Introduction
Loratadine is a second generation antihistamine used to manage symptoms of allergic rhinitis. 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.
Uses
Loratadine is a second generation antihistamine used to manage the symptoms of allergic rhinitis.
Loratadine is a 2nd generation antihistamine and is used to manage symptoms of allergic rhinitis, wheal formation, urticaria, and other allergic dermatologic conditions.
Associated Conditions
Pharmacodynamics
Like other 2nd generation antihistamines, loratadine is selective for peripheral H1 receptors. Loratadine does not penetrate effectively into the central nervous system and has poor affinity for CNS H1-receptors. These qualities result in a lack of CNS depressant effects such as drowsiness, sedation, and impaired psychomotor function.
Mechanism of Action
Histamine release is a key mediator in allergic rhinitis and urticaria. 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. 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. Histamine binding to the H1-receptor facilitates cross linking between transmembrane domains III and V, stabilizing the active form of the receptor. On the other hand, antihistamines bind to a different site on the H1 receptor favouring the inactive form.
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.
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.
In the rapid dissolve formulation, the pharmacokinetic parameters of loratadine are as follows: 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: 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: 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: Cmax = 3.66 ng/ml, Tmax = 1.97 hr, AUC = 48.4 ng x hr/ml
Volume of Distribution
The volume of distribution of loratadine is 120 L/Kg.
Protein Binding
97 - 99% of the loratadine is bound to plasma proteins.
Route of Elimination
Over a 10 day period, 40% of loratadine is excreted in the urine, and 42% is eliminated in the faeces.
Half Life
The elimination half life is approximately 10 hours for loratadine and 20 hours for descarboethoxyloratadine.
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. 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. It appears that an antihistamine with higher affinity for p-glycoprotein will have a lower incidence of CNS adverse effects.
Toxicity
Second generation antihistamines such as loratadine have very few adverse effects; however, insomnia, headache, fatigue, drowsiness and rash have been reported. Symptoms of loratadine overdose include gastrointestinal side effects, agitation, drowsiness, tachycardia, and headache. It is advised to obtain an ECG in the event of loratadine overdose.
Food Interactions
No interactions found.
Dosage
Children 2-12 years: Body weight over 30 kg: one Loratadine tablet once daily, below 30 kg: half Loratadine tablet once daily.
Below 2 years of age: Loratadine tablet is not recommended for use below 2 years of age since safety and efficacy has not been established.
