Case 5
Theophylline-enrofloxacin drug interaction
Signalment: Six year old male neutered Collie
Chief Complaint: Allergic rhinitis of 2 months duration. Radiographic evidence of lung-lobe consolidation and clinical signs compatible with pneumonia developed one week prior to presentation.
Pertinent History: Theophylline therapy begun 3 days prior to presentation. Patient began exhibiting signs of hyperactivity and restlessness 24 hours prior to presentation.
Other Drugs: Enrofloxacin 2.5 mg/kg every 12 hours orally (begun at same time as theophylline); prednisolone 1 mg/kg every 48 hours.
Drug of Interest: Theophylline
Concern: Toxicity
Dosing Regimen: 21 mg/kg orally every 12 hours (slow release product)
Duration of Current Regimen: 3 days
Patient Response: Restless, pacing, irritable
Drug Concentration:
47 mg/ml Time: 12 hours
31 mg/ml Time: 24 hours
Drug Elimination Half-Life: 19 hours
Volume of Distribution: NA
Predicted Peak: approx. 65 mg/ml
Predicted Trough: NA
Recommendation: Decrease the dose by half or decrease the dose by 25% and prolong the dosing interval by 12 hours to 24 hours. Retest at new steady-state (in three days) and upon discontinuation of enrofloxacin.
Follow-Up: Following monitoring, the dosing interval was prolonged to 24 hours and dose was decreased by 50% from 20 mg/kg to 10 mg/kg. Recheck revealed a peak and trough concentration of 12.3 mg/ml and 10.3 mg/ml at 2 and 22 hours respectively. Near sub therapeutic concentrations indicated that either the dose must be increased or the interval decreased to 12 hours.
Comments: The fluorinated quinolones can increase concentrations of theophylline when the two drugs are given simultaneously. The mechanism is presumed to be due to impaired drug metabolism by enrofloxacin with subsequent decreased theophylline clearance. This drug interaction is well established for ciprofloxacin in people and has been documented for enrofloxacin as well. The drug elimination half-life of theophylline in this patient while on enrofloxacin was 19 hours, which is twice that expected in dogs.
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