ATARAX TABLETS

Indications

• Allergic conditions
• Anxiety disorders
• Sedation prior to surgery
• Pruritus (itching)
• Nausea and vomiting

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Hydroxyzine functions as a potent inverse agonist at the H1 histamine receptors, which are involved in mediating allergic responses. By dampening the activity of these receptors, hydroxyzine alleviates symptoms associated with histamine release, including itching and inflammation. Its anxiolytic and sedative effects are thought to occur at the subcortical level of the CNS, while its antiemetic properties may arise from interactions with off-target sites.

Pharmacodynamics

Hydroxyzine effectively blocks histamine activity, leading to relief from allergic symptoms such as pruritus. The drug shows a relatively fast onset of action, typically occurring within 15 to 60 minutes, and its effects can last between 4 to 6 hours. Hydroxyzine may enhance the effects of CNS depressants, necessitating caution and dose adjustments when used in conjunction with such medications. Additionally, it has been associated with the prolongation of the QT/QTc interval, warranting careful monitoring in at-risk populations.

Pharmacokinetics

Hydroxyzine is rapidly absorbed and metabolized, with its effects manifesting within a short timeframe. The drug's pharmacokinetic profile indicates a duration of action of approximately 4 to 6 hours. Hydroxyzine does not significantly increase gastric secretions or acidity, and it may exert mild antisecretory effects. Its metabolism and clearance can be influenced by other medications, particularly those affecting the CNS.

Adverse effects

• Sedation
• Dizziness
• Dry mouth
• Headache
• Nausea
• QT/QTc prolongation

Interactions

• hydroxyzine+antiepileptics: Severe (increases risk of overheating and dehydration)
• hydroxyzine+zonisamide: Severe (increases risk of overheating and dehydration)

Precautions

• Use with caution in patients with a history of cardiac arrhythmias
• Monitor patients for signs of sedation when combined with other CNS depressants
• Assess risk factors for QTc prolongation before prescribing

Pregnancy

Hydroxyzine is not recommended during pregnancy unless the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Hydroxyzine is excreted in breast milk, and caution is advised when administered to nursing mothers.

Storage

Store in a cool, dry place away from direct light. Keep out of reach of children.

Formulations

• Tablets
• Capsules
• Syrup
• Injection

Indications

• Symptomatic relief of allergic conditions (hay fever, urticaria)
• Anxiety management
• Premedication for anesthesia
• Pruritus

Dosage

Children: Child 6 months–5 years: 5–15 mg daily in divided doses, adjusted according to weight; maximum 2 mg/kg per day.

Adults: Initially 25 mg daily, taken at night; may be increased to 25 mg 3–4 times a day if necessary, with a maximum of 32 mg per day.

Mechanism of action

Hydroxyzine exerts its antihistaminic effects by blocking H1 receptors, which inhibits the action of endogenous histamine. This leads to a decrease in allergic symptoms such as itching, swelling, and redness. Additionally, it has central nervous system effects that contribute to its sedative properties, further helping to reduce anxiety and promote sleep.

Pharmacodynamics

Hydroxyzine has a rapid onset of action, typically within 15 to 30 minutes when administered orally. Its sedative effects can last for up to 6 hours. The drug also exhibits anticholinergic effects, which can lead to side effects such as dry mouth and drowsiness. Hydroxyzine's effectiveness in treating anxiety is believed to be due to its ability to depress the central nervous system, providing a calming effect.

Pharmacokinetics

Hydroxyzine is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 2 hours after oral administration. It undergoes extensive first-pass metabolism in the liver, primarily by CYP3A4 and CYP2D6 enzymes, resulting in the active metabolite cetirizine. The elimination half-life of hydroxyzine ranges from 20 to 25 hours, and it is primarily excreted in urine as metabolites. Dosage adjustments may be necessary in patients with hepatic impairment.

Mechanism of action

The H₁ histamine receptor is responsible for mediating hypersensitivity and allergic reactions. Exposure to an allergen results in degranulation of mast cells and basophils, which then release histamine and other inflammatory mediators. Histamine binds to, and activates, H₁ receptors, which results in the further release of pro-inflammatory cytokines, such as interleukins, from basophils and mast cells. These downstream effects of histamine binding are responsible for a wide variety of allergic symptoms, such as pruritus, rhinorrhea, and watery eyes. Hydroxyzine is a potent inverse agonist of histamine H₁-receptors - inverse agonists are agents that are considered to have a "negative efficacy", so rather than simply blocking activity at a receptor they actively dampen its activity. Inverse agonism at these receptors is responsible for hydroxyzine's efficacy in the treatment of histaminic edema, flare, and pruritus. Hydroxyzine is not a cortical depressant, so its sedative properties likely occur at the subcortical level of the CNS. These sedative properties allow activity as an anxiolytic. Antiemetic efficacy is likely secondary to activity at off-targets. Hydroxyzine does not appear to increase gastric secretions or acidity, and usually has mild antisecretory effects. The antispasmodic activity of hydroxyzine is apparently mediated through interference with the mechanism that responds to spasmogenic agents such as acetylcholine, histamine, and serotonin. Hydroxyzine has CNS depressant, anticholinergic, antispasmodic, and local anesthetic activity, in addition to antihistaminic effects. The drug also has sedative and antiemetic activity. The sedative and tranquilizing effects of hydroxyzine are thought to result principally from suppression of activity at subcortical levels of the CNS; the drug does not have cortical depressant activity. The precise mechanism of antiemetic and antimotion sickness actions of hydroxyzine are unclear, but appear to result, at least in part, from its central anticholinergic and CNS depressant properties. The effects of the drug hydroxyzine on the activities of the rat liver monoamine oxidases (EC 1.4.3.6; MAO) and the membrane-bound and soluble forms of bovine semicarbazide-sensitive amine oxidase (EC 1.4.3.6; SSAO) were studied. Hydroxyzine was found to be a competitive inhibitor of MAO-B (Ki - 38 microM), whereas it had a low potency towards MAO-A (IC50 > 630 microM). Although it was a relatively potent competitive inhibitor of bovine plasma SSAO (Ki approximately 1.5 microM), it was a weak inhibitor of the membrane-bound form of the enzyme from bovine lung (IC50 approximately 1 mM). These findings extend our knowledge of the drug binding capabilities of the amine oxidases and suggest that these interactions may contribute to the complex actions of this drug.

Pharmacodynamics

Hydroxyzine blocks the activity of histamine to relieve allergic symptoms such as pruritus. Activity at off-targets also allows for its use as a sedative anxiolytic and an antiemetic in certain disease states. Hydroxyzine is relatively fast-acting, with an onset of effect that occurs between 15 and 60 minutes and a duration of action between 4-6 hours. Hydroxyzine may potentiate the effects of central nervous system (CNS) depressants following general anesthesia - patients maintained on hydroxyzine should receive reduced doses of any CNS depressants required. Hydroxyzine is reported to prolong the QT/QTc interval based on postmarketing reports of rare events of Torsade de Pointes, cardiac arrest, and sudden death, and should be used with caution in patients with an increased baseline risk for QTc prolongation.