Is oseltamivir (Tamiflu) safe to use during pregnancy?

Oseltamivir Use in Pregnancy

Pregnant women with suspected or confirmed influenza should receive oseltamivir 75 mg orally twice daily for 5 days immediately, without waiting for diagnostic test results, as pregnancy should not be considered a contraindication to oseltamivir use. 1, 2

Treatment Recommendations

Pregnant women are at substantially higher risk for severe influenza complications, including maternal death, stillbirths, preterm delivery, and low birth weight, making immediate antiviral treatment critical. 1, 2 The relative risk for hospitalization escalates dramatically as pregnancy progresses, increasing from 1.4 during weeks 14-20 to 4.7 during weeks 37-42 of gestation. 2

Dosing Regimen

• Treatment dose: 75 mg orally twice daily for 5 days (same as non-pregnant patients) 1, 2
• Prophylaxis dose: 75 mg once daily for 7-10 days after last known exposure 1, 2
• Treatment should begin as early as possible after symptom onset, ideally within 48 hours, though benefit may still occur if started later 2
• Zanamivir 10 mg (two 5 mg inhalations) twice daily for 5 days is an alternative if oseltamivir is contraindicated 2

Safety Profile in Pregnancy

The FDA classifies oseltamivir as Pregnancy Category C, meaning no controlled clinical trials have been conducted in pregnant women. 3, 4 However, extensive post-marketing surveillance and observational data demonstrate reassuring safety outcomes that supersede this cautious classification. 1

Evidence from Human Studies

• No adverse effects have been reported among women who received oseltamivir during pregnancy or among infants born to such women 1
• A prospective cohort study of 112 pregnant women exposed to oseltamivir found no increased risk of major birth defects (6.7% vs 7.9% in unexposed, RR 0.84,95% CI 0.19-2.80) 5
• Published observational studies of more than 5,000 women exposed to oseltamivir during pregnancy, including over 1,000 in the first trimester, showed no increased rate of congenital malformations above the general population 4
• One retrospective cohort found no association between oseltamivir use and preterm birth, premature rupture of membranes, malformations, or abnormal fetal weight 1
• No increased risk of spontaneous abortion, preterm delivery, or small-for-gestational-age infants has been demonstrated 5

Animal Studies

• Animal reproduction studies showed no adverse developmental effects at clinically relevant exposures 4
• Minor skeletal malformations occurred only at maternally toxic doses producing exposures 190 times the maximum recommended human dose 4

Important Clinical Caveats

The Advisory Committee on Immunization Practices' original statement that oseltamivir "should be used during pregnancy only if the potential benefit justifies the potential risk" predated extensive post-marketing surveillance and the 2009 H1N1 pandemic experience. 1 This cautious language does not reflect current evidence demonstrating both the severe risks of untreated influenza in pregnancy and the favorable safety profile of oseltamivir. 1

Pharmacokinetic Considerations

• Pregnancy produces significantly lower systemic levels of the active metabolite oseltamivir carboxylate due to increased renal clearance 6
• Despite lower drug levels, current guidelines maintain standard dosing (75 mg twice daily) rather than increased doses, as clinical efficacy has been demonstrated at this regimen 1, 2
• This represents a knowledge gap where pregnant women may be relatively underdosed, though no dose adjustment is currently recommended 6

Adverse Effects to Anticipate

• Nausea (10%) and vomiting (9%) are the most common side effects and can be reduced by taking oseltamivir with food 1, 4
• Vomiting occurs in approximately 14% of children versus 9% of adults 1
• Diarrhea occurs in less than 5% of patients 1
• Only 1% of patients discontinue treatment due to gastrointestinal side effects 3

Urgent Evaluation Indicators

Pregnant women on oseltamivir require urgent evaluation if they develop: 2

• Difficulty breathing or chest pain
• Persistent high fever despite treatment
• Decreased fetal movement
• Signs of preterm labor

Fever Management

Acetaminophen should be used for fever management, as fever itself can cause adverse fetal outcomes independent of the viral infection. 1