Paxlovid Side Effects and Drug Interactions

Healthbeautyidea.com | Paxlovid Side Effects and Drug Interactions – Paxlovid™ is a nirmatrelvir packaged with ritonavir. Paxlovid™ is indicated for mild-moderate COVID-19 procedures, with a positive result of SARS-CoV-2 virus examination, and a risk of progressive symptoms to severe, including hospitalization and death. [1]

Nirmatrelvir is a major protease inhibitor of SARS-CoV-2. Meanwhile, ritonavir is an inhibitor of HIV-1 proteases and an inhibitor of CYP3A. Ritonavir itself has no activity against SARS-CoV-2. Ritonavir acts as an inhibitor of YP3A enzyme-mediated nirmatrelvir metabolism. Nirmatrelvir should be given with ritonavir, so that the levels of nirmatrelvir in the plasma are sufficient to achieve therapeutic effects. [1,2]

On December 22, 2021, Paxlovid™ received an emergency use authorization (EUA) from the Food and Drug Administration (FDA) for use as a mild-moderate COVID-19 therapy in older patients and children aged 12 years or older, weighing at least 40 kg. [1,2]

Paxlovid™ should be given immediately after being diagnosed with COVID-19, within the first 5 days since symptoms appear. Paxlovid™ doses are nirmatrelvir 300 mg (2 tablets 150 mg) and ritonavir 100 mg (1 tablet 100 mg), which is given every 12 hours for 5 days. [1,2]

The most common Paxlovid side effects are dysgeusia and diarrhea. Contraindications to the use of Paxlovid™ is when there is a history of allergies to the active substances Paxlovid™ (nirmatrelvir and ritonavir), or other constituent components. [1,2]

In addition, Paxlovid™ is contraindicated on the co-administration of other drugs whose clearing depends on CYP3A, for example simvastatin, amiodarone, colchicine and piroxicam. This led to limited use of Paxlovid™, as the drugs are widely used in patients with comorbidities, who are at risk of severe COVID-19. Paxlovid™ is not recommended for use in pregnant and lactating women. [1,2]

Paxlovid™ can be given as an e-prescribing for COVID-19 therapy. However, there are no results of long-term studies on Paxlovid™, so it is necessary to be careful in its use.

Chemical name:

• Nirmatrelvir: (1R,2S,5S)-N-[(1S)-1-cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl]-3-[(2S)-3,3-dimethyl-2-[(2,2,2-trifluoroacetyl)amino]butanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide
• Ritonavir: 1,3-thiazol-5-ylmethyl N-[(2S,3S,5S)-3-hydroxy-5-[[(2S)-3-methyl-2-[[methyl-[(2-propan-2-yl-1,3-thiazol-4-yl)methyl]carbamoyl]amino]butanoyl]amino]-1,6-diphenylhexan-2-yl]carbamate[3,4]

Synonym: PF-07321332/nirmatrelvir [5,6]

Paxlovid Side Effects

The most common Paxlovid side effects administration are dysgeusia and diarrhea. There is a drug interaction between Paxlovid™ and various drugs that are often used in comorbid patients, who are at risk of suffering from severe COVID-19 symptoms. Drug interactions can occur with simvastatin, colchicine, piroxicam, amiodarone, and clozapine. [1,5]

A clinical trial conducted on 2,246 high-risk older person COVID-19 patients treated by the street reported that Paxlovid™ could reduce the risk of disease progression and have a good safety profile. However, clinicians need to remain cautious because these drugs have a lot of potential interactions with other drugs.

Paxlovid™ side effects reported based on phase 2/3 clinical trials, from a therapy period of up to 34 days from the last dose, are:

• Dysgeusia (6%)
• Diarrhea (3.9%)
• Hypertension (1%)
• Vomiting (1.3%) [1.5]

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Drug Interactions

Paxlovid™ (PF-07321332/ritonavir) is a CYP3A inhibitor that can significantly increase levels of other drugs metabolized by CYP3A. Here are some examples of drug interactions that can occur in the use of Paxlovid™. [1,2,5]

Table. Paxlovid’s™ Interactions with Other Drugs

No	Other Drugs Name	Interaction Mechanism
1.	Simvastatin, atorvastatin	Concomitant administration of Paxlovid™ is contraindicated, because of the potential to cause myopathy, including rhabdomyolysis. Stop using simvastatin 12 hours before starting Paxlovid™.
2.	Amlodipine, nikardipin, nifedipine (calcium channel blockers/CCB)	Paxlovid™ can increase blood levels of CCBs. A lower CCB dose adjustment and close monitoring may be required.
3.	Pethidine, piroxicam	Paxlovid™ has the potential to increase the concentration of norpetidine and piroxicam so that it can cause severe respiratory depression or hematologic abnormalities.
4.	Colchicine	There may be an increase in the concentration of colchicine. Life-threatening side effects have been reported, so concomitant use is contraindicated.
5.	Amiodarone	Concurrent use increases amiodarone levels and increases the risk of arrhythmias.
6.	Haloperidol, risperidone	Ritonavir inhibits CYP2D6, thereby increasing the concentrations of haloperidol and risperidone. Need close monitoring of therapy and side effects when given concurrently.
7.	Clozapine	Ritonavir can increase the plasma accretion of clozapine, so joint administration is contraindicated.
8.	Ketoconazole	Ritonavir can inhibit CYP3A-mediated metabolism of ketoconazole, potentially increasing the incidence of gastrointestinal and hepatic side effects..
9.	Clarithromy	Concomitant use with ritonavir may increase clarithromycin levels. In patients with impaired renal function, a reduction in the dose of clarithromycin should be considered.
10.	Rifampicin	Rifampicin is a strong inducer of CYP3A4 so it can reduce exposure to Paxlovid™ and decrease its effectiveness. The use of Paxlovid™ concurrently with rifampin is contraindicated.