Cetirizine Hydrochloride Oral Solution

INDICATIONS & USAGE Perennial Allergic Rhinitis: Cetirizine Hydrochloride Oral Solution, USP is indicated for the relief of symptoms associated with perennial allergic rhinitis due to allergens such as dust mites, animal dander and molds in children 6 to 23 months of age. Symptoms treated effectively include sneezing, rhinorrhea, postnasal discharge, nasal pruritus, ocular pruritus, and tearing. Chronic Urticaria: Cetirizine Hydrochloride Oral Solution, USP is indicated for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in children 6 months to 5 years of age. It significantly reduces the occurrence, severity, and duration of hives and significantly reduces pruritus.

DOSAGE & ADMINISTRATION Cetirizine Hydrochloride Oral Solution, USP can be taken without regard to food consumption. Children 2 to 5 Years for Chronic Urticaria: The recommended initial dose of Cetirizine Hydrochloride Oral Solution,USP in children aged 2 to 5 years is 2.5 mg (½ teaspoonful) oral solution once daily. The dosage in this age group can be increased to a maximum dose of 5 mg per day given as 1 teaspoonful oral solution once a day, or one ½ teaspoonful oral solution given every 12 hours. Children 6 months to < 2 years for Perennial Allergic Rhinitis and Chronic Urticaria: The recommended dose of Cetirizine Hydrochloride Oral Solution, USP in children 6 months to 23 months of age is 2.5 mg (½ teaspoonful) once daily. The dose in children 12 to 23 months of age can be increased to a maximum dose of 5 mg per day, given as ½ teaspoonful (2.5 mg) every 12 hours.

CONTRAINDICATIONS Cetirizine Hydrochloride Oral Solution, USP is contraindicated in those patients with a known hypersensitivity to it or any of its ingredients or hydroxyzine.

ADVERSE REACTIONS Pediatric studies were conducted with cetirizine hydrochloride. More than 1300 pediatric patients aged 6 to 11 years with more than 900 treated with cetirizine hydrochloride 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 hydrochloride were mild or moderate. In placebo-controlled trials, the incidence of discontinuations due to adverse reactions in pediatric patients receiving up to 10 mg of cetirizine hydrochloride was uncommon (0.4% on cetirizine hydrochloride vs. 1.0% on placebo). Table 1 lists adverse experiences which were reported for cetirizine hydrochloride 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 hydrochloride 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 trials 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 cetirizine compared to patients who received placebo (9.0% v. 5.3%). In those patients who received 5 mg or more per day of cetirizine as compared to patients who received placebo, fatigue (3.6% v. 1.3%) and malaise (3.6% v. 1.8%) occurred more frequently. Table 1. Adverse Experiences Reported in Pediatric Patients Aged 6 to 11 Years in Placebo-Controlled United States Cetirizine Hydrochloride Trials (5 or 10 mg Dose) Which Occurred at a Frequency of ≥ 2% in Either the 5 mg or the 10 mg Cetirizine Hydrochloride Group, and More Frequently Than in the Placebo Group Adverse Experiences Placebo (N=309) Cetirizine Hydrochloride 5 mg (N=161) 10mg (N=215) Headache 12.3% 11.0% 14.0% Pharyngitis 2.9% 6.2% 2.8% Abdominal Pains 1.9% 4.4% 5.6% Coughing 3.9% 4.4% 2.8% Somnolence 1.3% 1.9% 4.2% Diarrhea 1.3% 3.1% 1.9% Epistaxis 2.9% 3.7% 1.9% Bronchospasm 1.9% 3.1% 1.9% Nausea 1.9% 1.9% 2.8% Vomiting 1.0% 2.5% 2.3% The following events were observed infrequently (less than 2%), in either 3,982 adults and children 12 years and older or in 659 pediatric patients aged 6 to 11 years who received cetirizine hydrochloride in U.S. trials, including an open adult study of six months duration. A causal relationship of these infrequent events with cetirizine hydrochloride 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, hyperkinesia, hypertonia, hypoesthesia, leg cramps, migraine, myelitis, paralysis, paresthesia, ptosis, syncope, tremor, twitching, vertigo, visual field defect. 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 !ability, 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. Reticuloendothelial: lymphadenopathy. 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, enlarged 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 hydrochloride has been reported. Post-Marketing Experience In the post-marketing period, the following additional rare, but potentially severe adverse events have been reported: aggressive reaction, anaphylaxis, cholestasis, convulsions, glomerulonephritis, hallucinations, hemolytic anemia, hepatitis, orofacial dyskinesia, severe hypotension, stillbirth, suicidal ideation, suicide, thrombocytopenia, acute generalized exanthematous pustulosis (AGEP) and rebound pruritus-pruritus within a few days after discontinuation of cetirizine, usually after long-term use (e.g., months to years) of cetirizine. To report SUSPECTED ADVERSE REACTIONS, contact Apozeal Pharmaceuticals Inc. at tel: 1-833-688-7848 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.