Jocet-10

Cetirizine dihydrochloride.

Each film-coated tablet contains: Cetirizine dihydrochloride, BP 10 mg.
Cetirizine Dihydrochloride is a potent antihistamine with a low potential for drowsiness at pharmacologically active doses and with additional anti-allergic properties. It is a selective H₁ antagonist with negligible effects on other receptors and so virtually free from anti-cholinergic and anti-serotonin effects. Cetirizine Dihydrochloride inhibits the histamine-mediated 'early' phase of the allergic reaction and also reduces the migration of inflammatory cell such as eosinophils and the release of mediators associated with the 'late' allergic response.

Pharmacology: Pharmacokinetics: Peak blood levels of the order of 0.3 microorganisms/mL are reached between thirty and sixty minutes after oral administration at a 10 mg dose of Cetirizine Dihydrochloride. Its plasma half-life is approximately 11 hours. Absorption is very consistent from one subject to the next. Its renal clearance is 30 mL/minute and the excretion half-life is approximately nine hours. Cetirizine Dihydrochloride is strongly bound to plasma proteins.

Seasonal Allergic Rhinitis: Cetirizine Dihydrochloride is indicated for the relief of symptoms associated with seasonal allergic rhinitis due to allergens such as ragweed, grass and tree pollens in adults and children 2 years of age and older. Symptoms treated effectively include sneezing, rhinorrhea, nasal pruritus, ocular pruritus, tearing, and redness of the eyes.
Perennial Allergic Rhinitis: Cetirizine dihydrochloride is indicated for the relief of symptoms associated perennial allergic rhinitis due to allergens such as dust mites, animal dander and molds in adults and children 6 months of age and older. Symptoms treated effectively include sneezing, rhinorrhea, postnasal discharge, nasal pruritus, ocular pruritus and tearing.
Chronic Urticaria: Cetirizine dihydrochloride is indicated for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 6 months of age and older. It significantly reduces the occurrence, severity, and duration of hives and significantly reduces pruritus.

Adults and children 12 Years and Older: The recommended initial dose of Cetirizine dihydrochloride is 5 or 10 mg per day in adults and children 12 years and older, depending on symptom severity. Most patients in clinical trials started at 10 mg. Cetirizine dihydrochloride is given in a single daily dose, with or without food. The time of administration may be varied to such individual patient needs.
Children 6 to 11 years: The recommended initial dose of Cetirizine dihydrochloride in children 6 to 11 years is 5 or 10 mg (1 or 2 teaspoons) once daily depending on symptom severity. The time of administration may be varied to suit individual patient needs.
Children 2 to 5 years: The recommended initial dose of Cetirizine dihydrochloride syrup in children aged 2 to 5 years is 2.5 mg (½ teaspoon) once daily. The dosage in this age group can be increased to a maximum dose of 5 mg per day given as 1 teaspoon (5 mg) once daily, or as ½ teaspoonful (2.5 mg) given every 12 hours.
Children 6 months to <2 years: The recommended dose of Cetirizine dihydrochloride syrup in children 6 months to 23 months of age is 2.5 mg (½ teaspoon) 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.
Dose Adjustment for Renal and Hepatic Impairment: In patients 12 years of age and older with decreased renal function (creatinine clearance 11-31 mL/min), patients on hemodialysis (creatinine clearance 7 mL/min), and hepatically impaired patients, a dose of 5 mg once daily is recommended. Similarly, pediatric patients aged 6 to 11 years with impaired renal or hepatic function should use the lower recommended dose. Because of the difficulty in reliably administering doses of less than 2.5 mg (½ teaspoon) of Cetirizine dihydrochloride syrup and in the absence of pharmacokinetic and safety information for cetirizine in children below the age of 6 years with impaired renal or hepatic function, its use in this impaired patient population is not recommended. Or as prescribed by the physician.

Drowsiness can be a symptom of overdosage, occurring from administration of 50 mg of cetirizine as a single dose. To date, there is no specific antidote. In case of massive overdosage, gastric lavage should be performed as soon as possible. Usual supportive measures should be provided and routine observations carried out regularly.

Cetirizine dihydrochloride is contraindicated in those patients with a known hypersensitivity to it or any of its ingredients or hydroxyzine.

Activities Requiring Mental Alertness: In clinical trials, the occurrence of somnolence has been reported in some patients taking Cetirizine dihydrochloride, due caution should therefore be exercised when driving a car or operating potentially dangerous machinery. Concurrent use of Cetirizine dihydrochloride with alcohol or other CNS depressants should be avoided because additional reductions in alertness and additional impairment of CNS performance may occur.
Drug-Drug Interactions: No clinically significant drug interactions have been found with theophylline at a low dose, azithromycin, pseudoephedrine, ketoconazole, or erythromycin. There was a small decrease in the clearance of cetirizine caused by a 400-mg dose of theophylline, it is possible that larger theophylline doses could have a greater effect.
Carcinogenesis, Mutagenesis and Impairment of Fertility: In a 2-year carcinogenicity study in rats, cetirizine was not carcinogenic at dietary doses up to 20 mg/kg (approximately 15 times the maximum recommended daily oral dose in adults on a mg/m² basis, or approximately 7 times the maximum recommended daily oral dose in infants on a mg/m² basis). In a 2-year carcinogenicity study in mice, cetirizine caused an increased incidence of benign liver tumors in males at a dietary dose of 16 mg/kg (approximately 6 times the maximum recommended daily oral dose in adults on a mg/m² basis, or approximately 3 times the maximum recommended daily oral dose in infants on a mg/m² basis). No increase in the incidence of liver tumors was observed in mice at a dietary dose of 4 mg/kg (approximately 2 times the recommended maximum daily oral dose the maximum recommended daily dose in adults on a mg/m² basis or approximately 3 times the maximum recommended daily oral dose in infants on a mg/m² basis). The clinical significance of these findings during long-term use of Cetirizine dihydrochloride is not known.
Cetirizine was not mutagenic in the Ames test, and not clastogenic in the human lymphocyte assay, the mouse lymphoma assay, and in vivo micronucleus test in rats.
In a fertility and general reproductive performance study in mice, cetirizine did not impair fertility at an oral dose of 64 mg/kg (approximately 25 times the maximum recommended daily oral dose in adults on a mg/m² basis).
Pregnancy Category B: In mice, rats and rabbits, cetirizine was not teratogenic at oral doses up to 96, 225, and 135 mg/kg, respectively (approximately 40, 180, and 220 times the maximum recommended daily oral dose in adults on a mg/m²) basis. There are no adequate and well-controlled studies in pregnant women.
Because animal studies are not always predictive of human response, Cetirizine dihydrochloride should be used in pregnancy only if clearly needed.
Nursing Mothers: In mice, cetirizine caused retarded pup weight gain during lactation at an oral dose in dams of 96 mg/kg (approximately 40 times the maximum recommended daily oral dose in adults on a mg/m² basis). Studies in beagle dogs indicated that approximately 3% of the dose was excreted in milk. Cetirizine has been reported to be excreted in human breast milk. Because many drugs are excreted in human breast milk, use of Cetirizine dihydrochloride in nursing mothers is not recommended.
Use in Children: The safety of Cetirizine dihydrochloride has been demonstrated in pediatric patients aged 6 months to 11 years. The safety of Cetirizine dihydrochloride, at daily doses of 5 or 10 mg, has been demonstrated in 376 pediatric patients aged 6 to 11 years in placebo-controlled trials of up to 4 weeks and in 254 patients in a non-placebo-controlled 12-week trial. The safety of cetirizine has been demonstrated in 168 patients received between 0.2 and 0.4 mg/kg of cetirizine HCl. The safety of cetirizine in 399 patients aged 12 to 24 months has been demonstrated in a placebo-controlled 18-month trial, in which the average dose was 0.25 mg/kg bid, corresponding to a range of 4 to 11 mg/day. The safety of Cetirizine dihydrochloride syrup has been demonstrated in 42 patients aged 6 to 11 months in a placebo-controlled 7-day trial. The prescribed dose was 0.25 mg/kg, which corresponded to a mean of 4.5 mg/day with a range of 3.4 to 6.2 mg/day.
The effectiveness of Cetirizine dihydrochloride for the treatment of allergic rhinitis and chronic idiopathic urticaria in pediatric patient aged 6 to 11 years is based on an extrapolation of the demonstrated efficacy of Cetirizine dihydrochloride in adults with these conditions and the likelihood the disease course, pathophysiology and the drug's effect are substantially similar between these two populations. Efficacy is extrapolated down to 6 months of age for perennial allergic rhinitis and down to 2 years of age for seasonal allergic rhinitis because these diseases are thought to occur down to these ages in children. The recommended doses for the pediatric population are based on cross-study comparisons of the pharmacokinetics and pharmacodynamics of cetirizine in adults and pediatric subjects and on the safety profile of cetirizine in both adult and pediatric patients at doses equal to or higher than the recommended doses. The cetirizine AUC and C_max in pediatric subjects aged 6 to 11 years who received single dose of 20 mg of cetirizine tablets.
The saftey and effectiveness of cetirizine in pediatric patients under the age of 6 months have not been established.
Use in Elderly: Of the total number of patients in clinical studies of Cetirizine dihydrochloride, 186 patients were 65 years and older, and 39 patients were 75 years and older. No overall differences in safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. With regards to efficacy, clinical studies of Cetirizine dihydrochloride for each approved indication did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients.
Cetirizine dihydrochloride is known to be substantially excreted by the kidney and the risk of toxic reactions to the drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Pregnancy: No adverse effects have been reported in animal studies. There has been little or no use of cetirizine in pregnancy. As with other drugs the use of cetirizine should be avoided.

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.
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, 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.

No clinically significant drug interactions have been found with theophylline at a low dose, azithromycin, pseudoephedrine, ketoconazole, or erythromycin. There was a small decrease in the clearance of cetirizine caused by a 400-mg dose of theophylline; it is possible that larger theophylline doses could have a greater effect.

Store at temperatures not exceeding 30°C.

Antihistamines & Antiallergics

R06AE07 - cetirizine ; Belongs to the class of piperazine derivatives used as systemic antihistamines.

Non-Rx