What are the side effects of Tamiflu (oseltamivir)?

Tamiflu (Oseltamivir) Side Effects

The most common side effect of Tamiflu is gastrointestinal disturbance, specifically nausea (10%) and vomiting (9% in adults, 14% in children), which is typically mild, transient, and can be significantly reduced by taking the medication with food. 1

Common Gastrointestinal Side Effects

The gastrointestinal effects are the primary adverse events you'll encounter in clinical practice:

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

Other gastrointestinal symptoms including diarrhea, along with headache and dizziness, are each reported in less than 5% of patients 1, 2

Serious Neuropsychiatric Adverse Effects

The FDA advises close monitoring for abnormal behavior in all patients receiving oseltamivir, particularly adolescents. 1, 2

Transient neuropsychiatric events have been reported during postmarketing surveillance, including:

• Self-injury or delirium 1, 2
• Abnormal behavior, hallucinations, agitation, anxiety 2, 3
• Altered level of consciousness, confusion, nightmares, delusions 2
• Speech problems, shaky movements, seizures 3

Critical caveat: The majority of these neuropsychiatric reports were among adolescents and adults in Japan 1, 2. However, a review of controlled clinical trial data and ongoing surveillance has failed to establish a definitive causal link between oseltamivir and neurologic or psychiatric events 1. A large US insurance database study showed no evidence of increased risk of neuropsychiatric events for those receiving oseltamivir compared with those who did not 4.

Serious Allergic and Skin Reactions

Stop oseltamivir immediately and seek medical attention if allergic reactions develop. 3

Reported reactions include:

• Skin rash, hives, or blistering and peeling skin 3
• Oropharyngeal or facial edema 1, 2
• Blisters or sores in mouth 3
• Swelling of face, eyes, lips, tongue, or throat 3
• Trouble breathing, chest pain or tightness 3

A clear association between skin reactions and oseltamivir has not been definitively established in postmarketing surveillance 4.

Special Population Considerations

Children

• Vomiting is the most common adverse effect in pediatric patients (14% versus 8.5% with placebo) 1, 2
• In children younger than 1 year, diarrhea is also reported as a common side effect 1
• The only oseltamivir-attributable adverse effect significantly greater in 1- through 13-year-old children was vomiting (15% treated versus 9% placebo) 1

Pregnancy

• Oseltamivir is classified as "Pregnancy Category C" with no clinical studies assessing safety in pregnant women 1, 2
• However, no adverse effects have been reported among women who received oseltamivir during pregnancy or among infants born to such women 1, 2
• The drug should be used during pregnancy only if potential benefit justifies potential risk to the embryo or fetus 1, 2

Patients with Fructose Intolerance

• Oseltamivir oral suspension contains sorbitol and may cause stomach upset and diarrhea in people with fructose intolerance 3

Drug Interactions

Oseltamivir has minimal clinically significant drug interactions. 2

• The only documented interaction is with probenecid, which reduces oseltamivir carboxylate clearance by approximately 50% and increases plasma levels approximately twofold through competition for renal tubular secretion 1, 2
• No impairment of immunologic response to influenza vaccine has been demonstrated 1, 2
• Limited clinical data exist regarding other drug interactions, but oseltamivir is not metabolized by CYP3A4 and is not a substrate, inhibitor, or inducer of P-glycoprotein 5

Clinical Management Recommendations

To minimize side effects in practice:

• Administer oseltamivir with food to reduce gastrointestinal symptoms 1, 2, 5
• Monitor all patients, especially adolescents, closely for abnormal behavior during treatment 1, 2, 3
• Consider mild anti-emetic medication for nausea management 1
• Adjust dose for renal impairment (reduce by 50% if creatinine clearance <30 mL/min) 1, 5
• Report serious adverse events to FDA's MedWatch program 2

Overall Safety Profile

In clinical trials, serious adverse events on treatment were reported in 1.3% of oseltamivir 75mg twice daily recipients, 0.7% of oseltamivir 150mg twice daily recipients, and 1.2% of placebo recipients 4. Electrocardiogram parameters, including corrected QT interval, were unaffected by oseltamivir even at high doses 4. With over 4 million prescriptions dispensed worldwide in postmarketing surveillance, no important safety concerns have evolved that would limit the suitability of oseltamivir for treatment and prevention of influenza 4.