What are the indications, dosing regimens (including pediatric and renal adjustments), contraindications, and adverse effects of oseltamivir (Tamiflu) for treatment and prophylaxis of influenza?

Oseltamivir (Tamiflu): Comprehensive Clinical Guide

Indications for Treatment

Oseltamivir should be prescribed immediately for any patient with confirmed or suspected influenza who presents within 48 hours of symptom onset, and must be strongly considered beyond 48 hours for all hospitalized patients, those with severe or progressive disease, or any high-risk individual regardless of vaccination status. 1

Mandatory Treatment Groups (Treat Regardless of Timing)

• All hospitalized patients with presumed influenza 1
• Children younger than 5 years (especially those under 2 years) 1, 2
• Adults aged ≥65 years 1
• Pregnant women and women up to 2 weeks postpartum 1
• Immunocompromised patients (may require treatment >5 days) 1
• Patients with chronic conditions: cardiac, pulmonary, renal, hepatic, neurologic, hematologic, or metabolic disorders 1
• Residents of long-term care facilities 1
• Patients with severe, complicated, or progressive disease 1

Critical Timing Considerations

• Do not delay treatment while awaiting laboratory confirmation in high-risk patients, as rapid antigen tests have poor sensitivity 1
• Treatment within 48 hours reduces illness duration by approximately 1–1.5 days (24–36 hours) 1, 2, 3
• Even after 48 hours, treatment significantly reduces mortality in hospitalized and high-risk patients (odds ratio 0.21 for influenza pneumonia) 1
• Patients unable to mount a febrile response (immunocompromised, very elderly) remain eligible despite lack of documented fever 1

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Treatment Dosing Regimens

Adults and Adolescents (≥13 years)

• 75 mg orally twice daily for 5 days 4, 5, 1
• Administer with food to reduce nausea and vomiting 5

Pediatric Patients (≥12 months) – Weight-Based Dosing

Weight	Dose	Frequency	Duration
≤15 kg (≤33 lb)	30 mg (5 mL suspension)	Twice daily	5 days
>15–23 kg (>33–51 lb)	45 mg (7.5 mL suspension)	Twice daily	5 days
>23–40 kg (>51–88 lb)	60 mg (10 mL suspension)	Twice daily	5 days
>40 kg (>88 lb)	75 mg (12.5 mL suspension)	Twice daily	5 days

4, 5, 1, 2

Critical: Use weight-based dosing for all children ≥12 months; never use age-based dosing for this group 2

Infants (Term, ≥37 weeks gestation)

• 9–11 months: 3.5 mg/kg per dose twice daily for 5 days 4, 5, 1
• 0–8 months: 3.0 mg/kg per dose twice daily for 5 days 4, 5, 1

Preterm Infants (Postmenstrual Age-Based)

Postmenstrual Age	Dose	Frequency	Duration
<38 weeks	1.0 mg/kg	Twice daily	5 days
38–40 weeks	1.5 mg/kg	Twice daily	5 days
>40 weeks	3.0 mg/kg	Twice daily	5 days

4, 5, 1

Critical: Preterm infants require substantially lower doses due to immature renal function; using term-infant dosing can lead to toxic concentrations 5

Renal Impairment Adjustments (Treatment)

Creatinine Clearance	Dose	Frequency	Duration
>30–60 mL/min	30 mg	Twice daily	5 days
10–30 mL/min	75 mg	Once daily	5 days
ESRD on hemodialysis	30 mg immediately, then 30 mg after each dialysis session	—	Max 5 days

4, 5, 1

The treatment duration remains 5 days regardless of renal function; only the frequency changes. 5

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Prophylaxis Dosing Regimens

Indications for Prophylaxis

• Unvaccinated high-risk individuals exposed to confirmed influenza 1
• High-risk persons within 2 weeks of vaccination (before optimal immunity) 1
• Immunocompromised patients regardless of vaccination status 1
• Unvaccinated household contacts of high-risk individuals 1
• Outbreak control in closed settings with high-risk residents 1

Prophylaxis Dosing

Adults and Adolescents (≥13 years)

• 75 mg once daily for 10 days (post-exposure) 4, 5, 1
• Initiate within 48 hours of exposure 1

Children (≥12 months)

• Same weight-based doses as treatment, but once daily for 10 days 4, 5, 1

Weight	Prophylaxis Dose	Frequency	Duration
≤15 kg	30 mg	Once daily	10 days
>15–23 kg	45 mg	Once daily	10 days
>23–40 kg	60 mg	Once daily	10 days
>40 kg	75 mg	Once daily	10 days

4, 5, 1

Infants (3–11 months)

• 3.0 mg/kg once daily for 10 days 5, 1
• Prophylaxis is NOT recommended for infants <3 months unless the situation is judged critical due to limited safety data 4, 5, 1

Renal Impairment Adjustments (Prophylaxis)

For creatinine clearance 10–30 mL/min:

• Option 1: 30 mg once daily for 10 days 4, 5, 1
• Option 2: 75 mg every other day for 10 days (5 total doses) 4, 5, 1

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Pregnancy, Postpartum, and Lactation

Pregnant women receive the standard adult regimen of 75 mg twice daily for 5 days throughout all trimesters. 1

• Pregnancy substantially increases the risk of severe influenza complications 1
• Oseltamivir is preferred over zanamivir in pregnancy because zanamivir is inhaled and may cause respiratory complications 1
• Postpartum women (≤2 weeks after delivery) should receive the same dosing 4
• Breastfeeding is NOT a contraindication to oseltamivir use 4, 1

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Formulation and Administration

Available Formulations

• Capsules: 30 mg, 45 mg, 75 mg 4, 5
• Oral suspension: 6 mg/mL when reconstituted 4, 5

Administration Guidelines

• Administer with food to significantly reduce nausea and vomiting 5, 1
• Use the oral suspension (6 mg/mL) for children who cannot swallow capsules 5, 2
• Measure doses with a calibrated oral syringe (3 mL or 5 mL); never use household spoons 5
• Capsules can be opened and contents mixed with liquid if needed 5
• If commercial suspension is unavailable, pharmacies can compound a 6 mg/mL suspension per package insert instructions 4, 5

Suspension Volume Conversions

• 30 mg dose = 5 mL 4, 5
• 45 mg dose = 7.5 mL 4, 5
• 60 mg dose = 10 mL 4, 5
• 75 mg dose = 12.5 mL 4, 5

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Contraindications and Precautions

Absolute Contraindications

• Allergic reaction to oseltamivir or any component of the formulation 4

Drug Interactions

• Avoid live attenuated influenza vaccine (LAIV) within 48 hours before oseltamivir 5, 1
• Do not use oseltamivir for 14 days after LAIV vaccination 5, 1

Common Medical Conditions (NOT Contraindications)

Patients with the following conditions can and should receive oseltamivir:

• Asthma, chronic pulmonary disease 1
• Cardiovascular disease 1
• Diabetes 1
• Immunodeficiency 1
• Mild febrile illness 1

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Adverse Effects

Common Gastrointestinal Effects

• Nausea: occurs in approximately 10% of adults (3.66% above placebo; NNTH 28) 5, 6
• Vomiting: occurs in approximately 9% of adults (4.56% above placebo; NNTH 22) and 14.3% of children (5.34% above placebo; NNTH 19) 5, 6
• Diarrhea: reported but less common 5
• These effects are mild, transient, and significantly reduced when taken with food 5, 1
• Only approximately 1% of patients discontinue oseltamivir due to gastrointestinal side effects 5

Other Adverse Events

• Headache: increased risk in prophylaxis studies (3.15% above placebo; NNTH 32) 6
• Psychiatric events: increased risk in prophylaxis studies (1.06% above placebo; NNTH 94), with dose-response effect noted 6
• Renal events: slight increase in prophylaxis studies (0.67% above placebo) 6
• Skin reactions: may occur 5

Important: Controlled trials and post-marketing surveillance have not demonstrated a causal association between oseltamivir and neurologic or psychiatric adverse events in children 2

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Clinical Benefits

Treatment Benefits

• Reduces illness duration by 1–1.5 days (24–36 hours) in otherwise healthy patients 1, 2, 3, 7
• Reduces severity of illness by up to 38% when initiated within 36 hours 7
• Reduces risk of complications: pneumonia, bronchitis, hospitalization, and death 1, 2
• Reduces secondary bacterial infections (e.g., acute otitis media) by approximately 34% 2
• Reduces need for subsequent antibiotic therapy 5
• Fever resolves sooner and patients return to normal activities earlier 2
• Significantly reduces mortality in hospitalized and high-risk patients (odds ratio 0.21) 1

Prophylaxis Benefits

• Reduces symptomatic influenza by 55% in individuals (NNTB 33) 6
• Reduces household transmission by 13.6% (NNTB 7) 6
• Protective efficacy >70% in unvaccinated adults during local influenza activity 7
• 92% protective efficacy when used adjunctively in previously vaccinated high-risk elderly patients 7

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Critical Dosing Errors to Avoid

Pediatric Dosing Pitfalls

• Never round up to the next weight category: a child weighing exactly 15 kg receives 30 mg, not 45 mg 2
• Never use age-based dosing for children ≥12 months: weight-based dosing is mandatory 2
• Do not apply term-infant dosing to preterm infants: postmenstrual age-based dosing is required to avoid toxicity 5, 2
• Do not use the weight-based categorical dosing (≤15 kg = 30 mg) for infants <12 months: use mg/kg dosing instead 5

General Pitfalls

• Complete the full 5-day course even if symptoms improve; early discontinuation increases resistance risk 5, 2
• Do not withhold therapy for mild presentations: antiviral treatment is beneficial regardless of initial severity 2
• Do not delay treatment while awaiting laboratory confirmation in high-risk patients 1
• Do not use household spoons for measurement: always employ a calibrated oral dosing device 5, 2

Renal Dosing Pitfalls

• Always adjust dose for creatinine clearance <60 mL/min in adults 5
• The treatment duration remains 5 days regardless of renal function; only the frequency changes 5

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Special Populations

Elderly Patients (≥65 years)

• Standard dose remains 75 mg twice daily for treatment and 75 mg once daily for prophylaxis with normal renal function 5
• The most important consideration is renal function, not age: dose reductions are mandatory when creatinine clearance falls below 60 mL/min 5
• Serum concentrations increase proportionally with declining renal function 5

Immunocompromised Patients

• Treat regardless of time since symptom onset 1
• May require extended treatment duration beyond 5 days if illness is prolonged 1

Infants and Young Children

• FDA-approved for treatment in children as young as 2 weeks of age 4, 5, 1
• Can be used from birth (including preterm infants) because benefits outweigh risks 5, 1
• For extremely preterm infants (<28 weeks gestation), consult a pediatric infectious disease specialist before initiating therapy 5

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Duration of Therapy

The standard treatment course is 5 days for uncomplicated influenza, uniformly endorsed by FDA labeling, CDC guidelines, and all major professional societies. 5

• Do not stop therapy early even if symptoms improve before day 5; completing the full course ensures adequate viral suppression and prevents resistance 5
• The prior recommendation to discontinue antiviral therapy 24–48 hours after symptom resolution applied only to amantadine/rimantadine, not to neuraminidase inhibitors such as oseltamivir 5
• Double-dose oseltamivir therapy confers no significant survival benefit 8
• Extended therapy beyond 5 days is not supported by evidence except possibly in critically ill H1N1-infected ICU patients 8