Darunavir - Revision history

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Created page with "Darunavir is an HIV-1 protease inhibitor (PI) with potent activity against both wild-type and PI-resistant HIV-1. It '''must''' be coadministered with a pharmacokinetic booster — either ritonavir or cobicistat — and taken with food.<ref name="PrezistaPI">Prezista (darunavir) [prescribing information]. Titusville, NJ: Janssen Therapeutics; 2017.</ref> ==Administration== *Type: HIV-1 protease inhibitor (PI) *Dosage Forms: 75 mg, 150 mg, 300 mg, 400 mg, 600 mg, 800 mg..."

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Darunavir is an HIV-1 protease inhibitor (PI) with potent activity against both wild-type and PI-resistant HIV-1. It '''must''' be coadministered with a pharmacokinetic booster — either ritonavir or cobicistat — and taken with food.<ref name="PrezistaPI">Prezista (darunavir) [prescribing information]. Titusville, NJ: Janssen Therapeutics; 2017.</ref>

==Administration==
*Type: HIV-1 protease inhibitor (PI)
*Dosage Forms: 75 mg, 150 mg, 300 mg, 400 mg, 600 mg, 800 mg tablets; 100 mg/mL oral suspension
*Routes of Administration: Oral
*Common Trade Names: Prezista; also in fixed-dose combination: Prezcobix (darunavir/cobicistat), Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide)

==Adult Dosing==
'''Must''' be taken with a booster and with food:<ref name="PrezistaPI"/>
*'''Treatment-naive or treatment-experienced with no darunavir resistance mutations:''' 800 mg + ritonavir 100 mg PO once daily
*'''Treatment-experienced with ≥1 darunavir resistance mutation:''' 600 mg + ritonavir 100 mg PO twice daily
*May substitute cobicistat 150 mg for ritonavir in once-daily regimens (not for twice-daily dosing)<ref name="PrezistaPI"/>
*'''Must be taken with food''' (increases exposure ~30%)<ref name="Rittweger2007">Rittweger M, Arasteh K. Clinical pharmacokinetics of darunavir. ''Clin Pharmacokinet''. 2007;46(9):739-756.</ref>
*Contains a '''sulfonamide moiety''' — use with caution in sulfa-allergic patients (though cross-reactivity rate is low in clinical studies)<ref name="PrezistaPI"/>

==Pediatric Dosing==
*Approved for patients ≥3 years and ≥10 kg (with ritonavir); ≥15 kg (with cobicistat)<ref name="PrezistaPI"/>
*Weight-based dosing; consult prescribing information or pediatric ID
*'''Not recommended''' in children <3 years (toxicity and mortality observed in juvenile animal studies)<ref name="PrezistaPI"/>

==Special Populations==
===[[Drug pregnancy categories|Pregnancy Rating]]===
*No adequate controlled studies in pregnant women; no increased birth defect rate in registry data<ref name="PrezistaPI"/>
*'''Pregnancy dosing:''' 600 mg/ritonavir 100 mg PO twice daily is generally recommended; once-daily 800 mg/ritonavir 100 mg may be considered only in patients already virologically suppressed on that regimen prior to pregnancy<ref name="PrezistaPI"/>
*'''Do not initiate''' darunavir/cobicistat during pregnancy (lower darunavir exposure); switch to darunavir/ritonavir<ref name="PrezistaPI"/>
*Antiretroviral Pregnancy Registry: 1-800-258-4263

===Lactation risk===
*Present in rat milk; unknown in human milk. Women with HIV should not breastfeed (risk of HIV transmission)<ref name="PrezistaPI"/>

===Renal Dosing===
*Adult: No dose adjustment needed; renal clearance is minimal (~8% of dose as unchanged drug with ritonavir)<ref name="Rittweger2007"/>
**Not studied in severe impairment or ESRD, but unlikely removed by hemodialysis (95% protein bound)
*Pediatric: No specific data; no adjustment expected

===Hepatic Dosing===
*Adult: No adjustment for mild or moderate (Child-Pugh A or B) impairment; use with caution<ref name="PrezistaPI"/>
**Severe (Child-Pugh C): '''Not recommended''' (not studied)
*Pediatric: Not studied

==Contraindications==
*Allergy to class/drug
*Coadministration with drugs highly dependent on CYP3A for clearance where elevated levels cause serious/life-threatening events (e.g., alfuzosin, ergot derivatives, dronedarone, pimozide, lurasidone, oral midazolam, triazolam, rifampin, St. John's wort, simvastatin, lovastatin, sildenafil for PAH)<ref name="PrezistaPI"/>

==Adverse Reactions==
===Serious===
*'''Hepatotoxicity''' — drug-induced hepatitis and hepatic failure (including fatalities) reported; higher risk with pre-existing hepatic disease or hepatitis B/C co-infection<ref name="PrezistaPI"/>
*Severe skin reactions: [[Stevens-Johnson syndrome]], [[toxic epidermal necrolysis]], erythema multiforme, acute generalized exanthematous pustulosis<ref name="PrezistaPI"/>
*[[Immune reconstitution syndrome|Immune reconstitution inflammatory syndrome (IRIS)]]
*New-onset or worsening diabetes mellitus/hyperglycemia (class effect of PIs); diabetic ketoacidosis reported<ref name="PrezistaPI"/>

===Common===
*Diarrhea, nausea, rash, headache<ref name="PrezistaPI"/>
*Hyperlipidemia (elevated triglycerides and cholesterol — PI class effect)
*Lipodystrophy/fat redistribution (PI class effect)
*Transaminase elevations (higher rates in hepatitis B/C co-infection: up to 7% Grade 2–4 ALT elevations)<ref name="PrezistaPI"/>

==Pharmacology==
*Half-life: ~15 hours (when boosted with ritonavir)<ref name="Rittweger2007"/>
*Metabolism: Extensively metabolized by CYP3A4; bioavailability increases from ~37% to ~82% with ritonavir boosting<ref name="Rittweger2007"/>
*Excretion: ~79.5% feces, ~13.9% urine<ref name="Rittweger2007"/>

==Mechanism of Action==
Darunavir selectively inhibits the cleavage of HIV-1 Gag-Pol polyprotein precursors by binding to the active site of HIV-1 protease. This prevents processing of viral polyproteins into functional structural proteins and enzymes, resulting in the formation of immature, non-infectious viral particles.<ref name="PrezistaPI"/> Darunavir maintains activity against many PI-resistant HIV-1 strains due to its flexible molecular structure and tight binding to the protease active site.<ref name="Rittweger2007"/>

==Comments==
*'''Boosting is mandatory:''' Darunavir without ritonavir or cobicistat has insufficient plasma levels for antiviral effect — if a patient reports not taking the booster, the regimen is functionally not working<ref name="PrezistaPI"/>
*'''Strong CYP3A inhibitor:''' Darunavir/ritonavir (or cobicistat) '''significantly increases levels''' of many drugs metabolized by CYP3A4. This is the most important ED consideration:
**Common ED interactions: midazolam (IV acceptable with monitoring; '''oral midazolam contraindicated'''), fentanyl (increased levels — reduce dose and monitor), colchicine (contraindicated in renal/hepatic impairment; reduce dose otherwise), simvastatin/lovastatin (contraindicated), ergotamines (contraindicated)<ref name="PrezistaPI"/>
*'''Sulfonamide moiety:''' Contains a sulfonamide group. In clinical trials, rash rates were similar in patients with and without sulfa allergy history. Use with caution but it is not an absolute contraindication<ref name="PrezistaPI"/>
*'''Hepatitis co-infection:''' Monitor hepatic enzymes before initiating and at frequent intervals, especially in patients with hepatitis B/C<ref name="PrezistaPI"/>
*Overdose: No specific antidote; supportive care. Highly protein bound; unlikely removed by dialysis<ref name="PrezistaPI"/>

==See Also==
*[[HIV - AIDS (main)]]
*[[HIV post-exposure prophylaxis]]
*[[Immune reconstitution syndrome]]
*[[Emtricitabine/tenofovir]]

==References==
{{reflist|2}}
[[Category:Pharmacology]]

← Revisión anterior		Revisión del 09:10 22 mar 2026
Línea 1:		Línea 1:
	Darunavir is an HIV-1 protease inhibitor (PI) with potent activity against both wild-type and PI-resistant HIV-1. It ~~'''~~must~~'''~~ be coadministered with a pharmacokinetic booster — either ritonavir or cobicistat — and taken with food.<ref name="PrezistaPI">Prezista (darunavir) [prescribing information]. Titusville, NJ: Janssen Therapeutics; 2017.</ref>		Darunavir is an HIV-1 protease inhibitor (PI) with potent activity against both wild-type and PI-resistant HIV-1. It must be coadministered with a pharmacokinetic booster — either ritonavir or cobicistat — and taken with food.<ref name="PrezistaPI">Prezista (darunavir) [prescribing information]. Titusville, NJ: Janssen Therapeutics; 2017.</ref>

	==Administration==		==Administration==
Línea 8:		Línea 8:

	==Adult Dosing==		==Adult Dosing==
	~~'''~~Must~~'''~~ be taken with a booster and with food:<ref name="PrezistaPI"/>		Must be taken with a booster and with food:<ref name="PrezistaPI"/>
	*~~'''~~Treatment-naive or treatment-experienced with no darunavir resistance mutations:~~'''~~ 800 mg + ritonavir 100 mg PO once daily		*Treatment-naive or treatment-experienced with no darunavir resistance mutations: 800 mg + ritonavir 100 mg PO once daily
	*~~'''~~Treatment-experienced with ≥1 darunavir resistance mutation:~~'''~~ 600 mg + ritonavir 100 mg PO twice daily		*Treatment-experienced with ≥1 darunavir resistance mutation: 600 mg + ritonavir 100 mg PO twice daily
	*May substitute cobicistat 150 mg for ritonavir in once-daily regimens (not for twice-daily dosing)<ref name="PrezistaPI"/>		*May substitute cobicistat 150 mg for ritonavir in once-daily regimens (not for twice-daily dosing)<ref name="PrezistaPI"/>
	*~~'''~~Must be taken with food~~'''~~ (increases exposure ~30%)<ref name="Rittweger2007">Rittweger M, Arasteh K. Clinical pharmacokinetics of darunavir. ''Clin Pharmacokinet''. 2007;46(9):739-756.</ref>		*Must be taken with food (increases exposure ~30%)<ref name="Rittweger2007">Rittweger M, Arasteh K. Clinical pharmacokinetics of darunavir. ''Clin Pharmacokinet''. 2007;46(9):739-756.</ref>
	*Contains a ~~'''~~sulfonamide moiety~~'''~~ — use with caution in sulfa-allergic patients (though cross-reactivity rate is low in clinical studies)<ref name="PrezistaPI"/>		*Contains a sulfonamide moiety — use with caution in sulfa-allergic patients (though cross-reactivity rate is low in clinical studies)<ref name="PrezistaPI"/>

	==Pediatric Dosing==		==Pediatric Dosing==
	*Approved for patients ≥3 years and ≥10 kg (with ritonavir); ≥15 kg (with cobicistat)<ref name="PrezistaPI"/>		*Approved for patients ≥3 years and ≥10 kg (with ritonavir); ≥15 kg (with cobicistat)<ref name="PrezistaPI"/>
	*Weight-based dosing; consult prescribing information or pediatric ID		*Weight-based dosing; consult prescribing information or pediatric ID
	*~~'''~~Not recommended~~'''~~ in children <3 years (toxicity and mortality observed in juvenile animal studies)<ref name="PrezistaPI"/>		*Not recommended in children <3 years (toxicity and mortality observed in juvenile animal studies)<ref name="PrezistaPI"/>

	==Special Populations==		==Special Populations==
	===[[Drug pregnancy categories\|Pregnancy Rating]]===		===[[Drug pregnancy categories\|Pregnancy Rating]]===
	*No adequate controlled studies in pregnant women; no increased birth defect rate in registry data<ref name="PrezistaPI"/>		*No adequate controlled studies in pregnant women; no increased birth defect rate in registry data<ref name="PrezistaPI"/>
	*~~'''~~Pregnancy dosing:~~'''~~ 600 mg/ritonavir 100 mg PO twice daily is generally recommended; once-daily 800 mg/ritonavir 100 mg may be considered only in patients already virologically suppressed on that regimen prior to pregnancy<ref name="PrezistaPI"/>		*Pregnancy dosing: 600 mg/ritonavir 100 mg PO twice daily is generally recommended; once-daily 800 mg/ritonavir 100 mg may be considered only in patients already virologically suppressed on that regimen prior to pregnancy<ref name="PrezistaPI"/>
	*'''Do not initiate''' darunavir/cobicistat during pregnancy (lower darunavir exposure); switch to darunavir/ritonavir<ref name="PrezistaPI"/>		*'''Do not initiate''' darunavir/cobicistat during pregnancy (lower darunavir exposure); switch to darunavir/ritonavir<ref name="PrezistaPI"/>
	*Antiretroviral Pregnancy Registry: 1-800-258-4263		*Antiretroviral Pregnancy Registry: 1-800-258-4263
Línea 37:		Línea 37:
	===Hepatic Dosing===		===Hepatic Dosing===
	*Adult: No adjustment for mild or moderate (Child-Pugh A or B) impairment; use with caution<ref name="PrezistaPI"/>		*Adult: No adjustment for mild or moderate (Child-Pugh A or B) impairment; use with caution<ref name="PrezistaPI"/>
	**Severe (Child-Pugh C): ~~'''~~Not recommended~~'''~~ (not studied)		**Severe (Child-Pugh C): Not recommended (not studied)
	*Pediatric: Not studied		*Pediatric: Not studied

Línea 66:		Línea 66:

	==Comments==		==Comments==
	*~~'''~~Boosting is mandatory:~~'''~~ Darunavir without ritonavir or cobicistat has insufficient plasma levels for antiviral effect — if a patient reports not taking the booster, the regimen is functionally not working<ref name="PrezistaPI"/>		*Boosting is mandatory: Darunavir without ritonavir or cobicistat has insufficient plasma levels for antiviral effect — if a patient reports not taking the booster, the regimen is functionally not working<ref name="PrezistaPI"/>
	*~~'''~~Strong CYP3A inhibitor:~~'''~~ Darunavir/ritonavir (or cobicistat) ~~'''~~significantly increases levels~~'''~~ of many drugs metabolized by CYP3A4. This is the most important ED consideration:		*Strong CYP3A inhibitor: Darunavir/ritonavir (or cobicistat) significantly increases levels of many drugs metabolized by CYP3A4. This is the most important ED consideration:
	**Common ED interactions: midazolam (IV acceptable with monitoring; '''oral midazolam contraindicated'''), fentanyl (increased levels — reduce dose and monitor), colchicine (contraindicated in renal/hepatic impairment; reduce dose otherwise), simvastatin/lovastatin (contraindicated), ergotamines (contraindicated)<ref name="PrezistaPI"/>		**Common ED interactions: midazolam (IV acceptable with monitoring; '''oral midazolam contraindicated'''), fentanyl (increased levels — reduce dose and monitor), colchicine (contraindicated in renal/hepatic impairment; reduce dose otherwise), simvastatin/lovastatin (contraindicated), ergotamines (contraindicated)<ref name="PrezistaPI"/>
	*~~'''~~Sulfonamide moiety:~~'''~~ Contains a sulfonamide group. In clinical trials, rash rates were similar in patients with and without sulfa allergy history. Use with caution but it is not an absolute contraindication<ref name="PrezistaPI"/>		*Sulfonamide moiety: Contains a sulfonamide group. In clinical trials, rash rates were similar in patients with and without sulfa allergy history. Use with caution but it is not an absolute contraindication<ref name="PrezistaPI"/>
	*~~'''~~Hepatitis co-infection:~~'''~~ Monitor hepatic enzymes before initiating and at frequent intervals, especially in patients with hepatitis B/C<ref name="PrezistaPI"/>		*Hepatitis co-infection: Monitor hepatic enzymes before initiating and at frequent intervals, especially in patients with hepatitis B/C<ref name="PrezistaPI"/>
	*Overdose: No specific antidote; supportive care. Highly protein bound; unlikely removed by dialysis<ref name="PrezistaPI"/>		*Overdose: No specific antidote; supportive care. Highly protein bound; unlikely removed by dialysis<ref name="PrezistaPI"/>