Content Update for Chapter 11, "Disorders Related to Cold and Allergy"

FDA Approval of OTC Zyrtec & Zyrtec-D

Zyrtec (cetirizine hydrochloride) and Zyrtec-D (cetirizine hydrochloride/pseudoephedrine hydrochloride) have been approved for nonprescription use in adults and children.^1,2 The Food and Drug Administration (FDA) approvals for the two products were issued 1 week apart. The nonprescription products will be in stores in late January 2008 and will be marketed in their original prescription strengths.²

Zyrtec

Mechanism of Action

Cetirizine, a metabolite of hydroxyzine, is a second-generation antihistamine. This agent selectively inhibits peripheral H₁ receptors.³

Indications and Dosages

The manufacturer will market two distinct Zyrtec products, one for each approved indication, to be taken once daily:^1,2

• For adults and children 2 years of age and older: temporary relief of symptoms attributable to hay fever or other respiratory allergies (sneezing; runny nose; itchy, watery eyes; and itchy throat or nose).
• For adults and children 6 years of age and older: relief of itching due to hives.

Zyrtec products will be available in three oral dosage forms to be taken with or without food: tablets (5 mg and 10 mg), chewable tablets (5 mg and 10 mg), and syrup formulations (1 mg/mL).^2,3

• The tablets and chewable tablets are approved for adults and children 6 years of age and older for treatment of all indications (hayfever, other respiratory allergies, relief of itching due to hives).¹
• The syrup dosage form is approved for:

         —Adults and children 2 years of age and older for treatment of hay fever and other respiratory allergies.¹

         —Adults and children 6 years of age and older to relieve itching due to hives.¹

Dosage Guidelines for Nonprescription Zyrtec (Cetirizine HCl)
Adults and Children 6 Years and Older	Adults 65 Years and Older	Children 2 to under  6 Years	Children Under 2 Years and Patients with Liver or Kidney Disease
Syrup (1 mg/mL)*
1 teaspoonful (5 mL) or 2 teaspoonfuls (10 mL) once daily, depending on severity of symptoms Not to exceed 2 teaspoonfuls (10 mL) in 24 hours	1 teaspoonful (5 mL) once daily Not to exceed 1 teaspoonful (5 mL) in 24 hours	1/2 teaspoonful (2.5 mL) once daily If needed, can increase dose to maximum of 1 teaspoonful (5 mL) once daily, or 1/2 teaspoonful (2.5 mL every 12 hours Not to exceed 1 teaspoonful (5 mL) in 24 hours	Ask a doctor
Tablet and Chewable Tablet (5 mg)
1 to 2 tablets once daily, depending on severity of symptoms Not to exceed 2 tablets in 24 hours	1 tablet once daily Not to exceed 1 tablet in 24 hours	Ask a doctor	Ask a doctor
Tablet (10 mg)
1 tablet once daily Not to exceed 1 tablet in 24 hours 5 mg tablet may be appropriate for less severe symptoms	Ask a doctor	Ask a doctor	Ask a doctor

* Syrup is to be dispensed with only the dosing cup provided with the product.

Source: Zyrtec product insert. Fort Washington, Pa: McNeil Consumer Healthcare.

Safety Considerations

Common side effects of cetirizine hydrochloride are drowsiness, fatigue, and dry mouth. Other possible side effects include headache, sore throat, stomach pain, diarrhea, and vomiting. Although uncommon, occurrence of difficulty in breathing or swallowing requires immediate medical attention.⁴

    Contraindications to cetirizine include patients who are allergic to cetirizine or hydroxyzine (Atarax, Vistaril), and patients who have or ever had kidney or liver disease. Cetirizine should be taken only under medical supervision during pregnancy or breastfeeding.⁴

    Other label warnings include the following:

• Ask a doctor or pharmacist before using product if:

         —You are taking tranquilizers or sedatives.

         —You have liver or kidney disease. Your doctor should determine if you  need a different dose.

•  Drowsiness may occur.
• Avoid alcoholic drinks.
• Alcohol, sedatives, and tranquilizers may increase drowsiness.
• Use caution when driving a motor vehicle or operating machinery.
• Stop use and seek medical help immediately if an allergic reaction to the product occurs.
• If breastfeeding, do not use product.
• If pregnant, ask a health professional before use.
• Keep product out of reach of children.
• Use product  with enclosed dosing cup only.

    Clinically significant interactions were not found for cetirizine and pseudoephedrine, nor for cetirizine and azithromycin, ketoconazole, or erythromycin. A 400-mg dose of theophylline showed a small decrease in the clearance of cetirizine; larger theophylline doses could have a greater effect.³

Zyrtec-D

Nonprescription Zyrtec-D will contain the same active ingredients as the prescription product: cetirizine HCl (5 mg) and pseudoephedrine HCl (120 mg).²

Mechanism of Action

Pseudoephedrine hydrochloride is an adrenergic agonist (sympathomimetic). It constricts blood vessels, such as the sinusoid vessels, and decreases nasal mucosal edema by stimulation of α-adrenergic receptors.^5,6

Indications and Dosages

In addition to the indications listed for Zyrtec, nonprescription Zyrtec-D is approved for relief of nasal congestion in adults and children older than 12 years of age. Zyrtec-D will be marketed as a 12-hour, bilayer extended-release tablet.² The tablet should be taken with a full glass of water, but may be taken with or without food. As with other extended-release tablets, the tablet should be swallowed whole, and never broken or chewed.⁶

Dosage Guidelines for Nonprescription Zyrtec-D
Adults and Children 12 Years and Older	Adults 65 Years and Older	Children under 12 Years	Patients with Liver or Kidney Disease
Extended-Release Tablet : Cetirizine HCl 5 mg/Pseudoephedrine HCl 120 mg
1 tablet every 12 hours Not to exceed 2 tablets in 24 hours	Ask a doctor	Ask a doctor	Ask a doctor

Source: Zyrtec-D product insert. Fort Washington, Pa: McNeil Consumer Healthcare.

Safety Considerations

Pseudoephedrine stimulates the cardiovascular and central nervous systems. Cardiovascular adverse effects include elevated blood pressure, tachycar­dia, palpitation, or arrhythmias. Adverse effects on the central nervous system include restlessness, insomnia, anxiety, tremors, fear, or halluci­nations. Children and older adults are more likely to experience excitatory effects from this agent.⁵

    Pseudoephedrine is contraindicated in the following situations:⁶

• Patients with narrow-angle glaucoma or urinary retention.
• Patients receiving a monoamine oxidase inhibitor unless 14 days has elapsed since the last dose.
• Patients with severe hypertension or severe coronary artery disease.
• Patients with demonstrated hypersensitivity or idiosyncrasy to adrenergic agents or other drugs of similar chemical structures, such as insomnia, dizziness, weakness, tremor, or arrhythmias.

    In addition to the label warnings listed previously for Zyrtec, which contains only the antihistamine, the Zyrtec-D label also bears the warnings:

• Do not use this product if you are now taking a prescription monoamine oxidase inhibitor (MAOI) or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before using this product.
• Ask a doctor before using product if you have:

         —Heart disease, thyroid disease, diabetes, glaucoma, high blood pressure.
         —Trouble urinating due to an enlarged prostate gland.

   

    Table 11-6 of the Handbook of Nonprescription Drugs, 15th Edition, lists drug interactions for pseudoephedrine.^5,p.208

Sales Restrictions

Sales of nonprescription Zyrtec-D are subject to the anti-methamphetamine federal law requirements:⁷

• Limitation of sales to 3.6 g daily and 9 g monthly.
• Dispensing of product in blister packaging only.
• Placement of product behind the pharmacy counter or in a locked cabinet.
• Presentation of photo identification at purchase.
• Recording of purchases in a written or electronic logbook.
• Trained retail staff.

References

1. U.S. Food and Drug Administration. FDA Approves Zyrtec for Nonprescription Use in Adults and Children [news release]. Available at: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01750.html. Last accessed January 3, 2008.

2. FDA Approves the Johnson & Johnson Allergy Treatment ZYRTEC® for Use Without A Prescription [news release]. Available at: http://www.jnj.com/news/jnj_news/20071119_094915.htm. Last accessed January 3, 2008.

3. Drugs.com. Zyrtec. Available at: http://www.drugs.com/pro/zyrtec.html. Last accessed January 3, 2008.

4. Medline. Zyrtec. Available at: http://www.nlm.nih.gov/medlineplus/
druginfo/medmaster/a698026.html. Last accessed January 3, 2008.

5. Scolaro KL. Disorders related to colds and allergy. In: Berardi RR, Kroon, LA, McDermott JH, et al., eds. Handbook of Nonprescription Drugs. 15th ed. Washington, DC: American Pharmacists Association; 2006:201-228.

6. Drugs.com. Zyrtec-D 12 Hour. Available at: http://www.drugs.com/pro/zyrtec-d-12-hour.html. Last accessed January 3, 2008.

7. National Association of Chain Drug Stores Foundation. Federal restrictions for pseudoephedrine sales. The ePractice Memo [online serial]. March 2006:10(3). Available at: http://www.practicememo.com/Archives//html/2006/mar06.html. Last accessed January 3, 2008.