Narrow Therapeutic Index (NTI)

Narrow Therapeutic Index (NTI)

Narrow Therapeutic Index (NTI) is a very close margin between the concentration in the BLOOD circulation of a DRUG that is therapeutic and the concentration that is lethal (deadly). Pharmacists generally express the therapeutic index as a ratio between the median effective DOSE (ED50) and the median lethal dose (LD50). A drug has a narrow therapeutic index when there is less than a twofold difference between the ED50 and the LD50. With NTI drugs even very small changes in the dose, variations in product potency, or changes in the person’s health status can result in toxic levels of the drug with harmful or fatal consequences.

The current standard of practice is to maintain the course treatment with the same drug product rather than substituting across brand and generic products as commonly and safely occurs with non-NTI drugs. Some doctors prefer to use specific brand name products when prescribing NTI drugs. Some states mandate a nonsubstitution standard via law or regulatory code, requiring pharmacies to dispense the original drug product. Some clinical studies support such caution though others suggest that, at least with some NTI drugs, generic substitution maintains therapeutically acceptable consistency for potency and EFFICACY.

The current standard of practice calls for close monitoring of blood concentrations until the drug reaches the desired therapeutic level, with routine blood tests to monitor blood concentration over time, when the person begins taking a new drug, and when there is a change in the person’s health status (including significant change in body weight). Once the blood concentration of the drug reaches a steady state with the drug at a therapeutic level the NTI becomes less of a concern.

COMMONLY PRESCRIBED NARROW THERAPEUTIC INDEX (NTI) DRUGS
aminophylline carbamazepine clindamycin
clozapine cyclosporin digoxin
disopyramide isoproterenol levothyroxine
lithium metaproterenol phenytoin
prazosin primidone procainamide
quinidine valproic acid warfarin

See also BIOAVAILABILITY; BIOEQUIVALENCE; ORANGE BOOK, THE; PEAK LEVEL; THERAPEUTIC LEVEL; THERAPEUTIC WINDOW; TROUGH LEVEL.

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