Continuing Education Activity

Cetirizine is a medication used in the treatment of allergic rhinitis and urticaria. It is a second-generation antihistamine. This activity reviews the indications, action, and contraindications for cetirizine as a valuable agent in treating rhinitis and urticaria. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for members of the interprofessional team in the treatment of patients using cetirizine.

Objectives:

• Summarize the mechanism of action of cetirizine.
• Outline the adverse effects of cetirizine.
• Review the monitoring of cetirizine.
• Explain how healthcare professionals should educate patients on the POTENTIAL adverse effects of cetirizine, such as drowsiness and fatigue.

Indications

Cetirizine is an FDA-approved medication for the relief and treatment of allergic rhinitis and chronic urticaria.[1][2] Cetirizine is a second-generation antihistamine that effectively relieves sneezing, rhinorrhea, and watery eyes associated with both seasonal allergies and allergic rhinitis due to allergens such as dust mites and molds. Cetirizine also effectively reduces the severity of hives and significantly reduces pruritus in patients with idiopathic urticaria. Derived from the first-generation antihistamine hydroxyzine, cetirizine does not cross the blood-brain barrier to the extent of its first-generation counterparts; as a result, cetirizine is an effective treatment of allergic rhinitis that simultaneously minimizes the possibility of adverse sedative effects. Cetirizine is available as an over-the-counter medication. Though cetirizine is safe to use for the treatment of perennial allergic rhinitis and urticaria in adults and children over the age of 6 months, it is indicated for the treatment of seasonal allergies in adults and children two years and older. Cetirizine is also safe to use in the geriatric population.

Mechanism of Action

Cetirizine is a fast-acting, highly selective antagonist of the peripheral histamine H1-receptor. The H1-receptors inhibited by cetirizine are primarily on respiratory smooth muscle cells, vascular endothelial cells, immune cells, and in the gastrointestinal tract. Unlike first-generation antihistamines such as diphenhydramine and doxylamine, cetirizine does not cross the blood-brain barrier to a large extent, avoiding the neurons of the central nervous system. As a result, cetirizine produces minimal sedation compared to many of the first-generation antihistamines.[3]

Given its antagonism of histamine H1-receptors, cetirizine effectively reverses many of the effects of histamine. Like other second-generation antihistamines, cetirizine decreases vascular permeability, decreasing the amount of fluid escaping to tissues from capillaries.  Cetirizine is also an inhibitor of histamine-induced bronchospasm.[4]

Cetirizine has been found to exert significant anti-inflammatory activity, reducing the infiltration of inflammatory cells in the setting of allergic rhinitis.[5] Specifically, research has found that cetirizine reduces the migration of neutrophils and eosinophils.[6] 

Cetirizine is absorbed rapidly in the gastrointestinal tract and undergoes substantial excretion by the kidney. Cetirizine reaches peak plasma concentration after approximately one hour. Its effects typically begin after 20 to 60 minutes and persist for at least 24 hours. Notably, cetirizine does not undergo significant metabolism and is not a metabolite of the CYP450 system.[7][8]

Administration

The dosing of cetirizine depends on patient age. In adults and children 12 years or older, the recommended dose is 5 or 10 mg per day orally, depending on symptom severity.[9]

• In children 6 to 11 years old, 5 or 10 mg (1 or 2 teaspoons) once daily in syrup form is recommended depending on symptom severity.[10]
• In children 2 to 5 years old, the recommended dose is 2.5 mg (half teaspoon) in syrup form once daily.
• In children six months to 23 months old, the recommended dose is 2.5 mg (half teaspoon) in syrup form once daily.
• In patients six years or older with renal or hepatic impairment, a dose of 5 mg once daily is recommended.

Adverse Effects

Cetirizine is safe and relatively well-tolerated for the treatment of allergic rhinitis and urticaria. Although uncommon, its primary adverse effects in adults include somnolence, fatigue, and dry mouth.[1] Somnolence, as a result of cetirizine, appears to be dose-related. In some patients, research and experience have found cetirizine to contribute to daytime sleepiness.[11]

Children taking cetirizine most commonly experience similar side effects as adults taking cetirizine (somnolence, fatigue, and dry mouth). Children, in particular, are more likely than adults to experience headaches while taking cetirizine.

Contraindications

Cetirizine is contraindicated in anyone with a known hypersensitivity to it or any of its ingredients. Cetirizine is also contraindicated in anyone with a known hypersensitivity to hydroxyzine, as cetirizine is a metabolite of hydroxyzine.

Patients should not use cetirizine concurrently with alcohol or other central nervous system depressants as it may cause dose-related sedation.[12]

There are few well-controlled human studies on cetirizine in pregnant mothers, although these showed it to be safe during pregnancy in animal studies. Cetirizine should be used in pregnancy only when absolutely necessary. First-generation antihistamines, such as diphenhydramine and doxylamine, are safest to use during pregnancy.[13] However, first-generation antihistamines are more likely than second-generation antihistamines to cause somnolence; as such, patients should understand the potential adverse effects of whatever medication they choose to take in pregnancy.

Cetirizine is not recommended for nursing mothers as it gets excreted in breast milk.

Monitoring

Patients taking cetirizine require monitoring for the relief of symptoms. Healthcare team members should also monitor patients for adverse effects such as fatigue and somnolence in adults and headaches in children.

The kidney primarily excretes cetirizine; as a result, the risk of toxicity is typically higher in patients with impaired renal function. Patients with renal impairment should take a lower dosage of medication in their age bracket.[14]

Liver function and liver enzymes in patients with hepatic involvement should have close monitoring also. Healthcare providers should make dosage adjustments as needed for these patients.

Toxicity

In rats, research showed the minimal lethal dose to be approximately 460 times the maximum recommended daily dose for adults. The primary target of acute toxicity in rodents was the central nervous system. The primary target of multiple-dose toxicity in rodents was the liver. 

A small number of cases of cetirizine overdose appear in the literature. Many overdoses of cetirizine in children result from improper medication storage by adults living in the same home. Most overdose incidents that occur in children resolve spontaneously, with drowsiness and sedation being the main adverse effects observed. 

Drug-induced liver damage is common with numerous medications; there are reports of a small number of cases of cetirizine-induced liver damage; in all cases, liver enzyme values returned to normal after cessation of cetirizine.[15]

Enhancing Healthcare Team Outcomes

Cetirizine is a relatively safe and effective medication for the treatment of allergic rhinitis and urticaria. As cetirizine is available over-the-counter, healthcare providers should educate patients on possible side effects, such as drowsiness. Patients should not combine cetirizine with drugs that cause central nervous system depression. Care is necessary when prescribing cetirizine to patients with impaired renal or hepatic function. A careful drug history is essential to ensure that the patient is not taking any medications or supplements that could exacerbate cetirizine's adverse effects. Physicians, nurses, and pharmacists who prescribe or recommend cetirizine to patients should also provide education on the safe storage of cetirizine to prevent accidental overdose by children.