section name header

Pronunciation ⬇

da-RU-na-veer

Classifications ⬆ ⬇

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: protease inhibitors

Indications ⬆ ⬇

REMS

Action ⬆ ⬇

  • Inhibits HIV-1 protease, selectively inhibiting the cleavage of HIV-encoded specific polyproteins in infected cells. This prevents the formation of mature virus particles.
Therapeutic effects:
  • Increased CD4 cell counts and decreased viral load with subsequent slowed progression of HIV infection and its sequelae.

Pharmacokinetics ⬆ ⬇

Absorption: Without ritonavir: 37% absorbed following oral administration; with ritonavir: 82%. Food ↑ absorption by 30%.

Distribution: Unknown.

Protein Binding: 95%.

Metabolism/Excretion: Extensively metabolized by the CYP3A isoenzymes. 41% eliminated unchanged in feces, 8% in urine.

Half-Life: 15 hr.

Time/Action Profile ⬆ ⬇

ROUTEONSETPEAKDURATION
POunknown2.5–4 hr12 hr



Contraind./Precautions ⬆ ⬇

Contraindicated in:

  • Concurrent use of alfuzosin, dronedarone, colchicine (in renal/hepatic impairment), elbasvir/grazoprevir, ergot derivatives, ivabradine, lomitapide, lovastatin, lurasidone, midazolam (PO), naloxegol, pimozide, ranolazine, rifampin, sildenafil (Revatio), simvastatin, triazolam, or St. John’s wort;
  • Lactation: Avoid breastfeeding in mothers with HIV.

Use Cautiously in:

  • Hepatic impairment;
  • Sulfa allergy;
  • OB: Considered a preferred protease inhibitor (when combined with ritonavir) for pregnant females living with HIV who are antiretroviral-naive (as initial therapy), who have had antiretroviral therapy in the past but are restarting, or who require a new antiretroviral regimen (due to poor tolerance or poor virologic response of current regimen);
  • Pedi: Children <3 yr (safety and effectiveness not established);
  • Geri: Consider age-related impairment in hepatic function, concurrent chronic disease states, and drug therapy in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

Based on concurrent use with ritonavir

Derm: acute generalized exanthematous pustulosis, rash, DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

Endo: Graves’ disease, hyperglycemia

GI: autoimmune hepatitis, constipation, diarrhea, HEPATOTOXICITY, nausea, vomiting

Metab: body fat redistribution

MS: polymyositis

Neuro: Guillan-Barré syndrome

Misc: immune reconstitution syndrome

Interactions ⬆ ⬇

Drug-drug:

Drug-Natural Products:

  • St. John's wort↑ metabolism and may ↓ antiretroviral effectiveness; concurrent use contraindicated.

Route/Dosage ⬆ ⬇

  • Genotypic testing of the baseline virus is recommended prior to initiating treatment in therapy-experienced patients. This testing is performed to screen for darunavir resistance associated substitutions, which may be helpful in determining whether the patient’s HIV will be susceptible to darunavir.
  • PO (Adults ): Therapy-naive: 800 mg once daily with ritonavir 100 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution): 800 mg once daily with ritonavir 100 mg once daily; Therapy-experienced (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed): 600 mg twice daily with ritonavir 100 mg twice daily; Pregnancy: 600 mg twice daily with ritonavir 100 mg twice daily; if patient taking 800 mg once daily with ritonavir 100 mg once daily before pregnancy, may continue with this regimen if they are virologically suppressed (HIV-1 RNA <50 copies/mL), and if switch to twice daily regimen may compromise tolerability or compliance.
  • PO (Oral suspension or tablets)(Children 3–17 yr and ≥40 kg): Therapy-naive: 800 mg once daily with ritonavir 100 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution): 800 mg once daily with ritonavir 100 mg once daily; Therapy-experienced (with ≥1 darunavir resistance associated ­substitution or if genotypic testing not performed): 600 mg twice daily with ritonavir 100 mg twice daily.
  • PO (Oral suspension or tablets)(Children 3–17 yr and 30–39.9 kg): Therapy-naive: 675 mg once daily with ritonavir 100 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution): 675 mg once daily with ritonavir 100 mg once daily; Therapy-experienced­ (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed): 450 mg twice daily with ritonavir 60 mg twice daily.
  • PO (Oral suspension or tablets)(Children 3–17 yr and 15–29.9 kg): Therapy-naive: 600 mg once daily with ritonavir 100 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution): 600 mg once daily with ritonavir 100 mg once daily; Therapy-experienced (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed): 375 mg twice daily with ritonavir 48 mg twice daily.
  • PO (Oral suspension only)(Children 3–17 yr and 14–14.9 kg): Therapy-naive: 490 mg once daily with ritonavir 96 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution): 490 mg once daily with ritonavir 96 mg once daily; Therapy-experienced (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed): 280 mg twice daily with ritonavir 48 mg twice daily.
  • PO (Oral suspension only)(Children 3–17 yr and 13–13.9 kg): Therapy-naive: 455 mg once daily with ritonavir 80 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution): 455 mg once daily with ritonavir 80 mg once daily; Therapy-experienced (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed): 260 mg twice daily with ritonavir 40 mg twice daily.
  • PO (Oral suspension only)(Children 3–17 yr and 12–12.9 kg): Therapy-naive: 420 mg once daily with ritonavir 80 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution): 420 mg once daily with ritonavir 80 mg once daily; Therapy-experienced (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed): 240 mg twice daily with ritonavir 40 mg twice daily.
  • PO (Oral suspension only)(Children 3–17 yr and 11–11.9 kg): Therapy-naive: 385 mg once daily with ritonavir 64 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution): 385 mg once daily with ritonavir 64 mg once daily; Therapy-experienced (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed): 220 mg twice daily with ritonavir 32 mg twice daily.
  • PO (Oral suspension only)(Children 3–17 yr and 10–10.9 kg): Therapy-naive: 350 mg once daily with ritonavir 64 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution): 350 mg once daily with ritonavir 64 mg once daily; Therapy-experienced (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed): 200 mg twice daily with ritonavir 32 mg twice daily.

Availability ⬆ ⬇

(Generic available)
  • Oral suspension: 100 mg/mL
  • Tablets: 75 mg; 150 mg; 600 mg; 800 mg
  • In combination with:
  • cobicistat (Prezcobix); cobicistat, emtricitabine, tenofovir alafenamide (Symtuza). See Combination Drugs.

Assessment ⬆ ⬇

  • Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
  • Assess for allergy to sulfonamides.
  • Monitor patient for development of rash; usually maculopapular and self-limited. May cause Stevens-Johnson syndrome or toxic epidermal necrolysis. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.
  • Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling) associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.

Lab Test Considerations:

  • Obtain HIV genotypic testing for antiretroviral treatment experienced patients prior to starting therapy.
    • Monitor viral load and CD4 counts regularly during therapy.
    • May cause ↑ serum AST, ALT, GGT, total bilirubin, alkaline phosphatase, pancreatic amylase, pancreatic lipase, triglycerides, total cholesterol, and uric acid concentrations. Monitor hepatic function prior to and periodically during therapy. Hepatotoxicity may require interruption or discontinuation of therapy.

Implementation ⬆ ⬇

  • PO: Must be administered with a meal or light snack along with ritonavir 100 mg to be effective. The type of food is not important.
    • Administer oral suspension 8 mL dose as two 4-mL doses using syringe provided along with ritonavir and food.

Patient/Family Teaching ⬆ ⬇

  • Emphasize the importance of taking darunavir with ritonavir exactly as directed, at evenly spaced times throughout day. Do not take more than prescribed amount and do not stop taking without consulting health care professional. If a dose of darunavir or ritonavir is missed by more than 6 hr, wait and take next dose at regularly scheduled time. If missed by less than 6 hr, take darunavir and ritonavir immediately and then take next dose at regularly scheduled time. If a dose is skipped, do not double doses. Advise patient to read the Patient Information sheet before starting therapy and with each Rx renewal in case changes have been made.
  • Instruct patient that darunavir should not be shared with others.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John’s wort.
  • Inform patient that darunavir does not cure AIDS or prevent associated or opportunistic infections. Darunavir may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom during sexual contact and to avoid sharing needles or donating blood to prevent spreading HIV to others. Advise patient that the long-term effects of darunavir are unknown at this time.
  • Inform patient that darunavir may cause hyperglycemia, hepatotoxicity, and severe skin reactions. Advise patient to notify health care professional promptly if signs of hyperglycemia (increased thirst or hunger; unexplained weight loss; increased urination; fatigue; or dry, itchy skin), hepatotoxicity (unexplained fatigue, anorexia, nausea, jaundice, abdominal pain, or dark urine), DRESS, or rash occur.
  • Advise patient to notify health care professional if signs and symptoms of immune reconstitution syndrome (signs and symptoms of an infection) occur.
  • Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance. The cause and long-term effects are not known.
  • Rep: Instruct females of reproductive potential using hormonal contraceptives to use an alternative nonhormonal method of contraception. Advise patient to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding. If pregnant patient is exposed to darunavir, register patient in Antiretroviral Pregnancy Registry by calling 1-800-258-4263 to monitor pregnancy outcomes.
  • Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

Evaluation/Desired Outcomes ⬆ ⬇

  • Delayed progression of HIV and decreased opportunistic infections in patients with HIV.
  • Decrease in viral load and improvement in CD4 cell counts.

US Brand Names ⬆

Prezista