June 12, 1998
Dear Doctor:
Any drugs metabolized by the cytochrome P450 3A4 or 2D6 isoenzymes may interact with Posicor. Therefore, as a reminder, the co-administration of mibefradil with drugs metabolized by the 3A4 or 2D6 isoenzymes of the cytochrome P450 system may result in increased plasma levels of those drugs, so dose adjustments may be necessary as mibefradil is withdrawn.
The consequences of clinically relevant interactions depend on the side effect profile of the individual drug to be used. Posicor's inhibition of the CYP 450 3A4 and 2D6 isoenzymes may increase the side effects of the drugs metabolized by these enzymes or prevent the formation of active metabolites. It takes an average of 7 days, but can take up to 14 days, for sufficient elimination of the metabolites of Posicor to minimize the inhibition of CYP 450 system. You should consider this pharmacokinetic information along with the patient's medical history and current status when initiating drugs metabolized by the CYP 450 system, including those identified on the attached table.
If you have any questions, please call Roche Laboratories at 1-800-205-4611.
Sincerely,
Russell H. Ellison, MD
Vice President
Medical Affairs
Roche Laboratories Inc.
340 Kingsland Street
Nutley, New Jersey 07110-1199
GENERIC NAME: TRADE NAME
amiodarone: Cordarone
astemizole: Hismanal
bepridil: Vascor
cisapride: Propulsid
cyclosporine: Neoral, Sandimmune
cyclophosphamide: Cytoxan
desipramine: Norpramin
erythromycin: Erythrocin, Ilosone, others
etoposide: VePesid
flecainide: Tambocor
flutamide: Eulexin
halofantrine: Halfan
ifosfamide: Ifex
imipramine: Tofranil
lovastatin: Mevacor
mexiletine: Mexitil
pimozide: Orap
propafenone: Rythmol
quinidine: Cardioquin, Quinaglute, Quinidex, others
simvastatin: Zocor
tacrolimus: Prograf
tamoxifen: Nolvadex
terfenadine: Seldane
thioridazine: Mellaril
vinblastine: Velban
vincristine: Oncovin