Ritonavir-boosted nirmatrelvir - Revision history

Danbot: Strip excess bold

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	==== Particularly recommended for those who: ====		==== Particularly recommended for those who: ====
	* Are 65 years or older, ~~'''~~or~~'''~~		* Are 65 years or older, or
	* Are immunocompromised, ~~'''~~or~~'''~~		* Are immunocompromised, or
	* Have multiple medical comorbidities.		* Have multiple medical comorbidities.

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	==Pharmacology==		==Pharmacology==
	* ~~'''~~Metabolism~~'''~~: Νirmatrelvir (when given with ritonavir): Minimal; Ritonavir: Hepatic via CYP3A4 (major) and CYP2D6 (minor).		* Metabolism: Νirmatrelvir (when given with ritonavir): Minimal; Ritonavir: Hepatic via CYP3A4 (major) and CYP2D6 (minor).
	* ~~'''~~Time to peak~~'''~~: Νirmаtrelvir (when given with ritonavir): 3 hours; Ritonavir: 3.98 hours.		* Time to peak: Νirmаtrelvir (when given with ritonavir): 3 hours; Ritonavir: 3.98 hours.
	* ~~'''~~Half-life~~'''~~: Νirmаtrelvir (when given with ritonavir): 6.05 hours; Ritonavir: 6.15 hours.		* Half-life: Νirmаtrelvir (when given with ritonavir): 6.05 hours; Ritonavir: 6.15 hours.
	* ~~'''~~Excretion~~'''~~: Nirmаtrelvir (when given with ritonavir): Feces (27.5%); urine (55%); Ritonavir: Feces (86.4%); urine (3.5%).		* Excretion: Nirmаtrelvir (when given with ritonavir): Feces (27.5%); urine (55%); Ritonavir: Feces (86.4%); urine (3.5%).

	==Mechanism of Action==		==Mechanism of Action==

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Adverse Reactions

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	* Nervous system: Headache, malaise		* Nervous system: Headache, malaise
	* Respiratory: Dyspnea		* Respiratory: Dyspnea

			===Rebound===
			* Viral rebound with or without mild recurrent symptoms occurs in a minority of patients following initial improvement with nirmatrelvir-ritonavir.
			* Viral rebound warrants extension of the isolation period.
			* Advise patients of this possibility, but, for patients at risk for progression to severe disease, the potential benefits of treatment greatly outweigh any potential inconvenience from rebound.

	==Special Populations==		==Special Populations==

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Renal Dosing

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	===Renal Dosing===		===Renal Dosing===
	*Adult:		Addressed above in "Dosing" section.
	**Renally dosed: if eGFR 30-60, then 150 mg/100 mg dosing
	*Pediatric:

	===Hepatic Dosing===		===Hepatic Dosing===

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Hepatic Dosing

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	===Hepatic Dosing===		===Hepatic Dosing===
	*Adult:		*Adult:
	*Pediatric:		** Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
			** Severe impairment (Child-Pugh class C): Use is not recommended (has not been studied).

			*Pediatric (≥12 years old, weighing ≥40 kg):
			** Mild or moderate impairment: No dosage adjustment necessary.
			** Severe impairment: Not recommended for use (has not been studied).

	==Contraindications==		==Contraindications==

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Lactation risk

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	===Lactation risk===		===Lactation risk===
	*		* Information related to COVID-19 and breastfeeding is available from the [https://www.who.int/news/item/28-04-2020-new-faqs-address-healthcare-workers-questions-on-breastfeeding-and-covid-19 World Health Organization]

	===Renal Dosing===		===Renal Dosing===

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Adverse Reactions

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	** Many [https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-paxlovid-drug-drug-interactions/ drug interactions]		** Many [https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-paxlovid-drug-drug-interactions/ drug interactions]
	**E.g. Plavix, Phenytoin, Tacrolimus, Tramadol, Statins, Hydro/oxycodone/Codeine, Diazepam/Clonazepam/Alprazolam, Fentanyl, Tamsulosin		**E.g. Plavix, Phenytoin, Tacrolimus, Tramadol, Statins, Hydro/oxycodone/Codeine, Diazepam/Clonazepam/Alprazolam, Fentanyl, Tamsulosin

	~~==Adverse Reactions==~~
	~~===Serious===~~


	~~===Common===~~


	==Pharmacology==		==Pharmacology==

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Pharmacology

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	==Pharmacology==		==Pharmacology==
	*Half-life:		* '''Metabolism''': Νirmatrelvir (when given with ritonavir): Minimal; Ritonavir: Hepatic via CYP3A4 (major) and CYP2D6 (minor).
	*Metabolism:		* '''Time to peak''': Νirmаtrelvir (when given with ritonavir): 3 hours; Ritonavir: 3.98 hours.
	*Excretion:		* '''Half-life''': Νirmаtrelvir (when given with ritonavir): 6.05 hours; Ritonavir: 6.15 hours.
			* '''Excretion''': Nirmаtrelvir (when given with ritonavir): Feces (27.5%); urine (55%); Ritonavir: Feces (86.4%); urine (3.5%).

	==Mechanism of Action==		==Mechanism of Action==

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Pregnancy Rating

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	==Special Populations==		==Special Populations==
	===[[Drug pregnancy categories\|Pregnancy Rating]]===		===[[Drug pregnancy categories\|Pregnancy Rating]]===
	*		* US FDA pregnancy category: Not assigned.
			* Nirmatrelvir-ritonavir should not be used during pregnancy unless the benefit outweighs the risk to the fetus.

	===Lactation risk===		===Lactation risk===

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References

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	# Prescribing Nirmatrelvir-Ritonavir: How to Recognize and Manage Drug-Drug Interactions (https://pubmed.ncbi.nlm.nih.gov/35226530/)		# Prescribing Nirmatrelvir-Ritonavir: How to Recognize and Manage Drug-Drug Interactions (https://pubmed.ncbi.nlm.nih.gov/35226530/)
	# UpToDate: Nirmatrelvir and ritonavir: Drug information (https://www.uptodate.com/contents/nirmatrelvir-and-ritonavir-drug-information)		# UpToDate: Nirmatrelvir and ritonavir: Drug information (https://www.uptodate.com/contents/nirmatrelvir-and-ritonavir-drug-information)
			# UpToDate: COVID-19: Management of adults with acute illness in the outpatient setting (https://www.uptodate.com/contents/covid-19-management-of-adults-with-acute-illness-in-the-outpatient-setting)

	[[Category:Pharmacology]]		[[Category:Pharmacology]]

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Mechanism of Action

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	==Mechanism of Action==		==Mechanism of Action==

			* Nirmаtrelvir blocks the activity of the ЅΑRS-CoV-2-3CL protease, an enzyme required for viral replication.
			* Co-administration of nirmаtrelvir with ritonavir slows the metabolism of ոirmatrelvir so it remains active in the body for longer and at higher concentrations.

	==Comments==		==Comments==