African genomic data may reshape medicine dosing policies
A Wits-led policy brief says African genetic diversity should guide drug labels, clinical rules and safety monitoring for essential medicines.
By Priya Raghavan · Science Reporter
3 min read
A Wits University-led policy brief says African genomic data should play a larger role in how essential medicines are approved, labeled and prescribed. The brief argues that current dosing guidance for many drugs is drawn largely from European patient data, leaving gaps for African populations with high genetic diversity.
The Target Policy Profile Framework to Leverage African Genomic Heterogeneity, or TALAGH, released the brief, titled “Integrating Genomic Testing into African Drug Policies.” According to Wits University, the project found that more than 10% of essential medicines may need pharmacogenomic guidance, meaning prescribing advice based on how inherited genetic differences affect drug response.
Drug response varies by gene
The TALAGH brief points to several medicines where genetic variation can change risk or effectiveness. Wits University said efavirenz, an antiretroviral drug used in HIV treatment, is affected by CYP2B6 variation, which is common in Africa and can raise the risk of overexposure and neuropsychiatric side effects.
The brief also cites tamoxifen, a breast cancer drug that may work less well in some patients with CYP2D6-related differences in metabolism. Primaquine, used against malaria, can cause hemolytic anemia in people with G6PD deficiency, which Wits University said is common in malaria-endemic areas.
In kidney transplantation, TALAGH said dosing protocols developed mainly from European populations may give too little transplant medicine to some patients of African ancestry. The brief said that could have serious consequences for graft survival.
Distinguished Professor Collen Masimirembwa, the project’s principal investigator and a senior scientist at the Sydney Brenner Institute for Molecular Bioscience, said pharmacogenomics should be treated as a medicines policy issue. He said genomic evidence can be built into drug registration, product labeling, clinical guidelines, pharmacovigilance, health worker training and data systems.
Efavirenz as a policy example
Masimirembwa’s earlier work on efavirenz found neuropsychiatric adverse effects among patients taking the standard 600 mg daily dose, including many patients in Zimbabwe, Uganda, South Africa, Tanzania and Botswana, according to Wits University. The university said those findings helped lead Botswana to favor dolutegravir in HIV management policy, while the World Health Organization later recommended reducing efavirenz dosing from 600 mg to 400 mg daily.
Masimirembwa said prescribing guided by pharmacogenomics could identify patients who need a different dose, another medicine, closer monitoring or genetic testing before treatment. He said that approach could reduce adverse drug reactions, prevent treatment failure, avoid unnecessary switching between medicines and support more rational procurement.
Safety reporting remains a major gap, according to Wits University. The university said African countries account for only 1% of reports in VigiBase, the WHO global database for adverse drug reactions, even though Africans have up to 50% of global adverse drug reactions associated with efavirenz.
Regulators and manufacturers
The TALAGH project brought together regulators from more than 10 African countries, the South African Health Products Regulatory Authority and other stakeholders to share pharmacogenomics data, according to Wits University. The university said many regulators had not previously seen that evidence.
Masimirembwa said there is scope for a formal relationship with the African Medicines Agency, including a possible technical role for Wits in turning African pharmacogenomic evidence into regulatory guidance. Wits University also said local generic manufacturers, including companies in South Africa, could help produce formulations that match African clinical needs.
The TALAGH brief recommends pharmacogenomics-informed product labels, expert working groups inside medicines regulators, training for health care professionals, more research on African-enriched and African-specific variants, secure genomic data systems and a pan-African independent technical working group through the Consortium for Clinical Pharmacogenetics in Africa.
This story draws on original reporting from Medical Xpress.