Diferencia entre revisiones de «Darunavir»

(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>
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==
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==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
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===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


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==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"/>


Revisión actual - 09:10 22 mar 2026

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.[1]

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:[1]

  • 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)[1]
  • Must be taken with food (increases exposure ~30%)[2]
  • Contains a sulfonamide moiety — use with caution in sulfa-allergic patients (though cross-reactivity rate is low in clinical studies)[1]

Pediatric Dosing

  • Approved for patients ≥3 years and ≥10 kg (with ritonavir); ≥15 kg (with cobicistat)[1]
  • Weight-based dosing; consult prescribing information or pediatric ID
  • Not recommended in children <3 years (toxicity and mortality observed in juvenile animal studies)[1]

Special Populations

Pregnancy Rating

  • No adequate controlled studies in pregnant women; no increased birth defect rate in registry data[1]
  • 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[1]
  • Do not initiate darunavir/cobicistat during pregnancy (lower darunavir exposure); switch to darunavir/ritonavir[1]
  • 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)[1]

Renal Dosing

  • Adult: No dose adjustment needed; renal clearance is minimal (~8% of dose as unchanged drug with ritonavir)[2]
    • 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[1]
    • 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)[1]

Adverse Reactions

Serious

Common

  • Diarrhea, nausea, rash, headache[1]
  • 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)[1]

Pharmacology

  • Half-life: ~15 hours (when boosted with ritonavir)[2]
  • Metabolism: Extensively metabolized by CYP3A4; bioavailability increases from ~37% to ~82% with ritonavir boosting[2]
  • Excretion: ~79.5% feces, ~13.9% urine[2]

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.[1] Darunavir maintains activity against many PI-resistant HIV-1 strains due to its flexible molecular structure and tight binding to the protease active site.[2]

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[1]
  • 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)[1]
  • 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[1]
  • Hepatitis co-infection: Monitor hepatic enzymes before initiating and at frequent intervals, especially in patients with hepatitis B/C[1]
  • Overdose: No specific antidote; supportive care. Highly protein bound; unlikely removed by dialysis[1]

See Also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 Prezista (darunavir) [prescribing information]. Titusville, NJ: Janssen Therapeutics; 2017.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Rittweger M, Arasteh K. Clinical pharmacokinetics of darunavir. Clin Pharmacokinet. 2007;46(9):739-756.
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