UMEM Educational Pearls - By Alicia Pycraft

Nirmatrelvir-ritonavir (Paxlovid™) is a combination of two protease inhibitors used for the treatment of mild-moderate symptomatic COVID-19. Nirmatrelvir inhibits the SARS-CoV2 main protease, and ritonavir inhibits metabolism of nirmatrelvir, acting as a “booster” to increase nirmatrelvir concentrations. 

The EPIC-HR trial, which included non-hospitalized adults with mild-moderate COVID-19 who were unvaccinated and at risk of progressing to severe disease, showed an 89% reduction in COVID-19-related hospitalization or 28-day all-cause mortality in patients treated with nirmatrelvir-ritonavir compared to placebo. The efficacy rates in this trial were similar to remdesivir (87% relative risk reduction), and greater than molnupiravir (31% relative risk reduction), two alternative agents used for treatment of mild-moderate COVID-19. However, these three agents have never been directly compared. Nirmatrelvir-ritonavir was initially approved by the FDA under Emergency Use Authorization (EUA), but is now fully FDA-approved as of May 2023. 

Which patients benefit?

• Mild – moderate COVID-19 symptoms
  • ED or outpatients
  • Hospitalized patients who are admitted for reasons other than COVID-19
• Not requiring supplemental oxygen above baseline needs
• Presenting within 5-7 days of symptom onset
• Risk factor(s) for progression to severe disease
  • Age > 65
  • Comorbidities such as diabetes, chronic lung disease, asthma, malignancy, etc.
  • Immunocompromise

Drug-Drug Interactions:

• Ritonavir strongly inhibits the CYP3A4 enzyme, which may significantly increase serum concentrations of medications metabolized by CYP3A4. Several common medications are metabolized by this enzyme and concomitant use may pose serious risk of toxicity.
• In many cases, drug-drug interactions can be managed safely with close monitoring or dose adjustments. Some may require use of alternative COVID-19 therapies such as remdesivir or molnupiravir.

Dosing:

• eGFR 60 mL/min or above: Nirmatrelvir 300 mg (2 tabs) + ritonavir 100 mg (1 tab) twice daily for 5 days
• eGFR >30 - <60 mL/min: Nirmatrelvir 150 mg (1 tab) + ritonavir 100 mg (1 tab) twice daily for 5 days
• eGFR <30 mL/min: Use is not recommended per the manufacturer, but retrospective studies have shown that reduced dosing is well-tolerated.

Common side effects:

• Diarrhea (3%)
• Altered sense of taste (5%)

Bottom Line: Paxlovid is appropriate for patients with symptomatic mild-moderate COVID-19 with risk factors for progression to severe disease. Ask your pharmacist for assistance evaluating drug-drug interactions!

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Background: It is estimated that nearly 6% of U.S. adults and children report having a food allergy.^1,2 Epinephrine autoinjectors are used to provide life-saving pre-hospital treatment for patients experiencing anaphylaxis in the community, but can have serious consequences if administered incorrectly. Accidental finger-stick injuries with epinephrine auto-injector can result in significant pain and ischemia due to vasoconstriction and decreased blood flow to the digit. Treatments for digital epinephrine injection include supportive care, topical vasodilators, and injectable vasodilators.³

Supportive care^3,4:

• Warm compresses are preferred to increase local blood flow and enhance removal of the drug. Cold compresses may result in worsening ischemia. 
• Apply for 15 minutes every 6 hours

• Increases production of nitric oxide which relaxes smooth muscles and causes vasodilation
• Literature shows variable symptomatic improvement for adults and neonates, but safe use as an adjunct to injectable vasodilators or as monotherapy.
• Apply a 1-inch strip of nitroglycerin 2% ointment over the affected area and repeat every 8 hours until symptoms resolve
• Patients should be monitored for hypotension after application, as topical nitroglycerin is systemically absorbed.

• Alpha-1 adrenergic antagonist that competitively blocks alpha-adrenergic receptors to produce brief antagonism of circulating epinephrine and norepinephrine. Phentolamine also promotes vasodilation and increases capillary blood flow. 
• Evidence for use after accidental injection of epinephrine autoinjector is mostly described in case reports, but one study showed that phentolamine was more effective at vasodilation than either nitroglycerin or sodium nitroprusside for treatment of digital norepinephrine injection. In another study of epinephrine-injected patients, subjects reported normal fingertip sensation in an average of 120 minutes after injection of phentolamine compared to 549 minutes after injection of saline. It took an average of 85 minutes for the epinephrine-injected digits to return to normal color after phentolamine injection compared to an average of 320 minutes after injection with saline.
• Preparation/application: Dilute 5 mg of phentolamine in 10 mL of 0.9% sodium chloride. Inject small amounts subcutaneously into the affected area.

• Beta-2 adrenergic agonist that causes vasodilation and attenuates the effect of alpha adrenoreceptor-mediated vasoconstriction.
• Evidence shows that terbutaline has resulted in immediate and complete resolution of symptoms following accidental digital epinephrine injections if administered within 2 hours of the incident and it may be considered if phentolamine is not available.
• Preparation/application: Dilute 1 mg of terbutaline with 1 mL of 0.9% sodium chloride and inject subcutaneously into the affected area.
• May cause elevations in heart rate and blood pressure, as well as ECG changes. Terbutaline should be used cautiously in patients with cardiovascular disease.

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