Survival Guide: Common Drug Interactions in Small Animal Medicine

Drug–drug interactions may be pharmacodynamic (ie, one drug affects another at the site of biological activity with no change in systemic drug concentrations) or pharmacokinetic (ie, one drug affects the absorption, distribution, biotransformation, or excretion of another, leading to changes in systemic drug concentration). In veterinary medicine, the top potential offenders include:

• Sucralfate: Decreases bioavailability of ciprofloxacin, doxycycline, and minocycline in dogs; give antibiotic 2 hours before (not after) sucralfate to minimize or avoid this.

• Ketoconazole: Can decrease bioavailability and/or clearance of many drugs; ketoconazole and itraconazole should not be given with omeprazole, H2 blockers, or other antacids.

• Cyclosporine: Potential to interact with many drugs; concurrent use of St. John’s Wort in dogs should be avoided.

• Phenobarbital: Speeds metabolism of many drugs; increases levetiracetam clearance in dogs. Phenobarbital clearance is inhibited by chloramphenicol.

• Fluoroquinolones: Oral absorption of some impaired by drugs containing divalent or trivalent cations (eg, aluminum, zinc, iron). In dogs, enrofloxacin leads to higher plasma theophylline concentrations.

• Metoclopramide: Theoretically can enhance extrapyramidal effects when used in combination with phenothiazines or SSRIs.

• Furosemide: Can decrease renal clearance of some drugs (eg, digoxin); enhances nephrotoxicity of amikacin and gentamicin; increases renal loss of bromide; secondary hypokalemia from furosemide can blunt lidocaine antiarrhythmic effects.

• Cimetidine: A weaker inhibitor of P450 enzymes in dogs than in humans; still, effects on renal transporters have not been well studied.

• Omeprazole: Has not been shown to significantly decrease antiplatelet effects of clopidogrel in dogs (unlike in humans); concurrent use of mycophenolate mofetil in dogs and cats should be avoided.

• Clomipramine: Can have serious pharmacologic interactions with MAO inhibitors (eg, selegiline, amitraz). Likely should not be combined with azole antifungals without careful monitoring; may interact with drugs such as dextromethorphan.