The comparison of the quality of selected brands of antibiotics in Tanzania sourced from different geographical regions.

OBJECTIVES: The quality of amoxicillin capsules, ceftriaxone for injection, and ciprofloxacin tablets was evaluated to determine whether there is any difference in quality when comparing the country of origin. This was undertaken because it has been claimed that antibiotics manufactured in Europe are of superior quality to those originating from Africa or Asia. METHODS: Samples of amoxicillin capsules, ceftriaxone for injection, and ciprofloxacin tablets were collected from three randomly selected wholesale pharmacies in each city, namely Arusha, Dar es Salaam and Mwanza, Tanzania. The collected samples of collected brands were subjected to quality control testing as per their respective pharmacopoeial monographs. Amoxil 250 mg capsules (Glaxo Wellcome, Mayenne, France), Rocephin (Roche, Switzerland) and Cipro-Denk 500 (Allphamed Pharbil Arzneimittel GmbH, Gottingen, Germany) were used as reference brands for the other generic brands of amoxicillin, ceftriaxone and ciprofloxacin, respectively. RESULTS: A total of 31 brands (10 different brands of amoxicillin capsules, 9 of ceftriaxone sodium injections, and 12 of ciprofloxacin tablets) were collected from the targeted regions and subjected to quality control testing. All samples of collected brands complied with the requirements of their respective pharmacopoeial monographs. CONCLUSIONS: There was no significant difference in quality between brands of amoxicillin capsules, ceftriaxone for injection, and ciprofloxacin tablets manufactured in Africa and Asia against those manufactured in Europe in terms of compliance with the respective pharmacopoeial monographs.

Post marketing surveillance of selected veterinary medicines in Tanzania mainland.

BACKGROUND: Veterinary medicines have been widely used for the prevention and treatment of animal diseases. Globally, the veterinary medicine industry is growing. However, there is a significant increase of concern on the quality of veterinary medicines in various developing countries' legal markets. Poor-quality medicines are associated with treatment failure, development of drug resistance, increased healthcare cost, and death. These reasons warrant a need for monitoring the quality of the medicines circulating in the Tanzania Mainland. METHODS: This was a survey study and veterinary medicines samples were collected from 9 out of 26 regions of Tanzania mainland between 2014 and 2017. Veterinary medicines were sampled from wholesale pharmacies, retail pharmacies, veterinary clinics and Veterinary Accredited Drug Dispensing Outlets (ADDO-vet). All sampled medicines were subjected to product information review and full quality control testing at the Tanzania Medicines and Medical Devices Authority-World Health Organization prequalified laboratory. RESULTS: A total of 238 samples of veterinary medicines were collected. Out of these, 97.1% (231/238) were subjected to full quality control testing and product information review. All sampled veterinary medicines conformed to visual appearance, clarity, pH, solubility and sterility tests. Also, of the sampled veterinary medicines 97.8% (226/231) and 89.2% (206/231) passed identification and assay tests, respectively. As well as, the majority of the collected samples 92% (219/238) failed to comply with product information requirements. The most observed deficiencies on product information were inadequate information on the package insert 94.1% (224/238), inappropriate storage conditions 55.5% (132/238) and lack of Tanzania registration number 27% (64/238). CONCLUSION: Veterinary medicines with poor quality were found circulating in the legal markets of Tanzania. This can potentiate treatment failure and the development of drug resistance in animals and humans. Post marketing surveillance program will continue to be implemented to ensure that only good quality, safe and efficacious medicines are circulating in the Tanzania Mainland market.

Adverse Drug Reactions Resulting From the Use of Chiral Medicines Amoxicillin, Amoxicillin-Clavulanic Acid, and Ceftriaxone: A Mixed Prospective-Retrospective Cohort Study.

The use of chiral medicines (possessing center(s) of asymmetric carbon) may cause adverse drug reactions (ADRs). The safety assurance of these medicines is critical. We aimed to evaluate registered and commonly used anti-infective chiral medicines circulating in the Tanzanian market to establish their safety profile to protect public health. A mixed prospective-retrospective cohort study was conducted to assess the safety profile of amoxicillin, amoxicillin-clavulanic acid and ceftriaxone injection. ADRs causality assessment was conducted by using World Health Organization (WHO)-Algorithm criteria. Data were collected from 7 tertiary hospitals: Muhimbili National Hospital (MNH), Kilimanjaro Christian Medical Centre (KCMC), Bugando Medical Centre (BMC), Ligula Referral-Regional Hospital (LRRH), Kitete Referral-Regional Hospital (KRRH), Dodoma Referral-Regional Hospital (DRRH), and Mbeya Zonal-Referral Hospital (MZRH). Data were supplemented by those recorded in the WHO-Vigiflow/VigiLyze database within the same monitoring period. Data were analyzed using STATA version-15. The results were considered statistically significant when P < .05. A total of 2522 patients were enrolled in hospitals: MNH (499), KCMC (407), BMC (396), LRRH (387), KRRH (345), DRRH (249), and MZRH (239). Among those, 1197 (47.5%) were treated with ceftriaxone, 585 (23.2%) amoxicillin and 740(29.3%) amoxicillin-clavulanic acid. Out of those, 102 (4.5%) experienced adverse events (AEs), 49 (48%) were due to ceftriaxone, 37 (36.3%) amoxicillin-clavulanic acid and 16 (15.7%) amoxicillin (P-value .012). A total of 443 participants from the enrolled and WHO-Vigiflow/VigiLyze database were experienced with ADRs. The ADRs affected mainly gastro-intestinal system 234 (53%), skin and subcutaneous tissue 85 (19%), nervous system 49 (11%), respiratory thoracic 22 (5%), and general disorders 18(4%). In this study, approximately 90% of reported AEs were ADRs possible-related to the monitored medicines, with few plausible and certain. Ceftriaxone injection caused more ADRs. Amoxicillin-clavulanic acid was associated with more ADRs than amoxicillin alone. The safety profile of these medicines is still maintained; however, comprehensive monitoring of ADRs is recommended to improve patient safety and enhance overall treatment outcomes.

A high-performance thin-layer chromatography densitometric method for the separation of isomeric ceftriaxone in powder for injection formulation.

The aim of this study was to develop and validate a High-Performance Thin Layer Chromatographic (HPTLC) method for simultaneous determination of ceftriaxone and ceftriaxone e-isomer in powder for injection formulation. Ceftriaxone sodium injection is an antibiotic that used globally. It has Z/E geometrical conformation, in which ceftriaxone sodium and 3 ene-isomer have Z- conformation while (E)-isomer has E- conformation and the potential toxicity of ceftriaxone (E)-isomer has been reported. Thus, to safeguard the public health, a simple and easy to use, rapid and reliable method was developed for qualitative and quantitative determination of ceftriaxone sodium and its (E)-isomer. Samples were applied on HPTLC glass plates precoated with silica gel 60F254 by using Linomat semi-auto sampler. Separation was carried out using acetone, triethyl amine, water, chloroform and ethyl acetate as a mobile phase in different ratios. The Rf values of separated compounds were 0.51 ± 0.01 and 0.62 ± 0.01 for ceftriaxone sodium and ceftriaxone (E)-isomer respectively. The method was validated by studying Specificity, Linearity, Accuracy, Precision, Robustness, Limit of Detection (LOD) and Limit of Quantification (LOQ) and Solution stability. The developed method was successfully, sensitive, simple, precise, accurate, robust and applicable for the simultaneous determination of ceftriaxone sodium and ceftriaxone (E)-isomer in powder for injection formulation.

Effectiveness of a structured stimulated spontaneous safety monitoring of medicines reporting program in strengthening pharmacovigilance system in Tanzania.

Under-reporting of adverse drug events (ADEs) is a challenge facing developing countries including Tanzania. Given the high magnitude of under-reporting, it was necessary to develop and assess the effectiveness of a 'structured stimulated spontaneous safety monitoring' (SSSSM) reporting program of ADEs which aimed at strengthening pharmacovigilance system in Tanzania. A quasi-experimental design and data mining technique were used to assess the effect of intervention after the introduction of program in seven tertiary hospitals. ADEs reports were collected from a single group and compared for 18 months before (July 2017 to December, 2018) and after the program (January 2019 to June 2020). Out of 16,557 ADEs reports, 98.6% (16,332) were reported after intervention and 0.1% (23) death related to adverse drug reactions (ADRs) were reported. Reports increased from 20 to 11,637 after intervention in Dar es salaam, 49 to 316 in Kilimanjaro and 17 to 77 in Mbeya. The population-based reporting ratio per 1,000,000 inhabitants increased from 2 reports per million inhabitants in 2018 to 85 reports in 2019. The SSSSM program can increase the reporting rate of ADEs and was useful in detecting signals from all types of medicines. This was first effective developed spontaneous program to monitor medicine safety in Tanzania.

Quality of selected anti-retroviral medicines: Tanzania Mainland market as a case study.

BACKGROUND: Antiretroviral drugs (ARVs) have significantly reduced morbidity, mortality and improved the quality of life of people living with HIV infection. Poor quality ARVs may result in harmful consequences such as adverse drug reactions, treatment failure and development of drug resistant strains and sometimes death, which in turn may undermine the healthcare delivery system. To ensure optimal treatment outcomes, medicines quality control must be undertaken regularly. This study was aimed at evaluating the quality of ARVs circulating on the Tanzania Mainland market. METHODS: This was a survey study. ARVs samples were collected in 20 regions of Tanzania Mainland, between 2012 and 2018. All sampled ARVs were subjected to screening testing using the Global Pharma Health Fund® Mini-Lab kits. Sampled ARV's that failed screening test or yielded doubtful results and 10 % (10 %) of all that complied with the screening test requirements were selected for full quality control testing. Quality control testing was conducted at the Tanzania Medicines and Medical Devices Authority (TMDA) laboratory a World Health Organisation prequalified. Samples collected from the medicine distribution outlets were also, subjected to product information review. RESULTS: A total of 2,630 samples were collected, of which 83.7 % (2200/2630) were from port of entry (POEs). All sampled ARVs were screened and conformed to the specifications, except of the fixed dose combination (FDC) lopinavir/ritonavir 0.27 % (7/2630) and lamivudine/zidovudine/nevirapine 0.27 % (7/2630) that failed the disintegration test. Out of the 100 samples selected for full quality control testing, 3 % of them failed to comply with the specifications, of which FDC stavudine/lamivudine/nevirapine failed disintegration and assay tests 2 % (2/100) and 1 % (1/100), respectively. Samples failing the assay test had low content of stavudine (86.6 %) versus specification limits (90 -110 %). Out of the 430 samples which were subjected to product information review, 25.6 % (110/430) failed to comply with the TMDA packaging and labelling requirements. CONCLUSIONS: The quality of majority of ARVs circulating on the Tanzania Mainland market was good, even so, significant deficiencies on labelling and packaging were observed. These results call for continuous monitoring of quality of medicines circulating on the Tanzania Mainland market.

A retrospective cross-sectional study to determine chirality status of registered medicines in Tanzania.

Medicines with a stereogenic center (asymmetric carbon) are mainly present as racemates with a mixture of equal amounts of enantiomers. One enantiomer may be active while the other inactive, alternatively one may produce side-effects and even toxicity. However, there is lack of information on the chirality status (either racemates, single active enantiomer or achiral) of medicines circulated on the market particularly in African countries. We established the chirality status of registered medicines in Tanzania by conducting a retrospective cross-sectional study. Registration data for the past 15 years from 2003 to 2018 were extracted from TMDA-IMIS database to Microsoft excel for review and analysis. A total of 3,573 human medicines had valid registration. Out of which 2,150 (60%) were chiral and 1,423 (40%) achiral. Out of the chiral medicines, 1,591 (74%) and 559 (26%) were racemates and single active enantiomers, respectively. The proportion of racemates within chiral medicines was considerably higher than single enantiomer medicines. The use of racemates may cause harm to the public and may contribute to antimicrobial resistance due to potential existence of inactive and toxic enantiomers. In order to protect public health, regulatory bodies need to strengthen control of chiral medicines by conducting analysis of enantiomeric impurity.

Safety Profile of Artemether-Lumefantrine: A Cohort Event Monitoring Study in Public Health Facilities in Tanzania.

BACKGROUND AND OBJECTIVE: Artemisinin combination therapies such as artemether-lumefantrine (AL) are effective for first-line treatment of uncomplicated acute Plasmodium falciparum malaria. However, the safety profile of AL in large populations has not been fully assessed. The objective of this study was to establish the safety of AL in public health facilities in Tanzania using the Cohort Event Monitoring (CEM) method. METHODOLOGY: Patients who presented to public health facilities in four regions of Tanzania who were prescribed AL were enrolled in a CEM study, a prospective, observational cohort study to establish a profile of adverse events (AEs) for the medicine when used in routine clinical practice. Pre- and post-treatment forms were used to record baseline information and new health events before and 7 days after treatment. RESULTS: A total of 8040 patients were enrolled in the study, of whom 6147 were included in the analysis. Following treatment initiation, a total of 530 AEs were reported in 6% (383) of the patients. The most frequent post-treatment AEs were in alimentary system (42%), including vomiting, nausea, diarrhoea, abdominal pain and anorexia, followed by AEs in the neurological system (25%). Causality assessment of the events showed that 51.9% (275/530) were possibly related to AL. There was a significant difference in the frequency of AEs by age-group with an increase in the number of AEs as age increased (P < 0.001). There was no statistically significant difference in the frequency of the events between males and females (P = 0.504). The AE profile was consistent with the AEs reported in the product information and in other studies; no new adverse drug reactions were identified. The majority of the reported AEs were the same as the symptoms of malaria and therefore indistinguishable from the underlying disease. CONCLUSIONS: The safety profile of AL for treatment of malaria continues to be favourable. CEM as a pharmacovigilance tool has proven to provide reliable safety data in a short period.

In vitro evaluation of the quality of essential drugs on the Tanzanian market.

We evaluated the in vitro availability and its stability under simulated tropical conditions of various formulations of four essential drugs marketed in Tanzania. We obtained 22 formulations (containing paracetamol, acetylsalicylic acid, chloroquine or sulphadoxine/pyrimethamine) from wholesale pharmacies in Dar es Salaam and the Medical Stores Department (Tanzania). The drug content, in vitro availability (dissolution) and its stability under simulated tropical conditions were determined using methods specified in the United States Pharmacopoeia (USP) 24 monograph of the respective drugs. All formulations passed the pharmacopoeia requirements for the drug content. However, seven formulations (three acetylsalicylic acid, two sulphadoxine/pyrimethamine and two paracetamol) failed to meet the USP 24 tolerance limits for dissolution. Another five formulations (three paracetamol and two chloroquine) failed to meet the dissolution tolerance limits after being subjected to an accelerated stability test under simulated tropical conditions (75% RH/40 degrees C) for 6 months. The study has demonstrated the presence on the Tanzanian market of essential drug formulations that met potency requirements and yet had unsatisfactory in vitro availability as they were not robust enough to withstand storage under simulated tropical conditions.