From the FDA Drug Label
PAXLOVID is contraindicated in patients with a history of clinically significant hypersensitivity reactions [e.g., toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome] to its active ingredients (nirmatrelvir or ritonavir) or any other components of the product PAXLOVID is contraindicated with drugs that are primarily metabolized by CYP3A and for which elevated concentrations are associated with serious and/or life-threatening reactions and drugs that are strong CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance
The contraindications for Paxlovid (nirmatrelvir/ritonavir) are:
- Hypersensitivity reactions: history of clinically significant hypersensitivity reactions to nirmatrelvir, ritonavir, or any other components of the product
- CYP3A interactions:
- Drugs primarily metabolized by CYP3A with potential for serious and/or life-threatening reactions
- Strong CYP3A inducers that may reduce nirmatrelvir or ritonavir plasma concentrations, potentially leading to loss of virologic response and possible resistance Specific examples of contraindicated drugs include:
- Alpha 1-adrenoreceptor antagonist: alfuzosin
- Antianginal: ranolazine
- Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine
- Antipsychotics: lurasidone, pimozide
- Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine
- HMG-CoA reductase inhibitors: lovastatin, simvastatin
- Immunosuppressants: voclosporin
- Sedative/hypnotics: triazolam, oral midazolam
- Strong CYP3A inducers: apalutamide, carbamazepine, phenobarbital, primidone, phenytoin, rifampin, rifapentine, St. John's Wort (hypericum perforatum) 1
From the Research
Paxlovid is contraindicated in patients with severe kidney disease (eGFR <30 mL/min), severe liver impairment (Child-Pugh Class C), and those taking certain medications that are strong CYP3A inducers or depend on CYP3A for clearance, as well as in patients with a history of hypersensitivity to nirmatrelvir or ritonavir. The contraindications for Paxlovid (nirmatrelvir/ritonavir) are primarily due to the ritonavir component, which is a potent CYP3A inhibitor that can significantly alter the blood levels of certain medications, potentially causing serious or life-threatening reactions 2, 3. Some key points to consider when prescribing Paxlovid include:
- Severe kidney disease (eGFR <30 mL/min) is a contraindication due to the increased risk of adverse reactions 4
- Severe liver impairment (Child-Pugh Class C) is also a contraindication due to the potential for increased toxicity 4
- Certain medications, such as amiodarone, rivaroxaban, simvastatin, sildenafil (for pulmonary hypertension), St. John's wort, carbamazepine, phenobarbital, rifampin, and ergot derivatives, should be avoided due to the potential for serious interactions 5, 6
- Patients with a history of hypersensitivity to nirmatrelvir or ritonavir should not take Paxlovid 2
- For patients with moderate kidney impairment (eGFR 30-60 mL/min), a dose reduction to 150 mg nirmatrelvir with 100 mg ritonavir twice daily is required rather than complete avoidance 3 It is essential to carefully evaluate the potential risks and benefits of Paxlovid in each patient and to monitor for potential adverse reactions, particularly in patients with underlying medical conditions or those taking concomitant medications 2, 3.