Here are questions from our live presentation today:
Q: Does azithromycin have the same interactions as erythomycin? Our computer system lumps azithromycin into the same class and thus flags warnings for everything that interacts with erythomycin for azithromycin?
Q: Do you have any insight into interaction between QT interval prolongators? It seems that computer systems flag most drugs as at least potential QT interval prolongators.
Q: So what do you recommend with regards to patients using Plavix and PPIs?
Q: Does azithromycin have the same interactions as erythomycin? Our computer system lumps azithromycin into the same class and thus flags warnings for everything that interacts with erythomycin for azithromycin?
No, azithromycin does not share the CYP3A4 inhibition that is evident with erythromycin and clarithromycin. Azithromycin may demonstrate some weak P-glycoprotein inhibition, but to a much smaller degree than erythromycin. The lumping of all members of a drug class into one for the purpose of identifying drug interactions is often an oversimplification. Separating out the specific members of a class based on their DI potential is one of the things we do when we customize computerized drug interaction screening systems.
Q: Do you have any insight into interaction between QT interval prolongators? It seems that computer systems flag most drugs as at least potential QT interval prolongators.
Briefly, we have divided potential QT prolongation interactions into several subsets based on the suspected risk to patients. One has to be aware of both pharmacokinetic and pharmacodynamic interactions with QT prorogating drugs. Some drugs – antiarrhythmics, pimozide, levomethadyl, etc – produce clinically significant QT prolongation at therapeutic concentrations. Combining two of these drugs or one of them with an inhibitor of its elimination is probably best avoided. There are many drugs that can increase QT at supra-therapeutic concentrations. Using these with a drug that increases QT at therapeutic concentration and has a pharmacokinetic interaction should also be avoided. All other combinations represent a lower, but not zero, risk. For these, simple monitoring of the QT will identify patients who have excess QT intervals in whom dose adjustments or drug changes should be made. You can find a brief summary of QT interactions in the Aug 2009 Pharmacy Times or at www.hanstenandhorn.com, under the Current topics button.
Q: So what do you recommend with regards to patients using Plavix and PPIs?
The answer is not yet clear due to the limitations of the published studies. Until more information is known, I would suggest the following:
1) Evaluate the patient's need to be on a PPI. Avoidance of any drug interaction is the best response.
2) If CYP2C19 inhibition is the mechanism for the reported interaction, the concomitant use of omeprazole and clopidogrel should be avoided.
3) There is inadequate data to evaluate omeprazole / clopidogrel dose separation as a possible method to avoid an interaction based on competitive inhibition. Based on the short half-lives of the drugs, usual (20 mg omeprazole) dosing separated by 12-14 hours should minimize competitive inhibition between the compounds.
4) Avoid other drugs that may interfere with the conversion of clopidogrel to its active metabolite including: cimetidine, fluconazole, ketoconazole, voriconazole, fluoxetine, and fluvoxamine.
5) Several studies have demonstrated a large increase in the risk of GI bleeds in patients who are prescribed clopidogrel plus aspirin and not administered a PPI or other gastric acid suppressant. Stopping the PPI will increase the risk of GI bleeding, particularly in patients with a history of ulcer, GERD, NSAID-induced bleeding, or gastritis.
6) Platelet aggreation studies could be done to determine if adequate clopidogrel effect is present.
