions, but also have a high social cost because of the high rate of lawsuits against pharmaceutical companies and prescribing physicians, a medical research head said.

SCARs account for more than 50 percent of the government-funded Drug Relief Foundation’s annual compensation funds, said Chung Wen-hung (鍾文宏), director of Drug Hypersensitivity Clinical and Research Center at Chang Gung Memorial Hospital.

Given that a large number of patients are frequently exposed to multiple drugs and are at a higher risk of developing drug hypersensitivity, Chung and his research team have since 2002 been working on the identification of risk factors and genetic susceptibility of individuals who are at risk for SCAR.

The team has since found that carbamazepine (CBZ), a drug primarily used to control certain types of epileptic seizures, and allopurinol, a drug used to treat high uric acid levels, are more likely to induce SJS/TEN in people with certain genetic markers.

“We firstly reported a strong genetic marker of HLA-B*1502, [a particular human leukocyte antigen (HLA) allele] for CBZ-induced SJS/TEN in 2004,” Chung said in his presentation at the recent International Congress on Cutaneous Adverse Drug Reactions.

Chung said that both the US’ and Taiwan’s Food and Drug Administrations, followed by other countries, relabeled the drug warning information, recommending those of Asian ancestry — for the allele occurs almost exclusively in patients with Asian ancestry — to be screened for HLA-B*1502 before starting treatment with CBZ in 2007.

The National Health Insurance program has also started to cover the expense of the genetic screening for HLA-B*1502 in patients initiating CBZ since 2010.

The team reported another strong genetic marker of HLA-B*5801 for allopurinol-induced SCAR in 2005.

The risk of developing the serious adverse reaction for people with the marker can be 500 times higher than those without the marker, Chung said.

He added that NHI data show the drug causes about 20 deaths a year, with the risk group consisting of those with kidney disease, elders and people with the “three highs” — hypertension, hyperglycemia and hyperlipidemia.

Despite the genetic discovery, the drug is still widely used in Taiwan, Chung said.

Those with the genetic marker may suffer from adverse reactions, such as acute kidney failure, epidermal necrolysis, body rashes and swelling, and liver and kidney malfunctions, after taking allopurinol for two to three weeks.

Price is the main reason the drug is still widely used, while a genetic screening might cost thousands of dollars, Chung said, calling on the government to lift the National Health Insurance payment limit for the risk group’s drug replacement as new drugs for lowering uric acid are now available.

The research team has also found a genetic marker in people who are susceptible to SCAR induced by phenytoin, another anti-epileptic drug, and has scheduled to make the results public next year.