Propafenone

Pharmacogenomic Information in the Context of the FDA-Approved Drug Label*

Propafenone is used to treat cardiac arrhythmia, but should be used only if the condition is thought to be life-threatening.
Its metabolism is by CYP2D6,CYP3A4 and CYP1A2. The combination of propafenone, CYP3A4 inhibition and CYP2D6 inhibition or CYP2D6 genetic deficiency could be hazardous.

Excerpt from the propafenone drug label:

"Propafenone is metabolized by CYP2D6,CYP3A4,and CYP1A2 isoenzymes. Approximately 6% of Caucasians in the U.S. population are naturally deficient in CYP2D6 activity and to a somewhat lesser extent in other demographic groups. Drugs that inhibit these CYP pathways(such as desipramine,paroxetine,ritonavir,sertraline for CYP2D6; ketoconazole, erythromycin, saquinavir, and grapefruit juice for CYP3A4; and amiodarone and tobacco smoke for CYP1A2) can be expected to cause increased plasma levels of propafenone."

"There are two genetically determined patterns of propafenone metabolism. In over 90% of patients, the drug is rapidly and extensively metabolized with an elimination half-life from 2-10 hours. These patients metabolize propafenone into two active metabolites: 5-hydroxypropafenone which is formed by CYP2D6 and N-depropylpropafenone (norpropafenone) which is formed by both CYP3A4 and CYP1A2. In less than 10% of patients, metabolism of propafenone is slower because the 5-hydroxy metabolite is not formed or is minimally formed."

(For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Propafenone drug label PDF.)