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. |
Source:
- FDA. Fact sheet for healthcare providers Emergency Use Authorization (EUA) for PAXLOVID. US Food Drug Adm. 2021;1–29. https://www.fda.gov/media/155050/download
- FDA. Emergency Use Authorization PAXLOVID. US FDA.2021 https://www.fda.gov/media/155049/download
- National Center for Biotechnology Information. PubChem Compound Summary for CID 155903259, Nirmatrelvir. 2022 https://pubchem.ncbi.nlm.nih.gov/compound/Nirmatrelvir
- National Center for Biotechnology Information. PubChem Compound Summary for CID 392622,Ritonavir.2022 http://pubchem.ncbi.nlm.nih.gov/compound/ritonavir
- European Medicines Agency. EMA. Conditions of Use , Conditions for Distribution and Patients Targeted. 2021;1–6. https://www.ema.europa.eu/en/documents/referral/PAXLOVID-pf-07321332-ritonavir-covid-19-article-53-procedure-conditions-use-conditions-distribution_en.pdf
- Anonim. Nirmatrelvir. Drugbank.2022 https://go.drugbank.com/drugs/DB16691
- Image: Kches16414, CC BY-SA 4.0 https://creativecommons.org/licenses/by-sa/4.0, via Wikimedia Commons
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