Using nirmatrelvir and ritonavir (Paxlovid) in practice

Helen Davis, Director, North West Medicines Information CentrePublished Last updated See all updates
Topics: Oral antivirals

Use in patients taking interacting medicines, those with swallowing difficulties, or who are pregnant or breastfeeding, and signposting to patient advice.

Interacting medicines

Decision to prescribe

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

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

  • their confidence in completeness of patient medication and relevant medical history
  • their familiarity with prescribing and managing medication with complex interactions
  • their confidence the patient understands the risks and benefits and the patient will be followed up appropriately
  • availability of specialist advice from the patient’s usual care provider
  • practical issues such as additional monitoring
  • impact of stopping Paxlovid and reconsider management strategies used to facilitate safe use in someone taking interacting medicines.

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.

The Liverpool COVID-19 Drug Interaction checker includes published evidence as well as pragmatic advice from practicing clinicians and is regularly updated. There is also an easy to use app available

Swallowing difficulties

The SmPC advises the tablets should be swallowed whole and not chewed, broken or crushed. Data suggests reduced and unpredictable blood levels of ritonavir when the tablets are crushed.

Pregnancy

The SmPC states that there are no data on the use of nirmatrelvir and ritonavir (Paxlovid) in pregnancy and so, along with the other antivirals, it is not recommended during pregnancy.

The UTKIS monograph states that there is a large amount of published evidence relating to the safety of ritonavir in human pregnancy, collected from antiretroviral and HIV/AIDS pregnancy registries. Overall, these data do not provide evidence that ritonavir use in the first trimester is associated with an increased risk of malformation above the expected background rate of 2-3%. There is also no evidence that liponavir/ritonavir combination therapy in pregnancy had any detectable impact on postnatal development. Data investigating other adverse pregnancy outcomes (such as miscarriage, preterm delivery, fetal growth impairment or stillbirth risks) are lacking..

However, the MHRA have advised that a very cautious approach is taken and therefore use in pregnancy is not recommended.

Pregnancy prevention

Where patients are able to become pregnant they must use effective barrier contraception (for example a condom, female condom, diaphragm or cap) for the duration of treatment and until one full menstrual cycle is completed after the last dose of nirmatrelvir and ritonavir (Paxlovid). Nirmatrelvir and ritonavir (Paxlovid) can stop combined oral contraceptive pills (‘the pill’) from working properly. A barrier method of contraception in addition to the oral contraceptive pill must be used for the duration of treatment with nirmatrelvir and ritonavir (Paxlovid) and until one full menstrual cycle is completed after the last dose of nirmatrelvir and ritonavir (Paxlovid).

Pregnancy registry

Where patients are pregnant, or became pregnant while taking nirmatrelvir and ritonavir (Paxlovid), or shortly after this should be reported to the UK COVID-19 Antivirals in Pregnancy Registry on 0344 892 0909 so that they can be followed up.

For more information, go to bumps – best use of medicine in pregnancy.

Breastfeeding

It’s not known how much nirmatrelvir passes into breast milk. Ritonavir passes into breast milk in low amounts.

The SmPC states that breastfeeding is not recommended during treatment with Paxlovid and for 7 days after the last dose.

An individual risk assessment should be conducted for each patient, taking into account the benefits and risks of treatment with Paxlovid while breastfeeding.

Breastfeeding can continue if you have COVID-19 infection, or have had a COVID-19 vaccine.

Further SPS information and advice on Nirmatrelvir + ritonavir (Paxlovid) is available.

Patient Information

Typically, few patients are likely to read the Patient Information Leaflet so it is essential that they are provided with key information at every interaction with a healthcare professional.

Patients can also be referred to further NHS sources of information:

Other oral antiviral resources

Using molnupiravir in practice

Advice on swallowing difficulties, use in pregnancy and breastfeeding, and signposting to advice to give to patients.

Using COVID-19 oral antivirals in practice

Deployment should address a range of factors and be implemented through different mechanisms. Collecting data and learning will support continued safe use.

Change history

  1. Added section on principles to consider when prescribing in patients on interacting medicines
  1. Added new section on use in patients with swallowing difficulties
  1. Information on use in pregnancy added
  2. Removed reference to information on use in patients with swallowing difficulties.
  1. Definition of amount of ritonavir passing into breastmilk changed from negligible to low after review of literature resources.
  1. Published