Japan's Kobayashi Kako admits manufacturing mix-up led to patient's death

A "grave" manufacturing error in Japan tainted antifungal tablets with high doses of a sleep medication, leading to the death of one woman in her 70s and side effects in hundreds more people. 

Kobayashi Kako, the drugmaker behind the mix-up, said employees may have failed to follow company procedure when removing and mixing ingredients for the two highly divergent drugs, Osaka newspaper Asahi Shimbun reported.

The woman passed away Dec. 10 at a Tokyo-area hospital after taking Kobayashi's antifungal drug Itraconazole 50 Meek, the newspaper said.

The company's own investigation revealed 5 milligrams of a sleep med—identified by The Mainichi Shimbun as rilmazafone hydrochloride hydrate—had been added to each problematic tablet of Itraconazole 50 Meek. That amount is two-and-a-half times what's typically included in a single rilmazafone pill. 

The company is now pulling one lot of Itraconazole 50 Meek, which comprises 929 boxes of 100 tablets each. The tainted doses were made in June and July and shipped out to hospitals between September and December. Kobayashi is also recalling lots of 100-mg and 200-mg tablets, though these two dosage strengths appear to have been spared in the mix-up, Mainichi wrote. 

Itraconazole 50 was prescribed to 364 patients at hospitals in Tokyo and 30 other Japanese prefectures before the mistake was caught. As of Dec. 11, the company had received up to 134 patient side effect reports, plus reports of at least 15 traffic accidents linked to accidental consumption of the rilmazafone-tainted tablets, Asahi Shimbun said. 

To prevent these sorts of mistakes, Kobayashi said it keeps its drug ingredients in clearly differentiated containers. Components for its athlete's foot med go in a pulp-based, drum can-shaped container a little less than 3 feet tall, while its sleep med is stored in a flat box that clearly bears the drug's name. The company also requires two employees to work as a team when drug ingredients are removed and mixed.

Thing is, it didn't always work out this way. There was a period when a single staffer performed that task, Kobayashi Kako admitted to Asahi Shimbun. It suspects the mix-up may have happened then. 

“We made a grave error and are acutely aware of the gravity of our responsibility,” Hiroyuki Kobayashi, president of Kobayashi Kako, told reporters. 

The company is consulting with third-party experts to get to the bottom of the mishap and work out new procedures to ensure it doesn't happen again.

Inspectors from Fukui Prefecture, who visited the company Dec. 9, have since determined the drugmaker had committed the error in violation of Japanese health ministry procedures.  And as Kobayashi Kako pursues its own investigation, Fukui Prefecture is weighing whether to inspect the site again to see whether the company violated Japan's pharmaceuticals and medical devices act, Mainichi said. 

Drug recalls and manufacturing mix-ups, while never pleasant, aren't often fatal. Teva in 2013 was ordered by France's drug regulator to pull thousands of blister packs of its diuretic furosemide when its sleep aid Zopiclone was placed into packages instead—an error tied to a number of deaths.