Paxlovid Is Here: A Pharmacist's Prescribing Pearls

How does Paxlovid treat COVID-19?

Michael Ganio, PharmD

Paxlovid (Pfizer) is a combination of two oral antiviral medications: nirmatrelvir and ritonavir. Nirmatrelvir is a protease inhibitor that prevents viral replication. Ritonavir is used to boost the levels of nirmatrelvir by slowing its hepatic metabolism. Paxlovid has received emergency authorization for use in adults and children aged 12 years or older (and who weigh at least 88 lb) who have tested positive for COVID-19 and are at high risk for severe disease.

Paxlovid must be started within 5 days of symptom onset.

How is Paxlovid prescribed?

Paxlovid is available in two packaging configurations, with different doses of nirmatrelvir, depending on patient renal function.

Most patients (those with normal renal function or mild renal impairment (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min) should be prescribed the 300 mg nirmatrelvir/100 mg ritonavir dose pack.

Patients with moderate renal impairment (eGFR ≥ 30 to < 60 mL/min) should be prescribed the 150 mg nirmatrelvir/ 100 mg ritonavir dose pack. Paxlovid is not recommended in patients with severe renal impairment (< 30 mL/min).

Paxlovid is taken twice daily for 5 days. Prescriptions should specify the numeric dose of each active ingredient within Paxlovid and also specify that completion of the full 5-day treatment course and continued isolation in accordance with public health recommendations are important to maximize viral clearance and minimize transmission of SARS-CoV-2.

More information on dosing is available here.

Which drugs interact with Paxlovid?

Paxlovid's ritonavir component, which is used to slow the metabolism of nirmatrelvir, also slows the metabolism of many other drugs. Ritonavir is a CYP3A inhibitor, so the patient's medication list should be reviewed to identify any drug metabolized by CYP3A. A list of common medications metabolized by CYP3A that may have significant drug interactions with Paxlovid can be found in the emergency use authorization fact sheet for healthcare providers. Work closely with your pharmacist to discuss these interactions and develop a plan for your patients to safely receive Paxlovid.

Clinicians should carefully review the patient's medication list for drugs that may interact with Paxlovid and consider how best to manage the patient. For example, some oral medications used after solid organ transplant and some antiarrhythmic drugs can severely interact with ritonavir and their continued use may require an alternative treatment for COVID-19. Other medications, such as statins, may simply be paused during Paxlovid treatment and for a few days thereafter.

Does Paxlovid have other contraindications or significant adverse effects?

Paxlovid was well tolerated by patients during the clinical trials. The most common drug-related adverse events were dysgeusia (4.5% in the Paxlovid group; 0.2% in the placebo group) and diarrhea (1.3% in the Paxlovid group; 0.2% in the placebo group).

Do all pharmacies carry Paxlovid?

The federal government has set up a COVID-19 therapeutics locator website. However, the site contains voluntarily reported data, so clinicians and patients may need to try multiple locations before successfully finding available inventory. For each available location, the app tells you which COVID therapeutic is available (Paxlovid or molnupiravir) and directs patients to go to a healthcare provider for a prescription, or how to make an appointment for Test to Treat.

Is Paxlovid available in the federal Test to Treat program?

Yes. As of mid-April, just over 2100 pharmacies were enrolled in the Test to Treat initiative. This program allows individuals to be tested for COVID and, if they are positive, to receive a prescription for treatment at the same appointment. Test to Treat isn't available in every region; check the website to find the closest available site. Clinicians in those areas should know that the Test to Treat option is available for their patients if needed.

Evaluating a patient and finding a Test to Treat pharmacy with a COVID-19 antiviral in stock within 5 days of symptom onset may not be feasible for every clinician, so knowing that these sites are available may be the best option. The pharmacists at these locations should also be familiar with Paxlovid's drug interactions, so they are a good resource for clinicians with questions about a patient's medication list and potential interactions.

What other drugs are available to treat COVID-19?

The antiviral agent molnupiravir (Merck) showed promising clinical results during the first half of the clinical trial. The final outcomes data for molnupiravir were not as strong as the clinical trial results from the Paxlovid trial; however, these were not head-to-head studies. As of now, Paxlovid is the preferred treatment in the National Institutes of Health's COVID-19 Treatment Guidelines. Molnupiravir may be preferred for patients who are not eligible for Paxlovid due to drug interactions or not able to receive outpatient intravenous remdesivir or bebtelovimab.

If a patient cannot take Paxlovid and cannot access outpatient intravenous treatments, molnupiravir may be an option. Clinicians should not use molnupiravir in pregnant women owing to concern for fetal harm. All patients, both men and women, should use contraception during and after treatment with molnupiravir. Women should use contraception until 4 days after the last dose. Because the effects of molnupiravir on sperm are unknown, men should continue contraception for 3 months after the last dose.

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