Indications
HIV infection (must be used with ritonavir and with
other antiretrovirals).
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%.
Foodqabsorption by 30%.
Distribution: Unknown.
Protein Binding: 95% bound to plasma proteins.
Metabolism and Excretion: Extensively metabolized
by CYP3A enzyme system. 41% eliminated unchanged
in feces, 8% in urine.
Half-life: 15 hr.
TIME/ACTION PROFILE
ROUTE ONSET PEAK DURATION
PO unknown 2.5–4 hr 12 hr
Contraindications/Precautions
Contraindicated in: Concurrent alfuzosin, dronedarone,
colchicine (in renal/hepatic impairment), ranolazine,
sildenafil (Revatio), ergot derivatives, lurasidone,
midazolam (PO), pimozide, triazolam, lovastatin,
simvastatin, rifampin, or St. John’s wort; Lactation:
Avoid breast feeding (HIV may be transmitted in human
milk).
Use Cautiously in: Hepatic impairment; Sulfa allergy;
Geri: Consider age-related impairment in hepatic
function, concurrent chronic disease states and drug
therapy; OB: May be used during pregnancy (if benefits
of use generally outweigh fetal risk); Pedi: Children 3
yr (safety and efficacy not established).
Adverse Reactions/Side Effects
Based on concurrent use with ritonavir.
GI: HEPATOTOXICITY, constipation, diarrhea, nausea,
vomiting. Endo: hyperglycemia.Metab: body fat redistribution.
Derm: DRUG RASH WITH EOSINOPHILIA AND
SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME,
TOXIC EPIDERMAL NECROLYSIS, rash, acute generalized
exanthematous pustulosis. Misc: immune reconstitution
syndrome.
Interactions
Drug-Drug: Darunavir and ritonavir are both inhibitors
of CYP3A, CYP2D6, and P-gp and are metabolized
by CYP3A. Multiple drug-drug interactions can be expected
with drugs that share, inhibit, or induce these
pathways. Consult product information for more specific
details.qblood levels and risk of toxicity from ergot
derivatives (dihydroergotamine, ergotamine,
methylergonovine), sildenafil (Revatio), alfuzosin,
dronedarone, ranolazine, lurasidone, pimozide,
lovastatin, simvastatin, midazolam (oral),
and triazolam; concurrent use is contraindicated. May
qcolchicine levels and cause serious/life-threatening
reactions;pdose of colchicine; concurrent use contraindicated
in patients with renal or hepatic impairment.
Rifampinqmetabolism and maypantiretroviral effectiveness,
concurrent use is contraindicated. Concurrent
use with indinavir mayqdarunavir and indinavir levels.
qlevels and risk of myopathy from atorvastatin,
rosuvastatin, or pravastatin; use lowest dose of
these agents; do not exceed atorvastatin dose of 20 mg/
day. Concurrent use with efavirenz results inpdarunavir
levels andqefavirenz levels; use combination
cautiously. Lopinavir/ritonavir mayplevels; concurrent
use not recommended. Saquinavir mayplevels;
concurrent use not recommended. Mayqmaraviroc
levels;pmaraviroc dose to 150 mg twice daily. Mayq
levels of lidocaine, quinidine, disopyramide, mexiletine,
propafenone, flecainide, and amiodarone;
use cautiously and with available blood level monitoring.
qdigoxin levels; blood level monitoring recommended.
Mayqcarbamazepine levels; blood level
monitoring recommended. Maypphenytoin or phenobarbital
levels; blood level monitoring recommended.
Mayplevels of warfarin; monitor INR. May
qlevels of trazodone, amitriptyline, desipramine,
imipramine, and nortriptyline; use cautiously and
pdose if necessary. Mayqlevels of clarithromycin;p
dose of clarithromycin if CCr 60 mL/min. Mayqlevels
of ketoconazole and itraconazole; do not exceed
itraconazole or ketoconazole dose 200 m g/day. Ketoconazole
and itraconazole mayqlevels. Mayp
levels of voriconazole; concurrent use not recommended.
Concurrent use with rifabutinqrifabutin levels
andqdarunavir levels; (may be due to ritonavir);p
rifabutin dose to 150 mg every other day. Rifapentin
mayplevels; concurrent use not recommended. Mayq
levels of beta-blockers; may need topdose. Mayq
levels of amlodipine, diltiazem, felodipine, nifedipine,
nicardipine, or verapamil; monitor clinical response
carefully. Dexamethasone mayplevels and effectiveness.
Mayqlevels and the risk of Cushing’s
syndrome and adrenal suppression with systemic budesonide
and prednisone; consider alternative therapy.
Mayqlevels of inhaled/nasal fluticasone and budesonide;
choose alternative inhaled/nasal
corticosteroid. Mayqlevels of cyclosporine, tacrolimus,
or sirolimus; blood level monitoring recommended.
Mayqlevels of everolimus; concurrent use not recommended. Mayplevels of methadone. Mayq
risperidone and thioridazine levels; may need top
dose. Mayqlevels of sildenafil, vardenafil, tadalafil,
or avanafil; single dose should not exceed the following(
sildenafil 25 mg in 48 hr; vardenafil 2.5 mg in 72
hr; tadalafil 10 mg in 72 hr); concurrent use with avanafil
not recommended. Mayplevels of sertraline and
paroxetine; adjust dose by clinical response. Mayp
levels and contraceptive efficacy of some combined
hormonal contraceptives and progestin-only contraceptives
(alternative methods of nonhormonal contraception
recommended). Mayqlevels of salmeterol;
concurrent use not recommended. Mayq
bosentan levels; initiate bosentan at 62.5 mg once
daily or every other day once patient receiving darunavir
for 10 days; if patient already receiving bosentan,
discontinue bosentan 36 hr before initiation of darunavir
and then restart bosentan 10 days later at 62.5
mg once daily or every other day. Mayqtadalafil (Adcirca)
levels; initiate tadalafil (Adcirca) at 20 mg once
daily once patient receiving darunavir for 1 wk; if patient
already receiving tadalfil (Adcirca), discontinue
tadalafil (Adcirca) 24 hr before initiation of darunavir
and then restart tadalafil (Adcirca) 7 days later at 20
mg once daily. Concurrent use with simeprevir results
inqdarunavir levels andqsimeprevir levels; concurrent
use not recommended. Mayqlumefantrine levels
and risk of QT interval prolongation. Mayqquetiapine
levels;pquetiapine dose to 1⁄6 of current dose.
Mayqlevels of and risk of bleeding with apixaban,
dabigatran, and rivaroxaban; concurrent use not
recommended. Mayqdasatinib and nilotinib levels;
may need topdose orqdosing interval of dasatinib
and nilotinib. Mayqvinblastine and vincristine levels;
may need to temporarily hold darunavir-ritonavir
or initiate another antiretroviral regimen. Mayqlevels
of buspirone, diazepam, estazolam, midazolam
(IV), and zolpidem;pdose of sedative. Maypomeprazole
levels; considerqomeprazole dose (not to
exceed 40 mg/day).
Drug-Natural Products: St. John’s wortqmetabolism
and maypantiretroviral 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 HIV virus 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 supressed (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
Tablets: 75 mg, 150 mg, 600 mg, 800 mg. Oral suspension:
100 mg/mL. In combination with: cobicistat
(Prezcobix). See Appendix B.
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