oseltamivir (Tamiflu)
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Introduction
1st generic approved Aug 2016[23]
Indications
- influenza*
- treatment of influenza A & influenza B
- prophylaxis for influenza A & influenza B[4]
- for use (start of therapy) within 2 days of symptom onset
- marginal benefit in prevention & treatment of influenza[19]
- older, sicker patients with flu-like syndrome may benefit from oseltamivir with or without confirmed influenza infection[25]
* shortens duration of influenza symptoms (4 vs 5 days)[20]
* lowers risk of hospitalization (0.6 vs 1.7%)[20]
* oseltamivir is not associated with a reduced risk of hospitalization but is associated with increased GI events[26]
Contraindications
- do NOT use in infants < 2 weeks of age[4]
- resistance to influenza A-H1N1 (2008-2009) has been reported; monotherapy not recommended; use with rimantidine[8]
Benefit/risk
- small benefit for preventing influenza-like illness[19]
- no benefit for reducing transmission[19]
- number needed to harm
Dosage
- dosed in mg NOT mL; potential dosage errors may occur[9]
- 75 mg PO BID for 5 days (QD dosing for prevention)
- start therapy within 48 hours* of onset
- more effective if started within 12 hours* of onset[3]
- take with food to reduce nausea
- prophylaxis:
- 2 weeks until IgG antibodies from influenza vaccine appear[14]
- otherwise, 4-6 weeks
* if started within 12 hours of symptom onset, can reduce duration of symptoms by more than 3 days; NO benefit to therapy begun after 48 hours
Capsule: 75 mg
Suspension: Tamiflu suspension 12 mg/mL for children:
- 30-75 mg BID for 5 days (depending upon weight)
- new formulation (2011) 6 mg/mL to reduce froth when shaken[13]
- generic oral suspension FDA-approved Sept 2017[24]
Dosage adjustment in renal failure
Table
| creatinine clearance | dosage |
|---|---|
| > 50-90 mL/min | 75 mg every 12 hours |
| 10-50 mL/min | 75 mg every 24 hours |
| < 10 mL/min | no data (avoid) |
Pharmacokinetics
- metabolized in liver
- eliminated in urine, tubular secretion[12]
- elimination 1/2life 1-3 hours
Adverse effects
- GI effects (9%); nausea, vomiting
- reports of delirium & self-injury[7] hallicunations, fatal injury[8] most cases occur in setting of encephalopathy or encephalitis[8]
Drug interactions
- probenecid increases levels of oseltamivir[12]
Mechanism of action
- neuraminidase inhibitors
- reduces severity & duration of flu symptoms[22]
- resistance of influenza A is emerging[5]
- contains shikimic acid[6]
- effective if administered early[17]
Notes
- oseltamivir & zanamivir are modestly effective for symptoms of influenza in otherwise healthy adults
- when used prophylactically, they have no effect against in preventing influenza-like illness or asymptomatic influenza
- the drugs reduce influenza's symptoms by about a day
- benefit for very ill people in hospital is without supporting data[11]
- benefit in question[16]
More general terms
Additional terms
References
- ↑ The Prescriber's Letter, vol 6 #11, Nov 1999
- ↑ Journal Watch, Mass Med Soc 19(23):182 (Dec) 1999
- ↑ 3.0 3.1 Prescriber's Letter 7(10):57 2000
- ↑ 4.0 4.1 4.2 Prescriber's Letter 11(1):1 2004 Journal Watch 24(6):45-46, 2004 Hayden FG et al, J Infect Dis 189:440, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14745701
- ↑ 5.0 5.1 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;364(9436):759-65. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15337401
Moscona A. Oseltamivir-resistant influenza? Lancet. 2004 Aug 28;364(9436):733-4. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15337382 - ↑ 6.0 6.1 Prescriber's Letter 13(1): 2006 FDA alerts to Protect Public form Fraudelent Avian Flu Therapies Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220113&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 7.0 7.1 FDA Medwatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#tamiflu http://www.fda.gov/medwatch/safety/2006/safety06.htm#tamiflu
Prescriber's Letter 13(12): 2006 Tamiflu (Oseltamir) Pediatric Adverse Effects Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=221203&pb=PRL (subscription needed) http://www.prescribersletter.com - ↑ 8.0 8.1 8.2 8.3 Prescriber's Letter 16(2): 2009 CDC's Interim Influenza Antiviral Guidance for 2008-09 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250201&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 9.0 9.1 FDA MedWatch Tamiflu (oseltamivir) for Oral Suspension: Potential Medication Errors http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm183714.htm
- ↑ Prescriber's Letter 16(11): 2009 CHART: Tamiflu Expiration Date Extension COMMENTARY: Potential Medication Errors with Tamiflu Oral Suspension COMMENTARY: 2009-2010 Influenza Season: Issues Concerning Tamiflu and Relenza PDF: Tamiflu Emergency Compounding Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=251104&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 11.0 11.1 Jefferson T et al Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis BMJ 2009;339:b5106 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19995812 <Internet> http://www.bmj.com/cgi/content/full/339/dec07_2/b5106 http://dx.doi.org/10.1136/bmj.b5106
Freemantle N and Calvert M. What can we learn from observational studies of oseltamivir to treat influenza in healthy adults? BMJ 2009 Dec 8; 339:b5248. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19995814 <Internet> http://dx.doi.org/10.1136/bmj.b5248
Doshi P. Neuraminidase inhibitors - The story behind the Cochrane review. BMJ 2009 Dec 8; 339:b5164. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19995813 <Internet> http://dx.doi.org/10.1136/bmj.b5164
Godlee F and Clarke M. Why don't we have all the evidence on oseltamivir? BMJ 2009 Dec 8; 339:b5351. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19995815 <Internet> http://dx.doi.org/10.1136/bmj.b5351
Smith J. Roche replies to the authors of the Cochrane review on oseltamivir. BMJ 2009 Dec 8; 339:b5364. http://dx.doi.org/10.1136/bmj.b5364
Smith J. Point-by-point response from Roche to BMJ questions. BMJ 2009 Dec 8; 339:b5374. http://dx.doi.org/10.1136/bmj.b5374 - ↑ 12.0 12.1 12.2 Medical Knowledge Self Assessment Program (MKSAP) 15, American College of Physicians, Philadelphia 2009
- ↑ 13.0 13.1 FDA MedWatch 07/11/2011 Tamiflu (oseltamivir phosphate) for Oral Suspension: Label Change-New Concentration (6 mg/mL) http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm262432.htm
- ↑ 14.0 14.1 Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
- ↑ FDA News Release: Dec. 21, 2012 FDA expands Tamiflu's use to treat children younger than 1 year. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333205.htm
- ↑ 16.0 16.1 Krumholz HM et al Tamiflu: 14 flu seasons and still questions BMJ 2013;346:f547 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23355545 <Internet> http://www.bmj.com/content/346/bmj.f547
- ↑ 17.0 17.1 Muthuri SG et al. Impact of neuraminidase inhibitor treatment on outcomes of public health importance during the 2009-2010 influenza A (H1N1) pandemic: A systematic review and metaanalysis in hospitalized patients. J Infect Dis 2013 Feb 15; 207:553. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23204175
Aoki FY and Hayden FG. The beneficial effects of neuraminidase inhibitor drug therapy on severe patient outcomes during the 2009-2010 influenza A virus subtype H1N1 pandemic. J Infect Dis 2013 Feb 15; 207:547. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23204176 - ↑ 18.0 18.1 South East Asia Infectious Disease Clinical Research Network Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial. BMJ 2013;346:f3039 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23723457 <Internet> http://www.bmj.com/content/346/bmj.f3039
- ↑ 19.0 19.1 19.2 19.3 Jefferson T et al Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ 2014;348:g2545 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24811411 <Internet> http://www.bmj.com/content/348/bmj.g2545
Loder E et al The Tamiflu trials. BMJ 2014;348:g2630 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24811414 <Internet> http://www.bmj.com/content/348/bmj.g2630
Krumholz HM and Hines HH Neuraminidase inhibitors for influenza BMJ 2014;348:g2548 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24811413 <Internet> http://www.bmj.com/content/348/bmj.g2548 - ↑ 20.0 20.1 20.2 Dobson J et al Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet. Jan 29, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25640810 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2962449-1/abstract
- ↑ 21.0 21.1 The NNT: Neuraminidase Inhibitors Given for Influenza. http://www.thennt.com/nnt/neuraminidase-inhibitors-for-influenza/
- ↑ 22.0 22.1 22.2 Cheung DH et al. Association of oseltamivir treatment with virus shedding, illness, and household transmission of influenza viruses. J Infect Dis 2015 Aug 1; 212:391 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25646354 <Internet> http://jid.oxfordjournals.org/content/212/3/391
- ↑ 23.0 23.1 FDA Postmarker Drug Safety Information. Aug 3, 2016 The FDA approves first generic version of widely used influenza drug, Tamiflu. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm514854.htm
- ↑ 24.0 24.1 Brooks M FDA Clears First Generic Tamiflu for Oral Suspension. Medscape - Sep 15, 2017. http://www.medscape.com/viewarticle/885766
- ↑ 25.0 25.1 Butler CC, van der Velden AW, Bongard E et al. Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: An open-label, pragmatic, randomised controlled trial. Lancet 2020 Jan 4; 395:42 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31839279
- ↑ 26.0 26.1 Hanula R et al. Evaluation of oseltamivir used to prevent hospitalization in outpatients with influenza: A systematic review and meta-analysis. JAMA Intern Med 2023 Jun 12; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/37306992 PMCID: PMC10262060 Free PMC article https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2805976
- ↑ Tamiflu Prescribing Information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021087s068,021246s051lbl.pdf
Patient information
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