Safety and pharmacology of oseltamivir in clinical use

Drug Saf. 2003;26(11):787-801. doi: 10.2165/00002018-200326110-00004.

Abstract

Oseltamivir is a novel agent approved for the treatment and prevention of influenza infection and illnesses in adults and children. Assessment of data from the clinical trial programme, a US health insurance database study and postmarketing surveillance allowed a comprehensive review of the safety of oseltamivir in clinical use in subjects >1 year of age. Oseltamivir has been studied over the course of a 5-year development programme in >11000 subjects from North America, Europe and the Southern Hemisphere, including otherwise healthy adults, approximately 500 elderly/high-risk subjects, and children (>1000) aged 1-12 years. Safety evaluations included treatment-emergent adverse events, hospitalisations and deaths, as well as haematological and biochemical laboratory safety tests. The data reveals that oseltamivir has simple, uncomplicated pharmacology and lacks potential for drug-drug interactions. Electrocardiogram parameters, including corrected QT interval, were unaffected by oseltamivir even at high doses. Postmarketing studies confirmed that transient gastrointestinal disturbance is the major adverse effect of oseltamivir and that this can be reduced by taking oseltamivir after a light snack. On treatment serious adverse events were reported in 1.3% of oseltamivir 75mg twice daily, 0.7% of oseltamivir 150 mg twice daily and 1.2% of placebo recipients, respectively, in the clinical trial programme. Postmarketing, it is estimated that, to date, over 4 million oseltamivir prescriptions have been dispensed worldwide. Approximately 2300 spontaneous reports were received by the manufacturer over the three winter seasons of use. As these events are reported infrequently and from an unknown number of users, it is not possible to definitively assess causality or frequency of reported events. Most reports were of gastrointestinal and skin reactions. However, a clear association between the skin reactions and oseltamivir has not been established. A large study of insurance records, which permitted the assessment of the relative risk of medical events treated in the month following prescription of oseltamivir in general use, showed no evidence of increased risk of cardiac, neuropsychiatric or respiratory events for those receiving oseltamivir compared with those who did not. To conclude, no important safety concerns have evolved which might limit the suitability of oseltamivir for the treatment and prevention of influenza in all patient populations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetamides / administration & dosage
  • Acetamides / adverse effects
  • Acetamides / pharmacokinetics*
  • Adult
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacokinetics*
  • Child
  • Clinical Trials as Topic
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Humans
  • Influenza, Human / drug therapy*
  • Neuraminidase / antagonists & inhibitors
  • Oseltamivir
  • Product Surveillance, Postmarketing
  • Treatment Outcome

Substances

  • Acetamides
  • Antiviral Agents
  • Oseltamivir
  • Neuraminidase