Cetirizine

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| _other_data=(±)-[2-[4-[(4-Chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetic acid

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Cetirizine is a second-generation antihistamine used to treat allergic rhinitis (hay fever), dermatitis, and urticaria (hives).<ref name="BNF76" /> It is taken by mouth.<ref name="AHFS2019" /> Effects generally begin within thirty minutes and last for about a day.<ref name="AHFS2019" /> The degree of benefit is similar to other antihistamines such as diphenhydramine, which is a first-generation antihistamine.<ref name="AHFS2019" />

Common side effects include sleepiness, dry mouth, headache, and abdominal pain.<ref name=AHFS2019/> The degree of sleepiness that occurs is generally less than with first-generation antihistamines because second-generation antihistamines are more selective for the H1 receptor.<ref name=":3">Template:Cite journal</ref><ref name="BNF76" /> Compared to other second-generation antihistamines, cetirizine can cause drowsiness.<ref name=":3" /> Among second-generation antihistamines, cetirizine is more likely than fexofenadine and loratadine to cause drowsiness.<ref name=":3"/>

Use in pregnancy appears safe, but use during breastfeeding is not recommended.<ref name="Preg2019">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The medication works by blocking histamine H₁ receptors, mostly outside the brain.<ref name="AHFS2019">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Cetirizine can be used for paediatric patients. The main side effect to be cautious about is somnolence.<ref>Template:Cite journal</ref>

It was patented in 1983<ref name=":0" /><ref>Template:Cite patent.</ref> and came into medical use in 1987.<ref name=Fis2006>Template:Cite book</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO23rd">Template:Cite book</ref> It is available as a generic medication.<ref name=BNF76>Template:Cite book</ref> In 2022, it was the 43rd most commonly prescribed medication in the United States, with more than 13Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Template:TOC limit

Medical uses

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.<ref name=":1">Template:Cite book</ref>

Cetirizine is also commonly prescribed to treat acute and (in particular cases) chronic urticaria (hives), more efficiently than any other second-generation antihistamine.<ref name=":1" />

Available forms

Cetirizine is available over-the-counter in the US in the form of 5 and 10 mg tablets. A 20 mg strength is available by prescription only.<ref name="pmid14680442" /> It is also available as a 1 mg/mL syrup for oral administration by prescription. In the UK, up to 30 tablets of 10 mg are on the general sales list (of pharmaceuticals) and can be purchased without a prescription and pharmacist supervision.<ref name=":2">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The drug can be in the form of tablets, capsules or syrup.<ref name=":2" />

Adverse effects

Commonly reported side effects of cetirizine include headache, dry mouth, drowsiness, and fatigue, while more serious, but rare, adverse effects reported include tachycardia and edema.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Pruritus after discontinuation of cetirizine

Discontinuing cetirizine after prolonged use (typically, use beyond six months) may result in pruritus (generalized itchiness).<ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

The US Food and Drug Administration (FDA) analyzed cases of pruritus after stopping cetirizine in the FDA Adverse Event Reporting System (FAERS) database and medical literature through April 2017. Their report noted that some patients indicated the itchiness impacted their ability to work, sleep or perform normal daily activities.<ref>Template:Cite journal</ref> On 16 May 2025, the FDA issued a Drug Safety Communication regarding the pruritus that can occur after discontinuing long-term use of cetirizine and levocetirizine.<ref name="FDA DSC 2025">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

No specific schedule for weaning is provided in the drug information for cetirizine.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Template:Unreliable medical source

Pharmacology

File:Cetirizine structure racemic.svg

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

Pharmacodynamics

Cetirizine acts as a highly selective antagonist of the histamine H₁ receptor.<ref name="pmid14680442">Template:Cite journal</ref> The K_i values for the H₁ receptor are approximately 6 nM for cetirizine, 3 nM for levocetirizine, and 100 nM for dextrocetirizine, indicating that the levorotatory enantiomer is the main active form.<ref name="pmid14680442" /> Cetirizine has 600-fold or greater selectivity for the H₁ receptor over a wide variety of other sites, including muscarinic acetylcholine, serotonin, dopamine, and α-adrenergic receptors, among many others.<ref name="pmid14680442" /> The drug shows 20,000-fold or greater selectivity for the H₁ receptor over the five muscarinic acetylcholine receptors, and hence does not exhibit anticholinergic effects.<ref name="pmid23867423">Template:Cite journal</ref><ref name="pmid15627436">Template:Cite journal</ref> It shows negligible inhibition of the hERG channel (Template:Abbrlink > 30 μM)<ref name="pmid9658196">Template:Cite journal</ref> and no cardiotoxicity has been observed with cetirizine at doses of up to 60 mg/day, six times the normal recommended dose<ref name="pmid14680442" /> and the highest dose of cetirizine that has been studied in healthy subjects.<ref name="pmid17891537">Template:Cite journal</ref>

Cetirizine crosses the blood–brain barrier only slightly, and for this reason, produces minimal sedation compared to many other antihistamines.<ref name="blood-brain">Template:Cite journal</ref> A positron emission tomography (PET) study found that brain occupancy of the H₁ receptor was 12.6% for 10 mg cetirizine, 25.2% for 20 mg cetirizine, and 67.6% for 30 mg hydroxyzine.<ref name="pmid19697300">Template:Cite journal</ref> (A 10 mg dose of cetirizine equals about a 30 mg dose of hydroxyzine in terms of peripheral antihistamine effect.)<ref name="pmid28289538">Template:Cite journal</ref> PET studies with antihistamines have found that brain H₁ receptor occupancy of more than 50% is associated with a high prevalence of somnolence and cognitive decline, whereas brain H₁ receptor occupancy of less than 20% is considered to be non-sedative.<ref name="pmid16890992">Template:Cite journal</ref> In accordance, H₁ receptor occupancy correlated well with subjective sleepiness for 30 mg hydroxyzine but there was no correlation for 10 or 20 mg cetirizine.<ref name="pmid19697300" /> As such, brain penetration and brain H₁ receptor occupancy by cetirizine are dose-dependent, and in accordance, while cetirizine at doses of 5 to 10 mg have been reported to be non-sedating or mildly sedating, a higher dose of 20 mg has been found to induce significant drowsiness in other studies.<ref name="pmid19697300" />

Cetirizine also shows anti-inflammatory properties independent of H₁ receptors.<ref name="pmid8645978">Template:Cite journal</ref> The effect is exhibited through suppression of the NF-κB pathway, and by regulating the release of cytokines and chemokines, thereby regulating the recruitment of inflammatory cells.<ref name="pmid15631542">Template:Cite journal</ref><ref name="pmid8156449">Template:Cite journal</ref><ref name="pmid14741075">Template:Cite journal</ref><ref name="pmid15245363">Template:Cite journal</ref><ref name="pmid9602225">Template:Cite journal</ref> It has been shown to inhibit eosinophil chemotaxis and LTB4 release.<ref name="pmid11204513">Template:Cite journal</ref> At a dosage of 20 mg, Boone et al. found that it inhibited the expression of VCAM-1 in patients with atopic dermatitis.<ref name="pmid11204513" />

Pharmacokinetics

Absorption

Cetirizine is rapidly and extensively absorbed upon oral administration in tablet or syrup form.<ref name="pmid14680442" /> The oral bioavailability of cetirizine is at least 70% and of levocetirizine is at least 85%.<ref name="pmid18781943" /> The T_max of cetirizine is approximately 1.0 hour regardless of formulation.<ref name="pmid10384858" /> The pharmacokinetics of cetirizine have been found to increase linearly with dose across a range of 5 to 60 mg.<ref name="pmid14680442" /> Its C_max following a single dose has been found to be 257 ng/mL for 10 mg and 580 ng/mL for 20 mg.<ref name="pmid10384858">Template:Cite journal</ref> Food has no effect on the bioavailability of cetirizine but has been found to delay the T_max by 1.7 hours (i.e., to approximately 2.7 hours) and to decrease the C_max by 23%.<ref name="pmid14680442" /><ref name="pmid10384858" /><ref name="pmid28622592">Template:Cite journal</ref> Similar findings were reported for levocetirizine, which had its T_max delayed by 1.25 hours and its C_max decreased by about 36% when administered with a high-fat meal.<ref name="pmid28622592" /> Steady-state levels of cetirizine occur within 3 days and there is no accumulation of the drug with chronic administration.<ref name="pmid10384858" /> Following once-daily administration of 10 mg cetirizine for ten days, the mean C_max was 311 ng/mL.<ref name="pfizer_ceti_p3">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Distribution

The mean plasma protein binding of cetirizine has been found to be 93 to 96% across a range of 25 to 1,000 ng/mL independent of concentration.<ref name="pmid10384858" /> Plasma protein binding of 88 to 96% has also been reported across multiple studies.<ref name="pmid18781943" /> The drug is bound to albumin with high affinity, while α₁-acid glycoprotein and lipoproteins contribute much less to total plasma protein binding.<ref name="pmid18781943" /> The unbound or free fraction of levocetirizine has been reported to be 8%.<ref name="pmid18781943" /> The true volume of distribution of cetirizine is unknown but is estimated to be 0.3 to 0.45 L/kg.<ref name="pmid14680442" /><ref name="pmid18781943" /> Cetirizine poorly and slowly crosses the blood–brain barrier, which is thought to be due to its chemical properties and its activity as a P-glycoprotein substrate.<ref name="pmid26291661">Template:Cite journal</ref><ref name="pmid18781943" /><ref name="pmid23564211">Template:Cite journal</ref>

Metabolism

Cetirizine is notably not metabolized by the cytochrome P450 system.<ref name="Mahmoudi2016">Template:Cite book</ref> Because of this, it does not interact significantly with drugs that inhibit or induce cytochrome P450 enzymes such as theophylline, erythromycin, clarithromycin, cimetidine, or alcohol.<ref name="pmid14680442" /> Studies with cetirizine synthesized with radioactive carbon-14 show that 90% of excreted cetirizine is unchanged at 2 hours, 80% at 10 hours, and 70% at 24 hours, indicating limited and slow metabolism.<ref name="pmid10384858" /> While cetirizine does not undergo extensive metabolism or metabolism by the cytochrome P450 enzyme, it does undergo some metabolism by other means, the metabolic pathways of which include oxidation and conjugation.<ref name="pmid14680442" /><ref name="pmid10384858" /> The precise enzymes responsible for transformation of cetirizine have not been identified.<ref name="pmid14680442" />

Elimination

Cetirizine is eliminated approximately 70 to 85% in the urine and 10 to 13% in the feces.<ref name="pmid14680442" /> In total, about 60% of cetirizine eliminated in the urine is unchanged.<ref name="pmid14680442" /><ref name="pmid10384858" /> It is eliminated in the urine via an active transport mechanism.<ref name="pmid10384858" /> The elimination half-life of cetirizine ranges from 6.5 to 10 hours in healthy adults, with a mean across studies of approximately 8.3 hours.<ref name="pmid14680442" /><ref name="pmid10384858" /> The elimination half-life of cetirizine is increased in the elderly (to 12 hours), in hepatic impairment (to 14 hours), and in renal impairment (to 20 hours).<ref name="pmid10384858" /> Concentrations of cetirizine in the skin decline much slower than concentrations in the blood plasma.<ref name="pmid10384858" /> Its duration of action is at least 24 hours.<ref name="pmid10384858" />

Chemistry

Cetirizine contains L- and D-stereoisomers. Chemically, levocetirizine is the active L-enantiomer of cetirizine. The drug is a member of the diphenylmethylpiperazine group of antihistamines. Analogues include cyclizine and hydroxyzine.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Synthesis

File:Cetirizine synthesis.png

Cetirizine synthesis:<ref name=":0">Template:Cite patent</ref>

The 1-(4-chlorophenylmethyl)-piperazine is alkylated with methyl (2-chloroethoxy)-acetate in the presence of sodium carbonate and xylene solvent to produce the Sn2 substitution product in 28% yield. Saponification of the acetate ester is done by refluxing with potassium hydroxide in absolute ethanol to afford a 56% yield of the potassium salt intermediate. This is then hydrolyzed with aqueous HCl and extracted to give an 81% yield of the carboxylic acid product.<ref>Template:Cite journal</ref>

Availability

Cetirizine is available without a prescription.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In some countries, it is only available over-the-counter in packages containing seven or ten 10 mg doses.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Cetirizine is available as a combination medication with pseudoephedrine, a decongestant.<ref>Template:Cite journal</ref> The combination is often marketed using the same brand name as the cetirizine with a "-D" suffix (for example, Zyrtec-D).<ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Cetirizine is sold under various brand names including Alatrol, Alerid, Allacan, Allercet, Alzene, Cerchio, Cetirin, Cetizin, Cetriz, Cetzine, Cezin, Cetgel, Cirrus, Histec, Histazine, Humex, Letizen, Okacet (Cipla), Piriteze, Reactine, Razene, Rigix, Sensahist (Oethmann, South Africa), Triz, Zetop, Zirtec, Zirtek, Zodac, Zyllergy, Zynor, Zyrlek, and Zyrtec (Johnson & Johnson), inter alios.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Template:Failed verification