Key takeaways:
Narrow therapeutic index (NTI) drugs are medications with a small margin between a safe, effective dose and an ineffective or toxic dose. Common examples include warfarin (Coumadin, Jantiven) and lithium (Lithobid).
Your healthcare team will likely need to monitor you regularly while you’re taking an NTI drug. This is to make sure your medication level stays within a safe range. Be sure to keep your monitoring appointment and follow your prescriber’s instructions carefully.
Changes to your health or your diet can affect NTI drug levels. So be sure to let your healthcare team know if any changes occur. You also shouldn’t stop or start taking other medications without talking to your healthcare team first.
If you’re taking a medication that requires a specific diet or regular blood draws, it may be a narrow therapeutic index (NTI) drug.
But what exactly are narrow therapeutic index drugs? And why do they require special monitoring? Here’s what you need to know to protect your safety and get the most from your medication.
The “therapeutic index” is the difference between a safe, effective dose and a toxic dose. The larger (or wider) the therapeutic index, the safer the medication. Narrow therapeutic index (NTI) drugs have a small therapeutic index.
For NTI drugs, the amount of medication that’s safe and effective is very close to the amounts that are too much or too little. This means even small changes in your drug levels could push you out of the safe and effective window. As a result, the dose of NTI drugs must be carefully calculated, and medication levels are often monitored regularly.
If you’re taking an NTI drug, you’ll likely need therapeutic drug monitoring. This often involves regular blood draws to make sure your medication levels stay within the goal range. Your prescriber may also give you a specific diet or dosage schedule to follow to help ensure your levels remain stable.
The FDA doesn’t have a set list of NTI drugs, but some common examples include:
Warfarin (Coumadin, Jantoven)
Digoxin (Lanoxin)
Tacrolimus (Prograf)
Phenytoin (Dilantin)
Carbamazepine (Tegretol)
Levothyroxine (Synthroid)
Lithium (Lithobid)
Methotrexate (Trexall)
NTI drugs differ from other medications in several ways. Here are some key differences to be aware of:
They require frequent monitoring. Your healthcare team will likely monitor you to make sure your medication levels stay within the goal range. The way your medication is monitored, and how often, depends on what medication you’re taking. It may include directly measuring the amount of medication in your blood, such as with lithium or digoxin. It could also involve monitoring the effect of the drug, such as measuring the international normalized ratio (INR) if you’re taking warfarin.
You may need frequent dosage changes. Your starting dosage of an NTI drug typically depends on your age, body weight, and medical history. From there, your prescriber may adjust your dosage based on the results of your monitoring. In some cases, your dosage may change on a weekly basis. In others, changes may not happen as often.
You may need to follow a specific diet. Some NTI drug levels are impacted by your diet. For example, the amount of Vitamin K you eat can make warfarin more or less effective. Your prescriber may give you a specific meal plan to follow or specific foods to limit or avoid to help keep your medication levels within a safe range.
You shouldn’t switch between brand and generic forms without your prescriber’s OK. For most medications, there’s no difference between the brand-name medication and the approved generics. But with NTI drugs, there may be a small difference in absorption between different forms of the medication. And as mentioned, small changes can have a big impact on your health. So you shouldn’t change the form you’re taking without your prescriber’s OK.
NTI drugs are safe and effective treatment options, as long as you follow the guidance of your healthcare team. Here are some tips to help protect your safety:
Keep your monitoring appointments. As discussed, it’s important to keep an eye on your medication levels while you’re taking an NTI drug. Frequent monitoring appointments can feel overwhelming, but they exist to help keep you safe. Do your best to keep up with your appointments, and reschedule right away if you miss one. Talk to your healthcare team if you’re having trouble with your monitoring schedule. They can work with you to find a solution.
Let your prescriber know if you get sick or become pregnant. Changes to your overall health can impact how your body processes medications. For NTI drugs, these changes can be dangerous and may require a dose adjustment or change in your medication. So you should let your prescriber know right away about any changes to your health, even if they seem minor, such as a common cold.
Talk to your healthcare team before you start any new medications. Drug interactions are possible with all medications. But for NTI drugs, the risks are higher. Keeping a medication list and sharing it with your healthcare team is a good place to start. But you shouldn’t make any changes without checking with them first. This includes taking over-the-counter medications and supplements.
Follow dietary instructions carefully, and let your prescriber know if you slip up. As described above, some NTI medications are affected by the food you eat. Because of this, your prescriber may tell you to follow a specific diet. If you change what you’re eating, or even have a one-time slip, it can affect your medication levels. So it’s best to let your prescriber know if this happens. They can make adjustments if needed to keep you safe. If you’re unable (or unwilling) to follow the diet plan for your medication, let your prescriber know that, too. A different medication may be a safer option for you.
Know the signs of high medication levels. Your healthcare team will tell you about side effects that can happen if your medication levels are too high. Keep an eye out for these symptoms, and let your healthcare team know right away if they occur. If symptoms seem life-threatening, seek emergency care.
Take your medication as directed. NTI drugs can have irregular dosage schedules. And your dosage may change from week to week in some cases. This can make it harder to remember how to take it. Using strategies such as a medication reminder app can help. If you forget a dose of your medication, contact your healthcare team for instructions. Don’t take two doses at once to make up for one you missed.
Curious about Warfarin monitoring? Review this physician’s description of how and why your INR is monitored when you’re taking Warfarin.
Signs you’re taking too much lithium: Here are some symptoms that signal your lithium is too high.
Digoxin drug interactions: Our pharmacists describe common drug interactions when you’re taking digoxin.
Narrow therapeutic index (NTI) drugs are medications with a small difference between a safe level and a harmful one. Common examples include warfarin (Coumadin, Jantoven) and lithium (Lithobid). NTI drugs often require regular monitoring to make sure levels stay within the goal range. Your dosage may even change from week to week. Monitoring appointments may seem inconvenient, but they’re the best way to keep you safe while taking one of these medications.
Other medications, health changes, and even your diet can affect NTI drug levels in your body. So be sure to follow your prescriber's guidance for taking an NTI drug. And be sure to let them know if any changes occur.
Andrews, P., et al. (2023). Diagnosis and practical management of digoxin toxicity: A narrative review and consensus. European Journal of Emergency Medicine.
Jiang, W. (n.d.). FDA drug topics: Understanding generic narrow therapeutic index drugs. U.S. Food and Drug Administration.
MedlinePlus. (2024). Therapeutic drug monitoring.
Muller, P. Y., et al. (2012). The determination and interpretation of the therapeutic index in drug development. Nature Reviews.
Nederlof, M., et al. (2018). Monitoring of patients treated with lithium for bipolar disorder: An international survey. International Journal of Bipolar Disorders.
Straka, R. J., et al. (2017). Potential clinical and economic impact of switching branded medications to generics. American Journal of Therapeutics.
Tamargo, J., et al. (2015). Narrow therapeutic index drugs: A clinical pharmacological consideration to flecainide. European Journal of Clinical Pharmacology.
U.S. Food and Drug Administration. (2017). FY2015 regulatory science research report: Narrow therapeutic index drugs.
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