Risk of peripheral neuropathy with fluoroquinolones

Last year, the FDA issued a drug safety communication, warning about the risk of nerve damage from fluoroquinolone antibiotics.  You can read last year's post about the warning and other information on fluoroquinolones here: Serious peripheral neuropathy and fluoroquinolones.  


This issue was recently analyzed in a pharmacoepidemiologic study that matched cases each with four control subjects and calculated rate ratios for current fluoroquinolone users.  After identifying more than 6,000 cases and 24,000 controls, the authors found that fluoroquinolone users did indeed have a higher risk in developing peripheral neuropathy (RR = 1.83, 95% confidence interval [CI] 1.49-2.27).  There was no difference in the risk of peripheral neuropathy among ciprofloxacin, levofloxacin, or moxifloxacin users.

Results were adjusted to take into account postherpetic neuralgia, nitrofurantoin and metronidazole use (other medications also known to cause peripheral neuropathy), hypothyroidism, chronic renal failure, and chronic liver failure.  Patients with diabetes were excluded.1

Mechanism of neuropathy

Though fluoroquinolones' antibacterial activity is through inhibition of DNA gyrase and topoisomerase IV, the mechanism of neuropathic side effects is frequently discussed.  The mechanism is noncompetitive inhibition of GABA at the GABA-A receptor.  This causes the neuron to generate an impulse at a lower activation threshold.  Different fluoroquinolones were shown to inhibit the GABA-A receptor to varying extents with ciprofloxacin being one of the more potent agents.2 Other neuropathic adverse effects include seizures, psychosis, dizziness, insomnia, and tremor. 

Take home point:

• This study, showing a nearly two-fold increased risk of peripheral neuropathy, strengthens concerns regarding fluoroquinolones and the risk of neuropathic adverse effects, emphasizing the need for judicious prescribing practices.

References:
1.  Etminan M, Brophy JM, Samii A.  Oral fluoroquinolone use and risk of peripheral neuropathy.  Neurology  2014;83:1261-3.
2.  Yakushiji T, Shirasaki T, Akaike N.  Non-competitive inhibition of GABA-A responses by a new class of quinolones and non-steroidal anti-inflammatories in dissociated frog sensory neurones.  Br J Pharmacol  1992;105:13-8.

photo by david_shane