Deadly cough syrup: the real costs of cheap drug excipients

I wrote back in December about poisoning deaths in Panama due to a cough syrup substitution with diethylene glycol, a cheap industrial solvent that is toxic to the kidneys and nervous system when ingested. This same solvent was the cause of over a hundred deaths in the US in 1937, leading to passage of the most signficant drug purity laws in US history.

In this morning's New York Times, Walt Bogdanich and Jake Hooker present a comprehensive analysis of the Panamanian poisoning cases, tracing the diethylene glycol to a Chinese glycerine factory run by a former tailor. The Times reporters revealed that the factory was not certified to produce pharmaceutical ingredients. Glycerine, or glycerol, is a thick liquid used to create a syrupy consistency in drugs, foods, and cosmetics. It is cheap, but apparently not as cheap as diethlyene glycol is in China.

The article is a tremendous tour de force of tracking the misrepresented solvent as glycerine from China, through Spain, and into Panama. The article also details the astute clinical observations of an impressive Panamanian physician, Dr Néstor Sosa, that led to the discovery of the toxic substance in a cough syrup used to treat the side effect of the angiotensin-converting enzyme inhibitor, lisinopril.

With melamine being found to boost the apparent protein content of Chinese-sourced gluten intended for pet food and livestock feed, this story raises some very serious concerns about the global consumables market and, "shows how China's safety regulations have lagged behind its growing role as low-cost supplier to the world."

But before American readers think we are immune to such deadly adulterations of our drug products, the authors note:

Last week, the United States Food and Drug Administration warned drug makers and suppliers in the United States "to be especially vigilant" in watching for diethylene glycol. The warning did not specifically mention China, and it said there was "no reason to believe" that glycerin in this country was tainted. Even so, the agency asked that all glycerin shipments be tested for diethylene glycol, and said it was "exploring how supplies of glycerin become contaminated."

Moreover, buried in the article is evidence that importation of such misrepresented glycerin may have already occurred:

In fact, The Times found records showing that the same Chinese company implicated in the Haiti poisoning also shipped about 50 tons of counterfeit glycerin to the United States in 1995. Some of it was later resold to another American customer, Avatar Corporation, before the deception was discovered.

"Thank God we caught it when we did," said Phil Ternes, chief operating officer of Avatar, a Chicago-area supplier of bulk pharmaceuticals and nonmedicinal products. The F.D.A. said it was unaware of the shipment.

Not to be alarmist, but the diethylene glycol and melamine cases are bringing to light the real costs of our dependence on "cheap" commodity chemicals in the global market. Manufacturers and regulators alike need to renew their vigilance on the quality and purity of even the most common and seemingly innocuous of food and drug ingredients.

Similarly, clinicians around the world should be on the lookout for cases of unexplained neuropathies (weakness or tingling), particularly in the legs, that might be mistaken for Guillan-Barre syndrome, as it was initially in the Panamanian poisoning cases. Advanced cases of diethylene glycol poisoning result in renal failure and respiratory paralysis but these neuropathies, together with difficulty urinating, are early signs of poisoning.

Finally, the Times article closes with a zinger on the name of the misrepresented product that coursed through Spain before going on to Panama. The product was labeled as "TD" glycerin. A salesman from the Taixing Glycerine Factory told the reporters that TD stood for "tidai" - "substitute" in English.

Be sure to take time today to read this excellent, albeit lengthy, article. And on Monday, NYT reporter Walt Bogdanich will be answering questions about this article.