Released by FDA:  4/22/04.  Posted by FDA:  4/29/04

Robert B. Clark
Vice President, US Regulatory
Pfizer Inc.
Regulatory Affairs
235 East 42nd Street
New York, New York 10017

RE:   NDA #21-150
          Zyrtec-D 12 Hour® (cetirizine HC15 mg/pseudoephedrine HCl 120 mg) Extended Release Tablets
          MACMIS ID #11949

Dear Mr. Clark:

The Division of Drug Marketing, Advertising, and Communications (DDMAC) has reviewed a professional sales aid (Admis #150264) for Zyrtec-D 12 Hour® (cetirizine HC15 mg/pseudoephedrine HCl 120 mg) Extended Release Tablets (Zyrtec-D) submitted by Pfizer Inc. (Pfizer) under cover of Form FDA 2253.  Additionally, DDMAC has reviewed promotional statements for this drug that appear on a website (www.Zyrtec.com) maintained by or on behalf of Pfizer.  These materials omit information concerning the risks of Zyrtec-D and, therefore, misbrand the drug within the meaning of the Federal Food, Drug, and Cosmetic Act (the Act) and FDA implementing regulations. See 21 U.S.C. 201(n), 352(a) and (n); 21 C.F.R. 202.1(e)(5).  The omission of this risk information is a public health concern because Zyrtec-D is contraindicated for several patient populations, and the ingestion of pseudoephedrine may cause serious adverse health consequences.

Background

According to the Indications and Usage section of the FDA-approved professional labeling (PI):

ZYRTEC-D 12 HOUR Extended Release Tablets should be administered when both the antihistaminic properties of cetirizine hydrochloride and the nasal decongestant properties of pseudoephedrine hydrochloride are desired.

ZYRTEC-D 12 HOUR Extended Release Tablets are indicated for the relief of nasal and non-nasal symptoms associated with seasonal or perennial allergic rhinitis in adults and children 12 years of age and older.

The Contraindications section of the PI states (in pertinent part):

Due to its pseudoephedrine component, ZYRTEC-D 12 HOUR Extended Release Tablets are contraindicated in patients with narrow-angle glaucoma or urinary retention, and in patients receiving monoamine oxidase (MAO) inhibitor therapy or within fourteen (14) days of stopping such treatment (see PRECAUTIONS, Drug Interactions section). It is also contraindicated in patients with severe hypertension, or severe coronary artery disease, and in those who have shown hypersensitivity or idiosyncrasy to its components, to adrenergic agents, or to other drugs of similar chemical structures. Manifestations of patient idiosyncrasy to adrenergic agents include insomnia, dizziness, weakness, tremor, or arrhythmias.

According to the Warnings section of the PI:

Sympathomimetic amines should be used judiciously and sparingly in patients with hypertension, diabetes mellitus, ischemic heart disease, increased intraocular pressure, hyperthyroidism, renal impairment, or prostatic hypertrophy (see CONTRAINDICATIONS).  Sympathomimetic amines may produce central nervous system stimulation with convulsions or cardiovascular collapse with accompanying hypotension.  The elderly are more likely to have adverse reactions to sympathomimetic amines.

Omission of Risk Information

The sales aid and website fail to reveal facts that are material in light of the representations they make regarding the consequences that may result from using Zyrtec-D as they suggest.  Specifically, these materials fail to disclose the contraindications and warnings described above.

Conclusions and Requested Actions

DDMAC requests that Pfizer immediately cease the dissemination of promotional materials for ZyrtecD the same as or similar to those described above.  Please submit a written response to this letter on or before May 6, 2004, describing your intent to comply with this request, listing all promotional materials for Zyrtec-D the same as or similar to those described above, and explaining your plan for discontinuing use of such materials.  Please direct your response to me at the Food and Drug Administration, Division of Drug Marketing, Advertising, and Communications, HFD-42, Rm. 8B-45, 5600 Fishers Lane, Rockville, Maryland 20857, facsimile at 301-594-6759. In all future correspondence regarding this matter, please refer to MACMIS ID # 11949 in addition to the NDA number.  We remind you that only written communications are considered official.

The violations discussed in this letter do not necessarily constitute an exhaustive list. It is your responsibility to ensure that your promotional materials for Zyrtec-D comply with each applicable requirement of the Act and FDA implementing regulations.

Failure to correct the violations discussed above may result in FDA regulatory action, including seizure or injunction, without further notice.

Sincerely,

Christine Hemler Smith, Pharm.D.
Consumer Promotion Analyst
Regulatory Review Officer
Division of Drug Marketing,
   Advertising, and Communications