Cetirizine

Cetirizine

Systematic (IUPAC) name
(±) - [2- [4- [ (4-chlorophenyl)phenylmethyl] -1- piperazinyl] ethoxy]acetic acid, dihydrochloride
Identifiers
CAS number	83881-51-0
ATC code	R06AE07
PubChem	2678
DrugBank	APRD00630
ChemSpider	2577
Chemical data
Formula	C21H25ClN2O3
Mol. mass	388.89
SMILES	eMolecules & PubChem
Synonyms	Alatrol, Alzene, Cetirizina, Cetirin, Cetzine, Cetirizin, Humex, Letizen, Razene, Reactine, Zyrtec, Zirtec, Zodac, Zirtek, Zynor, Zyrlek, Zyllergy
Pharmacokinetic data
Bioavailability	well absorbed
Protein binding	93% avg
Metabolism	CYP3A4 (Cytochrome P450 3A4)
Half life	8.3 Hours
Excretion	Hepatic, urine or excrement (Small amounts)
Therapeutic considerations
Licence data	US FDA:link
Pregnancy cat.	B(US)
Legal status	GSL(UK) OTC(US) OTC in Canada
Routes	Oral
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Cetirizine hydrochloride (pronounced /sɛˈtɪrɨziːn/), an 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. The structural similarity of cetirizine to hydroxyzine, and its derivation from piperazine, attribute similar adverse reactions and properties to other piperazine derivatives.^{[citation needed]}

Formerly prescription-only in the US and Canada, cetirizine is now available over-the-counter in both countries as Zyrtec and Reactine respectively. Zyrtec was the top 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, 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.

Pharmacology

Cetirizine crosses the blood-brain barrier only slightly, eliminating the sedative side-effect common with older antihistamines; however it still causes mild drowsiness.^[2] 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.^[3]

Administration method and metabolisation

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;^[4] 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.^[5] 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.^[4][5] 70% of the drug is excreted or eliminated by kidney function within 72 hours, and 10% is removed through urine or excrement;^[4][5] of which half is observed as unchanged cetirizine compound.^[4][5]

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.)

Additionally, cetirizine HCl now^[when?] sold in combination with pseudoephedrine, is commonly known and marketed in the United States under the brand name,Zyrtec-D. Formerly^[when?] only available by a prescription, both Zyrtec and Zyrtec-D are currently^[when?] available over-the-counter in the United States.^[6] In the Philippines, a leading cetirizine is Aforvir.^{[citation needed]}

Levorotary isomer

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The levorotary enantiomer of cetirizine is known as levocetirizine. It is marketed under the names of Xyzal and Xusal.

Indications

Rhinovirus infection

Interleukin 6 and interleukin 8 have been shown to be elevated in acute respiratory distress syndrome.^[7] 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.^[8] 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.^[9] 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.^[9] 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;^[9]an agent suitable for the treatment of pruritus associated with such lesions.^[9] Asymptomatically, the patient's skin lesions disappeared after treatment with cetirizine, blood eosinophil counts became normal,^[9] corticosteroid effects were resolved,^[9] and a remission began within a period of two months.^[9] 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.^[9]

References

Books and journals

1. Anderson, P. O., Knoben, J. E., et al. (2002) Handbook of clinical drug data 10th ed. McGraw-Hill International
2. Pfizer Inc, et al. (2006) ZYRTEC (cetirizine hydrochloride) Tablets, Chewable Tablets and Syrup For Oral Use Pfizer Incorporated publications
3. Chetrit, E. B., Amir, G., Shalit, M. (2005). Cetirizine: an effective agent in Kimura's Disease Arthritis & Rheumatism (Arthritis care & research) Vol 53, p117-118

External links

• Zyrtec prescribing information Pfizer
• List of brand names
• US FDA approves Zyrtec-D for over the counter sales
• US FDA approves Zyrtec for over the counter sales