Medicines Management COVID-19

Position
Fever is a common symptom of COVID-19. The ability to develop a fever has been associated with a good prognosis in other respiratory infections so routine use of antipyretic medicines to reduce fever is not necessary.

Consider paracetamol, if it is necessary to use an antipyretic to reduce fever associated with COVID-19.

There is no strong evidence to associate ibuprofen or other non-steroidal anti-inflammatory medicines (NSAIDs) with worsening of COVID-19 symptoms. Patients taking NSAIDs routinely should continue with treatment.

Background
Symptoms of COVID-19 may include fever and this should be expected to be reduced with either paracetamol or a non-steroidal anti-inflammatory medicines (NSAIDs) such as ibuprofen.

There have been reports in France regarding the worsening of the condition of patients with COVID-19 with ibuprofen. The debate around these reports has been reviewed by the BMJ online.

Guidance from the Therapeutic Goods Administration (TGA) and the European Medicines Agency indicate there is no strong evidence between ibuprofen and worsening of COVID-19 symptoms.

The Royal College of General Practitioners has a commentary on the background around the use of antipyretics in COVID-19.

There is no research into a potential link between ibuprofen (or other NSAIDs) and the worsening of COVID-19 symptoms. Therefore, while we await further information it is recommended to use paracetamol to treat COVID-19 symptoms, unless paracetamol is unsuitable.

Consumers already taking ibuprofen or other NSAIDs as advised by their healthcare professional should continue to take them if they develop COVID-19 unless advised to stop. Further information is available from NPS MedicineWise.

There is debate that NSAIDs may slow recovery of acute respiratory infections. Indeed, the product information of some NSAIDs warns that anti-inflammatory effects may hide symptoms of a worsening infection. The need for routine use of an antipyretic may be unjustified.

The Commission gratefully acknowledges review of this position statement by the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT).

Date of revision: 29 April 2020

If you have feedback regarding this position statement, please email: medsafety@safetyandquality.gov.au

Position
COVID-19 is a respiratory illness caused by a new coronavirus. Symptoms include fever, coughing, a sore throat and shortness of breath. Some people will recover easily, and others may get very sick very quickly.

If it is necessary to take a medicine to relieve a sore throat, consider using paracetamol to ease the pain. Throat preparations may be used for symptomatic relief of a sore throat.

Povidone-iodine gargle / mouthwash solutions have virucidal activity against coronavirus. Although none have been tested in COVID-19 (Potential medicines to treat COVID-19).

Background
Respiratory viruses are also subject to airborne (particles B5 lm in size) or droplet ([5 lm) transmission, in which infected material is released by the infected individual breathing, coughing or sneezing.¹ Gargling represents an effective personal hygiene measure against airborne/droplet transmission, as it can reduce the microbe count at the pharynx.²

In 2002, a study compared the bactericidal activities of a povidone-iodine (PVP-1) gargle with two other gargles containing chlorhexidine gluconate (CHG) and cetylpiridium chloride (CPC).³ The reduction rate in the oral bacterial count after gargling as compared to the baseline count before gargling was determined for the 3 gargles tested. PVP-I showed the highest bactericidal rate and the highest reduction rate in oral bacterial count. The study also demonstrated that encouragement to use the PVP-I gargle decreased the absence rate from middle school due to common cold and influenza.

In a study published in 2013⁴, the in vitro bactericidal and virucidal efficacy of povidone-iodine (PVP-I) 7% gargle/mouthwash at defined dilution (equivalent to a concentration of 0.23% PVP-I) against oral and respiratory tract pathogens showed effective bactericidal activity against Klebsiella pneumoniae and Streptococcus pneumoniae and rapidly inactivated SARS-CoV, MERS-CoV, influenza virus A (H1N1) and rotavirus after 15 s of exposure. The authors concluded that povidone-iodine gargle / mouthwash may provide a protective oropharyngeal hygiene measure for individuals at high risk of exposure to oral and respiratory pathogens.

Further information
A number of brands of povidone-iodine sore throat gargle preparations are listed on the Australian Register of Therapeutic Goods.

References
¹ Gralton J, Tovey ER, McLaws ML, Rawlinson WD. Respiratory virus RNA is detectable in airborne and droplet particles. J Med Virol. 2013;85(12):2151–9.

² Eggers, M., Koburger-Janssen, T., Eickmann, M. et al. In Vitro Bactericidal and Virucidal Efficacy of Povidone-Iodine Gargle/Mouthwash Against Respiratory and Oral Tract Pathogens. Infect Dis Ther (2018); 7: 249–259. Available from https://link.springer.com/article/10.1007%2Fs40121-018-0200-7 [Accessed 3 April 2020]

³ Shiraishi T, Nakagawa Y. Evaluation of the bactericidal activity of povidone-iodine and commercially available gargle preparations. Dermatology (2002); 204 (suppl1): 37-41

⁴ Yung D, Tang M. Press release: 10 years after SARS—improper hand washing in the majority of HK people coupled with a 25% drop in cold & flu sick leave for reducing risk of spreading of germs doctor urges to regain strict personal hygiene habits. Hong Kong University Public Opinion Programme. 2013. Available from www.hkupop.hku.hk/english/report/postSARS/content/resources/pr.pdf [Accessed 6 April 2020]

The Commission gratefully acknowledges review of this position statement by the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT).

Date of revision: 29 April 2020

If you have feedback regarding this position statement, please email: medsafety@safetyandquality.gov.au

Position
Continue angiotensin converting enzyme inhibitors (ACEi) and angiotensin 2 receptor blockers (ARBs) as indicated, during the COVID-19 pandemic.^1,2

Background
The Coronavirus-19 disease (COVID-19) is caused by an acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Patients with pre-existing cardiovascular disease (CVD) seem to be more susceptible to developing life-threating SARS-Cov-2 infections.¹ Patients with CVD are also more likely to be prescribed an ACEi or ARBs as part of their usual therapy.

SARS-CoV-2 virus enters human cells via binding to ACE2 receptors found in the lungs and heart.^{3, 4} It has been hypothesised that ACEi and ARBs therapies may increase the risk of SAR-CoV-2 infections or worsen outcomes by raising the levels of ACE2 following treatment.² However, there is no clinical evidence to support this.

Studies conducted in animal models have shown that ACE2 enzymes may confer a protective effect in patients with serious lung complications and COVID-19. Therefore, withdrawal of an ACEi or ARB in this situation may be a disadvantage if proven in clinical practice.^3,4

Data in humans is too limited to support or refute these hypotheses. Additional data may further inform the treatment of high-risk patients with COVID-19. However, there should be consideration for unintended consequences of prematurely discontinuing proven therapies in response to hypothetical concerns that may be based on incomplete experimental evidence.⁴

References
¹ Cardiovascular disease and COVID-19: Australia/New Zealand consensus statement (endorsed by the CSANZ, ANZSCTS, National Heart Foundation (NHF), and the High Blood Pressure Research Council of Australia (HBPRCA). Med J Aust. 3 April 2020 www.mja.com.au/journal/2020/cardiovascular-disease-and-covid-19-australiannew-zealand-consensus-statement [Accessed 8 April 2020]

² Position Statement of the ESC council on Hypertension on ACE-inhibitors and Angiotensin Receptor Blockers. 13 March 2020. Available from www.escardio.org/Councils/Council-on-Hypertension-(CHT)/News/position-statement-of-the-esc-council-on-hypertension-on-ace-inhibitors-and-ang. [Accessed 8 April 2020]

³ Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19. NEJM. 30 March 2020 Available from www.nejm.org/doi/full/10.1056/NEJMsr2005760 [Accessed 8 April 2020]

⁴ Junyi G, Zheng H, Li L, Jiagao L. Coronavirus Disease 2019 (COVID‐19) and Cardiovascular Disease: A Viewpoint on the Potential Influence of Angiotensin‐Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection. JAHA 1 April 2020. Available from www.ahajournals.org/doi/10.1161/JAHA.120.016219 [Accessed 8 April 2020]

The Commission gratefully acknowledges review of this position statement by The Cardiac Society of Australia and New Zealand and The Heart Foundation.

Date of revision: 28 April 2020

If you have feedback regarding this position statement, please email: medsafety@safetyandquality.gov.au

Position
Clozapine is associated with a higher risk of pneumonia.  This is most likely due to sialorrhea and the associated increased risk of aspiration pneumonia¹. However, there is some suggestion that people on clozapine may have impaired immunological mechanisms.

Patients on clozapine presenting with any symptoms of COVID-19 infection should seek or be referred for urgent clinical assessment. A complete blood count with absolute neutrophil count (ANC) should be obtained.

If fever and/or pneumonia develop, clozapine levels should be monitored, and the dose lowered or ceased accordingly.

It has been suggested that if there are barriers to safe access to ANC testing during the COVID-19 pandemic, the frequency of ANC testing may be reduced to ensure ongoing access to clozapine. However, this is ‘off-label’ use and is not established as best practice.

Background
Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia². However, it is associated with a high adverse effect profile. Use is reserved for people with treatment refractory schizophrenia and directed by strict guidance and monitoring.

The National Inpatient Medication Chart (NIMC) (clozapine titration) is available for patients on a titrating clozapine regimen and is accompanied by a user guide.

The NIMC (clozapine titration) records the prescribing, monitoring and administration of clozapine titration for adult inpatients. The NIMC (acute) or NIMC (long-stay) should be used for initiation of patients on clozapine or maintenance of clozapine in long stay psychiatric facilities.

There is limited experience of clozapine in patients infected with COVID-19.  Clozapine is associated with increased risk of pneumonia³. There is evidence that clozapine may lead to secondary antibody deficiency, which may lead to people on clozapine being more susceptible to viral respiratory infections such as influenza and COVID-19.⁴

For patients on clozapine with symptoms of infection, including cough, fever and chills, sore throat or other flu-like symptoms, an urgent physician assessment including a complete blood count (with ANC) should be obtained.

A consensus statement published in the Journal of psychiatry and neuroscience (April 2020) outlines considerations for patients on clozapine during COVID-19. The statement suggests that during the COVID-19 pandemic, to ensure uninterrupted supply of clozapine, the frequency of ANC monitoring may be reduced to every 3 months for people fulfilling all of the following criteria:

• continuous clozapine treatment for >1 year;
• have never had an ANC <2000/μl (or <1500/μl if history of benign ethnic neutropenia);
• no safe or practical access to ANC testing.

Clozapine levels can increase during periods of acute infection⁵ or reductions in cigarettes smoked per day. Raised clozapine levels may be associated with clozapine toxicity, including sedation, myoclonus and seizures⁵. People on clozapine who develop COVID-19 or other respiratory infections may reduce their cigarette intake, both of which may lead to raised clozapine levels.  Clozapine levels should be tested, and consideration should be given to reducing the dose of clozapine during the period of acute infection if clozapine levels are elevated.

The Royal College of Psychiatry in the UK has published detailed guidance on the monitoring of blood dyscrasias in COVID-19.

For further information, South London and Maudsley NHS Foundation Trust published Clozapine and COVID-19 to cover initiation, continuation and special precautions on 30 March 2020⁶.

References
¹ de Leon J, et al. Pneumonia may be more frequent and have more fatal outcomes with clozapine than with other second‐generation antipsychotics. World Psychiatry 2020;19:120

² Siskind D, et al. Clozapine v. first-and second-generation antipsychotics in treatment-refractory schizophrenia: systematic review and meta-analysis. Br J Psychiatry 2016;209:385-92

³ Dr James Paul Pandarakalam, Consultant Psychiatrist. Letter to the Editor, BMJ Online. Potential isk of COVID-19 in Clozapine Treated Patients www.bmj.com/content/368/bmj.m1071/rr

⁴ Ponsford M, Castle D, Tahir T, Robinson R,Wade W, Steven R, Bramhall K, Moody M, Carne E,Ford C, Farewell D,Williams P, El-Shanawany T and Jolles S. Clozapine is associated with secondary antibody deficiency. The British Journal of Psychiatry 2018;1-7. doi: 10.1192/bjp.2018.152

⁵ Clark SR, et al. Elevated clozapine levels associated with infection: a systematic review. Schizophr Res 2018;192:50-6

⁶ Gee S, Gaughran F. Taylor D. Clozapine and COVID-19. Initiation, continuation and special precautions. South London and Maudsley NHS Foundation Trust. 30 March 2020

The Commission gratefully acknowledges review of this position statement by the Royal Australian and New Zealand College of Psychiatrists.

Date of revision 28 April 2020

If you have feedback regarding this position statement, please email: medsafety@safetyandquality.gov.au

Position
Management of patients who are on oral anticoagulants and who display COVID-19 symptoms needs special consideration due to the risk of coagulopathies – recommend haematologist involvement.

Where patients are well, but need regular anticoagulant blood monitoring consider flexible management approaches during periods of self-isolation or quarantine – review with usual prescriber.

Background
There is some evidence to suggest that anticoagulation therapy with low molecular weight heparins (LMWH) appears to be associated with better prognosis in patients with severe COVID-19 sepsis induced coagulopathies or elevated D-dimer results.¹ There is currently no evidence to suggest how clotting may be affected in patients with mild disease.

Patients prescribed a direct acting oral anticoagulant (DOAC) or warfarin should continue their usual therapy unless otherwise advised by their prescriber.

Patients, who present with COVID-19 symptoms and need management in hospital, may have their oral anticoagulation switched to an alternative agent based on specialist advice.²

Patients prescribed warfarin in the community setting who require ongoing Internationalised Normalised Ratio (INR) monitoring, may find it harder to have their blood taken during COVID-19 because of social distancing and quarantine rules.

Strategies to minimise this impact may include:

• Taking or testing blood from the patient at home especially where a patient has COVID-19 like symptoms. Utilising point-of-care INR testing could be considered where available.
• Extending the INR monitoring interval, up to 6 weeks or longer between INR tests for patients who have demonstrated good INR control and have achieved a time-to-treat (TTR) of >60 and are currently well.³
• Advising patients to attend pathology clinics during quieter periods, to support social distancing and avoid attending if they have COVID-19 like symptoms.
• Switching from warfarin to a DOAC may be a consideration. However, not all patients are suitable for a switch and specialist advice should be sought.^3,4,5

Additional guidance on switching, can be found on the specific DOAC Product Information Sheets for apixaban, dabigatran or rivaroxaban, hosted on the TGA website www.tga.gov.au/product-information-0

Avoid switching from an oral anticoagulant to an antiplatelet drug, for example aspirin. This is not an effective equivalent to an anticoagulant.³

Summarised guidance on DOACs and support information for patients is published by some states and territories, noting these resources may be under review.

• NSW Health Clinical Excellence Commission - NOAC Guidelines
   
• SA Health Clinical Guideline: Safe prescribing of new oral anticoagulants: apixaban, rivaroxaban and dabigatran
   
• WA Health Living with a direct-acting oral anticoagulant (DOAC) information for patients
   
• QLD Health
  Guideline for managing patients on a factor Xa inhibitor – Apixaban (Eliquis) or Rivaroxaban (Xarelto)
  Guidance for managing patients on dabigatran (Pradaxa)

References
¹ Tang, N., Bai, H., Chen, X., Gong, J., Li, D. and Sun, Z. (2020), Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. Accepted Author Manuscript. https://onlinelibrary.wiley.com/doi/epdf/10.1111/jth.14817

² Thrombosis and Haemostasis Society of Australia and New Zealand (THANZ) THANZ statement on Thromboprophylaxis and thrombosis in COVID 19 infected patients admitted to hospital. Published 16 April 2020. Available from www.thanz.org.au/news/thromboprophylaxis-and-thrombosis-in-covid-19-infected-patients-admitted-to-hospital [Accessed 22 April 2020]

³ Thrombosis and Haemostasis Society of Australia and New Zealand (THANZ) THANZ statement on outpatient INR monitoring for patients receiving warfarin during COVID-19 pandemic. Published 1 April 2020. Available from www.thanz.org.au/news/outpatient-inr-monitoring-for-patients-receiving-warfarin-during-covid-19-pandemic [Accessed 22 April 2020]

⁴ Williams H. Guidance for the safe switching of warfarin to direct oral anticoagulants (DOACs) for patients with non-valvular AF and venous thromboembolism (DVT/PE) during the coronavirus pandemic. Royal Pharmaceutical Society UK, 26 March 2020.  Available from www.rpharms.com/Portals/0/RPS%20document%20library/Open%20access/Coronavirus/FINAL%20Guidance%20on%20safe%20switching%20of%20warfarin%20to%20DOAC%20COVID-19%20Mar%202020.pdf?ver=2020-03-26-180945-627 [Accessed 7 April 2020]

⁵ Management of patients currently on warfarin during Covid-19. Specialist Pharmacy Services_NHS UK. Published 1 April 2020. Available from https://www.sps.nhs.uk/articles/management-of-patients-currently-on-warfarin-during-covid-19/ [Accessed 7 April 2020]

The Commission gratefully acknowledges review of this position statement by the Thrombosis and Haemostasis Society of Australia and New Zealand (THANZ) and the Australasian Society of Experimental Pharmacologists and Toxicologists (ASCEPT).

Date of revision 12 May 2020

If you have feedback regarding this position statement, please email: medsafety@safetyandquality.gov.au

Position
In severe cases, COVID-19 can be complicated by acute respiratory disease syndrome (ARDS), sepsis and septic shock.

Ascorbic acid (or vitamin C) is an antioxidant and cofactor for numerous physiologic reactions. In the presence of infection or sepsis serum concentrations of vitamin C may become deficient.

Use of ascorbic acid potentially supports host defences against infection and protects host cells against infection induced oxidative stress, for instance, during acute respiratory illness such as pneumonia.

However, there is no robust scientific evidence to support the usage of high dose intravenous ascorbic acid in the management of severe cases of COVID-19.

More research is needed before its use can be recommended.

Background
In early 2020, it was reported that China had initiated research on the use high-dose intravenous ascorbic acid in the management of ICU patients with severe COVID-19 – associated pneumonia.

On 27 March 2020, the TGA published an alert entitled No evidence to support intravenous high-dose vitamin C in the management of COVID-19.

In addition, the Society of Critical Care Medicine and the European Society of Intensive Care Medicine released new guidelines (March 2020) on the management of the critically ill with COVID-19. These guidelines do not include use of any form of ascorbic acid (vitamin C) in their recommendations: Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19).

In the US, according to the American Society of Health-System Pharmacists (ASHP) Assessment of evidence for COVID-19-Related Treatments, high dose infusion of ascorbic acid is not recommended.

Further information
A phase 2 randomised placebo-controlled trial is underway in China to evaluate high-dose intravenous ascorbic acid in ICU patients with severe COVID-19 – associated pneumonia. The dosage regimen studied is:

• Ascorbic acid 12 g intravenously every 12 hours for 7 days
• 12 g of drug diluted in sterile water for injection to total volume of 50 mL
• Intravenous infusion rate: 12 mL/hour.

Whilst this trial may provide more information for this specific use, the overall use of ascorbic acid has not been associated with any consistent clinical benefit in critical illness.

In addition, these are massive doses used in the above-mentioned study out of China for COVID-19 which would potentially rapidly deplete available supplies.

Various lower dosages of intravenous ascorbic acid have been used in sepsis studies, for example, 50 mg/kg every 6 hours for 4 days.

A recently published (JAMA 2020) multi-centre open-label randomised controlled trial was conducted in ICUs in Australia, New Zealand and Brazil, to assess whether “vitamin C, hydrocortisone, and thiamine are more effective than hydrocortisone alone in expediting resolution of septic shock”. The findings suggest that this combination of medicines does not lead to a more rapid resolution.

The World Health Organisation (WHO) has published ‘interim guidance’ (13 March 2020) on the Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected.

The Centre for Disease Control in the US do not include ascorbic acid as a treatment option for patients with COVID-19: Information for Clinicians on Therapeutic Options for COVID-19 Patients.

Oral supplementation
The effect of oral ascorbic acid supplementation has been studied extensively and is known to lead to a decrease in the duration of symptoms of the ‘common cold’.

Oral supplementation may also decrease incidence of the common cold in individuals under heavy physical stress but not in the overall population. There is limited study data available regarding ascorbic acid (oral) in hospitalised patients with pneumonia.

Date of revision: 12 May 2020

The Commission gratefully acknowledges review of this position statement by the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT)

If you have feedback regarding this position statement, please email: medsafety@safetyandquality.gov.au

A number of medicines are used in the acute care setting, including in intensive care.

The Australian and New Zealand Intensive Care Society (ANZICS) provides excellent updates. This includes COVID-19 guidelines with treatment of COVID-19.

The Australian Society of Anaesthetists note that procedures such as high flow nasal oxygenation, facemask ventilation, intubation, nebulisation, awake fibreoptic intubation, upper GI endoscopy and bronchoscopy are all procedures that risk aerosolisation of respiratory secretions, and transmission of droplet and contact spread viruses. This puts healthcare workers involved at particular risk without adequate training, equipment and processes.

In addition, the National COVID-19 Clinical Evidence Taskforce has been established in Australia to support clinicians with continually updated, evidence-based clinical guidelines, Including living guidelines and ‘decision algorithms’.

The medicines used in rapid sequencing intubation are described in the guidance on Rapid Sequence Intubation: Medications, dosages and recommendations.

The Commission has produced a number of resources to promote infection prevention and control in the COVID-19 environment. These illustrate the use of personal protective equipment (PPE). 

The Australian Guidelines for the Prevention and Control of Infection in Healthcare (2019)

Infection Prevention and Control COVID-19 Personal Protective Equipment

Special precautions for COVID-19 Designated Zones

Date of revision: 15 May 2020

If you have feedback regarding this position statement, please email: medsafety@safetyandquality.gov.au

Position
Adults – Avoid nebulisation.

Children – Avoid nebulisation. Do not withhold therapy if indicated.

Background
Nebulisation is NOT recommended in patients with COVID-19 as it may contribute to the spread of the virus.

For patients self-managing COVID-19
A puffer or spacer should be used in preference to a nebuliser.

Nebulisers do not work as well as puffers and spacers for people with asthma even during an acute attack. Nebulisers disperse infectious virus particles often metres around and can rapidly spread infection from respiratory viruses, such as influenza and SARS-CoV-2.

The National Asthma Council has issued advice for patients as has the Department of Health.

Additional advice
The National Asthma Council: Australian Asthma Handbook:

• Bronchodilator treatment
• Managing asthma during the COVID-19 pandemic.

In acute care of COVID-19
Nebulisers can be driven by air, piped oxygen, or an oxygen cylinder fitted with a high-flow regulator capable of delivering above 6 litres per minute. Salbutamol is used in either in intermittent or continuous nebulisation.

The use of nebulisers carries a high risk (to staff and patients) of viral nosocomial aerosol infection. Nebulisation induces coughing, and this may contribute to virus spreading.

If using a nebuliser, clinicians should follow their HSO’s infection control protocols to minimise spread of respiratory tract infections.

Additional advice

• The NSW Health Agency of Clinical Innovation has guidance on how to mitigate the risk of aerosol generating therapies
• Consensus statement: Safe Airway Society principles of airway management and tracheal intubation specific to the COVID-19 adult patient group
• Australian College of Emergency Medicine clinical guidelines.

In children
Whilst nebulisation in children should be avoided, treatment should not be withheld if indicated. Information on paediatric treatment is available from

• The Royal Children’s Hospital Melbourne clinical guideline: Airborne precautions (full PPE including N95 mask) must be maintained if child requires high-flow oxygen, non-invasive ventilation or nebulised therapy.
• Queensland Health: Children’s Health Queensland and Health Service advice brochure.

Further information
Aerosolisation is the production of small particles of water which, rather than falling to the ground as droplets, can flow through the air and spread more widely. The principles of managing the airway are to keep particle spread to a minimum and avoid aerosolisation as far as possible.

Nebulisation may be regarded as a non-aerosol generating procedure. However, nebuliser treatment induces coughing, and this may contribute to virus spreading. The Australian Society of Anaesthetists has developed a statement on processes and techniques required to protect staff and prevent transmission of infection during airway procedures for patients with known or suspected COVID-19 infection.

In addition, the risk of infection transmission via aerosols may increase during nebulisation due to the potential to generate a high volume of respiratory aerosols that may be propelled over a longer distance than occurs with natural dispersion.

Resources
The Commission has produced a number of resources to promote infection prevention and control in the COVID-19 environment. These illustrate the use of personal protective equipment (PPE). 

The Australian Guidelines for the Prevention and Control of Infection in Healthcare (2019)

Infection Prevention and Control COVID-19 Personal Protective Equipment

Special precautions for COVID-19 Designated Zones

References
The following references provide additional information on nebulisation as an AGP for consideration in COVID-19:

1. Simonds AK, Hanak A, Chatwin M, Morrell MJ, Hall A, Parker KH, et al. Evaluation of droplet dispersion during non-invasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic influenza and other airborne infections. Health Technol Assess 2010;14(46):131–172 www.ncbi.nlm.nih.gov/pubmed/20923611
2. Judson SD and Munster VJ. Nosocomial Transmission of Emerging Viruses via Aerosol-Generating Medical Procedures. Viruses 12 Oct 2019, 11, 940 www.ncbi.nlm.nih.gov/pmc/articles/PMC6832307/
3. Seto WH. Airborne transmission and precautions: facts and myths. Journal of Hospital Infection 2014;89:225-228 www.ncbi.nlm.nih.gov/pubmed/25578684
4. British Columbia Provincial Infection Control Network. Respiratory Infection Outbreak Guidelines for Health Care Facilities: Reference Document for use by Health Care Organizations for Internal Policy/Protocol Development. April 2018 www.picnet.ca/wp-content/uploads/Respiratory-Infection-Outbreak-Guidelines-for-Healthcare-Facilities-March-20.pdf

The Commission gratefully acknowledges review of this position statement by the Safe Airway Society and the National Asthma Council Australia.

Date of revision: 15 May 2020

Position
Reconsider intranasal administration of medicines in patients in acute care who are positive or suspected of having COVID-19.

Consider suitable alternatives to intranasal medicines as a first-line option for all patients presenting in acute care, including non-COVID-19 patients.

In the community, allergy sufferers should continue their normal use of intranasal corticosteroids.

Background
Intranasal administration of medicines can cause irritation of the nasal mucosa which can cause a person to sneeze.

The virus that causes COVID-19 is mainly transmitted through droplets generated when an infected person coughs, sneezes, or speaks. 

Intranasal administration of medicines is not recommended in patients with COVID-19 as it may increase the risk to staff caring for the patient and contribute to the spread of the virus.  

Medicines administered via the intranasal route
Corticosteroids (as well as antihistamines) are used routinely for the treatment of allergic conditions such as hay fever or allergic rhinitis. Self-management of allergic conditions and administration of these medicines via the intranasal route is common in the community setting.

Intranasal corticosteroids are well tolerated¹ and the more common (>1%) adverse effects include nasal stinging, itching, nose bleed, sneezing, sore throat, dry mouth, cough².

In the hospital setting and other acute care environments, corticosteroids and other medicines may be prescribed for administration via the intranasal route. Intranasal administration can facilitate delivery and rapid absorption, including during an emergency situation³. For example:

• Fentanyl intranasal for analgesia in children aged 1 year and older with mild to severe pain⁴
• Midazolam intranasal for adults² or children with seizures⁵.

In the community setting, where patient’s care is managed by clinicians with the assistance of other support workers, consideration should be given to the type(s) of medicine being administered via the intranasal route. In addition, the potential risk to the patient as well as the clinicians and support workers should be assessed. 

Where possible, alternative routes of administration for intranasal medicines may need to be considered. This should be assessed on an individual basis and subject to local conditions and requirements. In some situations administration via the intranasal route may be a safer option. For example, intranasal administration of midazolam, by appropriately trained disability support workers, to safely manage a patient experiencing a seizure⁶.

For patients self-managing in the community
Allergy (often accompanied by asthma) sufferers should continue their normal use of intranasal corticosteroids. During COVID-19 it is more important than ever for patients to keep their symptoms well controlled⁷.

A statement has been published by the American College of Asthma, Allergy & Immunology to assist patients in the community who are otherwise well with concern regarding the ongoing use of intranasal preparations: During COVID-19 pandemic, normal allergy and asthma medications should be continued’.

The Australasian Society of Clinical Immunology and Allergy (ASCIA) have published a fact sheet which includes advice to continue to treat symptoms which can be confused with COVID-19, for instance, sufferers of allergic rhinitis: www.allergy.org.au/images/pcc/ASCIA_PCC_COVID-19_FAQ_2020.pdf.

The National Asthma Council Australia has a range of resources that include advice on medicines that are used via the intranasal route of administration:

• Intranasal spray technique for people with allergic rhinitis
• Allergic rhinitis treatments chart
• Managing allergic rhinitis in patients with asthma (Clinician brochure)
• Hay fever (allergic rhinitis) and you asthma (Patient brochure)
• Australian Asthma Handbook: The National Guidelines for Health Professionals

Around 80% of people with asthma have allergic rhinitis. The National Asthma Council has published resources for Managing asthma during the COVID-19 pandemic.

In acute care
The use of intranasal medicines carries a high risk (to staff and patients) of viral nosocomial aerosol infection. Administration of medicines into the nose can induce sneezing, and this may also contribute to virus spreading.

Whilst it is important to treat allergic conditions, suitable alternatives to intranasal medications should be used as a first-line option in non-COVID-19 patients.

If administration via the intranasal route cannot be avoided, clinicians should follow their HSO’s infection control protocols to minimise spread of respiratory tract infections.

Guidelines on the safer intranasal administration of medicine during COVID-19 have been prepared by Women’s and Children’s Hospital Adelaide⁸. HSO’s should also refer to local policy guidelines if available.

References
¹ Cochrane Systematic Review. Intranasal corticosteroids for asthma control in people with coexisting asthma and rhinitis. July 2003.www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003570/full

² Australian Medicines Handbook. 2020 (online). Adelaide: Australian Medicines Handbook Pty Ltd; 2020 January. Available from: amhonline.amh.net.au/

³ Del Pezzo J, Callaghan JM. Intranasal medications in pediatric emergency. Pediatr Emerg Care. 2014;30(7):496-501. journals.lww.com/pec-online/Abstract/2014/07000/Intranasal_Medications_in_Pediatric_Emergency.13.aspx

⁴ Royal Children’s Hospital Melbourne. Clinical Practice Guideline: Intranasal Fentanyl. www.rch.org.au/clinicalguide/guideline_index/Intranasal_fentanyl/

⁵ SA Health. South Australian Neonatal Medication Guidelines: Midazolam. 2017. www.sahealth.sa.gov.au/wps/wcm/connect/cea62f804cd7e42bba05baa496684d9f/Midazolam_neo_v2.0.pdf?MOD=AJPERES&amp;CACHEID=ROOTWORKSPACE-cea62f804cd7e42bba05baa496684d9f-n5jfceQ

⁶ Department of Communities Tasmania. Disability Services Medication Management Framework. November 2017. www.communities.tas.gov.au/disability-community-services/publications/policies,_procedures_and_guidelines/medication_management_framework  

⁷ Bousquet J, et al. In press. Letter to the editor. Intranasal corticosteroids in allergic rhinitis in COVID-19 infected patients: An ARIA-EAACI statement https://onlinelibrary.wiley.com/doi/abs/10.1111/all.14302

⁸ Women’s and Children’s Hospital Adelaide. Guidelines on Administration of Intranasal Medication. 2 April 2020.

The Commission gratefully acknowledges review of this position statement by the National Asthma Council.

Date of revision: 19 May 2020

There are vulnerable groups where ongoing treatment is particularly critical and should be carefully managed to prevent medication error and harm. These include those with cancer, those with a mental health condition, and patients with chronic comorbidities, for example, diabetes and arthritis that may be taking multiple medicines.

Ongoing safe and quality use of medicines is essential for treatment of patients with comorbidities.

It is important to consider ongoing supply of medicines for both community as well as hospital outpatients more likely to have vulnerable groups accessing their medicines through hospitals only. For example, Aboriginal and Torres Strait Islanders attending dialysis clinics.

The My Health Record (MHR) should be used wherever possible for the documentation of medicines. In particular documentation at transitions of care should facilitate safe and quality medicines use. The Pharmacist Shared Medicines List contains information about the medicines a patient is taking at the time the list is created and is an excellent record for high-risk patients in particular who are managing multiple medicines.

The National COVID-19 Clinical Evidence Taskforce has been established in Australia to support clinicians with continually updated, evidence-based clinical guidelines, including ‘living guidelines’ and ‘decision algorithms’. These guidelines reference those developed by the Australian and New Zealand Intensive Care Society (ANZICS): COVID-19 Guidelines (Version 1). ANZICS 16 (March 2020).

In the US, the American Society of Health-System Pharmacists (ASHP) also provides a resource centre which aims to provide evidence-based information and tools for pharmacists and other healthcare professionals.

The Liverpool Hospital in the UK has published an extensive guide to drug interactions between medicines and medicines used to treat COVID-19. This includes experimental medicines that are listed as Potential medicines in COVID-19.

It is expected that further information will emerge over the period of increased use of antiretroviral and other experimental medicines.

The Therapeutic Goods Administration (TGA) has carriage for the pharmacovigilance activities, including reporting of adverse events such as drug interactions.

However, issues with safe and quality use of approved medicines in clinical practice may continue to emerge.

Date of revision: 28 April 2020

If you have feedback regarding this position statement, please email: medsafety@safetyandquality.gov.au

The TGA has carriage for the publication of medicines shortages as advised by the sponsors (manufacturers or suppliers) of those medicines.

From January 2019, sponsors are required to report all shortages of reportable medicines. The TGA mandatorily publishes information about all shortages that have a critical patient impact. Information about medium or low impact shortages may also be published where the sponsors agree to it or if the TGA determines that it is in the interest of public health. Search medicines here.

The Medicines Watch List is a legislative instrument setting out a list of known critical medicine ingredients. It assists sponsors and the TGA to simplify and speed decision-making when deciding if a medicine shortage or permanent discontinuation may have a critical patient impact. The Medicines Watch List was determined in December 2018. The list of ingredients included in the Medicines Watch List has been derived from a consensus review of existing state hospital Emergency and Life Saving Drug Lists and the World Health Organization's Model List of Essential Medicines that are contained in the Australian Register of Therapeutic Goods (ARTG).

Continuity of care for those discharged from hospital to a community setting becomes an increasing challenge during a pandemic. In a transition of care, management of medicines requires strong coordination between the discharging health service, the primary care practitioner and the consumer. Documentation of a patient’s medicines at discharge and communication to the primary care practitioner of the medication management plan potentially assume greater importance for people who were admitted to hospital because of positive diagnosis for COVID-19 and have recovered.

Community pharmacies are responding to the evolving COVID-19 pandemic. The Pharmacy Guild of Australia, the Pharmaceutical Society of Australia and a number of the state and territory Departments of Health have provided guidance for community pharmacies. The Royal Australian College of General Practitioners (RACGP) and the Australian Medical Association (AMA) also provide guidance.

Date of revision: 28 April 2020

If you have feedback regarding these guidelines, please email: medsafety@safetyandquality.gov.au