| Systematic (IUPAC) name | |
|---|---|
| (±)-[2-[4-[(4-chlorophenyl)phenylmethyl]-1- piperazinyl]ethoxy]acetic acid | |
| Clinical data | |
| Trade names | Zyrtec |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a698026 |
| Licence data | US FDA:link |
| Pregnancy cat. | B(US) |
| Legal status | GSL (UK) OTC (US) OTC in Canada |
| Routes | Oral |
| Pharmacokinetic data | |
| Bioavailability | well absorbed |
| Protein binding | ~93% |
| Metabolism | Excreted mainly unchanged |
| Half-life | 8.3 Hours |
| Excretion | Urine (mainly), hepatic or excrement (Small amounts) |
| Identifiers | |
| CAS number | 83881-51-0 |
| ATC code | R06AE07 |
| PubChem | CID 2678 |
| IUPHAR ligand | 1222 |
| DrugBank | APRD00630 |
| ChemSpider | 2577 |
| UNII | YO7261ME24 |
| KEGG | D07662 |
| ChEBI | CHEBI:3561 |
| ChEMBL | CHEMBL1000 |
| Synonyms | Alatrol, Alzene, Cetirizina, Cetirin, Cetzine, Cetirizin, Cezin, Humex, Letizen, Razene, Reactine, Zyrtec, Zirtec, Zodac, Zirtek, Zynor, Zyrlek, Zyllergy |
| Chemical data | |
| Formula | C21H25ClN2O3 |
| Mol. mass | 388.89 |
| SMILES | eMolecules & PubChem |
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Cetirizine ( /sɛˈtɪrɨziːn/), a second-generation antihistamine, is a major metabolite of hydroxyzine, and a racemic selective H1 receptor inverse agonist used in the treatment of allergies, hay fever, angioedema, and urticaria.
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Formerly prescription-only in the USA and Canada, cetirizine is now available over-the-counter in both countries 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.[1] It is also available as a generic drug. In Australia and New Zealand, Zyrtec is available over-the-counter in pharmacies and in the UK 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.[2] Norway, Sweden[3] and Finland also recognize Cetirizine as an over-the-counter medicine. In India it is sold over-the-counter as brand-name 'Cetzine', even though it remains classified as a Schedule H (prescription) drug[4]
Cetirizine crosses the blood-brain barrier only slightly, reducing the sedative side-effect common with older antihistamines. [5] 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.[6]
The levorotary enantiomer of cetirizine, known as levocetirizine, is the more active form.
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;[7] 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.[8] 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.[7][8]
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.)
Formerly only available by a prescription, both Zyrtec and Zyrtec-D in November 2007 became available over-the-counter in the United States.[9]
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.
Interleukin 6 and interleukin 8 have been shown to be elevated in acute respiratory distress syndrome.[10] Cetirizine contains L- and D-stereoisomers. Chemically, levocetirizine is the active L-enantiomer of cetirizine. In a recent study of airway epithelial cells the following was observed: Levocetirizine inhibits the production of intercellular adhesion molecule ICAM-1 and secretion of interleukin (IL)-6 and IL-8, which may have beneficial effects on the pathophysiologic changes related to human rhinovirus (HRV) infection. Levocetirizine treatment inhibited the HRV-induced increase in ICAM-1 mRNA and protein levels, as well as the HRV-induced expression of IL-6 and IL-8 mRNA and protein levels. Viral titer, as measured by culture in MRC-5 cells, was reduced by levocetirizine. Levocetirizine treatment also reduced the increased nuclear factor-kappa B (NF-κB) expression seen with HRV infection. Levocetirizine inhibited the expression of Toll-like receptor 3 (TLR3) mRNA and protein levels. These findings indicate that, in HNEC and A549 cells, levocetirizine inhibits HRV replication and HRV-induced upregulation of ICAM-1, IL-6, and IL-8, TLR3 expression and NF-κB activation. The results of this study suggest that levocetirizine may have a possible clinical application in the treatment of airway inflammation caused by HRV infection.[11] Airway inflammation caused from a cytokine storm secondary to acute respiratory distress syndrome could also theoretically benefit.
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.[12] 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.[12] 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;[12] an agent suitable for the treatment of pruritus associated with such lesions.[12] Asymptomatically, the patient's skin lesions disappeared after treatment with cetirizine, blood eosinophil counts became normal,[12] corticosteroid effects were resolved,[12] and a remission began within a period of two months.[12] 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.[12]
Dryness of the mouth, nose and throat, urinary retention, blurred vision and stomach ache are commonly reported side effects of this drug.[13]
The following synthesis of this compound was reported in 1985:[14]
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