What Is a Narrow Therapeutic Index?

According to the U.S. Food and Drug Administration (FDA), a drug with a narrow therapeutic range (NTI) is one with a narrow range between the drug’s risks and its benefits. The NTI is also known a narrow therapeutic index or critical dose drug. The FDA considers these drugs to be subject to “therapeutic drug concentration or pharmacodynamic monitoring.”

According to Nathan D. Pope writing in U.S. Pharmacist, NTI drugs have a less than twofold difference between the minimum effective concentration and the minimum toxic concentration in the body. Additionally, they may exhibit “limited or erratic” absorption and bioavailability depending on the formulation of the drug or on the patient taking it. For this reason, therapeutic monitoring of patient blood levels is required with NTI drugs.

The Therapeutic Products Directorate of Health Canada defines an NTI drug as one in which the ratio between the lowest concentration at which toxicity occurs and the median concentration at which the drug is clinically effective is less than or equal to two. In states such as North Carolina, prescriptions for NTI drugs must be dispensed using the same formulation as the last prescription filled; substitution is not permitted. However, the FDA does not limit substitution of NTI drugs, and the American Medical Association agrees that substitution should be allowed.

According to U.S. Pharmacist, the FDA list of NTI drugs includes digoxin, phenytoin, warfarin, theophylline and lithium. The list provided by the North Carolina Board of Pharmacy also includes carbamazepine, levothyroxine, procainamide hydrochloride and other drugs.