| CLARITIN® |
|Histamine H1-Receptor Antagonist |
|Action And Clinical Pharmacology: Loratadine is a long-acting tricyclic antihistamine with selective peripheral H1-receptor antagonistic activity. It exhibits a dose-related inhibition of the histamine-induced skin wheal and flare response in humans which is rapid in onset, is apparent at 2 hours and persists throughout the 24-hour observation period. Single oral doses up to 160 mg and repeat daily doses of 40 mg for up to 13 weeks were well tolerated with the incidence of sedation and dry mouth being no different from placebo.
Pharmacokinetics: 4C-loratadine is rapidly absorbed reaching Cmax values (4.7, 10.8 and 26.1 ng/mL) at 1.5, 1.0 and 1.3 hours for the 10, 20 and 40 mg dose, respectively. The loratadine elimination half-life (t 1/2 b) ranged from 7.8 to 11 hours. Descarboethoxyloratadine, the major active metabolite, reached Cmax values (4.0, 9.9 and 16.0 ng/mL) at 3.7, 1.5 and 2.0 hours after a dose of 10, 20 and 40 mg, respectively. Its t 1/2 b ranged from 17 to 24 hours. The accumulation indices, calculated by Cmax and the area under the curve (AUC) ratios, did not change after the 5th day, indicating little or no accumulation of either loratadine or its metabolite after a multiple once per day dosage regimen. The t 1/2 b at steady-state levels for loratadine and its metabolite were 14.4 and 18.7 hours, respectively, similar to that reported following a single oral dose.
The confidence intervals for Cmax and AUCo-ą are within the 80 to 125% range indicating that the Claritin Rapid Dissolve Tongue Tablets were bioequivalent with respect to the active metabolite descarboethoxyloratadine.
After administration of a single 10 mg dose of loratadine as either the Rapid Dissolve Tongue Tablet, a conventional tablet, or the syrup formulation (1mg/mL), peak plasma concentrations of loratadine and its metabolite were achieved at approximately 1 and 2 hours, respectively; mean elimination half-life of the active metabolite ranged between 19 and 21 hours. See Tables I and II.
Following administration of 10 mg of loratadine once daily for 10 days as either a Rapid Dissolve Tongue tablet or a conventional tablet, plasma concentrations of loratadine and its active metabolite were at steady state by day 5 with both formulations. Mean peak plasma concentrations (Tmax) of loratadine and its metabolite in both formulations were attained at 1.3 hours; peak to trough fluctuations observed for the Rapid Dissolve Tongue tablet and the conventional tablet were similar with respect to loratadine and its metabolite. Mean elimination half-life of the active metabolite was 20 hours for both formulations. See Table III.
In a single-dose, 2-way cross-over study with Claritin Rapid Dissolve Tongue Tablets, food increased the AUC of loratadine and descarboethoxyloratadine by 90% and 6% respectively. Food decreased the mean Cmax of loratadine and descarboethoxyloratadine by 9% and 15% respectively. The time to peak plasma concentration (Tmax) of loratadine and descarboethoxyloratadine were delayed by approximately 2.4 and 3.7 hours, respectively, when food was consumed prior to administration of Claritin Rapid Dissolve Tongue Tablets.
In a single-dose, randomized, 2-way cross-over study with 10 mg Claritin Rapid Dissolve Tongue Tablets in 24 subjects, under fasting condition, the mean AUC(tf) and Cmax values were increased by 84% and 30%, respectively, when administered without water compared to administration with water, demonstrating that bioavailability was not attenuated when Claritin Rapid Dissolve Tongue Tablet was dissolved on the tongue and subsequently swallowed without concomitant consumption of a liquid. The bioavailability of descarboethoxyloratadine was not different when administered without water.
Approximately 82% of the 4C-loratadine dose is excreted in the urine (40%) and feces (42%) over a 10-day period. Approximately 27% of the dose is eliminated in the urine during the first 24 hours largely in the conjugated form. Unchanged drug is present only in trace quantities in the urine and the active metabolite descarboethoxyloratadine represents only 0.4 to 0.6% of the administered loratadine dose.
In 2 randomized, multicentre, double-blind, placebo-controlled, parallel groups studies performed in patients with seasonal allergic rhinitis, the safety and efficacy of Claritin Rapid Dissolve Tongue Tablets and the conventional Claritin tablets vs placebo were evaluated. Claritin Rapid Dissolve Tongue Tablets administered as 10 mg once daily for 15 days, were significantly more effective than placebo in reducing physician-evaluated and patient daily-assessed total combined, total nasal, and total nonnasal symptoms in patients with seasonal allergic rhinitis. Claritin Rapid Dissolve Tongue Tablet had a clinical effect comparable to or greater than conventional Claritin tablet. Both of the drugs were safe and well tolerated in this patient population. From clinical studies conducted on healthy individuals with allergic rhinitis, no clinical consequences are anticipated in this population, whether or not Claritin Rapid Dissolve Tongue Tablets are administered with or without food.
Indications And Clinical Uses: Tablets and Rapid Dissolve Tongue Tablets: For the relief of symptoms associated with seasonal and perennial allergic rhinitis, such as sneezing, nasal discharge and itching, and ocular itching and burning, and for the relief of symptoms and signs of chronic urticaria and other allergic dermatologic disorders. Clinical studies to date support treatment for up to 6 months, thus medical recommendation is advised for longer-term use. The Rapid Dissolve Tongue Tablets should be taken on an empty stomach.
Syrup: For the relief of symptoms associated with seasonal allergic rhinitis, such as sneezing, nasal discharge and itching, and ocular itching and burning, and for the relief of symptoms and signs of chronic urticaria and other allergic dermatologic disorders. In children, it is intended for short-term use only unless taken under medical supervision.
Contra-Indications: In patients who have shown hypersensitivity or idiosyncrasy to the drug or its components.
Precautions: Patients with severe liver impairment should be administered a lower initial dose because they may have reduced clearance of loratadine; an initial dose of 5 mg once daily or 10 mg every other day is recommended.
Pregnancy and Lactation: The safe use of loratadine during pregnancy or lactation has not been established and therefore the compound should be used only if the potential benefit justifies the potential risk to fetus or infant.
Children: The safety and efficacy of loratadine in children younger than 2 years of age have not been established. Long-term safety and efficacy of loratadine in children between the ages of 2 and 12 have not been demonstrated. Therefore, it is desirable that loratadine not be administered to children between the ages of 2 and 12 for longer than 14 days, unless recommended by a physician.
Drug Interactions: When administered concomitantly with alcohol, loratadine has no potentiating effects as measured by psychomotor performance studies.
Increases in plasma concentrations of loratadine have been reported after concomitant use with ketoconazole, erythromycin or cimetidine in controlled clinical trials, but without clinically significant changes (including electrocardiographic). Other drugs known to inhibit hepatic metabolism should be coadministered with caution until definitive interaction studies can be completed.
Drug/Laboratory Test Interactions : Loratadine should be discontinued approximately 48 hours prior to skin testing procedures since antihistamines may prevent or diminish otherwise positive reactions to dermal reactivity indicators.
Adverse Reactions: Adverse experiences reported with conventional loratadine in adults during the clinical trials were mild and consisted of fatigue, headache, dry mouth, sedation, gastrointestinal disorders such as nausea, gastritis, and also allergic symptoms like rash. The incidence of sedation was similar to that of the comparative agents terfenadine, astemizole and placebo, but statistically different (p < 0.01) from clemastine. See Table IV. In addition to those listed in Table IV, the following were reported less frequently (<1%): appetite increased, coughing, dizziness, and palpitations.
During the marketing of loratadine, alopecia, anaphylaxis, and abnormal hepatic function have been reported rarely.
Loratadine Rapid Dissolve Tongue Tablets were well tolerated and did not cause local irritation or taste abnormalities. The most frequently reported adverse experience was headache. Overall, the incidence of adverse reactions was comparable to that of conventional loratadine tablets and to that of placebo (see Table V).
Adverse experiences reported in pediatric patients are shown in Table VI. Nervousness and hyperkinesia were among the reported adverse experiences. One case of hyperkinesia was graded as severe and was judged by the physician to be possibly related to loratadine treatment. Gastrointestinal adverse reactions reported during pediatric trials may have been slightly more frequent in the younger patients (less than or equal to 30 kg), but in older children (greater than 30 kg) are similar to placebo.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: Somnolence, tachycardia and headache have been reported with overdoses of the conventional loratadine formulation. A single acute ingestion of 160 mg produced no adverse effects.
Treatment: In the event of overdosage, treatment, which should be started immediately, is symptomatic and supportive. Discontinuation of use, gastric lavage or induction of emesis (except in patients with impaired consciousness) and support of vital functions are advised.
The patient should be induced to vomit, even if emesis has occurred spontaneously. Pharmacologically induced vomiting by administration of ipecac syrup is a preferred method. However, vomiting should not be induced in patients with impaired consciousness. The action of ipecac is facilitated by physical activity and by the administration of 240 to 360 mL of water. If emesis does not occur within 15 minutes, the dose of ipecac should be repeated. Precautions against aspiration should be taken, especially in children.
Following emesis, adsorption of any drug remaining in the stomach may be attempted by the administration of activated charcoal as a slurry with water. If vomiting is unsuccessful, or contraindicated, gastric lavage should be performed. Physiologic saline solution is the lavage solution of choice, particularly in children. In adults, tap water can be used; however, as much as possible of the amount administered should be removed before the next instillation. Saline cathartics draw water into the bowel by osmosis and therefore may be valuable for their action in rapid dilution of bowel content.
Loratadine is not cleared by hemodialysis to any appreciable extent; it is not known if loratadine is removed by peritoneal dialysis.
Dosage And Administration: Syrup: Adults, children over 10 years of age (body weight greater than 30 kg): 10 mL of syrup once daily.
Children 2 through 9 years of age (body weight less than or equal to 30 kg): 5 mL of syrup once daily.
Tablets: Adults and Children 12 years of age and over: 1 tablet (10 mg) once daily. One Rapid Dissolve Tongue Tablet (10 mg), placed in the mouth once daily. The tablet disperses instantly and water or other liquid is not needed.
Availability And Storage: Syrup: Each mL of clear, colorless to light yellow, peach-flavored syrup contains: loratadine 1 mg (as base). Nonmedicinal ingredients: artificial peach flavor, citric acid monohydrate, glycerin, propylene glycol, purified water, sodium benzoate and sucrose. Amber glass or amber plastic bottles of 100 mL. Store between 2 and 30°C.
Rapid Dissolve Tongue Tablets: Each white, round, tablet-shaped unit contains: micronized loratadine 10 mg (as base). Nonmedicinal ingredients: citric acid, gelatin, mannitol and mint flavor. Blister packages of 4, 8 and 12. Store between 2 and 30°C. Use within 6 months of opening sachet, immediately upon opening tablet blister. Protect from exposure to excessive moisture.
Tablets: Each white, oval, shallow, deep-scored tablet, with the flask and dish logo above the deep score and the number 10 below, contains: loratadine 10 mg (as base). Nonmedicinal ingredients: cornstarch, lactose and magnesium stearate. Blister packages of 6, 12 and 18. Bottles of 100. Store between 2 and 30°C. Protect from exposure to excessive moisture.