Cetirizine

Cetirizine, sold under the brand name Zyrtec among others, is a used to treat  (hay fever),, and. It is taken by mouth. Effects generally begin within an hour and last for about a day. The degree of benefit is similar to other antihistamines such as.

Common side effects include sleepiness, dry mouth, headache, and abdominal pain. The degree of sleepiness that occurs is generally less than with s. Serious side effects may include aggression and. Use in appears safe, but use during  is not recommended. The medication works by blocking, mostly outside the.

It was patented in 1981 and came into medical use in 1987. It is available as a. A month's supply in the United Kingdom costs the about £0.70 as of 2019. In the United States the wholesale cost of this amount is about US$2.50. In 2016 it was the 74th most prescribed medication in the United States, with more than 10 million prescriptions.

Allergies
Cetirizine's primary indication is for 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.

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

Available forms
Cetirizine is available over-the-counter in the US in the form of 5 and 10 mg. A 20 mg strength is available by prescription only. In the UK up to 30 tablets of 10mg are on the general sales list (of pharmaceuticals).

Adverse effects
Commonly reported side effects of cetirizine include (16%),  (5.7%),  (5–20%), and  (5.6%), while more serious but rare side effects include, , and.

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

Pharmacodynamics
Cetirizine acts as a highly  of the. The Ki values for the H1 receptor are approximately 6 nM for cetirizine, 3 nM for, and 100 nM for , indicating that the  is the main active form. Cetirizine has 600-fold or greater for the H1 receptor over a wide variety of other sites, including, , , and s, among many others. The drug shows 20,000-fold or greater selectivity for the H1 receptor over the five muscarinic acetylcholine receptors, and hence does not exhibit effects. It shows negligible inhibition of the channel (IC50 > 30 µM) and no  has been observed with cetirizine at doses of up to 60 mg/day, six times the normal recommended dose and the highest dose of cetirizine that has been studied in healthy subjects.

Cetirizine crosses the only slightly, and for this reason, it produces minimal sedation compared to many other antihistamines. A (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. (A 10 mg dose of cetirizine equals about a 30 mg dose of hydroxyzine in terms of peripheral antihistamine effect.) 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. 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. 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 in other studies.

Cetirizine has been shown to inhibit  and  release. At a dosage of 20 mg, Boone et al. found that it inhibited the expression of in patients with.

Absorption
Cetirizine is rapidly and extensively upon  in tablet or syrup form. The  of cetirizine is at least 70% and of levocetirizine is at least 85%. The of cetirizine is approximately 1.0 hour regardless of formulation. The of cetirizine have been found to increase linearly with dose across a range of 5 to 60 mg. Its  following a single dose has been found to be 257 ng/mL for 10 mg and 580 ng/mL for 20 mg. Food has no effect on the  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%. 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. of cetirizine occur within 3 days and there is no accumulation of the drug with chronic administration. Following once-daily administration of 10 mg cetirizine for 10 days, the mean Cmax was 311 ng/mL.

Distribution
The mean of cetirizine has been found to be 93 to 96% across a range of 25 to 1,000 ng/mL independent of concentration. Plasma protein binding of 88 to 96% has also been reported across multiple studies. The drug is bound to with high, while  and s contribute much less to total plasma protein binding. The unbound or free fraction of levocetirizine has been reported to be 8%. The true of cetirizine is unknown but is estimated to be 0.3 to 0.45 L/kg. Cetirizine poorly and slowly crosses the, which is due mainly to its chemical properties but also to a minor extent to its activity as a.

Metabolism
Cetirizine does not undergo extensive. It is notably not metabolized by the system. Because of this, it does not interact significantly with drugs that or  cytochrome P450 enzymes such as, , , , or. While cetirizine does not undergo extensive metabolism or metabolism by the cytochrome P450 enzyme, it does undergo some metabolism by other means, the s of which include and. 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. The enzymes responsible for of cetirizine have not been identified.

Elimination
Cetirizine is approximately 70 to 85% in the  and 10 to 13% in the. About 50 or 60% of cetirizine eliminated in the urine is unchanged. It is eliminated in the urine via an mechanism. The of cetirizine ranges from 6.5 to 10 hours in healthy adults, with a mean across studies of approximately 8.3 hours. Its is at least 24 hours. The elimination half-life of cetirizine is increased in the elderly (to 12 hours), in (to 14 hours), and in  (to 20 hours).

Chemistry
Cetirizine contains L - and D -s. Chemically, is the active L - of cetirizine. The drug is a member of the group of antihistamines. include and.

Synthesis


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 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.

Brand names
Cetirizine is marketed under the brand names Alatrol, Alerid, Alzene, Cetirin, Cetzine, Cezin, Cetgel, Histazine, Humex, Letizen, Reactine, Razene, Rigix, Sensahist (Oethmann, South Africa), Triz, Zetop, Zirtec, Zirtek, Zodac, Zyllergy, Zynor, Zyrlek, and Zyrtec, among others.

Availability
Formerly prescription-only in many countries, cetirizine is now available without prescription in most countries. In some countries it is available over-the-counter only in packages containing seven or ten 10 mg doses.

Like many other antihistamine medications, cetirizine is commonly prescribed in combination with, a. These combinations are often marketed using the same brand name as the cetirizine with a "-D" suffix (Zyrtec-D, Virlix-D, etc.)