Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Apr 6:14:1130636.
doi: 10.3389/fpsyt.2023.1130636. eCollection 2023.

Tolerability profile of paliperidone palmitate formulations: A pharmacovigilance analysis of the EUDRAVigilance database

Giuseppe Cicala  1 , Renato de Filippis  2 , Maria Antonietta Barbieri  1 , Paola Maria Cutroneo  3 , Pasquale De Fazio  2 , Georgios Schoretsanitis  4   5   6 , Edoardo Spina  1   3
Affiliations

Tolerability profile of paliperidone palmitate formulations: A pharmacovigilance analysis of the EUDRAVigilance database

Giuseppe Cicala et al. Front Psychiatry. .

Abstract

Introduction: Long-acting injectable antipsychotics (LAIs) have proven to be effective in the maintenance treatment of patients suffering from schizophrenia, and their safety and tolerability profiles represent a key factor in their long-term use and choice in clinical practice. Paliperidone palmitate (PP) is the only second-generation LAI (SGA-LAI), available in both one- (PP1M) and 3-month (PP3M) formulations. However, real-world prospective studies on PP1M and PP3M are still few and mostly conducted on small samples. In this context, we aimed to better define the safety and tolerability profile of PP using real world pharmacovigilance data.

Methods: We retrospectively analyzed the publicly available data regarding Individual Case Safety Reports (ICSRs), presenting PP1M and/or PP3M as suspected drugs, reported on EUDRAVigilance between 2011 and June 30th, 2022. ICSRs relative to at least one SGA-LAI other than PP, reported between 2003 and June 30th, 2022, were also examined as reference group. Data were evaluated with a descriptive analysis, and then, as disproportionality measures, crude reporting odds ratio (ROR) and 95% confidence interval (CI) were calculated.

Results: A total of 8,152 ICSRs met the inclusion criteria, of those 77.7% (n = 6,332) presented as suspected drug PP1M, 21.2% (n = 1,731) PP3M, while 89 cases indicated both PP1M and PP3M. Significantly higher probabilities of reporting in PP-related reports were observed for the primary Standardized MedDRA Queries "Sexual Dysfunctions" (ROR = 1.45; 95% CI 1.23-1.70), "Haemodynamic oedema, effusions and fluid overload" (ROR = 1.42; 1.18-1.70), as well as "Fertility disorders" (ROR = 2.69; 1.51-4.80).

Discussion: Our analysis indicates that the tolerability and safety profiles of PP are in line with what is known for the other SGA-LAIs. However, differences regarding endocrine system ADRs have been noticed. The results presented in this work do not discourage the prescription of SGA-LAI formulations but aim to enhance their safety.

Keywords: EUDRAVigliance; adverse drug reaction; antipsychotics; drug-induced reaction; long-acting injectable; paliperidone palmitate; pharmacovigilance; schizophrenia.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
PP-related ICSRs temporal distribution. ICSRs, Individual Case Safety Reports; PP, paliperidone palmitate; PP1M, paliperidone palmitate 1-month; PP3M, paliperidone palmitate 3-month.
Figure 2
Figure 2
Relative reporting frequencies of ADRs belonging to the 10 most frequently observed SOCs. ADR, adverse drug reaction; PP1M, paliperidone palmitate 1-month; PP3M, paliperidone palmitate 3-month; SOCs, system organ classes.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. de Bartolomeis A, Barone A, Begni V, Riva MA. Present and future antipsychotic drugs: a systematic review of the putative mechanisms of action for efficacy and a critical appraisal under a translational perspective. Pharmacol Res. (2022) 176:106078. doi: 10.1016/j.phrs.2022.106078, PMID: - DOI - PubMed
    1. Mailman R, Murthy V. Third generation antipsychotic drugs: partial Agonism or receptor functional selectivity? Curr Pharm Des. (2010) 16:488–501. doi: 10.2174/138161210790361461, PMID: - DOI - PMC - PubMed
    1. Lacro JP, Dunn LB, Dolder CR, Leckband SG, Jeste DV. Prevalence of and risk factors for medication nonadherence in patients with schizophrenia. J Clin Psychiatry. (2002) 63:892–909. doi: 10.4088/JCP.v63n1007 - DOI - PubMed
    1. Valenstein M, Ganoczy D, McCarthy JF, Kim HM, Lee TA, Blow FC. Antipsychotic adherence over time among patients receiving treatment for schizophrenia. J Clin Psychiatry. (2006) 67:1542–50. doi: 10.4088/JCP.v67n1008 - DOI - PubMed
    1. Velligan DI, Wang M, Diamond P, Glahn DC, Castillo D, Bendle S, et al. . Relationships among subjective and objective measures of adherence to Oral antipsychotic medications. Psychiatr Serv. (2007) 58:1187–92. doi: 10.1176/ps.2007.58.9.1187, PMID: - DOI - PubMed