Several new contraindications have been added to the product information for Paxlovid™ (nirmatrelvir/ritonavir). This medication is now contraindicated with the medications shown in Table 1.

Table 1. New contraindications added to Paxlovid™ product information

Interacting medicine Effect Comments
Eletriptan ↑ eletriptan Eletriptan is contraindicated within 72 hours of Paxlovid™. Potential for serious adverse effects, including cardiovascular and cerebrovascular events.
Silodosin ↑ silodosin Risk of postural hypotension
Eplerenone ↑ eplerenone Risk of hyperkalaemia
Ivabradine ↑ ivabradine Risk of bradycardia or conduction disturbances
Finerenone ↑ finerenone Risk of serious adverse reactions, including hyperkalemia, hypotension, and hyponatremia
Naloxegol ↑ naloxegol Potential for opioid withdrawal symptoms
Oral midazolam ↑ midazolam Risk of extreme sedation and respiratory

Depression (caution required for parenteral midazolam)
Tolvaptan ↑ tolvaptan Risk of dehydration, hypovolemia and hyperkalaemia
Primidone ↓ nirmatrelvir/

ritonavir

 Potential for reduced virologic response and resistance
Lumacaftor/Ivacaftor ↓ nirmatrelvir/

ritonavir

 Potential for reduced virologic response and resistance

Nirmatrelvir and ritonavir are both substrates of CYP3A, and ritonavir is also a strong inhibitor of this isoenzyme. Concomitant use of medicines that inhibit CYP3A may increase plasma levels of nirmatrelvir/ritonavir, while CYP3A inducers may decrease plasma levels of nirmatrelvir/ritonavir. In addition, nirmatrelvir/ritonavir may increase plasma concentrations of medications metabolised by CYP3A.

The potential consequences of these interactions are:

  • Adverse reactions due to increased exposure to concomitant medications;
  • Adverse reactions from greater exposure to nirmatrelvir/ritonavir; and
  • Reduced therapeutic effect of nirmatrelvir/ritonavir and possible development of viral resistance.

Ritonavir also has a high affinity for P-glycoprotein and several other CYP isoforms and may increase or decrease systemic exposure to many other medicines. Further information on potential drug interactions can be found in the product information or the COVID-19 Drug Interactions website administered by the University of Liverpool, United Kingdom.

 

References:

  1. Paxlovid™ (nirmatrelvir/ritonavir) Australian approved product information. Sydney: Pfizer Australia. Approved February 2023.

Subscribe Knowledge Centre Updates

Enter your details to receive Knowledge Centre updates