Controlled and uncontrolled clinical trials conducted in the United States and Canada included more than 6,000 patients aged 12 years and older, with more than 3,900 receiving Cetirizine dihydrochloride at doses of 5 to 20 mg per day. The duration of treatment ranged from 1 week to 6 months, with mean exposure of 30 days.
Most adverse reactions reported during therapy with Cetirizine dihydrochloride were mild to moderate. In placebo-controlled trails, the incidence of discontinuations due to adverse reactions in patients receiving Cetirizine dihydrochloride 5 or 10 mg was not significantly different from placebo (2.9% vs. 2.4%, respectively).
The most common adverse reaction in patients aged 12 years and older that occurred more frequently on Cetirizine dihydrochloride was dose related than placebo was somnolence. The incidence of somnolence associated with Cetirizine dihydrochloride was dose related, 6% in placebo. 11% at 5 mg and 14% at 10 mg. Discontinuation due to somnolence for Cetirizine dihydrochloride were uncommon (1.0% on Cetirizine dihydrochloride vs. 0.6% on placebo). Fatigue and dry mouth also appeared to be treatment-related adverse reactions.
Table 1 lists adverse experiences in patients aged 12 years and older which was reported for Cetirizine dihydrochloride 5 and 10 mg in controlled clinical trials in the United States and that were more common with Cetirizine dihydrochloride than placebo. (See Table 1.)
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In addition, headache and nausea occurred in more than 2% of the patients, but were common in placebo patients.
Pediatric studies were also conducted with Cetirizine dihydrochloride. More than 1300 pediatric patients aged 6 to 11 years with more than 900 treated with Cetirizine dihydrochloride at doses of 1.25 to 10 mg per day were included in controlled and uncontrolled clinical trials conducted in the United States. The duration of treatment ranged from 2 to 12 weeks. Placebo-controlled trials up to 4 weeks duration included 168 pediatric patients aged 2 to 5 years who received cetirizine, the majority of whom received single daily doses of 5 mg. A placebo-controlled trial 18 months in duration included 399 patients aged 12 to 24 months treated with cetirizine (0.25 mg/kg bid), and another placebo-controlled trial of 7 days duration included 42 patients aged 6 to 11 months who were treated with cetirizine (0.25 mg/kg bid).
The majority of adverse reactions reported in pediatric patients aged 2 to 11 years with Cetirizine dihydrochloride was uncommon (0.4% on Cetirizine dihydrochloride vs. 1.0% on placebo.
Table 2 lists adverse experiences which were reported for Cetirizine dihydrochloride 5 and 10 mg in pediatric patients aged 6 to 11 years in placebo-controlled clinical trials in the United States and were more common with Cetirizine dihydrochloride than placebo. Of these, abdominal pain was considered treatment-related and somnolence appeared to be dose-related. 1.3% in placebo, 1.9% at 5 mg, and 4.2 % at 10 mg. The adverse experiences reported in pediatric patients aged 2 to 5 years in placebo-controlled trials were qualitatively similar in nature and generally similar in frequency to those reported in trial with children aged 6 to 11 years.
In the placebo-controlled trials of pediatric patients 6 to 24 months of age, the incidences of adverse experiences, were similar in the cetirizine and placebo treatment groups in each study. Somnolence occurred with essentially the same frequency in patients who received cetirizine and patients who received placebo. In a study of 1-week duration in children 6-11 months of age, patients who received cetirizine exhibited greater irritability/fussiness than patients on placebo. In a study of 18 months duration in patients 12 months and older, insomnia occurred more frequently in patients who received placebo (9.0% v. 5.3%). In those patients who received placebo, fatigue (3.6% v. 1.3%) and malaise (3.6% v. 1.8%) occurred more frequently. (See Table 2.)
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The following events were observed infrequently (less than 2%), in either 3982 adults and children 12 years and older or in 659 pediatric patients aged 6 to 11 years who received Cetirizine dihydrochloride in U.S. trials, including an open adult study of six months duration. A causal relationship of these infrequent events with Cetirizine dihydrochloride administration has not been established.
Autonomic Nervous System: Anorexia, flushing, increased salivation, urinary retention.
Cardiovascular: Cardiac failure, hypertension, palpitation, tachycardia.
Central and Peripheral Nervous Systems: Abnormal coordination, ataxia, confusion, dysphonia, hyperesthesia, hypertonia, hypoesthesia, leg cramps, migraine, myelitis, paralysis, paresthesia, ptosis, syncope, tremor, twitching, vertigo, visual field effect.
Gastrointestinal: Abnormal hepatic function, aggravated tooth caries, constipation, dyspepsia, eructation, flatulence, gastritis, hemorrhoids, increased appetite, melena, rectal hemorrhage, stomatitis including ulcerative stomatitis, tongue discoloration, tongue edema.
Genitourinary: Cystitis, dysuria, hematuria, micturition frequency, polyuria, urinary incontinence, urinary tract infection.
Hearing and vestibular: Deafness, earache, ototoxicity, tinnitus.
Metabolic/Nutritional: Dehydration, diabetes mellitus, thirst.
Musculoskeletal: Arthralgia, arthritis, arthrosis, muscle weakness, myalgia.
Psychiatric: Abnormal thinking, agitation, amnesia, anxiety, decreased libido, depersonalization, depression, emotional liability, euphoria, impaired concentration, insomnia, nervousness, paroniria, sleep disorder.
Respiratory System: Bronchitis, dyspnea, hyperventilation, increased sputum, pneumonia, respiratory disorder, rhinitis, sinusitis, upper respiratory tract infection.
Reproductive: Dysmenorrhea, female breast pain, intermenstrual bleeding, leukorrhea, menorrhagia, vaginitis.
Skin: Acne, alopecia, angioedema, bullous eruption, dermatitis, dry skin, eczema, erythematous rash, furunculosis, hyperkeratosis, hypertrichosis, increased sweating, maculopapular rash, photosensitivity reaction, Photosensitivity toxic reaction, pruritus, purpura, rash, seborrhea, skin disorder, skin nodule, urticaria.
Special senses: Parosmia, taste loss, taste perversion.
Vision: Blindness, conjunctivitis, eye pain, glaucoma, loss of accommodation, ocular hemorrhage, xerophthalmia.
Body as a Whole: Accidental injury, asthenia, back pain, chest pain, enlarge abdomen, face edema, fever, generalized edema, hot flashes, increased weight, leg edema, malaise, nasal polyp, pain, pallor, periorbital edema, peripheral edema, rigors.
Occasional instances of transient, reversible hepatic transaminase elevations have occurred during cetirizine therapy. Hepatitis with significant transaminase elevation and elevated bilirubin in association with the use of Cetirizine dihydrochloride has been reported.
In foreign marketing experience the following additional rare, but potentially severe adverse events have been reported: Anaphylaxis, cholestasis, glomerulonephritis, hemolytic anemia, hepatitis, orofacial dyskinesia, severe hypotension, stillbirth, and thrombocytopenia.