Interacting medicines

Nirmatrelvir and ritonavir (Paxlovid) interact with a significant number of medicines. The relative importance of the interaction and management approach will vary between patients.

Decision to prescribe

Prescribing clinicians, especially those in non-specialist settings, will need to consider, where relevant:

• their confidence in the completeness of patient medication and relevant medical history
• their familiarity with prescribing and managing medication with complex interactions
• their confidence that the patient understands the risks and benefits and that the patient will be followed up appropriately
• availability of specialist advice from the patient’s usual care provider
• practical issues such as additional monitoring, ease of dose adjustments and whether an interacting medication might be safely withheld
• impact of stopping Paxlovid after course completion and subsequent need to reconsider management strategies used to facilitate safe use in someone taking interacting medicines when Paxlovid was initiated

Checking interacting medicines

There is no single comprehensive source of information about interacting medicines.

Freely available resources include the SmPC, BNF and University of Liverpool COVID-19 Drug Interaction checker.

University of Liverpool COVID-19 Drug Interaction checker

The checker includes published evidence and pragmatic advice from practising clinicians. It also includes several prescribing resources, including:

• assessing a patient for treatment with Paxlovid
• resuming medicines that are paused or dose-adjusted during Paxlovid treatment

The checker is available as an app which can be downloaded for use on Apple and Android devices.

Medicines Advice Service

If the clinical scenario is complex or you require further support, healthcare professionals working in primary care in England can seek further advice from our Medicines Advice service.

Swallowing difficulties

The Paxlovid SmPC advises the tablets should be swallowed whole and not chewed, broken or crushed. The NHSE COVID-19 antiviral treatment e-learning module suggests referring patients for sotrovimab where doubt exists over ability to swallow.

Both nirmatrelvir and ritonavir are immediate release tablets and we are aware of practice where they have been crushed or split to aid administration, or ritonavir sachets used to replace ritonavir tablets. If tablets are crushed or split, the manufacturer advises there is a risk that plasma concentrations may not be comparable to those obtained after taking intact tablets. This is because clinical studies have not been undertaken.

Crushing or splitting tablets is an off-label use.

Pregnancy

Use in pregnancy is not recommended. The Paxlovid SmPC states there are no data on use in pregnancy. The NHSE COVID-19 antiviral treatment e-learning module suggests referring pregnant patients for sotrovimab.

Exposure in pregnancy

The UK Teratology Information Service (UKTIS) monograph on medications used to treat COVID-19 in pregnancy  provides limited information on exposure to Paxlovid in pregnancy. Discussion with UKTIS (telephone 0344 892 0909, available Monday to Friday excluding Bank Holidays, 9am to 5pm) should take place in all cases, where COVID-19 antiviral treatment is being considered in pregnancy. 

Where individuals are pregnant, or become pregnant shortly after taking Paxlovid, this should  be reported to the UK COVID-19 Antivirals in Pregnancy Registry on 0344 892 0909, so that they can be followed up. 

Further information about the registry, such as who can report, is available via the best use of medicines in pregnancy website.

Paternal exposure

No effects on the baby are anticipated if the father has used Paxlovid.

Pregnancy prevention

Where patients are able to become pregnant, effective barrier contraception (for example a condom, female condom, diaphragm or cap) must be used for the duration of treatment and until one full menstrual cycle is completed after the last dose of Paxlovid.

This advice applies even if the individual is taking combined hormonal contraception, because nirmatrelvir boosted with ritonavir may decrease ethinylestridaol concentrations reducing the effectiveness of ethinylestradiol containing contraceptives.

Breastfeeding

See our guidance on Managing COVID-19 and breastfeeding for specific information relating to use of Paxlovid in breastfeeding and general guidance on breastfeeding in individuals with COVID-19 infection. It can be used to support an individual risk assessment for patients who are breastfeeding, taking into account the benefits and risks of treatment with Paxlovid.

Healthcare professionals, from all sectors, may contact our Breastfeeding Medicines Advice service for further support and advice.

Renal impairment

The Paxlovid SmPC recommends against use in individuals with severe renal impairment or renal failure, as the appropriate dose has not yet been determined. The NHSE COVID-19 antiviral treatment e-learning module suggests referring such patients for sotrovimab.

However, experience of use of Paxlovid in those with severe renal impairment or renal failure (off-label) is growing. New guidance, from the UK Renal Pharmacy group suggests the data for nirmatrelvir and ritonavir (Paxlovid) in adult patients with CKD stage 4 and 5 (excluding individuals taking tacrolimus, ciclosporin or sirolimus), shows it can be given safely in this cohort. Consider discussing with the patient’s specialist, if appropriate.

Patient Information

Patients may not read, or read in full, the Patient Information Leaflet, so it is important they are provided with key information, verbally, at every interaction with a healthcare professional.

Patients can be referred to:

• NHS website patient level information on Paxlovid
• UKHSA Patient information for Paxlovid
• Pfizer Paxlovid Patient Information Booklet

Referring for sotrovimab

Patients unsuitable for Paxlovid may be referred for sotrovimab, as a second-line treatment option. Referral pathways may differ based on location and services set up in your local area. You should familiarise yourself with local commissioning models to ensure you are referring appropriately. SPS are unable to provide advice on local referral pathways. 

Other treatments 

Remdesivir and molnupiravir are not recommended by NICE MTA [TA878]; an appeal is ongoing. However, NHSEs Interim clinical access policy for remdesivir and molnupiravir published on 11 May remains in place until the end of the NICE appeals process.  

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