Peringatan Keamanan

Human experience of acute overdose with ritonavir is limited. One patient in clinical trials took ritonavir 1500 mg/day for two days. The patient reported paresthesias which resolved after the dose was decreased. A post-marketing case of renal failure with eosinophilia has been reported with ritonavir overdose. The approximate lethal dose was found to be greater than 20 times the related human dose in rats and 10 times the related human dose in mice. Oral LD value in rats is >2500 mg/kg. Adverse effects of ritonavir may arise from drug-drug interactions. Other effects include hepatotoxicity, pancreatitis, and allergic reactions/hypersensitivity.

Ritonavir

DB00503

small molecule approved investigational

Deskripsi

Ritonavir is an HIV protease inhibitor that interferes with the reproductive cycle of HIV. Although it was initially developed as an independent antiviral agent, it has been shown to possess advantageous properties in combination regimens with low-dose ritonavir and other protease inhibitors. It is now more commonly used as a booster of other protease inhibitors and is available in both liquid formulations and as capsules.

While ritonavir is not an active antiviral agent against hepatitis C virus (HCV) infection, it is added in combination therapies indicated for the treatment of HCV infections as a booster. Ritonavir is a potent CYP3A inhibitor that increases peak and trough plasma drug concentrations of other protease inhibitors such as DB09297 and overall drug exposure. American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) guidelines recommend ritonavir-boosted combination therapies as first-line therapy for HCV Genotype 1a/b and 4 treatment-naïve patients with or without cirrhosis.

Ritonavir is found in a fixed-dose combination product with DB09296, DB09183, and DB09297 as the FDA-approved product Viekira Pak. First approved in December 2014, Viekira Pak is indicated for the treatment of HCV genotype 1b without cirrhosis or with compensated cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a without cirrhosis or with compensated cirrhosis.

Ritonavir is also available as a fixed-dose combination product with DB09296 and DB09297 as the FDA- and Health Canada-approved product Technivie. First approved in July 2015, Technivie is indicated in combination with Ribavirin for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis.

In Canada, ritonavir is also available as a fixed-dose combination product with DB09296, DB09183, and DB09297 as the Health Canada-approved, commercially available product Holkira Pak. First approved in January 2015, Holkira Pak is indicated for the treatment of HCV genotype 1b with or without cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a with or without cirrhosis. The inclusion of ritonavir can select for HIV-1 protease inhibitor resistance-associated substitutions. Any HCV/HIV-1 co-infected patients treated with ritonavir-containing combination therapies should also be on a suppressive antiretroviral drug regimen to reduce the risk of HIV-1 protease inhibitor drug resistance.

Ritonavir is combined with other drugs to treat coronavirus disease 2019 (COVID-19) in patients at risk for progressing into a severe form of the disease, such as nirmatrelvir.L40094

Struktur Molekul 2D

Berat 720.944
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The approximate half-life of ritonavir is 3-5 hours.[L3513]
Volume Distribusi The estimated volume of distribution of ritonavir is 0.41 ± 0.25 L/kg.[L3513]
Klirens (Clearance) The apparent oral clearance at steady-state is 8.8 ± 3.2 L/h.[L3513] Renal clearance is minimal and estimated to be <0.1 L/h.[L3513]

Absorpsi

The absolute bioavailability of ritonavir has not been determined.L3513 Following oral administration, peak concentrations are reached after approximately 2 hours and 4 hours (Tmax) after dosing under fasting and non-fasting conditions, respectively.L3513 It should be noted that ritonavir capsules and tablets are not considered bioequivalent.L3513

Metabolisme

Ritonavir circulates in the plasma predominantly as unchanged drug. Five metabolites have been identified.L3513 The isopropylthiazole oxidation metabolite (M-2) is the major metabolite in low plasma concentrations and retains similar antiviral activity to unchanged ritonavir. The cytochrome P450 enzymes CYP3A and CYP2D6 are the enzymes primarily involved in the metabolism of ritonavir.L3513

Rute Eliminasi

Ritonavir is primarily eliminated in the feces.L3513 Following oral administration of a single 600mg dose of radiolabeled ritonavir, approximately 11.3 ± 2.8% of the dose was excreted into the urine, of which 3.5 ± 1.8% was unchanged parent drug.L3513 The same study found that 86.4 ± 2.9% of the dose was excreted in the feces, of which 33.8 ± 10.8% was unchanged parent drug.L3513

Interaksi Makanan

1 Data
  • 1. Avoid St. John's Wort. Co-administration may reduce serum concentrations of ritonavir and interfere with virologic efficacy.

Interaksi Obat

1551 Data
Afatinib The serum concentration of Afatinib can be increased when it is combined with Ritonavir.
Bosutinib The serum concentration of Bosutinib can be increased when it is combined with Ritonavir.
Reserpine Reserpine may decrease the excretion rate of Ritonavir which could result in a higher serum level.
Ursodeoxycholic acid Ursodeoxycholic acid may decrease the excretion rate of Ritonavir which could result in a higher serum level.
Cholic Acid Cholic Acid may decrease the excretion rate of Ritonavir which could result in a higher serum level.
Valinomycin Valinomycin may decrease the excretion rate of Ritonavir which could result in a higher serum level.
Olmesartan Olmesartan may decrease the excretion rate of Ritonavir which could result in a higher serum level.
Edoxaban The serum concentration of Edoxaban can be increased when it is combined with Ritonavir.
Ledipasvir The serum concentration of Ledipasvir can be increased when it is combined with Ritonavir.
Naloxegol The serum concentration of Naloxegol can be increased when it is combined with Ritonavir.
Pazopanib The serum concentration of Pazopanib can be increased when it is combined with Ritonavir.
Prucalopride The serum concentration of Prucalopride can be increased when it is combined with Ritonavir.
Cyclosporine The serum concentration of Cyclosporine can be increased when it is combined with Ritonavir.
Silodosin The excretion of Silodosin can be decreased when combined with Ritonavir.
Topotecan The serum concentration of Topotecan can be increased when it is combined with Ritonavir.
Cilostazol The serum concentration of Cilostazol can be increased when it is combined with Ritonavir.
Eliglustat The metabolism of Eliglustat can be decreased when combined with Ritonavir.
Rifaximin The serum concentration of Rifaximin can be increased when it is combined with Ritonavir.
Abacavir The serum concentration of Abacavir can be decreased when it is combined with Ritonavir.
Cisapride The serum concentration of Cisapride can be increased when it is combined with Ritonavir.
Clarithromycin The serum concentration of Clarithromycin can be increased when it is combined with Ritonavir.
Cyclophosphamide The serum concentration of the active metabolites of Cyclophosphamide can be increased when Cyclophosphamide is used in combination with Ritonavir.
Enfuvirtide The serum concentration of Enfuvirtide can be increased when it is combined with Ritonavir.
Fentanyl The metabolism of Fentanyl can be decreased when combined with Ritonavir.
Iloperidone The metabolism of Iloperidone can be decreased when combined with Ritonavir.
Retapamulin The metabolism of Retapamulin can be decreased when combined with Ritonavir.
Tofacitinib The metabolism of Tofacitinib can be decreased when combined with Ritonavir.
Phenytoin The serum concentration of Ritonavir can be decreased when it is combined with Phenytoin.
Fosphenytoin The serum concentration of Ritonavir can be decreased when it is combined with Fosphenytoin.
Methadone The serum concentration of Methadone can be decreased when it is combined with Ritonavir.
Alprazolam The serum concentration of Alprazolam can be increased when it is combined with Ritonavir.
Atomoxetine The metabolism of Atomoxetine can be decreased when combined with Ritonavir.
Amiodarone The metabolism of Amiodarone can be decreased when combined with Ritonavir.
Aripiprazole The metabolism of Aripiprazole can be decreased when combined with Ritonavir.
Aripiprazole lauroxil The metabolism of Aripiprazole lauroxil can be decreased when combined with Ritonavir.
Atovaquone The serum concentration of Atovaquone can be decreased when it is combined with Ritonavir.
Boceprevir The serum concentration of Boceprevir can be decreased when it is combined with Ritonavir.
Bosentan The serum concentration of Bosentan can be increased when it is combined with Ritonavir.
Bupropion The metabolism of Bupropion can be increased when combined with Ritonavir.
Deferasirox The metabolism of Deferasirox can be increased when combined with Ritonavir.
Disulfiram The risk or severity of adverse effects can be increased when Ritonavir is combined with Disulfiram.
Efavirenz The risk or severity of adverse effects can be increased when Efavirenz is combined with Ritonavir.
Enzalutamide The serum concentration of Enzalutamide can be increased when it is combined with Ritonavir.
Etravirine The serum concentration of Etravirine can be decreased when it is combined with Ritonavir.
Itraconazole The serum concentration of Itraconazole can be increased when it is combined with Ritonavir.
Lamotrigine The serum concentration of Lamotrigine can be decreased when it is combined with Ritonavir.
Pioglitazone The serum concentration of Pioglitazone can be increased when it is combined with Ritonavir.
Proguanil The serum concentration of Proguanil can be decreased when it is combined with Ritonavir.
Quetiapine The serum concentration of Quetiapine can be increased when it is combined with Ritonavir.
Rifabutin The serum concentration of the active metabolites of Rifabutin can be increased when Rifabutin is used in combination with Ritonavir.
Telaprevir The serum concentration of Telaprevir can be decreased when it is combined with Ritonavir.
Treprostinil The serum concentration of Treprostinil can be increased when it is combined with Ritonavir.
Vinblastine The serum concentration of Vinblastine can be increased when it is combined with Ritonavir.
Vincristine The serum concentration of Vincristine can be increased when it is combined with Ritonavir.
Voriconazole The serum concentration of Voriconazole can be decreased when it is combined with Ritonavir.
Warfarin The serum concentration of Warfarin can be decreased when it is combined with Ritonavir.
Acenocoumarol The serum concentration of Acenocoumarol can be decreased when it is combined with Ritonavir.
(R)-warfarin The serum concentration of (R)-warfarin can be decreased when it is combined with Ritonavir.
R,S-Warfarin alcohol The serum concentration of R,S-Warfarin alcohol can be decreased when it is combined with Ritonavir.
S,R-Warfarin alcohol The serum concentration of S,R-Warfarin alcohol can be decreased when it is combined with Ritonavir.
(S)-Warfarin The serum concentration of (S)-Warfarin can be decreased when it is combined with Ritonavir.
Liothyronine The metabolism of Liothyronine can be increased when combined with Ritonavir.
Indomethacin The metabolism of Indomethacin can be increased when combined with Ritonavir.
Minoxidil The metabolism of Minoxidil can be increased when combined with Ritonavir.
Furosemide The metabolism of Furosemide can be increased when combined with Ritonavir.
Naltrexone The metabolism of Naltrexone can be increased when combined with Ritonavir.
Flurbiprofen The metabolism of Flurbiprofen can be increased when combined with Ritonavir.
Ezetimibe The metabolism of Ezetimibe can be increased when combined with Ritonavir.
Ketoprofen The metabolism of Ketoprofen can be increased when combined with Ritonavir.
Alvocidib The metabolism of Alvocidib can be increased when combined with Ritonavir.
Ezogabine The metabolism of Ezogabine can be increased when combined with Ritonavir.
Bazedoxifene The metabolism of Bazedoxifene can be increased when combined with Ritonavir.
Gavestinel The metabolism of Gavestinel can be increased when combined with Ritonavir.
Raltegravir The metabolism of Raltegravir can be increased when combined with Ritonavir.
Dolutegravir The metabolism of Dolutegravir can be increased when combined with Ritonavir.
Eslicarbazepine acetate The metabolism of Eslicarbazepine acetate can be increased when combined with Ritonavir.
Delafloxacin The metabolism of Delafloxacin can be increased when combined with Ritonavir.
Eslicarbazepine The metabolism of Eslicarbazepine can be increased when combined with Ritonavir.
Fulvestrant The metabolism of Fulvestrant can be increased when combined with Ritonavir.
Glipizide The metabolism of Glipizide can be increased when combined with Ritonavir.
Cabotegravir The metabolism of Cabotegravir can be increased when combined with Ritonavir.
Tacrolimus The serum concentration of Tacrolimus can be increased when it is combined with Ritonavir.
Metronidazole The risk or severity of adverse effects can be increased when Ritonavir is combined with Metronidazole.
Ketoconazole The bioavailability of Ketoconazole can be increased when combined with Ritonavir.
Rifampin The serum concentration of Ritonavir can be decreased when it is combined with Rifampicin.
Atorvastatin The metabolism of Atorvastatin can be decreased when combined with Ritonavir.
Mirabegron The serum concentration of Ritonavir can be increased when it is combined with Mirabegron.
Eluxadoline The serum concentration of Eluxadoline can be increased when it is combined with Ritonavir.
Garlic Garlic can cause a decrease in the absorption of Ritonavir resulting in a reduced serum concentration and potentially a decrease in efficacy.
Insulin human The therapeutic efficacy of Insulin human can be decreased when used in combination with Ritonavir.
Insulin lispro The therapeutic efficacy of Insulin lispro can be decreased when used in combination with Ritonavir.
Insulin glargine The therapeutic efficacy of Insulin glargine can be decreased when used in combination with Ritonavir.
Insulin pork The therapeutic efficacy of Insulin pork can be decreased when used in combination with Ritonavir.
Glimepiride The therapeutic efficacy of Glimepiride can be decreased when used in combination with Ritonavir.
Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Ritonavir.
Acetohexamide The therapeutic efficacy of Acetohexamide can be decreased when used in combination with Ritonavir.
Miglitol The therapeutic efficacy of Miglitol can be decreased when used in combination with Ritonavir.
Chlorpropamide The therapeutic efficacy of Chlorpropamide can be decreased when used in combination with Ritonavir.
Tolazamide The therapeutic efficacy of Tolazamide can be decreased when used in combination with Ritonavir.
Sulfamethoxazole The therapeutic efficacy of Sulfamethoxazole can be decreased when used in combination with Ritonavir.

Target Protein

Gag-Pol polyprotein gag-pol
Pol polyprotein pol
Nuclear receptor subfamily 1 group I member 2 NR1I2

Referensi & Sumber

Artikel (PubMed)
  • PMID: 21501034
    Hull MW, Montaner JS: Ritonavir-boosted protease inhibitors in HIV therapy. Ann Med. 2011 Aug;43(5):375-88. doi: 10.3109/07853890.2011.572905. Epub 2011 Apr 18.
  • PMID: 25585348
    Myers RP, Shah H, Burak KW, Cooper C, Feld JJ: An update on the management of chronic hepatitis C: 2015 Consensus guidelines from the Canadian Association for the Study of the Liver. Can J Gastroenterol Hepatol. 2015 Jan-Feb;29(1):19-34. Epub 2015 Jan 13.
  • PMID: 20937904
    Sevrioukova IF, Poulos TL: Structure and mechanism of the complex between cytochrome P4503A4 and ritonavir. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18422-7. doi: 10.1073/pnas.1010693107. Epub 2010 Oct 11.
  • PMID: 25274602
    Rock BM, Hengel SM, Rock DA, Wienkers LC, Kunze KL: Characterization of ritonavir-mediated inactivation of cytochrome P450 3A4. Mol Pharmacol. 2014 Dec;86(6):665-74. doi: 10.1124/mol.114.094862. Epub 2014 Oct 1.
  • PMID: 28627229
    Tseng A, Hughes CA, Wu J, Seet J, Phillips EJ: Cobicistat Versus Ritonavir: Similar Pharmacokinetic Enhancers But Some Important Differences. Ann Pharmacother. 2017 Nov;51(11):1008-1022. doi: 10.1177/1060028017717018. Epub 2017 Jun 19.

Contoh Produk & Brand

Produk: 107 • International brands: 3
Produk
  • Auro-ritonavir
    Tablet • 100 mg • Oral • Canada • Generic • Approved
  • Holkira Pak
    Kit; Tablet • - • Oral • Canada • Approved
  • Kaletra
    Tablet, film coated • - • Oral • US • Approved
  • Kaletra
    Tablet, film coated • - • Oral • US • Approved
  • Kaletra
    Tablet, film coated • - • Oral • US • Approved
  • Kaletra
    Tablet, film coated • - • Oral • US • Approved
  • Kaletra
    Tablet, film coated • - • Oral • US • Approved
  • Kaletra
    Tablet • - • Oral • US
Menampilkan 8 dari 107 produk.
International Brands
  • Busvir — Conifarma
  • Empetus — Emcure
  • Normune — Grey Inversiones

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
© 2025 Digital Pharmacy Research - Universitas Esa Unggul