Pharmacists routinely manage medicine shortages in practice, however, there is little population-level evidence quantifying how shortages affect utilisation of ophthalmic medicines or whether regulatory mitigation strategies maintain access.

This study demonstrates that the 2024–2025 timolol shortage in Australia resulted in a substantial decline in single-ingredient timolol dispensings, only partially mitigated by S19A PBS-listed imports and substitution with available alternatives. Although S19A PBS-listed imports accounted for more than half of timolol dispensings during the shortage, overall utilisation of timolol-containing products remained below pre-shortage levels by end of the study.

Mirroring standard practice, during the timolol shortage pharmacists were unable to independently substitute timolol-containing products unless it was from an ARTG-registered PBS product to an equivalent S19A PBS-listed product. Any other substitution, for example, strength, formulation or providing the individual products of a combination product separately required consultation with the prescriber. Advice from national and state-level medicine regulators and professional peak bodies was variable and predominantly limited to logistical information such as duration of supply and brief details on reason for the shortage [10, 19].

Dispensing trends indicated a sequential disruption, with extended-release formulations affected first, followed by standard-release products. Temporary increases in standard-release 5 mL dispensings suggest initial switching to available alternatives; however, this strategy likely became unsustainable once supply constraints extended across formulations. S19A PBS-listed products, particularly extended-release formulations, supported continuity of therapy and became the predominant products during the peak shortage period. Nevertheless, imported products represented only a proportion of expected utilisation, suggesting that S19A supply alone was insufficient to fully restore access. Contributing factors may have included limited formulation availability, constrained import volumes, and uncertainty regarding alternative products.

The effectiveness of S19A PBS-listed medicines depends on timeliness of implementation and alignment with clinical practice [20]. In this shortage, extended-release S19A products became available within one month of shortage recognition, demonstrating a rapid regulatory response. However, equivalent products were not available for all formulations, and imported medicines did not always align with routinely prescribed Australian products, potentially limiting prescriber confidence and patient acceptance.

Despite S19A availability, timolol utilisation remained below baseline levels. While dispensing data cannot determine causality, incomplete formulation equivalence and delays in pharmacy procurement may have contributed. Unlike routinely stocked medicines, S19A products are generally sourced after prescription receipt, introducing additional delays that may discourage treatment continuation. Therefore, regulatory approval alone may not ensure timely patient access.

Timolol-containing combination products demonstrated greater resilience than single-ingredient products, with relatively minor dispensing changes during the shortage. Limited changes in prostaglandin analogue and carbonic anhydrase inhibitor dispensing suggest that broad therapeutic substitution was uncommon. This is clinically important because alternative glaucoma therapies have distinct safety considerations. Topical beta-blockers and carbonic anhydrase inhibitors may undergo systemic absorption, increasing risks of adverse effects in patients with respiratory, cardiovascular, or renal comorbidities [21, 22]. Although prostaglandin analogues are first-line therapies with generally favourable safety profiles, they may cause irreversible hyperpigmentation, hyperaemia, and eyelash growth [23]. Given that glaucoma predominantly affects older adults with substantial comorbidity burden, therapeutic substitution requires careful consideration. Patients receiving specific timolol regimens may therefore experience challenges maintaining continuity of therapy during shortages.

Seasonal dispensing patterns and PBS safety net effects contributed to temporary increases in utilisation but did not represent sustained recovery. The increase observed in December 2024 likely reflected patients reaching annual PBS safety net thresholds before reset on 1 January [24]. Limited use of 60-day dispensing for single-ingredient timolol reduced the likelihood that extended supply intervals influenced observed trends.

International evidence highlights the broader vulnerability of ophthalmic medicines to shortages. A study of a 2018 dorzolamide/timolol shortage in the United States reported that clinically appropriate substitution maintained intraocular pressure control but increased administrative burden [8]. Similarly, recurrent ophthalmic shortages in the United States have disrupted clinical workflows and increased costs for patients [25]. A recent analysis identified 379 ophthalmic medicine shortages between 2001 and 2024, with shortages frequently prolonged and associated with manufacturing and supply–demand issues [7]. These findings align with the current study, demonstrating that mitigation strategies can provide partial rather than complete resilience [25].

A major strength of this study is the use of national PBS aggregate data over five years, enabling assessment of baseline utilisation, shortage disruption, and mitigation strategies. Classification by Anatomical Therapeutic Classification code and differentiation between ARTG-registered and S19A PBS-listed products enabled interpretation of potential substitution behaviours.

Private (non-PBS) supply of medicine was not captured, potentially underestimating timolol utilisation, particularly before S19A PBS-listed product availability. Shortage timing was inferred from public reports and dispensing changes, which may not precisely reflect local product availability. Seasonal PBS safety net effects may also have influenced apparent recovery in utilisation towards end of the year [4, 24].

Although interrupted time series analysis could provide statistical estimates of changes associated with the shortage, this was not undertaken because aggregate dispensing data for ophthalmic preparations are difficult to interpret in the context of variable treatment duration and formulation longevity. Descriptive time-series analysis was therefore considered the most appropriate approach for characterising national dispensing patterns during the shortage.

Dispensing data cannot fully capture clinical consequences. Differences in formulation characteristics may affect tolerability and adherence; for example, gel-forming timolol formulations reduce dosing frequency but may cause transient visual disturbance [26]. Substitution may also introduce class-specific adverse effects, including prostaglandin analogue-associated periorbitopathy [27].

Additionally, changes between unfixed and fixed combination therapies may influence intraocular pressure control, as unfixed regimens may provide superior diurnal control in some patients [28].

Importantly, continued medicine supply does not necessarily indicate stable disease control, as glaucoma progression requires structural and functional monitoring, including optical coherence tomography and visual field assessment [29].

These findings highlight the importance of proactive shortage management. Clinicians should anticipate formulation-specific vulnerabilities, establish switching plans, and collaborate with pharmacists and regulators to minimise disruption. Pharmacists have an important role in facilitating continuity of care by communicating S19A product availability and supporting patient counselling.

For policymakers, the timolol shortage demonstrates that regulatory responses require timely activation, alignment with clinical practice, and sufficient supply capacity. Future strategies should prioritise rapid S19A implementation, availability of clinically equivalent formulations, diversified supply pathways, and mechanisms such as Serious Scarcity Substitution Instruments to enable timely pharmacist-led substitution where appropriate [12]. Clear guidance regarding dose equivalence and communication strategies may improve uptake of alternative products.

Future research should link dispensing data with clinical outcomes and explore patient, pharmacist and prescriber experiences to better understand responses to medicine shortages.