Loratadine

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Treatment of overdosage would reasonably consist of emesis (ipecac syrup), except in patients with impaired consciousness, followed by the administration of activated charcoal to absorb any remaining drug. If vomiting is unsuccessful, or contraindicated, gastric lavage should be performed with normal saline. Saline cathartics may also be of value for rapid dilution of bowel contents. Loratadine is not eliminated by hemodialysis. It is not known if loratadine is eliminated by peritoneal dialysis. (L1712)

Concurrent use may potentiate the CNS depressant effects of either these medications /alcohol or other CNS depression-producing medications/ or antihistamines; also, concurrent use of maprotiline or tricyclic antidepressants may potentiate the anticholinergic effects of either antihistamines or these medications. /Antihistamines/

Anticholinergic effects may be potentiated when these medications /anticholinergics or other medications with anticholinergic activity/ are used concurrently with antihistamines; patients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy. /Antihistamines/

Concurrent use of monoamine oxidase (MAO) inhibitors with antihistamines may prolong the intensify the anticholinergic and CNS depressant effects of antihistamines; concurrent use is not recommended. /Antihistamines/

Concurrent use /of ototoxic medications/ with antihistamines may mask the symptoms of ototoxicity such as tinnitus, dizziness, or vertigo. /Antihistamines/

For more Interactions (Complete) data for LORATADINE (6 total), please visit the HSDB record page.

Although loratadine is a relatively safe and effective medication for treating allergic rhinitis, its primary adverse effects include headaches, dizziness, and gastrointestinal distress (diarrhea, abdominal pain, nausea, and vomiting). Loratadine may also cause sedation (a rare adverse effect), mydriasis, and xerostomia. These effects are primarily due to the drug's anticholinergic properties; anticholinergic adverse effects are minimal at therapeutic dosage. In a patient undergoing long-term loratadine treatment, a rare case of bilateral cystoid macular edema has been described, which resolved after discontinuation of loratadine. The potential pathophysiology remains unclear. It may involve dysfunction of H1-receptor–expressing retinal neurons and associated signal transduction, toxicity affecting Müller cells or retinal pigment epithelium cells, and intracellular fluid accumulation.

Signs and Symptoms of Overdose

Loratadine competes with free histamine and exhibits specific, selective peripheral H₁ antagonistic activity. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms (eg. nasal congestion, watery eyes) brought on by histamine. Loratadine has low affinity for cholinergic receptors and does not exhibit any appreciable alpha-adrenergic blocking activity in-vitro. Loratadine also appears to suppress the release of histamine and leukotrienes from animal mast cells, and the release of leukotrienes from human lung fragments, although the clinical importance of this is unknown.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=79794-75-5]

Somnolence, tachycardia, and headache have been reported with overdoses greater than 10 mg (40 to 180 mg).

The second generation H1 antagonists (eg, terfenadine, astemizole, loratadine) have no effect on muscarinic receptors.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Loratadine

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

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.

In an 18 month oncogenicity 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 (active metabolite) times higher than a human given 10 mg/kg. Exposure of rats given 25 mg/kg of loratadine was 28 (loratadine) and 67 (active metabolite) times higher than a human given 10 mg/day. 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 significant of these findings during long-term use of Claritin tablets is not known. /Claritin/

Loratadine administration produced hepatic microsomal enzyme induction in the mouse at 40 mg/kg and rat at 25 mg/kg, but not at lower doses.

There was no evidence of animal teratogenicity in studies performed in rats and rabbits at oral doses up to 96 mg/kg (75 times and 150 times, respectively, the recommended daily human dose on a mg/sq m basis).

Decreased fertility in male rats, shown by lower female conception rates, occurred at approximately 64 mg/kg and was reversible with cessation of dosing. Loratadine had no effect on male or female fertility or reproduction in the rat at doses of approximately 24 mg/kg.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Antihistaminic

Use (kg; approx.) in Germany (2009): >750

Used to treat allergies. A self-medication that is used alone or in combination with pseudoephedrine sulfate for the symptomatic relief of seasonal allergic rhinitis. Also used for the symptomatic relief of pruritus, erythema, and urticaria associated with chronic idiopathic urticaria in patients (not for children under 6 unless directed by a clincian).

Claritin 10 mg tablets; Claritin-D 5 mg loratadine in the tablet coating for immediate release and 120 mg pseudoephedrine sulfate, USP equally distributed between the tablet for immediate release and the barrier coated extended release core.