CONTRAINDICATIONS
Loratadine is contraindicated in patients who are hypersensitive to this medication or to
any of its ingredients.
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.)
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.