Loratadine: A Nonsedating Antihistamine with Once-Daily Dosing

Abstract

Loratadine is an addition to the class of nonsedating antihistamines which includes terfenadine, astemizole, and acrivastine. Loratadine is chemically related to the tricyclic antidepressants. Animal data have shown that insignificant amounts of loratadine enter the brain, and it has a threefold greater affinity for peripheral as compared with central histamine 1-receptors. Loratadine has one main metabolite, descarbethoxyloratadine, which is four times more active than the parent drug. Loratadine reaches peak plasma concentration in 1-2 hours; the metabolite does so in 3-4 hours. Their respective elimination half-lives are about 10 and 20 hours. Onset of action is within 1 hour and duration is at least 24 hours. Once-daily dosing is recommended. Generally, loratadine is as efficacious as existing antihistamines in relieving symptoms of allergic rhinitis, urticaria, and in suppressing wheal formation. Reports of sedation and other adverse reactions are no more frequent than found with placebo. Tachyphylaxis has not been noted in humans, and there is minimal potential for drug interactions based on animal data. Loratadine and terfenadine have comparable therapeutic applications. Both have shown minimal adverse effects, but loratadine has a quicker onset and longer duration of action. These two agents are useful for acute allergic reactions. In contrast, astemizole has an onset of action of several days and is most useful for prophylactic treatment of seasonal allergies.

Application of the Gastrointestinal Simulator (GIS) Coupled with In Silico Modeling to Measure the Impact of Coca-Cola® on the Luminal and Systemic Behavior of Loratadine (BCS Class 2b)

“…As mentioned by other authors, this estimated pKa and LogP value differs from the one stated by Stillhart et al (basic pKa of 5.3 and LogP value of 3.9) [ 15 ]. The molecule has one major active metabolite (descarbethoxyloratadine), being four times more active than the parent drug and showing a longer elimination half-life (20 versus 10 h, respectively) [ 33 , 34 ]. The ionized versus unionized microspecies distribution and the metabolic pathways are depicted in Figure 4 A,B, respectively.…”

Cardiac safety of second‐generation H1‐antihistamines when updosed in chronic spontaneous urticaria

“…Loratadine is a second‐generation piperidine antihistamine drug structurally related to azatadine and cyproheptadine . Loratadine is very well tolerated because it lacks anticholinergic activity and does not cross the blood‐brain barrier to cause sedation . After oral administration, this drug undergoes extensive first pass metabolism being converted by CYP3A4 and CYP2D6 to its active metabolite descarboethoxyloratadine (desloratadine), which is about four times more potent at H 1 receptors than loratadine itself .…”

“…Loratadine is very well tolerated because it lacks anticholinergic activity and does not cross the blood‐brain barrier to cause sedation . After oral administration, this drug undergoes extensive first pass metabolism being converted by CYP3A4 and CYP2D6 to its active metabolite descarboethoxyloratadine (desloratadine), which is about four times more potent at H 1 receptors than loratadine itself . Desloratadine has been developed as a drug with clinical indications similar to those of loratadine but with higher potency, longer half‐life and lower binding to plasma proteins .…”

Antiallergic Treatment of Bariatric Patients: Potentially Hampered Solubility/Dissolution and Bioavailability of Loratadine, but Not Desloratadine, Post-Bariatric Surgery

“…In fact, desloratadine is a major active metabolite of loratadine . Therefore, under normal conditions, therapeutic levels of desloratadine are accomplished either by direct administration of desloratadine in 5 mg dosage form or by the administration of 10 mg loratadine that undergoes metabolism to the pharmacodynamically more active , desloratadine by cytochrome P450 3A4 and 2D6 enzymes (Figure ).…”