Lopinavir - Revision history

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Ihearttroponin: /* Pediatric Dosing */

2020-03-22T19:25:43Z

Pediatric Dosing

← Older revision		Revision as of 19:25, 22 March 2020
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	*13 months and older, 15-40 kg: 10 mg/2.5 mg/kg PO BID (solution)		*13 months and older, 15-40 kg: 10 mg/2.5 mg/kg PO BID (solution)
	*13 months and older, >40 kg: 400 mg/100 mg PO BID (solution)		*13 months and older, >40 kg: 400 mg/100 mg PO BID (solution)




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

Ihearttroponin: /* Background */

2020-03-22T19:25:05Z

Background

← Older revision		Revision as of 19:25, 22 March 2020
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	==Background==		==Background==
	~~Ritonavir~~ is usually given in combination with ~~lopinavir~~ for both treatment of HIV and HIV post-exposure prophylaxis. It is currently being studied in the use of COVID-19 as well.		Lopinavir is usually given in combination with ritonavir for both treatment of HIV and HIV post-exposure prophylaxis. It is currently being studied in the use of COVID-19 as well.

	==Administration==		==Administration==

Ihearttroponin at 19:24, 22 March 2020

2020-03-22T19:24:25Z

← Older revision		Revision as of 19:24, 22 March 2020
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			==Background==
			Ritonavir is usually given in combination with lopinavir for both treatment of HIV and HIV post-exposure prophylaxis. It is currently being studied in the use of COVID-19 as well.

	==Administration==		==Administration==
	*Type:		*Type: [[antiviral]]
	*Dosage Forms:		*Dosage Forms: 100 mg/25 mg, 200 mg/50 mg (tabs); 400 mg/100 mg per 5 mL solution
	*Routes of Administration:		*Routes of Administration: PO
	*Common Trade Names:		*Common Trade Names: Kaletra (lopinavir/ritonavir)

	==Adult Dosing==		==Adult Dosing==
			*[[HIV]] treatment
			**400 mg/100 mg PO BID
			**Dose will need to be increased when used in combination with other [[HIV]] medications
			*[[HIV post-exposure prophylaxis]]
			**400 mg/100 mg PO BID

			==Pediatric Dosing==
			*[[HIV]] treatment
			**14 days-12 months old: 16mg/5mg/kg PO BID (solution)
			**13 months and older, <15 kg:
			***Treatment-naive: 12 mg/3 mg/kg PO BID (solution)
			***Treatment-experienced: 13 mg/3.25 mg/kg PO BID (solution)
			**13 months and older, 15-45 kg: 11 mg/2.75 mg/kg PO BID (solution)
			**13 months and older, >45 kg: 400 mg/100 mg PO BID (solution)
			*[[HIV post-exposure prophylaxis]]
			*14 days-12 months old: 16 mg/4 mg/kg PO BID (solution)
			*13 months and older, <15 kg: 12 mg/2 mg/kg PO BID (solution)
			*13 months and older, 15-40 kg: 10 mg/2.5 mg/kg PO BID (solution)
			*13 months and older, >40 kg: 400 mg/100 mg PO BID (solution)


	~~==Pediatric Dosing==~~


	==Special Populations==		==Special Populations==
	===[[Drug pregnancy categories\|Pregnancy Rating]]===		===[[Drug pregnancy categories\|Pregnancy Rating]]===
	*		Safe to use in pregnancy (avoid oral solution due to alcohol content)

	===Lactation risk===		===Lactation risk===
	*		*Avoid breastfeeding

	===Renal Dosing===		===Renal Dosing===
	*Adult:		*Adult: No adjustment
	*Pediatric:		*Pediatric: No adjustment

	===Hepatic Dosing===		===Hepatic Dosing===
	*Adult:		*Adult: Not defined, caution advised in hepatic impairment
	*Pediatric:		*Pediatric: Not defined, caution advised in hepatic impairment

	==Contraindications==		==Contraindications==
	*Allergy to class/drug		*Allergy to class/drug
			*Neonates <14 days old
			*[[Long QT syndrome]]
			*Hypokalemia

	==Adverse Reactions==		==Adverse Reactions==
	===Serious===		===Serious===
			*QT prolongation/[[Torsade de pointes]]
			*PR prolongation/AV block
			*Hyperglycemia/[[diabetes mellitus]]
			*Hypercholesterolemia/hypertriglyceridemia
			*Pancreatitis
			*Renal failure
			*Hepatotoxicity
			*Angioedema
			*[[Toxic epidermal necrolysis]]
			*[[Stevens-Johnson syndrome]]
			*[[Immune reconstitution syndrome]]
			*Autoimmune disorders
			*[[Hypertension]]
			*[[Syncope]]
			*[[Orthostatic hypotension]]
			*Myopathy
			*[[Thrombocytopenia]]

	===Common===		===Common===
			*Nausea/vomiting
			*Diarrhea
			*Paresthesia
			*Fatigue
			*Rash
			*Abdominal pain
			*Cough
			*[[Dysgeusia]]
			*Oropharyngeal pain
			*Dizziness
			*AST, ALT, CK elevation
			*Edema
			*Acne
			*Lipodystrophy

	==Pharmacology==		==Pharmacology==
	*Half-life:		*Half-life: 5-6 hr
	*Metabolism:		*Metabolism: Liver (CYP450)
	*Excretion:		*Excretion: Fecal

	==Mechanism of Action==		==Mechanism of Action==
			Binds to active site of HIV protease, preventing maturation of the virus

	==Comments==		==Comments==

Ihearttroponin: Created page with "==Administration== Type: Dosage Forms: Routes of Administration: Common Trade Names: ==Adult Dosing== ==Pediatric Dosing== ==Special Populations== ===Drug pregnan..."

2020-03-22T17:52:26Z

Created page with "==Administration== *Type: *Dosage Forms: *Routes of Administration: *Common Trade Names: ==Adult Dosing== ==Pediatric Dosing== ==Special Populations== ===Drug pregnan..."

New page

==Administration==
*Type:
*Dosage Forms:
*Routes of Administration:
*Common Trade Names:

==Adult Dosing==

==Pediatric Dosing==

==Special Populations==
===[[Drug pregnancy categories|Pregnancy Rating]]===
*

===Lactation risk===
*

===Renal Dosing===
*Adult:
*Pediatric:

===Hepatic Dosing===
*Adult:
*Pediatric:

==Contraindications==
*Allergy to class/drug

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

===Common===

==Pharmacology==
*Half-life:
*Metabolism:
*Excretion:

==Mechanism of Action==

==Comments==
A trial of lopinavir/ritonavir is currently being done to study use in COVID-19. So far, studies have not shown significant benefit in time to clinical improvement. Mortality at 28 days is lower but not statistically significant.<ref>Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19 [published online ahead of print, 2020 Mar 18]. N Engl J Med. 2020;10.1056/NEJMoa2001282. doi:10.1056/NEJMoa2001282</ref>

==See Also==
*[[HIV]]
*[[Ritonavir]]
*[[Coronavirus]]
*[[COVID-19]]

==References==
<references/>

[[Category:Pharmacology]]

← Older revision		Revision as of 09:12, 22 March 2026
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	==Background==		==Background==

	Lopinavir is a [[Special:MyLanguage/HIV\|HIV]] protease inhibitor always given in combination with low-dose [[Special:MyLanguage/ritonavir\|ritonavir]] (which boosts lopinavir plasma levels by inhibiting CYP3A4 metabolism). Although previously a preferred first-line protease inhibitor, lopinavir/ritonavir is ~~'''~~no longer recommended for treatment-naive adults~~'''~~ due to higher pill burden, GI intolerance, and metabolic side effects compared to newer alternatives (e.g., boosted darunavir, dolutegravir-based regimens).<ref name="NIH">HIVinfo. Kaletra Patient Drug Record. National Institutes of Health. https://clinicalinfo.hiv.gov/en/drugs/lopinavir-ritonavir/patient</ref> It remains in use in some resource-limited settings as a second-line option and in select pediatric populations.<ref name="aidsmap">Lopinavir/ritonavir. aidsmap. https://www.aidsmap.com/about-hiv/arv-background-information/lopinavirritonavir</ref>		Lopinavir is a [[Special:MyLanguage/HIV\|HIV]] protease inhibitor always given in combination with low-dose [[Special:MyLanguage/ritonavir\|ritonavir]] (which boosts lopinavir plasma levels by inhibiting CYP3A4 metabolism). Although previously a preferred first-line protease inhibitor, lopinavir/ritonavir is no longer recommended for treatment-naive adults due to higher pill burden, GI intolerance, and metabolic side effects compared to newer alternatives (e.g., boosted darunavir, dolutegravir-based regimens).<ref name="NIH">HIVinfo. Kaletra Patient Drug Record. National Institutes of Health. https://clinicalinfo.hiv.gov/en/drugs/lopinavir-ritonavir/patient</ref> It remains in use in some resource-limited settings as a second-line option and in select pediatric populations.<ref name="aidsmap">Lopinavir/ritonavir. aidsmap. https://www.aidsmap.com/about-hiv/arv-background-information/lopinavirritonavir</ref>

	Lopinavir/ritonavir was studied for COVID-19 treatment early in the pandemic. Multiple large randomized trials (RECOVERY, WHO SOLIDARITY) have ~~'''~~definitively shown no clinical benefit~~'''~~ for hospitalized COVID-19 patients (see Comments section).<ref name="RECOVERY">RECOVERY Collaborative Group. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2020;396(10259):1345-1352.</ref><ref name="SOLIDARITY">WHO Solidarity Trial Consortium. Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results. N Engl J Med. 2021;384(6):497-511.</ref>		Lopinavir/ritonavir was studied for COVID-19 treatment early in the pandemic. Multiple large randomized trials (RECOVERY, WHO SOLIDARITY) have definitively shown no clinical benefit for hospitalized COVID-19 patients (see Comments section).<ref name="RECOVERY">RECOVERY Collaborative Group. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2020;396(10259):1345-1352.</ref><ref name="SOLIDARITY">WHO Solidarity Trial Consortium. Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results. N Engl J Med. 2021;384(6):497-511.</ref>

	==Administration==		==Administration==
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	*Type: [[Special:MyLanguage/antiviral\|Antiviral]] (HIV protease inhibitor, boosted)		*Type: [[Special:MyLanguage/antiviral\|Antiviral]] (HIV protease inhibitor, boosted)
	*Dosage Forms: 100 mg/25 mg, 200 mg/50 mg (tabs); oral solution 80 mg/20 mg per mL (400 mg/100 mg per 5 mL)		*Dosage Forms: 100 mg/25 mg, 200 mg/50 mg (tabs); oral solution 80 mg/20 mg per mL (400 mg/100 mg per 5 mL)
	**~~'''~~Oral solution contains 42.4% alcohol (v/v) and 15.3% propylene glycol (w/v)~~'''~~ — relevant for neonates, pregnancy, and patients on metronidazole or disulfiram<ref name="FDAlabel">KALETRA (lopinavir and ritonavir) [package insert]. AbbVie Inc. FDA label. 2016.</ref>		**Oral solution contains 42.4% alcohol (v/v) and 15.3% propylene glycol (w/v) — relevant for neonates, pregnancy, and patients on metronidazole or disulfiram<ref name="FDAlabel">KALETRA (lopinavir and ritonavir) [package insert]. AbbVie Inc. FDA label. 2016.</ref>
	*Routes of Administration: PO		*Routes of Administration: PO
	*Common Trade Names: Kaletra (lopinavir/ritonavir)		*Common Trade Names: Kaletra (lopinavir/ritonavir)
	*Tablets can be taken with or without food; ~~'''~~oral solution should be taken with food~~'''~~<ref name="FDAlabel"/>		*Tablets can be taken with or without food; oral solution should be taken with food<ref name="FDAlabel"/>

	==Adult Dosing==		==Adult Dosing==
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	*Allergy to lopinavir or ritonavir		*Allergy to lopinavir or ritonavir
	*~~'''~~Neonates <14 days postnatal age~~'''~~ (or <42 weeks postmenstrual age) due to toxicity risk from alcohol and propylene glycol in the oral solution<ref name="FDAlabel"/>		*Neonates <14 days postnatal age (or <42 weeks postmenstrual age) due to toxicity risk from alcohol and propylene glycol in the oral solution<ref name="FDAlabel"/>
	*Congenital [[Special:MyLanguage/Long QT syndrome\|long QT syndrome]]		*Congenital [[Special:MyLanguage/Long QT syndrome\|long QT syndrome]]
	*[[Special:MyLanguage/Hypokalemia\|Hypokalemia]] (uncorrected)		*[[Special:MyLanguage/Hypokalemia\|Hypokalemia]] (uncorrected)
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	'''This is a critically important section for emergency physicians'''		'''This is a critically important section for emergency physicians'''

	*Lopinavir/ritonavir is a ~~'''~~potent CYP3A4 inhibitor~~'''~~ and a ~~'''~~P-glycoprotein inhibitor~~'''~~ — it significantly increases levels of many co-administered drugs<ref name="FDAlabel"/>		*Lopinavir/ritonavir is a potent CYP3A4 inhibitor and a P-glycoprotein inhibitor — it significantly increases levels of many co-administered drugs<ref name="FDAlabel"/>
	*'''Contraindicated combinations''' (risk of serious/life-threatening reactions):		*'''Contraindicated combinations''' (risk of serious/life-threatening reactions):
	**[[Special:MyLanguage/Amiodarone\|Amiodarone]], [[Special:MyLanguage/flecainide\|flecainide]] (cardiac arrhythmias)		**[[Special:MyLanguage/Amiodarone\|Amiodarone]], [[Special:MyLanguage/flecainide\|flecainide]] (cardiac arrhythmias)
	**[[Special:MyLanguage/Ergotamine\|Ergotamine]], dihydroergotamine (ergotism/vasospasm)		**[[Special:MyLanguage/Ergotamine\|Ergotamine]], dihydroergotamine (ergotism/vasospasm)
	**[[Special:MyLanguage/Midazolam\|Oral midazolam]], [[Special:MyLanguage/triazolam\|triazolam]] (prolonged sedation) — ~~'''~~IV midazolam may be used with caution and monitoring~~'''~~		**[[Special:MyLanguage/Midazolam\|Oral midazolam]], [[Special:MyLanguage/triazolam\|triazolam]] (prolonged sedation) — IV midazolam may be used with caution and monitoring
	**[[Special:MyLanguage/Simvastatin\|Simvastatin]], [[Special:MyLanguage/lovastatin\|lovastatin]] (rhabdomyolysis)		**[[Special:MyLanguage/Simvastatin\|Simvastatin]], [[Special:MyLanguage/lovastatin\|lovastatin]] (rhabdomyolysis)
	**Sildenafil when used for pulmonary arterial hypertension		**Sildenafil when used for pulmonary arterial hypertension
	**Rifampin (substantially decreases lopinavir levels)		**Rifampin (substantially decreases lopinavir levels)
	*~~'''~~Clinically significant interactions:~~'''~~		*Clinically significant interactions:
	**[[Special:MyLanguage/Warfarin\|Warfarin]] — monitor INR closely		**[[Special:MyLanguage/Warfarin\|Warfarin]] — monitor INR closely
	**[[Special:MyLanguage/Methadone\|Methadone]] — decreased methadone levels; may precipitate withdrawal		**[[Special:MyLanguage/Methadone\|Methadone]] — decreased methadone levels; may precipitate withdrawal
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	*Half-life: 5-6 hours		*Half-life: 5-6 hours
	*Metabolism: Hepatic, primarily via ~~'''~~CYP3A4~~'''~~ (ritonavir inhibits CYP3A4, markedly boosting lopinavir levels)		*Metabolism: Hepatic, primarily via CYP3A4 (ritonavir inhibits CYP3A4, markedly boosting lopinavir levels)
	*Excretion: Primarily fecal (~83%); renal (~11%)		*Excretion: Primarily fecal (~83%); renal (~11%)
	*Protein binding: 98-99% (bound to albumin and alpha-1-acid glycoprotein)		*Protein binding: 98-99% (bound to albumin and alpha-1-acid glycoprotein)
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	===COVID-19: No Benefit Demonstrated===		===COVID-19: No Benefit Demonstrated===

	Lopinavir/ritonavir was investigated for COVID-19 based on in-vitro activity against SARS-CoV-2 and prior data from SARS-CoV-1. Multiple large randomized controlled trials have now conclusively shown ~~'''~~no clinical benefit~~'''~~:		Lopinavir/ritonavir was investigated for COVID-19 based on in-vitro activity against SARS-CoV-2 and prior data from SARS-CoV-1. Multiple large randomized controlled trials have now conclusively shown no clinical benefit:

	*~~'''~~RECOVERY trial~~'''~~ (N=4,970): No significant difference in 28-day mortality (23% lopinavir/ritonavir vs 22% usual care; RR 1.03, 95% CI 0.91-1.17; p=0.60). No benefit in time to discharge or risk of progression to mechanical ventilation.<ref name="RECOVERY"/>		*RECOVERY trial (N=4,970): No significant difference in 28-day mortality (23% lopinavir/ritonavir vs 22% usual care; RR 1.03, 95% CI 0.91-1.17; p=0.60). No benefit in time to discharge or risk of progression to mechanical ventilation.<ref name="RECOVERY"/>
	*~~'''~~WHO SOLIDARITY trial~~'''~~ (>11,000 patients): No reduction in mortality, initiation of ventilation, or duration of hospitalization.<ref name="SOLIDARITY"/>		*WHO SOLIDARITY trial (>11,000 patients): No reduction in mortality, initiation of ventilation, or duration of hospitalization.<ref name="SOLIDARITY"/>
	*~~'''~~Cao et al.~~'''~~ (N=199, the initial Chinese RCT): No benefit in time to clinical improvement (HR 1.31, 95% CI 0.95-1.80).<ref name="Cao2020">Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020;382(19):1787-1799. doi:10.1056/NEJMoa2001282</ref>		*Cao et al. (N=199, the initial Chinese RCT): No benefit in time to clinical improvement (HR 1.31, 95% CI 0.95-1.80).<ref name="Cao2020">Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020;382(19):1787-1799. doi:10.1056/NEJMoa2001282</ref>

	Based on these results, ~~'''~~WHO halted the lopinavir/ritonavir arms of the SOLIDARITY trial in 2020~~'''~~, and lopinavir/ritonavir is ~~'''~~not recommended for COVID-19 treatment~~'''~~.<ref name="RECOVERY"/><ref name="SOLIDARITY"/>		Based on these results, WHO halted the lopinavir/ritonavir arms of the SOLIDARITY trial in 2020, and lopinavir/ritonavir is not recommended for COVID-19 treatment.<ref name="RECOVERY"/><ref name="SOLIDARITY"/>

	==See Also==		==See Also==