Expert: API Shortage for TB Treatments Causing Serious Concern in US

07-Apr-2013 - Last updated on 08-Apr-2013 at 08:37 GMT

Ongoing shortages of the API isoniazid are forcing US state health departments to ration TB (tuberculosis) drugs and - for some patients - forego treatment altogether, a Johns Hopkins University expert told us.

The US CDC and FDA are calling for the rationing of isoniazid and requiring its use only for serious active cases of TB, such as people who have fallen ill or might transmit it, Johns Hopkins TB clinic director Maunank Shah, told In-Pharmatechnologist.com.

According to the US FDA, the three manufacturers of the drug in the US – Teva, Sandoz and VersaPharm – are seeing shortages because of increased demand for the active ingredient.

Both Sandoz and Teva estimated near the end of 2012 that the shortages would be resolved by the late January but that has not been the case. VersaPharm said it expects to have the drug back on the market by January 2014 while Sandoz now says it expects to have product available in April.

The Association of Health-System Pharmacists also noted the shortage in a March bulletin, saying manufacturers Mylan Institutional, Sandoz, Versapharm, and West-Ward “could not provide a reason for the shortage.”

Shah said that he heard all three of the FDA-listed manufacturers obtain the active ingredient - isonicotinic acid, which is produced from 4-methylpyridine - from a single source and “that source is having manufacturing issues.” He added that he’s heard rumors the active ingredient is produced from a facility in Japan that was hit by the tsunami in 2011. None of the companies listed provided a response to the cause of the shortages by press time.

The FDA also recently highlighted shortages of other TB drugs, including Sanofi’s Rifamate and Pfizer’s injectable Rifampin. But Shah said the shortage of the injectable is less worrisome because they are not used as frequently as isoniazid or Rifamate, which contains isoniazid. He also noted that there are second line treatments that can be used in some cases but they are “not potent,” and treatment duration has to be extended.

Shortages Only in US

Countries outside of the US are also not seeing the same shortages of isoniazid, Shah said, noting there is plenty of treatment in Europe, Asia and Africa though none of their manufacturing sites have been approved by the FDA.

Shah said he believes the recent problems with compounding pharmacies and deadly fungal meningitis are stopping the FDA from being more lax in its approval of some of these foreign manufacturing sites to ease the shortages. He also questioned why the US is distributing some foreign TB drugs through programs such as PEPFAR (President's Emergency Plan for AIDS Relief) in foreign countries but “we can’t we use them here.”

The situation is not yet a full-blown public health crisis in the US because the numbers of active TB cases are still generally low, Shah said.

“The hope is that [the shortage] will be resolved but when is a big question,” he said. Part of the problem is that neither the CDC nor any state health departments stockpiled isoniazid and many of these programs are on a tight budget.

“This isn’t going to spin out of control unless rifampin goes into shortage as well,” he noted. Shah said he met recently with congressmen on Capitol Hill to discuss the shortages and try to come up with a resolution.