Major
Ciprofloxacin × Tramadol
Fluoroquinolone antibacterials×Other opioids
Mechanism
Dual risk: both drugs lower the seizure threshold. Ciprofloxacin also blocks CYP1A2 (a minor tramadol activation route) and weakly affects serotonergic activity.
Symptoms
Seizures, especially in patients with prior epilepsy or head injury. Serotonin syndrome may occur with other serotonergics on board (agitation, tremor, hyperthermia).
Management
Avoid the combination in patients with prior epilepsy. Alternative antibiotics: a cephalosporin or nitrofurantoin (no seizure threshold effect). Alternative analgesics: paracetamol, an NSAID, or morphine.