Hydroxyzine

Avoid combination with valerian and St. John’s wort as this may increase CNS depression.

Hydroxyzine may be taken with or without food.

Hydroxyzine may cross-react with the carbamazepine particle-enhanced turbidimetric inhibition immunoassay or PETINIA, resulting in false interpretation of serum carbamazepine concentration (false elevation). Hydroxyzine may interfere with the measurement of total tricyclic antidepressants (false elevation) using the fluorescence polarization immunoassay.

Hydroxyzine may interfere with allergy skin test antigens by masking the response via histamine antagonism. Discontinue hydroxyzine approximately 3 to 5 days prior to an allergen skin test, as it may suppress the reaction.

In patients with primary biliary cirrhosis, administer hydroxyzine every 24 hours.

The intramuscular route is preferred over the oral route in certain situations:

• if the patient is acutely disturbed and hysterical

  
  

• if the patient is an acute or chronic alcoholic experiencing anxiety, withdrawal symptoms or delirium tremens

  
  

• as adjunctive therapy in pre- and post-operative and post-partum settings to permit substantial reduction in dose of opioids and to control emesis.

Hydroxyzine accumulates in end-stage renal disease; dose as for GFR less than 10 mL/min.

prolonged penile erections.

increased peristalsis of the gastrointestinal tract, bitter taste.

tardive dyskinesia (long-term use).

im injection: local injection site discomfort, erythema, local irritation, tissue necrosis, localized subcutaneous tissue induration.

increased reaction time, headache, paradoxical excitation in young children and infants, CNS stimulation (insomnia, irritability, restlessness, tremor, nightmares, hallucination, convulsions), tremor and seizures (rare; reported with higher than recommended doses of hydroxyzine).

urticaria, livedoid dermatitis and severe necrosis with hydroxyzine im injection (Nicolau’s syndrome), drug eruptions (including fixed drug eruption of the penis), generalized maculopapular eruption, systemic contact dermatitis.

supraventricular tachycardia in a nine-year-old child (case report), hypotension in an overdose situation.

In general, avoid first-generation antihistamines in elderly patients (≥65 years) because of their increased susceptibility to cognitive impairment due to central anticholinergic effects, such as CNS stimulation and depression, and excessive daytime sedation (see Adverse Reactions). In elderly patients, hydroxyzine may increase the risk of complications, e.g., in patients with bladder outflow obstruction, hydroxyzine use may exacerbate urinary retention by decreasing urinary flow. Other complications include worsening of narrow-angle glaucoma and symptoms of benign prostatic hyperplasia. If hydroxyzine is used in the elderly, start at a low dose; however, antihistamines which lack anticholinergic effects, such as loratadine or cetirizine, may be preferred in the elderly when treating allergic reactions.

Caution is advised in young children as paradoxical excitement has been reported.

The elderly may be more susceptible to adverse effects of hydroxyzine such as drowsiness, anticholinergic effects and hypotension. Avoid hydroxyzine and other first-generation antihistamines in elderly patients (see Indications and Clinical Use).

Use with caution in patients with benign prostatic hyperplasia and bladder neck obstruction as hydroxyzine may exacerbate urinary retention by reducing urine flow.

Because hydroxyzine causes sedation, use caution when performing tasks requiring alertness such as driving or operating machinery.

Patients with angle-closure glaucoma should avoid using hydroxyzine, due to its ability to increase intraocular pressure.

The anticholinergic effects of hydroxyzine may dry salivary secretions.

Pregnancy Category C. Although neonatal withdrawal syndrome, including seizures, has been reported with high doses of hydroxyzine (600 mg/day) throughout pregnancy, seizures have also been reported with long term maternal administration of usual therapeutic doses of hydroxyzine (150 mg/day). A prospective, controlled, observational study found no statistically significant differences in rate of live births, spontaneous or therapeutic abortion or stillbirth between hydroxyzine or cetirizine groups versus placebo. The oral antihistamine of choice in pregnancy is chlorpheniramine and the injectable antihistamine of choice is diphenhydramine.

Avoid hydroxyzine in premature and newborn infants (see Contraindications). Paradoxical excitement may occur in young children. In one study looking at diphenhydramine and loratadine and their impact on school performance in children 8 to 10 years, no difference was seen in the verbal instruction score, reading test score, reaction time, or somnolence scale between these two antihistamines. However, hydroxyzine has been found to increase subjective somnolence. Thus, caution is advised.

There are no reports of the effects of hydroxyzine on the infant during breast-feeding. Because of its low molecular weight, excretion into breast milk is expected. Antihistamines given in relatively large doses by injection may decrease basal prolactin levels in women who are not lactating and in early postpartum women. Larger doses or prolonged use of hydroxyzine may cause drowsiness or paradoxical stimulation (irritability, restlessness) in the infant. Use hydroxyzine at bedtime after the last feeding of the day as this may minimize symptoms in the infant, or offer a nonsedating antihistamine that is compatible with breast-feeding, e.g., loratadine, fexofenadine.

Use with caution in patients with cardiovascular disease as hydroxyzine may cause hypotension.

The apparent volume of distribution in the elderly is increased to 23 L/kg following a 0.7 mg/kg dose of the syrup. The mean serum elimination half-life was reported as 29.3 hours following administration of hydroxyzine syrup 0.7 mg/kg in fasting subjects.

Hydroxyzine has a large volume of distribution; the apparent volume of distribution in adults ranges from 16 L/kg to 18.5 L/kg following a 0.7 mg/kg dose of hydroxyzine. Patients with primary biliary cirrhosis showed an increase in the apparent volume of distribution to 23 L/kg following a 0.7 mg/kg dose of hydroxyzine.

Hydroxyzine is well absorbed after oral administration. Peak serum concentrations were reached in approximately 2 hours following a 0.7 mg/kg oral dose of hydroxyzine. Sedation corresponds to peak serum concentration; onset occurs within 15 to 30 minutes and lasts approximately 4 to 6 hours. Therapeutic effects of hydroxyzine do not correspond to peak serum concentration or half-life. Onset of action occurs within 1 hour and lasts about 36 hours.

Hydroxyzine, a piperazine, is an H₁-receptor antagonist which reversibly competes with endogenous histamine for the H₁-receptor sites on effector cells in the gastrointestinal tract, blood vessels and respiratory tract, thereby preventing histamine binding and action. By acting on vascular smooth muscle cells and endothelial cells, histamine leads to vasodilation and an increase in vascular permeability. By blocking vasodilation and reducing capillary permeability, hydroxyzine reduces edema and wheal formation associated with histamine release. Hydroxyzine does not, however, inactivate or prevent histamine release from effector cells. In addition to antagonizing the effects of histamine, hydroxyzine may have effects on the adrenergic, serotonergic and cholinergic receptor and thus is more likely to cause anticholinergic side effects such as dry mouth, blurred vision, urinary retention and somnolence, due to penetration across the blood-brain barrier.

Serum half-lives vary considerably between patients; elimination half-life of hydroxyzine ranges from 3 to 20 hours. Elimination half-life of cetirizine ranges from 7 to 10 hours; in patients with end-stage renal disease, the half-life increases to 20 to 30 hours. Cetirizine is mostly excreted unchanged in the urine with the remainder in the feces.

Hydroxyzine is metabolized in the liver to cetirizine, its major metabolite.

The half-life increases with increasing age; 4 hours in 1-year-old patients and 11 hours in a 14-year-old patient.