Australia adopted a quick and stern response to the coronavirus disease 2019 (COVID-19) pandemic by closing international borders, as well as locking down localities and regions for varying periods of time to stop the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across the country. However, common beliefs fueled by celebrity endorsements caused a temporary rise in the use of some medications said to help prevent the infection or mitigate its severity.
A new study published on the preprint server medRxiv* describes the nature and extent of the shift in dispensing these medications, as well as its eventual outcome.
Study: Changes In Dispensing of Medicines Proposed for Re-Purposing in the First Year of the COVID-19 Pandemic in Australia. Image Credit: Horacio Selva / Shutterstock.com
Background
A number of medications were proposed to be effective in preventing COVID-19, treating the infection, and/or limiting the progression of the disease. Among these are undeniably useful drugs such as dexamethasone, as well as potentially useful drugs such as certain cytokine inhibitors and remdesivir.
Ivermectin, an anti-parasitic drug, hydroxychloroquine, an antimalarial and anti-rheumatic drug, and vitamin D, have been widely touted, in some cases by celebrities, as being highly effective in COVID-19 prevention and treatment. Despite the fact that their safety and efficacy in this regard are unsupported by large well-designed trials, these drugs are still being prescribed on a large scale.
Earlier studies of such trends have focused mainly on areas with a high incidence of COVID-19, such as the United States, where hydroxychloroquine prescriptions rose seven-fold in March 2020 over the previous year.
The current study aimed to explore changes in medicine prescribing in an area in Australia with a COVID-19 incidence of less than 120/100,000 population. This means that a jump in prescriptions of hydroxychloroquine, for instance, is unlikely to be due to its use in the actual management of COVID-19 cases. Rather, the chances are that it is being stored by rheumatic patients to avoid running short of it or to prevent COVID-19 in individuals who think it will be of benefit.
The National COVID-19 Clinical Evidence Taskforce, which was set up to continuously assess available evidence and issue current guidelines on COVID-19 prevention and management, undertook the current study to understand how these drugs are being dispensed since the start of the pandemic in Australia between March a d November 2020.
Study findings
The researchers found that all medications dispensed by community doctors went up by 20% above expected levels in March 2020 but then dropped for several months. Azithromycin dispensing was lower from April to November 2020, by about 64,000 dispensings.
Hydroxychloroquine dispensing went up by 25,000 in March 2020, or an astonishing 99.4% increase over the predicted level, but by 5,000 in April 2020. Thereafter, the prescriptions of this drug dropped such that the overall increase over expected values was 9,000 more over the whole study period. About 70% of the March increase was attributed to stockpiling by existing users, while there were over 700 new users during the study period.
New users in March and April 2020 were mostly female at 70% as compared to 75% over the same months in the previous year. General practitioners (GPs) contributed many additional new dispensings, at 43% as compared to 25% the previous year. Rheumatologists wrote 26% of the prescriptions in 2020, as compared to 45% in 2019.
Only 16 new prescriptions for hydroxychloroquine also contained a prescription for azithromycin during this period.
Ivermectin prescriptions rose between May to November 2020, peaking in May with a 56% increase above predicted demand. The dispensings rose by almost 2,000 over expected levels during the study period. Almost two of every three prescriptions were by GPs in both 2019 and 2020.
Colchicine dispensing rose in March, and smaller increases in June and September 2020, without any significant difference over the whole period, or new users.
Calcitriol is a form of vitamin D. This was prescribed more often in March, June, and September 2020, with the same pattern as colchicine.
Corticosteroids were prescribed less often overall, with a drop of 77,000 below expected levels.
Implications
The current study shows that hydroxychloroquine and ivermectin were prescribed more often than expected during the COVID-19 period. This was especially true at the beginning of the pandemic in March 2020, when all commonly prescribed drugs saw a rise in prescriptions by about 20%. This is partly due to hoarding as a result of shortage fear by people already using these drugs.
The rise in GP prescriptions for hydroxychloroquine is similar to that seen in the United States, where primary care physicians prescribed the drug at over ten-fold higher levels during the pandemic period. This drug is not known to be effective in treating or preventing COVID-19; therefore, the Taskforce recommends against its use.
The Therapeutic Goods Administration (TGA) in Australia regulated its prescription for new users on March 24, 2020, in response to such unwarranted prescriptions. An earlier study in the same country showed that half the new users of this drug who had received a prescription from their GPs actually had an indication for its use.
The drop in azithromycin prescriptions is likely due to the observed dramatic drop in the incidence of respiratory infections during this period. Ivermectin prescriptions rose later than hydroxychloroquine and persisted longer, probably because it was touted as an effective preventive against severe COVID-19 only from April 2020 onwards.
The Taskforce does not recommend Ivermectin either, as clinical trials are still going on to evaluate its efficacy. The relatively small increase in prescriptions indicates that some people still believed in its preventive effects.
The changes in prescriptions for stockpiling purposes can create shortages where there are none, or worsen existing ones. So far, people in Australia have not experienced drug shortages. Local policies and regulatory agencies can help avoid such events during supply chain disruptions, as happened with the ongoing pandemic, by quickly restricting the indications for vulnerable drugs and the practitioners who can prescribe them.
“Balanced and informed communication of the changing evidence, including up-to-date and reliable access to evidence-informed advice is necessary to minimise any negative health impacts related to re-purposing of medicines.”
*Important notice
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.