Usage
Hydroxyzine is prescribed for the short-term symptomatic relief of anxiety and tension associated with psychoneurosis. It is also used as an adjunct in organic disease states in which anxiety is a component. Additionally, it is indicated for the symptomatic relief of pruritus caused by allergic conditions such as chronic urticaria and atopic and contact dermatoses. It can also be used as a sedative before and after general anesthesia. Hydroxyzine belongs to the pharmacological class of antihistamines with anticholinergic and sedative properties. The mechanism of action involves suppressing activity in certain key regions of the subcortical area of the central nervous system.
Alternate Names
Hydroxyzine is also known as hydroxyzine hydrochloride or hydroxyzine pamoate, depending on the specific salt form. Brand names include Vistaril (hydroxyzine pamoate), and formerly Atarax (hydroxyzine hydrochloride, now discontinued).
How It Works
Pharmacodynamics: Hydroxyzine exerts its effects by antagonizing H1 histamine receptors and, to a lesser extent, muscarinic cholinergic receptors. It suppresses activity in specific subcortical regions of the central nervous system, leading to its anxiolytic, antipruritic, and sedative effects.
Pharmacokinetics: Hydroxyzine is well-absorbed after oral administration, reaching peak plasma concentrations within 1-3 hours. It is metabolized primarily in the liver by CYP3A4/5 enzymes. The primary metabolite is cetirizine, which also possesses antihistaminic activity. Elimination occurs primarily through renal excretion.
Mode of Action: Hydroxyzine’s primary mode of action is through competitive antagonism of H1 histamine receptors. It also exhibits some anticholinergic activity by blocking muscarinic receptors. This contributes to its sedative and drying effects.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Hydroxyzine binds to H1 histamine receptors and muscarinic cholinergic receptors. It inhibits the actions of histamine at these receptors. It does not directly inhibit CYP enzymes, though its metabolism is mediated by CYP3A4/5.
Elimination Pathways: Hydroxyzine is primarily metabolized in the liver by CYP3A4/5 and eliminated through renal excretion.
Dosage
Standard Dosage
Adults:
- Anxiety: 50-100 mg orally 3-4 times per day. Maximum daily dose: 400mg.
- Pruritus: 25 mg orally 3-4 times per day. Maximum daily dose: 100 mg.
- Sedation: 50-100 mg orally or IM once before the procedure. A second dose may be given after the procedure.
Children:
- Anxiety (Under 6 years): Up to 50 mg/day orally, divided into multiple doses.
- Anxiety (6 years and older): 50-100 mg/day orally, divided into multiple doses.
- Pruritus (Under 6 years): 50 mg/day orally, divided into multiple doses.
- Pruritus (6 years and older): 50-100 mg/day orally, divided into multiple doses.
- Sedation: 0.6 mg/kg orally or IM once before the procedure.
Special Cases:
- Elderly Patients: Initiate with half the usual adult dose and monitor for adverse effects. The maximum dose in the elderly is 50 mg daily.
- Patients with Renal Impairment: Reduce the dose by 50% in moderate to severe renal impairment.
- Patients with Hepatic Dysfunction: Reduce the dose by 33% in mild to moderate hepatic impairment. Avoid use in severe hepatic impairment.
- Patients with Comorbid Conditions: Use with caution in patients with cardiovascular disease, electrolyte imbalances, or those taking other medications that prolong the QT interval.
Clinical Use Cases
- Intubation: Hydroxyzine can be used as a premedication for intubation.
- Surgical Procedures: 50-100 mg IM or IV as a sedative pre- and post-operatively.
- Mechanical Ventilation: Can be used as an adjunctive sedative in mechanically ventilated patients.
- Intensive Care Unit (ICU) Use: Use with caution in critically ill patients due to the risk of delirium.
- Emergency Situations: 50-100 mg IM for acutely agitated or hysterical patients, or those experiencing alcohol withdrawal. The dose may be repeated every 4-6 hours as needed.
Dosage Adjustments
Dose adjustments are needed for elderly patients, patients with renal or hepatic dysfunction, and patients with concomitant use of CNS depressants or anticholinergics. Adjust doses based on patient response and clinical status.
Side Effects
Common Side Effects
- Drowsiness
- Dry mouth
- Dizziness
- Headache
Rare but Serious Side Effects
- QT prolongation
- Torsades de pointes
- Seizures
- Confusion
Long-Term Effects
Limited data are available on the long-term effects of hydroxyzine. Chronic use can potentially lead to tolerance and dependence.
Adverse Drug Reactions (ADR)
- Anaphylaxis
- Angioedema
- Hepatotoxicity
Contraindications
- Hypersensitivity to hydroxyzine, cetirizine, or other piperazine derivatives
- Congenital long QT syndrome
- History of torsades de pointes
- Concomitant use of other QT-prolonging drugs
- Early pregnancy
Drug Interactions
Hydroxyzine interacts with CNS depressants (alcohol, opioids, benzodiazepines), anticholinergics, QT-prolonging drugs, and CYP3A4/5 inhibitors. Concomitant use of these drugs can potentiate the sedative effects of hydroxyzine or increase the risk of cardiac arrhythmias.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C
- Fetal risks: Potential for fetal harm, especially in the first trimester.
- Drug excretion in breast milk: Hydroxyzine is excreted in breast milk.
- Neonatal side effects: Drowsiness, irritability.
Drug Profile Summary
- Mechanism of Action: H1 receptor antagonist, anticholinergic, CNS depressant
- Side Effects: Drowsiness, dry mouth, dizziness, QT prolongation, torsades de pointes
- Contraindications: Hypersensitivity, long QT syndrome, concomitant use of QT-prolonging drugs, early pregnancy
- Drug Interactions: CNS depressants, anticholinergics, QT-prolonging drugs, CYP3A4/5 inhibitors
- Pregnancy & Breastfeeding: Use with caution; potential for fetal harm and neonatal side effects
- Dosage: See detailed dosage guidelines above
- Monitoring Parameters: ECG, liver function tests, renal function tests
Popular Combinations
Hydroxyzine is sometimes used in combination with opioids for pre- and postoperative sedation and analgesia. This combination should be used cautiously due to the additive sedative effects.
Precautions
- Pre-screening is essential for allergies, cardiac conditions, hepatic or renal impairment, and concomitant medications.
- Pregnant Women: Avoid use during pregnancy, especially the first trimester, unless absolutely necessary.
- Breastfeeding Mothers: Use with caution; monitor the infant for drowsiness.
- Children & Elderly: Dose adjustments are needed for these populations.
- Lifestyle Considerations: Avoid alcohol and activities requiring alertness while taking hydroxyzine.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Hydroxyzine?
A: The dosage depends on the indication and patient factors. See the detailed dosage section above for specific recommendations.
Q2: What are the common side effects of Hydroxyzine?
A: Common side effects include drowsiness, dry mouth, dizziness, and headache.
Q3: Is Hydroxyzine safe to use during pregnancy?
A: Hydroxyzine is generally avoided during pregnancy, especially in the first trimester, due to potential fetal risks. Consult an obstetrician for individualized advice.
Q4: What are the serious side effects of Hydroxyzine?
A: Serious side effects include QT interval prolongation, torsades de pointes, and seizures.
Q5: Can Hydroxyzine be used long-term?
A: Hydroxyzine is typically prescribed for short-term use. Long-term use is generally not recommended due to the potential for tolerance and dependence.
Q6: What drug interactions should I be aware of with Hydroxyzine?
A: Hydroxyzine interacts with CNS depressants, anticholinergics, and QT-prolonging drugs. Avoid concomitant use of these medications or adjust dosages accordingly.
Q7: How does Hydroxyzine work to relieve itching?
A: Hydroxyzine blocks histamine receptors, which reduces the allergic response that causes itching.
Q8: Can Hydroxyzine be used to treat insomnia?
A: While sometimes prescribed off-label for insomnia, hydroxyzine is not FDA-approved for this indication. Its sedative properties can help with sleep, but it should not be a first-line treatment.
Q9: Can Hydroxyzine be used in patients with renal or hepatic impairment?
A: Dose adjustments are required in patients with renal or hepatic impairment. Consult the dosage guidelines for specific recommendations.
