Darunavir

Synonyms :
(3R,3AS,6ar)-hexahydrofuro[2,3-b]furan-3-yl N-((1S,2R)-1-benzyl-2-hydroxy-3-(N(1)-isobutylsulfanilamido)propyl)carbamate, (3R,3AS,6ar)-hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate, (3R,3AS,6ar)-tetrahydro-2H-furo[2,3-b]furan-3-yl (2S,3R)-4-(4-amino-N-isobutylphenylsulfonamido)-3-hydroxy-1-phenylbutan-2-ylcarbamate, (3R,3AS,6ar)-tetrahydro-2H-furo[2,3-b]furan-3-yl (2S,3R)-4-(4-amino-N-neopentylphenylsulfonamido)-3-hydroxy-1-phenylbutan-2-ylcarbamate, [(S)-3-[(4-Amino-benzenesulfonyl)-isobutyl-amino]-2-hydroxy-1-((R)-phenylmethyl)-propyl]-carbamic acid (3R,3as,6ar)-(hexahydro-furo[2,3-b]furan-3-yl) ester, {(1S,2R)-3-[(4-amino-benzenesulfonyl)-isobutyl-amino]-1-benzyl-2-hydroxy-propyl}-carbamic acid (3R,3as,6ar)-(hexahydro-furo[2,3-b]furan-3-yl) ester, Darunavir, Darunavirum, N-((1S,2R)-3-(((4-Aminophenyl)sulfonyl)(2-methylpropyl)amino)-2-hydroxy-1-benzylpropyl)((1S,2R,5R)-4,6-dioxabicyclo(3.3.0)oct-2-yloxy)carboxamide, TMC-114, TMC114

Status : approved

Category

HIV Protease Inhibitors

Therapeutic Classification

DIRECT ACTING ANTIVIRALS

ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS

Description

Darunavir is a protease inhibitor used to treat HIV. It acts on the HIV aspartyl protease which the virus needs to cleave the HIV polyprotein into its functional fragments.

Used

Darunavir, co-administered with ritonavir, and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment-experienced adult patients, such as those with HIV-1 strains resistant to more than one protease inhibitor.

Mechanism Of Action

Darunavir is a HIV protease inhibitor which prevents HIV replication by binding to the enzyme’s active site, thereby preventing the dimerization and the catalytic activity of the HIV-1 protease. Darunavir selectively inhibits the cleavage of HIV encoded Gag-Pol polyproteins in virus-infected cells, which prevents the formation of mature infectious virus particles. Structual analyses suggests that the close contact that darunavir has with the main chains of the protease active site amino acids (Asp-29 and Asp-30) is an important contributing factor to its potency and wide spectrum of activity against multi-protease inhibitor resistant HIV-1 variants. Darunavir can also adapt to the changing shape of a protease enzyme because of its molecular flexibility. Darunavir is known to bind to two distinct sites on the enzyme: the active site cavity and the surface of one of the flexible flaps in the protease dimer.

Dosage

Form Route Strength
Tablet oral 800 mg
Suspension oral 100 mg
Suspension oral 100 mg/mL
Tablet oral 150 mg
Tablet oral 300 mg
Tablet oral 400 mg
Tablet oral 600 mg
Tablet oral 75 mg
Tablet oral 800 mg
Tablet, film coated oral 150 mg
Tablet, film coated oral 400 mg
Tablet, film coated oral 600 mg
Tablet, film coated oral 75 mg
Tablet, film coated oral 800 mg

Pharmacodynamics

Darunavir is an inhibitor of the human immunodeficiency virus (HIV) protease. In studies, the drug, co-administered with ritonavir in combination therapy, significantly reduced viral load and increased CD4 cell counts in this treatment-experienced patient population (Tibotec, 2006, Product Monograph, Prezista 2006). Darunavir is used as an adjunct therapy with low dose ritonavir, which inhibits cytochrome P450 3A (CYP3A) which increases the bioavailability and half life of darunavir.

Metabolism

Hepatic. Darunavir is extensively metabolized by CYP enzymes, primarily by CYP3A.

Absorption

The absolute oral bioavailability of a single 600 mg dose of darunavir alone and after co-administration with 100 mg ritonavir twice daily was 37% and 82%, respectively.

Half Life

The terminal elimination half-life of darunavir was approximately 15 hours when combined with ritonavir.

Protein Binding

Darunavir is approximately 95% bound to plasma proteins. Darunavir binds primarily to plasma alpha 1-acid glycoprotein (AAG).

Elimination Route

Darunavir is primarily metabolized by CYP3A. Darunavir is extensively metabolized by CYP enzymes, primarily by CYP3A. A mass balance study in healthy volunteers showed that after single dose administration of 400 mg 14C-darunavir, co-administered with 100 mg ritonavir, approximately 79.5% and 13.9% of the administered dose of 14C-darunavir was recovered in the feces and urine, respectively.

Clearance

* 32.8 L/hr [Healthy volunteers receiving intravenous administration of 400 mg of darunavir] * 5.9 L/hr [Healthy volunteers receiving intravenous administrations of 400 mg of darunavir and 100 mg of ritonavir twice daily]

Chemical Classification

This compound belongs to the class of organic compounds known as aminobenzenesulfonamides. These are organic compounds containing a benzenesulfonamide moiety with an amine group attached to the benzene ring.

Aminobenzenesulfonamides

Organic compounds

Benzenoids

Benzene and substituted derivatives

Benzenesulfonamides

Chemical Name

(3R,3AS,6ar)-hexahydrofuro[2,3-b]furan-3-yl N-((1S,2R)-1-benzyl-2-hydroxy-3-(N(1)-isobutylsulfanilamido)propyl)carbamate

Brands

name Dosage form Country
Pat-darunavir tablet Canada
Pat-darunavir tablet Canada
Pat-darunavir tablet Canada
Pat-darunavir tablet Canada
Pat-darunavir tablet Canada
Prezcobix tablet Canada
Prezista tablet Canada
Prezista tablet Canada
Prezista tablet Canada
Prezista tablet, film coated US
Prezista tablet, film coated US
Prezista tablet Canada
Prezista tablet, film coated US
Prezista tablet Canada
Prezista tablet, film coated US
Prezista tablet, film coated US
Prezista tablet, film coated US
Prezista tablet, film coated US
Prezista suspension US
Prezista tablet, film coated US
Prezista suspension Canada
Prezista tablet Canada

Drug Drug Interactions

  •  Abacavir  : Protease Inhibitors may decrease the serum concentration of Abacavir.
  •  Acetohexamide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  ado-trastuzumab emtansine  : CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ado-trastuzumab emtansine. Specifically, strong CYP3A4 inhibitors may increase concentrations of the cytotoxic DM1 component.
  •  Afatinib  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib.
  •  Alfuzosin  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin.
  •  Alfuzosin  : Protease Inhibitors may increase the serum concentration of Alfuzosin.
  •  Almotriptan  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan.
  •  Alogliptin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Alosetron  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron.
  •  Alprazolam  : Protease Inhibitors may increase the serum concentration of Alprazolam.
  •  Amiodarone  : Darunavir may increase the serum concentration of Amiodarone.
  •  Amitriptyline  : May increase the serum concentration of CYP2D6 Substrates.
  •  Amoxapine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Apixaban  : Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Apixaban.
  •  Aripiprazole  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Aripiprazole.
  •  Astemizole  : Darunavir may increase the serum concentration of Astemizole.
  •  Atomoxetine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Atorvastatin  : Protease Inhibitors may increase the serum concentration of Atorvastatin.
  •  Avanafil  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avanafil.
  •  Axitinib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Batimastat  : May increase the serum concentration of other Protease Inhibitors.
  •  Bedaquiline  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bedaquiline.
  •  Boceprevir  : May decrease the serum concentration of Protease Inhibitors. Protease Inhibitors may decrease the serum concentration of Boceprevir.
  •  Bortezomib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib.
  •  Bosentan  : May decrease the serum concentration of Darunavir. Darunavir may increase the serum concentration of Bosentan.
  •  Bosutinib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib.
  •  Bosutinib  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib.
  •  Brentuximab vedotin  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brentuximab vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased.
  •  Brentuximab vedotin  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased.
  •  Brexpiprazole  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole.
  •  Brinzolamide  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brinzolamide.
  •  Cabazitaxel  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabazitaxel.
  •  Cabozantinib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabozantinib.
  •  Canagliflozin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Captopril  : May increase the serum concentration of CYP2D6 Substrates.
  •  Carbamazepine  : Darunavir may increase the serum concentration of Carbamazepine.
  •  Carvedilol  : May increase the serum concentration of CYP2D6 Substrates.
  •  Ceritinib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ceritinib.
  •  Chlorphenamine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Chlorpromazine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Chlorpropamide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Cilostazol  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilostazol.
  •  Cisapride  : Protease Inhibitors may increase the serum concentration of Cisapride. This may result in QTc prolongation and malignant cardiac arrhythmias.
  •  Clarithromycin  : Protease Inhibitors may diminish the therapeutic effect of Clarithromycin. Specifically, certain protease inhibitors may decrease formation of the active 14-hydroxy-clarithromycin metabolite, which may negatively impact clarithromycin effectiveness vs. H. influenzae and other non-MAC infections. Protease Inhibitors may increase the serum concentration of Clarithromycin. Clarithromycin dose adjustment in renally impaired patients may be needed. Clarithromycin may increase the serum concentration of Protease Inhibitors.
  •  Clomipramine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Codeine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Colchicine  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine.
  •  Colchicine  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased.
  •  Conivaptan  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan.
  •  Conivaptan  : May increase the serum concentration of CYP3A4 Substrates.
  •  Crizotinib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Crizotinib.
  •  Cyclophosphamide  : Protease Inhibitors may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, the incidences of neutropenia, infection, and mucositis may be increased.
  •  Dabigatran etexilate  : P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran etexilate.
  •  Dabrafenib  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Daclatasvir  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Daclatasvir.
  •  Dapoxetine  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dapoxetine.
  •  Dasatinib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dasatinib.
  •  Deferasirox  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Delavirdine  : Protease Inhibitors may decrease the serum concentration of Delavirdine. Delavirdine may increase the serum concentration of Protease Inhibitors.
  •  Desipramine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Desogestrel  : May decrease the serum concentration of Contraceptives (Progestins).
  •  Dextromethorphan  : May increase the serum concentration of CYP2D6 Substrates.
  •  Didanosine  : Darunavir may decrease the serum concentration of Didanosine. More specifically, this interaction is likely due to the effects of food (with which darunavir/ritonavir are taken) on didanosine, which is supposed to be given on an empty stomach.
  •  Dienogest  : May decrease the serum concentration of Contraceptives (Progestins).
  •  Digoxin  : Protease Inhibitors may increase the serum concentration of Digoxin. Increased serum concentrations of digoxin may increase risk of AV nodal blockade.
  •  Dofetilide  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dofetilide.
  •  Domperidone  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Domperidone.
  •  Doxepin  : May increase the serum concentration of CYP2D6 Substrates.
  •  Dronabinol  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronabinol.
  •  Dronabinol  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol.
  •  Dronedarone  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone.
  •  Drospirenone  : May decrease the serum concentration of Contraceptives (Progestins).
  •  Dutasteride  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride.
  •  Edoxaban  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban.
  •  Efavirenz  : Darunavir may increase the serum concentration of Efavirenz. Efavirenz may decrease the serum concentration of Darunavir.
  •  Eletriptan  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eletriptan.
  •  Eliglustat  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eliglustat.
  •  Elvitegravir  : Darunavir may increase the serum concentration of Elvitegravir.
  •  Enfuvirtide  : Protease Inhibitors may increase the serum concentration of Enfuvirtide. Enfuvirtide may increase the serum concentration of Protease Inhibitors.
  •  Eplerenone  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone.
  •  Erlotinib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erlotinib.
  •  Estazolam  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estazolam.
  •  Ethinyl Estradiol  : May decrease the serum concentration of Contraceptives (Progestins).
  •  Ethynodiol  : May decrease the serum concentration of Contraceptives (Progestins).
  •  Etonogestrel  : May decrease the serum concentration of Contraceptives (Progestins).
  •  Etravirine  : Darunavir may decrease the serum concentration of Etravirine.
  •  Everolimus  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus.
  •  Fentanyl  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fentanyl.
  •  Fesoterodine  : CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine.
  •  Flecainide  : May increase the serum concentration of CYP2D6 Substrates.
  •  Flibanserin  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Flibanserin.
  •  Fluoxetine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Fluphenazine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Fluvoxamine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Fosphenytoin  : May decrease the serum concentration of Darunavir.
  •  Gliclazide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Glimepiride  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Gliquidone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Glyburide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Guanfacine  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Guanfacine.
  •  Halofantrine  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine.
  •  Hydrocodone  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Hydrocodone.
  •  Ibrutinib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrutinib.
  •  Idelalisib  : May increase the serum concentration of CYP3A4 Substrates.
  •  Ifosfamide  : CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide.
  •  Iloperidone  : CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone.
  •  Imatinib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imatinib.
  •  Imipramine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Insulin Aspart  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Detemir  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Glargine  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Glulisine  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Lispro  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Regular  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin, isophane  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Irinotecan  : CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
  •  Isavuconazonium  : CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Strong) may increase isavuconazole serum concentrations.
  •  Isoflurophate  : May increase the serum concentration of other Protease Inhibitors.
  •  Itraconazole  : Darunavir may increase the serum concentration of Itraconazole. Itraconazole may increase the serum concentration of Darunavir.
  •  Ivabradine  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine.
  •  Ivacaftor  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivacaftor.
  •  Ixabepilone  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone.
  •  Ketoconazole  : May increase the serum concentration of Ketoconazole (Systemic). Ketoconazole (Systemic) may increase the serum concentration of Darunavir.
  •  Lacosamide  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lacosamide.
  •  Lapatinib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib.
  •  Ledipasvir  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ledipasvir.
  •  Lercanidipine  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lercanidipine.
  •  Levobupivacaine  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine.
  •  Levomilnacipran  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levomilnacipran.
  •  Levonorgestrel  : May decrease the serum concentration of Contraceptives (Progestins).
  •  Linagliptin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Lomitapide  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lomitapide.
  •  Lopinavir  : May decrease the serum concentration of Darunavir. Darunavir may increase the serum concentration of Lopinavir
  •  Lovastatin  : Protease Inhibitors may increase the serum concentration of Lovastatin.
  •  Lovastatin  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin.
  •  Luliconazole  : May increase the serum concentration of CYP3A4 Substrates.
  •  Lumefantrine  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumefantrine.
  •  Lurasidone  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone.
  •  MACITENTAN  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of MACITENTAN.
  •  Maprotiline  : May increase the serum concentration of CYP2D6 Substrates.
  •  Maraviroc  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
  •  Medroxyprogesterone Acetate  : May decrease the serum concentration of Contraceptives (Progestins).
  •  Mestranol  : May decrease the serum concentration of Norethindrone.
  •  Metformin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Methadone  : Darunavir may decrease the serum concentration of Methadone. More specifically, the combination of Darunavir and Ritonavir may decrease Methadone serum concentrations.
  •  Methamphetamine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Methylprednisolone  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Methylprednisolone.
  •  Metoprolol  : May increase the serum concentration of CYP2D6 Substrates.
  •  Mexiletine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Midazolam  : Protease Inhibitors may increase the serum concentration of Midazolam.
  •  Mifepristone  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mifepristone.
  •  Mifepristone  : May increase the serum concentration of CYP3A4 Substrates.
  •  Mitotane  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Naloxegol  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naloxegol.
  •  Nefazodone  : Protease Inhibitors may increase the serum concentration of Nefazodone.
  •  Netupitant  : May increase the serum concentration of CYP3A4 Substrates.
  •  Nevirapine  : Darunavir may increase the serum concentration of Nevirapine. Nevirapine may increase the serum concentration of Darunavir.
  •  Nilotinib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
  •  Nimodipine  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nimodipine.
  •  Nintedanib  : Combined Inhibitors of CYP3A4 and P-glycoprotein may increase the serum concentration of Nintedanib.
  •  Nisoldipine  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine.
  •  Norethindrone  : Darunavir may decrease the serum concentration of Norethindrone.
  •  Norgestimate  : May decrease the serum concentration of Contraceptives (Progestins).
  •  Nortriptyline  : May increase the serum concentration of CYP2D6 Substrates.
  •  Olaparib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Olaparib.
  •  Ospemifene  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ospemifene.
  •  Oxybutynin  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxybutynin.
  •  Oxycodone  : CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of Oxycodone. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxycodone. Serum concentrations of the active metabolite oxymorphone may also be increased.
  •  Palbociclib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palbociclib.
  •  Panobinostat  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Panobinostat.
  •  Parecoxib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of parecoxib.
  •  Paricalcitol  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol.
  •  Paroxetine  : Darunavir may decrease the serum concentration of Paroxetine.
  •  Pazopanib  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Pazopanib.
  •  Perphenazine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Pethidine  : Protease Inhibitors may enhance the adverse/toxic effect of Meperidine. Protease Inhibitors may decrease the serum concentration of Meperidine. Concentrations of the toxic Normeperidine metabolite may be increased.
  •  Phenobarbital  : Darunavir may decrease the serum concentration of Phenobarbital.
  •  Phenytoin  : Darunavir may decrease the serum concentration of Phenytoin.
  •  Pimecrolimus  : CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus.
  •  Pimozide  : Protease Inhibitors may increase the serum concentration of Pimozide.
  •  Pimozide  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimozide.
  •  Ponatinib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ponatinib.
  •  Pranlukast  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pranlukast.
  •  Prasugrel  : CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Prasugrel.
  •  Pravastatin  : Darunavir may increase the serum concentration of Pravastatin. This effect has only been demonstrated with darunavir/ritonavir. The individual contributions of darunavir and ritonavir are unknown.
  •  Prednisone  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Prednisone.
  •  Primaquine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Procainamide  : May increase the serum concentration of CYP2D6 Substrates.
  •  Promazine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Promethazine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Propafenone  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Propafenone.
  •  Propranolol  : May increase the serum concentration of CYP2D6 Substrates.
  •  Protriptyline  : May increase the serum concentration of CYP2D6 Substrates.
  •  Prucalopride  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of prucalopride.
  •  Quetiapine  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Quetiapine.
  •  Quinidine  : Darunavir may increase the serum concentration of Quinidine.
  •  Ramelteon  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ramelteon.
  •  Ranolazine  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine.
  •  Regorafenib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib.
  •  Repaglinide  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Repaglinide.
  •  Retapamulin  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Retapamulin.
  •  Rifabutin  : Darunavir may increase serum concentrations of the active metabolite(s) of Rifabutin. Rifabutin may increase the serum concentration of Darunavir. Darunavir may increase the serum concentration of Rifabutin.
  •  Rifampicin  : May decrease the serum concentration of Darunavir.
  •  Rifapentine  : May decrease the serum concentration of Darunavir.
  •  Rifaximin  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rifaximin.
  •  Rilpivirine  : Darunavir may increase the serum concentration of Rilpivirine.
  •  Riociguat  : Protease Inhibitors may increase the serum concentration of Riociguat.
  •  Risperidone  : May increase the serum concentration of CYP2D6 Substrates.
  •  Rivaroxaban  : Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Rivaroxaban.
  •  Romidepsin  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Romidepsin.
  •  Rosuvastatin  : Protease Inhibitors may increase the serum concentration of Rosuvastatin.
  •  Ruxolitinib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib.
  •  Salmeterol  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol.
  •  Saquinavir  : May decrease the serum concentration of Darunavir.
  •  Saxagliptin  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Saxagliptin.
  •  Sertraline  : Darunavir may decrease the serum concentration of Sertraline.
  •  Sildenafil  : Protease Inhibitors may increase the serum concentration of Sildenafil.
  •  Sildenafil  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sildenafil.
  •  Silodosin  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin.
  •  Silodosin  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin.
  •  Siltuximab  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Simeprevir  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir.
  •  Simeprevir  : Protease Inhibitors may increase the serum concentration of Simeprevir. Simeprevir may increase the serum concentration of Protease Inhibitors.
  •  Simvastatin  : Protease Inhibitors may increase the serum concentration of Simvastatin.
  •  Simvastatin  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simvastatin.
  •  Sonidegib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sonidegib.
  •  Sorafenib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sorafenib.
  •  Stiripentol  : May increase the serum concentration of CYP3A4 Substrates.
  •  Suvorexant  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Suvorexant.
  •  Tadalafil  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tadalafil.
  •  Tamsulosin  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin.
  •  Tasimelteon  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tasimelteon.
  •  Telaprevir  : Darunavir may decrease the serum concentration of Telaprevir. Telaprevir may decrease the serum concentration of Darunavir.
  •  Temsirolimus  : Protease Inhibitors may enhance the adverse/toxic effect of Temsirolimus. Levels of sirolimus, the active metabolite, may be increased, likely due to inhibition of CYP-mediated metabolism.
  •  Tenofovir  : May increase the serum concentration of Darunavir. Darunavir may increase the serum concentration of Tenofovir.
  •  Terfenadine  : Darunavir may increase the serum concentration of Terfenadine.
  •  Tetrabenazine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Thioridazine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Ticagrelor  : CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor.
  •  Timolol  : May increase the serum concentration of CYP2D6 Substrates.
  •  Tipranavir  : May decrease the serum concentration of Protease Inhibitors.
  •  Tocilizumab  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Tofacitinib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tofacitinib.
  •  Tolbutamide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Tolterodine  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolterodine.
  •  Tolvaptan  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan.
  •  Topotecan  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan.
  •  Toremifene  : CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of Toremifene. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene.
  •  Trabectedin  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Trabectedin.
  •  Tramadol  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tramadol.
  •  Trazodone  : Darunavir may increase the serum concentration of Trazodone.
  •  Triazolam  : Protease Inhibitors may increase the serum concentration of Triazolam.
  •  Ulipristal  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ulipristal.
  •  Vardenafil  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vardenafil.
  •  Vemurafenib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vemurafenib.
  •  Vilazodone  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone.
  •  Vildagliptin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Vindesine  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vindesine.
  •  Vorapaxar  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vorapaxar.
  •  Voriconazole  : Darunavir may decrease the serum concentration of Voriconazole.
  •  Vortioxetine  : May increase the serum concentration of CYP2D6 Substrates.
  •  Warfarin  : Darunavir may decrease the serum concentration of Warfarin.
  •  Zidovudine  : Protease Inhibitors may decrease the serum concentration of Zidovudine.
  •  Zopiclone  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zopiclone.
  •  Zuclopenthixol  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zuclopenthixol.

Food Interactions

  • Take with food – better absorption (+30%).

Calculated Property

kind Value Source
logP 1.76 ALOGPS
logS -3.9 ALOGPS
Water Solubility 6.68e-02 g/l ALOGPS
logP 2.82 ChemAxon
IUPAC Name (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)4-aminobenzenesulfonamido]-1-phenylbutan-2-yl]carbamate ChemAxon
Traditional IUPAC Name darunavir ChemAxon
Molecular Weight 547.664 ChemAxon
Monoisotopic Weight 547.235221243 ChemAxon
SMILES [H][C@@]12CCO[C@]1([H])OC[C@@H]2OC(=O)N[C@@H](CC1=CC=CC=C1)[C@H](O)CN(CC(C)C)S(=O)(=O)C1=CC=C(N)C=C1 ChemAxon
Molecular Formula C27H37N3O7S ChemAxon
InChI InChI=1S/C27H37N3O7S/c1-18(2)15-30(38(33,34)21-10-8-20(28)9-11-21)16-24(31)23(14-19-6-4-3-5-7-19)29-27(32)37-25-17-36-26-22(25)12-13-35-26/h3-11,18,22-26,31H,12-17,28H2,1-2H3,(H,29,32)/t22-,23-,24+,25-,26+/m0/s1 ChemAxon
InChIKey InChIKey=CJBJHOAVZSMMDJ-HEXNFIEUSA-N ChemAxon
Polar Surface Area (PSA) 140.42 ChemAxon
Refractivity 142.34 ChemAxon
Polarizability 57.24 ChemAxon
Rotatable Bond Count 11 ChemAxon
H Bond Acceptor Count 7 ChemAxon
H Bond Donor Count 3 ChemAxon
pKa (strongest acidic) 13.59 ChemAxon
pKa (strongest basic) 2.39 ChemAxon
Physiological Charge 0 ChemAxon
Number of Rings 4 ChemAxon
Bioavailability 0 ChemAxon
Rule of Five 0 ChemAxon
Ghose Filter 0 ChemAxon
MDDR-Like Rule 1 ChemAxon

Affected organism

Human Immunodeficiency Virus

Target within organism

  • Protease : in Human immunodeficiency virus 1