FDA and Well being Canada not too long ago accredited Paxlovid as an oral therapy choice for mild-to-moderate COVID-19 who’re at excessive threat of development to extreme COVID-19. It’s a mixture drug containing nirmatrelvir/ritonavir. Nirmatrelvir works by binding to SARS-CoV-2 3CL protease to in the end cease viral replication. Ritonavir doesn’t have any antiviral exercise in opposition to COVID-19 however will increase concentrations of nirmatrelvir by lowering its metabolism by CYP3A4 enzyme. Ritonavir is a potent inhibitor of CYP3A4 and numerous drug transporters similar to P-glycoprotein. CYP3A4 and P-glycoprotein are concerned within the metabolism and elimination of many generally pharmaceuticals. Thus it is extremely vital to overview a affected person’s present medicine routine to verify for clinically vital interactions.
Potential medicine interplay administration choices might embrace relying on the medicine:
- Holding the interacting medicine and resuming two days after finishing the Paxlovid course
- Utilizing an alternate medicine that doesn’t work together or adjusting the dose of the interacting medicine whereas on Paxlovid
- Use an alternate COVID-19 agent.
I’ll focus on Paxlovid interactions with some generally prescribed drugs and potential administration choices. It’s not an exhaustive record, and a pharmacist session with the affected person could also be useful earlier than prescribing Paxlovid for a complete overview of interactions.
CYP3A-4 inducing drugs
Paxlovid is contraindicated in sufferers taking any CYP3A4 inducing agent as these drugs considerably lower the focus of Paxlovid and thus lower its effectiveness. Holding the interacting medicines shouldn’t be an choice because the enzyme induction impact doesn’t instantly dissipate when a drugs is stopped. Various COVID therapy must be thought-about in sufferers which have taken an enzyme inducer inside the previous 14 days. Frequent medicine embrace anticonvulsants (carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, primidone), antimycobacterials (rifampin), and St. John’s Wort.
Medicines depending on CYP3A4 metabolism
The onset of CYP3A4 inhibition by ritonavir is fast and vital. It will possibly result in excessive serum concentrations of some drugs which might result in severe hostile occasions. For medicine with a protracted half-life, stopping the medicine is not going to assist scale back the interplay threat because the medicine is slowly eradicated from the physique, and an alternate COVID-19 therapy must be used. Frequent medicine embrace antiarrhythmics (amiodarone, dronedarone, flecainide, propafenone, quinidine), antipsychotics (lurasidone, clozapine), and fentanyl.
Some drugs might both be held, dose-adjusted, or modified to different remedy briefly whereas on Paxlovid.
Anticoagulants (apixaban, edoxaban, rivaroxaban): Use different COVID-19 agent if potential. In any other case, if used for venous thromboembolism; the anticoagulant must be held and restarted two days after finishing the Paxlovid course and the affected person must be bridged with a low molecular weight heparin. For atrial fibrillation, apixaban and edoxaban could also be dose adjusted or an alternate COVID-19 therapy must be thought-about. There isn’t any dose adjustment beneficial for rivaroxaban; an alternate must be thought-about. If clinically acceptable, sufferers on warfarin must be monitored for indicators of elevated bleeding/bruising and INR.
Alfuzosin: Alfuzosin ranges could also be elevated considerably; maintain and restart two days after Paxlovid is accomplished.
Opioids (hydrocodone, oxycodone, tramadol): Opioid dose must be decreased briefly and resume the same old dose two days after Paxlovid is accomplished.
Calcium channel blockers (amlodipine, diltiazem, felodipine, nifedipine, verapamil): Think about lowering the dose briefly and resume the same old dose two days after Paxlovid is accomplished.
Atorvastatin/rosuvastatin: Maintain and restart the same old dose two days after Paxlovid is accomplished. Dose discount could also be thought-about.
The record of interactions with Paxlovid is lengthy. These are a number of the generally used drugs that work together with Paxlovid and administration methods. Pharmacists could be a invaluable useful resource for assessing and serving to handle these interactions.
Param Patel is a pharmacist.
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