February 1998

IMPORTANT SAFETY INFORMATION

Janssen Pharmaceutica would like to inform you of important labeling changes concerning new contraindications, warnings, precautions, adverse events, and additional drug or food interactions with HISMANAL (astemizole). We wish to draw your attention to the following sections of the revised HISMANAL (astemizole) labeling. Bolded words denote newly added information. Please refer to the enclosed revised labeling for complete information.

CONTRAINDICATIONS
This section has been expanded to include:

Use in patients with severe hepatic impairment.

Coadministration of BIAXIN (clarithromycin), TAO (troleandomycin), or POSICOR (mibefradil dihydrochloride).

Astemizole is contraindicated in patients with severe hepatic impairment or who are taking other medications known to impair its metabolism. Qt prolongation has been demonstrated in patients taking astemizole in these settings and cases of serious cardiovascular events, including death, cardiac arrest, and torsades de pointes have been reported in these patient populations.

WARNINGS
This section has been expanded to include: modifications to the list of drugs which prolong the QT interval; background information and/or clinical consequences of use of HISMANAL in certain situations including but not limited to patients with hepatic impairment, patients with underlying cardiac disease, and concomitant administration of contraindicated drugs.

PRECAUTIONS
The list of substances not recommended for coadministration with HISMANAL has been expanded to include:

Serotonin reuptake inhibitors	PROZAC (fluoxetine), LUVOX (fluvoxamine), SERZONE (nefazodone), PAXIL (paroxetine), ZOLOFT (sertaline)
Protease inhibitors	NORVIR (ritonavir), CRIXIVAN (indinavir), INVIRASE (saquinavir), VIRACEPT (nelfinavir)
Others	ZYFLO (zileuton), grapefruit juice, other potent 3A4 inhibitors

The recommended daily dose of HISMANAL should not be exceeded. HISMANAL should not be used on an as-needed (i.e., prn) basis for immediate relief of symptoms. Patients should be advised that astemizole should not be taken with grapefruit juice because of the potential for grapefruit to influence the metabolism of astemizole.

PHARMACOLOGY
The pharmacology section has been expanded to include information from clinical trials in seasonal allergic rhinitis and idiopathic chronic urticaria, additional information about the cytochrome P-450 isozymes responsible for the metabolism of HISMANAL, and information on the effects of HISMANAL on cardiac repolarization.

ADVERSE REACTIONS
The adverse reaaction section of the labeling has ben updated to include more information on cardiovascular adverse events and rare reports of anaphylaxis, including anaphylactic shock in patients receiving astemizole.

Please carefully review the Clinical Pharmacology, Contraindications, Warnings, Precautions, Patient Information, and Adverse Events sections of the enclosed revised prescribing information. Please keep in mind, the use of HISMANAL is contraindicated in patients taking clarithromycin, troleandomycin, mibefradil dihydrochloride, and in patients with severe hepatic impairment. This is in addition to the previously contraindicated drugs ketoconazole, itraconazole, erythromycin and quinine.

We at Janssen want you to be aware of the revised prescribing information to ensure the proper use of HISMANAL in your patients. Worldwide experience indicates that HISMANAL is safe and effective when used in accordance with its labeling. Before prescribing or adding a newly available drug to the regimen of a patient receiving astemizole, 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 astemizole has been reported.

Please refer to the enclosed revised package insert for full prescribing information. For additional medical information, please call the Janssen One to One Customer Action Center at 1-800-JANSSEN (526-7736) between 8 AM and 8 PM Eastern Standard Time, Monday through Friday.

Sincerely,

Mark A. Klausner, M.D.
Vice President, Medical Affairs

The following brand names are registered trademarks of the companies listed below.
Abbott Laboratories	BIAXIN (clarithromycin), NORVIR (ritonvir), ZYLFO (zileuton)
Agouron	VIRACEPT (nelfinavir)
Bristol-Myers Squibb	SERZONE (nefazodone hydrochloride)
Dista	PROZAC (fluoxetine hydrochloride)
Janssen Pharmaceutica, Inc.	HISMANAL (astemizole), NIZORAL (ketoconazole), SPORANOX (itraconazole)
Merck & Co. Inc.	CRIXIVAN (indinavir sulfate)
Pfizer, Inc.	TAO (troleandomycin), ZOLFT (sertaline hydrochloride)
Roche Laboratories	POSICOR (mibefradil dihydrochloride), INVIRASE (saquinavir mesylate)
SmithKline Beecham	PAXIL (paroxetine hydrochloride)
Solvay	LUVOX (fluvozamine maleate)

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