A survey of US tuberculosis programs found that shortages of anti-tuberculosis drugs are common and sometimes result in delayed, interrupted, or inadequate treatment.
SAN FRANCISCO—Shortages of drugs to treat multidrug resistant tuberculosis (MDR-TB) occur frequently and often hinder treatment of the disease in the US, according to Neha Shah, MD MPH, of the CDC’s Division of Tuberculosis Elimination in Atlanta. (See also, “Anti-Infective Medication Shortages Affect Patient Care,” in the March issue of Pulmonary Reviews.)
“Interruptions in medications for MDR-TB treatment have been experienced by many TB programs nationally,” Shah told Pulmonary Reviews. “The interruptions have had serious consequences. Many agencies, staff, and resources are needed to resolve drug interruption issues.”
Shah and colleagues assessed the results of a National Tuberculosis Controller’s Association (NTCA) survey to determine the extent of anti-TB drug shortages and their effects on patient care and TB control. In turn, they planned to use the information to raise awareness of the shortages and guide policy and advocacy. Their findings were presented at the American Thoracic Society 2012 International Conference.
Shortages With Consequences
The NTCA surveyed all designated Tuberculosis Controllers of state, county, or local TB programs who were registered members of the NTCA in November 2010 and had registered and functioning e-mail addresses. The surveys, which included questions about drug procurement, costs, and treatment delays, were sent via e-mail and completed via the internet.
Among the 61 surveyed individuals, there were 33 (54%) respondents, 29 (88%) of whom represented state TB programs.
“Two-thirds of the respondents were from jurisdictions that reported 100 or more TB cases per year,” Shah noted. “Respondents included jurisdictions with the five highest case rates and the three highest reported numbers of cases.” Of the programs represented by the respondents, 21 supply MDR-TB medications to all patients directly, four provide medications to some patients, and eight have patients who are insured publicly or privately.
Twenty-six respondents reported that their programs had an MDR-TB case in the last five years, and 21 reported problems with obtaining MDR-TB drugs during that time. Drug interruptions often resulted in treatment delays (57%), treatment lapses or interruptions (32%), or use of inadequate regimens (32%), as well as substantial staff time dedicated to drug procurement (68%).
Sizing Up the Problem
In the US, about 100 MDR-TB cases are reported and about 1,500 people are exposed to the disease each year, Shah explained. She noted that each patient with untreated TB could infect another 10 to 15 people. MDR-TB patients require treatment with five to six drugs for 18 to 24 months.
“Since 2005, there have been interruptions in two of the four first-line anti-TB medications (isoniazid and rifampin) and recurring difficulty accessing second-line medications used to treat MDR-TB, including the crucial injectable medications that are the cornerstone for MDR-TB treatment,” Shah added. In June 2011 through February 2012, the injectable drug kanamycin was unavailable and the injectable drugs amikacin and capreomycin were allocated only on an emergency basis. Contributors to recent shortages have included drugs having a sole US manufacturer (capreomycin, cycloserine, Para-aminosalicylate, and streptomycin), no US manufacturer (kanamycin), high or rising prices (capreomycin, cycloserine, and linezolid), and a protracted approval process involving the FDA’s Investigational New Drug (IND) program and local institutional review boards (clofazimine).
Moving Toward Solutions
“A collaborative effort with federal, national, and international agencies is needed to address the challenge of anti-TB drug shortages,” according to Shah. This effort should include the CDC, the FDA, state and local TB programs, the WHO, pharmaceutical agencies, and international organizations, she said.
Shah and colleagues also suggested a number of potential ways of alleviating the problem. A national or regional MDR-TB drug repository, additional insurance coverage for second-line TB drugs, and a streamlined process for investigational drug use all could be helpful, they said. Pharmaceutical companies could be required to provide the FDA with early notification of drug shortages and discontinuations, as well as offered financial incentives to produce scarce TB drugs, the researchers suggested.
Several positive steps are already underway, Shah added. “In October 2011, President Obama issued an Executive Order directing the FDA and the Department of Justice to take action to help further reduce and prevent drug shortages, protect consumers, and prevent price gouging,” she said.
“The FDA, the CDC, and the Global Drug Facility are working together to determine if kanamycin can be imported from a non-US manufacturer during drug interruptions. The CDC also is applying to FDA for an IND exemption for clofazimine.”
US Food and Drug Administration. A review of FDA’s approach to medical product shortages. www.fda.gov/downloads/aboutfda/reportsmanualsforms/reports/ucm277755.pdf. Published October 31, 2011. Accessed July 16, 2012.
World Health Organization. The Stop tuberculosis Strategy: building on and enhancing DOTS to meet the tuberculosis-related Millennium Development Goals. www.who.int/tb/publications/2006/who_htm_tb_2006_368.pdf. Published 2006. Accessed July 16, 2012.