Can Cephalexin Cause Seizures? Understanding the Risks and Mechanism

October 12, 2025 •

4 min read

While most people tolerate cephalexin without incident, seizures are a rare but possible side effect, particularly in those with pre-existing risk factors. Cephalexin, a first-generation cephalosporin antibiotic, has been implicated in triggering neurological events, prompting caution among both prescribers and patients.

Quick Summary

Cephalexin can cause seizures in rare cases, primarily due to neurotoxicity resulting from the drug's accumulation. The risk is significantly higher in individuals with kidney problems, a history of epilepsy, or excessive dosage. Understanding the mechanism and risk factors is crucial for patient safety.

Key Points

Rare but Possible: Cephalexin-induced seizures are a rare side effect but are a documented risk, particularly in certain patient populations.
GABA Inhibition: The neurotoxic mechanism involves cephalosporins blocking GABA-A receptors in the brain, disrupting the primary inhibitory signals and increasing neuronal excitability.
Kidney Impairment is Key: Patients with kidney disease are at the highest risk because impaired renal clearance leads to toxic accumulation of the drug.
Other Risk Factors: A history of epilepsy, older age, and underlying central nervous system disorders also increase susceptibility to seizures from cephalexin.
Recognize Early Signs: Watch for pre-seizure neurological symptoms such as confusion, myoclonus, or agitation, and seek immediate medical attention if they appear.
Prompt Management: If a seizure occurs, immediate discontinuation of cephalexin is necessary, along with medical evaluation and, if needed, anticonvulsant therapy.

Understanding the Neurotoxic Potential of Cephalexin

Cephalexin, commonly known by the brand name Keflex, is a widely prescribed antibiotic from the cephalosporin class. While effective against various bacterial infections, it carries a very low but documented risk of causing central nervous system (CNS) side effects, including seizures. The neurotoxic effects associated with cephalosporins are a class effect, meaning they can occur with any drug in this family, though the frequency and severity can vary. A seizure is a serious adverse reaction that requires immediate medical attention and often leads to discontinuation of the medication.

How Cephalexin Can Trigger Seizures

The primary mechanism behind cephalosporin-induced seizures involves the inhibition of gamma-aminobutyric acid (GABA) A receptors in the brain. GABA is the main inhibitory neurotransmitter in the CNS, acting to dampen neuronal excitability. By competing with GABA for binding to its receptors, cephalosporins like cephalexin disrupt this crucial inhibitory function. This interference leads to increased excitatory neurotransmission, lowering the brain's seizure threshold and potentially triggering a seizure.

Drug accumulation is a key factor in this process. Cephalexin is eliminated from the body primarily by the kidneys. In healthy individuals with normal renal function, the drug is cleared efficiently, and concentrations in the central nervous system typically remain low. However, in patients with impaired kidney function, the drug can accumulate to toxic levels in the blood and cross the blood-brain barrier more easily, leading to the inhibition of GABA-A receptors and subsequent neurotoxicity.

Risk Factors for Cephalexin-Induced Seizures

Several factors significantly increase an individual's risk of experiencing a seizure while taking cephalexin:

Renal Impairment: This is the most important predisposing factor. Individuals with chronic kidney disease or acute renal failure are at high risk because their kidneys cannot effectively clear the drug, leading to toxic accumulation. Dosage adjustments are crucial in these patients.
History of Seizures or Epilepsy: Patients with a pre-existing seizure disorder have a lower seizure threshold and are more susceptible to the epileptogenic effects of cephalexins.
Elderly Patients: Older individuals often have age-related declines in kidney function and may have other comorbidities that increase their vulnerability to drug-induced neurotoxicity.
Underlying Central Nervous System Disorders: Conditions such as meningitis or head trauma can disrupt the blood-brain barrier, allowing higher concentrations of cephalexin to enter the CNS and increase neurotoxicity risk.
Excessive Dosage: Taking doses higher than recommended can cause toxic levels of the drug to build up in the body, especially in the presence of other risk factors.
Intravenous Administration: While cephalexin is typically oral, other cephalosporins, when administered intravenously, can carry a higher neurotoxicity risk.

Recognizing the Signs of Cephalosporin Neurotoxicity

Patients taking cephalexin should be aware of the signs of neurotoxicity, which can precede a seizure. These symptoms can be subtle and range from mild confusion to more severe neurological dysfunction. Common signs include:

Confusion or altered mental state
Myoclonus (brief, involuntary muscle jerks)
Agitation
Asterixis (flapping tremor)
Hallucinations
Encephalopathy (brain dysfunction)

If any of these symptoms appear while on cephalexin, a medical evaluation is necessary to determine if the drug is the cause. In many cases, these neurological symptoms, including seizures, resolve within days of discontinuing the antibiotic.

Comparing Neurotoxicity Risks of Cephalosporins

The risk of neurotoxicity, including seizures, varies among different cephalosporins. While all share the GABA inhibition mechanism, factors like blood-brain barrier penetration and renal clearance patterns influence their neurotoxic potential. The table below provides a general comparison, but individual patient factors remain the most important consideration. It is important to note that case reports and observed adverse event rates may not perfectly reflect the true incidence in practice.


Feature	Cephalexin (1st Generation)	Cefepime (4th Generation)	Other Cephalosporins (e.g., Ceftriaxone)
Route of Administration	Oral (typically)	Intravenous (typically)	Both oral and intravenous
CNS Penetration	Generally low in healthy individuals.	Higher, particularly with blood-brain barrier disruption.	Varies by drug and generation.
Risk of Neurotoxicity	Rare; reported cases typically involve risk factors like renal failure.	Higher risk documented, often associated with renal impairment and excessive dosing.	Varies; neurotoxicity reported across all generations.
Underlying Mechanism	GABA-A receptor antagonism.	GABA-A receptor antagonism.	GABA-A receptor antagonism.
Associated Symptoms	Seizures, confusion, myoclonus.	Encephalopathy, myoclonus, seizures.	Encephalopathy, seizures, myoclonus.

What to Do If You Experience a Seizure

If you or someone you know experiences a seizure while taking cephalexin, follow these critical steps:

Seek immediate medical help. Call your healthcare provider or emergency services. Seizures are a serious medical event.
Discontinue the medication. If seizures or other CNS side effects occur, your healthcare provider will likely advise you to stop taking cephalexin.
Provide medical history. When speaking with a healthcare professional, be sure to mention your use of cephalexin, your dosage, and any pre-existing conditions, especially kidney problems or a history of epilepsy.
Consider alternative treatments. A doctor can prescribe an alternative antibiotic or make appropriate dosage adjustments to minimize risk. In severe cases, anticonvulsant therapy may be required to manage ongoing seizures.

Conclusion

In conclusion, while seizures caused by cephalexin are rare, the risk is a real and important consideration, especially for vulnerable populations. The neurotoxic effects are linked to drug accumulation in the central nervous system due to the inhibition of GABA-A receptors, a risk amplified by factors like renal impairment, older age, and a history of seizure disorders. For at-risk patients, vigilant monitoring for neurological symptoms and careful dosage adjustment are essential preventive measures. Prompt medical attention and discontinuation of the drug upon recognition of symptoms are the most effective management strategies. Always inform your doctor about your complete medical history before starting any new medication, particularly if you have risk factors for adverse CNS events. For more detailed prescribing information, refer to the FDA label for Keflex.

Frequently Asked Questions

Seizures are a very rare but possible side effect of cephalexin. The risk is not significant for most people but increases substantially in those with certain pre-existing risk factors.

Cephalexin can cause seizures by inhibiting GABA-A receptors in the brain, which are responsible for calming neural activity. This disruption leads to an increase in excitatory signaling, which can trigger a seizure.

Yes, kidney impairment is the most significant risk factor. Since cephalexin is cleared by the kidneys, reduced kidney function causes the drug to accumulate to toxic levels in the body, increasing the risk of neurotoxicity and seizures.

If you have a history of epilepsy or seizures, you should inform your doctor. Cephalexin may trigger seizures in these individuals, and your doctor will need to assess the risk and may prescribe a lower dose or an alternative antibiotic.

Early signs can include confusion, altered mental status, agitation, and involuntary muscle twitches (myoclonus). These symptoms warrant prompt medical evaluation to prevent more severe complications like seizures.

If you or someone else has a seizure, seek immediate medical attention by calling your doctor or emergency services. The medication will likely be discontinued, and management may include anticonvulsant therapy.

No, the risk of neurotoxicity is a class effect, but it varies by specific drug. Some cephalosporins, like cefepime, have a higher association with neurotoxicity than cephalexin, particularly with intravenous use.