ZOTER 60MG TABLET

Indications

• Allergic rhinitis (hay fever)
• Urticaria (hives)
• Allergic conjunctivitis

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Terfenadine competes with histamine for binding at H1-receptor sites located in the gastrointestinal tract, uterus, large blood vessels, and bronchial muscle. This reversible binding suppresses the formation of edema, flare, and pruritus associated with histaminic activity. It exhibits both competitive and relatively irreversible antagonism of H1 receptors depending on the concentration. Terfenadine does not significantly cross the blood-brain barrier, resulting in minimal central nervous system depression.

Pharmacodynamics

As an H1-receptor antagonist, terfenadine acts to alleviate symptoms of allergic reactions without significant anticholinergic or antiserotonergic effects at standard doses. Its pharmacodynamic profile suggests a specific and selective antagonism of H1-receptors, with a slow binding and dissociation from these receptors contributing to its prolonged action. The active metabolite, fexofenadine, retains similar antihistamine properties.

Pharmacokinetics

Terfenadine has a molecular formula of C32H41NO2. It is extensively metabolized in the liver to fexofenadine, which is primarily responsible for its antihistaminic effects. The pharmacokinetics of terfenadine are characterized by a relatively long half-life, allowing for once-daily dosing. However, caution is advised due to potential drug interactions that may affect its metabolism and increase the risk of adverse effects.

Contra-indications

• Hypersensitivity to terfenadine or any of its ingredients
• Patients with a history of arrhythmias, particularly those with a prolonged QT interval
• Severe hepatic impairment

Adverse effects

• Headache
• Dizziness
• Somnolence
• Dry mouth
• Palpitations
• QT interval prolongation
• Tachycardia

Interactions

• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin) may increase terfenadine levels and risk of cardiotoxicity
• Certain antihistamines may have additive effects when used concurrently
• Alcohol may enhance sedative effects

Precautions

• Use with caution in patients with cardiovascular disorders
• Monitor for signs of liver dysfunction
• Avoid use in patients taking other medications that prolong the QT interval

Pregnancy

Terfenadine should be used during pregnancy only if clearly needed, as safety in pregnancy has not been established.

Breast-feeding

Terfenadine is excreted in breast milk; caution should be exercised when administered to nursing women.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets
• Syrup

Mechanism of action

Terfenadine competes with histamine for binding at H1-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle. This reversible binding of terfenadine to H1-receptors suppresses the formation of edema, flare, and pruritus resulting from histaminic activity. As the drug does not readily cross the blood-brain barrier, CNS depression is minimal. ... Terfenadine appears to have a dual effect on histamine H1-receptors. In vitro studies indicate that terfenadine competitively antagonizes the actions of histamine at concentrations of 15-47 ng/mL, while a relatively irreversible antagonism occurs at higher concentrations (ie, 150-470 ng/mL). Experimental evidence indicates that the drug exhibits a specific and selective antagonism of histamine H1-receptors and that the drug slowly binds to the H1-receptor and forms a stable complex from which it subsequently slowly dissociates. These finding suggest that the prolonged and generally irreversible nature of terfenadin's antagonism of histamine results principally from the drugs slow dissociation from the H1-receptors. Unlike many other antihistamines, terfenadine does not possess appreciable anticholinergic or antiserotonergic effects at usual antihistaminic doses in pharmacologic studies. However, in clinical trials there was no difference in the frequency of anticholinergic-like effects (eg, dryness of the nose, mouth, throat and/or lips)observed with terfenadine or other antihistamines (ie, chlopheniramine, clemastine, dexchlorpheniramine). Terfenadine also does not exhibit any appreciable alpha or beta-adrenergic blocking activity or histamine H2-receptor antagonism. Terfenadine has increased urinary bladder capacity in individuals with normal bladder function and in some patients with neurogenic bladder and overactive detrusor muscle function, probably via a histamine H1-antagonist effect on the detrusor muscle; this effect appears to vary diurnally, being maximal at night. The mechanism of the cardiotoxic effects of certain "nonsedating" antihistamines including terfenadine currently is not understood, and would appear to be contrary to what would be expected from studies on cardiac histamine H1-receptors; therefore, the possibility that H3-receptors (mediating a regulatory feedback mechanism) may be involved has been suggested. Limited evidence from animal models using terfenadine suggests that the cardiotoxic effects of the drug may result at least in part from blockade of the potassium channel involved in repolarization of cardiac cells (ie, blockade of the delayed rectifier potassium current IK). In some animal studies using fexofenadine, no blockade of the potassium channel involved in repolarization of cardiac cells was observed which may indicate a lack of fexofenadine-induced cardiotoxicity. In addition,in in vitro studies using fexofenadine, no effect was observed on delayed rectifier potassium channel cloned from human heart at fexofenadine concentrations up to 1.0X10-5M. Unlike with other antihistamines, anticholinergic and/or local anesthetic effects appear to be unlikely cause of the cardiac effects of certain "nonsedating" antihistamines, including terfenadine. Basophils in mononuclear cell populations were challenged with allergens, anti-immunoglobulin E (anti-IgE), C5a or formyl-methyl-leucyl-phenylalanine (FMLP), with or without a short pre-incubation with interleukin-3 (IL-3), in the presence of increasing concentrations of terfenadine. At doses of 0.1-1 ug/mL, terfenadine inhibits histamine release and generation of the sulfidoleukotrienes, leukotriene C4, D4 and E4 in basophils challenged with an IgE-dependent trigger. At concentrations above 10 ug/mL, however, terfenadine induces the histamine release but abolishes the formation of leukotrienes, and this may be due to a cytotoxic effect. In eosinophils, by contrast, terfenadine appears to inhibit the production of leukotrienes by eosinophils, triggered by FMLP only at concentrations abo

Pharmacodynamics

Terfenadine, an H1-receptor antagonist antihistamine, is similar in structure to astemizole and haloperidol, a butyrophenone antipsychotic. The active metabolite of terfenadine is fexofenadine.