Ritonavir-boosted nirmatrelvir

Administration

• Type:
• Dosage Forms: Oral
• Routes of Administration:
• Common Trade Names: Paxlovid

Indications for and selection of COVID-19-specific therapy for adult outpatients

Particularly recommended for adults who:

• Are 65 years or older, or
• Are immunocompromised, or
• Have multiple medical comorbidities.
• Initiate within 5 days of symptom onset.

Adult Dosing

• eGFR ≥ 60 mL/min: 300 mg nirmatrelvir plus 100 mg ritonavir orally, twice daily, for 5 days.
• eGFR ≥ 60 mL/min: 150 mg nirmatrelvir plus 100 mg ritonavir orally, twice daily, for 5 days.
• eGFR < 30 mL/min: Not recommended.

Pediatric Dosing

Children ≥ 12 years old, weighing ≥40 kg:

• eGFR ≥ 60 mL/min: 300 mg nirmatrelvir plus 100 mg ritonavir orally, twice daily, for 5 days.
• eGFR ≥ 60 mL/min: 150 mg nirmatrelvir plus 100 mg ritonavir orally, twice daily, for 5 days.
• eGFR < 30 mL/min: Not recommended.

Drug Interactions

Nirmatrelvir-ritonavir:

• An inhibitor of metabolic enzymes and transporters such as the CYP3A enzyme (predominantly because of the ritonavir component), and
• A substrate of CYP3A [1].

Prior to prescribing, review the patient's medications' list and assess specific drug interactions and potential ways to mitigate them. For example:

• Drug interactions program included with UpToDate
• Drug interaction checker from the University of Liverpool

Adverse Reactions

• 1% to 10%: Gastrointestinal: Diarrhea (3%), dysgeusia (5%)

Postmarketing:

• Cardiovascular: Bradycardia, hypertension, syncope
• Dermatologic: Pruritus, severe dermatological reaction (including Stevens-Johnson syndrome and toxic epidermal necrolysis), skin rash
• Gastrointestinal: Abdominal pain, nausea, pancreatitis, vomiting
• Hypersensitivity: Anaphylaxis, hypersensitivity reaction
• Nervous system: Headache, malaise
• Respiratory: Dyspnea

Pediatric Dosing

COVID

• 300 mg nirmatrelvir with 100 mg ritonavir, twice daily for 5 days
  • 12 years of age and older weighing at least 40 kilograms
  • Treatment of high risk patients with mild-to-moderate disease
  • Initiate within 5 days of symptom onset

Special Populations

Renal Dosing

• Adult:
  • Renally dosed: if eGFR 30-60, then 150 mg/100 mg dosing
• Pediatric:

Hepatic Dosing

• Adult:
• Pediatric:

Contraindications

• Allergy to class/drug
  • Many drug interactions
  • E.g. Plavix, Phenytoin, Tacrolimus, Tramadol, Statins, Hydro/oxycodone/Codeine, Diazepam/Clonazepam/Alprazolam, Fentanyl, Tamsulosin

Pharmacology

• Half-life:
• Metabolism:
• Excretion:

Comments

• 89% reduction in hospitalization or death in high risk population, and 70% reduction in hospitalizations with no deaths in standard risk population.

References

1. Prescribing Nirmatrelvir-Ritonavir: How to Recognize and Manage Drug-Drug Interactions (https://pubmed.ncbi.nlm.nih.gov/35226530/)