Key Prescribing Info: Nirmatrelvir & Ritonavir: FDA Authorized 1st Oral Antiviral for Treatment of COVID-19

Nirmatrelvir and Ritonavir is the first oral agent authorized by FDA (Emergency Use Authorization) for treatment of mild-to-moderate coronavirus disease in adults and pediatric patients.

In a randomized, double-blind, placebo-controlled clinical trial, Nirmatrelvir and Ritonavir significantly reduced the proportion of people with COVID-19 related hospitalization or death from any cause by 88% among patients treated within 5 days of symptom onset compared to placebo.

Available Brand

Key Prescribing Notes

Nirmatrelvir and Ritonavir are authorized for treatment of mild-to-moderate coronavirus disease (COVID-19) in individuals who are at high risk for progression to severe COVID-19, including hospitalization or death.

It is indicated for adults and pediatric patients (≥12 years weighing ≥40 kilograms).

It is administered as 3 tablets (two 150 mg tablets of nirmatrelvir and one 100 mg tablet of ritonavir) taken together orally twice daily for 5 days, for a total of 30 tablets.

Treatment should be based on positive laboratory detection of SARS-CoV-2.

Treatment should be initiated as soon as possible after diagnosis and within 5 days of symptom onset.

It is not authorized for the pre-exposure or post-exposure prevention of COVID-19 or for initiation of treatment in those requiring hospitalization due to severe or critical COVID-19.

Nirmatrelvir and Ritonavir are not recommended in patients with severe kidney or severe liver impairment.

Before prescribing ritonavir-boosted nirmatrelvir, clinicians should carefully review concomitant medications and herbal supplements, to evaluate the potential for drug-drug interactions.

Nirmatrelvir and Ritonavir are available by prescription only and should be initiated as soon as possible after diagnosis of COVID-19 and within five days of symptom onset.

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Contraindications

Nirmatrelvir + Ritonavir are contraindicated in patients with a history of clinically significant hypersensitivity reactions to its active ingredients (nirmatrelvir or ritonavir) or any other components of the product.

It is contraindicated with drugs that are highly dependent on CYP3A for clearance and for
which elevated concentrations are associated with serious and/or life-threatening reactions:

Drug highly dependent on CYP3A for clearance

Alpha1-adrenoreceptor antagonist: Alfuzosin
Analgesics: Pethidine, piroxicam, propoxyphene
Antianginal: Ranolazine
Antiarrhythmic: Amiodarone, dronedarone, flecainide, propafenone, quinidine
Antigout: Colchicine
Antipsychotics: Lurasidone, pimozide, clozapine
Ergot derivatives: Dihydroergotamine, ergotamine, methylergonovine
HMG-CoA reductase inhibitors: Lovastatin, simvastatin
PDE5 inhibitor: Sildenafil (Revatio) when used for pulmonary arterial hypertension (PAH)
Sedative/hypnotics: Triazolam, oral midazolam

Drugs that are potent CYP3A inducers

Anticancer drugs: Apalutamide
Anticonvulsant: Carbamazepine, phenobarbital, phenytoin
Antimycobacterials: Rifampin

Herbal products: St. John’s Wort (hypericum perforatum)

Precautions & Side Effects

Possible side effects include:

· Dysgeusia (impaired sense of taste 6%)

· Diarrhea (3%)

· Hypertension (1%)

· Myalgia (1%)

Precautions

It is not recommended in patients with severe kidney or severe liver impairment. In patients with moderate renal impairment, a reduced dose is needed. Using Nirmatrelvir and Ritonavir at the same time as certain other drugs may result in potentially significant drug interactions. Using Paxlovid in people with uncontrolled or undiagnosed HIV-1 infection may lead to HIV-1 drug resistance.

Pregnancy & Lactation

Pregnancy:

Nirmatrelvir

Human data are unavailable on use of nirmatrelvir during pregnancy to evaluate for drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Ritonavir

Observational studies on ritonavir use in pregnant females have not identified an increase in the risk of major birth defects
Studies with ritonavir are insufficient to identify a drug-associated risk of miscarriage

Based on the mechanisms of action for both nirmatrelvir and ritonavir and the available animal data, the Panel would not withhold ritonavir-boosted nirmatrelvir (Paxlovid) from a pregnant patient if the potential benefits outweighed the potential risks.

Lactation:

Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19

Nirmatrelvir

There are no available data on presence of nirmatrelvir in human or animal milk, effects on breastfed infants, or effects on milk production
Transient decrease in body weight observed in nursing offspring of rats administered nirmatrelvir

Ritonavir