Co-prescription of cytochrome P450 2D6/3A4 inhibitor-substrate pairs in clinical practice. A retrospective analysis of data from Norwegian primary pharmacies.
OBJECTIVE
Inhibition of cytochrome P (P450) (CYP) enzymes, in particular CYP3A4 and CYP2D6, is an important drug-interacting mechanism. The objective of our study was to assess how frequently CYP3A4 and CYP2D6 inhibitors are co-prescribed with substrates of the respective enzymes.


METHODS
Included inhibitors were clarithromycin, erythromycin, fluconazole, itraconazole, ketoconazole and nefazodone (CYP3A4 inhibitors) and bupropion, fluoxetine, paroxetine and terbinafine (CYP2D6 inhibitors). The inhibitors were combined with substrates shown to be pharmacokinetically sensitive towards inhibition (190 drug pairs in total). Lists of patients receiving inhibitors and substrates were drawn from prescription databases (approximately 43,500 patients) of three Norwegian primary pharmacies during a 6-month period (July 2002 to January 2003). The lists were matched on name and date of birth to identify patients using drug pairs. Concurrent use was made probable from dates of purchase and drug profiles.


RESULTS
Inhibitors were prescribed to 2,062 patients. Altogether, 369 events of substrate co-prescription were registered. The highest frequencies of co-prescribed substrates were found for paroxetine (101 events per 267 patients, 38%), fluoxetine (36 events per 110 patients, 33%) and clarithromycin (59 events per 242 patients, 24%). The drugs most often detected in combination with inhibitors were codeine (116 events) and metoprolol (38 events) for CYP2D6 and zopiclone (45 events) and simvastatin (26 events) for CYP3A4.


CONCLUSIONS
Several commonly used CYP2D6 and CYP3A4 inhibitors are frequently co-prescribed with substrates in Norwegian clinical practice. Alertness when inhibitors are prescribed would aid physicians and pharmacists to detect many drug combinations with potential interaction risk.
Molden
Espen
E
School of Pharmacy, University of Oslo, PO Box 1068, Blindern, 0316, Oslo, Norway. emolden@farmasi.uio.no
Garcia
Beate Hennie
BH
Braathen
Pia
P
Eggen
Anne Elise
AE
D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D003157:Community Pharmacy Services / Q000706:statistics & numerical data*; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D051544:Cytochrome P-450 CYP3A; D004347:Drug Interactions; D011307:Drug Prescriptions; D006801:Humans; D009664:Norway; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D010599:Pharmacokinetics; D010818:Practice Patterns, Physicians'; D012189:Retrospective Studies
D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004364:Pharmaceutical Preparations; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating