Peringatan Keamanan

Reports of overdoses with oseltamivir have been received from clinical trials and during postmarketing experience. In the majority of cases reporting overdose, no adverse reactions were reported. Adverse reactions reported following overdose were similar in nature to those observed with therapeutic doses of oseltamivir.

Oseltamivir

DB00198

small molecule approved

Deskripsi

Oseltamivir (marketed as the product Tamiflu?), is an antiviral neuraminidase inhibitor used for the treatment and prophylaxis of infection with influenza viruses A (including pandemic H1N1) and B. Oseltamivir exerts its antiviral activity by inhibiting the activity of the viral neuraminidase enzyme found on the surface of the virus, which prevents budding from the host cell, viral replication, and infectivity.

The clinical benefit of use of oseltamivir is greatest when administered within 48 hours of the onset of influenza symptoms since effectiveness decreases significantly after that point in time; there is generally no benefit in use beyond 48 hours for healthy, low-risk individuals as influenza is a self-limiting illness.A180574, L7267, A180580 However, antiviral treatment might be beneficial when initiated after 48 hours for patients with severe, complicated or progressive illness or for hospitalized patients.A180583 According to the CDC, data from clinical trials and observational studies have demonstrated that early antiviral treatment can shorten the duration of fever and illness symptoms, and may reduce the risk of some complications (including pneumonia and respiratory failure). They recommend the use of oseltamivir in people with a higher risk of developing complications including children younger than 2 years, people over 65 years, people with some chronic conditions or immunosuppression, pregnant women, residents of long term care facilities, and indigenous communities for example.L7264

The benefits of oseltamivir use are controversial; a 2014 Cochrane Review of the evidence found that oseltamivir treatment had limited benefit. The authors concluded that oseltamivir use in healthy adults had small, non-specific effects on symptoms (where the time to first alleviation of symptoms was only reduced from 7 to 6.3 days), it had no effect on hospitalizations, and that there was no evidence for any reductions in complications of influenza such as pneumonia.A179962, A179965, A179968 Due to the risk of adverse effects such as nausea, vomiting, psychiatric effects and renal adverse events in adults and vomiting in children, the harms are generally considered to outweigh the small clinical benefit of use of oseltamivir.

Notably, in 2017, the World Health Organization downgraded oseltamivir from its essential medicines list from a "core" drug to a "complementary" drug, due to limited cost-effectiveness.A179086 Yearly vaccination with the influenza vaccine is still considered the best preventative measure.

Struktur Molekul 2D

Berat 312.4045
Wujud solid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Plasma concentrations of oseltamivir declined with a half-life of 1 to 3 hours in most subjects after oral administration, although plasma concentrations of oseltamivir carboxylate declined with a half-life of 6 to 10 hours in most subjects after oral administration.[F3094, F3097]
Volume Distribusi The mean volume of distribution at steady state of the oseltamivir carboxylate ranges approximately between 23 and 26 liters in humans, a volume that is roughly equivalent to extracellular body fluid. Since neuraminidase activity is extracellular, oseltamivir carboxylate distributes to all sites of influenza virus spread.[F3094, F3097, L5161, F3115]
Klirens (Clearance) Renal clearance (18.8 l/h) of the drug exceeds glomerular filtration rate (7.5 l/h) indicating that tubular secretion occurs in addition to glomerular filtration.[F3097]

Absorpsi

Oseltamivir is readily absorbed from the gastrointestinal tract after oral administration of oseltamivir phosphate and is extensively converted by predominantly hepatic esterases to the active metabolite oseltamivir carboxylate. At least 75 % of an oral dose reaches the systemic circulation as the active metabolite. Exposure to the pro-drug is less than 5 % relative to the active metabolite. Plasma concentrations of both pro-drug and active metabolite are proportional to dose and are unaffected by co-administration with food.F3094, F3097, L5161, F3115 Pharmacokinetic parameters following twice daily dosing of oseltamivir 75mg capsules are as follows: Cmax of oseltamivir and oseltamivir carboxylate were found to be 65ng/mL and 348ng/mL, respectively, while AUC (0-12h) of oseltamivir and oseltamivir carboxylate were found to be 112ng·h/mL and 2719ng·h/mL, respectively.F3097

Metabolisme

Oseltamivir is extensively converted to the active metabolite, oseltamivir carboxylate, by esterases located predominantly in the liver. Oseltamivir carboxylate is not further metabolized. Neither oseltamivir nor oseltamivir carboxylate is a substrate for, or inhibitor of, cytochrome P450 isoforms. No phase 2 conjugates of either compound have been identified in vivo.F3094, F3097, L5161, F3115

Rute Eliminasi

Following absorption, oseltamivir is more than 90 % eliminated through conversion to oseltamivir carboxylate and subsequent elimination entirely through renal excretion. During clinical studies, less than 20 % of oral radiolabelled dose was found to be eliminated in faeces.F3094, F3097, L5161, F3115

Interaksi Makanan

1 Data
  • 1. Take with or without food. Co-administration with food does not affect pharmacokinetics but may enhance tolerability.

Interaksi Obat

787 Data
Probenecid The serum concentration of the active metabolites of Oseltamivir can be increased when Oseltamivir is used in combination with Probenecid.
Aspartame The excretion of Oseltamivir can be decreased when combined with Aspartame.
Pravastatin The excretion of Oseltamivir can be decreased when combined with Pravastatin.
Valproic acid The excretion of Oseltamivir can be decreased when combined with Valproic acid.
Aminohippuric acid The excretion of Oseltamivir can be decreased when combined with Aminohippuric acid.
Lansoprazole The excretion of Oseltamivir can be decreased when combined with Lansoprazole.
Zidovudine The excretion of Oseltamivir can be decreased when combined with Zidovudine.
Guanidine The excretion of Oseltamivir can be decreased when combined with Guanidine.
Enalapril The excretion of Oseltamivir can be decreased when combined with Enalapril.
Oxytetracycline The excretion of Oseltamivir can be decreased when combined with Oxytetracycline.
Leucovorin The excretion of Oseltamivir can be decreased when combined with Leucovorin.
Esomeprazole The excretion of Oseltamivir can be decreased when combined with Esomeprazole.
Dinoprostone The excretion of Oseltamivir can be decreased when combined with Dinoprostone.
Famotidine The excretion of Oseltamivir can be decreased when combined with Famotidine.
Minocycline The excretion of Oseltamivir can be decreased when combined with Minocycline.
Mercaptopurine The excretion of Oseltamivir can be decreased when combined with Mercaptopurine.
Novobiocin The excretion of Oseltamivir can be decreased when combined with Novobiocin.
Benzylpenicillin The excretion of Oseltamivir can be decreased when combined with Benzylpenicillin.
Melatonin The excretion of Oseltamivir can be decreased when combined with Melatonin.
Ouabain The excretion of Oseltamivir can be decreased when combined with Ouabain.
Rosuvastatin The excretion of Oseltamivir can be decreased when combined with Rosuvastatin.
Liotrix The excretion of Oseltamivir can be decreased when combined with Liotrix.
Cilastatin The excretion of Oseltamivir can be decreased when combined with Cilastatin.
Tazobactam The excretion of Oseltamivir can be decreased when combined with Tazobactam.
trans-2-hydroxycinnamic acid The excretion of Oseltamivir can be decreased when combined with trans-2-hydroxycinnamic acid.
Cholic Acid The excretion of Oseltamivir can be decreased when combined with Cholic Acid.
Glutaric Acid The excretion of Oseltamivir can be decreased when combined with Glutaric Acid.
Benzoic acid The excretion of Oseltamivir can be decreased when combined with Benzoic acid.
Taurocholic acid The excretion of Oseltamivir can be decreased when combined with Taurocholic acid.
Caprylic acid The excretion of Oseltamivir can be decreased when combined with Caprylic acid.
Ataluren The excretion of Oseltamivir can be decreased when combined with Ataluren.
Teriflunomide The excretion of Oseltamivir can be decreased when combined with Teriflunomide.
Dabrafenib The excretion of Oseltamivir can be decreased when combined with Dabrafenib.
Dolutegravir The excretion of Oseltamivir can be decreased when combined with Dolutegravir.
Lenvatinib The excretion of Oseltamivir can be decreased when combined with Lenvatinib.
Cabotegravir The excretion of Oseltamivir can be decreased when combined with Cabotegravir.
Pradigastat The excretion of Oseltamivir can be decreased when combined with Pradigastat.
Enasidenib The excretion of Oseltamivir can be decreased when combined with Enasidenib.
Cefotiam The excretion of Oseltamivir can be decreased when combined with Cefotiam.
Indomethacin The excretion of Oseltamivir can be decreased when combined with Indomethacin.
Cefalotin The excretion of Oseltamivir can be decreased when combined with Cefalotin.
Tenoxicam The excretion of Oseltamivir can be decreased when combined with Tenoxicam.
Cefotaxime The excretion of Oseltamivir can be decreased when combined with Cefotaxime.
Piroxicam The excretion of Oseltamivir can be decreased when combined with Piroxicam.
Methotrexate The excretion of Oseltamivir can be decreased when combined with Methotrexate.
Cephalexin The excretion of Oseltamivir can be decreased when combined with Cephalexin.
Diclofenac The excretion of Oseltamivir can be decreased when combined with Diclofenac.
Acyclovir The excretion of Oseltamivir can be decreased when combined with Acyclovir.
Phenylbutazone The excretion of Oseltamivir can be decreased when combined with Phenylbutazone.
Cefaclor The excretion of Oseltamivir can be decreased when combined with Cefaclor.
Salicylic acid The excretion of Oseltamivir can be decreased when combined with Salicylic acid.
Acetylsalicylic acid The excretion of Oseltamivir can be decreased when combined with Acetylsalicylic acid.
Ketoprofen The excretion of Oseltamivir can be decreased when combined with Ketoprofen.
Ibuprofen The excretion of Oseltamivir can be decreased when combined with Ibuprofen.
Cefadroxil The excretion of Oseltamivir can be decreased when combined with Cefadroxil.
Ceftriaxone The excretion of Oseltamivir can be decreased when combined with Ceftriaxone.
Cefamandole The excretion of Oseltamivir can be decreased when combined with Cefamandole.
Cefazolin The excretion of Oseltamivir can be decreased when combined with Cefazolin.
Cefoperazone The excretion of Oseltamivir can be decreased when combined with Cefoperazone.
Ceftizoxime The excretion of Oseltamivir can be decreased when combined with Ceftizoxime.
Cefacetrile The excretion of Oseltamivir can be decreased when combined with Cefacetrile.
Ceftibuten The excretion of Oseltamivir can be decreased when combined with Ceftibuten.
Cefaloridine The excretion of Oseltamivir can be decreased when combined with Cefaloridine.
Pantoprazole The excretion of Oseltamivir can be decreased when combined with Pantoprazole.
Liothyronine The excretion of Oseltamivir can be decreased when combined with Liothyronine.
Conjugated estrogens The excretion of Oseltamivir can be decreased when combined with Conjugated estrogens.
Cimetidine The excretion of Oseltamivir can be decreased when combined with Cimetidine.
Tetracycline The excretion of Oseltamivir can be decreased when combined with Tetracycline.
Ganciclovir The excretion of Oseltamivir can be decreased when combined with Ganciclovir.
Gemfibrozil The excretion of Oseltamivir can be decreased when combined with Gemfibrozil.
Topiroxostat The excretion of Oseltamivir can be decreased when combined with Topiroxostat.
Baricitinib Oseltamivir may decrease the excretion rate of Baricitinib which could result in a higher serum level.
Apalutamide The excretion of Oseltamivir can be decreased when combined with Apalutamide.
Dronedarone The excretion of Oseltamivir can be decreased when combined with Dronedarone.
Favipiravir The excretion of Oseltamivir can be decreased when combined with Favipiravir.
Tafamidis The excretion of Oseltamivir can be decreased when combined with Tafamidis.
Linezolid The excretion of Oseltamivir can be decreased when combined with Linezolid.
Cyclosporine Cyclosporine may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Icosapent Icosapent may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Mesalazine Mesalazine may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Cefmenoxime Cefmenoxime may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Cefmetazole Cefmetazole may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Pamidronic acid Pamidronic acid may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Tenofovir disoproxil Tenofovir disoproxil may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Cidofovir Cidofovir may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Cefpiramide Cefpiramide may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Ceftazidime Ceftazidime may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Loracarbef Loracarbef may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Nabumetone Nabumetone may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Ketorolac Ketorolac may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Celecoxib Celecoxib may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Tolmetin Tolmetin may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Foscarnet Foscarnet may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Rofecoxib Rofecoxib may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Fenoprofen Fenoprofen may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Valaciclovir Valaciclovir may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Valdecoxib Valdecoxib may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Sulindac Sulindac may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Bacitracin Bacitracin may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Amphotericin B Amphotericin B may decrease the excretion rate of Oseltamivir which could result in a higher serum level.

Target Protein

Neuraminidase NA
Sialidase-1 NEU1
Sialidase-2 NEU2

Referensi & Sumber

Artikel (PubMed)
  • PMID: 15702046
    Chokephaibulkit K, Uiprasertkul M, Puthavathana P, Chearskul P, Auewarakul P, Dowell SF, Vanprapar N: A child with avian influenza A (H5N1) infection. Pediatr Infect Dis J. 2005 Feb;24(2):162-6.
  • PMID: 16371632
    de Jong MD, Tran TT, Truong HK, Vo MH, Smith GJ, Nguyen VC, Bach VC, Phan TQ, Do QH, Guan Y, Peiris JS, Tran TH, Farrar J: Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med. 2005 Dec 22;353(25):2667-72.
  • PMID: 15337401
    Kiso M, Mitamura K, Sakai-Tagawa Y, Shiraishi K, Kawakami C, Kimura K, Hayden FG, Sugaya N, Kawaoka Y: Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet. 2004 Aug 28-Sep 3;364(9436):759-65.
  • PMID: 15709056
    Ward P, Small I, Smith J, Suter P, Dutkowski R: Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. J Antimicrob Chemother. 2005 Feb;55 Suppl 1:i5-i21.
  • PMID: 12791735
    Cooper NJ, Sutton AJ, Abrams KR, Wailoo A, Turner D, Nicholson KG: Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials. BMJ. 2003 Jun 7;326(7401):1235. doi: 10.1136/bmj.326.7401.1235.
  • PMID: 28607038
    Kmietowicz Z: WHO downgrades oseltamivir on drugs list after reviewing evidence. BMJ. 2017 Jun 12;357:j2841. doi: 10.1136/bmj.j2841.
  • PMID: 24718923
    Jefferson T, Jones MA, Doshi P, Del Mar CB, Hama R, Thompson MJ, Spencer EA, Onakpoya I, Mahtani KR, Nunan D, Howick J, Heneghan CJ: Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Cochrane Database Syst Rev. 2014 Apr 10;(4):CD008965. doi: 10.1002/14651858.CD008965.pub4.
  • PMID: 23565231
    Michiels B, Van Puyenbroeck K, Verhoeven V, Vermeire E, Coenen S: The value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews. PLoS One. 2013;8(4):e60348. doi: 10.1371/journal.pone.0060348. Epub 2013 Apr 2.
Menampilkan 8 dari 14 artikel.

Contoh Produk & Brand

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International Brands
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