Acute Porphyria Drug Database

N05BB01 - Hydroxyzine
Propably not porphyrinogenic
PNP

Rationale
Hydroxyzine is not listed as an inhibitor or inducer of any major CYP enzymes in vivo. Hydroxyzine is metabolised to cetirizine. For more information please refer to the monograph of cetirizine (ATC code: R06A E07).
Therapeutic characteristics
Hydroxyzine is indicated to assist in the management of anxiety in adults. It is also indicated for the management of pruritus associated with acute and chronic urticaria, including cholinergic and physical types, and atopic and contact dermatitis in adults and children. A less common side effect is nausea. Rare side effects are obstipation and vomiting.
Metabolism and pharmakokinetics
Hydroxyzine is metabolised via alcohol dehydrogenase and CYP3A4/5 (SPC). An active metabolite is cetirizine (SPC). For more information please refer to the monograph of cetirizine (ATC code: R06A E07). Hydroxyzine is an inhibitor of CYP2D6 in vivo (Polasek 2011 and SPC). It inhibits CYP2C9, CYP2C19 and CYP3A4 in vitro at concentrations higher than clinical relevant concentrations (SPC). Hydroxyzine is not listed as an inhibitor or inducer of any major CYP enzymes (Mouly 2009 and Polasek 2011). No drug-drug interactions with hydroxyzine as a perpetrator regarding CYP enzymes are observed (Interaksjoner), which indicate that hydroxyzine is not an inhibitor or inducer of CYP enzymes.
Published experience
Hydroxyzine has been suggested as a possible factor causing an acute attack in a 45 years old male with AIP (Asselbergs 2009), but nutritional factors resulting in a weight loss of 7 kg combined with a concomitant infection are regarded more likely to have precipitated the attack.
IPNet drug reports
Uneventful use reported in 5 patients with acute porphyria.

References

  1. Scientific articles
  2. Asselbergs FW, Kremer Hovinga TK, Bouwsma C, van Ingen J. Acute intermittent porphyria as a cause of respiratory failure: Case report. Am J Crit Care 2009, Mar;18(2):180-78. PMID 19255109. #4675
  3. Mouly S, Meune C, Bergmann JF. Mini-series: I. Basic science. Uncertainty and inaccuracy of predicting CYP-mediated in vivo drug interactions in the ICU from in vitro models: focus on CYP3A4. Intensive Care Med. 2009 Mar;35(3):417-29. PMID 19132343. #1008
  4. Polasek TM, Lin FP, et al. Perpetrators of pharmacokinetic drug-drug interactions arising from altered cytochrome P450 activity: a criteria-based assessment. Br J Clin Pharmacol. 2011 May;71(5):727-36. PMID 21223357. #4322
  5. Drug interaction databases
  6. Interaksjoner. Hydroxyzine #2675
  7. Summary of Product Characteristics
  8. Norwegian medicines agency. Summary of Product Characteristics (SPC). Atarax. #2676
  9. The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Atarax. #2677

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