On this page:
- Advice on off-label medicines for treatment and prophylaxis of COVID-19
- Statement on healthcare worker use of PPE when caring for suspected, or confirmed COVID-19 patients
- Statement on home isolation
- Statement on organ donation and transplantation during the COVID-19 pandemic
- Statement on rapid point of care lateral flow devices to detect antibodies to SARS-COV-2
Advice on off-label medicines for treatment and prophylaxis of COVID-19
AHPPC notes that there is currently very limited evidence to support the use of medications for the treatment of COVID-19. Several medications have been proposed as likely candidates to treat COVID-19. There are currently clinical trials both within Australia, and internationally, to test their efficacy and safety.
Broadly, the medication classes that have been suggested may help manage those with COVID-19 include:
- Antimalarial drugs (such as chloroquine and hydroxychloroquine)
- Antivirals (such as favipiravir, umifenovir, remdesivir)
- Antiretrovirals (such as Ritonavir + Lopinavir ("Kaletra"))
- Immune modulators (Interferon α, β, γ or λ; β looks most promising)
- Biologic Disease Modifying Anti-Rheumatic Drugs (Interleukin-6 inhibitors, such as tocilizumab and sarilumab)
Some of these medications are marketed within Australia for indications other than COVID-19, and have known pharmacokinetics, pharmacodynamics and side effect profiles. Others are novel drugs that have either not yet been tested in clinical trials, are undergoing testing, or are used in countries overseas, but not registered with the TGA.
Off-label medication use in Australia
Lopinovir/ritonavir and hydroxychloroquine (hydroxychloroquine; +/- azithromycin) are the most common drugs prescribed for therapy or prophylaxis against COVID-19. There are several clinical trials being undertaken to assess the efficacy of antiviral therapies in COVID-19 infection.
Summary
Due to safety concerns, and the unknown effects of prescribing these medications for off-label usage, such as for COVID-19 infection, there are no current recommendations to treat patients with mild to moderate COVID-19 illness. It is also not recommended to use medications prophylactically (McCreary 2020).
Appropriate dosage of medications for use in COVID-19 are not yet determined, and there is concern that if used inappropriately, off-label use of medications may cause toxicity and lead to adverse patient outcomes.
AHPPC recommends symptomatic support and supplemental oxygen therapy for those with severe illness because of COVID-19 infection. If the patient experiences extreme respiratory distress, or continues to deteriorate and cannot be effectively managed with supplemental oxygen, intubation and mechanical ventilation may be necessary. In cases of septic shock or haemodynamic instability, haemodynamic support including vasopressors, may be required in an Intensive Care Unit setting.
For deteriorating or critically ill patients, supportive care is still currently recommended as best practice. Experimental use of medications is not recommended, and should only be prescribed as part of a clinical trial.
Medications can continue to play a role in the management of a patient infected with COVID-19, but only if being prescribed for their original purposes. For example, administering oseltamivir if the patient is co-infected with influenza, or the use of corticosteroids in those critically ill where they would normally be used, for example COPD.
The health and safety of all Australians is of paramount importance, and at this time, the AHPPC considers the evidence supporting off-label usage of medications for COVID-19 is not sufficient. We will continue to monitor the outcomes of clinical trials, and will update our recommendations as more information becomes available.
Background
Chloroquine/hydroxychloroquine
Long acting immunomodulatory drugs that may prevent viral replication in cell phagolysosome. In vitro activity of hydroxychloroquine generally has greater efficacy than chloroquine. The optimal dose is uncertain and recommended regimens vary.
- A Chinese group reported "apparent efficacy" of chloroquine therapy with clinical and virologic benefit versus a comparison group and no severe adverse drug reactions. Potential cardiotoxicity was a concern (Gao et al, Biosci Trends, 2020). Results of peer-reviewed trials in China awaited.
- There have been two reports of experience with hydroxychloroquine +/- azithromycin in 20 patients and hydroxychloroquine + azithromycinin in 80 patients from French studies (Gautret et al., Int J Antimicrob Agents[1], 2020; Gautret, preprint only[2]). The second study included 80 admitted patients. They planned patients to receive hydroxychloroquine (200mg t.i.d for ten days) and azithromycin (500mg on the first day, 200mg q.d. for the next four days). Results: Claimed clinical and virological improvement with the combination. There are many problems with this study. This combination has increased risk of cardiac toxicity.
There are still several clinical trials in play, including a prophylaxis trial by Boulware et al in the United States of America against COVID-19.
Lopinivir/ritonavir
A protease inhibitor used in HIV directed against a specific sequence of the virus not present in SARS-CoV-2. It appears however, to block the main protease of SARS-CoV-1 and inhibit viral replication. It has shown mortality reduction in SARS. Early anaecdotal mono- or combination therapy reports of value are not interpretable.
There has been a recent open label randomised trial in hospitalised patients with severe pneumonia that compared 99 patients undergoing medication-based care versus 100 patients receiving standard care. The study showed no difference in reduction in viral load or primary composite EP (Cao et al., NEJM, 2020).
Note: median time to treatment was 13 days and in SARS-CoV-1 infection effective therapy is given early. However, there was significant toxicity. Conclusion: Ongoing clinical trial results are awaited, including combination therapy.
References
1. EK McCreary, J M Pogue JM. COVID-19 Treatment: A Review of Early and Emerging Options. Open Forum Infectious Diseases: http://doi.org/10.1093/ofid/ofaa105 (accessed 1 April 2020).
2. J Gao, Z Tian, X Yang. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends: http://doi.org/10.5582/bst.2020.01047 (accessed 1 April 2020).
3. P. Gautret, J.C. Lagiera, P. Parolaa, V.T. Hoanga, L. Meddeba, M. Mailhea, et al.
Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open label non-randomized clinical trial. Int J Antimicrob Agents http://doi.org/10.1016/j.ijantimicag.2020.105949 (accessed 17 March 2020).
4. B Cao, Y Wang, D Wen, W Liu, J Wang, G Fan et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. New England Journal of Medicine: http://doi.org/10.1056/NEJMoa2001282 (accessed 1 April 2020)
Footnotes
[1] Gautret: Unusual approach to reporting results - clinical correlation with nasopharyngeal clearance on day 6 unknown; several patients changed status converted from negative to positive within a few days of endpoint. The choice of this endpoint (EP) was not explained. 4/6 excluded patients had adverse outcomes (admission to ICU or death) at EP but were not counted in the analysis. Patients who refused to consent to the study group were included in the control arm, indicating unorthodox study enrolment
