Summary Of Exposure |
A) USES: Cetirizine is used to treat allergic rhinitis and idiopathic urticaria. It is available alone as tablets, chewable tablets, and as an oral syrup. It is also available as a bilayer tablet containing immediate release cetirizine and extended release pseudoephedrine.
B) PHARMACOLOGY: Cetirizine is an antihistamine; its principal effects are mediated via selective inhibition of peripheral H1 receptors.
C) TOXICOLOGY: Anticholinergic (primarily antimuscarinic) effects develop in overdose.
D) EPIDEMIOLOGY: Overdose is not common and serious toxicity is extremely rare.
E) WITH THERAPEUTIC USE
1) Reported effects following therapeutic administration include urticaria, constipation, diarrhea, abdominal pain, dry mouth, intrahepatic cholestasis, severe acute hepatitis, weight gain, asthenia, somnolence, sedation, fatigue, headache, and impaired cognition. No clinically significant prolongations of QTc have been observed.
F) WITH POISONING/EXPOSURE
1) MILD TO MODERATE POISONING: Effects are generally mild and include sedation, somnolence, fatigue, restlessness, irritability, and tachycardia. Anticholinergic effects may theoretically occur but have not been reported.
2) SEVERE POISONING: There is one report suggesting torsade de pointes following an ingestion, in a patient who had other risk factors (eg, hypokalemia, renal failure), but this has not been observed in other cases.
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Heent |
3.4.3) EYES
A) WITH THERAPEUTIC USE 1) Conjunctivitis, eye pain, loss of accommodation, ocular hemorrhage, and blindness were observed in less than 2% of 3982 adults and children 12 years and older or in 659 pediatric patients aged 6 to 11 years (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006). A cause and effect relationship has not been established.
2) Oculogyric crisis associated with cetirizine use was reported in 9 patients to the National Registry of Drug-Induced Ocular Side Effects and the Food and Drug Administration. Of these 9, 8 were pediatric patients (range 7 months to 54 years). Doses ranged from 5 mg to 10 mg daily, and symptoms appeared 3 to 184 days after initiation of therapy. All 9 patients had positive dechallenge data and 6 had positive rechallenge data (Fraunfelder & Fraunfelder, 2004).
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Cardiovascular |
3.5.2) CLINICAL EFFECTS
A) CARDIOVASCULAR FINDING 1) WITH THERAPEUTIC USE a) Hypertension, palpitation, tachycardia, and cardiac failure were observed in less than 2% of 3982 adults and children 12 years and older or in 659 pediatric patients aged 6 to 11 years (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
b) In a study in healthy adult males, cetirizine was given at doses up to 6 times the maximum clinical dose for 1 week, and no significant mean QTc prolongation occurred. In another study, cetirizine 20 mg caused a mean increase in QTc of 9.1 msec from baseline after 10 days of therapy. In a 4-week trial in children 6 to 11 years of age, cetirizine 5 mg or 10 mg did not increase QTc, compared with placebo (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
B) HYPOTENSIVE EPISODE 1) WITH THERAPEUTIC USE a) Severe hypotension has been reported rarely in the postmarketing period. No information regarding the population was available (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
C) TORSADES DE POINTES 1) WITH POISONING/EXPOSURE a) CASE REPORT: A 55-year-old woman, with a history of chronic renal failure, developed dizziness after a dialysis session. An ECG demonstrated torsades de pointes with a prolonged QTc interval of 517 ms. Laboratory analysis of the patient, at the end of her dialysis session, revealed hypokalemia (potassium 2.5 mmol/L). Despite treatment with IV magnesium sulfate and potassium chloride, the patient continued to experience episodes of torsades de pointes. Further interview of the patient revealed that she had been taking cetirizine for chronic pruritus. The initially prescribed dose was 10 mg/day for 10 weeks; however, after 2 weeks of treatment, the patient increased her dose to 20 mg/day for 6 weeks, then 30 mg/day for 15 days. The cetirizine was discontinued, and the patient continued her dialysis sessions enriched with potassium (current average potassium level 3.8 mmol/L), and without the recurrence of dysrhythmias. However, six months after discontinuation of the cetirizine, a repeat ECG demonstrated persistent QTc interval prolongation (506 ms) (Renard et al, 2005).
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Neurologic |
3.7.2) CLINICAL EFFECTS
A) ASTHENIA 1) WITH THERAPEUTIC USE a) Asthenia was reported in 5.2% (n=116) of patients receiving cetirizine 10 mg once daily for the treatment of seasonal allergic rhinitis (Gehanno et al, 1996).
B) CENTRAL NERVOUS SYSTEM FINDING 1) WITH THERAPEUTIC USE a) The most frequent CNS adverse reactions reported in placebo-controlled trials with cetirizine (n=2034) were somnolence (13.7%) and fatigue (5.9%). CNS adverse reactions appear to be dose related) (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006; Aaronson, 1996).
b) Clinical trials have shown that sedation may be dose dependent (Falliers et al, 1991; Falliers et al, 1991). In one study, sedation occurred in 23% and 25% of patients receiving cetirizine 10 mg and 20 mg, respectively, as opposed to 9% and 6% of patients receiving cetirizine 5 mg and placebo, respectively (p less than 0.05) (Falliers et al, 1991)
c) Hyperesthesia, hyperkinesia, hypertonia, hypoesthesia, paresthesia, paralysis, and tremor were observed in less than 2% of 3982 adults and children 12 years and older or in 659 pediatric patients aged 6 to 11 years (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
d) PEDIATRIC: In a 1-week study in children 6 to 11 months of age, those who received cetirizine were more irritable and fussy than those who received placebo. In an 18-month study in children 12 months and older, insomnia occurred in 9% of those who received cetirizine and 5.3% of those who received placebo. For patients who received 5 mg or more per day compared with placebo, malaise (3.6% vs 1.8%) and fatigue (3.6% vs 1.3%) occurred more frequently (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
2) WITH POISONING/EXPOSURE a) One adult patient developed somnolence after taking 150 mg of cetirizine but did not have any other clinical signs or abnormal hematology or blood chemistry results. An 18-month-old patient developed restlessness, irritability, and drowsiness after taking an overdose of cetirizine (approximately 180 mg). After a 3-day washout period, he resumed taking the medication as prescribed and exhibited no further signs or symptoms relating to the overdose (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006; Ridout & Tariq, 1997a).
C) HEADACHE 1) WITH THERAPEUTIC USE a) Headache has been reported to occur in up to 40% of patients receiving cetirizine in clinical trials. In some cases, the incidence of headache is similar to that observed in patients on placebo (Lockey et al, 1996).
b) One large study cited headache as the most frequently reported side effect of cetirizine, occurring in approximately 10% to 12% of patients taking 10 mg/day. However, a causal relationship was not established (Davies et al, 1989).
c) In patients aged 6 to 11 years, headache was reported in 12.3% of patients taking placebo (n=309), 11% of those taking 5 mg (n=161), and 14% of those taking 10 mg (n=215) (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
D) IMPAIRED COGNITION 1) WITH THERAPEUTIC USE a) Cetirizine shortens sleep latency (10-mg and 15-mg doses), increases subjective sleepiness (5- to 15-mg doses), and impairs tracking performance (5-mg and 15-mg doses). According to the Royal Air Force School of Aviation Medicine, cetirizine should not be used by air personnel (Nicholson & Turner, 1998). b) According to a study involving 15 healthy volunteers, cetirizine does not impair cognitive performance. Patients were given single doses of cetirizine 5, 10, and 20 mg, diphenhydramine 50 mg, or placebo. Following drug administration patients were subjected to several objective measures of mental performance, including automobile driving simulation, digit symbol substitution, and maze tracking. Measurements were made at 2, 4, 6, 8, and 24 hours postdosing. No differences were detected between placebo and cetirizine at any dose, while diphenhydramine impaired cognitive performance. In addition, diphenhydramine caused subjective feelings of drowsiness, while placebo and cetirizine did not (Gengo et al, 1990). c) In a 4-way, double-blind, randomized, crossover study, the psychomotor effects of cetirizine 10-mg and 20-mg doses were compared with hydroxyzine 25 mg and placebo in 12 subjects. Objective measurements of performance (critical flicker frequency, Stroop word testing, and visual analog drowsiness scales) were measured at 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 36 hours after single oral doses. 1) By all 3 tests, hydroxyzine produced significant decrements in performance compared with placebo at 2 and 4 hours after administration. Neither dose of cetirizine caused statistically significant changes in performance. Subjective symptoms of sedation were reported in 12 cases (100%) after hydroxyzine, twice (16.7%) after placebo, and in 3 subjects (25%) after cetirizine. The investigators concluded that cetirizine lacks significant CNS activity (Gengo et al, 1987).
E) SEDATION 1) WITH THERAPEUTIC USE a) In a single-dose study of cetirizine (0.25 mg/kg; 6.5 to 23.5 months), adverse effects were reported in 3 of 15 infants. These effects included sleepiness, mild vomiting, and increased irritability (Baelde & Dupont, 1992).
b) Somnolence has occurred in 8.6% to 13.7% of patients receiving cetirizine therapy (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006; Grant et al, 1995). However, in a study involving children 2 to 6 years of age, somnolence was reported in less than 2% of patients (Allegra et al, 1993). Generally, cetirizine is well tolerated and CNS adverse effects rarely result in the discontinuance of therapy.
c) Somnolence was reported in 25% of patients taking cetirizine 10 mg or 20 mg as opposed to 6% of patients on placebo. Approximately 50% of patience receiving cetirizine 20 mg described the somnolence as moderate rather than mild in severity (Falliers et al, 1991). It appears that the sedation associated with cetirizine is comparable to the sedation reported with first-generation antihistamines (Anon, 1993).
d) In children 6 to 11 years old, the occurrence of somnolence was 1.3% in placebo (n=309), 1.9% at 5 mg (n=161), and 4.2% at 10 mg (n=215) (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
e) Cetirizine shortens sleep latency (10-mg and 15-mg doses), increases subjective sleepiness (5- to 15-mg doses), and impairs tracking performance (5-mg and 15-mg doses). According to the Royal Air Force School of Aviation Medicine, cetirizine should not be used by air personnel (Nicholson & Turner, 1998).
f) In a pediatric study of children aged 2 to 6 years who had perennial allergic rhinitis, cetrizine treatment caused sleepiness in 8% of patients (n=50). None of the patients withdrew from the study due to side effects (De Benedictis et al, 1997).
g) Another study reported a 22% incidence of sedation in 26 patients taking 10 mg/day (Arendt & Bernheim, 1989).
h) In a study involving the symptomatic treatment of allergic rhinitis, there was a slightly higher incidence of drowsiness associated with the 20-mg dose compared with the 10-mg dose. Overall, the incidence of drowsiness was not statistically different between treatment groups and placebo (Mansmann et al, 1992).
i) In a comparative study, cetirizine 10 mg was associated with marked feelings of drowsiness. Patients tested for impaired driving ability demonstrated a slight degree of impairment in road tracking ability and in maintaining constant driving speed (Ramaekers et al, 1992).
j) No significant differences in sedation were observed between cetirizine 10 mg, terfenadine 120 mg, loratadine 10 mg, astemizole 10 mg, and placebo in a crossover, single-dose study (Simons et al, 1987).
2) WITH POISONING/EXPOSURE a) One adult patient developed somnolence after taking 150 mg of cetirizine but did not have any other clinical signs or abnormal hematology or blood chemistry results. An 18-month-old patient developed restlessness, irritability, and drowsiness after taking an overdose of cetirizine (approximately 180 mg). After a 3-day washout period, he resumed taking the medication as prescribed and exhibited no further signs or symptoms relating to the overdose (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006; Ridout & Tariq, 1997a).
b) A 4-year-old boy accidently ingested 60 mg of cetirizine. Vomiting was induced 1.5 hours following ingestion. He became severely drowsy; however, he recovered completely after 5 to 6 hours without any treatment. His ECG remained normal (Hansen & FeilbergJorgensen, 1998).
F) SEIZURE 1) WITH THERAPEUTIC USE a) Seizures have been reported rarely in the postmarketing period. No information regarding the population was available (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
G) EXTRAPYRAMIDAL MOVEMENTS 1) WITH THERAPEUTIC USE a) OROFACIAL DYSKINESIA 1) Orofacial dyskinesia has been reported rarely in the postmarketing period. No information regarding the population was available (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
b) DYSTONIA 1) CASE REPORT: A 6-year-old boy presented with dystonia after taking cetirizine (5 mg/day) for 3 days. His symptoms of involuntary deviation of the jaw to the left side and inability to swallow started 10 hours before presentation. Following the discontinuation of cetirizine and treatment with biperiden, his symptoms resolved completely (Esen et al, 2008).
2) CASE REPORT: A 4-year-old girl with a strong family history of drug-induced dystonia developed dystonic movements (unusual head and upper movements, eye tic, frequent shoulder shrugging, and intermittent retrocollis) after taking cetirizine 5 mg/day for 18 days. Eight weeks after the last dose of cetirizine, her symptoms resolved (Rajput & Baerg, 2006).
H) FATIGUE 1) WITH THERAPEUTIC USE a) In an 18-month study of children12 months and older, fatigue (3.6% vs 1.3%) and malaise (3.6% vs 1.8%) occurred more frequently in patients who received cetirizine 5 mg/day, compared with placebo (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
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Gastrointestinal |
3.8.2) CLINICAL EFFECTS
A) GASTROINTESTINAL TRACT FINDING 1) WITH THERAPEUTIC USE a) Cetirizine is well tolerated with minimal gastrointestinal (GI) side effects. In clinical trials (n=3982), the following side effects were reported in less than 2% of patients: eructation, increased appetite, dyspepsia, gastritis, melena, tongue edema and discoloration, abdominal pain, diarrhea, flatulence, constipation, vomiting, rectal hemorrhage, and ulcerative stomatitis. The causal relationship of these reported GI effects to cetirizine has not been established (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
B) CONSTIPATION 1) WITH THERAPEUTIC USE a) In a single study, constipation occurred in 1 patient taking cetirizine 10 mg daily. A cause-effect relationship was not established (Arendt & Bernheim, 1989).
C) DIARRHEA 1) WITH THERAPEUTIC USE a) Diarrhea has been noted occasionally with cetirizine doses of 20 mg/day (Kurzeja et al, 1989; Juhlin & Arendt, 1988).
D) APTYALISM 1) WITH THERAPEUTIC USE a) Xerostomia has been infrequently reported as a minor side effect with therapeutic doses of cetirizine (Arendt & Bernheim, 1989; Juhlin & Arendt, 1988).
b) Dry mouth occurred frequently in patients 12 years old or older, with an occurrence rate of 5% with cetirizine (n=2034) and 2.3% with placebo (n=1612) (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
E) ABDOMINAL PAIN 1) WITH THERAPEUTIC USE a) Abdominal pain occurred infrequently in children 6 to 11 years old, with an occurrence of 1.9% in placebo (n=309), 4.4% at 5 mg (n=161), and 5.6% at 10 mg (n=215) (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
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Hepatic |
3.9.2) CLINICAL EFFECTS
A) CHOLESTASIS 1) WITH THERAPEUTIC USE a) Intrahepatic cholestasis occurred in a 28-year-old man after a 2-year course of cetirizine 10 mg/day for allergic rhinitis; he had no history of hepatobiliary disease. Presenting symptoms included jaundice, scleral icterus, and generalized pruritus. Laboratory results showed alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, and total bilirubin to be abnormally high. The patient developed generalized fatigue, anorexia, weight loss (7 kg), and acholic stools. A percutaneous ultrasound-guided liver biopsy showed prominent hepatocanalicular cholestasis and mild hepatocellular necrosis. Cetirizine was withdrawn; hydroxyzine 50 mg 4 times a day was used as needed for pruritus. Ursodeoxycholic acid 250 mg/day titrated over 10 days to 1250 mg/day was given for cholestasis and continued for approximately 8 weeks. The patient gradually improved, and after 10 weeks, liver enzymes (except ALT) had decreased. A cause and effect relationship was not established (Fong et al, 2000).
B) INJURY OF LIVER 1) WITH THERAPEUTIC USE a) CASE REPORT: Severe acute hepatitis occurred in a 23-year-old man after use of cetirizine for atopic dermatitis. The patient had been taking cetirizine 10 mg/day for approximately 9 months prior to admission; cetirizine was the only medication he was using. He presented with jaundice and general malaise. Laboratory results included serum total bilirubin 5.8 mg/dL, AST 1728 units/L, ALT 2475 units/L, and prothrombin time 17.6 seconds. Prednisolone was initiated at 60 mg/day for 3 days, followed by 40 mg/day for 3 days, and 30 mg/day for 3 days. Serum total bilirubin peaked at 10.8 mg/dL on day 4 and gradually decreased. AST and ALT declined rapidly. Liver biopsy on day 38 indicated convalescent-stage acute hepatitis. By day 44, all laboratory values had normalized. A lymphocyte stimulation test to cetirizine hydrochloride was positive (Watanabe et al, 2001).
b) CASE REPORT: A 26-year-old man developed recurrent episodes of hepatitis associated with the use of cetirizine (Pompili et al, 2004).
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Genitourinary |
3.10.2) CLINICAL EFFECTS
A) GLOMERULONEPHRITIS 1) WITH THERAPEUTIC USE a) Glomerulonephritis has been reported rarely in the postmarketing period. No information regarding the population was available (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
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Hematologic |
3.13.2) CLINICAL EFFECTS
A) THROMBOCYTOPENIC DISORDER 1) WITH THERAPEUTIC USE a) Thrombocytopenia has been reported rarely in the postmarketing period. No information regarding the population was available (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
B) HEMOLYTIC ANEMIA 1) WITH THERAPEUTIC USE a) Hemolytic anemia has been reported rarely in the postmarketing period. No information regarding the population was available (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
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Dermatologic |
3.14.2) CLINICAL EFFECTS
A) URTICARIA 1) WITH THERAPEUTIC USE a) Several cases of generalized urticaria along with pruritus and facial edema have been reported 1 to 4 hours after administration of cetirizine 10 mg (Schroter et al, 2002; Calista et al, 2001; Tella et al, 2002).
b) Generalized urticaria developed in a 42-year-old woman 2 hours after she took a 10-mg tablet of cetirizine for allergic rhinitis. Her dermatitis resolved over 7 days with discontinuation of cetirizine and treatment with oral prednisolone. After a washout period, she underwent provacative testing. Cetirizine skin prick and intradermal tests were negative. Cetirizine drops of 5 mg orally elicited no response. However, when she received cetirizine 10 mg in oral drops, she developed wheals on her scalp after 30 minutes; progressive urticaria spread over her face, neck, trunk, and arms. A further course of prednisolone cleared this outbreak (Calista et al, 2001).
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Immunologic |
3.19.2) CLINICAL EFFECTS
A) ANAPHYLAXIS 1) WITH THERAPEUTIC USE a) Anaphylaxis has been reported rarely in the postmarketing period. No information regarding the population was available (Prod Info ZYRTEC(R) oral tablets, chewable oral tablets, oral syrup, 2006).
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Reproductive |
3.20.1) SUMMARY
A) Levocetirizine is in pregnancy category B. Cetirizine hydrochloride 5 mg/pseudoephedrine hydrochloride 120 mg is in pregnancy category C. Cetirizine was not teratogenic in experimental animals. Cetirizine has been reported to be excreted in human breastmilk.
3.20.2) TERATOGENICITY
A) LACK OF EFFECT 1) In a study of 39 women who were exposed to cetirizine during organogenesis, there was no significant difference in the rates of major or minor anomalies, compared with controls (Einarson et al, 1997).
B) ANIMAL STUDIES 1) CETIRIZINE a) In rabbits, rats, and mice, cetirizine was not teratogenic at oral doses up to 225, 135, and 96 mg/kg, respectively (approximately 220, 180, and 40 times the maximum recommended oral daily dose in adults on a mg/m(2) basis) (Prod Info Zyrtec(R), 2004).
2) LEVOCETIRIZINE a) In rat and rabbits, levocetirizine was not teratogenic at oral doses approximately 320 and 390, respectively, times the maximum recommended daily oral dose in adults on a mg/m(2) basis (Prod Info levocetirizine dihydrochloride oral tablets, 2015; Prod Info levocetirizine dihydrochloride oral solution, 2014)
3.20.3) EFFECTS IN PREGNANCY
A) CETIRIZINE HYDROCHLORIDE 1) RISK SUMMARY a) There are no adequate studies in pregnant women (Prod Info Zyrtec(R), 2004).
B) LEVOCETIRIZINE DIHYDROCHLORIDE 1) PREGNANCY CATEGORY a) Levocetirizine dihydrochloride is categorized as pregnancy category B (Prod Info levocetirizine dihydrochloride oral tablets, 2015; Prod Info levocetirizine dihydrochloride oral solution, 2014).
b) There are no adequate studies in pregnant women (Prod Info levocetirizine dihydrochloride oral tablets, 2015; Prod Info levocetirizine dihydrochloride oral solution, 2014).
C) CETIRIZINE HYDROCHLORIDE/PSEUDOEPHEDRINE HYDROCHLORIDE 1) PREGNANCY CATEGORY a) Cetirizine hydrochloride/pseudoephedrine hydrochloride is categorized as pregnancy category C (Prod Info ZYRTEC-D 12 HOUR(R) extended release tablets, 2003).
D) LACK OF EFFECT 1) A study of 39 women who were exposed to cetirizine during organogenesis revealed no significant differences, compared with controls, in pregnancy outcome: rate of live births, spontaneous abortion, stillbirth, mean birth weight, mode of delivery, presence of neonatal distress, or gestational age (Einarson et al, 1997).
3.20.4) EFFECTS DURING BREAST-FEEDING
A) HUMAN MILK 1) Cetirizine has been reported to be excreted in human breastmilk (Prod Info Zyrtec(R), 2004).
B) ANIMAL STUDIES 1) CETIRIZINE a) Cetirizine caused retarded pup weight gain in mice during lactation at an oral dose approximately 40 times the maximum recommended oral daily dose in adults on mg/m(2) basis). In beagle dogs, approximately 3% of the dose was excreted in milk (Prod Info Zyrtec(R), 2004).
3.20.5) FERTILITY
A) LACK OF EFFECT 1) In a study in mice, cetirizine did not impair fertility at an oral dose of 64 mg/kg (approximately 25 times the maximum recommended oral daily dose in adults on a mg/m(2) basis) (Prod Info Zyrtec(R), 2004).
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Carcinogenicity |
3.21.4) ANIMAL STUDIES
A) LIVER TUMORS 1) In a 2-year study in mice, an increased incidence of benign liver tumors was observed in males at a dietary dose of 16 mg/kg (approximately 3 times the maximum recommended daily oral dose in infants on a mg/m(2) basis or approximately 6 times the maximum recommended daily oral dose in adults on a mg/m(2) basis). a) At a dietary dose of of 4 mg/kg, there was no increase in the incidence of liver tumors in mice (approximately equivalent to the maximum recommended daily oral dose in infants on a mg/m(2) basis or approximately 2 times the maximum recommended daily oral dose in adults on a mg/m(2) basis (Prod Info Zyrtec(R), 2004).
B) LACK OF EFFECT 1) In a 2-year study in rats, cetirizine was not carcinogenic at doses up to 20 mg/kg (approximately 7 times the maximum recommended daily oral dose in infants on and mg/m(2) basis or approximately 15 times the maximum recommended daily oral dose in adults on a mg/m(2) basis) (Prod Info Zyrtec(R), 2004).
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Genotoxicity |
A) Cetirizine was not mutagenic in the Ames test, and not clastogenic in the mouse lymphoma assay, the human lymphocyte assay, and in vivo micronucleus test in rats (Prod Info Zyrtec(R), 2004).
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