Medicines and COVID-19

This page was last updated: 25 May 2020 at 12:50 PM

This site contains general information for health professionals in NZ regarding medicines and COVID-19. The information is compiled by a multidisciplinary team including pharmacists, pharmacologists and infectious diseases experts.

Written information for patients to address questions and concerns about medicines and COVID-19 can be found at MyMedicines.

If you feel there are additional areas we need to cover, or for questions relating to specific patients, please contact us. If you cannot make contact by phone then please use email.

Summary

  • Patients should be advised to keep at least 1-2 weeks’ supply of their medicines.
  • Prescribers should only prescribe the usual maximum supplies of medicines (one month for controlled drugs, three months for non-controlled drugs). Pharmacy dispensing is limited to one month except for oral contraceptives.
  • Access criteria to some medicines have changed (see Current supply section).
  • The Ministry of Health has released criteria (see Remote prescribing section) to allow remote prescribing of non-controlled medicines.
  • The treatment of COVID-19 is supportive. There are no medicines which should be prescribed for the direct treatment of COVID-19 outside of a clinical trial.
  • For symptomatic treatment of COVID-19 (pain and fever), paracetamol is preferred. NSAIDs are appropriate for refractory symptoms.
  • Enoxaparin is recommended for hospitalised patients with COVID-19.
  • There are no medicines which should be prescribed for the prevention of COVID-19 outside of a clinical trial.
  • Patients should be advised not to stop any regular medicines unless there is a conventional indication to do so.

Medicine supply

The global effects of COVID-19 on manufacturing plants and transportation are likely to result in disruptions to the medicine supply chain. PHARMAC are working closely with the Ministry of Health (MoH) and suppliers to help maintain medicine supply chains. See PHARMAC: Information for coronavirus/COVID-19

Current supply

Patients should be advised to keep at least 1-2 weeks’ supply of their medicines.

However, dispensing of non-controlled medicines, other than oral contraceptives, is limited to one month. This is to reduce stockpiling of medicines and ensure equitable access. Prescribers should adhere to the usual prescribing restrictions (three month supply for non-controlled medicines and one month for controlled medicines).

Access criteria to some medicines have changed.

For a list of medicines associated with supply issues, such as paracetamol, see PHARMAC: Medicine and device supply issues

For a list of medicines where PHARMAC have changed access criteria (either to facilitate access e.g. sacubitril with valsartan, or restrict access e.g. hydroxychloroquine) as part of the COVID-19 response, see: PHARMAC: Medicines with amended access criteria

Patients may be anxious about medicine shortages and ask to stock-up on their regular medicines. This practice will lead to earlier and more problematic medicine shortages. Reassure patients that PHARMAC, the MoH, pharmacies and suppliers are working together to ensure equitable access to medicines. Prescribers should not issue multiple prescriptions for the same medicine. Pharmacies should not dispense more than one month’s supply of non-controlled medicines, with the exception of oral contraceptives for which a three month supply can be dispensed.

National advice, produced at CDHB, can be found here: COVID-19 Advice for prescribers and pharmacists about medicine supply. If this document is inaccessible due to password protection, use this link to access an older version. 

Remote prescribing

Remote prescribing in the community is possible by NZePS and non-NZePS methods if Ministry of Health (MoH) criteria are met (see below).

The New Zealand ePrescription Service (NZePS) is a secure prescribing system for primary care. For general information, see MoH: NZePS.

To facilitate virtual care during the COVID-19 pandemic, a temporary exemption to the usual rules around physical signatures on prescriptions via NZePS and non-NZePS systems. For full details on signature-exempt prescriptions see MoH: new rules and signature exempt prescriptions: FAQs.

Prescriptions with a physical signature can be sent to pharmacies via fax and email. For details on the regulations, see MOH: Electronic Transmission of Prescriptions and to find a pharmacy email address, see Healthpoint: Pharmacy.

Medicines recommended for COVID-19

Enoxaparin

Enoxaparin should be routinely used for thromboprophylaxis in hospitalised patients with COVID-19.

COVID-19 induces a hypercoagulable state, particularly in severe cases. Patients have higher rates of venous thromboembolism (VTE) than many other medical conditions, although the exact incidence is not clearly defined. Predictably, incidence is highest in critically ill patients.

There are weak observational data in favour of low molecular weight heparin (LMWH) for VTE prophylaxis in COVID-19. However, there is a strong biological rationale, and stronger evidence for benefit of routine LMWH in other high-risk conditions.

Although the risks and benefits are not precisely defined, the overall data to date suggests benefit is more likely than harm. Therefore, we recommend the use of enoxaparin for thromboprophylaxis in hospitalised patients with COVID-19. The usual cautions and contraindications apply, for example renal impairment and patients with higher bleeding risk. Hospital HealthPathways gives advice on these issues, and the Medicines Information Service can be contacted for complex cases, particularly for advice on dosing.

Paracetamol

Paracetamol is recommended first-line for symptomatic relief in COVID-19.

Paracetamol treats symptoms but does not improve clinical outcomes in COVID-19.

Paracetamol is an effective treatment for pain and fever in COVID-19. It is relatively safe and therefore recommended first-line for symptomatic relief in COVID-19. NSAIDs are appropriate for refractory symptoms (see relevant section below).

There are reports on social media that paracetamol can “cure” COVID-19. There is no scientific evidence to support this claim, or a plausible theory. Patients should be advised to use paracetamol in a supportive role, but warned that it does not protect them from serious harm from COVID-19 and is therefore not a substitute for established methods of infection control.

For information on dispensing paracetamol see PHARMAC: Paracetamol supply issue.

Medicines not recommended for COVID-19

The treatment of COVID-19 is supportive. There are no medicines which should be prescribed for the direct treatment or prevention of COVID-19 outside of a clinical trial.

There are no direct treatments for COVID-19, recommended treatments are supportive only. Non-pharmacological prevention measures (handwashing, physical distancing, etc.) are the only approved measures to prevent COVID-19. 

The medicines in this section are based on a theoretical mechanism, in vitro data only, or weak observational data. None have sufficient rationale to justify use outside of a clinical trial.

CDHB memo: Specific medicines to treat COVID-19 infection

CDC: Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19)

WHO: Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected

Chloroquine and Hydroxychloroquine

Chloroquine and hydroxychloroquine currently have no role in the management of COVID-19, and may increase mortality.

There are now several published clinical trials investigating the use of hydroxychloroquine (HCQ) or chloroquine (CQ) for COVID-19. Three are placebo-controlled RCTs, two of which were Chinese studies comparing open-label HCQ with standard care and involved 30 and 150 patients respectively. Both showed no difference in viral clearance, clinical improvement, or mortality. The other RCT was a small, cluster-randomised French study of 36 patients but had significant methodological flaws which limit interpretation. There is a single further unpublished trial; a double-blind placebo-controlled RCT of HCQ (n=62) showing improvement in time to recovery with HCQ, but the trial is not peer-reviewed and, therefore, should not form the basis of clinical decision-making. There are several observational trials published, the largest with over 96,000 patients and showing increased mortality with HCQ or CQ in multivariant analysis. The remaining observational data show no benefit for HCQ or CQ.

Significant harm from HCQ and QC was identified in both the randomised and observational data. One trial of high-dose vs. low-dose CQ was stopped early due to excessive toxicity in the high-dose arm. The observational data suggested higher mortality with HCQ or CQ, and higher rates of ventricular arrhythmia (particularly when co-prescribed with azithromycin).

Overall, current evidence does not support HCQ or CQ being safe or effective treatments for COVID-19. Inappropriate use outside of clinical trials risks unnecessary adverse effects and creating a shortage of these medicines for established indications e.g. rheumatoid arthritis. Accordingly, PHARMAC has restricted funding of hydroxychloroquine to approved indications (rheumatoid arthritis, systemic or discoid lupus erythematosus, malaria).

Azithromycin (with hydroxychloroquine)

Azithromycin (with or without hydroxychloroquine) currently has no role in the management of COVID-19. 

Published evidence for COVID-19 is limited to one open-label, non-randomised controlled trial with significant limitations involving six patients using hydroxychloroquine with azithromycin compared to hydroxychloroquine alone. 

Using these medicines together increases the risk of QT prolongation. Widespread use of azithromycin increases the potential for bacterial resistance. The current evidence is insufficient to justify using azithromycin to treat COVID-19 outside of a clinical trial. 

Antivirals

Antivirals currently have no role in the management of COVID-19.

Oseltamivir inhibits neuraminidase, which influenza viruses use to replicate and spread. Coronaviruses do not use neuraminidase so oseltamivir has no activity against coronaviruses. Oseltamivir should be reserved for treating confirmed or suspected influenza. If started, it should be ceased if influenza is excluded. 

 

A number of other antivirals are being investigated for activity against coronaviruses:

  • Darunavir
    • Being evaluated in vitro for potential activity against coronavirus.
  • Favilavir (also known as favipiravir)
    • Published evidence is limited to two open-label trials with significant limitations.
  • Galidesivir
    • Clinical studies are awaited.
  • Lopinavir-ritonavir
    • While one randomised controlled trial (against standard care) of 199 patients did not show a significant difference in time to clinical improvement, larger trials are under way.
  • Remdesivir
    • A randomised controlled trial of 236 patients showed no benefit, although this was underpowered. Preliminary results of a second trial are promising, but full details are unavailable and the trial has not been subject to peer review. We do not recommend basing clinical decisions on preliminary data.
  • New molecules under development (e.g. EIDD-2801)

Overall, there are no published randomised controlled trials to support the use of these medicines to treat humans with suspected or confirmed COVID-19 infection.

Further, some studies show increased adverse reactions with the use of antivirals compared to standard care (e.g. nausea/vomiting/diarrhoea with lopinavir-ritonavir). Inappropriate use of antivirals places patients at risk of harm without demonstrated evidence of benefit.

Biologics

Biologics currently have no role in the management of COVID-19.

Biologics are being investigated for activity against coronaviruses:

  • Anakinra
    • The basis for using anakinra is purely theoretical. Severe COVID-19 is associated with a marked inflammatory response, which may be the basis of the inflammatory lung damage. Anakinra is a recombinant protein similar to the endogenous interleukin 1 receptor antagonist protein, and therefore reduces interleukin-1 mediated inflammation. There are no clinical data supporting the use of anakinra, however.
  • IL-6 inhibitors (e.g. tocilizumab, sarilumab)
    • The safety and efficacy of IL-6 inhibitors for the treatment of critically ill patients with COVID-19 is not currently established through any published clinical trials. IL-6 is a pleiotropic cytokine. A subgroup of patients with severe COVID-19 appear to develop features of a cytokine storm syndrome. Tocilizumab (an IL-6 receptor inhibitor) is licensed in the US and Europe for cytokine release syndrome due to chimeric antigen receptor T (CAR-T) therapy. A Chinese case series of 21 patients with critical or severe COVID-19 treated with tocilizumab in addition to routine therapy showed clinical and radiological improvement in the majority of the patients within a week. Systematic review of tocilizumab use in rheumatoid arthritis, however, have found increased risk of infectious respiratory adverse events. Multiple randomised controlled trials for tocilizumab and other IL6 inhibitors (e.g. sarilumab and situximab) in the setting of COVID-19 are currently planned or underway.
  • Interferons
    • Interferons are biologic response modifiers that possess antitumour, antiviral, and immunomodulating properties. Interferons are virus specific, binding to specific receptors. Interferons have shown activity against coronaviruses in animal and in vitro studies. In a large retrospective cohort study, interferons were not effective against MERS-CoV. Current clinical trials include interferons in combination with antiviral agents for activity against COVID-19

Protein and tyrosine kinase inhibitors (TKIs)

Tyrosine kinase inhibitors (TKIs) currently have no role in the management of COVID-19.

The safety and efficacy of TKIs for the treatment of patients with COVID-19 is not currently established through any published clinical trials. Baricitinib appears to be the preferred candidate in this class as it has been shown to reduce or interrupt the passage of virus into alveolar type 2 cells, and to inhibit JAK1- and JAK2-mediated cytokine release. Baricitinib is registered overseas for the treatment of rheumatoid arthritis. Two clinical trials are currently underway investigating baricitinib in the treatment of patients with COVID-19.

Corticosteroids

Corticosteroids currently do not have a routine role in the treatment of COVID-19.

Patients should continue prescribed corticosteroids while they remain well, even after potential COVID-19 exposure.

Patients with asthma and/or COPD who use corticosteroid inhalers or oral corticosteroids as part of their asthma/COPD plan should continue to do so.

Corticosteroids are not recommended for the treatment of pneumonia from COVID-19 except if there are other conventional indications e.g. exacerbation of chronic obstructive pulmonary disease (COPD). This recommendation is based on studies which found corticosteroid use was associated with delayed viral clearance and increased mortality in patients with influenza and Middle Eastern Respiratory Syndrome (MERS) coronavirus. During the Severe Acute Respiratory Syndrome (SARS) coronavirus pandemic, corticosteroids were widely used to manage SARS. However, there was no strong evidence of their effectiveness and some evidence of harm.

See CDC: Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19)

Patients who are using long-term oral or inhaled corticosteroids may have an increased risk of contracting coronavirus or developing more severe COVID-19 symptoms. However, patients should not stop long-term corticosteroids abruptly solely because of the current pandemic, or if they are exposed to someone with COVID-19 or develop COVID-19. Abrupt cessation is unlikely to be of benefit and more likely to cause harm e.g. adrenal crisis, uncontrolled asthma.

There is minimal systemic exposure from topical corticosteroids. There is no evidence that topical corticosteroids for dermatological conditions e.g. eczema, psoriasis increase the chance of COVID-19 when used appropriately.

Patients with moderate to severe asthma and COPD are at higher risk of developing more severe symptoms of COVID-19. These patients may have ‘back-pocket’ prescriptions for self-administration of systemic corticosteroids. Patients using ‘back-pocket’ prescriptions should continue to do so during the pandemic. However, the symptoms of COVID-19 may be mistaken for an exacerbation of asthma and/or COPD so patients should be advised to seek medical attention urgently if self-administering corticosteroids. Note, prescriptions can be issued remotely (see remote prescribing section) and most pharmacies will have contactless delivery services prioritised for high risk patients.

Ivermectin

Ivermectin currently has no role in the management of COVID-19. 

Published evidence for COVID-19 is limited to one in vitro study. To achieve the concentrations used in the in vitro experiment, potentially toxic doses of ivermectin would be required (based on both the physical and pharmacokinetic properties of ivermectin). Ivermectin has been used in a phase 3 clinical trial to treat dengue fever. In this trial ivermectin reduced serum concentrations of viral proteins but had no effect on viraemia or clinical outcomes. 

The current evidence is insufficient to justify using ivermectin to treat COVID-19 outside a clinical trial setting.  

Nitazoxanide

Nitazoxanide currently has no role in the management of COVID-19. 

The data for COVID-19 is limited to one in vitro study. Nitazoxanide has been used in a placebo-controlled RCT for patients hospitalised with influenza-like illness (n=260); nitazoxanide did not reduce the duration of hospital stay or confer other benefits.

The current evidence is insufficient to justify using nitazoxanide to treat COVID-19 outside a clinical trial setting. 

Acetylcysteine

Acetylcysteine currently has no role in the management of COVID-19.

Studies suggest acetylcysteine inhibits formation of proinflammatory cytokines in some strains of influenza. The activity of acetylcysteine is likely to be dependent on the strain of virus. There are no studies showing that acetylcysteine is effective against COVID-19 therefore, we do not recommend its use.

Bacillus Calmette-Guérin (BCG) vaccine

The BCG vaccine currently has no role in the prevention of COVID-19.

Published evidence from randomised controlled trials and observational studies has shown that BCG vaccination prevents non-tuberculous respiratory infections such as pneumonia and influenza, in children and the elderly. This relates to the non-specific effects of the BCG vaccine on the immune system. These effects have not been well characterised and their magnitude and duration is unknown.

There is a lack of evidence that BCG vaccine protects against COVID-19. However, two clinical trials are ongoing to determine if BCG vaccination protects healthcare workers against COVID-19.

Vitamin C

There are no clinical studies to support the use of oral vitamin C supplementation in the prevention of COVID-19.

There is currently insufficient evidence to support the use of vitamin C, via any route, in the management of COVID-19. Clinical trials using intravenous high-dose vitamin C in patients hospitalised with COVID-19 are underway.

Two recent open-label studies on the use of intravenous high-dose vitamin C in other types of infections associated with septic shock and acute respiratory distress syndrome (ARDS) infections showed there was no clear benefit of vitamin C. Septic shock and ARDS are conditions leading to ICU admission, ventilator support or death among those with severe COVID-19.

Vitamin D

There is no evidence that vitamin D supplementation is effective in preventing COVID-19 infection.

Vitamin D supplementation is only recommended for patients with documented deficiency, or the usual patient groups who are at risk of deficiency such as elderly people in residential care.

Zinc

Zinc supplements currently have no role in the prevention or treatment of COVID-19.

We found no published reports of zinc being used to prevent or treat COVID-19 infection. The role of zinc is based on a number of theories, including the finding from an in vitro study in 2010 that zinc inhibited RNA-dependent polymerase replication of SARS-CoV virus. The evidence that zinc lozenges can reduce the severity of common cold symptoms is weak and inconsistent.

The evidence to support the use of zinc in the management of COVID-19 is theoretical only and we do not recommend its use. Clinical trials using zinc and other vitamin supplements in COVID-19 have been registered.

Complementary and Alternative Medicines

Complementary and Alternative Medicines have no role in the prevention or treatment of COVID-19. 

A broad range of complementary and alternative medicines, including herbal products and dietary supplements, have been proposed for prevention and treatment of COVID-19. There is no evidence to support these claims. Additionally, these products pose several risks

 

  • They are unregulated and therefore of uncertain quality
  • They risk unnecessary adverse effects and drug interactions
  • They potentially reduce adherence with effective prevention (such as handwashing) by providing false reassurance 
  • Effective supportive treatments, such as paracetamol, may be deferred
  • They are a preventable financial burden to patients

Complementary and alternative medicines are therefore not recommended for prevention or treatment of COVID-19.

Famotidine

Famotidine currently has no role in the management of COVID-19.

Retrospective observational data from Wuhan, combined with computerised modelling data, has led to a theory that famotidine may inhibit an enzyme involved in viral replication. An RCT in hospitalised patients with COVID-19 is underway, using high dose intravenous famotidine. Until the study results become available, we do not recommend the use of famotidine in COVID-19.

Povidone-iodine gargle

Povidone-iodine gargle has no role in the management of COVID-19.

An in vitro study suggests that povidone-iodine gargle reduces viral load (including MERS-CoV and SARS-CoV) in the oral cavity and the oropharynx, which could indicate that it might help prevent viral transmission. This study was funded by a pharmaceutical company. The clinical relevance has not been established.

The role of povidone-iodine in COVID-19 is as a topical disinfectant within standard infection control protocols.

Medicines reported to worsen COVID-19

There are no clinical studies showing increased harm from any medicine use in relation to COVID-19. Patients should be advised not to stop any regular medicines unless there is a conventional indication to do so.

COVID-19 uses angiotension-coverting enzyme 2 (ACE2) to enter cells. There is pre-clinical data from in vitro and animal studies that some medicines may upregulate ACE2, raising concerns that these medicines could increase the severity of COVID-19 infection. However, there are no clinical data (including the publications from the large number of cases in China) to support this theory.

Immunosuppression theoretically increases the risk of coronavirus infection but there is no clinical evidence to support this.

Some medicines are associated with pneumonia or respiratory depression, but the risk is too small or uncertain to justify altering usual prescribing of these agents.

Angiotensin Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs)

Patients already taking ACEIs or ARBs should continue them unless there is a conventional reason not to (e.g. hyperkalaemia, acute kidney injury).

ACEIs and ARBs upregulate ACE2 in animal studies (see above). ACE2 receptors have been shown to be the entry point into human cells for SARS-CoV-2. However, it is not clear that ACEIs or ARBs upregulate ACE2 in humans. Additionally, observational data to date shows no increase in mortality for patients taking ACEIs or ARBs when infected with COVID-19. There are also theoretical benefits to ACEIs and ARBs for viral infection, and very weak observational data supporting these. There are multiple clinical trials investigating these agents for the treatment of COVID-19.

We support the current consensus in New Zealand and internationally (for example European Medicines Agency, International Hypertension Society, American College of Cardiology) to continue normal usage of ACEIs and ARBs. The usual contraindications and cautions still apply, for example patients with hyperkalaemia or hypotension.

Antidiabetic Medicines

Patients already taking thiazolidinediones (e.g. pioglitazone) should continue them unless there is a conventional reason not to (e.g. heart failure, history of bladder cancer).

Thiazolidinediones, such as pioglitazone, upregulate ACE2 in animal studies (see above). Observational studies of patients with COVID-19 have shown increased hospitalisation and mortality for patients with diabetes (7.3% vs 0.9%). Reports have suggested this could be due to ACEI and ARB use, however there are no data to substantiate this. Diabetes has separately been shown to upregulate ACE2 and increases the risk of other infections, both of which add to the confounding in the observational data.

The usual contraindications and cautions still apply to ACEI and ARB use as they did prior to COVID-19, for example patients with heart failure or a history of bladder cancer. We recommend clinicians continue usual practice around the use of pioglitazone during the COVID-19 pandemic.

Ibuprofen and other Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Patients on long-term NSAIDs should continue to take them unless there is a conventional reason to stop (e.g. bleeding or acute kidney injury).

Paracetamol is preferred for symptomatic treatment of COVID-19, particularly in older patients or patients with comorbidities who are more vulnerable to adverse effects of NSAIDs. However, NSAIDs may still be used for refractory symptoms.

There has been longstanding concern over NSAIDs in viral infections. Randomised controlled trials and observational data comparing NSAIDs and paracetamol have produced mixed results that some showing no difference and others a small effect of NSAIDs. Overall, the data are too few to draw a convincing conclusion.

This existing concern has been compounded over the potential for NSAIDs to upregulate ACE2 in animal models. However, there are no clinical studies looking specifically at NSAIDs and COVID-19. Additionally, there are no data to support NSAIDs increasing the probability of becoming infected with COVID-19, or transmitting COVID-19. The European Medicines Agency (EMA) and World Health Organisation (WHO) have both acknowledged the theoretical concerns but still permit use of NSAIDs with COVID-19.

The usual contraindications and cautions still apply to NSAID use as they did prior to COVID-19, for example patients with renal impairment, heart failure or increased risk of gastrointestinal bleeding.

Immunosuppressants

Patients should continue immunosuppressants while they remain well, even after potential COVID-19 exposure.

We refer to immunosuppressants as any medicine dampening immune response, including those described as “immunomodulatory” rather than immunosuppressive. Examples of these medicines include corticosteroids, Disease Modifying Anti-Rheumatic Drugs (DMARDs), and monoclonal antibodies that affect the immune system.

Immunosuppressants theoretically increase the chances of contracting coronavirus, or developing more severe infection. However, the extent of this effect is uncertain. Ceasing immunosuppressants could destabilise control of the underlying disease resulting in direct patient harm from disease, risk of hospitalisation (and COVID-19 exposure), and use of more immunosuppressing regimens (such as high-dose corticosteroids) to regain disease control. The long duration of effect of most immunosuppressants means omitting doses after COVID-19 exposure, for example, confers little or no short-term reduction of immunosuppression.

The management of immunosuppression for patients with an active infection is dependent on individual factors, such as the indication for immunosuppression and severity of the infection. It is therefore not possible to provide explicit guidance here, but clinicians are advised to use the same approach as applies to other significant viral infections, such as influenza. Discussion with the relevant specialist is recommended.

Antipsychotics

Patients taking antipsychotics should continue to take them unless there is a conventional reason to stop (e.g. falls or sedation).

Antipsychotics are associated with an almost 2-fold increase in risk of pneumonia in observational studies. However, depending on the baseline risk of pneumonia the number needed to treat to cause one case of pneumonia is between 86 and over 1,126. The risk is much lower than other significant adverse effects of antipsychotics. A causal relationship between antipsychotics and pneumonia has not been definitively established.

Antipsychotic cessation could result in withdrawal or destabilisation of the underlying condition. Therefore, we do not advocate changing antipsychotic prescribing solely on the basis of COVID-19 risk.

Proton pump inhibitors (PPIs)

Patients taking PPIs should continue to take them unless there is a conventional reason to stop (e.g. hyponatraemia or acute kidney injury).

Large meta-analyses of observational studies and randomised trials have demonstrated an association between PPIs and pneumonia with an approximately 1.5-fold increase in risk. The effect appears greatest in the first month of treatment. Randomised data suggests a causal relationship.

The absolute increase in risk, however, is small. PPI cessation could result in worsening reflux (through withdrawal or reduced acid suppression) when PPIs are used for treatment, or gastrointestinal bleeding when PPIs are used prophylactically. Therefore, we do not advocate changing PPI prescribing solely on the basis of COVID-19 risk.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin–noradrenaline reuptake inhibitors (SNRIs)

Patients taking SSRIs/SNRIs should continue to take them unless there is a conventional reason to stop (e.g. fatigue or nausea).

A single observational study has suggested a small increase in respiratory infections in older patients with COPD newly prescribed SSRIs or SNRIs. This has not been studied in other populations, and a causal relationship has not been established.

SSRI/SNRI cessation could result in withdrawal and/or destabilisation of the underlying condition. Therefore, we do not advocate changing SSRI or SNRI prescribing solely on the basis of COVID-19 risk.

Other anticholinergics

Patients taking anticholinergic medicines, such as oxybutynin, should continue to take them unless there is a conventional reason to stop (e.g. falls or sedation).

Several observational studies of older adults have demonstrated an association between anticholinergic medicines and pneumonia. The extent of the effect is unclear due to variability in study results and design.  A causal relationship between anticholinergic medicines and pneumonia has not been definitively established.

Anticholinergic cessation could result in withdrawal and/or destabilisation of the underlying condition. Therefore, we do not advocate changing anticholinergic prescribing solely on the basis of COVID-19 risk.

Opioids

Patients taking long term opioids should continue to take them unless there is a conventional reason to stop (e.g. opioid toxicity).

Opioids may be useful for acute dyspnoea from COVID-19 in palliative patients.

Chronic opioid use is appropriate in some circumstances, including for patients with advanced lung disease and chronic, refractory dyspnoea. In these circumstances, respiratory depression is very rare. There is no evidence to suggest that this risk is increased in acute respiratory infections. Opioid cessation risks withdrawal and worsening of the underlying condition. We therefore do not recommend changes to chronic opioids solely on the basis of risk of COVID-19.

Opioids may be beneficial for acute dyspnoea, although studies supporting this are lacking. The frequency of respiratory failure with acute opioid use for dyspnoea is poorly characterised; it is likely to be rare but more common than with chronic use. Consensus guidelines support the use of opioids for dyspnoea in palliative care, but there are no guidelines advocating for or against opioids to treat acute dyspnoea outside of a palliative setting.

Other medicines associated with respiratory depression

Patients should be advised not to stop any regular medicines unless there is a conventional indication to do so.

Gabapentinoids (gabapentin and pregabalin) are rarely associated with respiratory depression, irrespective of concomitant medicines. There is no evidence to suggest that this risk is increased in acute respiratory infections.

Benzodiazepines are associated with respiratory depression and developing pneumonia in observational studies, and this may be worse with underlying lung disease. The precise extent of the risk is unclear. Zopiclone is associated with respiratory depression although there is weak evidence that the extent is less than that of benzodiazepines. There is no evidence to suggest that this risk is increased in acute respiratory infections.

Cessation of all of these medicines is associated with withdrawal and worsening of the underlying condition. We therefore do not recommend changes to prescribing of these medicines solely on the basis of risk of COVID-19.

Medicines monitoring in COVID-19

Clozapine

Standard Medsafe monitoring requirements should be followed whenever possible. If testing is not safe or practical, complete blood count (CBC) monitoring may be relaxed to 3-monthly if criteria are met (see below).

Anyone on clozapine showing signs of infection, including COVID-19, requires an urgent CBC.

Clozapine is subject to close monitoring requirements regulated by Medsafe, including routine testing of absolute neutrophil count weekly during the first 18 weeks of therapy and at least every four weeks thereafter throughout treatment.

The Ministry of Health’s technical advisory group (TAG) has endorsed an international consensus statement for monitoring clozapine during the COVID-19 pandemic. In patients with no safe or practical access to blood testing, CBC monitoring can be reduced to once every 3 months if clozapine prescribing has been stable for over one year and there is no history of neutropenia. See, JPN: Consensus Statement. If changes to clozapine monitoring are necessary, this becomes ‘an unapproved use of clozapine’. See, Medsafe: Unapproved. This advice is valid until October 2020.

See HealthPathways: Clozapine Monitoring (includes a link to patient information).

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