LORFAST

Indications

• Allergic rhinitis
• Seasonal allergic rhinitis
• Perennial allergic rhinitis
• Chronic urticaria
• Allergic conjunctivitis

Dosage

Children: For children aged 2 to 12 years, the recommended dose is 5 mg once daily for those weighing less than 30 kg, and 10 mg once daily for those weighing 30 kg or more. For children under 2 years, refer to the BNF for Children for appropriate dosing.

Adults: The usual adult dose is 10 mg once daily.

Mechanism of action

Loratadine exerts its antihistaminic effects by binding to H1 histamine receptors on various cell types, including epithelial cells, eosinophils, and vascular smooth muscle cells. It acts as an inverse agonist, stabilizing the H1 receptor in its inactive form, which prevents histamine from exerting its effects. This mechanism is crucial in alleviating symptoms of allergic reactions, as it inhibits the actions of histamine that lead to symptoms such as itching, sneezing, and increased vascular permeability.

Pharmacodynamics

As a selective peripheral H1 receptor antagonist, loratadine demonstrates minimal penetration into the central nervous system, resulting in a significantly reduced incidence of sedation and drowsiness compared to first-generation antihistamines. This selectivity allows loratadine to effectively alleviate allergy symptoms while minimizing adverse effects on cognitive and motor functions.

Pharmacokinetics

Loratadine is rapidly absorbed after oral administration, with peak plasma concentrations occurring approximately 1 to 2 hours post-dose. It has a relatively long half-life of about 8 to 12 hours, allowing for once-daily dosing. The drug is extensively metabolized in the liver to its active metabolite, desloratadine, which contributes to its antihistaminic effects. It is primarily excreted in the urine, with only a small fraction eliminated unchanged.

Adverse effects

• Headache
• Somnolence
• Fatigue
• Dry mouth
• Nausea
• Rash

Precautions

• Use with caution in patients with hepatic impairment.
• Care should be taken in patients with renal impairment.

Pregnancy

Loratadine is classified as category B. Animal studies have not demonstrated a risk to the fetus, but there are no adequate studies in pregnant women.

Breast-feeding

Loratadine is excreted in breast milk. Caution is advised when administered to nursing mothers.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets
• Syrup
• Orally disintegrating tablets

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. All of the available H1 receptor antagonists are reversible, competitive inhibitors of the interaction of histamine with H1 receptors. /H1 Receptor Antagonists/ H1 antagonists inhibit most responses of smooth muscle to histamine. /H1 Antagonists Receptors/ Within the vascular tree, the H1 antagonists inhibit both the vasoconstrictor effects of histamine and, to a degree, the more rapid vasodilator effects that are mediated by H1 receptors on endothelial cells. /H1 Receptor Antagonists/ H1 antagonists strongly block the action of histamine that results in increased capillary permeability and formation of edema and wheal. /H1 Receptor Antagonists/ For more Mechanism of Action (Complete) data for LORATADINE (6 total), please visit the HSDB record page.

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.