Neurontin Toxicity: A Hidden Risk Many Patients (and Providers) Overlook

As an ER physician, I see a wide range of medication-related issues, but every so often a case comes through the

doors that perfectly illustrates how easily a “routine” combination of medications can turn into something dangerous.

Recently, I treated a patient whose symptoms were caused by an interaction many people, including healthcare

professionals, often underestimate: Gabapentin (Neurontin) toxicity triggered by acute kidney injury (AKI) from Bactrim.

This case is important to talk about because Gabapentin is prescribed frequently, for neuropathy, chronic pain, sleep,

restless legs, mood disorders, and more. And yet most patients (and even many clinicians) don’t fully appreciate how dependent it is on healthy kidney function. When renal function drops suddenly, Gabapentin levels can climb fast,

leading to alarming neurological symptoms.Let’s walk through what happened, what caused it, and what patients and providers need to know.

The Case: Shaking, Weakness, and a Sudden Decline

My patient was an older woman who came to the ER with two days of progressive shaking, tremors, and weakness in

both her arms and legs. She had difficulty walking, felt unsteady, and said she “just didn’t feel right.” These symptoms

had developed rapidly and were getting worse.

Her medication list included:

• Bactrim (trimethoprim-sulfamethoxazole) for a recent urinary tract infection

• Neurontin (Gabapentin) prescribed for neuropathy

When we examined her, the neurological findings didn’t match a stroke or acute intracranial process. But she clearly

had impaired coordination and significant tremors in all four extremities. That raised a red flag: this was systemic, not

localized.

The Hidden Trigger: Bactrim-Induced Acute Kidney Injury

Her labs told the story.

She had developed acute kidney injury, and the likely culprit was Bactrim. This antibiotic is widely used and generally

safe, but in older adults — especially those who may be dehydrated, on diuretics, or taking other nephrotoxic

medications — it can impair kidney function surprisingly quickly.

Her creatinine had spiked. When your kidneys aren’t filtering properly, medications that depend on renal clearance

begin to accumulate. And Gabapentin is near the top of that list.

Why Neurontin Levels Rise So Quickly

Gabapentin is 100% excreted by the kidneys.Unlike many other medications, it is not metabolized by the liver. It

simply passes through the kidneys unchanged.

So when kidney function suddenly decreases, the drug can accumulate to toxic levels within a short period of time —

even when the patient is taking their prescribed dose correctly.

High Gabapentin levels can cause:

• Tremors

• Ataxia (loss of coordination)

• Confusion

• Lethargy

• Dizziness

• Slurred speech

• Myoclonus

• Gait instability

My patient had classic symptoms of gabapentin neurotoxicity, caused indirectly by Bactrim setting off a chain reaction.

How We Treated It

Fortunately, once we identified the cause, treatment was straightforward:

1. Stopped the offending medications

   • Bactrim was discontinued

   • Gabapentin was held to allow levels to fall

2. IV hydration to support kidney recovery

3. Monitoring for improvement

   
   

   Over the next 24 hours, tremors improved dramatically as her renal function stabilized and the excess Neurontin

   cleared. She made a full recovery.

The Bigger Lesson: Medication Interactions Are Not Always Obvious

What makes this case so important is that:

• The patient took the medications exactly as prescribed

• Neither drug alone would have caused this reaction

• It wasn’t an overdose — it was physiology

When kidney function changes, drug levels can become dangerous without the patient doing anything wrong.

This is especially true in:

• Older adults

• Patients with chronic kidney disease

• Anyone taking multiple medications

• Anyone who becomes dehydrated or acutely ill

And this isn’t just about Gabapentin. Bactrim can worsen renal function and interact with medications that rely on

kidney clearance.

What Patients Should Know

If you take Gabapentin (Neurontin), keep these points in mind:

• Monitor your kidney function if you’re starting a new medication like Bactrim.

• Stay hydrated, especially during illness.

• Report new neurological symptoms immediately, including shaking, tremors, instability, or confusion.

• Never assume symptoms are “just aging” — toxicity can be subtle at first.

• Ask your doctor or pharmacist if any new medication affects kidney function.

Gabapentin is safe when used properly, but like any medication, it has risks when the body can’t clear it.

What Healthcare Providers Should Remember

For clinicians, especially those prescribing Bactrim to older adults:

• Always consider renal function before starting or continuing Gabapentin.

• Recheck kidney function in vulnerable patients, especially during acute illness.

• Educate patients to report neurological symptoms early.

• Recognize that Bactrim — often thought of as benign — can absolutely trigger AKI.

• Don’t overlook the possibility of medication toxicity in patients presenting with non-specific neurological symptoms.

Final Thoughts

This case was a powerful reminder that even common medications can interact in unexpected ways. A simple UTI

treatment led to a cascade that caused a frightening neurological decline — all because kidney function dropped and Gabapentin accumulated.

The good news is that with awareness, early recognition, and proper management, Neurontin toxicity is completely

reversible. For patients and clinicians alike, understanding how these interactions happen is the key to preventing them.

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