Deaths of Japanese Patients Prompt Label Change for Simeprevir

The maker of Sovriad (simeprevir) has revised its package insert labeling on the order of Japanese health officials following the deaths of three people who took the hepatitis C drug.

Janssen in Japan revised the labeling of Sovriad, known generically as simeprevir, to include a warning that states cases of fatalities preceded by significant elevation in blood bilirubin levels have been reported following administration of simeprevir, according to an e-mail from Lisa Vaga, the director of Janssen’s Product Communication Global Pharmaceuticals Communication & Public Affairs. Three patients in Japan, 40 to 60 years old, died after taking the drug as treatment for chronic hepatitis C virus infection.

“The safety and well-being of patients are our top priorities and we take all reports of adverse events seriously,” Vaga said in response to questions about the drug.

The Pharmaceuticals and Medical Devices Agency (PMDA) of Japan posted a “rapid safety communication” Blue Letter on its website, which Janssen Japan will distribute to healthcare professionals alerting them to the revision. The type of letter contains information that should be promptly provided to alert healthcare professionals and is issued by PMDA when important safety information requires immediate communication.

“Cases of remarkable increase blood bilirubin levels followed by hepatic dysfunction and/or renal impairment, etc. leading to death have been reported in patients treated with this drug.” states the letter which advises that attention should be paid to blood bilirubin testing, abnormalities and increases while the drug is taken and even after it is discontinued.

To date, more than 18,900 patients in Japan have been prescribed simeprevir, anNS3/4A protease inhibitor, which is given as a combination treatment along with peginterferon and ribavirin. Simeprevir is also approved under the trade name Olysio for treatment of chronic hepatitis C in the United States and Europe.

The Food and Drug Administration has not reviewed the deaths that occurred in Japan butthe agency is working with the drugmaker and Japanese health officials to obtain necessary information about the cases, Stephanie Yao, an FDA spokesperson said in an email. She noted that a recent FDA review of “simeprevir postmarketing cases was consistent with safety information already included in the product labeling.”

Vaga said that treatment information was available for the three fatal cases described in the Blue Letter issued by Japanese regulators. In each case, evaluation of specific drug causality is confounded by concomitant treatments, including peginterferon and ribavirin, as well as the patient’s condition, she said.

“Janssen carefully monitors reports about the use of our medicines and shares information with regulatory authorities to address benefits and risks, as well as to discuss information for prescribers and patients about appropriate use,” Vaga said. “The frequency of adverse events related to simeprevir is provided in the product labeling, based on clinical trial information and spontaneous reports.”

In other countries outside of Japan where its drug is marketed, Janssen is monitoring for adverse events, according to Vaga. However, the company maintains that there is no present need to further update prescribing information for simeprevir because it adequately reflects the information regarding the occurrence and significance of blood bilirubin elevations.

“We will work transparently with health authorities and healthcare professionals to evaluate if any actions are necessary,” Vaga said in relation to the possibility of similar label changes in other countries.

“It’s important to note, if patients are uncertain about their simeprevir, peginterferon and ribavirin combination treatment or have any questions about the therapy, they should speak to their healthcare professional,” Vaga said. “Patients should not discontinue their simeprevir, peginterferon and ribavirin combination treatment without the guidance of a trained physician.”