Do Levofloxacin (Levaquin) or Sulfamethoxazole/Trimethoprim (Bactrim) lower the seizure threshold?

From the Guidelines

Both Levofloxacin (Levaquin) and Sulfamethoxazole/Trimethoprim (Bactrim) can potentially lower the seizure threshold, but the evidence does not strongly support this association for Levofloxacin. According to the guideline for antibacterial prophylaxis administration in pediatric cancer and hematopoietic stem cell transplantation 1, Levofloxacin is the preferred agent if antibacterial prophylaxis is planned, with no mention of its potential to lower seizure threshold. Some key points to consider when prescribing these medications include:

• The risk of lowering seizure threshold is more commonly associated with other medications, and the evidence for Levofloxacin and Bactrim is not as strong.
• Patients with a history of seizures or those taking other medications that lower seizure threshold should use these medications with caution.
• The guideline recommends informing patients and families about potential short- and long-term fluoroquinolone-related adverse effects prior to administration 1.
• If these medications must be used, close monitoring is essential, especially during the first few days of treatment.
• Patients should be advised to report any unusual neurological symptoms immediately. It is essential to weigh the benefits and risks of using these medications, considering the individual patient's medical history and current medications. Levofloxacin is still the preferred agent for antibacterial prophylaxis due to its broad-spectrum activity and recent large pediatric trial showing benefits 1.

From the FDA Drug Label

As with other fluoroquinolones, levofloxacin should be used with caution in patients with a known or suspected central nervous system (CNS) disorder that may predispose them to seizures or lower the seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose them to seizures or lower the seizure threshold (e.g., certain drug therapy, renal dysfunction) Seizures have been reported in people who take fluoroquinolone antibiotics including levofloxacin tablets The concomitant administration of a non-steroidal anti-inflammatory drug with a fluoroquinolone, including levofloxacin, may increase the risk of CNS stimulation and convulsive seizures

Levofloxacin (Levaquin) may lower the seizure threshold in certain patients, particularly those with a history of seizures or CNS disorders.

• Key factors that may increase the risk of seizures include: + CNS disorders (e.g., severe cerebral arteriosclerosis, epilepsy) + Certain drug therapy + Renal dysfunction + Concomitant use of non-steroidal anti-inflammatory drugs There is no information in the provided drug labels about Sulfamethoxazole/Trimethoprim (Bactrim) lowering the seizure threshold. 2, 3, 4

From the Research

Seizure Threshold and Antibiotics

• Levofloxacin (Levaquin) has been associated with seizures in some cases, particularly in patients with electrolyte imbalances or those taking concomitant medications that lower the seizure threshold 5.
• Fluoroquinolones, including levofloxacin, may have a proconvulsive effect, although the risk is considered low 6, 7.
• Sulfamethoxazole/Trimethoprim (Bactrim) is not specifically mentioned as a medication that lowers the seizure threshold in the provided studies.
• Antibiotics such as penicillins, cephalosporins, and carbapenems may trigger epileptic seizures or status epilepticus by decreasing inhibitory transmission in the brain, thus lowering the seizure threshold 6.
• Risk factors for antibiotic-induced seizures include a history of epilepsy or seizures, electrolyte imbalances, dose unadjusted for renal insufficiency, and concomitant treatment with agents that lower the seizure threshold 5, 6, 8.

Comparative Risk of Seizures

• A retrospective study found that the incidence of seizures associated with fluoroquinolones, including levofloxacin, was low and did not significantly exceed that of macrolides 7.
• The study estimated an odds ratio of 1.44 for seizures among patients treated with fluoroquinolones compared to those treated with macrolides, although this result was not statistically significant 7.
• Other medications, such as antipsychotics, may also lower the seizure threshold, although the risk varies depending on the specific medication and individual patient factors 9.