What are the risks of taking Tamiflu (oseltamivir)?

Risks of Taking Tamiflu (Oseltamivir)

The most common risks of taking Tamiflu are mild gastrointestinal symptoms—nausea (10%) and vomiting (8-9% in adults, 14% in children)—which are typically transient and can be reduced by taking the medication with food. 1, 2

Common Adverse Effects (Occur in >1% of patients)

Gastrointestinal symptoms are the predominant adverse effects:

• Nausea without vomiting occurs in approximately 10% of adults (versus 6% with placebo) 3, 1
• Vomiting occurs in approximately 9% of adults (versus 3% with placebo) and 14% of children (versus 8.5% with placebo) 3, 1
• Only 1% of patients discontinue treatment due to gastrointestinal side effects 3, 1
• Taking oseltamivir with food significantly reduces the severity of nausea and vomiting 3, 1, 2

Other common adverse effects include:

• Headache (reported in <5% of patients) 3, 2
• Diarrhea (reported in <5% of patients) 3, 1
• Dizziness (reported in <5% of patients) 3, 1

Serious Adverse Effects (Rare but Important)

Neuropsychiatric events have been reported during postmarketing surveillance:

• Transient neuropsychiatric events including self-injury, delirium, abnormal behavior, hallucinations, agitation, anxiety, altered level of consciousness, confusion, nightmares, and delusions 3, 1, 2
• The majority of these reports occurred among adolescents and adults in Japan 3, 1
• The FDA advises close monitoring for abnormal behavior in all patients receiving oseltamivir, particularly adolescents 3, 1, 2
• A large insurance database study showed no evidence of increased risk of neuropsychiatric events compared to those not receiving oseltamivir 4
• One case report documented manic symptoms developing on the fourth day after cessation of a 5-day course, suggesting monitoring should extend beyond 48 hours 5

Serious skin and hypersensitivity reactions (rare):

• Stevens-Johnson Syndrome, toxic epidermal necrolysis, and erythema multiforme have been reported 2
• Allergic reactions including oropharyngeal or facial edema, anaphylactic/anaphylactoid reactions 3, 1, 2
• Oseltamivir should be discontinued immediately if allergic-like reactions occur or are suspected 2

Other serious adverse effects reported during postmarketing surveillance:

• Gastrointestinal bleeding and hemorrhagic colitis 2
• Cardiac arrhythmias 2
• Hepatitis and abnormal liver function tests 2
• Seizures 2
• Aggravation of diabetes 2

Special Population Considerations

Pregnancy (FDA Pregnancy Category C):

• No clinical studies have assessed safety in pregnant women, but extensive postmarketing surveillance shows no adverse effects reported among women who received oseltamivir during pregnancy or their infants 3, 1
• Published observational studies of >5,000 pregnant women exposed to oseltamivir showed no increased rate of congenital malformations 2
• Pregnancy should not be considered a contraindication to oseltamivir use, as pregnant women are at higher risk for severe influenza complications including maternal death, stillbirths, and preterm delivery 1

Renal impairment:

• Patients with end-stage renal disease require dose adjustments to avoid toxicity 6, 2
• A study in dialysis patients using prophylactic dosing (75 mg every 5 days) found side effects were mild and tolerable with no life-threatening events 7
• Oseltamivir is not recommended for patients with end-stage renal disease not undergoing dialysis 2

Pediatric patients:

• Vomiting is the most common adverse effect in children (14% versus 8.5% with placebo) 3, 1
• The safety profile in children as young as 2 weeks of age has been established 3, 1, 2
• A review of controlled clinical trial data and ongoing surveillance failed to establish a link between oseltamivir and neurologic or psychiatric events in children 3

Elderly patients:

• The safety profile in elderly and high-risk patients is similar to that in otherwise healthy adults 8, 4
• Renal function assessment is critical, as dose adjustments are mandatory when creatinine clearance falls below 60 mL/min 6

Drug Interactions

Live attenuated influenza vaccine (LAIV):

• Avoid administration of LAIV within 2 weeks before or 48 hours after oseltamivir use, as oseltamivir may inhibit replication of live vaccine virus and reduce LAIV efficacy 6, 2

Probenecid:

• Coadministration results in approximately 50% reduced clearance of oseltamivir carboxylate and approximately twofold increase in plasma levels 3, 1

No clinically significant interactions with amoxicillin, acetaminophen, aspirin, cimetidine, antacids, rimantadine, amantadine, or warfarin 2

Clinical Monitoring Recommendations

• Monitor all patients, particularly adolescents, closely for abnormal behavior during and after treatment 3, 1, 2
• Monitor for signs of allergic reactions, especially during initial doses 2
• Consider monitoring beyond 48 hours after treatment completion, as delayed neuropsychiatric effects have been reported 5
• Assess renal function before prescribing, especially in elderly patients and those with known kidney disease 6, 2

Important Clinical Context

The overall safety profile of oseltamivir is favorable, with serious adverse events reported in only 1.3% of patients receiving 75 mg twice daily (versus 1.2% with placebo) in clinical trials 4. Postmarketing surveillance of over 4 million prescriptions worldwide has confirmed that transient gastrointestinal disturbance is the major adverse effect, and this can be reduced by taking oseltamivir with food 4. A large insurance database study showed no evidence of increased risk of cardiac, neuropsychiatric, or respiratory events compared to those not receiving oseltamivir 4.