What is the recommended treatment regimen for Covid-19 using Paxlovid (nirmatrelvir and ritonavir) and Decadron (dexamethasone)?

COVID-19 Treatment with Paxlovid and Dexamethasone

For COVID-19 treatment, Paxlovid (nirmatrelvir/ritonavir) is recommended for high-risk outpatients with mild-to-moderate disease within 5 days of symptom onset, while dexamethasone is recommended only for patients requiring oxygen supplementation or with moderate-to-severe disease. 1

Patient Selection and Timing

Paxlovid (Nirmatrelvir/Ritonavir)

• Indicated for patients with mild-to-moderate COVID-19 at high risk for disease progression 2, 1
• Must be initiated within 5 days of symptom onset 1
• Strong recommendation for use in non-severe COVID-19 patients at high risk of hospitalization 2
• High-risk factors include:
  • Advanced age (especially ≥65 years)
  • Uncontrolled chronic medical conditions
  • Immunocompromised status
  • Unvaccinated status
  • Pregnancy 1

Dexamethasone

• Should NOT be used for mild COVID-19 2
• Recommended for moderate COVID-19 (requiring O₂ support, saturation >90%) or severe COVID-19 (saturation <90-94%, respiratory rate >30/min) 2
• Standard dose: 6 mg daily for up to 10 days

Standard Dosing Regimens

Paxlovid

• Standard dose: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), taken together twice daily for 5 days 1, 3
• Take at approximately the same time each day 1
• Can be taken with or without food 1

Dexamethasone

• 6 mg once daily for up to 10 days when indicated for moderate-to-severe disease 2, 1
• Only start when patient requires oxygen or has evidence of COVID-19-related inflammation 2

Renal Dose Adjustments for Paxlovid

Renal Function	Dose
Normal	300 mg nirmatrelvir with 100 mg ritonavir, twice daily for 5 days
Moderate impairment (eGFR ≥30 to <60 mL/min)	150 mg nirmatrelvir with 100 mg ritonavir, twice daily for 5 days
Severe impairment (eGFR <30 mL/min)	Day 1: 300 mg nirmatrelvir with 100 mg ritonavir once; Days 2-5: 150 mg nirmatrelvir with 100 mg ritonavir once daily

For patients on hemodialysis, administer after dialysis 1, 3

Important Contraindications and Drug Interactions

Paxlovid Contraindications

• History of clinically significant hypersensitivity to nirmatrelvir or ritonavir 3
• Co-administration with drugs highly dependent on CYP3A for clearance 3
• Co-administration with potent CYP3A inducers 3

Critical Drug Interactions

• Ritonavir is a strong CYP3A inhibitor that can significantly increase serum levels of many medications 1, 4
• For immunosuppressive drugs:
  • Tacrolimus: Should be discontinued or reduced to microdose on day 1 4
  • Cyclosporine: Reduce to 20% of initial dosage during antiviral treatment 4
  • mTOR inhibitors: Require dosage adjustments 4
• Review ALL patient medications before prescribing Paxlovid 1, 5

Treatment Algorithm

1. Assess COVID-19 severity:

   • Mild-to-moderate (no oxygen requirement): Consider Paxlovid if high risk
   • Moderate-to-severe (oxygen requirement): Consider dexamethasone

2. For mild-to-moderate disease in high-risk patients:

   • Confirm COVID-19 diagnosis and symptom onset within 5 days
   • Screen for drug interactions and contraindications
   • Assess renal function and adjust Paxlovid dose accordingly
   • Prescribe Paxlovid for 5 days

3. For moderate-to-severe disease:

   • Start dexamethasone 6 mg daily for up to 10 days
   • Consider adding remdesivir if early in disease course 2, 6
   • For worsening despite dexamethasone with COVID-19-related inflammation, consider adding second immunosuppressant (anti-IL-6, anti-IL-1, or JAK inhibitor) 2

Clinical Pearls and Pitfalls

• Do not combine Paxlovid and dexamethasone for mild COVID-19 as dexamethasone is not indicated in this setting 2
• Paxlovid reduces hospitalization risk by 86% and mortality by 100% compared to placebo when used appropriately 1
• Paxlovid is effective in both vaccinated and unvaccinated patients 1
• The most common adverse effects of Paxlovid are dysgeusia (taste disturbance) and diarrhea 2
• Always check for drug interactions before prescribing Paxlovid, as ritonavir can significantly affect metabolism of many medications 5
• Consider remdesivir as an alternative when Paxlovid is contraindicated due to drug interactions 1, 6