Diabetics use the "new crown special drug" Paxlovid, these 5 questions must be known, it is recommended to collect!

Since the national optimization and adjustment of epidemic prevention and control policies, all provinces and cities across the country have successively liberalized prevention and control, and although the virus toxicity has weakened, the transmission power is still very strong
.
Diabetic patients belong to the new crown susceptible group and are also at high risk of
critical illness.
As an endocrinologist, in addition to the efficacy of the new crown, we are also very concerned about the impact of Paxlovid on hypoglycemic therapy, which hypoglycemic drugs will interact with Paxlovid and which can be used safely?

1.
What is the "new crown drug" Paxlovid?

Paxlovid is a combination antiviral drug with generic name nirmatevir/ritonavir tablets, consisting of
nimatevir (the main active ingredient) and ritonavir (CYP3A inhibitor).

➤Nematevir: the main active ingredient of Paxlovid, can inhibit SARS-CoV-2 main protease Mpro (also known as 3C-like protease, 3CLpro), making it unable to process multiprotein precursors to produce functional proteins, thereby preventing viral replication and proliferation;

➤Ritonavir: is a CYP3A inhibitor that increases the level of exposure in vivo by slowing down the metabolism of nematevir, so that nematevir prolongs the action time in the body, increases blood concentration, and exerts a synergistic effect
.

Which patients is Paxlovid suitable for?

In February 2022, the China Food and Drug Administration (NMPA) conditionally approved the import registration
of Paxlovid in accordance with the special approval procedure for drugs.
In January 2023, China's "Diagnosis and Treatment Plan for Novel Coronavirus Infection (Trial Version 10)" further clarified that Paxlovid is suitable for adult patients
with mild and medium-sized patients with high-risk factors for progression to severe disease within 5 days of onset.
Factors at high risk for severe illness from the novel coronavirus (COVID-19) include:

➤ Over 65 years old, especially those who have not been fully vaccinated against the new coronavirus;

➤Patients with cardiovascular and cerebrovascular diseases (including hypertension), chronic lung diseases, diabetes, chronic liver, kidney diseases, tumors and other underlying diseases, as well as maintenance dialysis patients;

➤ Immunodeficiency (eg, immunodeficiency state due to long-term use of corticosteroids or other immunosuppressive drugs in AIDS patients);

➤ Obesity (body mass index≥ 30kg/m^2);

➤ Women in late pregnancy and perinatal period;

➤ Heavy smokers
.

Which patients does Paxlovid not apply to?

➤ symptomatic patients without risk factors for progression to severe disease;

➤ Asymptomatic SARS-CoV-2 infected people
.

How to use Paxlovid correctly? What should I do if I miss a dose?

Take 300 mg of nematevir (2 tablets of 150 mg) and ritonavir 100 mg (1 tablet) 2 times a day for 5 days
at a time.
It should be initiated
as soon as possible within 5 days of symptom onset after diagnosis of COVID-19.
Note that:

1.
The first day of symptom onset is considered as day 0, day 2 is regarded as day 1, and so on
.

2.
It should be swallowed whole, not chewed, broken or crushed
.

3.
If a dose is missed but not more than 8 hours after the usual time of taking the drug, it should be supplemented as soon as possible and continue to take the drug
according to the normal dosing schedule.
If the missed dose is missed and more than 8 hours, the missed dose should not be retaken, but the next dose should be taken according to the prescribed time, and do not take a double dose
to make up for the missed medication.

4.
What kind of hypoglycemic drugs can Paxlovid be combined with? What should be used sparingly?

Paxlovid is both an inhibitor of liver enzymes (such as CYP3A) and transporters (P-gp, BCRP, and OATP1B1) and a substrate of CYP3A, and some hypoglycemic drugs have clinically meaningful interactions
with Paxlovid.
Before giving nirmatevir/ritonavir, physicians should review prescription drugs, over-the-counter drugs (including herbal preparations), and any other substances used by the patient and evaluate potential drug interactions (see Table 1).

➤ Red: No combination;

➤ Orange: potentially clinically significant interactions that may require additional monitoring, changing drug dose or timing of administration;

➤ Yellow: potential interactions, weak intensity, unlikely to require additional measures/monitoring or dose adjustment;

➤ Green: No significant clinical interactions
are expected.

Table 1 Interactions and recommendations of Paxlovid with common hypoglycemic drugs

When there is a drug interaction, what is the correct way to deal with it?

The dose
of nematevir/ritonavir should not be adjusted to avoid potential drug interactions.
Where there is a serious interaction, it is reasonable to:

1.
Avoid the use of nematevir/ritonavir;

2.
Discontinue or reduce the dose of drugs that have interactions (not suitable for drugs with a long half-life, such as amiodarone).

Short-term administration of nimatevir/ritonavir is not expected to result in sustained suppression of CYP3A, so discontinuation or resumption of the original dose can be resumed 3 days after the end of the five-day course; In older patients (nirmatevir/ritonavir inhibitory effect may last a little longer) and for drugs with a narrow treatment window, it is advisable to wait longer before resuming dosing
.

Fifth, diabetes combined with hepatic/renal insufficiency, Paxlovid medication attention?

1.
Diabetic patients such as renal insufficiency

In patients with diabetes with renal insufficiency, the dose of Paxlovid should be adjusted accordingly according to renal function status:

➤Patients with glomerular filtration rate (eGFR) ≥ 60 mL/min: dose adjustment is not required;

➤Patients with glomerular filtration rate (eGFR) of 30-59 mL/min: 2 times a day, each dose is simultaneously oral nematevir 150 mg (1 tablet of 150 mg) and 1 tablet of ritonavir of 100 mg for 5 days;

➤Patients with glomerular filtration rate (eGFR) < 30mL/min (including end-stage renal disease under hemodialysis): This is an off-label medication and requires consultation
.

2.
Diabetic patients with liver insufficiency

According to the Child-Pugh rating:

➤ Patients with Child-Pugh A and Child-Pugh B: dose adjustment is not required;

➤ Patients with Child-Pugh class C: Not recommended
.

References:

[1] Abraham S, Nohria A, Neilan TG, et al.
Cardiovascular Drug Interactions With Nirmatrelvir/Ritonavir in Patients With COVID-19: JACC Review Topic of the Week [J].
J Am Coll Cardiol.
2022, 80(20): 1912-1924.

[2] Packaging instructions for nematevir tablets/ritonavir tablets, Sinopharm HJ20220006.
Approval date: 2022.
02.
11[Z].

[3] General Office of the National Health Commission, General Department of the State Administration of Traditional Chinese Medicine.
"Diagnosis and Treatment Plan for Novel Coronavirus Infection (Trial Version 10)" [EB/OL].
(2023-01-05)/[2023-01-07].
style="white-space: normal;" _msthash="251180" _msttexthash="16660800">[4] Guangdong Pharmaceutical Association.
Clinical Pharmacy Guidelines for Antiviral Treatment of Novel Coronavirus Pneumonia (Updated Edition).
Pharmacy Today.
2022, 32(08): 561-572.

[5] University Of Liverpool.
Liverpool Covid-19 Interactions [EB/OL].
(2022-09-07)/[2023-01-07].
style="white-space: normal;" _msthash="251182" _msttexthash="19534034">[6] Clinical pharmacy guidelines for the use of nematevir/ritonavir tablets (Paxlovid) in cardiovascular patients in Guangdong Province.
style="white-space: normal;">

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