Cetirizine

Cetirizine is a second-generation antihistamine used in the treatment of hay fever, allergies, angioedema, and urticaria. It is a major metabolite of hydroxyzine, and a racemic selective H₁ receptor inverse agonist.

Availability

Formerly prescription-only in the USA and Canada, cetirizine is now available over-the-counter in both countries^[2] as Zyrtec and Reactine, respectively. Zyrtec was the highest-grossing new non-food product of 2008 in the US, generating sales of $315.9 million.^[3] It is also available as a generic drug. In Turkey, Australia and New Zealand, Zyrtec is available over-the-counter in pharmacies and in the UK and The Netherlands cetirizine can be sold in limited quantities off-the-shelf in any outlet and is often available in supermarkets. As of 2009, Germany made many generic drugs containing cetirizine available in pharmacies without prescription.^[4] Norway, Sweden,^[5] Finland, Poland and Israel also recognize Cetirizine as an over-the-counter medicine. In India, it is sold over-the-counter as brand-name "CTZ" (formerly called "Cetzine"), even though it remains classified as a Schedule H (prescription) drug.^[6] India also classifies Cetirizine as an OTC drug, and uses it as an alternative to Pheniramine (Avil) which is no longer provided OTC in India.

Pharmacology

Cetirizine crosses the blood–brain barrier only slightly, reducing the sedative side-effect common with older antihistamines.^[7] It has also been shown to inhibit eosinophil chemotaxis and LTB4 release. At a dosage of 20 mg, Boone et al. found that it inhibited the expression of VCAM-1 in patients with atopic dermatitis.^[8] Unlike many other antihistamines, Cetirizine does not exhibit anticholinergic properties.^[9]

The levorotary enantiomer of cetirizine, known as levocetirizine, is the more active form.

L-Stereoisomer, levocetirizine (top) and D-stereoisomer of cetirizine

Administration method and metabolism

Chewable, non-chewable, and syrup forms of cetirizine are similarly absorbed rapidly and effectively, with absorbed food minutely affecting the absorption rate which yields a peak serum level one hour after administration;^[10] in a study of healthy volunteers prescribed 10 mg tablets, once daily for 10 days, a mean peak serum level of 311 ng/mL was observed.^[11] The metabolic effects of cetirizine are long acting, remaining in the system for a maximum of 21 hours before being excreted; the average elimination half-life is 8 hours. About 70% of the drug is removed through urination, of which half is observed as unchanged cetirizine compound. Another 10% is excreted.^[10][11]

Like many other antihistamine medications, cetirizine is commonly prescribed in combination with pseudoephedrine hydrochloride, a decongestant. These combinations are marketed using the same brand name as the cetirizine with a "-D" suffix (Zyrtec-D, Virlix-D, etc.)

Indications

Allergies

Cetirizine's primary indication is for hay fever and other allergies. Because the symptoms of itching and redness in these conditions are caused by histamine acting on the H1 receptor, blocking those receptors temporarily relieves those symptoms.

Cetirizine is also commonly prescribed to treat acute and (in particular cases) chronic urticaria, more efficiently than any other second-generation antihistamine. It is preferred over diphenhydramine in many countries because, while being as effective as it for treating hives-related skin diseases, cetirizine does not affect the regular functioning of the brain.

Rhinovirus infection

Interleukin 6 and interleukin 8 have been shown to be elevated in acute respiratory distress syndrome.^[12] Cetirizine contains L- and D-stereoisomers. Chemically, levocetirizine is the active L-enantiomer of cetirizine. One recent study of airway epithelial cells showed that Levocetirizine may have beneficial effects on the pathophysiologic changes related to human rhinovirus (HRV) infection.^[13] Airway inflammation caused from a cytokine storm secondary to acute respiratory distress syndrome could also theoretically benefit.

Kimura's disease

Cetirizine is an effective agent in treating the symptoms of Kimura's disease, which mostly occurs in young Asian men, affecting the lymph nodes and soft tissue of the head and neck in the form of tumor-like lesions. Cetirizine's properties of being effective both in the treatment of pruritus (itching) and as an anti-inflammatory agent make it suitable for the treatment of the pruritus associated with these lesions.^[14] In a 2005 study, the American College of Rheumatology conducted treatments initially using prednisone, followed by steroid dosages and azathioprine, omeprazole, and calcium and vitamin D supplements over the course of two years.^[14] The skin condition of the patient began to improve and the skin lesions lessened. However, there were symptoms of cushingoid and hirsutism observed before the patient was removed from the courses of steroids and placed on 10 mg/day of cetirizine to prevent skin lesions;^[14] an agent suitable for the treatment of pruritus associated with such lesions.^[14] Asymptomatically, the patient's skin lesions disappeared after treatment with cetirizine, blood eosinophil counts became normal,^[14] corticosteroid effects were resolved,^[14] and a remission began within a period of two months.^[14] It is also thought that the inhibition of eosinophils may be the key to treatment of Kimura's disease due to the role of eosinophils, rather than other cells with regards to the lesions of the skin.^[14]

Side effects

Dryness of the mouth, nose and throat, drowsiness, urinary retention, blurred vision, nightmares and headaches are commonly reported side effects of this drug (in over 40% of the patients). Stomach aches are usually rare, but mostly present in patients with lactose intolerance.^[15] Cetirizine does not block the action of the muscarinic acetylcholine receptors, even though these side effects can occur in some patients. Also, cetirizine does not have antidopaminergic properties. In 2012, the FDA added cetirizine in Drugs to Watch List for oculogyric crisis.^[16]

Patients report that going off the drug can cause intense itching and hives.^[17][18]

Synthesis

The following synthesis of this compound was reported in 1985:^[19]

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