セチリジン

Pharmaceuticals -> Used in Switzerland

Pharmaceuticals

Breast Feeding; Lactation; Milk, Human; Antihistamines

Pharmaceuticals

Antiallergics and medicines used in anaphylaxis

110-115°C

110-115 °C

112.5 °C

195.6 Ų [M+Na]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID2044268]

200.8 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

197.02 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 10 reports by companies from 1 notifications to the ECHA C&L Inventory.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl cetirizine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Cetirizine hydrochloride/

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed over-the-counter drug products, incl cetirizine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Cetirizine hydrochloride/

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

A 72-year-old woman with renal insufficiency who was taking oral pilsicainide (150 mg/d) complained of feeling faint 3 days after she was prescribed oral cetirizine (20 mg/d). She was found to have a wide QRS wave with bradycardia. Her symptoms were relieved by termination of pilsicainide. The plasma concentrations of both drugs were significantly increased during the coadministration, and the cetirizine concentration decreased on cessation of pilsicainide despite the fact that treatment with cetirizine was continued, which suggested that the fainting was induced by the pharmacokinetic drug interaction. A pharmacokinetic study in 6 healthy male volunteers after a single dose of either cetirizine (20 mg) or pilsicainide (50 mg), or both, found that the renal clearance of each drug was significantly decreased by the coadministration of the drugs (from 475 +/- 101 mL/min to 279 +/- 117 mL/min for pilsicainide and from 189 +/- 37 mL/min to 118 +/- 28 mL/min for cetirizine; P = .008 and .009, respectively). In vitro studies using Xenopus oocytes with microinjected human organic cation transporter 2 and renal cells transfected with human multidrug resistance protein 1 revealed that the transport of the substrates of these transporters was inhibited by either cetirizine or pilsicainide. Thus elevated concentrations of these drugs as a result of a pharmacokinetic drug-drug interaction via either human multidrug resistance protein 1 or human organic cation transporter 2 (or both) in the renal tubular cells might have caused the arrhythmia in our patient. Although cetirizine has less potential for causing arrhythmias than other histamine 1 blockers, such an interaction should be considered, especially in patients with renal insufficiency who are receiving pilsicainide.

The case of an 88-yr-old man who developed an increase in anticoagulant activity while taking cetirizine and acenocoumarol together is reported. The patient had been treated for 1 yr with acenocoumarol 1 mg daily for deep vein thrombosis. Three laboratory tests performed during the last 8 wk before hospitalization revealed prothrombin values of 58, 59, and 59% with an international normalized ratio (INR) of 1.5. After an accidental fall, the patient presented to the emergency department with epistaxis, which was severe and did not stop with the usual therapy. Laboratory tests revealed serum total protein 7.5 g/dL, serum creatinine 1.4 mg/dL, and platelet count 564x103/cu mm; the prothrombin was less than 10% with an INR of more than 14. Three days before admission, oral cetirizine 10 mg daily was prescribed for allergic rhinitis. On admission, cetirizine was stopped and the patient received factor IX complex. After the treatment the prothrombin increased to 100%. The patient was discharged 1 wk later with an INR of 1.42.

The pharmacokinetics of the histamine H(1)-antagonist cetirizine and the effects of pretreatment with the antiparasitic macrocyclic lactone ivermectin on the pharmacokinetics of cetirizine were studied in horses. After oral administration of cetirizine at 0.2 mg/kg bw, the mean terminal half-life was 3.4 hr (range 2.9-3.7 hr) and the maximal plasma concentration 132 ng/mL (101-196 ng/mL). The time to reach maximal plasma concentration was 0.7 hr (0.5-0.8 hr). Ivermectin (0.2 mg/kg bw) given orally 1.5 hr before cetirizine did not affect its pharmacokinetics. However, ivermectin pretreatment 12 hr before cetirizine increased the area under the plasma concentration-time curve by 60%. The maximal plasma concentration, terminal half-life and mean residence time also increased significantly following the 12 hr pretreatment. Ivermectin is an inhibitor of P-glycoprotein, which is a major drug efflux transporter in cellular membranes at various sites. The elevated plasma levels of cetirizine following the pretreatment with ivermectin may mainly be due to decreased renal secretion, related to inhibition of the P-glycoprotein in the proximal tubular cells of the kidney. ...

Overdosage has been reported with ZYRTEC (cetirizine) . In one adult patient who took 150 mg of ZYRTEC (cetirizine) , the patient was somnolent but did not display any other clinical signs or abnormal blood chemistry or hematology results. In an 18 month old pediatric patient who took an overdose of ZYRTEC (cetirizine) (approximately 180 mg), restlessness and irritability were observed initially; this was followed by drowsiness. (L1712)

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 200(SRC), determined from a log Kow of 1.70(2) and a regression-derived equation(3), indicates that cetirizine is expected to have moderate mobility in soil(SRC). Estimated pKa values of 2.7, 3.6 and 7.6 for pKa1, pKa2 and pKa3(4), respectively, indicate that this compound will exist as an ion in the environment and ions generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization from moist soil may not be an important environmental fate because the base exists in ion form and ions do not volatilize. Cetirizine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.0X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(6). Biodegradation data were not available(SRC, 2009).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 200(SRC), determined from a log Kow of 1.70(2) and a regression-derived equation(3), indicates that cetirizine is expected to adsorb to suspended solids and sediment(SRC). Estimated pKa values of 2.7, 3.6 and 7.6 for pKa1, pKa2 and pKa3(4), respectively, indicate that cetirizine will exist in an ion form at pH values of 5 to 9(5) and therefore volatilization from water surfaces is not expected to be an important fate process. According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2009).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), cetirizine, which has an estimated vapor pressure of 3.0X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase cetirizine may be removed from the air by wet or dry deposition(SRC). Cetirizine does not contain chromophores that absorb at wavelengths >290 nm(3) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Animal studies

Cetirizine competes with histamine for binding at H₁-receptor sites on the effector cell surface, resulting in suppression of histaminic edema, flare, and pruritus. The low incidence of sedation can be attributed to reduced penetration of cetirizine into the CNS as a result of the less lipophilic carboxyl group on the ethylamine side chain.

The Koc of cetirizine is estimated as 200(SRC), using a log Kow of 1.70(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that cetirizine is expected to have moderate mobility in soil. Estimated pKa values of 2.7, 3.6 and 7.6 for pKa1, pKa2 and pKa3(4), respectively, indicate that this compound will exist in an ionic form in the environment and ions generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterpartss(5).

/CASE REPORTS/ In one adult patient who took 150 mg of Zyrtec, the patient was somnolent but did not display any other clinical signs or abnormal blood chemistry or hematology results. In an 18 month old pediatric patient who took an overdose of Zyrtec (approximately 180 mg), restlessness and irritability were observed initially; this was followed by drowsiness.

/CASE REPORTS/ Dystonia is a movement disorder that causes involuntary contractions of the muscles. Dystonia can affect just one muscle, a group of muscles, or all of the muscles. The most common cause of acquired dystonia in childhood is drugs. Cetirizine is widely used for allergic disorders in childhood. It is without central nervous system side effects at recommended dosages. ... A case of cetirizine-induced acute acquired dystonia whose symptoms completely resolved after the discontinuation of the drug /is reported/.

/CASE REPORTS/ The case of a 29-yr-old woman with pruritus sine materiae who was receiving treatment with oral tablets of 20 mg of cetirizine hydrochloride daily, after which she developed generalized chronic urticaria associated with cetirizine administration is presented. The patient was admitted for diagnostic purposes, and cetirizine was stopped on admission. Surprisingly, the patient's urticarial lesions resolved completely within 4 days. Subsequently, the patient showed a pseudoallergic response to a cellular antigen stimulation test performed with cetirizine. The patient was rechallenged with cetirizine 7 wk after discharge. The patient developed a generalized wheal reaction 15 min after an oral dose of 5 mg of cetirizine.

/CASE REPORTS/ ... The case of a 18-year-old female with the history of anorexia for 2 years, who was admitted to a Clinic of Toxicology because of suicidal attempt with use of cetirizine /is presented/. The laboratory results revealed metabolic acidosis with the pH 7.13; pO2 88 mm Hg; pCO2 36 mm Hg; HCO3 12.0 mmol/L; BE (-)17 mmol/L; SO2 100% and hypokalemia (K+ 3.1 mmol/L). On physical examination blood pressure was 70/40 mm Hg, heart rate was 36-40 beats/min. Convulsions were observed. After about two hours of intensive treatment there was a cardiac arrest in the form of ventricular fibrillation. The resuscitation procedures which lasted for over 2.5 hours were ineffective. The high dose (270 mg) of cetirizine as well as anorexia and hypokalemia could have been the cause of the unique character of the symptoms in this case. Further investigations should be carried out to confirm the safety of cetirizine in the conditions of massive intoxication and with coexistence of other risk factors.

For more Human Toxicity Excerpts (Complete) data for Cetirizine (12 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl cetirizine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Cetirizine hydrochloride/

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed over-the-counter drug products, incl cetirizine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Cetirizine hydrochloride/

R06AE07

R - Respiratory system

S - Sensory organs

QS - Sensory organs

QR - Respiratory system

**General effects and respiratory effects** Cetirizine, the active metabolite of the piperazine H₁-receptor antagonist hydroxyzine, minimizes or eliminates the symptoms of chronic idiopathic urticaria, perennial allergic rhinitis, seasonal allergic rhinitis, allergic asthma, physical urticaria, and atopic dermatitis. The clinical efficacy of cetirizine for allergic respiratory diseases has been well established in numerous trials. **Effects on urticaria/anti-inflammatory effects** It has anti-inflammatory properties that may play a role in asthma management. There is evidence that cetirizine improves symptoms of urticaria. Marked clinical inhibition of a wheal and flare response occurs in infants, children as well as adults within 20 minutes of one oral dose and lasts for 24 h. Concomitant use of cetirizine reduces the duration and dose of topical anti-inflammatory formulas used for the treatment of atopic dermatitis.

Cetirizine, a metabolite of _hydroxyzine_, is an antihistamine drug. Its main effects are achieved through selective inhibition of peripheral H1 receptors. The antihistamine activity of cetirizine has been shown in a variety of animal and human models. _In vivo_ and _ex vivo_ animal models have shown insignificant anticholinergic and antiserotonergic effects. In clinical studies, however, dry mouth was found to be more frequent with cetirizine than with a placebo. In vitro receptor binding studies have demonstrated no detectable affinity of cetirizine for histamine receptors other than the H1 receptors. Studies with radiolabeled cetirizine administration in the rat have demonstrated insignificant penetration into the brain. _Ex vivo_ studies in the mouse have shown that systemically administered cetirizine does not occupy cerebral H1 receptors significantly.

Cetirizine, a human metabolite of hydroxyzine, is an antihistamine; its principal effects are mediated via selective inhibition of peripheral H1 receptors. The antihistaminic activity of cetirizine has been clearly documented in a variety of animal and human models. In vivo and ex vivo animal models have shown negligible anticholinergic and antiserotonergic activity. In clinical studies, however, dry mouth was more common with cetirizine than with placebo. In vitro receptor binding studies have shown no measurable affinity for other than H1 receptors. Autoradiographic studies with radiolabeled cetirizine in the rat have shown negligible penetration into the brain. Ex vivo experiments in the mouse have shown that systemically administered cetirizine does not significantly occupy cerebral H1 receptors.

Plasma elimination half-life is 8.3 hours.

The mean elimination half-life in 146 healthy volunteers across multiple pharmacokinetic studies was 8.3 hours ... .

The pharmacokinetics of the second generation H1-receptor antagonist cetirizine were studied in 15 infants and toddlers (mean +/- SD age, 12.3 +/- 5.4 months) who were treated with a single 0.25 mg/kg dose of cetirizine solution. ... The elimination half-life was 3.1 +/- 1.8 hours ...

A mass balance clinical trial comprised of 6 healthy male study volunteers showed that 70% of the administered radioactivity was measured in the urine and 10% in the feces after cetirizine administration. About 50% of the radioactivity was measured in the urine as unchanged cetirizine. Most of the rapid increase in peak plasma radioactivity was related to the parent drug, implying a low level of first pass metabolism. This prevents potential interactions of cetirizine with drugs interacting with hepatic cytochrome enzymes. Cetirizine is metabolized partially by oxidative O-dealkylation to a metabolite with insignificant antihistaminic activity. The enzyme or enzymes responsible for this step in cetirizine metabolism have not yet been identified.

A mass balance study in 6 healthy male volunteers indicated that 70% of the administered radioactivity was recovered in the urine and 10% in the feces. Approximately 50% of the radioactivity was identified in the urine as unchanged drug. Most of the rapid increase in peak plasma radioactivity was associated with parent drug, suggesting a low degree of first-pass metabolism. Cetirizine is metabolized to a limited extent by oxidative O-dealkylation to a metabolite with negligible antihistaminic activity. The enzyme or enzymes responsible for this metabolism have not been identified.

Pharmacokinetic parameters of hydroxyzine and its active metabolite cetirizine were determined after oral and intravenous administration of 2 mg kg(-1) of hydroxyzine to six healthy dogs. Plasma drug levels were determined with high-pressure liquid chromatography. Pharmacodynamic studies evaluated the suppressive effect on histamine and anticanine IgE-mediated cutaneous wheal formation. Pharmacokinetic and pharmacodynamic correlations were determined with computer modelling. The mean systemic availability of oral hydroxyzine was 72%. Hydroxyzine was rapidly converted to cetirizine regardless of the route of administration. The mean area-under-the-curve was eight and ten times higher for cetirizine than hydroxyzine after intravenous and oral dosing, respectively. After oral administration of hydroxyzine, the mean peak concentration of cetirizine was approximately 2.2 microg mL(-1) and that of hydroxyzine 0.16 ug mL(-1). The terminal half-life for cetirizine varied between 10 and 11 hr after intravenous and oral administration of hydroxyzine. A sigmoidal relationship was fit to the data comparing cetirizine plasma concentration to wheal suppression. Maximum inhibition (82% and 69% for histamine and anticanine IgE-mediated skin reactions, respectively) was observed during the first 8 hr, which correlated with a plasma concentration of cetirizine greater than 1.5 ug mL(-1). Pharmacological modelling suggested that increasing either hydroxyzine dosages or frequencies of administration would not result in histamine inhibition superior to that obtained with twice daily hydroxyzine at 2 mg kg(-1). In conclusion, there was rapid conversion of hydroxyzine to cetirizine. The reduction of wheal formation appeared almost entirely due to cetirizine. Pharmacodynamic modelling predicted that maximal antihistamine effect would occur with twice daily oral administration of hydroxyzine at 2 mg kg(-1).

Half Life: 8.3 hours

YO7261ME24

CETIRIZINE

Mechanisms of Action [MoA] - Histamine H1 Receptor Antagonists

Established Pharmacologic Class [EPC] - Histamine-1 Receptor Antagonist

Cetirizine is a Histamine-1 Receptor Antagonist. The mechanism of action of cetirizine is as a Histamine H1 Receptor Antagonist.

CETIRIZINE

Agents that are used to treat allergic reactions. Most of these drugs act by preventing the release of inflammatory mediators or inhibiting the actions of released mediators on their target cells. (From AMA Drug Evaluations Annual, 1994, p475)

A class of non-sedating drugs that bind to but do not activate histamine receptors (DRUG INVERSE AGONISM), thereby blocking the actions of histamine or histamine agonists. These antihistamines represent a heterogenous group of compounds with differing chemical structures, adverse effects, distribution, and metabolism. Compared to the early (first generation) antihistamines, these non-sedating antihistamines have greater receptor specificity, lower penetration of BLOOD-BRAIN BARRIER, and are less likely to cause drowsiness or psychomotor impairment.

Cetirizine was rapidly absorbed with a time to maximum concentration (Tmax) of about 1 hour after oral administration of tablets or syrup formulation in adult volunteers. Bioavailability was found to be similar between the tablet and syrup dosage forms. When healthy study volunteers were given several doses of cetirizine (10 mg tablets once daily for 10 days), a mean peak plasma concentration (Cmax) of 311 ng/mL was measured. **Effect of food on absorption** Food had no effect on cetirizine exposure (AUC), however, Tmax was delayed by 1.7 hours and Cmax was decreased by 23% in the fed state.

Mainly eliminated in the urine,. Between 70 – 85% of an orally administered dose can be found in the urine and 10 – 13% in the feces.

Apparent volume of distribution: 0.44 +/- 0.19 L/kg.

Apparent total body clearance: approximately 53 mL/min. Cetirizine is mainly eliminated by the kidneys,. Dose adjustment is required for patients with moderate to severe renal impairment and in patients on hemodialysis.

A mass balance study in 6 healthy male volunteers indicated that 70% of the administered radioactivity was recovered in the urine and 10% in the feces. Approximately 50% of the radioactivity was identified in the urine as unchanged drug. Most of the rapid increase in peak plasma radioactivity was associated with parent drug, suggesting a low degree of first-pass metabolism. Cetirizine is metabolized to a limited extent by oxidative O-dealkylation to a metabolite with negligible antihistaminic activity. The enzyme or enzymes responsible for this metabolism have not been identified.

The mean plasma protein binding of cetirizine is 93%, independent of concentration in the range of 25-1000 ng/mL, which includes the therapeutic plasma levels observed.

A second-generation histamine H1 antagonist that is effective in the treatment of allergic rhinitis, chronic urticaria, and pollen-induced asthma.

THERAP CAT: Antihistaminic

Use (kg) in Switzerland (2009): >100

For the relief of symptoms associated with seasonal allergic rhinitis, perennial allergic rhinitis and the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria

Oxidative metabolization of hydroxyzine afforded the active metabolite cetirizine.

Preparation: E. Baltes et al., EP 58146; eidem, US 4525358 (1982, 1985 both to UCB)

Table: Cetirizine Hydrochloride Preparations [Table#7405]

Table: Cetirizine Hydrochloride Combination Preparations [Table#7406]

Pharmaceuticals -> Antihistamines

Pharmaceuticals