From the Guidelines
When taking Paxlovid, several medications need to be stopped or have their doses adjusted due to potential dangerous drug interactions, including certain statins, heart rhythm medications, ergot derivatives, St. John's Wort, and some psychiatric medications. These interactions occur because Paxlovid contains ritonavir, which strongly inhibits the CYP3A4 enzyme system responsible for metabolizing many medications, potentially causing dangerous increases in blood levels of these drugs 1. Some medications that should be temporarily discontinued include colchicine, sildenafil for pulmonary hypertension, and certain cancer drugs. Blood thinners like rivaroxaban, apixaban, and clopidogrel may require dose adjustments, and other medications can be safely paused during the 5-day Paxlovid course, while others may need dose adjustments under medical supervision. It is essential to consult with a healthcare provider before starting Paxlovid, as they will review the complete medication list and make appropriate recommendations for each specific medication, taking into account the potential for drug interactions and the need for dose adjustments or temporary discontinuation of certain medications 1. Some key medications to avoid or adjust when taking Paxlovid include:
- Certain statins (lovastatin, simvastatin)
- Heart rhythm medications (amiodarone, flecainide)
- Ergot derivatives
- St. John's Wort
- Psychiatric medications (pimozide, lurasidone)
- Blood thinners (rivaroxaban, apixaban, clopidogrel)
- Colchicine
- Sildenafil for pulmonary hypertension
- Certain cancer drugs Always consult with a healthcare provider before starting Paxlovid to ensure safe and effective treatment.
From the FDA Drug Label
Contraindicated due to potential for serious and/or life-threatening reactions [see Contraindications (4)] Contraindicated due to potential for cardiac arrhythmias [see Contraindications (4)] Contraindicated due to potential for acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system [see Contraindications (4)] Contraindicated due to potential for cardiac arrhythmias [see Contraindications (4)] Contraindicated due to potential for loss of virologic response and possible resistance to ritonavir or to the class of protease inhibitors [see Contraindications (4)] Contraindicated due to potential for myopathy including rhabdomyolysis [see Contraindications (4)] Concomitant use of moderate or strong CYP3A4 inhibitors with lomitapide is contraindicated due to potential for hepatotoxicity [see Contraindications (4)]
The following medications should be stopped when taking Paxlovid (which contains ritonavir):
- Lurasidone
- Pimozide
- Ergot derivatives (such as dihydroergotamine, ergotamine, methylergonovine)
- Cisapride
- St John's Wort (hypericum perforatum)
- Lovastatin
- Simvastatin
- Lomitapide 2
From the Research
Medications to be Stopped with Paxlovid
When considering the use of Paxlovid (nirmatrelvir/ritonavir) for the treatment of COVID-19, it is crucial to assess potential drug interactions. Paxlovid is known to interact with various medications due to its component ritonavir, a potent inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme.
- Statins: The use of Paxlovid with certain statins may require caution or dose adjustment due to the increased risk of myopathy. Specifically, simvastatin and lovastatin are contraindicated with Paxlovid because ritonavir can significantly increase their plasma concentrations, leading to an increased risk of myopathy and rhabdomyolysis 3, 4. Atorvastatin and rosuvastatin may be used with caution, but their doses may need to be adjusted 5, 6.
- Amiodarone: Concurrent use of amiodarone with statins, especially simvastatin, increases the risk of muscle toxicity 3, 4. Given Paxlovid's interaction with statins, caution is advised when co-administering amiodarone with Paxlovid, particularly if the patient is also on a statin.
- Other medications: Any medication that is a substrate of CYP3A4 may have its levels increased by ritonavir, potentially leading to toxicity. Examples include but are not limited to certain antiarrhythmics, antihistamines, and benzodiazepines. The decision to stop or adjust the dose of these medications should be made on a case-by-case basis, considering the potential benefits and risks of the interaction 5.
Considerations for Healthcare Providers
Healthcare providers should carefully review a patient's medication list before initiating Paxlovid therapy. They should be aware of the potential for significant drug interactions, especially with statins and other CYP3A4 substrates. Monitoring for signs of toxicity or adverse effects is crucial when co-administering Paxlovid with other medications 7, 6.