Could anticipatory deprescribing allow better COVID treatment?

Earlier this year, a head-to-head trial of the two oral antivirals available in Australia – nirmatrelvir-ritonavir (Paxlovid) and molnupiravir (Lagevrio) – suggested the former is better at preventing deaths and reducing the length of hospital stays.
 
But while Australia has secured one million treatment courses of the medication, compared to just 300,000 for molnupiravir, the latter has been prescribed at a rate 4.5 times higher than the former (123,000 vs 27,000).
 
One likely factor is likely to be the number of drug–drug interactions (DDIs) clinicians need to consider when prescribing, especially for older patients who stand to benefit the most from the treatment.
 
However, a recently released study has explored the potential for anticipatory deprescribing in this cohort, which the authors suggest could have the duel benefit of reducing polypharmacy and also giving vulnerable patients more COVID treatment options.
 
‘In a population of older adults with polypharmacy, DDIs with nirmatrelvir-ritonavir were common,’ they wrote.
 
‘Many DDIs involved PIMs [potentially inappropriate medicines], which were candidate drugs for deprescribing. Because of these DDIs, many older adults with polypharmacy could not safely receive nirmatrelvir-ritonavir.
 
‘Intercurrent health conditions can be an opportune time to deprescribe PIMs. Symptomatic COVID-19 and potential treatment with nirmatrelvir-ritonavir should prompt a thorough medication review for DDIs, at which point deprescribing could be considered.’
 
Another advantage of assessing opportunities for deprescribing prior to a COVID diagnosis, according to the authors, is that it gives more space for a ‘washout’ period for certain medications, and for tapering those that cannot be stopped immediately.
 
‘Not all DDIs could be mitigated by simply holding or dose-reducing a medication,’ they wrote.
 
‘Some medications required anticipatory deprescribing to prevent adverse drug withdrawal events attributed to sudden stopping [eg benzodiazepines] or prolonged half-life [eg amiodarone].’
 
Professor Dimity Pond, a GP with a special interest in aged care and member of the RACGP Silver Book Expert Advisory Group (EAG), thinks the concept is a ‘fantastic idea’.
 
‘I’ve not heard of anyone suggesting that you could use this as a bit of a rethink [in terms of prescribing],’ she told newsGP.
 
‘But there are far too many people on far too many medications, really.
 
‘It affects quality of life and … often the ageing brain and the ageing body don’t cope with the level of tablet that they could 10 years earlier.’
 
When assessing patients for deprescribing, Professor Pond said she considers their age, physical health and estimated life expectancy, the indications for the various medications and how many are being taken.
 
‘[For example], I’ve got a lot of older patients with dementia, and I tend to take them off their statins because dementia is a terminal illness and statins are only going to stop you having a heart attack or stroke in the next 15 years,’ she said.
 
‘Well, we’re not looking at 15 years with someone who has moderate-to-severe dementia anyway, if they’re 85 years old.
 
‘It can be hard for people to swallow when they get older, and it can be hard for them to remember everything. And if they’re on shovelfuls of tablets three or four times a day, it’s just awful.’
 
Associate Professor Paresh Dawda, who is Vice Chair of RACGP Expert Committee – Quality Care and also a member of the Silver Book EAG, also thinks anticipatory deprescribing could be justified in some instances.
 
However, he qualified those remarks by pointing out that the study involved hospitalised patients, rather than potentially more frail and vulnerable people in residential aged care.
 
‘If the reason for nirmatrelvir-ritonavir not being suitable was a potential drug-interaction and if there was an opportunity to appropriately deprescribe that drug, then GPs should certainly consider that,’ he told newsGP. 
 
‘The current guidelines from the National COVID-19 taskforce in their guidance for older people speak of polypharmacy and reducing this if possible, [as well as] ensuring early discussion with the patient around goals of care, which may include active disease-directed care.
 
‘They also recommend multidisciplinary collaboration amongst the health and social/community care teams within the decision-making process when managing people with multimorbidity, cognitive impairment and functional decline.
 
‘Early specialist advice should be considered in older people living with frailty and/or cognitive impairment.’
 
Nearly 5700 patients aged 71–86 were assessed as part of the trial, all of whom were on 8–14 daily medications, approximately 1–4 of which were considered potentially inappropriate.
 
More than two thirds (67.9%) received at least one medicine that would react with nirmtrelavir-ritonavir, the most common of which were antithrombotic medications (37.4%) or statins (33.4%).
 
‘Among the 3869 patients with interacting medication prescriptions, 823 [21.3%] had
at least one PIM, of whom 627 [76.2%] had a high-risk DDI with nirmatrelvir-ritonavir,’ the authors wrote.
 
‘Common deprescribing opportunities included dual anticoagulant therapy without a recent coronary event or intervention [41%], alfuzosin or tamsulosin for benign prostatic hypertrophy in a person with orthostatic hypotension or recurrent falls [22.3%], and antipsychotics for sleep or agitation [22.6%].’
 
Professor Pond agrees that it would likely be appropriate to explore anticipatory deprescribing in these cases.
 
She also believes GPs are the best-placed clinicians to make these decisions.
 
‘A lot of GPs say, “Well, a specialist prescribed whatever it is, and I’m reluctant to stop it in case the specialist gets upset”. But when the patient has five different specialists, each with three medications, then you’ve got 15 medications,’ Professor Pond said.
 
‘I think we’re the specialists for this general overview of the patient – their medications and drug interactions, and how much effect the specialist treatment is having when you look at it in the big picture.
 
‘We’ve got a right as GPs to really reconsider whether all the medications prescribed by specialists, who are just thinking about their own little bit of the body, is right from a whole, patient-centred, holistic view.
 
‘That’s an ideal … role for us. We just need to think it through, and document and monitor any effects from reducing or stopping.’
 
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COVID-19 drug–drug interactions Lagevrio molnupiravir nirmatrelvir-ritonavir oral antivirals Paxlovid