Zyrtec D (Cetirizine; Pseudoephedrine)
Cetirizine; Pseudoephedrine
Zyrtec® D | Zyrtec-D 12 Hour®
Classification:
Antihistamines
Autonomic Agents
Respiratory Agents
NOTE: This monograph discusses the use of cetirizine and pseudoephedrine combination products for the relief of nasal congestion and allergic rhinitis. Clinicians may wish to consult the individual drug monographs for more specific information.
Description: Cetirizine and extended-release pseudoephedrine are used together in an oral preparation for the relief of nasal and non-nasal symptoms associated with seasonal or perennial allergic rhinitis. Specifically, the combination may relieve nasal congestion, rhinorrhea, sneezing, itching of the nose or throat, and itchy, watery eyes. Cetirizine is the active metabolite of hydroxyzine, a piperazine H1-receptor antagonist, but has negligible anticholinergic activity. Cetirizine has not been shown to prolong the QTc interval. Pseudoephedrine is a sympathomimetic agent that stimulates alpha1-adrenergic receptors in vascular smooth muscle. This causes vasoconstriction, resulting in shrinkage of nasal mucous membranes, reduction of tissue hyperemia and edema, and an increase in nasal airway patency. The Zyrtec-D® combination product was approved by the FDA in August 2001.
Mechanism of Action: Cetirizine and pseudoephedrine are used together to provide antihistaminic and decongestant properties to relieve the symptoms associated with seasonal and perennial allergic rhinitis.
- Cetirizine: Cetirizine has high affinity for histamine H1-receptors. It has less affinity, however, than terfenadine or hydroxyzine for calcium-channel, alpha-adrenergic, D2-dopamine, 5HT2-serotonin, and muscarinic receptors. In both atopic and normal human volunteers, cetirizine reduction of histamine wheal and flare is similar to that of clemastine, hydroxyzine, and terfenadine. The addition of the less lipophilic carboxyl group to the ethylamine side chain reduces the penetration of cetirizine into the CNS. Consequently, cetirizine produces a lower incidence of sedation compared with older antihistamines. Drowsiness may, nevertheless, be dose-related.
In mildly asthmatic patients, cetirizine 5 to 20 mg blocked bronchoconstriction due to nebulized histamine, with total blockade after the 20 mg dose. Pulmonary function has not been altered in asthmatic patients by cetirizine. There are no studies evaluating cetirizine; pseudoephedrine in asthmatic patients.
- Pseudoephedrine: Pseudoephedrine is an agonist at both alpha- and, to a lesser degree, beta-adrenergic receptors. Like ephedrine, pseudoephedrine also has an indirect effect by releasing norepinephrine from its storage sites. By stimulating alpha-adrenergic receptors in the mucosa of the respiratory tract, pseudoephedrine shrinks swollen nasal mucous membranes, reduces tissue hyperemia, edema, and nasal congestion, and increases nasal airway patency. Also, drainage of sinus secretions is increased, and obstructed eustachian ostia may be opened. In some patients, especially those with preexisting cardiac disease receiving higher doses, pseudoephedrine may increase blood pressure or irritability of the heart muscle and may affect ventricular conduction.
Pharmacokinetics: Cetirizine; pseudoephedrine is given orally.
- Cetirizine: When cetirizine is given in conjunction with pseudoephedrine, the bioavailability is similar to that when cetirizine is given alone; coadministration of cetirizine with pseudoephedrine does not affect the bioavailability of either component. Cetirizine has a rapid onset of 1 - 2 hours and a long duration of action. The overall bioavailability of cetirizine is not altered by the presence of food, although the rate of absorption can be slightly reduced. Penetration into the CNS is poor; CSF concentrations are less than 10% of peak serum concentrations. Cetirizine is distributed into human milk. Protein binding of cetirizine is reported to be 93%. Cetirizine is metabolized to a limited extent via O-dealkylation to a metabolite with negligible activity; the enzyme(s) responsible for metabolism have not been determined. The mean elimination half-life of cetirizine from the combination product is 7.9 hours. Overall recovery of an administered dose is roughly 70% in the urine, of which 50% is unchanged drug. First pass metabolism is low. Overall recovery from the feces is roughly 10%.
- Pseudoephedrine: When pseudoephedrine is given in conjunction with cetirizine, the bioavailability is similar to that when pseudoephedrine is given alone. Pseudoephedrine is rapidly absorbed from the combination tablet; therapeutic blood concentrations of pseudoephedrine are reported to be between 0.21 and 0.77 mg/L. Plasma protein binding has not been demonstrated. Pseudoephedrine is presumed to cross the placenta, blood brain barrier, and is distributed into breast milk. Pseudoephedrine is incompletely metabolized in the liver to norpseudoephedrine, the primary active metabolite of the parent. Elimination is primarily renal, with 55 - 75% of a dose being eliminated unchanged. The mean elimination half-life of pseudoephedrine from the cetirizine; pseudoephedrine combination product is 6 hours; however, pseudoephedrine elimination is pH-dependent.
Zyrtec-D 12 Hour Extended Release(Tab ER 5;120 mg) 
Special Populations: Cetirizine clearance may be affected by renal impairment and by hepatic disease. Pharmacokinetic studies have shown the clearance of cetirizine to be similar in subjects with normal renal function and those with mild renal impairment (i.e., CrCl 42 - 77 ml/min). According to the manufacturer, patients with moderate renal impairment (i.e., CrCl 11 - 31 ml/min) and patients on hemodialysis had a 3-fold increase in half-life and a 70% decrease in clearance compared to normal subjects. Less than 10% of a cetirizine dose is removed by hemodialysis. In elderly subjects with a mean age of 77 years, cetirizine half-life was prolonged by 50% and clearance was reduced by 40% after a single 10 mg dose. Although CrCl was not reported in these subjects, the reduction in clearance may be related to reduced renal function. Patients with chronic liver disease (hepatocellular, cholestatic and biliary cirrhosis) had a 50% increase in cetirizine half-life along with a 40% decrease in clearance compared to normal subjects.
Renal impairment reduces pseudoephedrine clearance. Roughly 65% of a pseudoephedrine dose is excreted unchanged in the urine. The effect of hemodialysis on the removal of extended-release pseudoephedrine is unknown; however, 38% of immediate-release pseudoephedrine is removed by hemodialysis. The effect of liver disease on pseudoephedrine pharmacokinetics is unknown.
References
. Campoli-Richards SM, Buckley MT, Fitton A. Cetirizine. A review of its pharmacological properties and clinical potential in allergic rhinitis, pollen-induced asthma, and chronic urticaria. Drugs 1990;40:762 - 81.
. Gengo FM, Gabos C. Antihistamines, drowsiness, and psychomotor impairment: central nervous system effect of cetirizine. Ann Allergy 1987;59:53 - 7.
[ Revised 8/22/2005 4:45:00 PM ]
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