What medications should be avoided when prescribed Paxlovid (nirmatrelvir/ritonavir)?

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From the FDA Drug Label

PAXLOVID can interact with other medicines causing severe or life-threatening side effects or death. It is important to know the medicines that should not be taken with PAXLOVID Do not take PAXLOVID if: • you are taking any of the following medicines: o alfuzosin o amiodarone o apalutamide o carbamazepine o colchicine o dihydroergotamine o dronedarone o eletriptan o eplerenone o ergotamine o finerenone o flecainide o flibanserin o ivabradine o lomitapide o lovastatin o lumacaftor/ivacaftor o lurasidone o methylergonovine o midazolam (oral) o naloxegol o phenobarbital o phenytoin o pimozide o primidone o propafenone o quinidine o ranolazine o rifampin o rifapentine o St. John’s Wort (hypericum perforatum) o sildenafil (Revatio®) for pulmonary arterial hypertension o silodosin o simvastatin o tolvaptan o triazolam o ubrogepant o voclosporin

The medications to avoid when taking Paxlovid include:

  • Alpha 1-adrenoreceptor antagonist: alfuzosin
  • Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine
  • Antipsychotics: lurasidone, pimozide
  • Benign prostatic hyperplasia agents: silodosin
  • Cardiovascular agents: eplerenone, ivabradine
  • Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine
  • HMG-CoA reductase inhibitors: lovastatin, simvastatin
  • Immunosuppressants: voclosporin
  • Migraine medications: eletriptan, ubrogepant
  • Mineralocorticoid receptor antagonists: finerenone
  • Opioid antagonists: naloxegol
  • PDE5 inhibitor: sildenafil (Revatio®) for pulmonary arterial hypertension
  • Sedative/hypnotics: triazolam, oral midazolam
  • Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin
  • Vasopressin receptor antagonists: tolvaptan
  • Strong CYP3A inducers: apalutamide, carbamazepine, phenobarbital, primidone, phenytoin, rifampin, rifapentine, St. John's Wort (hypericum perforatum) 1 1 1

From the Research

When prescribed Paxlovid, you should avoid several medications that can interact dangerously with it, including certain heart medications, blood thinners, psychiatric medications, cholesterol-lowering statins, pain medications, and erectile dysfunction medications, as they can cause dangerous increases in their blood levels due to the strong inhibition of the CYP3A4 enzyme by ritonavir 2.

Medications to Avoid

  • Certain heart medications like amiodarone, flecainide, and propafenone
  • Blood thinners such as rivaroxaban and apixaban
  • Psychiatric medications including clozapine, quetiapine, and lurasidone
  • Cholesterol-lowering statins like lovastatin and simvastatin, as they can increase the risk of myopathy and rhabdomyolysis due to the inhibition of CYP3A4 3
  • Pain medications such as fentanyl
  • Erectile dysfunction medications like sildenafil when used for pulmonary hypertension
  • Other important medications to avoid include colchicine, St. John's Wort, and immunosuppressants like tacrolimus and cyclosporine

Importance of CYP3A4 Inhibition

The inhibition of CYP3A4 by ritonavir can cause unfavorable and long-lasting drug-drug interactions, and potentially fatal toxicity, depending on many factors associated with the enzyme, drugs, and the patients 4.

Recommendations

Always provide your healthcare provider with a complete list of all medications you take, including over-the-counter drugs and supplements, before starting Paxlovid to ensure safety and prevent potentially life-threatening interactions. Some medications may need dose adjustments rather than complete avoidance, and therapeutic drug monitoring may be necessary for drugs with narrow therapeutic indices 4.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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