Neutralising monoclonal antibodies (nMABs) and antivirals for COVID-19 

Patients who do not require hospitalisation for COVID-19

Antivirals and the nMAB, sotrovimab, are recommended for non-hospitalised patients with COVID-19 who have risk factors for progression to severe COVID-19. Criteria for treatment are outlined in NICE TA878 and a national clinical commissioning policy. For further information, refer to COVID-19 treatments for patients who do not require hospitalisation. 

Antivirals

MHRA Drug Safety Update (February 2022): COVID-19 antivirals: reporting to the UK COVID-19 Antivirals Pregnancy Registry

• Healthcare professionals (as well as patients and their partners) can report an exposure to a COVID-19 antiviral during pregnancy or around the time of conception, or of partners on a COVID-19 antiviral around the time of conception.
• To report to the registry, telephone: 0344 892 0909 (available 9:00am to 5:00pm, Monday to Friday, excluding bank holidays) – for more information see the UKTIS website

Paxlovid

(Nirmatrelvir and ritonavir)

• Each pack contains five daily blister cards (total of 30 tablets; £2.50). Each daily blister card contains:
  • four nirmatrelvir 150mg tablets
  • two ritonavir 100mg tablets

• Patient must meet all initial assessment criteria for a COVID-19 treatment. Do not prescribe Paxlovid without carefully considering whether it is appropriate for the patient – Refer to COVID-19 treatments for patients who do not require hospitalisation

Indications and dose

• COVID-19 infection in adults in line with NICE TA878:
  • 300mg nirmatrelvir (two 150mg tablets) with 100mg ritonavir (one 100mg tablet) all taken together orally twice daily for 5 days
  • Mild renal impairment: no dose adjustment
  • Moderate renal impairment (eGFR ≥30 to <60 mL/min/1.73m²): nirmatrelvir/ritonavir 150mg/100mg (1 tablet of each) twice daily for 5 days. The remaining tablet of nirmatrelvir should be disposed of in accordance with local requirements.
  • Severe renal impairment (eGFR <30mL/min/1.73m²) or renal failure: contraindicated as appropriate dose yet to be determined
  • Hepatic impairment: No dose adjustment in mild or moderate hepatic impairment. Contraindicated in severe hepatic impairment due to lack of data

Notes

1. Prompt review is required: Paxlovid should be given as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 5 days of onset of symptoms.
2. Drug interactions: There is a significant risk of potentially serious or harmful drug interactions with Paxlovid, leading to increased toxicity from, or reduced effectiveness of concomitant medications, or reduced effectiveness of Paxlovid. Particular care should be taken to check for drug interactions. For further information, refer to COVID-19 treatments for patients who do not require hospitalisation  and note 7 below for the MHRA Drug Safety Update.
3. Paxlovid is not recommended during pregnancy and in women of child-bearing potential not using effective contraception:
   1. Use of ritonavir may reduce the efficacy of combined hormonal contraceptives. Patients using combined hormonal contraceptives should be advised to use an effective alternative contraceptive method or an additional barrier method of contraception during treatment and until after one complete menstrual cycle after stopping Paxlovid.
   2. All healthcare professionals are asked to ensure that any patients who receive a COVID antiviral while pregnant are 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 http://www.uktis.org.
   3. Clinicians are advised to refer to the Paxlovid SmPC and the UK Teratology Information Service Monograph for more information on use during pregnancy.
4. Breastfeeding: The Paxlovid SmPC recommends breastfeeding should be discontinued during treatment with Paxlovid and for 7 days after the last dose. Other sources indicate this may not be necessary with careful monitoring of the infant for adverse effects. Seek specialist advice (see clinical referral guidance).
5. Nirmatrelvir tablets are oval-shaped with a dimension of approximately 17.6mm in length and 8.6mm in width. Ritonavir tablets are capsule-shaped with a dimension of approximately 17.1mm in length and 9.1mm in width. Tablets should be swallowed whole and not chewed, broken or crushed (Paxlovid SmPC). Patients who are unable to swallow these tablets should be referred (see COVID-19 treatments for patients who do not require hospitalisation).
6. Note for community pharmacies: Paxlovid can be ordered from Alliance Healthcare. Treatment should commence within 5 days of onset of COVID-19 symptoms. Inform the patient or their representative if the medication will not be available within the 5 day ‘treatment window’ and ask them to report this to their GP, who can make a referral to a Covid Medicines Delivery Unit. For further information on ordering Paxlovid, see Community Pharmacy England: Stocking COVID-19 antivirals.
7. NICE TA878: Nirmatrelvir plus ritonavir, sotrovimab and tocilizumab for treating COVID-19 (March 2023, updated March 2024):
   1. Nirmatrelvir plus ritonavir is recommended as an option for treating COVID-19 in adults, only if they:
      1. do not need supplemental oxygen for COVID-19 and 
      2. they are in any of the following patient groups: 
         1. an increased risk for progression to severe COVID-19, as defined in section 5
         2. aged 85 years and over
         3. end-stage heart failure who have a long-term ventricular assistance device
         4. on the organ transplant waiting list
         5. aged 70 years and over, or who have a BMI of 35kg/m² or more, diabetes or heart failure, and are resident in a care home or are already hospitalised
      3. NICE has recommended a phased implementation of new TA878 recommendations for Paxlovid starting with the addition of the patient groups listed above in addition to the existing patient groups listed in section 5 of TA878
8. MHRA Drug Safety Update (November 2023): Nirmatrelvir, ritonavir (Paxlovid): be alert to the risk of drug interactions with ritonavir
   1. There is a risk of potentially serious drug interactions with the ritonavir component of Paxlovid leading to increased toxicity from, or reduced effectiveness of concomitant medications.
   2. Ritonavir is a potent CYP3A4 inhibitor. As many commonly used drugs are metabolised by CYP3A4, the risk of harmful drug interactions with Paxlovid is significant.
   3. Drug interactions may also reduce the effectiveness of Paxlovid, in the treatment of COVID-19.
   4. Obtain a thorough history of patients’ current medications, including over the counter (OTC) medications, herbal remedies and illicit or recreational drug use.
   5. Refer to the Paxlovid SmPC (especially sections 4.3, 4.4 and 4.5) before prescribing Paxlovid to check for contraindications and potential interactions – links to other resources to assist with this are listed in the Drug Safety Update.
   6. For advice to give to patients, refer to the Drug Safety Update.

Molnupiravir

• Capsules 200mg (Pack of 40 capsules = £2.50)

Indications and dose

• Non-hospitalised adults aged 18 years and above with COVID-19 in accordance with the criteria set out in the UK interim clinical commissioning policy (11 May 2023)
  • 800mg (four 200mg capsules) taken orally every 12 hours for 5 days
  • No dose adjustment required for renal or hepatic impairment

Notes

1. Molnupiravir may be prescribed on the advice of a specialist. Refer to COVID-19 treatments for patients who do not require hospitalisation.
2. Molnupiravir should be given as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 5 days of onset of symptoms. 
3. Molnupiravir is not recommended during pregnancy.
   1. Individuals of childbearing potential should use effective contraception for the duration of treatment and for 4 days after the last dose of molnupiravir.
   2. All healthcare professionals are asked to ensure that any patients who receive a COVID antiviral while pregnant are 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 http://www.uktis.org.
   3. Clinicians are advised to refer to the molnupiravir SmPC and the UK Teratology Information Service monograph for more information on use during pregnancy
4. Breastfeeding: The molnupiravir SmPC indicates that breastfeeding is not recommended during treatment and for 4 days after the last dose. Seek specialist advice (see clinical referral guidance).
5. Note for community pharmacies: Molnupiravir can be ordered from Alliance Healthcare. Treatment should commence within 5 days of onset of COVID-19 symptoms. Inform the patient or their representative if the medication will not be available within the 5 day ‘treatment window’ and ask them to report this to their GP, who can make a referral to a COVID Medicines Delivery Unit. For further information on ordering molnupiravir, see Community Pharmacy England: Stocking COVID-19 antivirals.

Remdesivir

• Concentrate for solution for intravenous infusion 5mg/ml vials
• Powder for concentrate for solution for intravenous infusion 100mg vials

Notes

1. Remdesivir is recommended as a treatment option for patients with COVID-19 in hospital in line with NICE TA791.
2. Remdesivir should be avoided in pregnancy unless clinicians believe the benefits of treatment outweigh the risks to the individual. Women of child-bearing potential have to use effective contraception during treatment. 
   1. All healthcare professionals are asked to ensure that any patients who receive a COVID antiviral while pregnant are 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 http://www.uktis.org. 
   2. Clinicians are advised to refer to the Summary of Product Characteristics for remdesivir for more information on use during pregnancy or lactation.
3. Further information on the timing of COVID-19 vaccination following administration of remdesivir is available at the University of Liverpool COVID-19 Drug Interaction Checker.
4. NICE TA971 (May 2024): Remdesivir is recommended as an option for treating COVID-19 in hospitals in: 
   1. adults, only if they have a high risk of serious illness (risk factors as defined in section 5 of NICE's technology appraisal guidance on nirmatrelvir plus ritonavir, sotrovimab and tocilizumab for treating COVID-19) 
   2. babies, children and young people, only if they:
      1. are aged 4 weeks to 17 years and weigh at least 3 kg, and:
         1. have pneumonia, and 
         2. need supplemental oxygen, or 
      2. weigh at least 40 kg, and have a high risk of serious illness (risk factors as defined in section 5 of NICE's technology appraisal guidance on nirmatrelvir plus ritonavir, sotrovimab and tocilizumab for treating COVID-19).
   3. Remdesivir is only recommended if the company provides it according to the commercial arrangement.

Neutralising monoclonal antibodies (nMABs)

Sotrovimab

• Concentrate for solution for intravenous infusion 500mg/8ml (62.5mg/ml) vials
  

Notes

1. NICE TA878: Casirivimab plus imdevimab, nirmatrelvir plus ritonavir, sotrovimab and tocilizumab for treating COVID-19 (March 2023):
   1. Sotrovimab is recommended as an option for treating COVID-19 in adults and young people aged 12 years and over and weighing at least 40kg, only if:
      1. they do not need supplemental oxygen for COVID-19 and
      2. they have an increased risk for progression to severe COVID-19, as defined in section 5 and
      3. nirmatrelvir plus ritonavir is contraindicated or unsuitable.
   2. Sotrovimab is only recommended if the company provides it according to the commercial arrangement.

Tixagevimab plus cilgavimab (Evushield)

1. NICE TA900 (June 2023): Tixagevimab plus cilgavimab is not recommended, within its marketing authorisation, for the pre-exposure prophylaxis of COVID-19 in adults who are not currently infected with SARS-CoV-2 and who have not had a known recent exposure to someone infected with SARS-CoV-2:
   1. who are unlikely to have an adequate immune response to COVID 19 vaccination, or 
   2. for whom COVID 19 vaccination is not recommended
2. NICE TA971 (May 2024): Tixagevimab plus cilgavimab is not recommended, within its marketing authorisation, for treating COVID-19 in adults who do not need supplemental oxygen and who have an increased risk of progression to severe COVID-19.