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Oseltamivir

Class: Neuraminidase Inhibitors
- Sialic Acid Derivatives
VA Class: AM800
Chemical Name: [3R-(3α,4β,5α)]-ethyl 4-(acetylamino)-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate
Molecular Formula: C16H28N2O4•H3PO4
CAS Number: 204255-11-8
Brands: Tamiflu

Medically reviewed by Drugs.com on Sep 22, 2020. Written by ASHP.

Warning

Special Alerts:

For information on the use of this drug in patients with coronavirus disease 2019 (COVID-19), see the document “Assessment of the Evidence for COVID-19-Related Treatments” on ASHP's COVID-19 Resource Center. To view this document, please click here: [Web]

Introduction

Antiviral; neuraminidase inhibitor; sialic acid analog.

Uses for Oseltamivir

Treatment of Seasonal Influenza A and B Virus Infections

Treatment of acute, uncomplicated illness caused by influenza A or B viruses in adults, adolescents, and pediatric patients ≥2 weeks of age. Although safety and efficacy not established in neonates <2 weeks of age, also recommended when treatment of influenza considered necessary in this age group.

Although efficacy not established in immunocompromised patients, has been used to treat seasonal influenza A or B virus infections in bone marrow transplant (BMT) recipients and to treat seasonal influenza infections in hematopoietic stem cell transplant (HSCT) recipients.

CDC, US Public Health Service Advisory Committee on Immunization Practices (ACIP), AAP, and others recommend antiviral treatment of seasonal influenza illness initiated as soon as possible in all individuals with suspected or confirmed influenza who require hospitalization or have severe, complicated, or progressive illness (regardless of vaccination status or underlying illness). Early empiric antiviral treatment also recommended in individuals with suspected or confirmed influenza of any severity if they are at high risk of developing influenza-related complications because of age or underlying medical conditions. This includes children <2 years of age, adults ≥65 years of age, individuals of any age with certain chronic medical or immunosuppressive conditions, women who are pregnant women or up to 2 weeks postpartum, individuals <19 years of age receiving long-term aspirin therapy, American Indians, Alaskan natives, morbidly obese individuals with body mass index (BMI) ≥40, and residents of any age in nursing homes or other long-term care facilities.

CDC, ACIP, and AAP also state empiric antiviral treatment can be considered in previously healthy, symptomatic individuals with suspected or confirmed influenza who are not known to be at increased risk of developing severe or complicated illness if such treatment can be initiated within 48 hours of illness onset. Although these individuals typically do not require treatment, early empiric antiviral treatment might provide some benefit (e.g., shortened duration of illness).

If indicated, initiate antiviral treatment as soon as possible after illness onset (ideally within 48 hours); do not delay initiation of treatment while waiting for laboratory confirmation.

Although manufacturer states use for treatment of influenza only in patients who have been symptomatic for ≤48 hours, there is some evidence from observational studies of hospitalized patients that antiviral treatment might still be beneficial when initiated up to 4 or 5 days after illness onset. CDC, ACIP, and AAP recommend that antiviral treatment be initiated in all patients with severe, complicated, or progressive illness attributable to influenza and all hospitalized patients and patients at increased risk of influenza complications (either hospitalized or outpatient) who have suspected or confirmed influenza, even if it has been >48 hours after illness onset. Base decisions regarding use of empiric antiviral treatment in outpatients, especially high-risk patients, on disease severity and progression, age, underlying medical conditions, likelihood of influenza, and time since onset of symptoms. If empiric antiviral treatment considered warranted in previously healthy, symptomatic outpatients not considered at increased risk of influenza complications, initiate within 48 hours after illness onset, but some experts state treatment can be considered in such patients even if it has been >48 hours after illness onset.

When treatment of suspected or confirmed acute, uncomplicated seasonal influenza indicated, use age-appropriate antiviral (oral oseltamivir, IV peramivir, inhaled zanamivir). Oseltamivir usually preferred for hospitalized patients and patients with severe or complicated influenza since data are lacking regarding use of IV peramivir or inhaled zanamivir in such patients. Oseltamivir also preferred for treatment of suspected or confirmed influenza in pregnant women. (See Pregnancy under Cautions.)

Consider viral surveillance data available from local and state health departments and CDC when selecting an antiviral for treatment of seasonal influenza. Strains of circulating influenza viruses and the antiviral susceptibility of these strains constantly evolve; emergence of oseltamivir-resistant influenza virus may decrease effectiveness of the drug. Although influenza A and B viruses circulating in US during last few years generally have been susceptible to oseltamivir, consult most recent information.

CDC issues recommendations concerning use of antiviral agents for treatment of influenza, and these recommendations are updated as needed during each influenza season. Information regarding influenza surveillance and updated recommendations for treatment of seasonal influenza are available from CDC at [Web].

Prevention of Seasonal Influenza A and B Virus Infections

Prevention of illness caused by seasonal influenza A or B viruses in adults, adolescents, and children ≥1 year of age.

Although efficacy not established in immunocompromised patients, oseltamivir has been used for prophylaxis of seasonal influenza in immunocompromised individuals, including cancer patients, BMT recipients, HSCT recipients, and solid organ transplant recipients.

Annual vaccination with seasonal influenza virus vaccine, as recommended by ACIP, is the primary means of preventing seasonal influenza and its severe complications. Prophylaxis with an appropriate antiviral active against circulating influenza strains is considered an adjunct to vaccination for control and prevention of influenza.

Indiscriminate use of antivirals for prophylaxis may promote resistance or reduce availability of antivirals for treatment. Base decisions regarding use of antivirals for prophylaxis of influenza on exposed person's risk for influenza complications, vaccination status, type and duration of contact, recommendations from local or public health authorities, and clinical judgment. Generally use postexposure prophylaxis only if it can be initiated within 48 hours of most recent exposure.

When seasonal influenza viruses are circulating in the community, postexposure prophylaxis with oseltamivir or zanamivir can be considered for certain individuals, including those at high risk of developing influenza complications for whom influenza vaccine is contraindicated, unavailable, or expected to have low efficacy (e.g., immunocompromised individuals). Other possible candidates for antiviral prophylaxis include unvaccinated health care personnel, public health workers, and first responders with unprotected, close-contact exposure to a patient with confirmed, probable, or suspected influenza during the time when the patient was infectious. Also consider antiviral prophylaxis for controlling influenza outbreaks in nursing and long-term care facilities or other closed or semi-closed settings with large numbers of individuals at high risk for influenza complications. In individuals at high risk of influenza complications who receive influenza virus vaccine inactivated, prophylaxis can be considered during the 2 weeks after vaccination to provide protection until an adequate immune response develops. (See Specific Drugs under Interactions.)

Consider viral surveillance data available from local and state health departments and CDC when selecting an antiviral for prophylaxis of influenza. The most appropriate antiviral for prevention of influenza is based on the likelihood that the influenza strain is susceptible and the known adverse effects of the drug. Strains of circulating influenza viruses and the antiviral susceptibility of these strains constantly evolve; emergence of oseltamivir-resistant influenza virus may decrease effectiveness of the drug.

CDC issues recommendations concerning use of antivirals for prophylaxis of influenza, and these recommendations are updated as needed during each influenza season. Information regarding influenza surveillance and updated recommendations for prevention of seasonal influenza are available from CDC at [Web].

Avian Influenza A Virus Infections

Treatment or prevention of infections caused by avian influenza A viruses (e.g., H1N1, H7N3, H7N7, H7N9).

CDC and WHO state that oseltamivir is drug of choice for treatment or prophylaxis of infections caused by highly pathogenic avian influenza A (H5N1); zanamivir is an alternative.

Oseltamivir also drug of choice for treatment of infections caused by avian influenza A (H7N9), especially in hospitalized patients and patients with severe or complicated illness. Because of limited data, zanamivir not recommended for treatment of severe avian influenza A (H7N9) infections, but may be considered in uncomplicated infections. Either oseltamivir or zanamivir can be used for prophylaxis in close contacts of patients with confirmed or probable avian influenza A (H7N9) infection.

Most recent information regarding avian influenza A infections is available at WHO website at [Web] and CDC website at [Web].

Variant Influenza Virus Infections

Treatment of infections cause by variant influenza viruses.

Influenza viruses that circulate in swine are called swine influenza viruses when isolated from swine, but are called variant influenza viruses when isolated from humans. Influenza A (H1N1) variant (H1N1v), influenza A (H1N2) variant (H1N2v), and influenza A (H3N2) variant (H3N2v) infections reported in US. Limited data to date indicate variant influenza viruses are susceptible to neuraminidase inhibitor antivirals (oseltamivir, peramivir, zanamivir).

CDC states management of infections caused by variant influenza viruses is similar to management of seasonal influenza virus infections. Early initiation of oseltamivir recommended by CDC for treatment of hospitalized patients, those with severe and progressive illness, and any high-risk patient with suspected or confirmed variant influenza virus infection. Antiviral treatment with a neuraminidase inhibitor also recommended for outpatients with suspected influenza, including variant influenza virus infection, if individual considered at high risk for influenza complications. Antiviral treatment can be considered for any previously healthy, symptomatic outpatient not at high risk who has confirmed or suspected variant virus infection on the basis of clinical judgment, if treatment can be initiated ≤48 hours after illness onset.

CDC does not recommend antiviral prophylaxis before or after exposure to swine.

Pandemic Influenza

Treatment or prevention of pandemic influenza caused by susceptible strains of influenza virus.

Influenza viruses can cause pandemics, during which rates of illness and death from influenza-related complications can increase dramatically worldwide.

Most recent influenza pandemic occurred during 2009 and was related to a novel influenza A (H1N1) strain, influenza A (H1N1)pdm09. In the US, the pandemic was characterized by a substantial increase in influenza activity that peaked in late October and early November 2009 and returned to seasonal baseline levels by January 2010. During that time, ≥99% of influenza viruses circulating in the US were influenza A (H1N1)pdm09. In August 2010, the WHO declared that the world was in a post-pandemic period; since that time, influenza A (H1N1)pdm09 has become a seasonal influenza virus and continues to circulate with other seasonal viruses.

The spread of the highly pathogenic H5N1 strain of avian influenza A in poultry in Asia and other countries that was first identified in 2003 represents a potential future pandemic threat.

Consult CDC pandemic influenza website (https://www.cdc.gov/flu/pandemic-resources/index.htm) for information on pandemic influenza preparation and response, including use of antiviral agents.

Oseltamivir Dosage and Administration

Administration

Oral Administration

Administer orally without regard to meals; administration with meals may improve GI tolerability.

Commercially available as 30-, 45-, and 75-mg capsules and as a powder for oral suspension that is reconstituted to provide an oral suspension containing 6 mg/mL.

Reconstituted oseltamivir oral suspension is the preferred preparation for individuals unable to swallow capsules. Alternatively, if the oral suspension not available from the manufacturer or wholesaler, the appropriate dosage can be administered by opening the appropriate strength of commercially available capsules and mixing the contents with a sweet liquid (e.g., regular or sugar-free chocolate syrup, corn syrup, caramel topping, light brown sugar dissolved in water).

During emergency situations if the powder for oral suspension not available and the appropriate strength of oseltamivir capsules not available to mix with sweetened liquids, a pharmacist can prepare an emergency supply of extemporaneous oral suspension using 75-mg oseltamivir capsules and simple syrup, cherry syrup vehicle (Humco), or Ora-Sweet SF (Paddock). Consult manufacturer's information for specific instructions.

Reconstitution

Reconstitute commercially available powder for oral suspension at the time of dispensing. Tap bottle to thoroughly loosen white powder and then add the amount of water specified on the bottle; shake well for 15 seconds.

Reconstituted oral suspension contains 6 mg/mL; each 12.5 mL contains 75 mg of oseltamivir.

Provide an oral dosing device that can accurately measure the appropriate volume in mL; counsel patient and/or caregiver how to use the oral dosing dispenser to correctly measure and administer the appropriate dose.

Shake suspension well prior to each dose.

Dosage

Available as oseltamivir phosphate; dosage expressed in terms of oseltamivir.

Pediatric Patients

Treatment of Seasonal Influenza A and B Virus Infections
Oral

Initiate treatment as soon as possible (preferably within 48 hours of symptom onset). Although efficacy only established when given within 48 hours after onset of symptoms, there is some evidence from hospitalized patients that antiviral treatment initiated up to 4 or 5 days after onset of symptoms may still be beneficial. (See Uses: Treatment of Seasonal Influenza A and B Virus Infections.)

Usual duration of antiviral treatment is 5 days, but hospitalized patients with severe infections (e.g., those with prolonged infection or admitted into an intensive care unit) or immunosuppressed individuals may require >5 days of treatment.

Infants 2 weeks to <1 year of age: 3 mg/kg twice daily for 5 days recommended by manufacturer.

Neonates and infants <1 year of age: AAP recommends 3.5 mg/kg twice daily for 5 days in infants 9 through 11 months of age and 3 mg/kg twice daily for 5 days in full-term neonates and infants through 8 months of age. Although safety and efficacy not established in neonates <2 weeks of age, AAP states the drug can be used for treatment of influenza in neonates from birth because of its known safety profile. (See Pediatric Use under Cautions.)

Dosage recommended for full-term infants may be excessive in preterm neonates. Limited data suggest that, if the drug is considered necessary for treatment of influenza in preterm neonates, dosage should be based on postmenstrual age (i.e., gestational age plus chronological age). CDC and AAP recommend 1 mg/kg twice daily in preterm neonates with postmenstrual age <38 weeks, 1.5 mg/kg twice daily in those with postmenstrual age of 38 through 40 weeks, and 3 mg/kg twice daily in those with postmenstrual age >40 weeks. Consult pediatric infectious disease expert if treatment of influenza considered necessary in extremely premature neonates (postmenstrual age <28 weeks).

Children 1–12 years of age: Dosage is based on weight. (See Table 1.)

Adolescents ≥13 years of age: 75 mg twice daily for 5 days. Each dose can be given as single 75-mg capsule or 12.5 mL of oral suspension containing 6 mg/mL.

Table 1. Oseltamivir Dosage for Treatment of Seasonal Influenza A and B in Children 1–12 Years of Age1

Weight (kg)

Daily Dosage (mg)

Daily Dosage (Volume of Reconstituted Oral Suspension Containing 6 mg/mL)

Daily Dosage (Capsules)

≤15

30 mg twice daily for 5 days

5 mL twice daily for 5 days

One 30-mg capsule twice daily for 5 days

15.1–23

45 mg twice daily for 5 days

7.5 mL twice daily for 5 days

One 45-mg capsule twice daily for 5 days

23.1–40

60 mg twice daily for 5 days

10 mL twice daily for 5 days

Two 30-mg capsules twice daily for 5 days

≥40.1

75 mg twice daily for 5 days

12.5 mL twice daily for 5 days

One 75-mg capsule twice daily for 5 days

Prevention of Seasonal Influenza A and B Virus Infections
Oral

Initiate prophylaxis within 48 hours after exposure (e.g., close contact with infected individual). Protection lasts as long as the drug is continued.

CDC recommends prophylaxis be continued for 10 days after household exposure and 7 days after most recent exposure in other situations. When outbreak is occurring in a long-term care facility or hospital, continue for at least 2 weeks and up to 7 days after last known case is identified.

Manufacturer states prophylaxis may be continued for up to 6 weeks in immunocompetent individuals and for up to 12 weeks in immunocompromised individuals during community outbreaks.

Although safety and efficacy not established for prophylaxis of influenza in infants <1 year of age, CDC and ACIP state infants 3 months to <1 year of age can receive 3 mg/kg once daily for 10 days if considered necessary. AAP recommends 3.5 mg/kg once daily for 10 days in infants 9 through 11 months of age and 3 mg/kg once daily for 10 days in infants 3 through 8 months of age.

Because of limited safety and efficacy data, CDC, ACIP, and AAP do not recommend use for prophylaxis of influenza in full-term or premature infants <3 months of age unless situation is judged critical.

Children 1–12 years of age: Dosage is based on weight. (See Table 2.)

Adolescents ≥13 years of age: 75 mg once daily for at least 10 days. Manufacturer states continue prophylaxis for at least 10 days following close contact with infected individual; during community outbreaks, prophylaxis may be continued for up to 6 weeks in immunocompetent individuals and for up to 12 weeks in immunocompromised individuals.

Manufacturer states continue prophylaxis in pediatric patients for 10 days following close contact with infected individual; during community outbreaks, may continue prophylaxis for up to 6 weeks in immunocompetent individuals (up to 12 weeks in immunocompromised individuals).

Table 2. Oseltamivir Dosage for Prevention of Seasonal Influenza A and B in Children 1–12 Years of Age1

Weight (kg)

Daily Dosage (mg)

Daily Dosage (Volume of Reconstituted Oral Suspension Containing 6 mg/mL)

Daily Dosage (Capsules)

≤15

30 mg once daily for 10 days

5 mL once daily for 10 days

One 30-mg capsule once daily for 10 days

15.1–23

45 mg once daily for 10 days

7.5 mL once daily for 10 days

One 45-mg capsule once daily for 10 days

23.1–40

60 mg once daily for 10 days

10 mL once daily for 10 days

Two 30-mg capsules once daily for 10 days

≥40.1

75 mg once daily for 10 days

12.5 mL once daily for 10 days

One 75-mg capsule once daily for 10 days

Avian Influenza A Virus Infection
Treatment of Avian Influenza A Virus Infections†
Oral

Optimum dosage and duration of treatment unknown, especially for severe or complicated infections.

Dosage usually recommended for treatment of seasonal influenza A and B virus infections has been recommended. (See Treatment of Seasonal Influenza A and B Virus Infections under Dosage and Administration.) Although some experts have suggested that severely ill hospitalized patients or immunocompromised patients may benefit from higher dosage, limited data from those with severe influenza, including some with avian influenza A (H1N1) infection, suggest that higher dosage may not provide additional clinical benefit. Although 5 days of treatment may be adequate for uncomplicated illness, consider longer duration of treatment (i.e., 7–10 days) in severely ill hospitalized patients and immunosuppressed individuals.

Initiate treatment as early as possible. May be most beneficial if initiated within 2 days of symptom onset, but is warranted even if initiated >48 hours after illness onset or in patients who present for care in later stages of illness.

Prevention of Avian Influenza A Virus Infections†
Oral

Prophylaxis of highly pathogenic avian influenza A (H5N1) infection in close contacts: CDC and WHO state that the once-daily dosage usually recommended for prophylaxis of seasonal influenza A and B virus infections can be used. (See Prevention of Seasonal Influenza A and B Virus Infections under Dosage and Administration.) Continue prophylaxis for 7–10 days after last known exposure.

Prophylaxis of avian influenza virus A (H7N9) infection in close contacts: CDC recommends that the twice-daily dosage usually recommended for treatment of seasonal influenza A and B virus infections be given for 5–10 days. (See Treatment of Seasonal Influenza A and B Virus Infections under Dosage and Administration.)

Pandemic Influenza†
Oral

Dosage usually recommended for treatment or prophylaxis of seasonal influenza A and B virus infections is considered the minimum dosage required for treatment or prophylaxis of influenza in a pandemic situation.

Adults

Treatment of Seasonal Influenza A and B Virus Infections
Oral

75 mg twice daily for 5 days.

Initiate treatment as soon as possible (preferably within 48 hours of symptom onset). Although efficacy only established when given within 2 days after onset of symptoms, there is some evidence from hospitalized patients that antiviral treatment initiated up to 4 or 5 days after onset of symptoms may still be beneficial. (See Uses: Treatment of Seasonal Influenza A and B Virus Infections.)

Usual duration of antiviral treatment is 5 days, but hospitalized patients with severe infections (e.g., those with prolonged infection or admitted into an intensive care unit) or individuals with immunosuppression may require >5 days of treatment.

Prevention of Seasonal Influenza A and B Virus Infections
Oral

75 mg once daily for at least 10 days.

Initiate prophylaxis within 48 hours after exposure (e.g., close contact with infected individual). Protection lasts as long as the drug is continued.

CDC recommends prophylaxis be continued for 10 days after household exposure and 7 days after most recent exposure in other situations. When outbreak is occurring in a long-term care facility (e.g., nursing home) or hospital, continue for at least 2 weeks and up to 7 days after last known case is identified.

Manufacturer states prophylaxis may be continued for up to 6 weeks in immunocompetent individuals and for up to 12 weeks in immunocompromised individuals during community outbreaks.

Avian Influenza A Virus Infections
Treatment of Avian Influenza A Virus Infections†
Oral

Optimum dosage and duration of treatment unknown, especially for severe or complicated infections.

Dosage usually recommended for treatment of seasonal influenza A and B virus infections has been recommended. (See Treatment of Seasonal Influenza A and B Virus Infections under Dosage and Administration.) Although some experts have suggested that severely ill patients may benefit from higher dosage (i.e., 150 mg twice daily in adults with normal renal function), limited data from those with severe influenza, including some with avian influenza A (H1N1) infection, suggest that higher dosage may not provide additional clinical benefit. Although 5 days may be adequate for uncomplicated illness, consider longer duration of treatment (i.e., 7–10 days) in severely ill hospitalized patients and immunosuppressed individuals.

Initiate treatment as early as possible. May be most beneficial if initiated within 2 days of symptom onset, but is warranted even if initiated >48 hours after illness onset or in patients who present for care in the later stages of illness.

Prevention of Avian Influenza A Virus Infections†
Oral

Prophylaxis of highly pathogenic avian influenza A (H5N1) infection in close contacts: CDC and WHO state that the once-daily dosage usually recommended for prophylaxis of seasonal influenza A and B virus infections can be used. (See Prevention of Seasonal Influenza A and B Virus Infections under Dosage and Administration.) Continue prophylaxis for 7–10 days after last known exposure.

Prophylaxis of avian influenza virus A (H7N9) infection in close contacts: CDC recommends that the twice-daily dosage usually recommended for treatment of seasonal influenza A and B virus infections be given for 5–10 days. (See Treatment of Seasonal Influenza A and B Virus Infections under Dosage and Administration.)

During avian influenza A (H7N7) outbreaks, 75 mg daily has been used for prophylaxis in exposed individuals.

Pandemic Influenza†
Oral

Dosage recommended for treatment or prophylaxis of seasonal influenza A and B virus infections is considered the minimum dosage required for treatment or prophylaxis of influenza in a pandemic situation.

Special Populations

Hepatic Impairment

Usual dosage can be used in patients with mild to moderate hepatic impairment (Child-Pugh score ≤9). Safety and pharmacokinetics not evaluated in those with severe hepatic impairment.

Renal Impairment

Adjust dosage in adults with Clcr 10–60 mL/minute and in those with end-stage renal disease (ESRD; Clcr ≤10 mL/minute) undergoing hemodialysis or continuous peritoneal dialysis. (See Table 3 and Table 4.)

Not recommended in adults with ESRD who are not undergoing dialysis.

Dosage recommendations not available for pediatric patients with renal impairment; CDC states dosage recommendations for adults with renal impairment may be useful for treatment or prevention of influenza in children with renal impairment who weigh >40 kg.

Dosage assumes 3 hemodialysis sessions in the 5-day period. If influenza symptoms developed during the 48 hours between hemodialysis sessions, give initial oseltamivir dose immediately and give the post-hemodialysis dose regardless of when initial dose was given.

Data derived from studies in patients undergoing CAPD.

Table 3. Oseltamivir Dosage for Treatment of Influenza in Adults with Renal Impairment1137

Clcr (mL/minute)

Dosage

>30 to 60

30 mg twice daily for 5 days

>10 to 30

30 mg once daily for 5 days

≤10 (ESRD receiving hemodialysis)

30 mg given immediately and then 30 mg after each hemodialysis cycle for maximum of 5 days

≤10 (ESRD receiving continuous peritoneal dialysis)

Single 30-mg dose given immediately

ESRD not receiving dialysis

Not recommended

Manufacturer states prophylaxis during community outbreaks may be continued for up to 6 weeks in immunocompetent individuals (up to 12 weeks in immunocompromised individuals).

Data derived from studies in patients undergoing CAPD.

Table 4. Oseltamivir Dosage for Prevention of Influenza in Adults with Renal Impairment1137

Clcr (mL/minute)

Dosage

>30 to 60

30 mg once daily for ≥10 days

>10 to 30

30 mg once every other day for ≥10 days

≤10 (ESRD receiving hemodialysis)

30 mg given immediately and then 30 mg after alternate hemodialysis cycles

≤10 (ESRD receiving continuous peritoneal dialysis)

30 mg given immediately and then 30 mg once weekly

ESRD not receiving dialysis

Not recommended

Geriatric Patients

Dosage adjustments not needed except those related to renal impairment.

Cautions for Oseltamivir

Contraindications

  • Known hypersensitivity to oseltamivir or any ingredient in the formulations.

Warnings/Precautions

Sensitivity Reactions

Dermatologic and Hypersensitivity Reactions

Anaphylaxis and serious skin reactions, including toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme, reported.

Rash, swelling of the face or tongue, allergy, dermatitis, eczema, or urticaria reported during postmarketing experience.

If an allergic reaction occurs or is suspected, discontinue oseltamivir and institute appropriate therapy.

Neuropsychiatric Events

Adverse neuropsychiatric events (e.g., agitation, anxiety, self-injury, delirium, hallucinations, altered level of consciousness, confusion, nightmares, delusions, abnormal behavior, seizures) and death reported.

Postmarketing cases of delirium and abnormal behavior leading to injury reported mainly in Japanese children. Cases generally had an abrupt onset and rapid resolution. Role of oseltamivir not determined.

Influenza itself can be associated with neurologic and behavioral symptoms (e.g., hallucinations, delirium, abnormal behavior) and fatalities can occur. Although such events may occur in the setting of encephalitis or encephalopathy, they can occur without obvious severe disease.

Closely monitor patients with influenza for signs of abnormal behavior. If neuropsychiatric symptoms develop, consider risks versus benefits of continued therapy.

Bacterial Infections

Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications of influenza. No evidence that oseltamivir prevents such complications.

No evidence of efficacy in illness caused by any organisms other than influenza viruses.

Consider potential for secondary bacterial infections; if such infections occur, treat appropriately.

Concomitant Illness

Efficacy for treatment of influenza in patients with chronic cardiac disease and/or underlying pulmonary disease not established; no evidence to date of increased risk of adverse effects in this population.

Although efficacy for treatment or prevention of influenza not established in immunocompromised patients, safety of oseltamivir prophylaxis has been demonstrated for up to 12 weeks in immunocompromised patients. Has been used for treatment or prevention of influenza in some immunocompromised individuals, including BMT recipients, HSCT recipients, solid organ transplant recipients, and chemotherapy patients. (See Uses.)

No data available regarding use for treatment of influenza in patients with any medical condition severe or unstable enough to require inpatient care.

Influenza Vaccination

Not a substitute for annual vaccination with a seasonal influenza vaccine (influenza virus vaccine inactivated, influenza vaccine live intranasal, influenza vaccine recombinant).

Although antivirals used for treatment or prevention of influenza, including oseltamivir, may be used concomitantly with or at any time before or after influenza virus vaccine inactivated, these antivirals may inhibit the vaccine virus contained in influenza vaccine live intranasal. (See Specific Drugs under Interactions.)

Sorbitol

When the commercially available oral suspension containing 6 mg/mL is used, each 75-mg dose of oseltamivir contains 2 g of sorbitol. This amount of sorbitol exceeds the maximum daily limit of sorbitol for individuals with hereditary fructose intolerance and may result in dyspepsia and diarrhea.

Specific Populations

Pregnancy

Category C.

Pregnant women are at increased risk for severe complications from influenza, which may lead to adverse pregnancy and/or fetal outcomes including maternal death, still births, birth defects, preterm delivery, low birthweight, and small size for gestational age.

CDC and ACIP state that pregnancy is not a contraindication to use of oseltamivir for treatment or prevention of influenza; oseltamivir regimens recommended in pregnant women are the same as those for other adults.

CDC and ACIP state that oseltamivir may be preferred when a neuraminidase inhibitor is indicated for treatment of influenza in a woman who is pregnant or up to 2 weeks postpartum, but drug of choice for prophylaxis of these infections is less clear. Zanamivir may be preferred by some clinicians for prophylaxis in pregnant women because of its limited systemic absorption; however, consider respiratory complications that may be associated with zanamivir because of its route of administration, especially in women at risk for respiratory problems.

Lactation

Distributed into human milk in low concentrations that are considered unlikely to cause toxicity in nursing infants.

Use with caution in nursing women.

Pediatric Use

Safety and efficacy for treatment of influenza not established in infants <2 weeks of age.

Safety and efficacy for prophylaxis of influenza not established in infants <1 year of age.

Manufacturer states efficacy not established in pediatric patients with asthma.

Young children, especially those <2 years of age, are at increased risk of influenza infection, hospitalization, and complications. During the 2009 influenza A (H1N1)pdm09 pandemic, FDA issued an emergency use authorization (EUA) that temporarily allowed use of oseltamivir for emergency treatment or prevention of these infections in infants <1 year of age. Although the EUA expired in June 2010, AAP states that, because of the known safety profile of the drug, use for treatment of influenza in full-term or preterm neonates from birth or for prevention of influenza in infants ≥3 months of age is appropriate if indicated. ACIP and AAP state that oseltamivir not recommended for prevention of influenza in infants <3 months of age unless situation is judged critical. (See Pediatric Patients under Dosage and Administration.)

Unusual adverse neurologic and/or psychiatric effects (e.g., self-injury, delirium, hallucinations, mental confusion, abnormal behavior, seizures) and deaths reported in Japanese children (≤16 years of age) receiving oseltamivir for treatment of influenza; role of oseltamivir not determined. (See Neuropsychiatric Events under Cautions.)

Geriatric Use

No overall differences in safety or efficacy compared with younger adults.

Hepatic Impairment

Safety and pharmacokinetics not evaluated in patients with severe hepatic impairment.

Renal Impairment

Decreased clearance; possible increased risk of adverse effects.

Dosage adjustments recommended in adults with Clcr 10–60 mL/minute and adults with ESRD (Clcr ≤10 mL/minute) undergoing dialysis. Not recommended in adults with ESRD not undergoing dialysis. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (nausea, vomiting, diarrhea, abdominal pain), headache, bronchitis, insomnia, vertigo.

Interactions for Oseltamivir

Oseltamivir phosphate and its active metabolite not metabolized by and do not inhibit CYP isoenzymes; drug interactions with drugs that are substrates or inhibitors of these enzymes unlikely.

Specific Drugs

Drug

Interaction

Comments

Acetaminophen

No clinically important pharmacokinetic interactions

Dosage adjustments not needed

Amantadine

No clinically important pharmacokinetic interactions

Dosage adjustments not needed

Amoxicillin

No clinically important pharmacokinetic interactions

Dosage adjustments not needed

Antacids (containing magnesium, aluminum, or calcium carbonate)

No clinically important pharmacokinetic interactions

Dosage adjustments not needed

Aspirin

No clinically important pharmacokinetic interactions

Dosage adjustments not needed

Cimetidine

No clinically important pharmacokinetic interactions

Dosage adjustments not needed

Influenza virus vaccines

Influenza virus vaccine inactivated: No specific studies, but interference with antibody response to the vaccine not expected; oseltamivir does not interfere with humoral antibody response to influenza infection

Influenza vaccine live intranasal: No specific studies; oseltamivir potentially could decrease antibody response and decrease efficacy of the live vaccine

Influenza virus vaccine inactivated: May be administered simultaneously with or at any time before or after oseltamivir

Influenza vaccine live intranasal: Do not administer the live vaccine until ≥48 hours after oseltamivir discontinued; do not administer oseltamivir until ≥2 weeks after the vaccine; if oseltamivir and intranasal live influenza vaccine administered concomitantly, consider revaccination if appropriate; if oseltamivir given 2 days before to 14 days after intranasal live vaccine, ACIP recommends revaccination using parenteral inactivated influenza vaccine or parenteral recombinant influenza vaccine

Peramivir

No evidence of drug interactions when oral oseltamivir used concomitantly with IV peramivir

Probenecid

Increased systemic exposure to oseltamivir carboxylate because of decreased renal tubular secretion

Not expected to be clinically important; dosage adjustments not needed

Rimantadine

No clinically important pharmacokinetic interactions

Dosage adjustments not needed

Warfarin

No clinically important pharmacokinetic interactions

Dosage adjustments not needed

Oseltamivir Pharmacokinetics

Absorption

Bioavailability

Oseltamivir phosphate readily absorbed following oral administration and then extensively converted to the active metabolite (oseltamivir carboxylate).

Absolute bioavailability of oseltamivir carboxylate 80% following oral administration of oseltamivir phosphate; peak concentrations of active metabolite attained within 3–4 hours.

Food

Administration of oseltamivir phosphate with food has no effect on peak plasma concentrations or AUC of oseltamivir carboxylate.

Distribution

Extent

Following oral administration of oseltamivir phosphate, oseltamivir carboxylate distributed throughout body, including upper and lower respiratory tract.

Placental transfer of oseltamivir carboxylate demonstrated in rats and rabbits; not known whether oseltamivir or oseltamivir carboxylate crosses the placenta in humans.

Oseltamivir and oseltamivir carboxylate are distributed into milk.

Plasma Protein Binding

Oseltamivir phosphate 42% bound to plasma proteins; oseltamivir carboxylate 3% bound to plasma proteins.

Elimination

Metabolism

Oseltamivir phosphate extensively (>90%) converted to oseltamivir carboxylate, principally by hepatic esterases. No further metabolism of oseltamivir carboxylate occurs.

Oseltamivir phosphate and oseltamivir carboxylate not metabolized by CYP enzymes.

Elimination Route

Oseltamivir carboxylate eliminated (>99%) by renal excretion; <20% of dose eliminated in feces.

Half-life

Plasma half-life of oseltamivir phosphate is 1–3 hours; half-life of oseltamivir carboxylate is 6–10 hours.

Special Populations

Renal impairment: Systemic exposure to oseltamivir carboxylate increases with declining renal function. In patients undergoing CAPD, peak concentrations following a single 30-mg dose of oseltamivir or once-weekly oseltamivir was approximately threefold higher than peak concentrations in patients with normal renal function receiving 75 mg twice daily.

Mild or moderate hepatic impairment: Systemic exposure to oseltamivir carboxylate is comparable to that in individuals without hepatic impairment.

Pediatric patients: Clearance of both oseltamivir phosphate and oseltamivir carboxylate increased in younger pediatric patients compared with adults. Total clearance of oseltamivir carboxylate decreases linearly with increasing age (up to 12 years of age); pharmacokinetics in those >12 years of age similar to adults.

Geriatric patients: Exposure to oseltamivir carboxylate at steady state approximately 25–35% higher in those 65–78 years of age compared with younger adults; half-lives in geriatric individuals are similar to those in younger adults.

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).

Powder for Suspension

25°C (may be exposed to 15–30°C).

Following reconstitution, store suspension at 2–8°C for up to 17 days. Alternatively, may be stored for up to 10 days at 25°C (may be exposed to 15–30°). Do not freeze.

Extemporaneous Oral Suspension

Extemporaneous oral suspensions prepared according to manufacturer's directions using 75-mg oseltamivir capsules and simple syrup, cherry syrup vehicle, or Ora-Sweet SF are stable for 5 weeks at 2–8°C or 5 days at 25°C.

Actions and Spectrum

  • Oseltamivir phosphate is prodrug and is inactive until hydrolyzed by hepatic esterases to oseltamivir carboxylate, the active metabolite.

  • Oseltamivir carboxylate is a potent selective competitive inhibitor of influenza virus neuraminidase, an enzyme essential for viral replication; possibly alters virus particle aggregation and release.

  • Active against influenza A and B viruses, including amantadine- and rimantadine-resistant isolates. Majority of seasonal influenza A (H3N2), influenza A (H1N1)pdm09, and influenza B viruses circulating during influenza seasons 2011–2012 through 2016–2017 have been susceptible to oseltamivir.

  • Beginning in the 2007–2008 influenza season, a significant increase in the prevalence of oseltamivir-resistant seasonal influenza A (H1N1) was reported worldwide; almost all seasonal influenza A (H1N1) strains tested in the US in 2008, 2009, and beginning of 2010 were resistant to oseltamivir. During the 2010–2011 influenza season, the former seasonal influenza A (H1N1) was rarely detected; almost all circulating influenza A (H1N1) reported since that time have been the 2009 pandemic influenza A (H1N1)pdm09 virus.

  • Although almost all isolates of influenza A (H1N1)pdm09 virus have been susceptible to oseltamivir in vitro, resistance has been reported rarely. Oseltamivir-resistant influenza A (H1N1)pdm09 have emerged during oseltamivir treatment or prophylaxis, including in immunosuppressed individuals receiving oseltamivir treatment and in individuals who developed influenza illness while receiving oseltamivir prophylaxis.

  • Active in vitro against some avian influenza A viruses, including avian influenza A (H5N1) and other avian influenza A viruses (e.g., H7N2, H7N9, H9N2, H10N8). However, avian influenza A (H5N1) and influenza A (H7N9) with reduced in vitro susceptibility or resistance to oseltamivir have been reported rarely.

  • Cross-resistance between oseltamivir and other neuraminidase inhibitors (e.g., peramivir, zanamivir) reported in influenza A and B viruses. However, because oseltamivir, peramivir, and zanamivir bind to different sites on the neuraminidase enzyme or interact differently with binding sites, cross-resistance among the drugs is variable. Reduced in vitro susceptibility to all 3 drugs (oseltamivir, peramivir, zanamivir) reported in some influenza A and influenza B strains with certain resistance-associated neuraminidase substitutions. Some influenza A or B strains may have reduced in vitro susceptibility to oseltamivir and/or peramivir, but are susceptible to zanamivir; other strains may have reduced in vitro susceptibility to zanamivir, but are susceptible to oseltamivir and/or peramivir. To date, influenza A (H1N1)pdm09 isolates with the H275Y mutation are cross-resistant to oseltamivir and peramivir, but susceptible to zanamivir in vitro. Avian influenza A (H5N1) with the H274Y mutation that are resistant to oseltamivir have been susceptible to zanamivir in vitro.

Advice to Patients

  • Importance of using the appropriate graduated oral dosing dispenser to measure and administer dose of reconstituted oral suspension.

  • Importance of initiating oseltamivir treatment as soon as possible after appearance of influenza symptoms (within 48 hours after symptom onset); efficacy not established if treatment begins >48 hours after symptoms have been established.

  • Importance of initiating oseltamivir prophylaxis as soon as possible after exposure to influenza (within 48 hours after exposure).

  • Importance of complying with the entire drug regimen. Importance of taking missed dose as soon as remembered, except if within 2 hours of the next scheduled dose.

  • Advise patients and/or caregivers of the risk of severe allergic reactions (including anaphylaxis) or serious skin reactions. Instruct patients and/or caregiver to discontinue oseltamivir and seek immediate medical attention if an allergic-like reaction occurs or is suspected.

  • Advise patients and/or caregivers of risk of neuropsychiatric events; importance of informing clinician if signs of unusual behavior develop.

  • Inform patients with hereditary fructose intolerance that a 75-mg dose of oseltamivir oral suspension delivers 2 g of sorbitol; this is above the daily maximum limit of sorbitol and may cause dyspepsia and diarrhea.

  • Advise patients that oseltamivir is not a substitute for annual vaccination with influenza virus vaccine.

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Oseltamivir Phosphate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

30 mg (of oseltamivir)

Tamiflu

Genentech

45 mg (of oseltamivir)

Tamiflu

Genentech

75 mg (of oseltamivir)

Tamiflu

Genentech

For suspension

6 mg (of oseltamivir) per mL

Tamiflu

Genentech

AHFS DI Essentials™. © Copyright 2021, Selected Revisions October 2, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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