What are the management steps for an elderly patient with impaired renal function who has taken an overdose of levofloxacin (750mg)?

Management of Levofloxacin Overdose in Elderly Patients with Renal Impairment

Immediately discontinue levofloxacin and initiate supportive care with close monitoring for neurotoxicity, as elderly patients with impaired renal function are at substantially increased risk for drug accumulation and severe adverse effects, including seizures and altered mental status. 1, 2

Immediate Assessment and Discontinuation

• Stop levofloxacin immediately upon recognition of overdose, as the drug is substantially excreted by the kidney and accumulation is inevitable in renal impairment 1
• Assess the patient's creatinine clearance, as clearance of levofloxacin is substantially reduced and plasma elimination half-life is substantially prolonged when creatinine clearance is <50 mL/min 1
• Monitor for signs of neurotoxicity including altered mental status, seizures, tremor, confusion, or focal neurological deficits, as these are the primary manifestations of fluoroquinolone toxicity in elderly patients with kidney disease 2, 3

Monitoring for Specific Toxicities

Neurological toxicity is the most critical concern in levofloxacin overdose, particularly in elderly patients with renal impairment. 2

• Watch for seizures, encephalopathy, or transient focal neurological deficits that may mimic stroke, as a case report documented hemiparesis from acute levofloxacin overdose (7g) that resolved within 24 hours 3
• Monitor ECG for QT prolongation, as elderly patients are more susceptible to drug-associated effects on the QT interval, especially when combined with other QT-prolonging medications 1
• Assess for signs of hepatotoxicity, as severe and sometimes fatal hepatotoxicity has been reported postmarketing in patients ≥65 years of age 1
• Evaluate for tendon pain or inflammation, as elderly patients are at increased risk for severe tendon disorders including rupture, though this typically occurs with therapeutic dosing rather than acute overdose 1

Role of Hemodialysis

Consider urgent hemodialysis for symptomatic patients with severe neurotoxicity, despite FDA labeling stating it is not effective for drug removal. 2

• The FDA label states that neither hemodialysis nor continuous ambulatory peritoneal dialysis (CAPD) is effective in removal of levofloxacin from the body 1
• However, two case reports demonstrated successful treatment of levofloxacin-induced neurotoxicity in elderly patients with kidney failure using frequent hemodialysis, resulting in full resolution of symptoms 2
• This represents a critical divergence between official labeling and clinical evidence: while pharmacokinetic data suggest limited dialyzability, clinical outcomes in neurotoxic patients showed benefit from aggressive dialysis 2
• Hemodialysis should be strongly considered for rapid resolution of neurotoxicity in patients with impaired kidney function who develop severe symptoms, as supportive care alone may be insufficient given prolonged drug half-life in renal impairment 2

Supportive Care Measures

• Provide symptomatic treatment for any neurological manifestations, including anticonvulsants if seizures occur 2
• Maintain adequate hydration to support any residual renal function, though this will have limited impact on drug clearance given the degree of renal impairment 1
• Monitor renal function closely, as the risk of toxic reactions is greater in patients with impaired renal function 1
• Avoid administering supplemental doses, as no additional levofloxacin is required following hemodialysis or CAPD 1

Critical Pitfalls to Avoid

• Do not assume standard overdose management applies: the combination of elderly age, renal impairment, and a 750mg dose (which is already the high-dose formulation) creates a particularly high-risk scenario 1, 4
• Do not dismiss neurological symptoms as unrelated to the medication, as fluoroquinolone neurotoxicity can present with stroke-like symptoms that fully resolve 3
• Do not rely solely on the FDA label's statement that hemodialysis is ineffective, as clinical case reports demonstrate benefit in symptomatic patients with neurotoxicity 2
• Recognize that elderly patients with moderate to severe renal impairment may have inadequate drug clearance even with reduced dosing regimens, making overdose particularly dangerous 4

Expected Clinical Course

• The mean terminal plasma elimination half-life in elderly patients is approximately 7.6 hours with normal renal function, but is substantially prolonged with creatinine clearance <50 mL/min 1
• Symptoms may persist for an extended period given the prolonged half-life in renal impairment, potentially requiring days of supportive care if hemodialysis is not performed 1, 2
• Full neurological recovery is expected if the patient survives the acute toxicity, as demonstrated in case reports where symptoms completely resolved 2, 3