Dear Seldane Prescriber: (Dear Pharmacist:)

Hoechst Marion Roussel, Inc. would like to inform you about an important new contraindication and additional drug and food interactions that have been added to the SELDANE (terfenadine) and SELDANE-D (terfenadine and pseudoephedrine) package inserts. In addition, a new dosage regimen has been added for patients with renal impairment. The following is a summary of changes that have been made in the attached labeling:

Co-administration of the recently approved agent, POSICOR (mibefradil dihydrochloride) with SELDANE/SELDANE-D is contraindicated.

This contraindication is based on a pharmacologic drug interaction study which showed that POSICOR altered the pharmacokinetic and pharmacodynamic parameters of terfenadine in a manner similar to that of other previously identified cytochrome P450 (CYP) 3A4 enzyme inhibitors, such as ketoconazole. Significant elevation of terfenadine plasma levels and QTc prolongation were reported in this study conducted by Roche Laboratories Inc.

In addition, the drug interactions section of the labeling has been updated to include the following: HIV protease inhibitors [e.g., indinavir (Crixivan), ritonavir (Norvir), saquinavir (Invirase), and nelfinavir (Viracept)], serotonin reuptake inhibitors [e.g., fluvoxamine (Luvox), nefazodone (Serzone), and sertaline (Zoloft)], zileuton (Zyflo), cisapride (Propulsid), and sparfloxacin (Zagam). The newly listed interactions are the result of CYP 3A4 inhibition or additive QTc prolongation, and represent previously identified pharmacokinetic and pharmacodynamic mechanisms of interaction with terfenadine. Additionally, patients should be advised that terfenadine should not be taken with grapefruit juice, due to drug/food interaction studies which suggest that the simultaneous administration of grapefruit juice with terfenadine may lead to accumulation of unmetabolized parent terfenadine.

In addition to the above, the package insert has also been updated with pharmacokinetic information to recommend dosage adjustment of Seldane/Seldane-D to one (1) tablet daily for patients with significant renal impairment, particularly in patients with a creatinine clearance below 40 mL/min.

Please carefully review the Contraindications, Warnings, Precautions, and Patient Information sections of the enclosed prescribing information. Please be reminded that the use of Seldane/Seldane-D is contraindicated in patients taking ketoconazole, itraconazole, erythromycin, clarithromycin, troleandomycin, or mibefradil dihydrochloride, or in patients with significant hepatic dysfunction. The recommended daily dose of Seldane/Seldane-D should not be exceeded.

Hoechst Marion Roussel, Inc. is dedicated to providing important new information about our products to health-care providers. The safety and efficacy of Seldane/Seldane-D have been demonstrated when they are used in accordance with the enclosed full prescribing information. However, before prescribing or adding a newly available drug to a patient receiving terfenadine, the package insert of the new drug and/or the medical literature should be consulted to determine if an interaction between the new drug and terfenadine has been reported.

The Medical Community can further our understanding of adverse events by reporting all cases to Hoechst Marion Roussel, Inc. at 1-800-633-1610 or to the FDA MEDWATCH program by phone 1-800-FDA-1088, by fax at 1-800-FDA-1078, or by mail to MEDWATCH, HF-2, FDA, 5600 Fishers Lane, Rockville, Maryland 20857.

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