Table of Contents  
Year : 2011  |  Volume : 2  |  Issue : 2  |  Page : 100-103  

Adverse drug reaction profile of oseltamivir in children

1 Department of Pharmacology, MP Shah Medical College, Jamnagar 361 008, Gujarat, India
2 Department of Pediatrics, MP Shah Medical College, Jamnagar 361 008, Gujarat, India

Date of Web Publication6-Jun-2011

Correspondence Address:
Prashant S Dalvi
Department of Pharmacology, M.P. Shah Medical College, Jamnagar 361 008, Gujarat
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0976-500X.81901

Rights and Permissions

Aim: To monitor and evaluate the pattern of ADRs to oseltamivir in pediatric population suffering from H1N1 influenza at a tertiary care hospital. Materials and Methods: Children offered oseltamivir for treatment and chemoprophylaxis were monitored for adverse events by direct questioning for symptoms and clinical examination on day 5 and day 10. Assessment of neurological events was done by asking the parents or guardians regarding development of specific symptoms. Adverse events obtained were analyzed for severity, causality and age-group wise. Results: Out of 191 children (median age, 3 years), 69 (36.1%) developed ADRs. Most common symptoms were vomiting (16.2%) followed by diarrhea (12.0%), ear disorders (8.9%), and insomnia (6.8%). The incidence of neuropsychiatric symptoms was 12.6% which were mild-to-moderate on severity scale. There was no significant difference in the incidence of adverse events between children less than 1 year and other age groups. Conclusion: Oseltamivir is well tolerated in Indian children with suspected or confirmed H1N1 influenza. Our study also indicates safety of oseltamivir in infants.

Keywords: Adverse drug reactions, antiviral agent, child, infant, oseltamivir

How to cite this article:
Dalvi PS, Singh A, Trivedi HR, Mistry SD, Vyas BR. Adverse drug reaction profile of oseltamivir in children. J Pharmacol Pharmacother 2011;2:100-3

How to cite this URL:
Dalvi PS, Singh A, Trivedi HR, Mistry SD, Vyas BR. Adverse drug reaction profile of oseltamivir in children. J Pharmacol Pharmacother [serial online] 2011 [cited 2022 Jan 25];2:100-3. Available from:

   Introduction Top

Monitoring and documentation of adverse drug reactions (ADR) encourage safe use of drugs by ensuring benefits outweighs the risks that may be associated with use of drugs. For newer drugs, available safety data is mainly from clinical trials, conditions of which differ from actual clinical use. [1],[2] In pediatric population, ADRs are responsible for significant morbidity and deaths. Since, clinical trials involving neonates, infants, children, and adolescents are limited, the safety and tolerability of newer drugs are not established until they are used in large number of patients in postmarketing phase. [3],[4],[5]

Oseltamivir is an ethyl ester prodrug indicated for treatment and prevention of infections due to influenza A and B virus. It inhibits viral neuraminidase, blocking its ability to cleave sialic acid residues on the surface of infected cells and to release progeny virions. [6] Recent pandemic of swine flu (H1N1) in India resulted in significant morbidity in children and adolescents. Oseltamivir is the mainstay in treatment and chemoprophylaxis of swine-origin influenza A. Oseltamivir is generally well tolerated, adverse effects in adults being gastrointestinal disturbances, headache, insomnia, vertigo, bronchitis and hypersensitivity reactions. [7] Information regarding the safety profile of oseltamivir in pediatric population is limited, especially in Indian population. Acute onset of neuropsychiatric manifestations and sudden deaths have been reported mainly in children and adolescents in Japan. [8],[9] Concerns were also raised regarding safety of oseltamivir in infants under 1 year of age. [10] The use of oseltamivir in infants is based on the emergency use authorization granted by United States - Food and drug administration (US-FDA). Our study was designed to investigate the ADR profile of oseltamivir in pediatric population in a tertiary care hospital.

   Materials and Methods Top

This was a prospective study carried out among patients of pediatric age group visiting the swine flu Outpatient Department of a tertiary care hospital. The study was carried out over 3 months from January to March 2010. Ethical Clearance was obtained from the Institutional Ethics Committee prior to initiation of study.

The study included children of age less than 12 years of either gender who were offered oseltamivir as treatment and chemoprophylaxis. Patients with significant gastrointestinal and/or neurological disorders and critically ill patients receiving oseltamivir were excluded from the study. Informed consent was obtained from parents/legally acceptable representatives of the children for participating in the study. Data regarding age, sex, presenting complaints, indication for oseltamivir, and concomitant drug therapy were obtained from the patients. No changes in treatment decision, dose or duration were made as a part of study. The recommended dose of oseltamivir (on basis of weight and age) is to be taken twice a day for 5 days as treatment and once a day for 10 days as prophylaxis. The children were followed up for adverse events for a period of 10 days after receiving first dose of oseltamivir. The parents or guardians of children were asked to note development of new symptoms or worsening of existing symptoms in children and to report it to the hospital if necessary during the study period. Monitoring for adverse events to oseltamivir was done by direct questioning for symptoms and clinical examination on day 5 and day 10. Assessment of neurological adverse events included questions to parents or guardians and children (>5 years) regarding development of symptoms of unconsciousness, dizziness, seizures, involuntary movements, headache, irritability, hyperactivity, aggressive behavior, hallucinations (>5 years), vision or hearing problems, and sleeping disturbances during the study period. Parents were also encouraged to report such symptoms developed after the study period and within 30 days of receiving first dose of oseltamivir. Causality of ADRs was assessed using Naranjo's algorithm and the severity of ADRs was assessed using modified Hartwig and Seigel scale.

   Results Top

One-hundred ninety one children were included in the study group with age range from 2 months to 11 years [Table 1]. One-hundred seventy two children completed full course of 10 doses of oseltamivir. One-hundred forty six adverse events were documented in 69 children (36.1%). Most frequently reported symptoms were vomiting followed by diarrhea, ear disorders, and insomnia [Table 2]. Incidence of adverse outcomes did not differ significantly in age groups less than 1 year, 1 year, 1 - 4 years and 5 - 12 years [Table 3]. Severity was assessed using modified Hartwig and Seigel criteria with 113 ADRs categorized as mild and 33 categorized as moderate grade. All the ADRs belonged to possible and probable category according to Naranjo's Algorithm.
Table 1: Preliminary data of children receiving oseltamivir (n = 191)

Click here to view
Table 2: Suspected ADRs in children receiving oseltamivir

Click here to view
Table 3: Age-group wise distribution of ADRs

Click here to view

   Discussion Top

Oseltamivir is indicated in treatment and prophylaxis of influenza A and B in adults and children. Previously healthy children between the ages of 1 and 12 years with laboratory diagnosis of influenza showed a reduction of 36 h in the median duration of illness after treatment with oseltamivir. [11],[12] Prophylaxis with oseltamivir provided protective efficacy of 80% in pediatric population. [11] In our study, oseltamivir was administered according to the guidelines issued by the Directorate General of Health Services (DGHS), Ministry of Health and Family Welfare (MOHFW), India which did not require laboratory diagnosis of influenza for administration of oseltamivir for treatment. [13] In phase III trials of oseltamivir involving patients aged 1-12 years, the most frequently reported adverse event was vomiting (15%) followed by diarrhea (9.5%), otitis media (8.7%), and abdominal pain (4.7%). Others included nausea, epistaxis, pneumonia, sinusitis, bronchitis, conjunctivitis, dermatitis, and lymphadenopathy. [7] Rare adverse events reported from postmarketing surveillance include serious skin hypersensitivity reactions, cardiac arrhythmias, and neuropsychiatric episodes. The most common ADRs to oseltamivir in our study were gastrointestinal ADRs like vomiting and diarrhea, the incidences of which were comparable to that of published literature. [11],[14] Though none of the gastrointestinal adverse event required discontinuation of oseltamivir, few required treatment in form of antiemetics and rehydration therapy.

Neuropsychiatric manifestations including deaths have been reported in children and adolescents less than 17 years of age mainly from Japan. These included delirium with prominent behavioral disturbances, suicidal events, panic attacks, delusions and disturbances in consciousness. [8],[9] Most of the symptoms had temporal relationship to that of oseltamivir intake and had onset within one day. The neuropsychiatric events were probably related to central depressant effect of oseltamivir. [15] A review of available information on safety of oseltamivir in pediatric patients by United States- Food and Drug Administration (US-FDA) suggested that increased reports of these events were due to increased awareness of influenza associated encephalopathy, increased access to oseltamivir and coincident period of intensive monitoring. [16] An internet based cross-sectional study of oseltamivir side effects among children taking oseltamivir as prophylaxis reported neuropsychiatric side effects in one out of five children with sleeping problems as most common. [14] The overall incidence of neuropsychiatric symptoms in our study was less than 13% and was mostly sleeping difficulties, dizziness/vertigo and headache. All adverse events resolved spontaneously and none required discontinuation of oseltamivir. There is also possibility that the neuropsychiatric manifestations might be due to influenza infection. Disorders reported in children with influenza include ataxia, changes in mental state, confusion, delirium, encephalitis, encephalopathy, hallucinations, inappropriate behavior, psychosis, and seizures. [17]

Oseltamivir is currently not recommended for use in infants younger than 1 year of age because of lack of data on safety and effectiveness in this age group. Concerns were raised about use of oseltamivir in infants due to poorly developed blood--brain barrier. An animal study showed that mortality occurred in oseltamivir-treated infant rats in which the concentration in brain was 1500 times higher than adult rats. [10] However, US-FDA has granted Emergency Use Authorization for oseltamivir in infants of age in anticipation that this group would require prophylaxis and treatment. [18] Guidelines issued by DGHS, MOHFW, India for pandemic Influenza A (H1N1) recommend oseltamivir in dose of 12, 20, and 25mg in infants younger than 3 months, 3--5 months and 6--11 months, respectively. The oseltamivir use in our study in infants less than one year of age (n = 36) was not associated with increase in adverse events including neurological symptoms when compared to other age groups. These results were consistent with other studies which concluded no association of increased adverse events including neurological disorders and oseltamivir use in infants. [19],[20]

Limitations of our study include small sample size for rare adverse events and no definitive laboratory diagnosis for influenza (H1N1) for all patients who received oseltamivir for treatment.

   References Top

1.Le J, Nguyen T, Law AV, Hodding J. Adverse Drug Reactions Among Children Over a 10-Year Period. Pediatrics 2006;118:555-62.  Back to cited text no. 1
2.Health Canada. Reporting Adverse Reactions to Antiviral Drugs During an Influenza Pandemic-Guidelines for Health Professionals and Consumers. [Updated 2009 May 8]. Available from: [Cited on 2010 May 8].  Back to cited text no. 2
3.Impicciatore P, Choonara I, Clarkson A, Provasi D, Pandolfini C, Bonati M. Incidence of adverse drug reactions in paediatric in/out-patients: A systematic review and meta-analysis of prospective studies. Br J Clin Pharmacol 2001;52:77-83.  Back to cited text no. 3
4.Dharnidharka VR, Kandoth PN, Anaud RK. Adverse drug reaction in paediatrics with a study of in-hospital intensive surveillance. Indian paediatr 1993;30:745-51.  Back to cited text no. 4
5.Kshirsagar NA, Karande S. Adverse Drug Reaction Monitoring in Pediatric Practice. Indian Paediatr 1996;33:993-8.  Back to cited text no. 5
6.McNicholl IR, McNicholl JJ. Neuraminidase inhibitors: Zanamivir and oseltamivir. Ann Pharmacother 2001;35:57-70.  Back to cited text no. 6
7.Tamiflu product information. Roche Pharmaceuticals. [Updated 2000 Dec]. Available from: [Cited on 2010 May 7].  Back to cited text no. 7
8.Department of Health and Human Services, Public Health Service, Food and Drug Administration Center for Drug Evaluation and Research. Memorandum ODS PID#: D060309. [Updated 2006 Sep 20]. Available at: [Cited on 2010 May 5].  Back to cited text no. 8
9.Maxwell SR. Tamiflu and neuropsychiatric disturbance in adolescents. BMJ 2007;334:1232-3.  Back to cited text no. 9
10.US Food and Drug Administration. Alert letter. [2003 Dec]. Available from: [Cited on 2010 May 8].  Back to cited text no. 10
11.Matheson NJ, Harnden AR, Perera R, Sheikh A, Symmonds-Abrahams M. Neuraminidase inhibitors for preventing and treating influenza in children. Cochrane Database Syst Rev 2007;1:CD002744.  Back to cited text no. 11
12.Cooper NJ, Sutton AJ, Abrams KR, Wailoo A, Turner DA, 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;326:1235-9.  Back to cited text no. 12
13.Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India. Guidelines on categorization of Influenza A H1N1 cases during screening for home isolation, testing treatment, and hospitalization. Available from: [Cited on 2010 May 8].  Back to cited text no. 13
14. Kitching A, Roche A, Balasegaram S, Heathcock R, Maguire H. Oseltamivir adherence and side effects among children in three london schools affected by influenza A(H1N1)v, May 2009 - an internet based cross sectional survey. Euro Surveill 2009;14:1-4.  Back to cited text no. 14
15.Hama R. Fatal neuropsychiatric adverse reactions to oseltamivir: Case series and overview of causal relationships. Int J Risk Safety Med 2008;20:5-36.  Back to cited text no. 15
16.US Food and Drug Administration (FDA). Tamiflu Pediatric Adverse Events: Questions and Answers. [Updated 2005 Nov 17]. Available from: [Cited on 2010 May 7].  Back to cited text no. 16
17.Nicholson KG. Clinical features of influenza. Semin Respir Infect 1992;7:26-37.  Back to cited text no. 17
18.Emergency dosing recommendations for treatment and prophylaxis of influenza in pediatric patients less than 1 year old. Available from: [Cited on 2010 May 10].  Back to cited text no. 18
19.Tamura D, Miura T, Kikuchi Y. Oseltamivir Phosphate in Infants Under 1 Year of Age with Influenza Infection. Pediatr Int 2005;47:484.  Back to cited text no. 19
20.Okamato S, Kamiya I, Kishida K, Fukui T, Morimoto T. Experience with Oseltamivir for Infants Younger than 1 year old in Japan. Pediatr Infect Dis J 2005;24:575-6.  Back to cited text no. 20


  [Table 1], [Table 2], [Table 3]

This article has been cited by
1 Delayed Onset of Manic Symptoms in a Patient with Influenza A (H1N1) after administration of Oseltamivir (Tamiflu): A Case Report
Min Jhon, Ju-Wan Kim, Hee-Ju Kang, Seon-Young Kim, Ju-Yeon Lee, Sung-Wan Kim, Il-Seon Shin, Jae-Min Kim
Clinical Psychopharmacology and Neuroscience. 2021; 19(1): 166
[Pubmed] | [DOI]
2 Association study of genetic polymorphisms in proteins involved in oseltamivir transport, metabolism, and interactions with adverse reactions in Mexican patients with acute respiratory diseases
Mario Bermúdez de León, Rafael B. R. León-Cachón, Beatriz Silva-Ramírez, Rosa Nelly González-Ríos, Brenda Escobedo-Guajardo, Roberto Leyva-Parra, Benjamín Tovar-Cisneros, Everardo González-González, Abdiel Alvarado-Díaz, Ofelia Vázquez-Monsiváis, Viviana Mata-Tijerina, Lorena Puente-Lugo, Erick Álvarez-Galván, María José Currás-Tuala, Miguel Aguado-Barrera, Fabiola Castorena-Torres, Juan Manuel Alcocer-González, Guillermo Elizondo, Ana María Salinas-Martínez
The Pharmacogenomics Journal. 2020; 20(4): 613
[Pubmed] | [DOI]
3 Prophylactic oseltamivir during major seasonal influenza H1N1 outbreak might reduce both H1N1 and associated pulmonary aspergillosis in children undergoing haploidentical transplantation
Sarita Rani Jaiswal, Gitali Bhagwati, Mayank Soni, Atul Thatai, Hemamalini Aiyer, Suparno Chakrabarti
Transplant Infectious Disease. 2020; 22(5)
[Pubmed] | [DOI]
4 Research Progress of Oseltamivir Phosphate
?? ?
Hans Journal of Chemical Engineering and Technology. 2020; 10(06): 449
[Pubmed] | [DOI]
5 Adverse Drug Reactions During COVID-19 Treatment
Turkish Journal of Pediatric Disease. 2020; : 65
[Pubmed] | [DOI]
6 Suspected Oseltamivir-Induced Bradycardia in a Pediatric Patient: A Case Report from King Abdullah Specialist Children’s Hospital, Riyadh, Saudi Arabia
Hisham Arabi, Ahmed Abou Zaid, Mohammed Alreefi, Salman Alahmed
Clinics and Practice. 2018; 8(4): 102
[Pubmed] | [DOI]
7 Pharmacokinetics of oseltamivir in infants under the age of 1 year
Rashmi Dixit,Slade Matthews,Gulam Khandaker,Karen Walker,Marino Festa,Robert Booy
Clinical and Translational Medicine. 2016; 5(1)
[Pubmed] | [DOI]
8 A prospective study of adverse drug reactions to antiepileptic drugs in children
M. Anderson,O. Egunsola,J. Cherrill,C. Millward,A. Fakis,I. Choonara
BMJ Open. 2015; 5(6): e008298
[Pubmed] | [DOI]
9 Effectiveness and safety of oseltamivir for treating influenza: an updated meta-analysis of clinical trials
Sangsang Qiu,Ye Shen,Hongqiu Pan,Jianming Wang,Qun Zhang
Infectious Diseases. 2015; 47(11): 808
[Pubmed] | [DOI]
10 Oseltamivir produces hypothermic and neuromuscular effects by inhibition of nicotinic acetylcholine receptor functions: Comparison to procaine and bupropion
Akihiro Fukushima,Kaori Chazono,Yuichi Hashimoto,Yui Iwajima,Shohei Yamamoto,Yasuhiro Maeda,Masahiro Ohsawa,Hideki Ono
European Journal of Pharmacology. 2015; 762: 275
[Pubmed] | [DOI]
11 A prospective observational study of oseltamivir safety and tolerability in infants and young children =24?months
Barbara A. Rath,William A. Blumentals,Mary K. Miller,Kathryn Starzyk,Boguslaw Tetiurka,Martina Wollenhaupt
Pharmacoepidemiology and Drug Safety. 2014; : n/a
[Pubmed] | [DOI]
12 Reduction in Sympathetic Nerve Activity as a Possible Mechanism for the Hypothermic Effect of Oseltamivir, an Anti-influenza Virus Drug, in Normal Mice
Hideki Ono,Yui Iwajima,Yuko Nagano,Kaori Chazono,Yasuhiro Maeda,Masahiro Ohsawa,Shohei Yamamoto
Basic & Clinical Pharmacology & Toxicology. 2013; 113(1): 25
[Pubmed] | [DOI]
13 Reduction in sympathetic nerve activity as a possible mechanism for the hypothermic effect of oseltamivir, an anti-influenza virus drug, in normal mice
Ono, H. and Iwajima, Y. and Nagano, Y. and Chazono, K. and Maeda, Y. and Ohsawa, M. and Yamamoto, S.
Basic and Clinical Pharmacology and Toxicology. 2013; 113(1): 25-30
14 Development and evaluation of a dry powder formulation of liposome-encapsulated oseltamivir phosphate for inhalation
Yue Tang,Heyang Zhang,Xifeng Lu,Liqun Jiang,Xinyuan Xi,Jianping Liu,Jiabi Zhu
Drug Delivery. 2013; : 1
[Pubmed] | [DOI]
15 Two years after pandemic influenza A/2009/H1N1: what have we learned?
Cheng VC, To KK, Tse H, Hung IF, Yuen KY.
Clin Microbiol Rev.. 2012; 25(2): 223-263
[Pubmed] | [DOI]
16 Antivirals used for influenza chemoprophylaxis
Tsiodras, S. and Nikolopoulos, G. and Bonovas, S.
Current Medicinal Chemistry. 2012; 19(35): 5947-5956
17 Two seasonsæ experience with pandemic A H1N1 influenza infection in neonates
Martic, J. and Savic, N. and Jankovic, B. and Nedeljkovic, J. and Rakonjac, Z. and Pejic, K. and Markovic-Sovtic, G.
Turkish Journal of Pediatrics. 2012; 54(6): 612-616
18 Adverse drug reaction of oseltamivir in pediatric patients
Wiwanitkit, S. and Wiwanitkit, V.
Journal of Pharmacology and Pharmacotherapeutics. 2012; 3(1): 81


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
    Materials and Me...
    Article Tables

 Article Access Statistics
    PDF Downloaded755    
    Comments [Add]    
    Cited by others 18    

Recommend this journal