Cetirizine

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Cetirizine
Cetirizine structure.svg
Cetirizine-ball-and-stick.png
Clinical data
Pronunciation /sɛˈtɪrɪziːn/
Trade names Allacan, Piriteze, Zyrtec, others
AHFS/Drugs.com Monograph
MedlinePlus a698026
License data
Pregnancy
category
  • AU:B2
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
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]
Identifiers
  • (±)-[2-[4-[(4-Chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.223.545 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C21H25ClN2O3
Molar mass 388.89 g·mol−1
3D model (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) Yes check.svgY
  • Key:ZKLPARSLTMPFCP-UHFFFAOYSA-N Yes check.svgY
   (verify)

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]

Contents

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 antihistamines, cetirizine can cause drowsiness. [7] Among second-generation antihistamines, cetirizine is more likely than fexofenadine and loratadine to cause drowsiness. [8]

Use in pregnancy appears safe, but use during breastfeeding is not recommended. [9] 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. [10]

It was patented in 1983 [11] [12] and came into medical use in 1987. [13] It is on the World Health Organization's List of Essential Medicines. [14] It is available as a generic medication. [5] In 2022, it was the 43rd most commonly prescribed medication in the United States, with more than 13 million prescriptions. [15] [16]

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. [17]

Cetirizine is also commonly prescribed to treat acute and (in particular cases) chronic urticaria (hives), more efficiently than any other second-generation antihistamine. [17]

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. [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 pharmacist supervision. [18] The drug can be in the form of tablets, capsules or syrup. [18]

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. [19]

Pruritus after discontinuation of cetirizine

Discontinuing cetirizine after prolonged use (typically, use beyond six months) may result in pruritus (generalized itchiness). [20] [21] [22]

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. [23]

No specific schedule for weaning is currently provided in the drug information for cetirizine. [24]

Pharmacology

L-Stereoisomer, levocetirizine (top) and D-stereoisomer of cetirizine. 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. [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. [25] [26] It shows negligible inhibition of the hERG channel (IC50 Tooltip half-maximal inhibitory concentration > 30 μM) [27] 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. [28]

Cetirizine crosses the blood–brain barrier only slightly, and for this reason, produces minimal sedation compared to many other antihistamines. [29] 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. [30] (A 10 mg dose of cetirizine equals about a 30 mg dose of hydroxyzine in terms of peripheral antihistamine effect.) [31] 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. [32] 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. [30] 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. [30]

Cetirizine also shows anti-inflammatory properties independent of H1 receptors. [33] 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. [34] [35] [36] [37] [38] It has been shown to inhibit eosinophil chemotaxis and LTB4 release. [39] At a dosage of 20 mg, Boone et al. found that it inhibited the expression of VCAM-1 in patients with atopic dermatitis. [39]

Pharmacokinetics

Absorption

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] [40] 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. [40] 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. [41]

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. [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. [42] [1] [43]

Metabolism

Cetirizine is notably not metabolized by the cytochrome P450 system. [44] 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 precise enzymes responsible for transformation of cetirizine have not been identified. [2]

Elimination

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]

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. [45]

Synthesis

Cetirizine synthesis: Cetirizine synthesis.png
Cetirizine 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 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. [46]

Availability

Cetirizine10.JPG
A package of 10 mg cetirizine tablets.
Zyrtec-D blister pack.png
Zyrtec-D, a combination of cetirizine and pseudoephedrine.

Cetirizine is available without a prescription. [47] In some countries, it is only available over-the-counter in packages containing seven or ten 10 mg doses. [48] [49]

Cetirizine is available as a combination medication with pseudoephedrine, a decongestant. [50] The combination is often marketed using the same brand name as the cetirizine with a "-D" suffix (for example, Zyrtec-D). [51] [52]

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. [53] [54] [ failed verification ]

Related Research Articles

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.

<span class="mw-page-title-main">Diphenhydramine</span> Antihistamine medication

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<span class="mw-page-title-main">Chlorphenamine</span> Antihistamine used to treat allergies

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<span class="mw-page-title-main">Hydroxyzine</span> Antihistamine drug

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<span class="mw-page-title-main">Fexofenadine</span> Antihistamine medication

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<span class="mw-page-title-main">Doxylamine</span> First-generation antihistamine used as a short-term sedative and hypnotic (sleep aid)

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<span class="mw-page-title-main">Doxepin</span> Medication to treat depressive disorder, anxiety disorders, chronic hives, and trouble sleeping

Doxepin is a medication belonging to the tricyclic antidepressant (TCA) class of drugs used to treat major depressive disorder, anxiety disorders, chronic hives, and insomnia. For hives it is a less preferred alternative to antihistamines. It has a mild to moderate benefit for sleeping problems. It is used as a cream for itchiness due to atopic dermatitis or lichen simplex chronicus.

<span class="mw-page-title-main">Levocetirizine</span> Antihistamine drug

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Histamine H<sub>1</sub> receptor Histamine receptor

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<span class="mw-page-title-main">Dexchlorpheniramine</span> Chemical compound

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<span class="mw-page-title-main">Tripelennamine</span> Chemical compound

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<span class="mw-page-title-main">Antihistamine</span> Drug that blocks histamine or histamine agonists

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<span class="mw-page-title-main">Bilastine</span> Antihistamine medication

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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.

References

  1. 1 2 3 4 5 6 7 8 Chen C (2008). "Physicochemical, pharmacological and pharmacokinetic properties of the zwitterionic antihistamines cetirizine and levocetirizine". Current Medicinal Chemistry. 15 (21): 2173–2191. doi:10.2174/092986708785747625. PMID   18781943.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Portnoy JM, Dinakar C (January 2004). "Review of cetirizine hydrochloride for the treatment of allergic disorders". Expert Opinion on Pharmacotherapy. 5 (1): 125–135. doi:10.1517/14656566.5.1.125. PMID   14680442. S2CID   28946859.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Simons FE, Simons KJ (May 1999). "Clinical pharmacology of new histamine H1 receptor antagonists". Clinical Pharmacokinetics. 36 (5): 329–352. doi:10.2165/00003088-199936050-00003. PMID   10384858. S2CID   21360079.
  4. 1 2 Simons FE (December 2002). "Comparative pharmacology of H1 antihistamines: clinical relevance". The American Journal of Medicine. 113 (Suppl 9A): 38S–46S. doi:10.1016/s0002-9343(02)01436-5. PMID   12517581.
  5. 1 2 3 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 279. ISBN   9780857113382.
  6. 1 2 3 4 5 "Cetirizine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 28 August 2021. Retrieved 3 March 2019.
  7. 1 2 Slater JW, Zechnich AD, Haxby DG (January 1999). "Second-generation antihistamines: a comparative review". Drugs. 57 (1): 31–47. doi:10.2165/00003495-199957010-00004. PMID   9951950. S2CID   46984477.
  8. ↑
  9. ↑ "Cetirizine Pregnancy and Breastfeeding Warnings". Drugs.com. Archived from the original on 6 March 2019. Retrieved 3 March 2019.
  10. ↑ Zhou P, Jia Q, Wang Z, Zhao R, Zhou W (25 August 2022). "Cetirizine for the treatment of allergic diseases in children: A systematic review and meta-analysis". Frontiers in Pediatrics. 10: 940213. doi: 10.3389/fped.2022.940213 . PMC   9452751 . PMID   36090559.
  11. 1 2 USpatent 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.
  12. ↑ US4525358A,Baltes, Eugene; Lannoy, Jean de& Rodriguez, Ludovic,"2-[4-(Diphenylmethyl)-1-piperazinyl]-acetic acids and their amides",issued 1985-06-25
  13. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 549. ISBN   9783527607495. Archived from the original on 8 October 2022. Retrieved 19 September 2020.
  14. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl: 10665/371090 . WHO/MHP/HPS/EML/2023.02.
  15. ↑ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  16. ↑ "Cetirizine Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  17. 1 2 Rang HP, Dale MM, Flower RJ, Henderson G (21 January 2015). Rang and Dale's pharmacology (Eighth ed.). [United Kingdom]. p. 332. ISBN   978-0-7020-5362-7. OCLC   903083639.{{cite book}}: CS1 maint: location missing publisher (link)
  18. 1 2 "CETIRIZINE HYDROCHLORIDE". Archived from the original on 10 October 2022. Retrieved 17 October 2020.
  19. ↑ "Zyrtec Side Effects". drugs.com. Archived from the original on 23 July 2019. Retrieved 21 August 2015.
  20. ↑ Ekhart C, van der Horst P, van Hunsel F (December 2016). "Unbearable Pruritus After Withdrawal of (Levo)cetirizine". Drug Safety: Case Reports. 3 (1): 16. doi:10.1007/s40800-016-0041-9. PMC   5124431 . PMID   27889900.
  21. ↑ "Cetirizine (Zyrtec) Withdrawal & Unbearable Itching". People's Pharmacy. Archived from the original on 14 August 2013. Retrieved 9 September 2017.
  22. ↑ "addicted to zyrtec?". MedHelp. Archived from the original on 16 September 2017. Retrieved 9 September 2017.
  23. ↑ Chung AH, La Grenade L, Harinstein LM (2019). "Pruritus after discontinuation of cetirizine". Therapeutic Advances in Drug Safety. 10: 2042098619859996. doi:10.1177/2042098619859996. PMC   6613055 . PMID   31308927.
  24. ↑ Borst H (18 May 2023). "Did you know stopping Zyrtec can cause withdrawal?". The Checkup. Retrieved 23 July 2023.
  25. ↑ Zhang L, Cheng L, Hong J (2013). "The clinical use of cetirizine in the treatment of allergic rhinitis". Pharmacology. 92 (1–2): 14–25. doi: 10.1159/000351843 . PMID   23867423.
  26. ↑ Orzechowski RF, Currie DS, Valancius CA (January 2005). "Comparative anticholinergic activities of 10 histamine H1 receptor antagonists in two functional models". European Journal of Pharmacology. 506 (3): 257–264. doi:10.1016/j.ejphar.2004.11.006. PMID   15627436.
  27. ↑ Taglialatela M, Pannaccione A, Castaldo P, Giorgio G, Zhou Z, January CT, et al. (July 1998). "Molecular basis for the lack of HERG K+ channel block-related cardiotoxicity by the H1 receptor blocker cetirizine compared with other second-generation antihistamines". Molecular Pharmacology. 54 (1): 113–121. doi:10.1124/mol.54.1.113. PMID   9658196.
  28. ↑ Hulhoven R, Rosillon D, Letiexhe M, Meeus MA, Daoust A, Stockis A (November 2007). "Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study". European Journal of Clinical Pharmacology. 63 (11): 1011–1017. doi:10.1007/s00228-007-0366-5. PMID   17891537. S2CID   36218027. The equivalent dose of 60 mg cetirizine is also the highest dose ever administered in healthy subjects [13].
  29. ↑ Gupta A, Chatelain P, Massingham R, Jonsson EN, Hammarlund-Udenaes M (February 2006). "Brain distribution of cetirizine enantiomers: comparison of three different tissue-to-plasma partition coefficients: K(p), K(p,u), and K(p,uu)". Drug Metabolism and Disposition. 34 (2): 318–323. doi:10.1124/dmd.105.007211. PMID   16303872. S2CID   9111905.
  30. 1 2 3 Tashiro M, Kato M, Miyake M, Watanuki S, Funaki Y, Ishikawa Y, et al. (October 2009). "Dose dependency of brain histamine H(1) receptor occupancy following oral administration of cetirizine hydrochloride measured using PET with [11C]doxepin". Human Psychopharmacology. 24 (7): 540–548. doi:10.1002/hup.1051. PMID   19697300. S2CID   5596000.
  31. ↑ van den Elzen MT, van Os-Medendorp H, van den Brink I, van den Hurk K, Kouznetsova OI, Lokin AS, et al. (2017). "Effectiveness and safety of antihistamines up to fourfold or higher in treatment of chronic spontaneous urticaria". Clinical and Translational Allergy. 7: 4. doi: 10.1186/s13601-017-0141-3 . PMC   5309999 . PMID   28289538. [...] 30 mg of hydroxyzine equals about 10 mg cetirizine [11] [...]
  32. ↑ Yanai K, Tashiro M (January 2007). "The physiological and pathophysiological roles of neuronal histamine: an insight from human positron emission tomography studies". Pharmacology & Therapeutics. 113 (1): 1–15. doi:10.1016/j.pharmthera.2006.06.008. PMID   16890992.
  33. ↑ Köller M, Hilger RA, Rihoux JP, König W (May 1996). "Cetirizine exerts anti-inflammatory effects on human neutrophils". International Archives of Allergy and Immunology. 110 (1): 52–56. doi:10.1159/000237310. PMID   8645978.
  34. ↑ Bielory L, Lien KW, Bigelsen S (2005). "Efficacy and tolerability of newer antihistamines in the treatment of allergic conjunctivitis". Drugs. 65 (2): 215–228. doi:10.2165/00003495-200565020-00004. PMID   15631542. S2CID   46791611.
  35. ↑ Walsh GM (January 1994). "The anti-inflammatory effects of cetirizine". Clinical and Experimental Allergy. 24 (1): 81–85. doi:10.1111/j.1365-2222.1994.tb00921.x. PMID   8156449. S2CID   32269456.
  36. ↑ Gelfand EW, Appajosyula S, Meeves S (January 2004). "Anti-inflammatory activity of H1-receptor antagonists: review of recent experimental research". Current Medical Research and Opinion. 20 (1): 73–81. doi:10.1185/030079903125002586. PMID   14741075. S2CID   20451677.
  37. ↑ Fumagalli F, Baiardini I, Pasquali M, Compalati E, Guerra L, Massacane P, et al. (August 2004). "Antihistamines: do they work? Further well-controlled trials involving larger samples are needed". Allergy. 59 (Suppl 78): 74–77. doi:10.1111/j.1398-9995.2004.00573.x. PMID   15245363. S2CID   39936983.
  38. ↑ Grob JJ, Castelain M, Richard MA, Bonniol JP, Béraud V, Adhoute H, et al. (May 1998). "Antiinflammatory properties of cetirizine in a human contact dermatitis model. Clinical evaluation of patch tests is not hampered by antihistamines". Acta Dermato-Venereologica. 78 (3): 194–197. doi: 10.1080/000155598441512 . PMID   9602225.
  39. 1 2 Boone M, Lespagnard L, Renard N, Song M, Rihoux JP (July 2000). "Adhesion molecule profiles in atopic dermatitis vs. allergic contact dermatitis: pharmacological modulation by cetirizine". Journal of the European Academy of Dermatology and Venereology. 14 (4): 263–266. doi:10.1046/j.1468-3083.2000.00017.x. PMID   11204513. S2CID   24026684.
  40. 1 2 Paśko P, Rodacki T, Domagała-Rodacka R, Palimonka K, Marcinkowska M, Owczarek D (September 2017). "Second generation H1 - antihistamines interaction with food and alcohol-A systematic review". Biomedicine & Pharmacotherapy. 93: 27–39. doi:10.1016/j.biopha.2017.06.008. PMID   28622592.
  41. ↑ "Zyrtec prescribing information" (PDF). May 2006. Archived from the original (PDF) on 4 January 2010. Retrieved 19 November 2009.
  42. ↑ Hu Y, Sieck DE, Hsu WH (October 2015). "Why are second-generation H1-antihistamines minimally sedating?". European Journal of Pharmacology. 765: 100–106. doi:10.1016/j.ejphar.2015.08.016. PMID   26291661.
  43. ↑ Conen S, Theunissen EL, Vermeeren A, van Ruitenbeek P, Stiers P, Mehta MA, et al. (September 2013). "The role of P-glycoprotein in CNS antihistamine effects". Psychopharmacology. 229 (1): 9–19. doi:10.1007/s00213-013-3075-z. PMID   23564211. S2CID   10416220.
  44. ↑ Mahmoudi M (2 June 2016). Allergy and Asthma: Practical Diagnosis and Management. Springer. pp. 574–. ISBN   978-3-319-30835-7.
  45. ↑ "Cetirizine". PubChem. U.S. National Library of Medicine. Retrieved 4 April 2022.
  46. ↑ Reiter J, Trinka P, Bartha FL, Pongó L, Volk B, Simig G (20 July 2012). "New Manufacturing Procedure of Cetirizine". Organic Process Research & Development. 16 (7): 1279–1282. doi:10.1021/op300009y. ISSN   1083-6160.
  47. ↑ "Cetirizine: Clinical Review". U.S. Food and Drug Administration. 11 September 2016.
  48. ↑ Aaronson DW (May 1996). "Evaluation of cetirizine in patients with allergic rhinitis and perennial asthma". Annals of Allergy, Asthma & Immunology. 76 (5): 440–446. doi:10.1016/s1081-1206(10)63461-8. PMID   8630718.
  49. ↑ Jobst S, van den Wijngaart W, Schubert A, van de Venne H (September 1994). "Assessment of the efficacy and safety of three dose levels of cetirizine given once daily in children with perennial allergic rhinitis". Allergy. 49 (8): 598–604. doi:10.1111/j.1398-9995.1994.tb00125.x. PMID   7653736. S2CID   46312788.
  50. ↑ Wellington K, Jarvis B (2001). "Cetirizine/pseudoephedrine". Drugs. 61 (15): 2231–2240. doi:10.2165/00003495-200161150-00009. PMID   11772135. S2CID   263997602.
  51. ↑ Nathan RA, Finn AF, LaForce C, Ratner P, Chapman D, de Guia EC, et al. (September 2006). "Comparison of cetirizine-pseudoephedrine and placebo in patients with seasonal allergic rhinitis and concomitant mild-to-moderate asthma: randomized, double-blind study". Annals of Allergy, Asthma & Immunology. 97 (3): 389–396. doi:10.1016/S1081-1206(10)60806-X. PMID   17042147.
  52. ↑ "Antihistamine/Decongestant Combination (Oral Route) Description and Brand Names". Mayo Clinic. 7 February 2023. Retrieved 23 February 2023.
  53. ↑ "Cetirizine: antihistamine that relieves allergy symptoms". nhs.uk. 30 October 2018. Retrieved 23 October 2023.
  54. ↑ "Protriptyline". AHFS Patient Medication Information [Internet]. Bethesda (MD): American Society of Health-System Pharmacists, Inc. 2019 – via Medlineplus.
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