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Warfarin Sensitivity Genotyping



Differential Effect of Drugs

Slide 24

August 2008

In addition there are differential effects of drugs, some drugs will increase the amount of the transcription of CYP2C9 gene, and other drugs may decrease the transcription of the gene and the amount of enzyme that is actually synthesized.

 CYP2C9 inducers will increase the transcription of the gene and this will cause an increase in the concentration of the metabolic enzymes. The inducers are things like barbiturates, rifampin, carbamazephine, phenytoin, primidone and surprisingly St. John’s Wort.  While a doctor may be prescribing most of these as drugs, the patient could be taking St. John’s Wort surreptitiously by getting it at a health food store.

If these inducers are being given to the patient as co-medications they should be monitored frequently and at dosing changes or discontinuation of the medication since the INR will likely change.

CYP2C9 inhibitors on the other hand decrease the enzymatic activity of enzymes involved in the metabolism of warfarin. Some of these are frequently given along with warfarin. For example if there is atrial fibrillation or an atrial flutter the patient may be prescribed Amiodarone so this has to be taken into consideration for the warfarin dose. In addition to Amiodarone, fenofibrate, gemfibrozil, propafenone, androgens, danazol, fluvoxamine, and some statins as well as tamoxifen, zafirlukast are also well documented inhibitors of CYP2C9. The INR should be monitored frequently during initiation of co-medications that are inhibitors of CYP2C9 or during dose changes or discontinuation until the INR is stable.

Differential Effect of Drugs

 


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