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Claritin (Loratadine) - Warnings and Precautions

 
 



WARNINGS

No information provided.

PRECAUTIONS

General:

Patients with liver impairment or renal insufficiency (GFR <30 ml/min) should be given a lower initial dose (10 mg every other day). (See CLINICAL PHARMACOLOGY, Special Populations.)

DRUG INTERACTIONS

Loratadine (10 mg once daily) has been coadministered with therapeutic doses of erythromycin, cimetidine, and ketoconazole in controlled clinical pharmacology studies in adult volunteers. Although increased plasma concentrations (AUC 0-24 hrs) of loratadine and/or descarboethoxyloratadine were observed following coadministration of loratadine with each of these drugs in normal volunteers (n = 24 in each study), there were no clinically relevant changes in the safety profile of loratadine, as assessed by electrocardiographic parameters, clinical laboratory tests, vital signs, and adverse events. There were no significant effects on QTc intervals, and no reports of sedation or syncope. No effects on plasma concentrations of cimetidine or ketoconazole were observed. Plasma concentrations (AUC 0-24 hrs) of erythromycin decreased 15% with coadministration of loratadine relative to that observed with erythromycin alone. The clinical relevance of this difference is unknown. These above findings are summarized in the following table:

Effects on Plasma Concentrations (AUC 0-24 hrs) of Loratadine and Descarboethoxyloratadine After 10 Days of Coadministration (Loratadine 10 mg) in Normal Volunteers
Loratadine Descarboethoxyloratadine
Erythromycin (500 mg q8h) + 40% +46%
Cimetidine (300 mg qid) +103% +6%
Ketoconazole (200 mg q12h) +307% +73%

There does not appear to be an increase in adverse events in subjects who received oral contraceptives and loratadine.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

In an 18-month carcinogenicity study in mice and a 2-year study in rats, loratadine was administered in the diet at doses up to 40 mg/kg (mice) and 25 mg/kg (rats). In the carcinogenicity studies, pharmacokinetic assessments were carried out to determine animal exposure to the drug. AUC data demonstrated that the exposure of mice given 40 mg/kg of loratadine was 3.6 (loratadine) and 18 (descarboethoxyloratadine) times higher than in humans given the maximum recommended daily oral dose. Exposure of rats given 25 mg/kg of loratadine was 28 (loratadine) and 67 (descarboethoxyloratadine) times higher than in humans given the maximum recommended daily oral dose. Male mice given 40 mg/kg had a significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) than concurrent controls. In rats, a significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) was observed in males given 10 mg/kg and males and females given 25 mg/kg. The clinical significance of these findings during long-term use of loratadine is not known.
In mutagenicity studies, there was no evidence of mutagenic potential in reverse (Ames) or forward point mutation (CHO-HGPRT) assays, or in the assay for DNA damage (rat primary hepatocyte unscheduled DNA assay) or in two assays for chromosomal aberrations (human peripheral blood lymphocyte clastogenesis assay and the mouse bone marrow erythrocyte micronucleus assay). In the mouse lymphoma assay, a positive finding occurred in the nonactivated but not the activated phase of the study.

Decreased fertility in male rats, shown by lower female conception rates, occurred at an oral dose of 64 mg/kg (approximately 50 times the maximum recommended human daily oral dose on a mg/m2 basis) and was reversible with cessation of dosing. Loratadine had no effect on male or female fertility or reproduction in the rat at an oral dose of approximately 24 mg/kg (approximately 20 times the maximum recommended human daily oral dose on a mg/m2 basis).

Pregnancy Category B

There was no evidence of animal teratogenicity in studies performed in rats and rabbits at oral doses up to 96 mg/kg (approximately 75 times and 150 times, respectively, the maximum recommended human daily oral dose on a mg/m2 basis). There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, loratadine should be used during pregnancy only if clearly needed.

Nursing Mothers

Loratadine and its metabolite, descarboethoxyloratadine, pass easily into breast milk and achieve concentrations that are equivalent to plasma levels with an AUCmilk/AUCplasma ratio of 1.17 and 0.85 for loratadine and descarboethoxyloratadine, respectively. Following a single oral dose of 40 mg, a small amount of loratadine and descarboethoxyloratadine was excreted into the breast milk (approximately 0.03% of 40 mg over 48 hours). A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Caution should be exercised when loratadine is administered to a nursing woman.

Pediatric Use

The safety of loratadine syrup at a daily dose of 10 mg has been demonstrated in 188 pediatric patients 6 to 12 years of age in placebo-controlled 2-week trials. The effectiveness of loratadine for the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria in this pediatric age group is based on an extrapolation of the demonstrated efficacy of loratadine in adults in these conditions and the likelihood that the disease course, pathophysiology, and the drug's effect are substantially similar to that of the adults. The recommended dose for the pediatric population is based on cross-study comparison of the pharmacokinetics of loratadine in adults and pediatric subjects and on the safety profile of loratadine in both adults and pediatric patients at doses equal to or higher than the recommended doses. The safety and effectiveness of loratadine in pediatric patients under 6 years of age have not been established.

PATIENT INFORMATION

See CONTRAINDICATIONS Section.

Page last updated: 2006-01-09

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