(184) Lopinavir Induced Hypospadias: New Signal Detection for Lopinavir by Disproportionality Analysis Using USFDA Database

Publication Number: 515

Background: Drug induced congenital anomalies can be averted if the health care practitioners of kept informed of the adverse outcomes in pregnant females. Hypospadias are commonly observed with anticonvulsants. In the current study, hypospadias was detected as a new signal for lopinavir.

Objectives: The current study explored the medications associated to cause hypospadias by analyzing the data mined from the US FDA adverse event reporting system (US FAERS) database.

Methods: It is a case-non case study employing the data mining algorithms. A disproportionality analysis was performed to identify the drug event combinations (DEC). The adverse events reported in FAERS were retrieved with the preferred therapeutic term hypospadias. The data was mined from the first quarter of 2006 to November 2021 using the OpenVigil 2.1 database. Proportional reporting ratio (PRR>1) and reporting odds ratio (ROR>2) with 95% confidence intervals (CI) and drug event combinations >10 was used as the criteria for predicting the drugs associated to cause hypospadias. Subgroup analysis was done to determine the congenital anomalies.

Results: Lopinavir is a protease inhibitor reported to cause congenital hypospadias in the USFDA database. The PRR observed for lopinavir is 18.75 and ROR is 18.8(13.55,26.07) with 37 events. The medication reported to cause highest PRR is fluphenazine enanthate with PRR 4712.53 and ROR 14315.6(2586.83,77243.26) with 4 events. Anticonvulsants, antivirals and selective serotonin reuptake inhibitors (SSRIs) are commonly reported to cause hypospadias. Among the anticonvulsants, valproate exhibited higher PRR 48.8 and ROR 49.1 with 109 events. Among antivirals, nelfinavir showed 136.55 and ROR 139.12 with 55 events. Among SSRIs, fluoxetine PRR 10.17, ROR 10.18 and drug-event as 20. The subgroup analysis revealed a higher rate of anomalies for tenofovir.

Conclusions: Lopinavir associated hypospadias is a new signal generated to alert the health care practitioners to monitor the administration of lopinavir among pregnant females. Lopinavir should be administered with caution in pregnant females with Human immunodeficiency viral infection I.