A Comparability Of Paxlovid As opposed to Molnupiravir: The First Oral COVID Antivirals

On this article an infectious sicknesses pharmacist compares Paxlovid as opposed to molnupiravir – the primary oral COVID-19 antivirals with FDA Emergency Use Authorization.



Authored By way of: Timothy P. Gauthier, Pharm.D., BCPS, BCIDP


Article Posted 24 December 2021

The FDA has launched emergency use authorizations for Pfizer’s COVID-19 tablet Paxlovid (generic title nirmatrelvir/ ritonavir) in addition to Merck’s COVID-19 tablet molnupiravir (UK emblem title Lagevrio). There are a large number of questions on those two new oral COVID-19 treatments.  This text supplies an summary evaluating the 2.

Notice that issues are evolving abruptly and the content material introduced right here could also be rendered faulty or flawed as issues alternate. To arrange this submit I’ve applied the next assets, which can be matter to long term updates:

  • Paxlovid
  • Molnupiravir

Of observe, nirmatrelvir is the lively element in Paxlovid. Ritonavir has some antiviral homes (no longer in opposition to the SARS-CoV-2 virus regardless that) and works as a booster to extend nirmatrelvir concentrations. Ritonavir (RTV, Norvir) has lengthy been used as a booster in HIV treatment regimens.


LEARN ANTIBIOTICS


Here’s a desk offering a comparability of Paxlovid to molnupiravir…

Generic Title

Nirmatrelvir/ritonavir

Molnupiravir

Branded Names

Paxlovid

Lagevrio

Producer

Pfizer

Merck

FDA EUA Date

12/22/2021

12/23/2021

Drug Elegance

SARS-CoV-2 primary protease inhibitor (nirmatrelvir)

HIV-1 protease inhibitor & CYP3A inhibitor (ritonavir)

Nucleoside analogue

Drug Kind

Antiviral

Antiviral

Mechanism of Motion as opposed to SARS-CoV-2

Inhibits mPRO, fighting viral replication

Viral deadly mutagenesis

Move-Resistance with Anti-SARS-CoV-2 Monoclonal Antibodies

No longer anticipated

No longer Anticipated

Move-Resistance with Remdesivir

No longer Anticipated

No longer Anticipated

Delta Variant Task

Sure

Sure

Omicron Variant Task

Anticipated

Anticipated

Indication

In danger sufferers with mild-moderate COVID-19

In danger sufferers with mild-moderate COVID-19

Age Restrict

Will have to be 12 years or older

Will have to be 18 years or older

Weight Restrict

Will have to be 40 kg or extra

None mentioned

Want Certain Direct SARS-CoV-2 Take a look at?

Sure

Sure

Can Begin if Hospitalized for COVID-19?

No

No

Can Proceed if Hospitalized All over Remedy?

Sure

Sure

Licensed for Pre or Submit Publicity Prophylaxis?

No

No

Will have to Supply Affected person/ Caregiver Reality Sheet?

Sure

Sure

MedWatch Med Mistakes/ Critical Adversarial Match Reporting Required?

Sure

Sure

When to Get started

Inside of 5 days symptom onset

Inside of 5 days symptom onset

Direction

Oral

Oral

Dose

300 mg nirmatrelvir with

100 mg ritonavir each and every 12 hours

800 mg each and every 12 hours

Capsules in step with Dose

3

4

Period of Remedy

5 days

5 days

Tablet Imprint

“PFE” and “3CL” for nirmatrelvir

“a” and “NK” for ritonavir

“82”

How Provided

5 day-to-day dose blister playing cards

40 depend bottles

Garage

Room Temperature

Room Temperature

NDC

NDC-0069-1085-30

NDC-0069-1085-06

NDC-0006-5055-06

NDC-0006-5055-07

Take with Meals?

Without or with, however excessive fats meal will increase absorption ~15%

Without or with

Alright to Weigh down?

No

No

Renal Dose Adjustment

For eGFR 30 to under 60

Keep away from if eGFR under 30

None

Hepatic Dose Adjustment

Keep away from in serious hepatic impairment (Kid-Pugh Elegance C)

None

Contraindications

Hypersensitive reaction to elements

Use with sure medicine that experience CYP3A4 interactions

None indexed

Warnings

Beware drug interactions

Hepatotoxicity

HIV-1 drug resistance in sufferers with HIV-1 an infection

Embryo-fetal toxicity

Bone and cartilage toxicity

Maximum Not unusual Adversarial Reactions

Dysguesia, diarrhea, high blood pressure, myalgia

Diarrhea, nausea, dizziness

Particular Populations

No human knowledge on use in being pregnant or breastfeeding

No longer really useful in being pregnant

No longer really useful if breastfeeding

(Has being pregnant surveillance program)

Drug Interactions

Many, see under

None recognized so far

HCP Reality Sheet Duration

29 pages

18 pages

Lessons To be had in First US Allocation

64,970 classes

300,620 classes

Prescription Wanted?

Sure

Sure

Price to US Gov’t

$530 in step with path

$712 in step with path

Price to Affected person

$0

$0

Transient Abstract of Scientific Find out about Information – Molnupiravir

MOVe-OUT Trial randomized 1,433 high-risk non-hospitalized grownup topics with mild-moderate COVID-19. 709 sufferers gained molnupiravir and 699 sufferers gained placebo. All-cause hospitalization 24 hours or extra for acute care or loss of life at day 29 used to be 6.8% for molnupiravir (n=48) and 9.7% for placebo (n=68). Mortality at day 29 used to be 0.1% for molnupiravir (n=1) and 1.3% for placebo (n=9).

Transient Abstract of Scientific Find out about – Paxlovid

EPIC-HR Trial randomized 2,246 high-risk non-hospitalized symptomatic adults with COVID-19. 1,039 sufferers gained Paxlovid and 1,046 gained placebo. Within the changed intent to regard research, COVID-19 similar hospitalization or loss of life from any trigger thru day 28 used to be 0.8% within the Paxlovid arm (n=8) and six.3% within the placebo arm (n=66). All trigger mortality thru day 28 used to be 0% within the Paxlovid arm and 1.1% within the placebo arm (n=12).

Paxlovid as opposed to molnupiravir – Determine 1 equipped in HCP Reality Sheet

Paxlovid HCP Reality Sheet Main points

Molnupiravir HCP Reality Sheet Main points

Paxlovid drug-drug interactions indexed as contraindications

CYP3A inducers will accelerate the metabolism (i.e. lower concentrations) of gear that use the CYP3A4 pathway. CYP3A inhibitors will gradual the metabolism (i.e., building up concentrations) of gear that use the CYP3A4 pathway. CYP3A4 substrates use the CYP3A4 pathway.

  • Contraindicated medicine extremely depending on CYP3A for clearance:
    • Alpha1-adrenoreceptor antagonist: alfuzosin
    • Analgesics: pethidine, piroxicam, propoxyphene
    • Antianginal: ranolazine
    • Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine
    • Anti-gout: colchicine
    • Antipsychotics: lurasidone, pimozide, clozapine
    • Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine
    • 5-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors: lovastatin, simvastatin
    • PDE5 inhibitor: sildenafil (Revatio®) when used for pulmonary arterial high blood pressure (PAH)
    • Sedative/hypnotics: triazolam, oral midazolam
  • Contraindicated medicine or herbals which might be potent CYP3A4 inducers:
    • Anticancer medicine: apalutamide
    • Anticonvulsant: carbamazepine, phenobarbital, phenytoin
    • Antimycobacterials: rifampin
    • Natural merchandise: St. John’s Wort (hypericum perforatum)

Of observe, ritonavir in Paxlovid would possibly scale back the efficacy of blended hormonal contraceptives. This isn’t a contraindication to Paxlovid use, however will have to be integrated in affected person counseling when related. There are lots of drug interactions no longer indexed right here, confer with HCP Reality Sheet for extra, the assets will also be useful:

Final feedback

I am hoping that you’ve discovered this useful. Please get entry to the assets cited initially of this text for the freshest data on those new oral COVID drugs.


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