COVID Antivirals Paxlovid and Molnupiravir
Cardiac drug interactions and suggestions for management, in the context of each patient.
The benefit from Paxlovid in reducing severity of a COVID infection is significant. It is also significantly more effective than Molnupiravir (which is also available and doesn’t appear to have significant drug interactions).
Paxlovid is an inhibitor of CYP3A and is renally cleared. It is contraindicated with severe hepatic failure
Recommended doses
eGFR ≥ 60 nirmatrelvir 300mg (2x150mg tablets)/rivatonavir 100mg
eGFR 30 – 59 nirmatrelvir 150mg (1 tablet)/ rivatonavir 100mg
eGFR < 30 Discuss with ID (they are tending to give it off label rather than use Molnupiravir
Drug interactions
For a full list of interactions please use the Liverpool Checker (University of Liverpool)
Anticoagulants
Warfarin – continue but keep a close eye on INR
NOACs – discontinue where possible for 5/7 of treatment as significant increased risk of bleeding If high thrombotic risk Haematology are recommending bridging enoxaparin.
Antiarrhythmics
Arrhythmias often occur with acute COVID infections
1c (flecainide, propafenone) discontinue for 5/7 or reduce dose (high risk of toxicity)
Amiodarone – interacts but has very long half life, wide therapeutic window and is often given for severe arrhythmias. Continue
Diltiazem/ verapamil – although their blood level will increase it is unlikely to be a problem unless very low BP
Betablockers – no interaction (includes sotalol)
Digoxin – withhold
Statins
Increased risk of rhabdomyolysis. Whilst probably only a risk with 80mg of simvastatin or atorvastatin it is easiest to withhold them.
Heart Failure Medicines
ACE/ARB – no interaction
Beta blockers – no interaction
Thiazide diuretics – no interaction
Spironolactone – no interaction
Eplerenone – risk of hyperkalaemia (withhold)
SGLT2 inhibitors – dapagliflozin/empagliflozin – no interaction
Frusemide – no interaction
Antiplatelet medication
Aspirin – no interaction
Clopidogrel – likely to be less effective
Ticagrelor – withhold (significant increase in blood level). If PCI was in the previous 3 months please liaise with Cardiology.
Phosphodiesterase inhibitors
Sildenafil, Tadalafil – withhold
For any other interactions please consult the Liverpool Guidelines.
Molnupiravir (Lagevrio) has been shown to have only modest efficacy. In the major trial of 1433 randomised individuals, 48 (6.8%) Molnupiravir and 68 (9.7%) placebo patients were hospitalised or died (1 vs 9 patients), a 30% reduction, or 3% absolute risk reduction (Ref 1). It should be started as soon as possible after a diagnosis of COVID-19 has been made, and within 5 days of symptom onset. The dose is four of 200mg capsules twice daily for 5 days, orally.
Nirmatrelvir with ritonavir (Paxlovid) is likely to be more effective than Molnupiravir, although no direct comparison trials have been undertaken. Nirmatrelvir is rapidly metabolised by cytochrome P450 3A4 (CYP3A4) and is therefore administered together with a low dose of the potent inhibitor of that enzyme, ritonavir. In the major trial of 2246 randomised individuals, at the planned (early) interim analysis, 3 of 389 (0.8%) Nirmatrelvir/ritonavir and 27 of 385 (7%) placebo patients were hospitalised or died (0 vs 7 patients), an 89% reduction, or 6% absolute risk reduction (Ref 2). Again, treatment is recommended to be initiated as soon as possible after a diagnosis of COVID-19 has been made, and within 5 days of symptoms
References:
- MOVe-OUT Study Group. NEJM 10Feb22; 386 (6): 509-520.
- EPIC-HR Investigators. NEJM 14April22; 386 (15): 1397-1408.