Version May 2024
Influenza, seasonal, prophylaxis: Oral: 75 mg once daily.
Postexposure prophylaxis: Note: Consider use in patients at very high risk for influenza complications (eg, patients who are severely immunocompromised) who have had close contact within the past 48 hours with a person with confirmed or suspected influenza during that person's infectious period (Ref). Some experts also suggest use in patients at high risk (see Persons at increased risk for complications below) (Ref). Continue for 1 week after last exposure (if previously vaccinated) or 2 weeks (if unvaccinated) (Ref).
Institutional outbreaks: Recommended for all residents regardless of vaccination status and continued for at least 2 weeks and 1 week after the last known case (Ref). Consider prophylaxis in employees, depending on vaccination status (Ref).
Preexposure prophylaxis: Only during widespread outbreaks for persons at very high risk for influenza complications (eg, patients who are severely immunocompromised) not protected by vaccination. Continue for the duration of influenza activity or for 2 weeks following vaccination (Ref).
Influenza, seasonal, treatment: Oral: 75 mg twice daily. Note: Higher doses (150 mg twice daily) are not currently recommended even in severely ill or immunocompromised patients (Ref).
Timing of initiation/target population: In patients with severe, complicated, or progressive illness; hospitalized patients; or those at increased risk for complications (see Persons at increased risk for complications below), initiate treatment as soon as possible even if >48 hours have elapsed since illness onset and do not delay for laboratory confirmation. For symptomatic outpatients with mild illness not at increased risk for complications, treatment can be considered only if it can be initiated ≤48 hours following illness onset (Ref).
Duration of therapy : Usual duration: 5 days; a longer duration may be considered in patients who are severely ill or immunocompromised (Ref).
Influenza A, avian, postexposure prophylaxis (off-label use): Oral: 75 mg twice daily for 5 days (from the last known exposure) if exposure was time-limited and not ongoing or 10 days if exposure is likely to be ongoing (eg, household setting) due to potential for prolonged infectiousness in the case-patient (Ref).
Influenza A, avian, treatment (off-label use): Oral: 75 mg twice daily (Ref). Note: Higher doses (150 mg twice daily) are not currently recommended even in severely ill or immunocompromised patients (Ref). Initiate as soon as possible, even if >48 hours have elapsed since illness onset. Do not delay treatment while awaiting lab results. The usual duration is 5 days, but consider longer courses (eg, 10 days) for severely ill hospitalized patients (Ref).
Note: Persons at increased risk for complications: Adults ≥65 years of age, people who are pregnant or postpartum (within 2 weeks after delivery), residents of long-term care facilities, non-Hispanic Black persons, Hispanic or Latino persons, American Indians and Alaska natives, persons with BMI ≥40 kg/m2 and individuals with certain chronic medical conditions (eg, pulmonary, cardiovascular, endocrine [eg, diabetes mellitus], renal, hepatic, hematologic, metabolic, neurologic, HIV, malignancy) or those receiving immunosuppressive medications (Ref).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
|
CrCl |
If the usual indication-specific dose is 75 mg once daily (eg, seasonal influenza prophylaxis) |
If the usual indication-specific dose is 75 mg twice daily (eg, seasonal influenza treatment) |
|---|---|---|
|
a References (unless otherwise specified): Kamal 2015a; manufacturer’s labeling. | ||
|
b Jones 2021. | ||
|
c Expert opinion. | ||
|
≥60 mL/minute |
No dosage adjustment necessary |
No dosage adjustment necessary |
|
>30 to <60 mL/minute |
30 mg once daily |
75 mg × 1 dose,b then 30 mg twice daily |
|
>10 to 30 mL/minute |
30 mg every other day |
30 mg once daily |
|
≤10 mL/minute |
30 mg once weeklyc |
30 mg every other dayc |
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
Influenza, seasonal, treatment: There are no clinical or pharmacokinetic data available (has not been studied); however, a dose of 75 mg twice daily (up to 150 mg twice daily) may be considered (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (~50%) (Ref):
Influenza, seasonal, treatment: 30 mg immediately and then 30 mg after every hemodialysis session for at least 5 days. Note: Assumes 3 hemodialysis sessions in the 5-day period (Ref).
Influenza, seasonal, prophylaxis: 30 mg immediately and then 30 mg after every other hemodialysis session for the recommended prophylaxis duration (Ref).
Peritoneal dialysis:
Influenza, seasonal, treatment: 75 mg immediately as a single dose (single dose provides a 5-day duration) (Ref).
Influenza, seasonal, prophylaxis: 30 mg immediately and then 30 mg once weekly for the recommended prophylaxis duration (Ref).
CRRT: Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour), unless otherwise noted. Close monitoring of response and adverse reactions (eg, neuropsychiatric) due to drug accumulation is important.
Influenza, seasonal, treatment: 75 mg once daily (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neuropsychiatric) due to drug accumulation is important.
Influenza, seasonal, treatment:
PIRRT days: 75 mg once daily; administer dose after PIRRT session when possible (Ref).
Non-PIRRT days: Dose as for CrCl ≤10 mL/minute (Ref).
Mild-to-moderate impairment: No dosage adjustment necessary.
Severe impairment: No dosage adjustment provided in manufacturer’s labeling (has not been studied).
The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.
Class 1, 2, or 3 obesity (BMI ≥30 kg/m2):
Oral: No dosage adjustment is necessary; refer to adult dosing for indication-specific doses (Ref).
Rationale for recommendations: A study evaluating oseltamivir pharmacokinetics in patients with BMI ≥40 kg/m2 found that apparent clearance was poorly correlated with body weight for both oseltamivir and oseltamivir carboxylate (active metabolite), and pharmacokinetic parameters were similar to those seen in normal-weight subjects (Ref). Pharmacokinetic studies comparing obese (BMI ≥30 kg/m2) and nonobese subjects showed a decrease in systemic exposure of oseltamivir in subjects with obesity (Ref); however, systemic exposure of oseltamivir carboxylate was similar (Ref).
Refer to adult dosing.
(For additional information see "Oseltamivir: Pediatric drug information")
Influenza, treatment:
Note: Clinical benefit is greatest if initiated within 48 hours. In patients with severe, complicated, or progressive illness, hospitalized patients, or those at increased risk for complications (see "Use" for details), initiate treatment as soon as possible even if >48 hours have elapsed since illness onset and do not delay for laboratory confirmation. For symptomatic outpatients with mild illness not at increased risk for complications, treatment can be considered if it can be initiated ≤48 hours following illness onset. Usual duration of therapy is 5 days; a longer duration can be considered in severely ill or immunocompromised patients (Ref).
Infants ≤8 months: Oral: 3 mg/kg/dose twice daily (Ref).
Infants ≥9 months: Oral: 3.5 mg/kg/dose twice daily (Ref); some experts still recommend manufacturer labeled dosing of 3 mg/kg/dose twice daily (Ref).
Children and Adolescents:
≤15 kg: Oral: 30 mg twice daily.
>15 to 23 kg: Oral: 45 mg twice daily.
>23 to 40 kg: Oral: 60 mg twice daily.
>40 kg: Oral: 75 mg twice daily.
Influenza, prophylaxis: Note: Recommendations for patient selection for prophylaxis are variable. Duration of chemoprophylaxis varies with exposure or outbreak type, influenza vaccination status, presence of immunosuppression, and risk of severe complications from infection; in general, duration for a community/household exposure is 7 days from last known exposure and duration for an institutional outbreak is a minimum of 2 weeks and at least 1 week after the last identified case. See current guidelines for details (Ref).
Infants 3 to 8 months: Limited data available: Oral: 3 mg/kg/dose once daily (Ref).
Infants ≥9 months: Limited data available: Oral: 3.5 mg/kg/dose once daily (Ref); some experts still recommend 3 mg/kg/dose once daily (Ref).
Children and Adolescents:
≤15 kg: Oral: 30 mg once daily.
>15 kg to 23 kg: Oral: 45 mg once daily.
>23 kg to 40 kg: Oral: 60 mg once daily.
>40 kg: Oral: 75 mg once daily.
Children and Adolescents:
Treatment: Limited data available (Ref):
Intermittent hemodialysis (IHD): Fixed dosing:
≤15 kg: 7.5 mg after each hemodialysis session.
>15 kg to ≤23 kg: 10 mg after each hemodialysis session.
>23 kg to ≤40 kg: 15 mg after each hemodialysis session.
>40 kg: 30 mg after each hemodialysis session.
Prophylaxis: There are no pediatric specific recommendations; based on experience in adult patients, dosage adjustment suggested.
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: There are no dosage adjustments provided in manufacturer's labeling (has not been studied).
Oseltamivir commonly causes nausea and vomiting (Ref). Most GI adverse reactions are transient and are unlikely to require discontinuation of therapy (Ref).
Mechanism: Dose-related (Ref); exact mechanism is unknown (Ref).
Onset: Rapid; most often within the first 2 days of treatment (Ref).
Risk factors:
• Increasing doses (Ref)
Rare occurrences of neuropsychiatric events (including confusion, delirium, hallucination, and/or self-injury) with oseltamivir have been reported primarily in children and adolescents from postmarketing surveillance. Clinicians should note that influenza infection may also be associated with behavioral and neurologic changes, including cases resulting in fatal outcomes; these events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe influenza disease.
Direct causation has not been established and data are conflicting. Several recent studies have shown either no difference in the estimated incidence of life-threatening abnormal behavior or a lower estimated risk of severe neuropsychiatric events in patients who received neuraminidase inhibitors, including oseltamivir (Ref); whereas others have continued to demonstrate an increased risk of psychiatric events (Ref).
Mechanism: Direct causation has not been established; exact mechanism is unknown, and effect may also be a result of the natural disease course of influenza (Ref). It is possible that inhibition of nicotinic acetylcholine receptors and monoamine oxidase-A receptors by oseltamivir is related to observed abnormal behaviors; action at NMDA and GABA receptors (similar to that which is seen with ketamine) or stimulation of D2 dopaminergic receptors may also be implicated (Ref).
Onset: Rapid; reports of neuropsychiatric events often occur within 2 days of both the influenza diagnosis and the initiation of oseltamivir treatment (Ref).
Risk factors: Note: Causality has not been established; therefore, risk factors listed below may reflect epidemiologic data as opposed to true risk factors.
• Children and adolescents 10 to 19 years of age (Ref)
• Males (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Vomiting (2% to 16%) (table 1)
|
Drug (Oseltamivir) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Oseltamivir) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
8% |
2% |
Children |
30 to 60 mg once daily for 10 days |
Prophylaxis |
148 |
N/A |
|
16% |
8% |
Children |
2 mg per kg twice daily for 5 days or weight-band dosing |
Treatment |
859 |
N/A |
|
2% |
1% |
Adolescents & adults |
75 mg once daily for up to 6 weeks |
Prophylaxis |
1,943 |
1,586 |
|
8% |
3% |
Adolescents & adults |
75 mg twice daily for 5 days |
Treatment |
2,646 |
1,977 |
Nervous system: Headache (adolescents and adults: 2% to 17%)
1% to 10%:
Gastrointestinal: Nausea (adolescents and adults: 8% to 10%) (table 2)
|
Drug (Oseltamivir) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Oseltamivir) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
8% |
4% |
Adolescents & adults |
75 mg once daily for up to 6 weeks |
Prophylaxis |
1,943 |
1,586 |
|
10% |
6% |
Adolescents & adults |
75 mg twice daily for 5 days |
Treatment |
2,646 |
1,977 |
Nervous system: Pain (adolescents and adults: 4%)
Postmarketing:
Cardiovascular: Bradycardia (Karplus 2010), cardiac arrhythmia
Dermatologic: Dermatitis, eczema, erythema multiforme, skin rash (Kaji 2005), Stevens-Johnson syndrome (Smith 2010), toxic epidermal necrolysis (Zuo 2019), urticaria
Endocrine & metabolic: Exacerbation of diabetes mellitus
Gastrointestinal: Gastrointestinal hemorrhage (Fang 2018), hemorrhagic colitis (Nakagawa 2011)
Hepatic: Abnormal hepatic function tests (Fang 2018), hepatitis
Hypersensitivity: Anaphylaxis (Hirschfeld 2008), facial edema, nonimmune anaphylaxis, swollen tongue (Kalsi 2011)
Nervous system: Abnormal behavior (Chen 2019), agitation (Kohen 2007), anxiety, confusion (rare: <1%) (Kohen 2007), delirium (rare: <1%) (Kohen 2007), delusion (Chen 2019), hallucination (rare: <1%) (Chen 2019, Nakamura 2010), hypothermia, impaired consciousness, nightmares, seizure
Hypersensitivity to oseltamivir or any component of the formulation
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with severe hepatic impairment; safety and efficacy have not been established.
• Renal impairment: Use with caution; dosage adjustment is required for patients with renal impairment.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Sorbitol: Oral suspension contains sorbitol (delivers ~2 g sorbitol per 75 mg dose) which is greater than the maximum daily limit for patients with hereditary fructose intolerance; may cause diarrhea and dyspepsia; use with caution.
Other warnings/precautions:
• Appropriate use: Oseltamivir is not a substitute for the influenza virus vaccine. It has not been shown to prevent primary or concomitant bacterial infections that may occur with influenza virus. Antiviral treatment should begin within 48 hours of symptom onset; however, the CDC recommends that treatment may still be beneficial and should be started in patients with severe, complicated or progressive illness, and in hospitalized patients if >48 hours. Treatment should not be delayed while awaiting results of laboratory tests for influenza (CDC 2022a).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as phosphate:
Tamiflu: 30 mg, 45 mg, 75 mg
Generic: 30 mg, 45 mg, 75 mg
Suspension Reconstituted, Oral, as base:
Tamiflu: 6 mg/mL (60 mL) [contains saccharin sodium, sodium benzoate, sorbitol; tutti-frutti flavor]
Generic: 6 mg/mL (60 mL)
Yes
Capsules (Oseltamivir Phosphate Oral)
30 mg (per each): $5.27 - $14.18
45 mg (per each): $5.27 - $14.18
75 mg (per each): $5.27 - $15.46
Capsules (Tamiflu Oral)
30 mg (per each): $16.72
45 mg (per each): $16.72
75 mg (per each): $18.23
Suspension (reconstituted) (Oseltamivir Phosphate Oral)
6 mg/mL (per mL): $0.88 - $2.89
Suspension (reconstituted) (Tamiflu Oral)
6 mg/mL (per mL): $3.04
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as phosphate:
Tamiflu: 30 mg, 45 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Tamiflu: 75 mg [contains corn starch]
Generic: 30 mg, 45 mg, 75 mg
Suspension Reconstituted, Oral, as base:
Tamiflu: 6 mg/mL (65 mL) [contains saccharin sodium, sodium benzoate]
Generic: 6 mg/mL (65 mL)
May be administered without regard to meals; take with food to improve tolerance.
Capsules may be opened and mixed with sweetened liquid (eg, chocolate syrup, corn syrup, caramel topping, light brown sugar dissolved in water). Administer oral suspension using an oral dosing dispenser that measures the appropriate volume in milliliters; shake well before each use. When oral suspension is not available and/or age-appropriate strength of capsules are not available to mix with sweetened liquids, an extemporaneous preparation may be prepared (refer to “extemporaneously prepared” section of monograph for further details).
Mechanically ventilated critically ill patients: May administer via naso- or orogastric (NG/OG) tube. Dissolve powder from capsules in 20 mL of sterile water and inject down the NG/OG tube; follow with a 10 mL sterile water flush (Ref).
Oral: May administer with or without food; may decrease stomach upset if administered with food.
Capsules: May be opened and mixed with sweetened liquid (eg, chocolate syrup, corn syrup, caramel topping, light brown sugar [dissolved in water]). May be administered via naso- or orogastric tube in mechanically ventilated patients; for a 150 mg dose (in adults), dissolve powder from two 75 mg capsules in 20 mL of sterile water and inject down the NG/OG tube; follow with a 10 mL sterile water flush (Ref). However, a prospective cohort study in critically ill pediatric patients (n=11; age range: 8 months to 19 years) found the concentration of oseltamivir carboxylate (active metabolite) to be lower when administered by enteral tube compared to oral administration; clinical significance is unclear; closely monitor patient response (Ref).
Oral suspension: Shake suspension well before use; measure dose in an appropriately sized calibrated oral syringe that provides accurate measurement of prescribed dose.
Influenza, seasonal, prophylaxis: Prophylaxis of influenza (A or B) infection in patients ≥1 year of age.
Influenza, seasonal, treatment: Treatment of uncomplicated acute illness due to influenza (A or B) infection in patients ≥2 weeks of age who have been symptomatic for ≤48 hours.
Limitations of use: Not a substitute for annual influenza vaccination. Consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use oseltamivir. Not recommended for patients with end-stage renal disease not undergoing dialysis.
Influenza A, avian, postexposure prophylaxis; Influenza A, avian, treatment
Tamiflu may be confused with Tambocor, Thera-Flu
Oseltamivir (Tamiflu) oral suspension is available in a 6 mg/mL concentration. Instructions to the patient should be provided based on these units of measure (ie, mL). When providing oseltamivir suspension, ensure the patient has an appropriately sized calibrated oral syringe that allows for accurate measurement of the prescribed dose.
When commercially-prepared oseltamivir oral suspension is not available, an extemporaneously prepared suspension may be compounded to provide a 6 mg/mL concentration.
Substrate of OAT1/3
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Dichlorphenamide: May increase the serum concentration of Oseltamivir. Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Management: Avoid use of fexinidazole with OAT1/3 substrates when possible. If combined, monitor for increased OAT1/3 substrate toxicities. Risk D: Consider therapy modification
Influenza Virus Vaccine (Live/Attenuated): Antiviral Agents (Influenza A and B) may diminish the therapeutic effect of Influenza Virus Vaccine (Live/Attenuated). Management: Avoid administration of live influenza virus vaccine (LAIV) within 2 weeks before or 48 hours after administration of antiviral agents. Consider avoiding LAIV if peramivir was given within the last 5 days or baloxavir was given within the last 17 days. Risk D: Consider therapy modification
Leflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Nitisinone: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Pretomanid: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Probenecid: May increase serum concentrations of the active metabolite(s) of Oseltamivir. Risk C: Monitor therapy
Taurursodiol: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk X: Avoid combination
Teriflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Vaborbactam: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Oseltamivir phosphate and its active metabolite oseltamivir carboxylate cross the placenta (Meijer 2012).
Based on multiple studies, the maternal use of oral oseltamivir is acceptable for use during pregnancy (CDC 2022a; CDC 2022e).
Pregnant and postpartum patients (≤2 weeks after delivery) have a higher risk for complications from untreated seasonal influenza, including preterm delivery, pneumonia, admission to a hospital or ICU, and maternal and fetal death. Underlying maternal medical conditions increase these risks (ACOG 2018; CDC 2022a). Treatment with oseltamivir prevents maternal respiratory failure and death when started <3 days of the onset of illness; benefit is still obtained when started 3 to 4 days after onset in comparison to ≥5 days (CDC 2022a; CDC 2022e).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of oseltamivir may be altered (Beigi 2011; Greer 2011a; Pillai 2015). Dosing is the same as in nonpregnant patients (CDC 2022a; CDC 2022e). Higher doses may be needed in some patients; however, safety data for higher dosing during pregnancy are not available (CDC 2022e).
Oral oseltamivir is the preferred neuraminidase inhibitor for the treatment and prophylaxis of seasonal influenza during pregnancy. Pregnant patients with known or suspected influenza can be treated with antiviral medications, regardless of trimester, vaccination status, or laboratory test results. Postexposure antiviral prophylaxis may be considered for pregnant and postpartum patients (including following pregnancy loss) (ACOG 2018; CDC 2022a; CDC 2022e).
An algorithm is available for the treatment of pregnant patients with known or suspected seasonal influenza (ACOG 2018). Refer to the Centers for Disease Control and Prevention recommendations for treatment updates based on resistance patterns (ACOG 2018; CDC 2022a).
Oseltamivir and oseltamivir carboxylate are present in breast milk.
Data related to the presence of oseltamivir in breast milk are available from 2 studies:
• Breast milk was sampled following maternal administration of oral oseltamivir 75 mg twice daily for 5 days for the treatment of H5N1 influenza in 1 lactating patient at 9 months postpartum. Eleven breast milk samples were obtained over the dosing period. Using the maximum breast milk concentration of oseltamivir plus oseltamivir carboxylate (81.6 ng/mL), the authors of the study calculated the relative infant dose (RID) of oseltamivir to be 0.5% of the weight-adjusted maternal dose of 2.5 mg/kg/day, providing an estimated daily infant dose via breast milk of 0.012 mg/kg/day (Wentges-van Holthe 2008). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).
• A second study included 7 women given a single dose oseltamivir 75 mg immediately postpartum. Breast milk was collected for 24 hours after the dose. The maximum breast milk concentrations occurred at 3.4 ± 2.2 hours for oseltamivir and 18.9 ± 6.4 hours for oseltamivir carboxylate. The half-life of oseltamivir was ~4 hours in both the maternal serum and breast milk. Small amounts of oseltamivir carboxylate continued to be measurable in breast milk 24 hours after the single dose (~30 ng/mL) (Greer 2011b).
• Adverse events following exposure to oseltamivir via breast milk are unlikely due to poor excretion into breast milk (CDC 2021b).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. However, breastfeeding does not need to be discontinued during oseltamivir treatment (IDSA [Uyeki 2019]). Due to limited excretion into breast milk, oseltamivir may be the preferred neuraminidase inhibitor for the treatment of seasonal influenza in patients who are breastfeeding. Infectious patients should take precautions to avoid influenza transmission to the breastfed infant. If the mother is too ill to breastfeed, expressed breast milk can be given to the infant by a healthy caregiver who does not have influenza (CDC 2021b).
Take without regard to meals; take with food to improve tolerance.
Signs or symptoms of unusual behavior, including attempts at self-injury, confusion, and/or delirium
Critically ill patients: Repeat rRT-PCR or viral culture may help to determine on-going viral replication
Oseltamivir, a prodrug, is hydrolyzed to the active form, oseltamivir carboxylate (OC). OC inhibits influenza virus neuraminidase, an enzyme known to cleave the budding viral progeny from its cellular envelope attachment point (neuraminic acid) just prior to release.
Note: Concurrent use of extracorporeal membrane oxygenation (ECMO): When used alone, ECMO has been shown not to impact oseltamivir carboxylate Cmax and AUC in 2 small studies (Lemaitre 2012; Mulla 2013). Pharmacokinetics in children ≥12 years and adolescents are similar to adults.
Absorption: Well absorbed.
Distribution: Vd: Oseltamivir carboxylate:
Pediatric patients (Kimberlin 2013):
≤2 months: Median: 5.8 L/kg; Range: 2.97 to 44.91 L/kg.
3 to 5 months: Median: 10.4 L/kg; Range: 4.03 to 13.94 L/kg.
6 to 8 months: Median: 10.19 L/kg; Range: 1.39 to 107.59 L/kg.
9 to 11 months:
3 mg/kg: Median: 15.13 L/kg; Range: 5.46 to 95.3 L/kg.
3.5 mg/kg: Median: 10.41 L/kg; Range: 7.04 to 21.56 L/kg.
12 to 23 months:
3.5 mg/kg: Median: 24.36 L/kg; Range: 8.97 to 47.37 L/kg.
30 mg (fixed dose): Median: 13.92 L/kg; Range: 5.89 to 53.31 L/kg.
Adults: 23 to 26 L; may be significantly increased in patients receiving ECMO (Lemaitre 2012; Mulla 2013).
Protein binding, plasma: Oseltamivir carboxylate: 3%; Oseltamivir: 42%.
Metabolism: Hepatic (90%) to oseltamivir carboxylate; neither the parent drug nor active metabolite has any effect on the cytochrome P450 system.
Bioavailability: 75% as oseltamivir carboxylate.
Half-life elimination:
Pediatric patients (Kimberlin 2013): Oseltamivir carboxylate:
≤2 months: Median: 6.64 hours; Range: 4.65 to 28.71 hours.
3 to 5 months: Median: 9.09 hours; Range: 6.25 to 19 hours.
6 to 8 months: Median:10.29 hours; Range: 1.02 to 78.26 hours.
9 to 11 months:
3 mg/kg: Median: 11.13 hours; Range: 5.4 to 51.86 hours.
3.5 mg/kg: Median: 14.56 hours; Range: 7.22 to 25.67 hours.
12 to 23 months:
3.5 mg/kg: Median: 14.82 hours; Range: 8.13 to 20.16 hours.
30 mg (fixed dose): Median: 7.98 hours; Range: 4.49 to 17.11 hours.
Adults: Oseltamivir: 1 to 3 hours; Oseltamivir carboxylate: 6 to 10 hours.
Excretion: Urine (>99% as oseltamivir carboxylate); feces (<20%).
Altered kidney function: Exposure to the active metabolite is inversely proportional to declining renal function. In continuous ambulatory peritoneal dialysis (CAPD) patients, the peak concentration of the active metabolite following a single 30 mg oseltamivir dose or once-weekly oseltamivir was 3-fold higher than in patients with normal renal function receiving the approved adult dose. Administration of 30 mg once weekly to CAPD patients resulted in plasma concentrations of active metabolite comparable to patients with normal renal function receiving the approved adult doses.
Pediatric: Preterm neonates have decreased clearance of oseltamivir due to immature renal function (Acosta 2010). Exposure to active metabolite (oseltamivir carboxylate) is more variable in neonates and young infants (<9 months of age) due to maturation and greater variability of the carboxylesterase HCE-1; formation of active metabolite may be delayed, but overall exposure is similar. Clearance of the active metabolite increases throughout infancy. Exposures in these patients may be lower for similar mg/kg doses, particularly beginning at age 9 months (Kimberlin 2013). Children ≤12 years of age clear the prodrug and active metabolite faster than adults, resulting in a lower exposure with a given mg/kg dose. The pharmacokinetics of the prodrug in patients >12 years of age are similar to adult patients.
Older adult: Exposure to the active metabolite at steady state was 25% to 35% higher in elderly patients.
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