Nitrosamine impurities have now been found in two tuberculosis drugs, prompting the US Food and Drug administration (FDA) to clarify how it will handle elevated levels of the potential carcinogen in life-saving antibiotics.
FDA recently became aware of nitrosamine impurities in certain samples of rifampin and rifapentine. These are antibacterial drugs used to treat tuberculosis; rifampin is also used to treat other serious infections.
Elevated levels of nitrosamines have been found in samples of both substances: the nitrosamine 1-methyl-4-nitrosopiperazine (MNP) was found above the acceptable intake limit of 0.16 parts per million (PPM) in rifampin. Rifapentin samples had another nitrosamine, 1-cyclopentyl-4-nitrosopiperazine (CPNP), at levels above that substance’s acceptable intake limit of 0.1 ppm.
FDA states “The acceptable intake limits are 0.16 parts per million (ppm) for MNP in rifampin and 0.1 ppm for CPNP in rifapentine. The agency will not object to certain manufacturers temporarily distributing rifampin containing MNP below 5 parts per million (ppm). The agency also will not object to certain manufacturers temporarily distributing rifapentine containing CPNP below 14 ppm. FDA will not object to these higher exposures to maintain patient access to these life-saving medications’.
The decision was based on a risk-benefit analysis of withholding important medication for those with tuberculosis, a potentially fatal disease, said FDA.
Manufacturers should contact the Center for Drug Evaluation and Research’s Drug Shortages Staff when their testing of rifampin or rifapentine shows levels of nitrosamines that exceed the acceptable intake limits of 0.16 ppm for MNP and 0.1 ppm for CPNP. FDA will determine on a case-by-case basis whether those drugs should be released for distribution, said FDA.
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