FDA and Well being Canada not too long ago authorised 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 finally 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 varied drug transporters similar to P-glycoprotein. CYP3A4 and P-glycoprotein are concerned within the metabolism and elimination of many generally pharmaceuticals. Thus it is rather essential to evaluate a affected person’s present treatment routine to test for clinically vital interactions.
Potential treatment interplay administration choices might embody relying on the treatment:
- Holding the interacting treatment and resuming two days after finishing the Paxlovid course
- Utilizing an alternate treatment that doesn’t work together or adjusting the dose of the interacting treatment whereas on Paxlovid
- Use an alternate COVID-19 agent.
I’ll focus on Paxlovid interactions with some generally prescribed medicines and potential administration choices. It isn’t an exhaustive checklist, and a pharmacist session with the affected person could also be useful earlier than prescribing Paxlovid for a complete evaluate of interactions.
CYP3A-4 inducing medicines
Paxlovid is contraindicated in sufferers taking any CYP3A4 inducing agent as these medicines 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. Different COVID therapy must be thought of in sufferers which have taken an enzyme inducer throughout the previous 14 days. Widespread medication embody 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 might result in excessive serum concentrations of some medicines which may result in critical adversarial occasions. For medication with a protracted half-life, stopping the treatment is not going to assist cut back the interplay threat because the treatment is slowly eradicated from the physique, and an alternate COVID-19 therapy must be used. Widespread medication embody antiarrhythmics (amiodarone, dronedarone, flecainide, propafenone, quinidine), antipsychotics (lurasidone, clozapine), and fentanyl.
Some medicines might both be held, dose-adjusted, or modified to various remedy briefly whereas on Paxlovid.
Anticoagulants (apixaban, edoxaban, rivaroxaban): Use various COVID-19 agent if doable. 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 of. There is no such thing as a dose adjustment beneficial for rivaroxaban; an alternate must be thought of. If clinically applicable, 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 diminished 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 of.
The checklist of interactions with Paxlovid is lengthy. These are a few of the generally used medicines that work together with Paxlovid and administration methods. Pharmacists could be a useful useful resource for assessing and serving to handle these interactions.
Param Patel is a pharmacist.
Picture credit score: Shutterstock.com