What are Narrow-Therapeutic Index Drugs?
What are narrow-therapeutic index drugs?
Not all drugs act equally. For some drugs, a very small change in dose or blood concentration can lead to drastically different therapeutic outcomes – even the risk of death. For these drugs, very close monitoring is required.
These medicines have a narrow therapeutic index (NTI) – a narrow window in which they act in the way they were prescribed. However, a prescriber may wish to alter the dose. With narrow-therapeutic index medicines, that small change in dose can have a profound impact. There is less predictability with the effects of NTI drugs. That’s why, once these dose changes are made, patients must be monitored to ensure no significant adverse drug reactions take place.
Take warfarin, for example.
Warfarin is an anticoagulant medicine; a drug used to treat/prevent blood clots, such as deep vein thrombosis (DVT). Patients on warfarin are monitored using the INR – international normalized ratio. Ordinarily, a normal INR reading for a patient not on warfarin therapy is between 0.8 and 1.2. In the case of warfarin treatment, the anticoagulation target may be set between 2 and 3. However, a small change in dose may result in over-coagulation (> than 3), which substantially increases the risk of bleeding. Furthermore, the patient’s diet matters too, because vitamin K found within green-leafy vegetables can disrupt where warfarin falls within INR monitoring.
The same type of close monitoring is required with other narrow-therapeutic index drugs. Blood levels of lithium – a drug used to treat bipolar disorder – must also be monitored. Patients taking clozapine, an antipsychotic drug, must be closely monitored for the risk of agranulocytosis, which is a severe form of low white blood cell count (leucopenia). Heparin – another anticoagulant drug – must also be monitored, this time using the activated partial thromboplastin time (APPT). Not all drugs are monitored in the same way.
Adverse drug reactions are more likely to occur with NTI drugs in the following patient groups:
- Patients of advanced age
- Patients with comorbid illnesses
- Patients on polypharmacy
To ensure adequate safety and efficacy of these drugs, the FDA requires more stringent quality and standards, though this is not always possible.
Narrow-Therapeutic Index Drugs
Below, we’ve put together a non-exhaustive list of some of the most commonly encountered narrow-therapeutic index drugs in the pharmacy setting.
For the PTCB exam, candidates are expected to have knowledge of:
- The definition of narrow-therapeutic index drugs
- Why these drugs require close monitoring
- Understanding the reasons why some drugs have a narrow index
- Examples of commonly encountered NTI medicines
With these syllabus requirements in mind, let’s review some of the most widely known NTI medicines – the top 20 NTI medicines and their indications.
Seizures, bipolar disorder, neuropathic pain
Seizures, bipolar disorder
|Thrombosis / blood clots|
|Theophylline||Asthma / COPD|
A variety of cancers
Organ transplant rejection
Rheumatoid arthritis / psoriasis
|Vancomycin||Severe Gram-positive bacterial infections|
|Amphotericin B||Severe fungal infections|
|Amiodarone||Class III antiarrhythmic drug|
Caused by Gram-negative aerobes
Mycobacterium avium complex
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