November 10, 2009


What are some common medications classified as weak, moderate and strong inhibitors of CYP3A4?


The cytochrome P450 (CYP) is a well known superfamily of enzymes that are responsible for the oxidative and reductive metabolic transformation of medications used in clinical practice.1-3  In addition, the CYP enzymes are commonly associated with causing many clinically relevant drug-drug interactions.  Of the CYP enzymes, CYP3A4 is not only the most prevalent CYP enzyme in the liver, but is used by more than 50% of medications on the market for their metabolism and elimination from the body.1  In addition, the CYP3A4 activity can be induced (or accelerated) or it can be inhibited (decreased), thereby changing the drug concentrations present in the body and its pharmacokinetic profile.1-4  As it relates to this newsletter issue, the inhibition of CYP3A4 can result in the accumulation of parent drug concentrations that can put the patient at increased risk for side effects and possible toxicity.  

What are common medications known to be inhibitors of CYP3A4 that can decrease the metabolism of known substrates of CYP3A4 thereby increasing the risk for side effects and adverse drug reactions?
While the below table is clearly not an exhaustive list of every medication known to inhibit CYP3A4, these are the most common medications used in clinical practice that are known to interact with other medications that are substrates of CYP3A4.  It is also important to note that not all medications within a particular drug class have the same effect.  For example, within the macrolide antibiotics, all of them are known inhibitors of CYP3A4 with the exception of azithromycin.  For the calcium channel blockers, it is only the non-dihydropyridine calcium channel blockers that are known inhibitors of CYP3A4, but not amlodipine or nifedipine.  Lastly, within the non-nucleoside reverse transcriptase inhibitors (NNRTI) used in the management of HIV, only delavirdine is an inhibitor of CYP3A4 whereas the other NNRTIs in the class are considered to be inducers of CYP3A4.7-9  This is important as it reveals that the pharmacokinetic profiles do not always completely follow a class effect. Therefore, anytime the medications listed in the provided table are initiated in a patient already on stable does of other medications, the chances of a clinically relevant drug interaction is likely and should be taken into consideration upon initiation. The medications known to be CYP3A4 inhibitors are summarized in the below table based on their class of medications and classifications.1,2,5,6

(PW Drug Interact Newsl 2009;1(43):1-4.) ©2009 Pharmacology Weekly, Inc. 

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