Paxlovid® (Nirmatrelvir/ritonavir) for in-patients

Drug class: Antiviral

Nirmatrelvir is a peptidomimetic inhibitor of coronavirus 3C-like protease. Ritonavir inhibits CYP 3A4 mediated metabolism of nirmatrelvir.

Restricted: Treatment of symptomatic COVID-19 in adults who do not require supplemental oxygen and meet the criteria as defined in NICE TA878 (see sections 1 and 5). 

Paxlovid^® (Nirmatrelvir/ritonavir) can be initiated by all consultants in acute general medicine areas, infectious diseases, respiratory HDU and Critical Care.

A Blueteq form must be completed.

To be commenced within 5-7 days of symptom onset.

The recommended course length is 5 days.

Both nirmatrelvir tablet(s) and ritonavir tablet should be taken TOGETHER.

*For patients requiring a dose reduction, the additional nirmatrelvir tablet will be removed by pharmacy at the point of dispensing.

Renal Impairment

For further information on use in renal impairment please refer to UK Renal Pharmacy Group COVID-19 dosing information

Dosing in obesity

No dose adjustment required.

Use in hepatic impairment

Hepatic transaminase elevations, clinical hepatitis and jaundice have occurred in patients receiving ritonavir. Therefore, caution should be exercised when administering Paxlovid^® to patients with pre-existing liver diseases, liver enzyme abnormalities or hepatitis.

Paxlovid^® (Nirmatrelvir/ritonavir) has an extensive list of drug-drug interactions.

This includes medications that are dependent on CYP3A for clearance and medications which are potent inducers or inhibitors of CYP3A.

• Paxlovid^® (Nirmatrelvir/ritonavir) should NOT be prescribed and supplied until a FULL drug history (including prescribed medications, clinical trial medications, over the counter and herbal medicines) has been confirmed.
• All interactions should be checked using The Liverpool COVID-19 Drug Interaction Checker including Resources for Nirmatrelvir/ritonavir (Paxlovid® ; 5 day administration).
• All RED interactions: Paxlovid^® must be avoided. AMBER interactions that suggest dose modification should be discussed with Micro/ID, a pharmacist or the relevant specialist team. 
• Note, use of Paxlovid^® in a patient receiving apixaban requires a risk-based approach and should be discussed with Micro/ID or a pharmacist.

Other useful resources for checking interactions include:

• The BNF Interaction Checker
• Paxlovid Summary of Product Characteristics  
• electronic medicines compendium (emc)

• Ritonavir may reduce the efficacy of combined hormonal contraceptives. Patients should use an alternative form of contraception or an additional barrier method of contraception during treatment and until after one complete menstrual cycle after stopping Paxlovid^® (nirmatrelvir/ritonavir).
• As nirmatrelvir is co-administered with ritonavir, there may be a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection. Discuss with Micro/ID.
• Discharge letters to primary care, and other handovers of clinical care, should explicitly record the treatment that has been given, together with the dose and date of administration.
• Patients discharged before completing treatment should continue the course on discharge. The patient should be counselled on how to take the medication and on any adjustments made to other medication prior to discharge.

Pregnancy – Paxlovid^® (nirmatrelvir/ritonavir) should NOT be used during pregnancy.

Breastfeeding:

Although the manufacturer recommends breast-feeding should be discontinued during treatment with Paxlovid^® and for 7 days after the last dose the Specialist Pharmacy Service advises Paxlovid^® can be used with caution in breastfeeding:

• Risk of accumulation in the infant is very low. As a precaution monitor infant for poor feeding, adequate weight gain, vomiting, diarrhoea, poor sleeping, and signs of jaundice.
• Moderate amount of published evidence shows negligible levels of ritonavir in breast milk resulting in variable infant serum levels, ranging from undetectable to low. No adverse effects reported in breastfed infants to date.
• No published evidence for the excretion of nirmatrelvir into breast milk, but it is likely to pass into breast milk in very low amounts due to its favourable pharmacokinetics.

Consent for use of Paxlovid^® during breastfeeding must be documented.

1. Paxlovid 150mg/100mg film-coated tablets [online]. Manufacturer – Pfizer Ltd. Last updated: 2022 Oct. Accessed via: www.emc.medicines.org.uk [Accessed 2023 Aug 04]
2. National Institute for Health and Care Excellence. Technology appraisal guidance 878: Casirivimab plus imdevimab, nirmatrelvir plus ritonavir, sotrovimab and tocilizumab for treating COVID-19. Last updated: 2024 Mar 13. Accessed via: www.nice.org.uk. [Accessed 2024 Apr 24]
3. Specialist Pharmacy Service. Nirmatrelvir + ritonavir (Paxlovid). Published 2021 Dec 20. Accessed via: www.sps.nhs.uk [Accessed 2023 Aug 04]
4. Department of Health and Social Care. Independent report: Defining the highest risk clinical subgroups upon community infection with SARS-CoV-2 when considering the use of neutralising monoclonal antibodies (nMABs) and antiviral drugs. Last updated: 2023 Apr 05. Accessed via: www.gov.uk [Accessed 2023 Aug 08]
5. UK Renal Pharmacy Group. Dosing advice for Paxlovid and Remdesivir in CKD 4&5. Last updated: 2023 Apr. Available via: www.ukkidney.org. [Accessed 2023 Aug 04]
6. Stockley’s Drug Interactions [online]. Accessed via: www.medicinescomplete.com. [Accessed 2023 Aug 04]