Cetirizine

Source: Wikipedia, the free encyclopedia.

Cetirizine
Clinical data
Pronunciation/sɛˈtɪrɪziːn/
Trade namesAllacan, Piriteze, Zyrtec, others
AHFS/Drugs.comMonograph
MedlinePlusa698026
License data
Pregnancy
category
  • AU: B2
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • AU: Unscheduled
  • CA: OTC
  • NZ: OTC
  • UK:
    General sales list
    (GSL, OTC) / P
  • US: OTC / Rx-only
  • OTC / Rx-only
Pharmacokinetic data
BioavailabilityWell-absorbed (>70%)[1]
Protein binding88–96%[1]
MetabolismMinimal (non-cytochrome P450-mediated)[3][2]
Onset of action20–42 minutes[2]
Elimination half-lifeMean: 8.3 hours[3][2]
Range: 6.5–10 hours[4]
Duration of action≥24 hours[4]
ExcretionUrine: 70–85%[3]
Feces: 10–13%[3]
Identifiers
  • (±)-[2-[4-[(4-Chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetic acid
JSmol)
  • Clc1ccc(cc1)C(c2ccccc2)N3CCN(CC3)CCOCC(=O)O
  • InChI=1S/C21H25ClN2O3/c22-19-8-6-18(7-9-19)21(17-4-2-1-3-5-17)24-12-10-23(11-13-24)14-15-27-16-20(25)26/h1-9,21H,10-16H2,(H,25,26) checkY
  • Key:ZKLPARSLTMPFCP-UHFFFAOYSA-N checkY
  (verify)

Cetirizine is a

first-generation antihistamine.[6]

Common side effects include sleepiness, dry mouth, headache, and abdominal pain.

first-generation antihistamines because second-generation antihistamines are more selective for the H1 receptor.[7][5] Compared to other second-generation anti-histamines, cetirizine can cause drowsiness.[7] Second-generation antihistamines that do not cause drowsiness are fexofenadine, and loratadine.[7]

Use in pregnancy appears safe, but use during breastfeeding is not recommended.[8] The medication works by blocking histamine H1 receptors, mostly outside the brain.[6]

Cetirizine can be used for paediatric patients. The main side effect to be cautious about is somnolence.[9]

It was patented in 1983

generic medication.[5] In 2021, it was the 49th most commonly prescribed medication in the United States, with more than 13 million prescriptions.[14][15]

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.[16]

Cetirizine is also commonly prescribed to treat acute and (in particular cases) chronic urticaria, more efficiently than any other second-generation antihistamine.[16]

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.[3] 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 without pharmacist supervision.[17] The drug can be in the form of tablets, capsules or a syrup.[17]

Adverse effects

Commonly reported side effects of cetirizine include

fatigue, while more serious, but rare, adverse effects reported include tachycardia and edema.[18]

Pruritus after discontinuation of cetirizine

Discontinuing cetirizine after prolonged use (typically, use beyond six months) may result in pruritus (generalized

itchiness).[19][20][21]

The United States 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 24 April 2017. Their report noted that some patients indicated the itchiness impacted their ability to work, sleep or perform normal daily activities.[22]

No specific schedule for weaning is currently provided in the drug information for cetirizine.[23]

Pharmacology

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

Pharmacodynamics

Cetirizine acts as a highly

IC50Tooltip half-maximal inhibitory concentration > 30 μM)[26] and no cardiotoxicity has been observed with cetirizine at doses of up to 60 mg/day, six times the normal recommended dose[3] and the highest dose of cetirizine that has been studied in healthy subjects.[27]

Cetirizine crosses the blood–brain barrier only slightly, and for this reason, produces minimal sedation compared to many other antihistamines.[28] 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.[29] (A 10 mg dose of cetirizine equals about a 30 mg dose of hydroxyzine in terms of peripheral antihistamine effect.)[30] 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.[31] 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.[29] 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.[29]

Cetirizine also shows anti-inflammatory properties independent of H1 receptors.

LTB4 release.[38] At a dosage of 20 mg, Boone et al. found that it inhibited the expression of VCAM-1 in patients with atopic dermatitis.[38]

Pharmacokinetics

Absorption

Cetirizine is rapidly and extensively

Steady-state levels of cetirizine occur within 3 days and there is no accumulation of the drug with chronic administration.[2] Following once-daily administration of 10 mg cetirizine for ten days, the mean Cmax was 311 ng/mL.[40]

Distribution

The mean

substrate.[41][1][42]

Metabolism

Cetirizine does not undergo extensive

conjugation.[3][2] Plasma radioactivity attributed to unchanged cetirizine is more than 90% at 2 hours, 80% at 10 hours, and 70% at 24 hours, indicating limited and slow metabolism.[2] The enzymes responsible for transformation of cetirizine have not been identified.[3]

Elimination

Cetirizine is

renal impairment (to 20 hours).[2]

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.[44]

Synthesis

Cetirizine synthesis:[10]

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.[45]

Availability

A package of 10 mg cetirizine tablets.
Zyrtec-D, a combination of cetirizine and pseudoephedrine.

Cetirizine is available without a prescription.[46] In some countries it is available over-the-counter only in packages containing seven or ten 10 mg doses.[47][48]

Cetirizine is available as a

combination medication with pseudoephedrine, a decongestant.[49] The combination is often marketed using the same brand name as the cetirizine with a "-D" suffix (for example, Zyrtec-D).[50][51]

Cetirizine is marketed under the brand names 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.[52][53][failed verification]

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  10. ^ a b US patent 4525358, Baltes E, De Lannoy J, Rodriguez L, "2-[4-(Diphenylmethyl)-1-piperazinyl]-acetic acids and their amides", issued 25 June 1985, assigned to UCB Pharmaceuticals, Inc. 
  11. ^ US4525358A, Baltes, Eugene; Lannoy, Jean de & Rodriguez, Ludovic, "2-[4-(Diphenylmethyl)-1-piperazinyl]-acetic acids and their amides", issued 1985-06-25 
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