Description

Simple

A medication used to manage allergy symptoms such as itchy eyes and runny nose.

Clinical

A second generation antihistamine used to manage the symptoms of allergic rhinitis.

Overview

Loratadine is a second generation antihistamine used to manage symptoms of allergic rhinitis.[5] A lack of sedative and CNS adverse effects make loratadine, along with other second generation antihistamines, preferable over their 1st generation counterparts in many clinical situations.[7]

Pharmacology

Indication

Loratadine is a 2nd generation antihistamine and is used to manage symptoms of allergic rhinitis, wheal formation, urticaria, and other allergic dermatologic conditions.[ Read more

Loratadine is a 2nd generation antihistamine and is used to manage symptoms of allergic rhinitis, wheal formation, urticaria, and other allergic dermatologic conditions.[5][6][17] Read Less

Pharmacodynamic

Like other 2nd generation antihistamines, loratadine is selective for peripheral H1 receptors.[ Read more

Like other 2nd generation antihistamines, loratadine is selective for peripheral H1 receptors.[9] Loratadine does not penetrate effectively into the central nervous system and has poor affinity for CNS H1-receptors.[9] These qualities result in a lack of CNS depressant effects such as drowsiness, sedation, and impaired psychomotor function.[9] Read Less

Mechanism of action

Histamine release is a key mediator in allergic rhinitis and urticaria.[12][ Read more

Histamine release is a key mediator in allergic rhinitis and urticaria.[12][7][8] As a result, loratadine exerts it's effect by targeting H1 histamine receptors.

Loratadine binds to H1 histamine receptors found on the surface of epithelial cells, endothelial cells, eosinophils, neutrophils, airway cells, and vascular smooth muscle cells among others.[7] H1 histamine receptors fall under the wider umbrella of G-protein coupled receptors, and exist in a state of equilibrium between the active and inactive forms.[7][8] Histamine binding to the H1-receptor facilitates cross linking between transmembrane domains III and V, stabilizing the active form of the receptor.[7][8] On the other hand, antihistamines bind to a different site on the H1 receptor favouring the inactive form.[7][8]

Hence, loratadine can more accurately be classified as an "inverse agonist" as opposed to a "histamine antagonist", and can prevent or reduce the severity of histamine mediated symptoms.[7][8][17] Read Less

Absorption

Loratadine is rapidly absorbed and achieves peak plasma concentration in 1-2 hours, while it's main metabolite achieves peak plasma concentration in 3-4 hours.[ Read more

Loratadine is rapidly absorbed and achieves peak plasma concentration in 1-2 hours, while it's main metabolite achieves peak plasma concentration in 3-4 hours.[6]

In the rapid dissolve formulation, the pharmacokinetic parameters of loratadine are as follows[17]: Cmax = 2.56 ng/ml, Tmax = 1.14 hrs, AUC = 6.14 ng x hr/ml.

In the rapid dissolve formulation, the pharmacokinetic parameters of descarboethoxyloratadine are as follows[17]: Cmax = 3.72 ng/ml, Tmax = 1.97 hr, AUC = 49.1 ng x hr/ml.

In the conventional formulation, the pharmacokinetic parameters of loratadine are as follows[17]: Cmax = 2.11 ng/ml, Tmax = 1.00 hr, AUC = 4.64 ng x hr/ml

In the conventional formulation, the pharmacokinetic parameters of descarboethoxyloratadine are as follows[17]: Cmax = 3.66 ng/ml, Tmax = 1.97 hr, AUC = 48.4 ng x hr/ml Read Less

Protein binding

97 - 99% of the loratadine is bound to plasma proteins.[17]

97 - 99% of the loratadine is bound to plasma proteins.[17] Read Less

Volume of distribution

The volume of distribution of loratadine is 120 L/Kg.[18]

The volume of distribution of loratadine is 120 L/Kg.[18] Read Less

Clearance

The clearance of loratadine after single oral doses of 20 mg and 40 mg are 12 L/h/kg and 9 L/h/kg respectively.[ Read more

The clearance of loratadine after single oral doses of 20 mg and 40 mg are 12 L/h/kg and 9 L/h/kg respectively.[9]P-glycoprotein is involved in the clearance of many 2nd generation antihistamines, including loratadine, from the central nervous system. 1st generation antihistamines are not cleared by P-glycoprotein, which may help explain why they have a different central nervous system adverse effect profile compared to their 2nd generation counterparts.[18][13] It appears that an antihistamine with higher affinity for p-glycoprotein will have a lower incidence of CNS adverse effects.[14] Read Less

Half life

The elimination half life is approximately 10 hours for loratadine and 20 hours for descarboethoxyloratadine.[6]

The elimination half life is approximately 10 hours for loratadine and 20 hours for descarboethoxyloratadine.[6] Read Less

Route of elimination

Over a 10 day period, 40% of loratadine is excreted in the urine, and 42% is eliminated in the faeces.[17]

Over a 10 day period, 40% of loratadine is excreted in the urine, and 42% is eliminated in the faeces.[17]

Read Less

Toxicity

Second generation antihistamines such as loratadine have very few adverse effects; however, insomnia, headache, fatigue, drowsiness and rash have been reported.[ Read more

Second generation antihistamines such as loratadine have very few adverse effects; however, insomnia, headache, fatigue, drowsiness and rash have been reported.[7] Symptoms of loratadine overdose include gastrointestinal side effects, agitation, drowsiness, tachycardia, and headache.[7] It is advised to obtain an ECG in the event of loratadine overdose.[7] Read Less

Adverse Effects

Contraindications