Pill Identifier App

Oseltamivir Phosphate

Pronunciation

Class: Neuraminidase Inhibitors
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

Introduction

Antiviral; neuraminidase inhibitor; sialic acid analog.1 2 3 4 5 6 9 64 144

Uses for Oseltamivir Phosphate

Treatment of Seasonal Influenza A and B Virus Infections

Symptomatic treatment of uncomplicated acute illness caused by susceptible influenza A or B viruses in adults, adolescents, and children ≥2 weeks of age who have been symptomatic for ≤2 days.1 2 4 5 15 65 105 112 116 144

Although efficacy not established in immunocompromised patients,1 oseltamivir has been used to treat seasonal influenza A or B virus infections in bone marrow transplant (BMT) recipients74 and to treat seasonal influenza infections in hematopoietic stem cell transplant (HSCT) recipients.101

CDC, US Public Health Service Advisory Committee on Immunization Practices (ACIP), AAP, and others recommend antiviral treatment of 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).105 112 116 137 144 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.112 137 144 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.112 116 137

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.105 112 137 144 Although these individuals typically do not require treatment, early empiric antiviral treatment might provide some benefit (e.g., shortened duration of illness).144

If indicated, initiate treatment with an appropriate antiviral as early as possible since benefit is greatest if started within 48 hours of symptom onset.105 112 137 144 Because there is some evidence that antiviral treatment initiated up to 96 hours after illness onset might still be beneficial in reducing morbidity and mortality in hospitalized patients and in those with severe, complicated, or progressive illness, some experts state that antiviral treatment can be initiated >48 hours after illness onset in such patients.137 144 Do not delay initiation of treatment while waiting for laboratory confirmation.112 137 144

Slideshow: Worried About Ebola? You’re More Likely to Get These 10 Serious Infections

When treatment of seasonal influenza indicated, oseltamivir or zanamivir usually recommended.112 137 144 Oseltamivir usually preferred for hospitalized patients and patients with severe or complicated influenza since data are lacking regarding use of inhaled zanamivir in such patients.161

Consider viral surveillance data available from local and state health departments and the CDC when selecting an antiviral for treatment of seasonal influenza.112 116 137 144 Strains of circulating influenza viruses and the antiviral susceptibility of these strains constantly evolve;116 144 emergence of oseltamivir-resistant influenza virus may decrease effectiveness of the drug.1 Although influenza A and B viruses circulating in US during last few years generally have been susceptible to oseltamivir, consult most recent information.137 144

CDC issues recommendations concerning use of antiviral agents for treatment of influenza, and these recommendations are updated as needed during each influenza season.137 144 Information regarding influenza surveillance and updated recommendations for treatment of seasonal influenza are available from CDC at .

Prevention of Seasonal Influenza A and B Virus Infections

Prevention of illness caused by influenza A or B viruses in adults, adolescents, and children ≥1 year of age.1 16 30 105 112 116

Although efficacy not established in immunocompromised patients,1 oseltamivir has been used for prophylaxis of seasonal influenza in immunocompromised individuals, including cancer patients, BMT recipients, HSCT recipients, and solid organ transplant recipients.1 75

Annual vaccination with seasonal influenza virus vaccine, as recommended by ACIP, is the primary means of preventing seasonal influenza and its severe complications.105 112 116 137 488 Prophylaxis with an appropriate antiviral active against circulating influenza strains is considered an adjunct to vaccination for control and prevention of influenza.1 105 112 116 137 488

Indiscriminate use of antivirals for prophylaxis may promote resistance or reduce availability of antivirals for treatment.137 144 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.144 Generally use postexposure prophylaxis only if it can be initiated within 48 hours of most recent exposure.137 144

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).112 116 137 144 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.112 137 144 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.112 116 137 144 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.112 116 (See Specific Drugs under Interactions.)

Consider viral surveillance data available from local and state health departments and the CDC when selecting an antiviral for prophylaxis of influenza.112 116 137 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.137 144 Strains of circulating influenza viruses and the antiviral susceptibility of these strains constantly evolve;116 137 144 emergence of oseltamivir-resistant influenza virus may decrease effectiveness of the drug.1

CDC issues recommendations concerning use of antivirals for prophylaxis of influenza, and these recommendations are updated as needed during each influenza season.137 144 Information regarding influenza surveillance and updated recommendations for prevention of seasonal influenza are available from CDC at .

Avian Influenza A Virus Infections

Treatment or prevention of infections caused by avian influenza A viruses (e.g., H1N1, H7N3, H7N7, H7N9).46 47 50 61 68 94 104 152 555 556 558

CDC and WHO state that oseltamivir is drug of choice for treatment or prophylaxis of infections caused by highly pathogenic avian influenza A (H5N1);50 68 94 104 zanamivir is an alternative.50 94

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.50 104 Because of limited data, zanamivir not recommended for treatment of severe avian influenza A (H7N9) infections, but may be considered in uncomplicated infections.50 Either oseltamivir or zanamivir can be used for prophylaxis in close contacts of patients with confirmed or probable avian influenza A (H7N9) infection.50

Pandemic Influenza

Treatment or prevention of pandemic influenza caused by susceptible strains of influenza virus.52 151

Influenza viruses can cause pandemics, during which rates of illness and death from influenza-related complications can increase dramatically worldwide.52 104 488

Most recent influenza pandemic occurred during 2009 and was related to a novel influenza A (H1N1) strain, influenza A (H1N1)pdm09.52 134 144 151 488 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 2010.123 488 During that time, ≥99% of influenza viruses circulating in the US were influenza A (H1N1)pdm09.123 488 In August 2010, the WHO declared that the world was in a post-pandemic period;148 since that time, influenza A (H1N1)pdm09 has become a seasonal influenza virus and continues to circulate with other seasonal viruses.144 551 553

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.50 54 55 56 104 147

Oseltamivir Phosphate Dosage and Administration

Administration

Oral Administration

Administer orally without regard to meals;1 administration with meals may improve GI tolerability.1 2

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.1

Reconstituted oseltamivir oral suspension is the preferred preparation for individuals unable to swallow capsules.1 Alternatively, if the oral suspension not available, the appropriate dosage of oseltamivir capsules can be administered by opening the appropriate strength of 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).1 141

If the commercially available powder for oral suspension is not available and the appropriate strength of oseltamivir capsules is not available to mix with sweetened liquids (e.g., shortage during an emergency), a pharmacist can prepare an extemporaneous oral suspension using 75-mg oseltamivir capsules and simple syrup, cherry syrup vehicle (Humco), or Ora-Sweet SF (Paddock).1 Consult manufacturer's information for specific instructions.1

Reconstitution

Reconstitute commercially available powder for oral suspension at the time of dispensing.1 Tap bottle to thoroughly loosen powder and then add the amount of water specified on the bottle; shake well for 15 seconds.1

Reconstituted oral suspension contains 6 mg/mL; each 12.5 mL contains 75 mg of oseltamivir.1

Provide an oral dosing device that can accurately measure the appropriate volume in mL;1 counsel patient and/or caregiver how to use the oral dosing dispenser to correctly measure and administer the appropriate dose.1

Shake suspension well prior to each dose.1

Dosage

Available as oseltamivir phosphate; dosage expressed in terms of oseltamivir.1

Pediatric Patients

Treatment of Seasonal Influenza A and B Virus Infections
Oral

Initiate treatment within 2 days after onset of symptoms.1 Although efficacy not established,1 there is some evidence that antiviral treatment initiated up to 96 hours after onset of symptoms still may be beneficial in hospitalized patients and those with severe, complicated, or progressive influenza.112 116 137 144 Although usual duration of antiviral treatment is 5 days, 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.137 144

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

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.112 Although safety and efficacy not established in neonates <2 weeks of age,1 AAP states the drug can be used for treatment of influenza in neonates from birth because of its known safety profile.112 (See Pediatric Use under Cautions.)

Dosage recommended for full-term infants may be excessive in preterm neonates.112 144 Some experts state data insufficient to make dosage recommendations for preterm infants.144 Others state that, if the drug is considered necessary for treatment of influenza in preterm neonates, base dosage on postmenstrual age (i.e., gestational age plus chronological age).112 These experts 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.112

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

Adolescents ≥13 years of age: 75 mg twice daily for 5 days.1

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)

≤15

30 mg twice daily for 5 days

5 mL twice daily for 5 day

15.1–23

45 mg twice daily for 5 days

7.5 mL twice daily for 5 day

23.1–40

60 mg twice daily for 5 days

10 mL twice daily for 5 day

≥40.1

75 mg twice daily for 5 days

12.5 mL twice daily for 5 day

Prevention of Seasonal Influenza A and B Virus Infections
Oral

Initiate prophylaxis within 2 days after exposure (e.g., close contact with infected individual).1 137 Usual duration is 10 days.1 CDC recommends prophylaxis be continued for 7 days after last known exposure;137 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.137 May be continued for up to 6 weeks during a community influenza outbreak.1

Although safety and efficacy not established for prophylaxis of influenza in infants <1 year of age,1 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.137 144 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.112

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.112 137 144

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

Adolescents ≥13 years of age: 75 mg once daily for at least 10 days.1

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)

≤15

30 mg once daily for 10 days

5 mL once daily for 10 days

15.1–23

45 mg once daily for 10 days

7.5 mL once daily for 10 days

23.1–40

60 mg once daily for 10 days

10 mL once daily for 10 days

≥40.1

75 mg once daily for 10 days

12.5 mL 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.50 63 68 104

Dosage usually recommended for treatment of seasonal influenza A and B virus infections has been recommended.63 104 (See Treatment of Seasonal Influenza A and B Virus Infections under Dosage and Administration.) This dosage may be reasonable for early, mild cases of avian influenza A infection,63 68 85 but CDC, WHO, and others state that severely ill patients may benefit from higher dosage.50 63 68 85 104 In addition, 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.50 63 68 85 104

Initiate treatment as early as possible.50 104 152 555 May be most beneficial if initiated within 2 days of symptom onset,152 but is warranted even if initiated >48 hours after illness onset or in patients who present for care in later stages of illness.50 104 152 555

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.50 94 (See Prevention of Seasonal Influenza A and B Virus Infections under Dosage and Administration.) Continue prophylaxis for 7–10 days after last known exposure.50 94

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.50 (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.43 52

Adults

Treatment of Seasonal Influenza A and B Virus Infections
Oral

75 mg twice daily for 5 days.1

Initiate treatment within 2 days after onset of symptoms.1 Although efficacy not established,1 there is some evidence that antiviral treatment initiated up to 96 hours after onset of symptoms may still be beneficial in hospitalized patients and those with severe, complicated, or progressive influenza.112 116 137 144 Although usual duration of antiviral treatment is 5 days, 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.137 144

Prevention of Seasonal Influenza A and B Virus Infections
Oral

75 mg once daily for at least 10 days.1

Initiate prophylaxis within 2 days after exposure (e.g., close contact with infected individual).1 137 Usual duration is 10 days.1 CDC recommends prophylaxis be continued for 7 days after last known exposure;137 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.137 Safety and efficacy of prophylaxis demonstrated for up to 6 weeks in immunocompetent individuals;1 safety of prophylaxis demonstrated for up to 12 weeks in immunocompromised individuals.1

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.50 63 68 104

Dosage usually recommended for treatment of seasonal influenza A and B virus infections has been recommended.63 104 (See Treatment of Seasonal Influenza A and B Virus Infections under Dosage and Administration.) This dosage may be reasonable for early, mild cases of avian influenza A infection,63 68 85 but CDC, WHO, and others state that severely ill patients may benefit from higher dosage (i.e., 150 mg twice daily in adults with normal renal function).50 63 68 85 104 In addition, 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.50 63 68 85 104

Initiate treatment as early as possible.50 104 152 555 May be most beneficial if initiated within 2 days of symptom onset,152 but is warranted even if initiated >48 hours after illness onset or in patients who present for care in the later stages of illness.50 104 152 555

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.50 94 (See Prevention of Seasonal Influenza A and B Virus Infections under Dosage and Administration.) Continue prophylaxis for 7–10 days after last known exposure.50 94

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.50 (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.61

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.43

Special Populations

Hepatic Impairment

Usual dosage can be used in those with mild to moderate hepatic impairment (Child-Pugh score ≤9).1 42

Renal Impairment

Treatment of influenza A or B virus infections in patients with Clcr 10–30 mL/minute: 75 mg once daily for 5 days.1

Prevention of influenza A or B virus infections in patients with Clcr 10–30 mL/minute: 75 mg once every other day or 30 mg once daily for 10 days after last known exposure to a confirmed case.1

Dosage recommendations not available for patients with end-stage renal disease (Clcr <10 mL/minute) or those undergoing routine hemodialysis or CAPD.1

Geriatric Patients

No dosage adjustments except those related to renal impairment.1

Cautions for Oseltamivir Phosphate

Contraindications

  • Known hypersensitivity to oseltamivir or any ingredient in the formulations.1

Warnings/Precautions

Sensitivity Reactions

Dermatologic and Hypersensitivity Reactions

Anaphylaxis and serious skin reactions, including toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme, reported.1

If an allergic reaction occurs or is suspected, discontinue oseltamivir and institute appropriate therapy.1

Neuropsychiatric Events

Adverse neuropsychiatric events (e.g., self-injury, delirium, hallucinations, confusion, abnormal behavior, seizures) and death reported.1 84 88

Postmarketing reports of delirium and abnormal behavior leading to injury mainly involved children from Japan.1 84 88 Cases generally had an abrupt onset and rapid resolution.1 Role of oseltamivir not determined.1

Influenza itself can be associated with neurologic and behavioral symptoms (e.g., hallucinations, delirium, abnormal behavior) and fatalities can occur.1 Although such events may occur in the setting of encephalitis or encephalopathy, they can occur without obvious severe disease.1

Closely monitor patients with influenza for signs of abnormal behavior.1 If neuropsychiatric symptoms develop, consider risks versus benefits of continued therapy.1

Bacterial Infections

Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications of influenza.1 No evidence that oseltamivir prevents such complications.1

No evidence of efficacy in illness caused by any organisms other than influenza A or B.1

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.1

Although efficacy for treatment or prevention of influenza not established in immunocompromised patients,1 safety of oseltamivir prophylaxis has been demonstrated for up to 12 weeks in immunocompromised patients.1 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.1 74 75 101 (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.1

Influenza Vaccination

Not a substitute for annual vaccination with a seasonal influenza vaccine (influenza virus vaccine inactivated, influenza vaccine live intranasal, influenza vaccine recombinant).1 144

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,1 100 these antivirals may inhibit the vaccine virus contained in influenza vaccine live intranasal.1 100 (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.1 This amount of sorbitol exceeds the maximum daily limit of sorbitol for individuals with hereditary fructose intolerance and may result in dyspepsia and diarrhea.1

Specific Populations

Pregnancy

Category C.1

Pregnant women are at increased risk for severe complications and death from influenza.142 144

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.142 144

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,142 144 but drug of choice for prophylaxis of these infections is less clear.142 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.142 144

Lactation

Use with caution and only if potential benefits justify possible risks to breast-fed infant.1

Distributed into milk in rats; not known whether distributed into human milk.1

Pediatric Use

Safety and efficacy for treatment of influenza not established in infants <2 weeks of age.1

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

Young children, especially those <2 years of age, are at increased risk of influenza infection, hospitalization, and complications.112 144 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.121 150 Although the EUA expired in June 2010,150 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.112 ACIP and AAP state that oseltamivir not recommended for prevention of influenza in infants <3 months of age unless situation is judged critical.112 144 (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.1 83 84 (See Neuropsychiatric Events under Cautions.)

Geriatric Use

No overall differences in safety or efficacy compared with younger adults, but increased sensitivity cannot be ruled out.1

Hepatic Impairment

Safety and pharmacokinetics not evaluated in patients with severe hepatic impairment.1

Renal Impairment

Decreased clearance.1 Dosage adjustment recommended if Clcr is 10–30 mL/minute.1 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (nausea, vomiting, diarrhea, abdominal pain), headache, bronchitis, insomnia, vertigo.1 2 3 4

Interactions for Oseltamivir Phosphate

Oseltamivir phosphate and its active metabolite not metabolized by and do not inhibit CYP isoenzymes;1 25 drug interactions with drugs that are substrates or inhibitors of these enzymes unlikely.1

Drugs Eliminated by Renal Excretion

Potential pharmacokinetic interaction when used concomitantly with other drugs eliminated by renal tubular secretion (e.g., probenecid);1 clinically important interactions unlikely.1

Specific Drugs

Drug

Interaction

Comments

Acetaminophen

No evidence of pharmacokinetic interaction1

Amoxicillin

No evidence of pharmacokinetic interaction1

Antacids (containing magnesium, aluminum, or calcium carbonate)

No clinically important effect on oseltamivir pharmacokinetics1 92

Anticoagulants, oral

No evidence of pharmacokinetic interaction1

Aspirin

Pharmacokinetic interactions unlikely1 33

Cimetidine

No evidence of pharmacokinetic interaction1

Influenza virus vaccines

Influenza virus vaccine inactivated: Oseltamivir does not interfere with the antibody response to the vaccine1

Influenza vaccine live intranasal: Oseltamivir may inhibit the vaccine virus and interfere with antibody response to the live vaccine;1 100 no specific studies1 100

Influenza virus vaccine inactivated: May be administered concomitantly with or at any time before or after oseltamivir1 100

Influenza vaccine live intranasal: Do not administer the live vaccine until ≥48 hours after oseltamivir is discontinued; do not administer oseltamivir until ≥2 weeks after administration of the vaccine, unless medically indicated;1 100 if oseltamivir given within 2 weeks after the vaccine, repeat vaccine dose ≥48 hours after last antiviral dose;100 alternatively, if oseltamivir given 2 days before to 14 days after the vaccine, revaccinate using the parenteral inactivated vaccine or parenteral recombinant vaccine100

Probenecid

Potential increased systemic exposure to oseltamivir carboxylate because of decreased renal tubular secretion1

Not expected to be clinically important;1 use usual dosages1

Oseltamivir Phosphate Pharmacokinetics

Absorption

Bioavailability

Oseltamivir phosphate readily absorbed following oral administration and then extensively converted to the active metabolite (oseltamivir carboxylate).1 24 25

Absolute bioavailability of oseltamivir carboxylate 80% following oral administration of oseltamivir phosphate;25 peak concentrations of active metabolite attained within 3–4 hours.1

Food

Administration of oseltamivir phosphate with food has no effect on peak plasma concentrations or AUC of oseltamivir carboxylate.1

Distribution

Extent

Following oral administration of oseltamivir phosphate, oseltamivir carboxylate distributed throughout body, including upper and lower respiratory tract.24 25

Placental transfer of oseltamivir carboxylate demonstrated in rats and rabbits; not known whether oseltamivir or oseltamivir carboxylate crosses the placenta in humans.1

Distributed into milk in rats; not known whether oseltamivir or oseltamivir carboxylate distributed into human milk.1

Plasma Protein Binding

Oseltamivir phosphate 42% bound to plasma proteins; oseltamivir carboxylate 3% bound to plasma proteins.1 24

Elimination

Metabolism

Oseltamivir phosphate extensively converted to oseltamivir carboxylate, principally by hepatic esterases.1

Oseltamivir phosphate and oseltamivir carboxylate not metabolized by CYP enzymes.1 25

Elimination Route

Oseltamivir phosphate principally (>90%) eliminated by conversion to oseltamivir carboxylate.1 25 No further metabolism.1

Oseltamivir carboxylate principally eliminated by glomerular filtration and tubular secretion;1 24 25 <20% of dose eliminated in feces.1

Half-life

Plasma half-life of oseltamivir phosphate 1–3 hours;1 24 half-life of oseltamivir carboxylate 6–10 hours.1 25

Special Populations

Renal clearance decreased in patients with impaired renal function.1 25

Systemic exposure to oseltamivir carboxylate in individuals with mild or moderate hepatic impairment is comparable to that in individuals without hepatic impairment.1 42

Clearance of both oseltamivir phosphate and oseltamivir carboxylate increased in younger pediatric patients compared with adults.1 Total clearance of oseltamivir carboxylate decreases linearly with increasing age (up to 12 years of age);1 pharmacokinetics in those >12 years of age similar to adults.1

Exposure to oseltamivir carboxylate at steady-state approximately 25–35% higher in geriatric individuals (65–78 years of age) compared with younger adults;1 3 similar plasma half-life.1

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).1

Powder for Suspension

25°C (may be exposed to 15–30°C).1

Following reconstitution, store suspension at 2–8°C for up to 17 days.1 Alternatively, may be stored for up to 10 days at 25°C (may be exposed to 15–30°).1 Do not freeze.1

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 (35 days) at 2–8°C or 5 days at 25°C.1

Actions and Spectrum

  • Oseltamivir phosphate is prodrug and is inactive until hydrolyzed by hepatic esterases to oseltamivir carboxylate, the active metabolite.1 2 3 4 5 6 7 8 9

  • Oseltamivir carboxylate is a potent selective competitive inhibitor of influenza virus neuraminidase, an enzyme essential for viral replication;1 2 3 8 9 possibly alters virus particle aggregation and release.1

  • Active against influenza A and B viruses, including amantadine- and rimantadine-resistant isolates.1 2 3 7 8 The majority of seasonal influenza A (H3N2), influenza A (H1N1)pdm09, and influenza B viruses circulating during recent influenza seasons have been susceptible to oseltamivir.551 552

  • Beginning in the 2007–2008 influenza season, a significant increase in the prevalence of oseltamivir-resistant seasonal influenza A (H1N1) was reported worldwide;144 153 488 almost all seasonal influenza A (H1N1) strains tested in the US in 2008, 2009, and beginning of 2010 were resistant to oseltamivir.488 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.163 551 552

  • Although almost all isolates of influenza A (H1N1)pdm09 virus have been susceptible to oseltamivir in vitro,144 163 167 551 552 resistance has been reported rarely.123 144 155 156 157 163 167 551 552 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.144

  • 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).26 27 50 58 61 104 555 557 560 However, avian influenza A (H5N1)50 68 73 81 104 557 and influenza A (H7N9)558 559 with reduced in vitro susceptibility or resistance to oseltamivir have been reported rarely.

  • Influenza strains cross-resistant to zanamivir and oseltamivir have been generated in cell culture; only limited data available regarding possible emergence of clinical isolates with cross-resistance to both drugs.1 9 36 37 62 To date, influenza A (H1N1)pdm09 isolates with the H275Y mutation144 163 167 552 and avian influenza A (H5N1) with the H274Y mutation94 that are resistant to oseltamivir have been susceptible to zanamivir.

Advice to Patients

  • Importance of using the appropriate graduated oral dosing dispenser to measure and administer dose of reconstituted oral suspension.1

  • Importance of initiating oseltamivir treatment as soon as possible after appearance of influenza symptoms (within 2 days after symptom onset);1 efficacy not established if treatment begins >48 hours after symptoms have been established.1

  • Importance of initiating oseltamivir prophylaxis as soon as possible after exposure to influenza (within 2 days after exposure).1

  • Importance of complying with the entire drug regimen.1 Importance of taking missed dose as soon as remembered, except if within 2 hours of the next scheduled dose.1

  • Importance of informing clinician if signs of unusual behavior develop.1

  • Advise patients that oseltamivir is not a substitute for annual vaccination with influenza virus vaccine.1

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

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

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

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 05/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Tamiflu 12MG/ML Suspension (GENENTECH): 25/$53.54 or 75/$145.91

Tamiflu 30MG Capsules (GENENTECH): 10/$110.08 or 30/$321.51

Tamiflu 45MG Capsules (GENENTECH): 10/$110.08 or 30/$321.51

Tamiflu 75MG Capsules (GENENTECH): 10/$110.99 or 30/$321.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions April 29, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

1. Genentech, Inc. Tamiflu (oseltamivir phosphate) capsules and for oral suspension prescribing information. South San Francisco, CA: 2013 Jan.

2. Hayden FG, Treanor JJ, Fritz RS et al. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment. JAMA. 1999; 282:1240-6. [IDIS 434353] [PubMed 10517426]

3. Hayden FG, Atmar RL, Schilling M et al. Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med. 1999; 341:1336-43. [IDIS 435926] [PubMed 10536125]

4. Treanor JJ, Hayden FG, Vrooman PS et al for the US Oral Neuraminidase Study Group. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. JAMA. 2000; 283:1016-24. [IDIS 440764] [PubMed 10697061]

5. Nicholson KG, Aoki FY, Osterhaus ADME et al on behalf of the Neuraminidase Inhibitor Flu Treatment Investigator Group. Efficacy and safety of oseltamivir in treatment of acute influenza: a randomized controlled trial. Lancet. 2000; 355:1845-50. [IDIS 447775] [PubMed 10866439]

6. Kim CU, Chen X, Mendel DB. Neuraminidase inhibitors as anti-influenza virus agents. Antivir Chem Chemother. 1999; 10:141-54. [PubMed 10480735]

7. Cox NJ, Hughes JM. New options for the prevention of influenza. N Engl J Med. 1999; 341:1387-8. [IDIS 435927] [PubMed 10536132]

8. Sidwell RW, Huffman JH, Barnard DL et al. Inhibition of influenza virus infections in mice by GS4104, an orally effective influenza virus neuraminidase inhibitor. Antiviral Res. 1998; 37:107-20. [PubMed 9588843]

9. Calfee DP, Hayden FG. New approaches to influenza chemotherapy: neuraminidase inhibitors. Drugs. 1998; 45:537-53.

12. Roche, Nutley, NJ: Personal communication.

15. Whitley RJ, Hayden FG, Reisinger KS et al. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J. 2001; 20:127-33. [IDIS 460096] [PubMed 11224828]

16. Welliver R, Monto AS, Carewicz O et al for the Oseltamivir Post Exposure Prophylaxis Investigator Group. Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial. JAMA. 2001; 285:748-54. [IDIS 459757] [PubMed 11176912]

22. Kaiser L, Wat C, Mills T et al. Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations. Arch Intern Med. 2003; 163:1667-72. [IDIS 502465] [PubMed 12885681]

24. Doucette KE, Aoki FY. Oseltamivir: a clinical and pharmacological perspective. Expert Opin Pharmacother. 2001; 2:1671-83. [PubMed 11825310]

25. He G, Massarella J, Ward P. Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite Ro 64-0802. Clin Pharmacokinet. 1999; 37:471-84. [PubMed 10628898]

26. Govorkova EA, Leneva IA, Goloubeva OG et al. Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses. Antimicrob Agents Chemother. 2001; 45:2723-32. [PubMed 11557461]

27. Leneva IA, Roberts N, Govorkova EA et al. The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses. Antiviral Res. 2000; 48:101-15. [PubMed 11114412]

28. Johnston SL, Ferrero F, Garcia ML et al. Oral oseltamivir improves pulmonary function and reduces exacerbation frequency for influenza-infected children with asthma. Pediatr Infect Dis J. 2005; 24:225-32.

29. Peters PH Jr, Gravenstein S, Norwood P et al. Long-term use of oseltamivir for the prophylaxis of influenza in a vaccinated frail older population. J Am Geriatr Soc. 2001; 49:1025-31. [IDIS 469940] [PubMed 11555062]

30. Hayden FG, Belshe R, Villanueva C et al. Management of influenza in households: a prospective, randomized comparison of oseltamivir treatment with or without postexposure prophylaxis. J Infect Dis. 2004; 189:440-9. [IDIS 517387] [PubMed 14745701]

31. Monto AS, Rotthoff J, Teich E et al. Detection and control of influenza outbreaks in well-vaccinated nursing home populations. Clin Infect Dis. 2004; 39:459-64. [IDIS 521708] [PubMed 15356805]

33. Oo C, Barrett J, Dorr A et al. Lack of pharmacokinetic interaction between the oral anti-influenza prodrug oseltamivir and aspirin. Antimicrob Agents Chemother. 2002; 46:1993-5. [IDIS 481645] [PubMed 12019123]

34. Hill G, Cihlar T, Oo C et al. The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions via renal secretion—correlation of in vivo and in vitro studies. Drug Metab Disp. 2002; 30:13-9.

35. Hayden FG. Pandemic influenza: is an antiviral response realistic? Pediatr Infect Dis J. 2004; 23(Suppl):S262-9.

36. McKimm-Breschkin J, Trivedi T, Hampson A et al. Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir. Antimicrob Agents Chemother. 2003; 47:2264-72.

37. Gubareva LV, Kaiser L, Matrosovich MN et al. Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir. J Infect Dis. 2001; 183:523-31. [IDIS 460496] [PubMed 11170976]

38. Gubareva LV, Webster RG, Hayden FG. Comparison of the activities of zanamivir, oseltamivir, and RWJ-270201 against clinical isolates of influenza virus and neuraminidase inhibitor-resistant variants. Antimicrob Agents Chemother. 2001; 45:3403-8. [PubMed 11709315]

39. Oo C, Barrett J, Hill G et al. Pharmacokinetics and dosage recommendations for an oseltamivir oral suspension for the treatment of influenza in children. Paediatr Drugs. 2001; 3:229-36. (Erratum in Paediatr Drugs. 2001; 3:246.) [PubMed 11310719]

40. Oo C, Hill G, Dorr A et al. Pharmacokinetics of anti-influenza prodrug oseltamivir in children aged 1–5 years. Eur J Clin Pharmacol. 2003; 59:411-5. [IDIS 508474] [PubMed 12910331]

42. Snell P, Dave N, Wilson K et al. Lack of effect of moderate hepatic impairment on the pharmacokinetics of oral oseltamivir and its metabolite oseltamivir carboxylate. Br J Clin Pharmacol. 2005; 59:598-601. (Erratum in Br J Clin Pharmacol. 2005; 60:115.) [IDIS 542717] [PubMed 15842560]

43. Ward P, Small I, Smith J et al. Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. J Antimicrob Chemother. 2005; 55(Suppl S1):i5-21. [IDIS 546365] [PubMed 15709056]

44. Wetherall NT, Trivedi T, Zeller J et al. Evaluation of neuraminidase enzyme assays using different substrates to measure susceptibility of influenza virus clinical isolates to neuraminidase inhibitors: report of the neuraminidase inhibitor susceptibility network. J Clin Microbiol. 2003; 41:742-50. [PubMed 12574276]

46. Hien TT, Liem NT, Dung NT et al. Avian influenza A (H5N1) in 10 patients in Vietnam. N Engl J Med. 2004; 350:1179-88. [PubMed 14985470]

47. Chokephaibulkit K, Uiprasertkul M, Puthavathana P et al. A child with avian influenza A (H5N1) infection. Pediatr Infect Dis J. 2005; 24:162-6.

50. US Centers for Disease Control and Prevention. Information on avian influenza. From CDC website. Accessed 2014 Feb 4.

52. World Health Organization. WHO guidelines for pharmacological management of pandemic influenza A (H1N1) 2009 and other influenza viruses. Revised February 2010. Part I. Recommendations. From WHO website. Accessed 2014 Feb 4.

54. Longini IM Jr, Nizam A, Xu S et al. Containing pandemic influenza at the source. Sciencexpress. 2005 Aug 3.

55. Tsang KWT, Eng P, Liam CK et al. H5N1 influenza pandemic: contingency plans. Lancet. 2005; 366:533-4. Editorial. [PubMed 16099278]

56. Ferguson NM, Cummings DAT, Cauchemez S et al. Strategies for containing an emerging influenza pandemic in Southeast Asia. Nature. Published online at Nature.com on 3 August 2005.

58. Yen HL, Monto AS, Webster RG et al. Virulence may determine the necessary duration and dosage of oseltamivir treatment for highly pathogenic A/Vietnam/1203/04 influenza virus in mice. J Infect Dis. 2005; 192:665-72. [PubMed 16028136]

60. Nuzzo J. Federal advisory groups recommend priorities for vaccination and antivirals during a pandemic. CBN Weekly Bulletin. 2005 Aug 2.

61. Koopmans M, Wilbrink B, Conyn M et al. Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands. Lancet. 2004; 363:587-93. [PubMed 14987882]

62. Yen H-L, Herlocher LM, Hoffman E et al. Neuraminidase inhibitor-resistant influenza viruses may differ substantially in fitness and transmissibility. Antimicrob Agents Chemother. 2005: 49: 4075-84.

63. Reviewers’ comments (personal observations).

64. Moscona A. Neuraminidase inhibitors for influenza. N Engl J Med. 2005; 353:1363-73. [IDIS 540075] [PubMed 16192481]

65. Cooper NJ, Sutton AJ, Abrams KR et al. Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analysis of randomized controlled trials. BMJ. 2003; 326:1235-40. [IDIS 499352] [PubMed 12791735]

66. Bowles SK, Lee W, Simor AE et al. Use of oseltamivir during influenza outbreaks in Ontario nursing homes, 1999-2000. J Am Geriatr Soc. 2002; 50:608-16. [IDIS 480242] [PubMed 11982659]

67. Nordstrom BL, Sung I, et al Suter P. Risk of pneumonia and other complications of influenza-like illness in patients treated with oseltamivir. Curr Med Res Opin. 2005; 21:761-8. [PubMed 15969875]

68. Writing Committee of the World Health Organization (WHO) consultation on human influenza A/H5. Avian influenza A (H5N1) infection in humans. N Engl J Med. 2005; 353:1374-85. [IDIS 540076] [PubMed 16192482]

69. Ungchusak K, Auewarakul P, Dowell SF et al. Probable person-to-person transmission of Avian influenza A (H5N1). N Engl J Med. 2005; 352:333-40. [PubMed 15668219]

70. Kiso M, Mitamura K, Sakai-Tagawa Y et al. Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet. 2004; 364:759-65. [IDIS 521344] [PubMed 15337401]

73. Le QM, Kiso M, Someya K et al. Isolation of drug-resistant H5N1 virus. Nature. 2005; 437.

74. Machado CM, Boas LSV, Mendes AVA et al. Use of oseltamivir to control influenza complications after bone marrow transplantation. Bone Marrow Transplant. 2004; 34:111-4. [IDIS 518119] [PubMed 15094755]

75. Chik KW, Li CK, Chan PKS et al. Oseltamivir prophylaxis during the influenza season in a paediatric cancer centre: prospective observational study. Hong Kong Med J. 2004; 10:103-6. [PubMed 15075430]

81. deJong MD, Tran TT, Truong HK et al. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med. 2005; 353:2667-72. [PubMed 16371632]

83. Edwards ET, Truffa MM. One-year post pediatric exclusivity postmarketing adverse events review. Drug: oseltamivir phosphate. 24 Aug 2005. From FDA website. Accessed 10 Jan 2006.

84. US Food and Drug Administration. Pediatric safety update for Tamiflu-Pediatric Advisory Committee meeting. 18 Nov 2005. From FDA website. Accessed 10 Jan 2006.

85. Moscona A. Oseltamivir resistance-disabling our influenza defenses. N Engl J Med. 2005; 353:2633-6. [PubMed 16371626]

88. US Food and Drug Administration. Tamiflu pediatric adverse events: questions and answers. From FDA website. Accessed 17 Mar 2006.

92. Snell P, Oo C, Dorr A et al. Lack of pharmacokinetic interaction between the oral anti-influenza neuraminidase inhibitor prodrug oseltamivir and antacids. Clin Pharmacol. 2002; 54:372-7.

93. Ison MG, Gubareva LV, Atmar RL et al. Recovery of drug-resistant influenza virus from immunocompromised patients: a case series. J Infect Dis. 2006; 193:760-4. [PubMed 16479508]

94. World Health Organization. WHO rapid advice guidelines on pharmacological management of humans infected with avian influenza A (H5N1) virus. World Health Organization 2006. From WHO website. Accessed 2014 Feb 4.

100. Influenza Division, National Center for Immunization and Respiratory Diseases, CDC. Prevention and control of seasonal influenza with vaccines. MMWR Recomm Rep. 2013; 62(RR-07):1-43. [PubMed 24048214]

101. Nichols WG, Guthrie KA, Corey L, Boeckh M. Influenza infections after hematopoietic stem cell transplantation: risk factors, mortality, and the effect of antiviral therapy. Clin Infect Dis. 2004; 39:1300-6. [PubMed 15494906]

104. World Health Organization. Avian influenza. From WHO website. Accessed 2014 Feb 4.

105. American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.

112. Committee on Infectious Disease. Recommendations for Prevention and Control of Influenza in Children, 2013–2014. Pediatrics. 2013; :.

114. Centers for Disease Control and Prevention. Update: Swine influenza A (H1N1) infections–California and Texas, April 2009. MMWR Morb Mortal Wkly Rep. 2009; 58:435-7.

116. Harper SA, Bradley JS, Englund JA et al. Seasonal influenza in adults and children--diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2009; 48:1003-32. [PubMed 19281331]

118. Centers for Disease Control and Prevention. Swine-origin influenza A (H1N1) virus infection in a school–New York City, April 2009. MMWR Morb Mortal Wkly Rep. 2009; 58 (Dispatch):1-3. [PubMed 19145219]

119. Centers for Disease Control and Prevention. Outbreak of swine-origin influenza A (H1N1) virus infection–Mexico, March-April 2009. MMWR Morb Mortal Wkly Rep. 2009; 58 (Dispatch):1-3. [PubMed 19145219]

121. Food and Drug Administration. Tamiflu letter for emergency use authorization. April 27, 2009. From FDA website.

123. Centers for Disease Control and Prevention (CDC). Update: influenza activity - United States, August 30, 2009-March 27, 2010, and composition of the 2010-11 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2010; 59:423-30. [PubMed 20395936]

124. Centers for Disease Control and Prevention. Update: drug susceptibility of swine-origin influenza A (H1N1) viruses, April 2009. MMWR Morb Mortal Wkly Rep. 2009; 58:433-4. [PubMed 19407738]

132. Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Eng J Med. 2009; 361.

134. Centers for Disease Control and Prevention. The 2009 H1N1 pandemic: summary highlights, April 2009–April 2010. From CDC website. Accessed 28 Oct 2010.

137. Centers for Disease Control and Prevention. Influenza antiviral medications: summary for clinicians. From CDC website. Accessed 2014 Feb 10.

141. Barron H. Dear healthcare provider letter regarding Tamiflu (oseltamivir). Nutley, NJ: Roche; 2009 Sep 23.

142. Centers for Disease Control and Prevention. Recommendations for obstetric health care providers related to use of antiviral medications in the treatment and prevention of influenza. From CDC website. Accessed 2014 Jan 28.

144. Fiore AE, Fry A, Shay D et al. Antiviral agents for the treatment and chemoprophylaxis of influenza --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011; 60:1-24. [PubMed 21248682]

147. . Summary of human infection with highly pathogenic avian influenza A (H5N1) virus reported to WHO, January 2003-March 2009: cluster-associated cases. Wkly Epidemiol Rec. 2010; 85:13-20. [PubMed 20095108]

148. World Health Organization. Global alert and response (GAR). WHO recommendations for the post-pandemic period. From WHO website. Accessed Sep 29, 2010.

150. Food and Drug Administration. Tamiflu and relenza emergency use authorization disposition letters and question and answer attachments. June 22, 2010. From FDA website. Accessed 2010 Oct 1.

151. Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 Influenza, Bautista E, Chotpitayasunondh T et al. Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med. 2010; 362:1708-19. [PubMed 20445182]

152. Adisasmito W, Chan PK, Lee N et al. Effectiveness of antiviral treatment in human influenza A(H5N1) infections: analysis of a Global Patient Registry. J Infect Dis. 2010; 202:1154-60. [PubMed 20831384]

153. Ujike M, Shimabukuro K, Mochizuki K et al. Oseltamivir-resistant influenza viruses A (H1N1) during 2007-2009 influenza seasons, Japan. Emerg Infect Dis. 2010; 16:926-35. [PubMed 20507742]

154. Inoue M, Barkham T, Leo YS et al. Emergence of Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus within 48 Hours. Emerg Infect Dis. 2010; 16:1633-6. [PubMed 20875299]

155. Tramontana AR, George B, Hurt AC et al. Oseltamivir resistance in adult oncology and hematology patients infected with pandemic (H1N1) 2009 virus, Australia. Emerg Infect Dis. 2010; 16:1068-75. [PubMed 20587176]

156. Hill-Cawthorne GA, Schelenz S, Lawes M et al. Oseltamivir-resistant pandemic (H1N1) 2009 in patient with impaired immune system. Emerg Infect Dis. 2010; 16:1185-6. [PubMed 20587208]

157. van der Vries E, Stelma FF, Boucher CA. Emergence of a multidrug-resistant pandemic influenza A (H1N1) virus. N Engl J Med. 2010; 363:1381-2. [PubMed 20879894]

158. Cheng PK, To AP, Leung TW et al. Oseltamivir- and amantadine-resistant influenza virus A (H1N1). Emerg Infect Dis. 2010; 16:155-6. [PubMed 20031069]

161. Centers for Disease Control and Prevention. Intravenous influenza antiviral medications and CDC considerations related to investigational use of intravenous zanamivir for 2013–2014 influenza season. From CDC website. Accessed 2014 Feb 3.

162. Hayden FG, de Jong MD. Emerging influenza antiviral resistance threats. J Infect Dis. 2011; 203:6-10. [PubMed 21148489]

163. . Recommended composition of influenza virus vaccines for use in the 2011-2012 northern hemisphere influenza season. Wkly Epidemiol Rec. 2011; 86:81-91.

167. . Review of the 2010-2011 winter influenza season, northern hemisphere. Wkly Epidemiol Rec. 2011; 86:221-32. [PubMed 21661270]

487. World Health Organization. Cumulative number of confirmed human cases of avian influenza A(H5N1) reported to WHO, 2003-2014. From WHO website.

488. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases. 12th ed. Washington DC: Public Health Foundation; 2012 May. Updates may be available at CDC website.

551. Centers for Disease Control and Prevention (CDC). Influenza activity--United States, 2012-13 season and composition of the 2013-14 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2013; 62:473-9. [PubMed 23760189]

552. . Recommended composition of influenza virus vaccines for use in the 2013–2014 northern hemisphere influenza season. Wkly Epidemiol Rec. 2013; 88:101-14. [PubMed 23544236]

553. World Health Organization (WHO). Standardization of terminology of the pandemic A(H1N1)2009 virus. October 2011. From WHO website. Accessed 2013 Jul.

555. Centers for Disease Control and Prevention (CDC). Emergence of avian influenza A(H7N9) virus causing severe human illness - China, February-April 2013. MMWR Morb Mortal Wkly Rep. 2013; 62:366-71. [PubMed 23657113]

556. Gao HN, Lu HZ, Cao B et al. Clinical findings in 111 cases of influenza A (H7N9) virus infection. N Engl J Med. 2013; 368:2277-85. [PubMed 23697469]

557. Govorkova EA, Baranovich T, Seiler P et al. Antiviral resistance among highly pathogenic influenza A (H5N1) viruses isolated worldwide in 2002-2012 shows need for continued monitoring. Antiviral Res. 2013; 98:297-304. [PubMed 23458714]

558. Hu Y, Lu S, Song Z et al. Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance. Lancet. 2013; 381:2273-9. [PubMed 23726392]

559. Wu Y, Bi Y, Vavricka CJ et al. Characterization of two distinct neuraminidases from avian-origin human-infecting H7N9 influenza viruses. Cell Res. 2013; 23:1347-55. [PubMed 24165891]

560. Chen H, Yuan H, Gao R et al. Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: a descriptive study. Lancet. 2014; 383:714-21. [PubMed 24507376]

Hide
(web2)