Is hydroxyzine (an antihistamine) safe to use in patients with prolonged QTc (corrected QT interval) interval?

Hydroxyzine is Contraindicated in Patients with Prolonged QTc

Hydroxyzine is absolutely contraindicated in patients with prolonged QT interval and should never be used in this population. The FDA drug label explicitly states that "hydroxyzine is contraindicated in patients with a prolonged QT interval" 1. This is a black-and-white contraindication with no room for clinical judgment or "careful monitoring."

Why This Contraindication Exists

• Hydroxyzine directly inhibits human ether-a-go-go-related gene (hERG) potassium channels in a concentration-dependent manner, the same mechanism responsible for most drug-induced torsades de pointes 2, 3
• Post-marketing surveillance has identified 59 cases of QT prolongation and/or torsades de pointes potentially linked to hydroxyzine use between 1955 and 2016 2
• A documented case exists of a patient with an underlying HERG mutation who experienced recurrent syncope (likely from torsades de pointes) after taking hydroxyzine, with QTc prolonging from baseline to 630 ms 3
• The FDA warns that cases of QT prolongation and torsades de pointes have been reported during post-marketing use, with the majority occurring in patients with other risk factors 1

Clinical Context: When Hydroxyzine Might Seem Tempting

Hydroxyzine is commonly used for anxiety, pruritus, and as an antiemetic. However, in patients with prolonged QTc:

• For anxiety: Benzodiazepines like lorazepam are safe alternatives, as they do not prolong QT interval 4
• For nausea/vomiting: While most antiemetics (5-HT3 antagonists, metoclopramide, prochlorperazine) also prolong QTc 5, non-pharmacologic approaches or careful electrolyte management should be prioritized
• For pruritus: First-generation antihistamines like hydroxyzine should be avoided; cetirizine and loratadine carry minimal QT prolongation risk and are safer alternatives 6

Critical Risk Factors That Make This Worse

Even if a patient doesn't have baseline QT prolongation, hydroxyzine should be used with extreme caution in patients with 1, 2:

• Congenital long QT syndrome or family history of long QT syndrome
• Risk factors for QT prolongation: female sex, age >65 years, hypokalemia, hypomagnesemia, bradycardia, heart failure 7, 8
• Concomitant use of other QT-prolonging drugs (Class IA or III antiarrhythmics, certain antipsychotics, antidepressants, antibiotics like azithromycin) 1
• Recent myocardial infarction or uncompensated heart failure 1

What Defines "Prolonged QTc"

• QTc ≥500 ms is universally considered high-risk and represents an absolute contraindication to hydroxyzine 7, 8
• QTc 470-500 ms in males or 480-500 ms in females represents borderline prolongation where hydroxyzine should be avoided 8
• Normal QTc is <450 ms for men and <460 ms for women 9

Common Pitfall to Avoid

Do not assume that "monitoring" makes hydroxyzine safe in prolonged QTc. The FDA contraindication is absolute, not conditional 1. Unlike some medications where careful monitoring might allow use in high-risk patients, hydroxyzine's contraindication in prolonged QTc means it should not be prescribed regardless of monitoring intensity. The pharmacovigilance data shows that even with other risk factors present, the combination can be fatal 2.

The Bottom Line Algorithm

1. Check baseline QTc before considering hydroxyzine
2. If QTc ≥500 ms: Hydroxyzine is absolutely contraindicated 1
3. If QTc 470-500 ms (males) or 480-500 ms (females): Hydroxyzine should be avoided; choose alternative agents 8
4. If QTc is normal but patient has congenital long QT syndrome: Hydroxyzine is contraindicated 1
5. If QTc is normal but multiple risk factors exist (female, elderly, hypokalemia, other QT-prolonging drugs): Use extreme caution and consider alternatives 1, 2