Prof Snyman, a highly respected authority in Clinical Pharmacology, has made a substantial contribution to advancing the discipline in South Africa through research, education, regulatory science and policy development. He has lectured extensively both locally and internationally and has served in numerous academic, leadership and advisory roles.
Opening his presentation, Prof Snyman stressed that NTI medicines are not simply about pharmacology but about ensuring that patients, prescribers and pharmacists all understand the importance of treatment adherence and consistent medicine use.
He explained that the therapeutic window of NTI medicines is extremely narrow, meaning that even small changes in dose or blood concentration can have profound clinical consequences. Slightly lower drug concentrations may result in treatment failure, while slightly higher concentrations can lead to serious, and sometimes life-threatening, toxicity.
Central to understanding NTI medicines is pharmacokinetics – the processes of drug absorption, distribution, metabolism and elimination. Prof Snyman emphasised that every patient metabolises medicines differently, influenced by liver and kidney function, genetic variation, concomitant medications and even dietary factors. Consequently, achieving the correct drug concentration requires far more than selecting an appropriate dose.
Examples such as grapefruit juice, which inhibits hepatic enzymes, and St John's wort, which induces drug metabolism, illustrate how common foods and supplements can significantly alter medicine concentrations. Likewise, genetic differences in drug-metabolising enzymes explain why identical doses may produce very different responses in different patients.
Prof Snyman highlighted five key characteristics that define NTI medicines: A narrow separation between therapeutic and toxic concentrations; a clear relationship between drug concentration and clinical effect; the potential for serious therapeutic failure when concentrations fall below target; the need for therapeutic drug monitoring; and the requirement for small, carefully titrated dose adjustments.
Medicines commonly regarded as NTI drugs include warfarin, digoxin, lithium, phenytoin, carbamazepine, tacrolimus, cyclosporine, theophylline and levothyroxine. Many are used to treat life-threatening conditions, including epilepsy, organ transplantation, heart failure and anticoagulation.
A major focus of the presentation was bioequivalence and the appropriate use of generic medicines. Prof Snyman stressed that generic medicines play an essential role in improving access and reducing healthcare costs, provided they meet stringent regulatory requirements for quality, safety and efficacy.
However, he cautioned that NTI medicines require more rigorous bioequivalence standards than medicines with wider therapeutic windows. While conventional bioequivalence studies generally accept plasma concentration ranges between 80% and 125% of the reference product, considerably tighter limits are required for NTI medicines because even small differences may have important clinical consequences.
Prof Snyman noted that South African Health Products Regulatory Authority (SAHPRA) guidance has recently aligned more closely with international regulatory agencies, including the US Food and Drug Administration and the European Medicines Agency, recognising the unique requirements of NTI medicines.
Despite these regulatory advances, he cautioned that substitution of NTI medicines should never be regarded as routine. Any switch between products should involve the prescribing clinician, the pharmacist and, critically, the patient. Where appropriate, therapeutic drug monitoring should be performed after switching to confirm that drug concentrations remain within the desired therapeutic range.
Patient adherence emerged as one of the strongest themes throughout the presentation. According to Prof Snyman, even when medicines are clinically equivalent, changing the appearance, colour or packaging of tablets may confuse patients and reduce adherence. Many patients associate their medicine with its appearance rather than its active ingredient, making unplanned switching particularly problematic in chronic disease management.
He argued that successful treatment depends not only on prescribing the correct medicine but also on ensuring that patients understand why they are receiving it, recognise potential adverse effects and appreciate the importance of taking it consistently.
Pharmacists play a particularly important role because they have regular contact with patients during medicine refills. Beyond dispensing medicines, pharmacists should reinforce adherence, educate patients about treatment, identify potential adverse effects and communicate any concerns to the prescribing clinician.
Prof Snyman also emphasised that therapeutic drug monitoring should not be viewed as a laboratory exercise alone but as an essential component of clinical care. Monitoring trough or peak drug concentrations, depending on the medicine involved, enables clinicians to optimise efficacy while avoiding toxicity. This is particularly important in transplant recipients, where inadequate immunosuppression may lead to graft rejection, while excessive exposure increases the risk of toxicity.
The discussion also highlighted the importance of considering individual patient circumstances. Factors such as age, co-morbidities, organ function, ethnicity, genetic variability, dietary habits and concurrent medications all influence drug disposition and response. Precision prescribing therefore requires a holistic understanding of the patient rather than focusing solely on the medicine.
Concluding his presentation, Prof Snyman reiterated that NTI medicines require precision throughout the treatment pathway—from prescribing and dispensing to patient education and ongoing monitoring. While generic substitution remains appropriate for many medicines, NTI drugs demand greater caution, structured follow-up and clear communication between healthcare professionals and patients.
Ultimately, he said, improving outcomes depends on informed clinical decision-making, robust regulatory oversight and, most importantly, ensuring that patients understand and actively participate in their treatment. For NTI medicines, successful therapy is achieved not simply by selecting the right drug, but by maintaining the right concentration in the right patient, every time.
To watch a replay of the webinar, click here https://event.webinarjam.com/9pqmp/replay/r46v4i8rva06wun1wby38l3. Don’t forget to let John Woodford know that you watched the replay to earn your CEU. Send an email to john.woodford@media24.com. Include the name of the webinar, the date (8 July) and your MP number. If you are not registered with the HPCSA, you can request a certificate of attendance from John to submit to your council.
