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Pronunciation | /sɛˈtɪrɪziːn/ |
Trade names | Allacan, Piriteze, Zyrtec, others |
AHFS/Drugs.com | Monograph |
MedlinePlus | a698026 |
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Routes of administration | By mouth |
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Bioavailability | Well-absorbed (>70%) [1] |
Protein binding | 88–96% [1] |
Metabolism | Minimal (non-cytochrome P450-mediated) [2] [3] |
Onset of action | 20–42 minutes [3] |
Elimination half-life | Mean: 8.3 hours [2] [3] Range: 6.5–10 hours [4] |
Duration of action | ≥24 hours [4] |
Excretion | Urine: 70–85% [2] Feces: 10–13% [2] |
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ECHA InfoCard | 100.223.545 |
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Formula | C21H25ClN2O3 |
Molar mass | 388.89 g·mol−1 |
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Cetirizine is a second-generation antihistamine used to treat allergic rhinitis (hay fever), dermatitis, and urticaria (hives). [5] It is taken by mouth. [6] Effects generally begin within thirty minutes and last for about a day. [6] The degree of benefit is similar to other antihistamines such as diphenhydramine, which is a first-generation antihistamine. [6]
Common side effects include sleepiness, dry mouth, headache, and abdominal pain. [6] 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. [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 [10] [11] and came into medical use in 1987. [12] It is on the World Health Organization's List of Essential Medicines. [13] It is available as a 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]
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 (hives), more efficiently than any other second-generation antihistamine. [16]
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. [2] 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]
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. [18]
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]
Cetirizine acts as a highly selective antagonist of the histamine H1 receptor. [2] The Ki 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. [2] 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. [2] 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. [24] [25] It shows negligible inhibition of the hERG channel (IC50 > 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 [2] 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. [32] 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. [33] [34] [35] [36] [37] It has been shown to inhibit eosinophil chemotaxis and 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]
Cetirizine is rapidly and extensively absorbed upon oral administration in tablet or syrup form. [2] The oral bioavailability of cetirizine is at least 70% and of levocetirizine is at least 85%. [1] The Tmax of cetirizine is approximately 1.0 hour regardless of formulation. [3] The pharmacokinetics of cetirizine have been found to increase linearly with dose across a range of 5 to 60 mg. [2] Its Cmax following a single dose has been found to be 257 ng/mL for 10 mg and 580 ng/mL for 20 mg. [3] Food has no effect on the bioavailability of cetirizine but has been found to delay the Tmax by 1.7 hours (i.e., to approximately 2.7 hours) and to decrease the Cmax by 23%. [2] [3] [39] Similar findings were reported for levocetirizine, which had its Tmax delayed by 1.25 hours and its Cmax decreased by about 36% when administered with a high-fat meal. [39] Steady-state levels of cetirizine occur within 3 days and there is no accumulation of the drug with chronic administration. [3] Following once-daily administration of 10 mg cetirizine for ten days, the mean Cmax was 311 ng/mL. [40]
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. [3] Plasma protein binding of 88 to 96% has also been reported across multiple studies. [1] The drug is bound to albumin with high affinity, while α1-acid glycoprotein and lipoproteins contribute much less to total plasma protein binding. [1] The unbound or free fraction of levocetirizine has been reported to be 8%. [1] The true volume of distribution of cetirizine is unknown but is estimated to be 0.3 to 0.45 L/kg. [2] [1] 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. [41] [1] [42]
Cetirizine is notably not metabolized by the cytochrome P450 system. [43] 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. [2] 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. [3] 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. [2] [3] The enzymes precise enzymes responsible for transformation of cetirizine have not been identified. [2]
Cetirizine is eliminated approximately 70 to 85% in the urine and 10 to 13% in the feces. [2] In total, about 60% of cetirizine eliminated in the urine is unchanged. [2] [3] It is eliminated in the urine via an active transport mechanism. [3] 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. [2] [3] 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). [3] Concentrations of cetirizine in the skin decline much slower than concentrations in the blood plasma. [3] Its duration of action is at least 24 hours. [3]
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]
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]
Cetirizine is available without a prescription. [46] In some countries, it is only available over-the-counter 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 ]
H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines; other agents may have antihistaminergic action but are not true antihistamines.
Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremors in parkinsonism, and nausea. It is taken by mouth, injected into a vein, injected into a muscle, or applied to the skin. Maximal effect is typically around two hours after a dose, and effects can last for up to seven hours.
Loratadine, sold under the brand name Claritin among others, is a medication used to treat allergies. This includes allergic rhinitis and hives. It is also available in drug combinations such as loratadine/pseudoephedrine, in which it is combined with pseudoephedrine, a nasal decongestant. It is taken orally.
Chlorphenamine, also known as chlorpheniramine, is an antihistamine used to treat the symptoms of allergic conditions such as allergic rhinitis. It is taken orally. The medication takes effect within two hours and lasts for about 4–6 hours. It is a first-generation antihistamine and works by blocking the H1 receptor.
Hydroxyzine, sold under the brand names Atarax and Vistaril among others, is an antihistamine medication. It is used in the treatment of itchiness, insomnia, anxiety, and nausea, including that due to motion sickness. It is used either by mouth or injection into a muscle.
Desloratadine. sold under the brand name Clarinex among others, is a tricyclic H1 inverse agonist that is used to treat allergies. It is an active metabolite of loratadine.
Fexofenadine, sold under the brand name Allegra among others, is an antihistamine pharmaceutical drug used in the treatment of allergy symptoms, such as hay fever and urticaria.
Clemastine, also known as meclastin, is a first-generation H1 histamine antagonist (antihistamine) with anticholinergic properties (drying) and sedative side effects. Like all first-generation antihistamines, it is sedating.
Levocetirizine, sold under the brand name Xyzal, among others, is a second-generation antihistamine used for the treatment of allergic rhinitis and long-term hives of unclear cause. It is less sedating than older antihistamines. It is taken by mouth.
The H1 receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. This receptor is activated by the biogenic amine histamine. It is expressed in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system. The H1 receptor is linked to an intracellular G-protein (Gq) that activates phospholipase C and the inositol triphosphate (IP3) signalling pathway. Antihistamines, which act on this receptor, are used as anti-allergy drugs. The crystal structure of the receptor has been determined (shown on the right/below) and used to discover new histamine H1 receptor ligands in structure-based virtual screening studies.
Dexchlorpheniramine is an antihistamine with anticholinergic properties used to treat allergic conditions such as hay fever or urticaria. It is the pharmacologically active dextrorotatory isomer of chlorpheniramine.
Azelastine, sold under the brand name Astelin among others, is a H1 receptor-blocking medication primarily used as a nasal spray to treat allergic rhinitis (hay fever) and as eye drops for allergic conjunctivitis. Other uses may include asthma and skin rashes for which it is taken by mouth. Onset of effects is within minutes when used in the eyes and within an hour when used in the nose. Effects last for up to 12 hours.
Acrivastine is a medication used for the treatment of allergies and hay fever. It is a second-generation H1-receptor antagonist antihistamine and works by blocking histamine H1 receptors.
Tripelennamine, sold under the brand name Pyribenzamine by Novartis, is a drug that is used as an antipruritic and first-generation antihistamine. It can be used in the treatment of asthma, hay fever, rhinitis, and urticaria, but is now less common as it has been replaced by newer antihistamines. The drug was patented at CIBA, which merged with Geigy into Ciba-Geigy, and eventually becoming Novartis.
Ebastine is a H1 antihistamine with low potential for causing drowsiness.
Rupatadine is a second generation antihistamine and platelet-activating factor antagonist used to treat allergies. It was discovered and developed by Uriach and is marketed as Rupafin and under several other trade names.
Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic drug that can be bought without a prescription and provides relief from nasal congestion, sneezing, or hives caused by pollen, dust mites, or animal allergy with few side effects. Antihistamines are usually for short-term treatment. Chronic allergies increase the risk of health problems which antihistamines might not treat, including asthma, sinusitis, and lower respiratory tract infection. Consultation of a medical professional is recommended for those who intend to take antihistamines for longer-term use.
Bilastine is an antihistamine medication used to treat hives (urticaria), allergic rhinitis and itchy inflamed eyes (allergic conjunctivitis) caused by an allergy. It is a second-generation antihistamine and takes effect by selectively inhibiting the histamine H1 receptor, preventing these allergic reactions. Bilastine has an effectiveness similar to cetirizine, fexofenadine, and desloratadine.
Cetirizine/pseudoephedrine (Zyrtec-D) is an antihistamine and decongestant formulation. It is a fixed-dose combination drug containing 5 mg cetirizine hydrochloride and 120 mg pseudoephedrine hydrochloride for symptoms related to seasonal allergic rhinitis. Cetirizine/pseudoephedrine gained approval from the U.S. Food and Drug Administration in 2001 as a prescription drug and became over-the-counter (OTC) in 2007.
Anti-allergic agents are medications used to treat allergic reactions. Anti-allergic agents have existed since 3000 B.C in countries such as China and Egypt. It was not until 1933 when antihistamines, the first type of anti-allergic agents, were developed. Common allergic diseases include allergic rhinitis, allergic asthma and atopic dermatitis with varying symptoms, including runny nose, watery eyes, itchiness, coughing, and shortness of breath. More than one-third of the world's population is currently being affected by one or more allergic conditions.
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: CS1 maint: location missing publisher (link)The equivalent dose of 60 mg cetirizine is also the highest dose ever administered in healthy subjects [13].
[...] 30 mg of hydroxyzine equals about 10 mg cetirizine [11] [...]