What are the indications, dosing regimens, contraindications, precautions, and common adverse effects of Tamiflu (oseltamivir) for treatment and prophylaxis of influenza in adults and children?

Tamiflu (Oseltamivir): Comprehensive Clinical Guide

Indications

Oseltamivir is indicated for treatment of acute uncomplicated influenza A and B in patients ≥2 weeks of age and for prophylaxis in patients ≥1 year of age. 1

Treatment Indications

• Acute influenza illness in otherwise healthy patients when initiated within 48 hours of symptom onset 2, 1
• High-risk patients (children <2 years, adults ≥65 years, pregnant women, immunocompromised, chronic cardiac/pulmonary disease, diabetes) should receive treatment regardless of vaccination status 2
• Hospitalized patients with moderate to severe disease, even if presenting >48 hours after symptom onset 2

Prophylaxis Indications

• Post-exposure prophylaxis for household contacts of confirmed influenza cases, initiated within 48 hours of exposure 3
• High-risk individuals during community outbreaks, particularly if unvaccinated or within 2 weeks of vaccination 3
• Severely immunocompromised patients may receive prophylaxis for up to 12 weeks during outbreaks 3

---

Dosing Regimens

Treatment Dosing (5 days, twice daily)

Adults and Adolescents (≥13 years)

• 75 mg orally twice daily for 5 days 1
• Initiate within 48 hours of symptom onset for maximum benefit; earlier initiation (within 12-24 hours) provides additional 1-3 days of symptom reduction 4

Children (≥12 months) – Weight-Based

• ≤15 kg: 30 mg twice daily (5 mL suspension) 1, 5
• >15-23 kg: 45 mg twice daily (7.5 mL suspension) 1, 5
• >23-40 kg: 60 mg twice daily (10 mL suspension) 1, 5
• >40 kg: 75 mg twice daily (12.5 mL suspension) 1, 5

Infants (<12 months) – Age-Based

• 9-11 months: 3.5 mg/kg per dose twice daily 1
• Term infants 0-8 months: 3 mg/kg per dose twice daily 1

Preterm Infants – Postmenstrual Age-Based

• <38 weeks PMA: 1.0 mg/kg twice daily 1
• 38-40 weeks PMA: 1.5 mg/kg twice daily 1
• >40 weeks PMA: 3.0 mg/kg twice daily 1

Critical caveat: Never use weight-based categorical dosing (≤15 kg = 30 mg) for infants <12 months; this causes toxic concentrations due to immature renal function. 1

---

Prophylaxis Dosing (10 days, once daily)

Adults and Adolescents (≥13 years)

• 75 mg orally once daily for 10 days after exposure 3
• Initiate within 48 hours of exposure; do not start if >48 hours elapsed 3

Children (≥12 months) – Weight-Based

• Same weight categories as treatment, but once daily for 10 days 1
• ≤15 kg: 30 mg once daily; >15-23 kg: 45 mg once daily; >23-40 kg: 60 mg once daily; >40 kg: 75 mg once daily 1

Infants (3-11 months)

• 3 mg/kg once daily for 10 days 1
• Not recommended for infants <3 months unless situation is critical due to limited safety data 1

---

Renal Impairment Adjustments

Dose adjustment is mandatory for creatinine clearance <60 mL/min, not based on age alone. 1

CrCl 10-30 mL/min

• Treatment: 75 mg once daily (instead of twice daily) for 5 days 1
• Prophylaxis: 30 mg once daily OR 75 mg every other day for 10 days (5 total doses) 1

End-Stage Renal Disease

• Oseltamivir not recommended for patients not on dialysis 1
• Hemodialysis contributes minimally to clearance 1

---

Formulations and Administration

Available Forms

• Capsules: 30 mg, 45 mg, 75 mg 1
• Oral suspension: 6 mg/mL when reconstituted 1

Administration Instructions

• Take with food to reduce nausea and vomiting (occurs in 10-15% of patients vs. 6-9% with placebo) 1, 4
• Capsules may be opened and mixed with liquid if patient cannot swallow whole 1
• Use calibrated 3-5 mL oral syringe for infants; never use household spoons or the manufacturer-supplied syringe for small volumes 1
• If commercial suspension unavailable, pharmacies can compound 6 mg/mL suspension per package insert instructions 1

---

Contraindications and Precautions

Absolute Contraindications

• Hypersensitivity to oseltamivir or any component 1

Precautions and Special Populations

Pregnancy and Lactation

• No contraindication to use during pregnancy; benefits outweigh risks 1
• Recommended for pregnant women in high-risk exposure groups 3

Renal Impairment

• Mandatory dose reduction for CrCl <60 mL/min 1
• Monitor for toxicity in elderly patients (assess renal function, not age) 1

Preterm and Young Infants

• FDA-approved from 2 weeks of age for treatment, but AAP supports use from birth when benefits outweigh risks 1
• Consult pediatric infectious disease specialist for extremely preterm infants (<28 weeks gestation) 1
• Prophylaxis not recommended <3 months unless critical situation 1

Neuropsychiatric Events

• Post-marketing surveillance from Japan raised concerns, but systematic review failed to establish causal link between oseltamivir and neuropsychiatric events 2

---

Common Adverse Effects

Gastrointestinal (Most Common)

• Nausea: ~10% (vs. 6% placebo) 1
• Vomiting: 9-15% in adults, 14.3% in children (vs. 8.5% placebo) 2, 1
• Diarrhea: Less common 1
• Symptoms are mild, transient (1-2 days), and significantly reduced when taken with food 4, 6
• Only ~1% discontinue due to GI effects 1

Other Adverse Effects

• Headache 1
• Skin reactions (causality not clearly established) 6

---

Drug Interactions and Vaccine Considerations

Live Attenuated Influenza Vaccine (LAIV)

• Avoid LAIV within 48 hours before oseltamivir 1
• Do not use oseltamivir for 14 days after LAIV (diminishes vaccine effectiveness) 1, 3

Inactivated Influenza Vaccine (IIV)

• No interaction; oseltamivir does not interfere with antibody response to IIV 3
• Can administer simultaneously in high-risk patients within 2 weeks of vaccination (before optimal immunity) 3

Other Medications

• Low potential for drug-drug interactions due to simple pharmacology 7, 6
• No effect on QT interval even at high doses 6

---

Clinical Efficacy and Timing

Treatment Benefits

• Reduces illness duration by 1-1.5 days (26-36% reduction) when started within 48 hours 5, 8
• Earlier initiation provides greater benefit: within 12 hours reduces duration by additional 74.6 hours vs. 48-hour initiation 4
• Decreases secondary complications (otitis media by 44%, bronchitis, pneumonia, sinusitis) 5, 4
• Reduces antibiotic use 8

Prophylaxis Efficacy

• 74-82% reduction in laboratory-confirmed influenza during community outbreaks 3
• 58-84% protective efficacy in household contacts when started within 48 hours 3
• Protection lasts only during medication use; susceptibility returns after stopping 3

---

Critical Clinical Pearls

• Complete the full 5-day treatment course even if symptoms improve; stopping early risks inadequate viral suppression and resistance 1
• Do not delay treatment while awaiting laboratory confirmation in high-risk patients with influenza-like illness during flu season 2
• Treatment after 48 hours still provides benefit in moderate-to-severe or progressive disease 2
• Prophylaxis is not a substitute for vaccination, which remains the primary prevention strategy 3
• For infants <12 months, always calculate exact mg/kg dose; do not round inappropriately 1
• Assess renal function in elderly patients before dosing; age alone does not require adjustment 1
• If symptoms develop during prophylaxis, switch to treatment dosing (twice daily) and test for influenza 3