This information is taken from a UKCPA webinar presentation given in February 2022 by Kirsteen Hill, Antimicrobial/HIV Pharmacist at NHS Tayside
Paxlovid® (Nirmatrelvir/Ritonavir) is an outpatient treatment for COVID-19 patients. A retrospective review was undertaken of patients who had been prescribed treatment from the COVID-19 outpatient treatment pathway since 22 December 2021 in NHS Tayside to ascertain who could have been eligible for Paxlovid. This review looked at 75 patients who had been prescribed Sotrovimab or Molnupiravir or who were eligible for treatment but declined.
The review process included looking at the electronic hospital outpatient medical records, clinical portal including GP prescribed medication, blood test results and speciality notes.
Out of 75 patients, 53 would have been eligible for Paxlovid. Thirty of these were deemed to have no prescribing issues and could have been safely prescribed Paxlovid. Twenty-three would have been categorised as ‘yes with caveats’, meaning that a pharmacist would have provided advice for the prescriber or patient.
Advice categories included temporary withholding or dose changing for a patient’s long-term medicine or additional monitoring suggestions and warning regarding potential short term side effects. Around one third (22 out of 75 patients) would have been deemed unsuitable for Paxlovid treatment. Reasons for these exclusions included significant drug-interactions (n=16), insufficient renal function (n=6), pregnancy (n=1) and aged under 18 years (n=1).
Drug-drug interactions with Paxlovid
Ritonavir is a CYP3A4 enzyme inhibitor so has the potential for numerous drug-drug interactions. As part of the patient review, potential drug-drug interactions (DDIs) with Paxlovid® were checked using a variety of databases.
The University of Liverpool COVID-19 drug interactions website categorises DDIs as either red, amber, green or yellow. Green and yellow flags on the drug interactions website suggest that no clinically significant DDI exists, whilst a red flag indicates significant cause for concern. An amber flag does not preclude co-administration (since DDIs are usually manageable) but rather indicates the need to consider risks and benefit for that patient for whom treatment is considered. A red flag can also be managed by short term withholding of a patient’s long-term medicine. An example of this is temporary stopping of a statin whilst the Paxlovid® short course is prescribed.
Other resources used to find information about drug interactions with Paxlovid® include the specific product characteristic for each drug, along with the HIV drug interactions database, the Specialist Pharmacy Service COVID-19 database and the National Institute for Health COVID-19 treatment guidelines statement on paxlovid-drug-interactions. Based on the experience in Tayside, an assessment tool was developed to help prescribers review patients for Paxlovid. The tool is one of the documents on the prescribing resources page of the University of Liverpool Covid-19 drug interactions website.
In summary, Paxlovid® has many more drug-drug interactions compared to sotrovimab or molnupirivir. To safely offer this treatment to as many eligible patients as possible will need pharmacist input.
Frequently asked questions
Q: How much time does it take for pharmacists to check the Paxlovid® prescriptions?
This may vary depending on the time to check an individual prescription for a patient. Finding the information for a full medicines reconciliation or drug history can be time consuming and difficult when trying to access information from specialist service records, such as oncology or renal services. The total time to check each prescription often takes between 5-20 minutes per patient.
Q: What is the significance of potential drug interactions between oral and inhaled corticosteroids and Paxlovid®?
The Liverpool COVID-19 drug interactions tracker lists a green flag for oral/inhaled corticosteroids with Ritonavir. There doesn’t appear to be significant interactions with short term use of inhaled steroids compared to long term co-prescription of corticosteroids and ritonavir.
Q: What are the risks of prescribing Paxlovid® in patients with Stage 3 CKD?
Trial work is currently being undertaken in the USA about dose adjustment of Paxlovid® in patients with significant renal impairment. For patients in the UK who would not be able to attend hospital for an intravenous COVID-19 antiviral/nMAB, there is potential to reduce the dose for oral treatments such Paxlovid®. However, this needs to be balanced against the safety of labelling the drug with dosage guidelines, which was reported as a concern. Sotrovimab would be safer to prescribe for patients with severe renal impairment. The time since blood test results were last reported for patients to ascertain renal function should be considered; for example, patients who have stable renal function whose blood tests had been checked within three months are potentially safe.
Q: What if the patient was on Day 5 since onset of symptoms and a positive COVID-19 result but treatment would not be able to start for a further 24-48 hours?
The guidelines suggest that treatment should be started within five days of onset of symptoms and a positive COVID-19 result by PCR or LFT. However, service constraints may mean that treatment is unable to start for a further 24-48 hours (for example, aseptic dispensing services may only be five day rather than seven day services). There is a drop in efficacy for treatment between 5-7 days but, in practice, patients are being initiated on treatment starting day 6 or 7 and there is an allowance for this in the UK Commissioning Policy.
Summary:
- Paxlovid® is currently considered the most effective oral treatment option for patients with mild to moderate COVID-19 to reduce the risk of hospitalisation or death.
- Individualised patient assessment and clinical decision-making is key to ensuring that as many patients as possible can receive treatment. The input of pharmacists here is key.
- Potential for drug interactions exist but most interactions can be managed with available tools and resources
- If Paxlovid® is not considered to be suitable other treatment options are available.
The opinions expressed in this article are those of the author. They do not purport to reflect the opinions or views of the UKCPA or its members. We encourage readers to follow links and references to primary research papers and guidance.
Competing interest statement:
The author declares: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
