Skip to Content

Oseltamivir

Medically reviewed on Nov 15, 2018

Pronunciation

(oh sel TAM i vir)

Index Terms

  • Oseltamivir Phosphate

Dosage Forms

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)

Brand Names: U.S.

  • Tamiflu

Pharmacologic Category

  • Antiviral Agent
  • Neuraminidase Inhibitor

Pharmacology

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.

Absorption

Well absorbed

Distribution

Vd: 23 to 26 L (oseltamivir carboxylate); may be significantly increased in patients receiving ECMO (Lemaitre 2012; Mulla 2013)

Metabolism

Hepatic (90%) to oseltamivir carboxylate; neither the parent drug nor active metabolite has any effect on the cytochrome P450 system

Excretion

Urine (>99% as oseltamivir carboxylate); feces (<20%)

Half-Life Elimination

Oseltamivir: 1 to 3 hours; Oseltamivir carboxylate: 6 to 10 hours

Protein Binding

Plasma: Oseltamivir carboxylate: 3%; Oseltamivir: 42%

Special Populations: Renal Function Impairment

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.

Special Populations: Elderly

Exposure to the active metabolite at steady state was 25% to 35% higher in elderly patients.

Special Populations: Children

Children ≤12 years of age clear the prodrug and active metabolite faster than adult patients, resulting in a lower exposure to a given mg/kg dose. The pharmacokinetics of the prodrug in patients >12 years of age are similar to adult patients.

Use: Labeled Indications

Influenza, seasonal: Prophylaxis of influenza (A or B) infection in patients ≥1 year of age.

Influenza, seasonal: Treatment of uncomplicated acute illness due to influenza (A or B) infection in patients ≥2 weeks of age who have been symptomatic for no more than 48 hours.

Note: The Advisory Committee on Immunization Practices (ACIP) recommends that treatment and prophylaxis be given to children <1 year of age when indicated (CDC 2011).

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 phosphate oral. Not recommended for patients with end-stage renal disease not undergoing dialysis.

Off Label Uses

Influenza, avian A H7N9 ("Asian H7N9"), prophylaxis

Based on CDC interim guidance on influenza antiviral chemoprophylaxis of persons exposed to birds with Avian Influenza A virus, oseltamivir may be considered for postexposure prophylaxis in all persons exposed to avian influenza A viruses associated with severe human disease or with the potential to cause severe human disease.

Influenza, avian A H7N9 ("Asian H7N9"), treatment

Based on CDC interim guidance on the use of antiviral medications for treatment of human infections with novel Influenza A viruses associated with severe human disease, oseltamivir is recommended for treatment of influenza in hospitalized patients and outpatients with severe, complicated, or progressive illness due to avian influenza A virus. Oseltamivir may also be considered in outpatients with uncomplicated illness due to avian influenza A virus. Most human infections of avian influenza A H7N9 virus occur after exposure to infected poultry or contaminated environments. Rare instances of limited person-to-person spread have been identified in China but there is no evidence of sustained person-to-person spread. Some human infections with Asian H7N9 have been reported outside of mainland China, Hong Kong or Macao, but all of these infections have occurred among people who had traveled to China before becoming ill. To date, Asian H7N9 viruses have not been detected in people or birds in the US (CDC 2018b).

Contraindications

Hypersensitivity to oseltamivir or any component of the formulation

Dosing: Adult

Influenza, seasonal (strains A or B), prophylaxis:

Postexposure prophylaxis: Oral: 75 mg once daily; postexposure chemoprophylaxis should generally only be used within 48 hours of the most recent exposure (CDC 2011; CDC 2018a). In patients who are previously unvaccinated, administer the influenza vaccine upon presentation, if possible.

Target population (when antiviral supplies are not limited): Those at increased risk for influenza complications (see Persons at increased risk for influenza complications section below) and who have had close contact (ie, cared for or lived with) or been in a setting where there was a high likelihood of contact with respiratory droplets and/or body fluids with a person who has confirmed or suspected influenza during that person's infectious period (CDC 2011; CDC 2018a; Zachary 2018a).

Vaccine status of target population (to aid in decision to offer postexposure chemoprophylaxis):

Previously unvaccinated with an indication for chemoprophylaxis: Chemoprophylaxis should be offered (Harper 2009, Zachary 2018a).

Previously vaccinated with an indication for chemoprophylaxis: During seasons in which there is not a good match between vaccine antigens and circulating viruses, vaccinated individuals should be managed as if they are unvaccinated and prophylaxis should be offered (Harper 2009; Zachary 2018a). Chemoprophylaxis should be considered in newly-vaccinated persons at high risk of influenza complications during the first 2 weeks following vaccination after exposure (CDC 2018a).

Pregnant women and postpartum women (within 2 weeks of delivery) with an indication for chemoprophylaxis: ACIP and CDC recommend chemoprophylaxis be considered (vaccine status not specified in recommendations) (CDC 2011; CDC 2017); however, some experts suggest chemoprophylaxis only for unvaccinated pregnant women during the second trimester (with certain comorbidities) or for unvaccinated pregnant women during the third trimester (regardless of comorbidities) due to data showing risk increases by trimester and with associated comorbidities (Zachary 2018a).

Institutional (eg, long-term care facilities) outbreaks (regardless of vaccination status): For influenza outbreaks in institutions (eg, nursing homes and other chronic care facilities), chemoprophylaxis is a key component of outbreak control and is recommended for all residents (CDC 2011; Harper 2009).

Duration of oseltamivir therapy for postexposure chemoprophylaxis (varies by indication/factors):

Previously unvaccinated patients: 14 days following vaccination administration (Harper 2009; Zachary 2018a)

Previously vaccinated patients: 7 days after the last known exposure (CDC 2018a)

Pregnant women and postpartum women (within 2 weeks of delivery): 7 days after most recent exposure (CDC 2017); some experts recommend continuing chemoprophylaxis for 10 days after close contact with someone likely to have been infected with influenza or after household exposure (ACOG 2018; Jamieson 2018; Harper 2009).

Institutional (eg, long-term care facilities) outbreaks: All residents (regardless of vaccination status): At least 2 weeks and for 1 week after the last known identified case (CDC 2018a). Consider offering chemoprophylaxis in both unvaccinated and vaccinated employees based on CDC recommendations (CDC 2011; CDC 2018a). Note: Infection control policies for employees may vary by institution.

Influenza, seasonal (strains A or B), prophylaxis: Preexposure prophylaxis: Note: For persons at very high risk for influenza complications (eg, severely immunocompromised hosts) who cannot be protected by any other means (CDC 2011). Oral: 75 mg once daily for the duration of time when exposure might occur which depends on the duration of community influenza activity; regimens up to 42 days of oseltamivir have been well tolerated (CDC 2011; Harper 2009).

Influenza, seasonal (strains A or B), treatment: Oral: 75 mg twice daily (CDC 2018a). Note: Increasing the dose to 150 mg twice daily in severely ill or immunocompromised patients, which had previously been suggested during the H1N1 pandemic of 2009 to 2010, is not currently recommended by experts for seasonal influenza (Zachary 2018b); available data suggest that standard doses of 75 mg twice daily are adequately absorbed in critically-ill patients and produce adequate therapeutic levels (Ariano 2010; CDC 2018a).

Timing of initiation/target population: Initiate as soon as possible (and ideally, within 48 hours of illness) in any patient with severe, complicated or progressive illness; who is hospitalized; or who is at higher risk for influenza complications (see Persons at increased risk for influenza complications section below); initiation should not be delayed for laboratory confirmation in these patients since clinical benefit is greatest when treatment is initiated as soon as possible after illness onset, especially within 48 hours (CDC 2018a). If any of these patients present >48 hours after symptom onset, treatment should not be withheld. Patients with mild illness and without an increased risk for influenza complications (see Persons at increased risk for influenza complications section below) are unlikely to benefit if treatment is initiated >48 hours after symptom onset, and most experts would not treat these patients (Zachary 2018b).

Duration of therapy: Usual duration: 5 days; however, some experts would consider a longer duration in severely-ill or immunocompromised patients (CDC 2018a; Zachary 2018b).

Influenza, avian A H7N9 ("Asian H7N9"), prophylaxis (off-label use): Postexposure prophylaxis: Oral: 75 mg twice daily (CDC interim guidance 2016a)

Target population: Postexposure chemoprophylaxis can be considered for all exposed persons; decisions to initiate antiviral chemoprophylaxis should be based on clinical judgement with consideration given to the type of exposure and to whether the person is at high risk for complications from influenza (see Persons at increased risk for influenza complications section below). Also refer to the CDC website for additional information (CDC interim guidance 2016a).

Duration of therapy: 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 (up to 10 days incubation period) in the case-patient (CDC interim guidance 2016a; Thorner 2018).

Influenza, avian A H7N9 ("Asian H7N9"), treatment (off-label use):

Hospitalized patients and outpatients with severe, complicated, or progressive illness: Limited data available; recommendations based on expert opinion: Oral: 75 mg twice daily; however, the optimal dose for severe or complicated avian influenza A H7N9 is uncertain (CDC interim guidance 2016b). Increasing the dose to 150 mg twice daily in severely ill or immunocompromised patients has previously been suggested by some experts in the setting of other influenza viruses (eg, H1N1 pandemic of 2009 to 2010); however, available data suggest that standard doses of 75 mg twice daily are adequately absorbed in critically-ill patients, and produce adequate therapeutic levels (Ariano 2010; CDC 2018a).

Timing of initiation: Initiate as soon as possible, even if >48 hours has elapsed since illness onset. Treatment should not be delayed while waiting for lab results (CDC interim guidance 2016b).

Duration of therapy: The optimal duration for severe or complicated avian influenza is uncertain; pending further data, longer courses of treatment (eg, 10 days) should be considered (CDC interim guidance 2016b).

Uncomplicated illness, outpatients: Limited data available; recommendations based on expert opinion: Oral: 75 mg twice daily (CDC interim guidance 2016b).

Timing of initiation:Initiate as soon as possible, even if >48 hours has elapsed since illness onset, in patients with confirmed, probable, or cases under investigation based on exposure criteria. Treatment is not currently recommended for uncomplicated illness in outpatients whose exposure criteria consists only of travel to an area with human cases of H7N9, or where these viruses are known to be circulating in animals. Treatment in outpatients with uncomplicated disease in whom fever is absent and symptoms are nearly resolved should be based on clinical judgment and on a case-by-case basis; additional guidance can be found on the CDC website (CDC interim guidance 2016b).

Duration of therapy: Usual duration: 5 days (CDC interim guidance 2016b).

Persons at increased risk for influenza complications: Adults ≥65 years, children <5 years, but especially <2 years (with rates of hospitalization and mortality highest among those <6 months), women who are pregnant or postpartum [within 2 weeks after delivery], residents of nursing homes and other chronic care facilities, Native Americans and Alaska natives, and persons with extreme obesity (BMI ≥40). Individuals with certain chronic medical conditions including pulmonary (includes asthma), cardiovascular (excludes hypertension alone), renal, hepatic, hematologic (includes sickle cell disease), metabolic disorders (includes diabetes mellitus), neurologic/neurodevelopment conditions (includes cerebral palsy, seizure disorders, stroke, intellectual disability, muscular dystrophy, spinal cord injury), immunosuppressed due to disease (eg, HIV, cancer) or medication (eg, chronic glucocorticoids), and persons <19 years of age on long-term aspirin therapy (CDC 2011; CDC 2018c).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Influenza, seasonal (strains A or B), treatment: Note: Treatment should ideally begin within 48 hours; however, initiation after 48 hours may decrease mortality or duration of illness. Hospitalized patients may require longer (eg, ≥10 days) treatment courses. Initiate as early as possible in any hospitalized patient with suspected/confirmed influenza (CDC 2011).

Infants:

Weight-based dosing (preferred):

CDC recommendations (independent of HIV status) (CDC 2018a; DHHS [pediatric] 2013): Manufacturer's labeling: Oral: 3 mg/kg/dose twice daily for 5 days

IDSA/PIDS recommendations (Bradley 2011): Oral:

1 to 8 months: 3 mg/kg/dose twice daily

9 to 11 months: 3.5 mg/kg/dose twice daily

Fixed dosing (use only if weight not available) (AAP 2010): Limited data available: Oral:

<3 months: 12 mg twice daily for 5 days

3 to 5 months: 20 mg twice daily for 5 days

6 to 11 months: 25 mg twice daily for 5 days

Children 12 to 23 months:

CDC recommendations (independent of HIV status) (CDC 2018a; DHHS [pediatric] 2013): Oral:

≤15 kg: 30 mg twice daily for 5 days

>15 to 23 kg: 45 mg twice daily for 5 days

>23 kg: See dosage recommendations below for children ≥2 years

IDSA/PIDS recommendations (Bradley 2011): Oral: 3.5 mg/kg/dose twice daily; weight-dependent maximum dose: Weight ≤15 kg: 30 mg; Weight >15 to 23 kg: 45 mg

Children ≥2 to 12 years and Adolescents (independent of HIV status): Note: Manufacturer's labeling consistent with current CDC and IDSA/PIDS recommendations (Bradley 2011; CDC 2018a; DHHS [pediatric] 2013): Oral:

≤15 kg: 30 mg twice daily for 5 days

>15 to 23 kg: 45 mg twice daily for 5 days

>23 to 40 kg: 60 mg twice daily for 5 days

>40 kg: 75 mg twice daily for 5 days

Influenza, seasonal (strains A or B), prophylaxis: Note: Initiate treatment within 48 hours of contact with an infected individual. Duration of prophylaxis dependent upon type of exposure or outbreak (eg, household exposure vs hospital outbreak); see below for further details.

Infants: Limited data available

Weight-directed dosing (preferred):

CDC recommendation (independent of HIV status) (CDC 2018a; DHHS [pediatric] 2013): Oral:

<3 months: Not recommended unless clinically critical

3 to 11 months: 3 mg/kg/dose once daily

IDSA/PIDS recommendations (Bradley 2011): Oral:

3 to 8 months: 3 mg/kg/dose once daily

9 to 11 months: 3.5 mg/kg/dose once daily

Fixed dosing (use only if weight not available) (AAP 2010): Oral:

<3 months: Not recommended unless clinically critical

3 to 5 months: 20 mg once daily

6 to 11 months: 25 mg once daily

Children 12 to 23 months:

CDC Recommendations (independent of HIV status) (CDC 2018a; DHHS [pediatric] 2013): Oral:

≤15 kg: 30 mg once daily

>15 to 23 kg: 45 mg dose once daily

>23 kg: See dosage recommendations below for weight.

IDSA/PIDS Recommendations (Bradley 2011): Oral: 3.5 mg/kg/dose once daily; weight-dependent maximum dose: Weight: ≤15 kg: 30 mg; Weight >15 to 23 kg: 45 mg

Children: 2 to 12 years and Adolescents (independent of HIV status): Note: Manufacturer's labeling consistent with current CDC and IDSA/PIDS recommendations (Bradley 2011; CDC 2018a; DHHS [pediatric] 2013): Oral:

≤15 kg: 30 mg once daily

>15 kg to ≤23 kg: 45 mg once daily

>23 kg to ≤40 kg: 60 mg once daily

>40 kg: 75 mg once daily

Prophylaxis duration:

Individual/household exposure:

Manufacturer's labeling: 10 days

Alternate recommendations:

Non-HIV-exposed/-positive: 7 days (CDC 2018a)

HIV-exposed/-positive: 10 days for household exposure; 7 days for other exposures (DHHS [pediatric] 2013)

Community/institutional outbreak:

Manufacturer's recommendation: May be used for up to 6 weeks

Alternate recommendations: Continue for ≥2 weeks and until ~7 days after identification of illness onset in the last patient (CDC 2018a) or until influenza activity in community subsides or immunity obtained from immunization (Bradley 2011). During community outbreaks, duration of protection lasts for length of dosing period; safety and efficacy have been demonstrated for use up to 6 weeks in immunocompetent patients and safety has been demonstrated for use up to 12 weeks in patients who are immunocompromised.

Persons at increased risk for influenza complications: Refer to adult dosing.

Dosing: Renal Impairment

Treatment: Adults:

CrCl >60 mL/minute: No dosage adjustment necessary

CrCl >30 to 60 mL/minute: 30 mg twice daily

CrCl >10 to 30 mL/minute: 30 mg once daily

ESRD not undergoing dialysis: Use is not recommended (has not been studied)

Prophylaxis: Adults:

CrCl >60 mL/minute: No dosage adjustment necessary

CrCl >30 to 60 mL/minute: 30 mg once daily

CrCl >10 to 30 mL/minute: 30 mg every other day

ESRD not undergoing dialysis: Use is not recommended (has not been studied)

Intermittent hemodialysis (IHD) (CrCl ≤10 mL/minute):

Adults:

Treatment: 30 mg immediately and then 30 mg after every hemodialysis session for 5 days. Note: Assumes three hemodialysis sessions in the 5-day period.

Alternative recommendations: Treatment (AMMI Canada [Aoki 2012]):

Low-flux hemodialysis: 30 mg after each dialysis session for 5 days

High-flux hemodialysis: 75 mg after each dialysis session for 5 days

Prophylaxis: 30 mg immediately and then 30 mg after every other hemodialysis sessions for the recommended prophylaxis duration.

Children >1 year of age (off-label dose; Schreuder 2010): Treatment:

≤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

Continuous ambulatory peritoneal dialysis (CAPD): Adults:

Treatment: 30 mg immediately as a single dose (single dose provides a 5-day duration)

Prophylaxis: 30 mg immediately and then 30 mg once weekly for the recommended prophylaxis duration

Note: For patients receiving aggressive automated peritoneal dialysis (APD) with negligible or low residual renal function, a small pharmacokinetic study suggests that 75 mg as a single dose for treatment would produce drug exposure at the upper limit of the safety margin (Patel 2015).

Continuous renal replacement therapy (CRRT) (high-flux):

Treatment (off-label dose; limited data): 30 mg once daily for 5 days or 75 mg every 48 hours to provide a 5-day duration (AMMI Canada [Aoki 2012]; Ariano 2010)

Prophylaxis (off-label): No data (AMMI Canada [Aoki 2012])

Continuous veno-venous hemodialysis (CVVHD): Adults: Note: Limited information available; optimal dosing has not been established: 150 mg twice daily administered via nasogastric or postpyloric feeding tube for suspected or confirmed H1N1 influenza demonstrated supratherapeutic oseltamivir carboxylate concentrations at effluent rates of 3,300 ± 919 mL/hour; the authors determined that the manufacturer recommended dosage of 75 mg once daily for patients with CrCl 10 to 30 mL/minute will likely achieve concentrations necessary to inhibit viral neuraminidase activity at these effluent rates; however, doses >75 mg once daily may be required when using higher effluent rates (Eyler 2012).

CVVHD and concurrent use of ECMO: Adults: Lower oseltamivir carboxylate concentrations (~981 ng/mL) were observed as compared to those with the use of CVVHD alone (~2,760 ng/mL) when patients were administered 150 mg twice daily for suspected or confirmed H1N1 influenza (n=4; Eyler 2012).

Dosing: Hepatic Impairment

Mild-to-moderate impairment: No dosage adjustment necessary.

Severe impairment: No dosage adjustment provided in manufacturer’s labeling (has not been studied).

Dosing: Obesity

In adult morbidly obese patients (BMI >40 kg/m2), systemic exposure of oseltamivir carboxylate was not reduced; therefore, no dosage adjustment is necessary (Thorne-Humphrey 2011).

Reconstitution

Oral suspension: Reconstitute with 55 mL of water to a final concentration of 6 mg/mL (to make 60 mL total suspension).

Extemporaneously Prepared

If the commercially prepared oral suspension is not available, the manufacturer provides the following compounding information to prepare a 6 mg/mL suspension in emergency situations.

1. Place the specified amount of water into a polyethyleneterephthalate (PET) or glass bottle.

2. Carefully separate the capsule body and cap and pour the contents of the required number of 75 mg capsules into the PET or glass bottle.

3. Gently swirl the suspension to ensure adequate wetting of the powder for at least 2 minutes.

4. Slowly add the specified amount of vehicle to the bottle.

5. Close the bottle using a child-resistant cap and shake well for 30 seconds to completely dissolve the active drug.

6. Label “Shake Well Before Use.”

Stable for 35 days at 2°C to 8°C (36°F to 46°F) or 5 days at 25° C (77°F). Alternate recommendations suggest that preparations made with water containing preservative (ie, 0.05% sodium benzoate) are stable for 49 days at 2°C to 8°C (36°F to 46°F) and 10 days at 25°C (77°F) (Tamiflu Canadian product labeling 2017). Shake gently prior to use. Do not dispense with dosing device provided with commercially-available product.

Preparation of Oseltamivir 6 mg/mL Suspension

Body Weight

Total Volume per Patient1

# of 75 mg Capsules2

Required Volume of Water

Required Volume of Vehicle2,3

Treatment Dose (wt based)4

Prophylactic Dose (wt based)4

1Entire course of therapy.

2Based on total volume per patient.

3Acceptable vehicles are cherry syrup (Humco®), Ora-Sweet® SF, or simple syrup.

4Using 6 mg/mL suspension.

≤15 kg

75 mL

6

5 mL

69 mL

5 mL (30 mg) twice daily for 5 days

5 mL (30 mg) once daily for 10 days

16 to 23 kg

100 mL

8

7 mL

91 mL

7.5 mL (45 mg) twice daily for 5 days

7.5 mL (45 mg) once daily for 10 days

24 to 40 kg

125 mL

10

8 mL

115 mL

10 mL (60 mg) twice daily for 5 days

10 mL (60 mg) once daily for 10 days

≥41 kg

150 mL

12

10 mL

137 mL

12.5 mL (75 mg) twice daily for 5 days

12.5 mL (75 mg) once daily for 10 days

Table has been converted to the following text.

Preparation of Oseltamivir 6 mg/mL Suspension

Weight-based details:

≤15 kg: To make a 6 mg/mL suspension, open six 75 mg capsules. Mix with 5 mL water and 69 mL vehicle to provide a total of 75 mL. Treatment dose is 5 mL (30 mg) twice daily for 5 days. Prophylactic dose is 5 mL (30 mg) once daily for 10 days.

16 to 23 kg: To make a 6 mg/mL suspension, open eight 75 mg capsules. Mix with 7 mL water and 91 mL vehicle to provide a total of 100 mL. Treatment dose is 7.5 mL (45 mg) twice daily for 5 days. Prophylactic dose is 7.5 mL (45 mg) once daily for 10 days.

24 to 40 kg: To make a 6 mg/mL suspension, open ten 75 mg capsules. Mix with 8 mL water and 115 mL vehicle to provide a total of 125 mL. Treatment dose is 10 mL (60 mg) twice daily for 5 days. Prophylactic dose is 10 mL (60 mg) once daily for 10 days.

≥41 kg: To make a 6 mg/mL suspension, open twelve 75 mg capsules. Mix with 10 mL water and 137 mL vehicle to provide a total of 150 mL. Treatment dose is 12.5 mL (75 mg) twice daily for 5 days. Prophylactic dose is 12.5 mL (75 mg) once daily for 10 days.

Alternate recommendations (Tamiflu Canadian product labeling 2017):

Preparation of Oseltamivir 6 mg/mL Suspension: (using water with preservative [ie, 0.05% sodium benzoate])

Body Weight

Total Volume per Patient1

# of 75 mg Capsules2

Required Volume of Water (with preservative)

Treatment Dose (wt based)2,3

Prophylactic Dose (wt based)2,3

1Entire course of therapy.

2Using 6 mg/mL suspension.

3Measured dose should be mixed with an equal amount of sweetened liquid (eg, chocolate syrup, cherry syrup) to mask bitter taste.

≤15 kg

75 mL

6

74 mL

5 mL (30 mg) twice daily for 5 days

5 mL (30 mg) once daily for 10 days

16 to 23 kg

100 mL

8

98 mL

7.5 mL (45 mg) twice daily for 5 days

7.5 mL (45 mg) once daily for 10 days

24 to 40 kg

125 mL

10

123 mL

10 mL (60 mg) twice daily for 5 days

10 mL (60 mg) once daily for 10 days

≥41 kg

150 mL

12

147 mL

12.5 mL (75 mg) twice daily for 5 days

12.5 mL (75 mg) once daily for 10 days

Table has been converted to the following text.

Preparation of Oseltamivir 6 mg/mL Suspension

(using water with preservative [ie, 0.05% sodium benzoate]) (Tamiflu Canadian product labeling 2017)

Weight-based details:

≤15 kg: To make a 6 mg/mL suspension, open six 75 mg capsules. Mix with 74 mL water with preservative to provide a total of 75 mL. Treatment dose is 5 mL (30 mg) twice daily for 5 days. Prophylactic dose is 5 mL (30 mg) once daily for 10 days.

16 to 23 kg: To make a 6 mg/mL suspension, open eight 75 mg capsules. Mix with 98 mL water with preservative to provide a total of 100 mL. Treatment dose is 7.5 mL (45 mg) twice daily for 5 days. Prophylactic dose is 7.5 mL (45 mg) once daily for 10 days.

24 to 40 kg: To make a 6 mg/mL suspension, open ten 75 mg capsules. Mix with 123 mL water with preservative to provide a total of 125 mL. Treatment dose is 10 mL (60 mg) twice daily for 5 days. Prophylactic dose is 10 mL (60 mg) once daily for 10 days.

≥41 kg: To make a 6 mg/mL suspension, open twelve 75 mg capsules. Mix with 147 mL water with preservative to provide a total of 150 mL. Treatment dose is 12.5 mL (75 mg) twice daily for 5 days. Prophylactic dose is 12.5 mL (75 mg) once daily for 10 days.

Administration

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 (Taylor 2008).

Dietary Considerations

Take without regard to meals; take with food to improve tolerance.

Storage

Capsules: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Oral suspension: Store powder for suspension at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Once reconstituted, store oral suspension under refrigeration at 2°C to 8°C (36°F to 46°F) or at room temperature; do not freeze. Use within 10 days of preparation if stored at room temperature or within 17 days of preparation if stored under refrigeration.

Drug Interactions

Influenza Virus Vaccine (Live/Attenuated): Antiviral Agents (Influenza A and B) may diminish the therapeutic effect of Influenza Virus Vaccine (Live/Attenuated). Management: Avoid anti-influenza antivirals during the period beginning 48 hours prior to and ending 2 weeks after live influenza virus vaccine administration. Consider therapy modification

Probenecid: May increase serum concentrations of the active metabolite(s) of Oseltamivir. Management: Consider a change in therapy when using oseltamivir together with probenecid; reduced oseltamivir dose may be necessary. Increase monitoring for adverse events, such as thrombocytopenia. Consider therapy modification

Adverse Reactions

>10%:

Central nervous system: Headache (adolescents and adults: 2% to 17%)

Gastrointestinal: Vomiting (2% to 16%)

1% to 10%:

Central nervous system: Pain (adolescents and adults: 4%)

Gastrointestinal: Nausea (adolescents and adults: 8% to 10%)

<1%, postmarketing, and/or case reports: Abnormal behavior, abnormal hepatic function tests, accidental injury, agitation, anaphylactoid reaction, anaphylaxis, anxiety, cardiac arrhythmia, confusion, delirium, delusions, dermatitis, eczema, erythema multiforme, exacerbation of diabetes mellitus, facial edema, gastrointestinal hemorrhage, hallucination, hemorrhagic colitis, hepatitis, hypersensitivity reaction, hypothermia, impaired consciousness, nightmares, seizure, skin rash, Stevens-Johnson syndrome, swollen tongue, toxic epidermal necrolysis, urticaria

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis/hypersensitivity: Rare but severe hypersensitivity reactions, including anaphylaxis and severe dermatologic reactions (eg, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme), have been associated with use. Discontinue use immediately if hypersensitivity occurs or is suspected and treat appropriately.

• Neuropsychiatric events: Rare occurrences of neuropsychiatric events (including confusion, delirium, hallucinations, and/or self-injury) have been reported primarily in pediatric patients from postmarketing surveillance; direct causation is difficult to establish (influenza infection may also be associated with behavioral and neurologic changes, in some cases resulting in fatal outcomes). These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease. Monitor closely for signs of any unusual behavior.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with chronic cardiac disease.

• 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. Not recommended for patients with end stage renal disease (ESRD) not undergoing dialysis.

• Respiratory disease: Use with caution in patients with respiratory disease.

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 hospitalized patients with severe, complicated or progressive illness if >48 hours. Treatment should not be delayed while awaiting results of laboratory tests for influenza. Nonhospitalized persons who are not at high risk for developing severe or complicated illness and who have a mild disease are not likely to benefit if treatment is started >48 hours after symptom onset. Nonhospitalized persons who are already beginning to recover do not need treatment.

Monitoring Parameters

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

Pregnancy Risk Factor

C

Pregnancy Considerations

Oseltamivir phosphate and its active metabolite oseltamivir carboxylate cross the placenta (Meijer 2012).

An increased risk of adverse neonatal or maternal outcomes has generally not been observed following maternal use of oseltamivir during pregnancy (CDC 60[1] 2011).

Untreated influenza infection is associated with an increased risk of adverse events to the fetus and an increased risk of complications or death to the mother. Oseltamivir is currently recommended for the treatment or prophylaxis of influenza in pregnant women and women up to 2 weeks' postpartum (ACOG 2018; CDC 60[1] 2011).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea, nausea, vomiting, or headache. Have patient report immediately to prescriber confusion, behavioral changes, difficulty speaking, tremors, seizures, hallucinations, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Hide