Microsoft powerpoint - scottfreeland

UPDATES IN CARDIOLOGY
DECEMBER 4, 2009
Drug-Drug Interactions
Drug Interactions
ƒ Pharmacodynamics (PD):
„ What the drug does to the body ƒ Pharmacokinetics (PK):
„ What the body does to the drug ƒ Primary source for drug interactions
CYP-450 Enzymes
CYP-2E1 CYP-1A2
Deficient in 7% of caucasions
Adapted from Pharmacotherapy 15:848-998, 1995
Clopidogrel and Proton
Pump Inhibitors (PPI’s)
ƒ > 100 million combined prescriptions /yr
„ 2008 ACC/AHA/ACG Clinical Expert Consensus Document„ 2007 ACC/AHA Unstable Angina/NESTMI Guidelines Clopidogrel – “Prodrug”
ƒ Converted to its active form by metabolic enzymes (CYP450- ƒ PPI’s
„ Inhibits the activity of CYP-450 (2C19) enzyme
„ Reduced activity/efficacy of clopidogrel
‡ Platelet Inhibition Reactivity (PRI) – lab assay „ Higher platelet activity compared with „ Higher observed rates of MACE (AMI; Stent Clopidogrel + PPI’s
„ COGENT trial – No difference in clinical events Clopidogrel + PPI’s
‡ Omeprazole ~ esomeprazole >>> pantoprazole > „ PPI: Pantoprazole / Lansoprazole / Rabeprazole Prasugrel (Effiant®) and PPI’s
CYP (3A4 / 2B6) >>>> CYP(2C9) and CYP (2C19)
Conclusions: not affected by concurrent PPI’s Ticagrelor (Investigational) – Not affected DRONEDARONE (Multaq®)
Added methane sulfonyl
group shortened T½ and
Dronedarone
reduce accumulations
Amiodarone
Dronedarone (Multaq®)
„ Dronedarone increases digoxin exposure by 2.5 fold „ Follow similar dosing guidelines as amiodarone when Warfarin
„ Dronedarone increased S-warfarin isomer by 1.2 fold „ No observed excess risk of bleeding when dronedarone „ No dosage adjustment of warfarin required
Simvastatin
„ Dronedarone ↑ simvastatin exposure by 4 fold „ Recommend following same guidelines as amiodarone Not a Class Effect
Lipophilic
Hydrophlic
Higher rate of Drug
Lower rate of Drug Interactions
Interactions
Use if potential drug
interactions due to CYP-450
metabolism
ED drugs and Nitrates
Concurrent Drug
Findings
RECOMMENDAITON
Nitrates + PDE
Combination -
contraindicated
The length of time required
Nitrates
between discontinuation of
nitroglycerin therapy and
safe administration of
Nitroprusside
sildenafil, etc. is not
Alpha Blocker
Recommendations:
(Cardura, Hytrin)
Sildanafil (T½ 4hr) > 24hrs
Tacalafil (T½ 17hr) > 24 hrs
Vardenafil (T½ 4hr) > 24 ?
CYP- 450(3A4)
(INHIBITORS)
ƒErythromycin
ƒAntifungal

Source: http://www.cardiofoundation.org/educational_series/presentations/09_richter_lecture/Scott%20Freeland%20DrugInt.pdf