Life Threatening Drug Interactions

Includes both pharmacokinetic (change in concentration) and pharmacodynamic (change in effect) interactions

Sulfonylureas/Warfarin + Bactrim/Flagyl/Fluconazole/amio/SSRI’s

Sulfonylureas/Warfarin are substrates for CYP2C9 and  these antimicrobials are CYP2C9 inhibitors – increase sulfonylurea or warfarin concentrations and can be life threatening. Consider Amoxicillin which does not affect CYP2C9.

Digoxin/diltiazem/cyclosporin/dabigatran + clarithromycin/verapamil

PGP pump exports dig/dilt/cyclosporin/dabigatran and is inhibited by clarithromycin/verapamil leading to increased concentrations.

Warfarin + acetaminophen

APAP metabolites affects same Vit K reducing enzyme that warfarin targets. Can dramatically elevate INR.

Warfarin + NSAIDS

Gastropathy risk for bleeding

Warfarin + ASA or other anti platelet

Increased bleeding risk

Trimethoprim + ACEIs/ARBS/Diabetics

All increased risk for hyperK+ and death

Strategies

• Careful w/ pts on sulfonylureas, opioids, digoxin, warfarin
• Antibiotics (esp Septra), dilt, verapamil should all trigger double check of meds
• pharmacy practice website