Hydroxyzine

May rarely cause acute generalized exanthematous pustulosis (AGEP), a serious skin reaction involving fever, pustules and large areas of edematous erythema. Discontinue at first sign of skin rash, worsening of pre-existing skin reactions or any other sign of hypersensitivity; if signs or symptoms suggest AGEP, do not resume therapy.

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

Has been reported, with the majority occurring in patients with other risk factors for QT prolongation/torsades de pointes (eg, preexisting cardiac disease, electrolyte imbalances, concomitant arrhythmogenic use). Use with caution in patients with risk factors for QT prolongation, congenital long QT syndrome, a family history of long QT syndrome, other conditions that predispose to QT prolongation and ventricular arrhythmia, as well as recent myocardial infarction, uncompensated heart failure, and bradyarrhythmias. Oral hydroxyzine is contraindicated in patients with a prolonged QT interval. Disease-related concerns:

Use with caution in patients with narrow-angle glaucoma; condition may be exacerbated by cholinergic blockade. Screening is recommended.

Use with caution in patients with prostatic hyperplasia and/or urinary stricture.

Use with caution in patients with asthma or chronic obstructive pulmonary disease (COPD). Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations: Elderly: May cause over sedation in the elderly; initiate elderly patients on low does and monitor closely. Dosage form specific issues:

Some dosage forms may contain benzyl alcohol and/or sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggest that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol and/or benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.

Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling. Other warnings/precautions:

Parenteral: For IM use only. Severe injection-site reactions have been reported with IM administration (eg, extensive tissue damage, necrosis, gangrene) requiring surgical intervention (including debridement, skin grafting, and amputation). SubQ, IV, and intra-arterial routes of administration are contraindicated. Intravascular hemolysis, thrombosis, and digital gangrene have been reported with IV or intra-arterial administration (Baumgartner 1979); SubQ administration may result in significant tissue damage. If inadvertent IV administration results in extravasation, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity.

The effectiveness of hydroxyzine for long-term use (>4 months) has not been assessed; periodically reassess use.