Recommendations for Obstetric Health Care Providers Related to Use of Antiviral Medications in the Treatment and Prevention of Influenza
These recommendations provide guidance for obstetric health care providers about prescribing antiviral medications for treatment and prevention of influenza during the 2020-2021 season. These recommendations are consistent with current recommendations for antiviral treatment from the Advisory Committee on Immunization Practices, the Infectious Diseases Society of America (Uyeki et al., 2018), and the American College of Obstetrics and Gynecology (ACOG Committee Opinion, 2018). These recommendations also build off recommendations from a meeting of experts convened by CDC in 2010, to review the evidence on treatment and prevention of influenza during pregnancy (Rasmussen et al., 2009; Rasmussen et al., 2011).
Influenza during Pregnancy and the Postpartum Period
- Pregnant women are at increased risk for severe illness from influenza compared to non-pregnant women of reproductive age. Changes in the immune, respiratory, and cardiovascular systems that occur during pregnancy put pregnant women at risk of being more severely affected by certain infections, including influenza.
- Postpartum women, who are in transition to normal immune, cardiac, and respiratory function, should be considered to be at increased risk of influenza-related complications up to 2 weeks postpartum (including following pregnancy loss) (Louie et al., 2010; Louie et al., 2011).
- Observational studies from the 2009 pandemic showed that pregnant women who were treated early with antiviral medications were less likely to require intensive care and less likely to die (Siston et al., 2010; Louie et al., 2010). A pooled analysis of studies from the 2009 pandemic also showed that hospitalized pregnant women with influenza who were treated at any point during illness were less likely to die than untreated women (Muthuri et al., 2014). In addition, a study conducted during seasonal epidemics showed that women treated early (within 2 days of admission) with influenza antiviral medications had shorter hospital stays than those who were treated later (Oboho et al., 2016).
- Antiviral treatment should be initiated as early as possible because studies show that treatment initiated early (i.e., within 48 hours of illness onset) is more likely to provide benefit. However, some studies of hospitalized patients with influenza, including an analysis of hospitalized pregnant women (Muthuri et al., 2014) have suggested benefit of antiviral treatment even when treatment was started more than 48 hours after illness onset.
- Decisions to start antiviral treatment should not wait for laboratory confirmation of influenza because laboratory testing can delay treatment and because a negative rapid influenza diagnostic test result does not rule out influenza. Pregnant women are considered to be at higher risk of influenza complications by the Advisory Committee on Immunization Practices, and thus, empiric treatment is recommended. Treatment decisions, especially those involving empiric treatments, should be informed by knowledge of influenza activity in the community.
- Treatment with antiviral medications is recommended for pregnant women or women who are up to 2 weeks postpartum (including following pregnancy loss) with suspected or confirmed influenza and can be taken during any trimester of pregnancy.
- Oseltamivir, zanamivir, peramivir, and baloxavir are antiviral medications that are FDA approved for treatment of influenza.
- Oral oseltamivir, zanamivir, and peramivir are “Pregnancy Category Cexternal icon” medications, indicating that controlled clinical studies have not been conducted to assess the safety of these medications for pregnant women. However, multiple observational studies of treatment with oral oseltamivir or zanamivir during pregnancy have shown that antiviral treatment with these medications is safe during pregnancy and does not increase risk of adverse events or adverse pregnancy outcomes (Beau et al., 2014; Dunstan et al., 2014; Ehrenstein et al., 2018; Graner et al., 2017; Greer et al., 2011; Saito et al., 2009; Svensson et al., 2011; Tanaka et al., 2009; Wollenhaupt et al., 2014; Xie et al. 2013). Fewer data are available from human studies on safety of peramivir during pregnancy.
- For treatment of pregnant women or women who are up to 2 weeks postpartum with suspected or confirmed influenza, oral oseltamivir is preferred because it has the most studies available to suggest that it is safe and beneficial. The duration of antiviral treatment with oseltamivir is 5 days. See Table 2 in Summary for Clinicians for dosing information.
- Baloxavir was licensed for treatment of uncomplicated influenza within 2 days of onset in persons aged 12 years and older in the United States in October 2018. However, CDC does not recommend use of baloxavir for treatment of pregnant women or breastfeeding mothers because there are no available efficacy or safety data in pregnant women, and there are no available data on the presence of baloxavir in human milk, the effects on the breastfed infant, or the effects on milk production.
- The available risk-benefit data indicate that pregnant women with suspected or confirmed influenza should receive prompt antiviral therapy. Hospitalized patients with severe infections (such as those with prolonged infection or who require intensive care unit admission) might require longer treatment courses. Some data also suggest that a higher dose of oseltamivir (105 mg twice daily for treatment) may be needed to attain similar blood levels of the drug in pregnant women compared to non-pregnant women because of differences in renal filtration and excretion during pregnancy (Beigi et al., 2011; Pillai et al., 2015). Treatment with higher doses of oseltamivir may be considered for pregnant women in specific instances, although there are no safety data on higher dosing of oseltamivir in this population.
- At this time, nearly all circulating influenza viruses are susceptible to oseltamivir, zanamivir, and peramivir. However, recommended antiviral treatment regimens might change in the future depending on new antiviral resistance or viral surveillance information.
- Since rapid access to antiviral medications is important, health care providers who care for pregnant and postpartum (including following pregnancy loss) women should develop methods to ensure that treatment can be started quickly after symptom onset. Actions that will support early treatment initiation include:
- Informing pregnant and postpartum women of signs and symptoms of influenza and the need for early antiviral treatment after onset of symptoms. Typical manifestations of influenza include fever, cough, rhinorrhea, sore throat, headache, shortness of breath, and myalgia. Some patients with influenza have vomiting, diarrhea, or conjunctivitis, and some have respiratory symptoms without fever.
- Ensuring rapid access to telephone consultation and clinical evaluation for pregnant and postpartum women
- Considering empiric antiviral treatment of pregnant women and women who are up to 2 weeks postpartum based on telephone contact if hospitalization is not indicated and if this will substantially reduce delay before treatment is initiated
- Fever in pregnant women should be treated because of the risk that it appears to pose to the fetus. Acetaminophen appears to be the best option for treatment of fever during pregnancy.
- Post-exposure antiviral chemoprophylaxis can be considered for certain pregnant women and women who are up to 2 weeks postpartum (including following pregnancy loss) who have had close contact with someone likely to have been infectious with influenza and who
- cannot receive an influenza vaccination due to a contraindication or because vaccine is not available, or
- have severe immune deficiencies or other medical conditions that make them unlikely to respond to influenza vaccination
- Close contact, for the purposes of this document, is defined as having cared for or lived with a person who has confirmed, probable, or suspected influenza, or having been in a setting where there was a high likelihood of contact with respiratory droplets of such a person, including having talked face-to-face with a person with suspected or confirmed influenza illness.
- Oseltamivir and zanamivir are FDA approved for chemoprophylaxis of influenza. Oseltamivir is considered the drug of choice for chemoprophylaxis in pregnant women by the American Society of Obstetrics and Gynecology and the Infectious Diseases Society of America (ACOG Committee Opinion, 2018; Uyeki et al., 2018). The duration of antiviral chemoprophylaxis post-exposure is 7 days after the last known exposure. See Table 2 in Summary for Clinicians for medication and dosing information. Baloxavir is FDA-approved for post-exposure chemoprophylaxis of influenza in persons aged 12 years and older, but is not recommended for use in pregnant women or breastfeeding mother due to the lack of safety or efficacy data in pregnant women or data on baloxavir in human milk, breastfeeding infants, or effects on milk production.
- Pregnant women and women who are up to 2 weeks postpartum (including following pregnancy loss) who are given post-exposure antiviral chemoprophylaxis should be informed that the chemoprophylaxis lowers but does not eliminate the risk of influenza and that protection stops when the medication course is stopped. Those receiving chemoprophylaxis should be encouraged to seek medical evaluation as soon as they develop a febrile respiratory illness that might indicate influenza.
- All pregnant women should be counseled about the early signs and symptoms of influenza virus infection and advised to immediately call for evaluation if clinical signs or symptoms develop while these women are pregnant or are in the first two weeks after delivery or pregnancy loss.
- Early antiviral treatment if women develop symptoms of influenza is an alternative to chemoprophylaxis for some pregnant and postpartum women who have had contact with someone likely to have been infectious with influenza. Clinical judgment is an important factor in treatment decisions.
ACOG Committee Opinion No. 753 Summary: Assessment and Treatment of Pregnant Women With Suspected or Confirmed Influenza. Obstet Gynecol 2018;132:1077-9.
Beau AB, Hurault-Delarue C, Vial T, Montastruc JL, Damase-Michel C, Lacroix I. Safety of oseltamivir during pregnancy: a comparative study using the EFEMERIS database. BJOG 2014;121:895-900.
Beigi RH, Pillai VC, Venkataramanan R, Caritis SN. Oseltamivir for the treatment of H1N1 influenza during pregnancy. Clin Pharmacol Ther 2015;98:403-5.
Dunstan HJ, Mill AC, Stephens S, Yates LM, Thomas SH. Pregnancy outcome following maternal use of zanamivir or oseltamivir during the 2009 influenza A/H1N1 pandemic: a national prospective surveillance study. BJOG 2014;121:901-6.
Ehrenstein V, Kristensen NR, Monz BU, Clinch B, Kenwright A, Sorensen HT. Oseltamivir in pregnancy and birth outcomes. BMC Infect Dis 2018;18:519.
Graner S, Svensson T, Beau AB, et al. Neuraminidase inhibitors during pregnancy and risk of adverse neonatal outcomes and congenital malformations: population based European register study. BMJ 2017;356:j629.
Greer LG, Sheffield JS, Rogers VL, et al. Maternal and neonatal outcomes after antepartum treatment of influenza with antiviral medications. Obstet Gynecol 2010;115:711-6.
Louie JK, Acosta M, Jamieson DJ, Honein MA. Severe 2009 H1N1 influenza in pregnant and postpartum women in California. N Engl J Med 2010;362:27-35.
Louie JK, Jamieson DJ, Rasmussen SA. 2009 pandemic influenza A (H1N1) virus infection in postpartum women in California. Am J Obstet Gynecol. 2011 Feb;204(2):144.e1-6.
Muthuri SG, Venkatesan S, Myles PR, et al. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med. 2014 May;2(5):395-404.
Pillai VC, Han K, Beigi RH, et al. Population pharmacokinetics of oseltamivir in non-pregnant and pregnant women. Br J Clin Pharmacol 2015;80:1042-50.
Rasmussen SA, Jamieson DJ, MacFarlane K, et al. Pandemic influenza and pregnant women: Summary of a meeting of experts. Am J Public Health 2009;99 S248-54.
Rasmussen SA, Kissin DM, Yeung LF, et al. Preparing for influenza after 2009 H1N1: special considerations for pregnant women and newborns. Am J Obstet Gynecol. 2011; 204(6 Suppl 1): S13-20.
Saito S, Minakami H, Nakai A, et al. Outcomes of infants exposed to oseltamivir or zanamivir in utero during pandemic (H1N1) 2009. Am J Obstet Gynecol 2013;209:130 e1-9.
Siston AM, Rasmussen SA, Honein MA, et al. Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. JAMA 2010;303:1517-25.
Svensson T, Granath F, Stephansson O, Kieler H. Birth outcomes among women exposed to neuraminidase inhibitors during pregnancy. Pharmacoepidemiol Drug Saf 2011;20:1030-4.
Tanaka T, Nakajima K, Murashima A, et al. Safety of neuraminidase inhibitors against novel influenza A (H1N1) in pregnant and breastfeeding women. CMAJ 2009;181:55-8.
Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza. Clin Infect Dis 2018.
Wollenhaupt M, Chandrasekaran A, Tomianovic D. The safety of oseltamivir in pregnancy: an updated review of post-marketing data. Pharmacoepidemiol Drug Saf 2014;23:1035-42.
Xie HY, Yasseen AS, 3rd, Xie RH, et al. Infant outcomes among pregnant women who used oseltamivir for treatment of influenza during the H1N1 epidemic. Am J Obstet Gynecol 2013;208:293 e1-7.