Cetirizine

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.