title: An analysis of potentially prolactin-related adverse events and abnormal prolactin values in randomized clinical trials with paliperidone palmitate.
abstract: BACKGROUND
  Paliperidone palmitate has been associated with serum prolactin elevations in some patients. However, few individuals with elevated prolactin levels (hyperprolactinemia) have symptomatic potentially prolactin-related adverse events (PPR-AEs).
  
  
  OBJECTIVE
  To quantify rates of hyperprolactinemia in subjects treated with the newly marketed paliperidone palmitate long-acting injection (PP-LAI) in randomized clinical trials, summarize rates of PPR-AEs in those trials by sex and dose, and determine how many PPR-AEs required treatment.
  
  
  METHODS
  Numbers and rates of investigator-reported hyperprolactinemia and PPR-AEs were obtained from the sponsor's clinical trial database and have been included in regulatory filings. Results were tabulated for males, females, and overall, and by dose administered, using descriptive statistics. Those requiring treatment were described as well.
  
  
  RESULTS
  There were 3173 subjects (61.4% males) exposed to PP-LAI in 10 clinical trials; 2831 (89.2%) patients had recorded prolactin levels, including 1759 males (90.3% of exposed males) and 1072 females (87.5% of exposed females). Overall, at any time, prolactin levels were elevated for 38.8% of the subjects (39.5% for males and 37.7% for females; p = 0.354 between sexes). However, there was no significant correlation between monthly dose and proportion of subjects with elevated prolactin levels (p = 0.109). There were 115 PPR-AEs in 107 patients (3.4%); 51 (44.3% of PPR-AEs) cases represented asymptomatic hyperprolactinemia. The remaining 64 symptomatic PPR-AEs affected 2.0% of the total number of subjects. Fifteen events in 13 participants (0.41% of patients or 4.7 events/1000 patients) required treatment.
  
  
  CONCLUSIONS
  Clinicians should periodically assess patients on paliperidone palmitate for any PPR-AEs and carefully assess the benefits and risks when managing these effects.
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Ontario, Canada. t.einarson@rogers.com
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Einarson
authors.forename: Michiel E H
authors.initials: ME
authors.lastname: Hemels
authors.forename: Isaac
authors.initials: I
authors.lastname: Nuamah
authors.forename: Srihari
authors.initials: S
authors.lastname: Gopal
authors.forename: Danielle
authors.initials: D
authors.lastname: Coppola
authors.forename: David
authors.initials: D
authors.lastname: Hough
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006966:Hyperprolactinemia / Q000097:blood / Q000139:chemically induced*; D007555:Isoxazoles / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D010168:Palmitates / Q000009:adverse effects*; D011388:Prolactin / Q000097:blood; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D007555:Isoxazoles; D010168:Palmitates; D011388:Prolactin; D000068882:Paliperidone Palmitate