Reported adverse drug reactions of antiretroviral therapy generic formulations in Uganda

Abstract

Background: Generic Antiretroviral drugs are commonly used in the developing countries and this has greatly contributed to the scaling up of ART. Generics vary in formulation including excipients, the production conditions and process as well as quality control procedures. This could result in differing safety and efficacy profiles during treatment and whenever patients switch between different generics as available at the hospitals. Even with demonstrated bioequivalence to innovator products there is need to monitor safety and efficacy. Unfortunately, ADRs owed to change of generics of ART combinations are underreported. Main Objective: To assess the reported adverse drug reactions of the first line ART generic formulations containing Tenofovir, Lamivudine and Efavirenz or Dolutegravir (TDF/3TC/EFV or DTG). Methods: This was a cross-sectional, exploratory sequential mixed methods study. Patient files belonging to PLHIV receiving generics of TDF/3TC/EFV(TLE) or TDF/3TC/DTG (TLD) as first line ART were reviewed and semi structured interviews were conducted with patients on TLE or TLD. The National Pharmacovigilance Centre data was also checked to look out for the ADRs related to the different generics of TLD or TLE. Health workers were interviewed to obtain further information on ADRs and their reporting. Data was entered in Open Data Kit (ODK) and analyzed using STATA version 17. Descriptive statistics and analytical comparisons were used to present and compare the ADRs between those on TLD generics as well as the TLE generics. Statistical significance was determined ad a P-value<0.05 while qualitative data was coded and analysed thematically. Results: A total of 1146 files were reviewed and 845 patients interviewed. Majority of them were females (69.8%) and on TLD regimen (99.6%). Overall, there were a total of 5,991 ADRs of which 5880 were among patients on TLD regimen and 111 among TLE. For the TLD generics, the aurobindo brand accounted for 28.6% of all the reactions reported by the patients followed by Mylan (19.7%), and Cipla (17.1%). For the TLE generics, Mylan accounted for 31.5% of the reactions followed by Laurus (27.7%) and Aurobindo (19.8%). The commonly reported reactions among TLD generics were numbness, headache, reduced libido, forgetfulness and backpain at varying frequencies and severity. There was a significant difference between ADR profiles by severity between TLD generics (P-value <0.001) and no significant difference in the ADR severity of the TLE generics (P- Value

0.480) Out of 1,389 ADRs from the patient files, there were 361 ADRs among 322 participants on the current regimen type. There were 348 cases of ADRs among 312 participants on TLD and 13cases of ADR among 10 participants on TLE. ADR reporting by health workers was mainly done by Clinical Officers, medical officers and Pharmacists. Health workers reported recording the reactions from different drugs at their health facilities in the files or registers and later submitting to NDA. However, the recorded ADRs in the NPCU database do not also specify the brand/generic involved. Conclusion There is a clear variation in the ADR profile and their severity of ART generics as reported by patients while taking different generics of the same ART regimen. These generics should further be analyzed to ascertain the chemical differences. The health workers in the ART clinics are quite knowledgeable about ADR reporting, however, they need to specify the generic/brand involved to ease the ADR monitoring.