PlainMeds guide, sources read October 8, 2026
Narrow therapeutic index drugs
A narrow therapeutic index (NTI) drug is one where a small difference in dose or blood level can mean the medicine fails or causes serious harm. The FDA names warfarin and levothyroxine as examples, and applies tighter generic bioequivalence standards to NTI drugs.
What makes a drug an NTI drug?
FDA, Setting and Implementing Standards for Narrow Therapeutic Index DrugsFor NTI drugs, small differences in dose or blood concentration (the amount of drug in the body) may lead to therapeutic failures (that is to say, the drug is not working because it is the wrong amount for the patient) or adverse side effects that can be life-threatening or result in significant disability.
The FDA lists five general characteristics: little separation between therapeutic and toxic doses; serious therapeutic failure or side effects when levels are too low or too high; dosing guided by blood-level monitoring; low variability within the same person; and doses adjusted in very small steps.
Source: FDA, CDER Conversation on narrow therapeutic index drugs (content current as of February 26, 2024)
Which medicines has the FDA named as NTI drugs?
There is no complete official list: the FDA itself notes that most potential NTI drugs lack an NTI classification. The medicines below are the ones FDA documents name: warfarin and levothyroxine as examples, and tacrolimus, phenytoin tablets, levothyroxine and carbamazepine in its draft bioequivalence guidances that recommend replicate-design studies for NTI drugs.
| Medicine | Brand names | Generic labelers (all forms) | Pharmacy cost | Boxed warning | Shortage | Recalls since 2012 |
|---|---|---|---|---|---|---|
| Warfarin | Jantoven | 19 labelers | $0.093 per tablet 2 mg tablet | Yes | No current entry | 7 |
| Levothyroxine | Tirosint, Synthroid, Unithroid | 36 labelers | $0.0588 per tablet 112 mcg tablet | Yes | No current entry | 128 |
| Tacrolimus | Prograf, Astagraf, Envarsus | 33 labelers | $0.970 per gram 0.1% ointment | Yes | No current entry | 9 |
| Phenytoin | Dilantin, Phenytek | 29 labelers | $0.145 per capsule 100 mg capsule | No | No current entry | 11 |
| Carbamazepine | Tegretol, Carbatrol, Equetro | 42 labelers | $0.119 per tablet 200 mg tablet | Yes | A presentation being discontinued | 11 |
Source: FDA CDER Conversation; FDA FY2015 Regulatory Science Research Report: Narrow Therapeutic Index Drugs; records from openFDA and CMS NADAC
Are generic NTI drugs held to a different standard?
FDA, Setting and Implementing Standards for Narrow Therapeutic Index DrugsOGD applies tighter quality and BE criteria for generic NTI drugs than for generic non-NTI drugs. Generic NTI drugs, like all generic drugs, are FDA-approved as clinically substitutable with their brand-name versions.
Each record above shows how many generic labelers the FDA's NDC Directory lists. Whether to switch between makers of an NTI medicine is a question for the prescriber and pharmacist, who may check blood levels after a change.
Source: FDA CDER Conversation