Oseltamivir

Oseltamivir
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

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Overview

Oseltamivir is a antiviral that is FDA approved for the treatment of influenza A and influenza B (flu) virus. Common adverse reactions include rash, dermatitis, urticaria, eczema, toxic epidermal necrolysis, Stevens-Johnson Syndrome, erythema multiforme, hepatitis, liver function tests abnormal, arrhythmia, gastrointestinal bleeding, hemorrhagic colitis, seizure, aggravation of diabetes, psychiatric conditions.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Treatment of Influenza

• Ostelmavir is indicated for the treatment of uncomplicated acute illness due to influenza infection in patients 1 year and older who have been symptomatic for no more than 2 days.

Prophylaxis of Influenza

• TAMIFLU is indicated for the prophylaxis of influenza in patients 1 year and older.

Limitations of Use

The following points should be considered before initiating treatment or prophylaxis with oseltamivir.

• Efficacy of oseltamivir in patients who begin treatment after 48 hours of symptoms has not been established.
• Oseltamivir is not a substitute for early influenza vaccination on an annual basis as recommended by the Centers for Disease Control and Prevention * Advisory Committee on Immunization Practices.
• There is no evidence for efficacy of oseltamivir in any illness caused by agents other than influenza viruses types A and B.
• Influenza viruses change over time. Emergence of resistance mutations could decrease drug effectiveness.
• Prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use oseltamivir.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Oseltamivir in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Oseltamivir in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

• The safety and efficacy of TAMIFLU in pediatric patients younger than 1 year of age have not been studied. TAMIFLU is not indicated for either treatment or prophylaxis of influenza in pediatric patients younger than 1 year of age because of the unknown clinical significance of nonclinical animal toxicology data for human infants.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Oseltamivir in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Oseltamivir in pediatric patients.

Contraindications

• TAMIFLU is contraindicated in patients with known serious hypersensitivity to oseltamivir or any component of the product. Severe allergic reactions have included anaphylaxis and serious skin reactions including toxic epidermal necrolysis, Stevens-Johnson Syndrome, and erythema multiforme.

Warnings

Serious Skin/Hypersensitivity Reactions

• Cases of anaphylaxis and serious skin reactions including toxic epidermal necrolysis, Stevens-Johnson Syndrome, and erythema multiforme have been reported in postmarketing experience with TAMIFLU. TAMIFLU should be stopped and appropriate treatment instituted if an allergic-like reaction occurs or is suspected.

Neuropsychiatric Events

• Influenza can be associated with a variety of neurologic and behavioral symptoms that can include events such as hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease.
• There have been postmarketing reports (mostly from Japan) of delirium and abnormal behavior leading to injury, and in some cases resulting in fatal outcomes, in patients with influenza who were receiving TAMIFLU. Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made but they appear to be uncommon based on TAMIFLU usage data. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of TAMIFLU to these events has not been established. Closely monitor patients with influenza for signs of abnormal behavior. If neuropsychiatric symptoms occur, evaluate the risks and benefits of continuing treatment for each patient.

Bacterial Infections

• Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications during the course of influenza. TAMIFLU has not been shown to prevent such complications.
• Limitations of Populations Studied

Efficacy of TAMIFLU in the treatment of influenza in patients with chronic cardiac disease and/or respiratory disease has not been established. No difference in the incidence of complications was observed between the treatment and placebo groups in this population. No information is available regarding treatment of influenza in patients with any medical condition sufficiently severe or unstable to be considered at imminent risk of requiring hospitalization.

• Efficacy of TAMIFLU for treatment or prophylaxis of influenza has not been established in immunocompromised patients.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Oseltamivir Clinical Trials Experience in the drug label.

Postmarketing Experience

• The following adverse reactions have been identified during postapproval use of TAMIFLU. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to TAMIFLU exposure.

Hypersensitivity reacttions

• Swelling of the face or tongue, allergy, anaphylactic/anaphylactoid reactions, hypothermia

Skin

Rash, dermatitis, urticaria, eczema, toxic epidermal necrolysis, Stevens-Johnson Syndrome, erythema multiforme. Hepatitis, liver function tests abnormal.

Others

• Arrhythmia
• Gastrointestinal bleeding, hemorrhagic colitis
• Seizure
• Aggravation of diabetes
• Abnormal behavior, delirium, including symptoms such as hallucinations, agitation, anxiety, altered level of consciousness, confusion, nightmares, delusions

Drug Interactions

Influenza Vaccines

• The concurrent use of TAMIFLU with live attenuated influenza vaccine (LAIV) intranasal has not been evaluated. However, because of the potential for interference between these products, LAIV should not be administered within 2 weeks before or 48 hours after administration of TAMIFLU, unless medically indicated. The concern about possible interference arises from the potential for antiviral drugs to inhibit replication of live vaccine virus. Trivalent inactivated influenza vaccine can be administered at any time relative to use of TAMIFLU.
• Overall Drug Interaction Profile for Oseltamivir

• Information derived from pharmacology and pharmacokinetic studies of oseltamivir suggests that clinically significant drug interactions are unlikely.
• Oseltamivir is extensively converted to oseltamivir carboxylate by esterases, located predominantly in the liver. Drug interactions involving competition for esterases have not been extensively reported in literature. Low protein binding of oseltamivir and oseltamivir carboxylate suggests that the probability of drug displacement interactions is low.
• In vitro studies demonstrate that neither oseltamivir nor oseltamivir carboxylate is a good substrate for P450 mixed-function oxidases or for glucuronyl transferases.
• Clinically important drug interactions involving competition for renal tubular secretion are unlikely due to the known safety margin for most of these drugs, the elimination characteristics of oseltamivir carboxylate (glomerular filtration and anionic tubular secretion) and the excretion capacity of these pathways. Coadministration of probenecid results in an approximate two-fold increase in exposure to oseltamivir carboxylate due to a decrease in active anionic tubular secretion in the kidney. However, due to the safety margin of oseltamivir carboxylate, no dose adjustments are required when coadministering with probenecid.
• No pharmacokinetic interactions have been observed when coadministering oseltamivir with amoxicillin, acetaminophen, aspirin, cimetidine, antacids (magnesium and aluminum hydroxides and calcium carbonates), or warfarin.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

• There are insufficient human data upon which to base an evaluation of risk of TAMIFLU to the pregnant woman or developing fetus.
• Studies for effects on embryo-fetal development were conducted in rats (50, 250, and 1500 mg/kg/day) and rabbits (50, 150, and 500 mg/kg/day) by the oral route. Relative exposures at these doses were, respectively, 2, 13, and 100 times human exposure in the rat and 4, 8, and 50 times human exposure in the rabbit.
• Pharmacokinetic studies indicated that fetal exposure was seen in both species. In the rat study, minimal maternal toxicity was reported in the 1500 mg/kg/day group. In the rabbit study, slight and marked maternal toxicities were observed, respectively, in the 150 and 500 mg/kg/day groups. There was a dose-dependent increase in the incidence rates of a variety of minor skeletal abnormalities and variants in the exposed offspring in these studies. However, the individual incidence rate of each skeletal abnormality or variant remained within the background rates of occurrence in the species studied.
• Because animal reproductive studies may not be predictive of human response and there are no adequate and well-controlled studies in pregnant women, TAMIFLU should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Oseltamivir in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Oseltamivir during labor and delivery.

Nursing Mothers

• In lactating rats, oseltamivir and oseltamivir carboxylate are excreted in the milk. It is not known whether oseltamivir or oseltamivir carboxylate is excreted in human milk. TAMIFLU should, therefore, be used only if the potential benefit for the lactating mother justifies the potential risk to the breast-fed infant.

Pediatric Use

There is no FDA guidance on the use of Oseltamivir in pediatric settings.

Geriatic Use

• Of the total number of subjects in clinical studies of TAMIFLU for the treatment of influenza, 19% were 65 and over, while 7% were 75 and over. Of the total number of patients in clinical studies of TAMIFLU for the prophylaxis of influenza, 25% were 65 and over, while 18% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects.
• The safety of TAMIFLU in geriatric subjects has been established in clinical studies that enrolled 741 subjects (374 received placebo and 362 received TAMIFLU). Some seasonal variability was noted in the clinical efficacy outcomes.
• Safety and efficacy have been demonstrated in elderly residents of nursing homes who took TAMIFLU for up to 42 days for the prevention of influenza. Many of these individuals had cardiac and/or respiratory disease, and most had received vaccine that season.

Gender

There is no FDA guidance on the use of Oseltamivir with respect to specific gender populations.

Race

There is no FDA guidance on the use of Oseltamivir with respect to specific racial populations.

Renal Impairment

• Dose adjustment is recommended for patients with a serum creatinine clearance between 10 and 30 mL/min. No recommended dosing regimens are available for patients with end-stage renal disease undergoing routine hemodialysis or continuous peritoneal dialysis treatment.

Hepatic Impairment

• No dosage adjustment is required in patients with mild to moderate hepatic impairment. The safety and pharmacokinetics in patients with severe hepatic impairment have not been evaluated.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Oseltamivir in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Oseltamivir in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Oseltamivir Administration in the drug label.

Monitoring

There is limited information regarding Oseltamivir Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Oseltamivir and IV administrations.

Overdosage

• At present, there has been no experience with overdose. Single doses of up to 1000 mg of TAMIFLU have been associated with nausea and/or vomiting.

Pharmacology

Oseltamivir
Systematic (IUPAC) name
ethyl (3R,4R,5S)-5-amino-4-acetamido-3-(pentan-3-yloxy)-cyclohex-1-ene-1-carboxylate
Identifiers
CAS number	196618-13-0
ATC code	J05AH02
PubChem	65028
DrugBank	DB00198
Chemical data
Formula	Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox
Mol. mass	312.4 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	>80%
Protein binding	42% (parent drug), 3% (active metabolite)
Metabolism	Hepatic, to oseltamivir carboxylate
Half life	1-3 hours, 6-10 hours (active metabolite)
Excretion	Urine (>90% as oseltamivir carboxylate), faeces
Therapeutic considerations
Licence data	US
Pregnancy cat.	B1(AU) C(US)
Legal status	Prescription Only (S4)(AU) POM(UK) [[Prescription drug|Template:Unicode-only]](US)
Routes	oral

Mechanism of Action

Oseltamivir is an antiviral drug

Structure

• TAMIFLU (oseltamivir phosphate) is available as capsules containing 30 mg, 45 mg, or 75 mg oseltamivir for oral use, in the form of oseltamivir phosphate, and as a powder for oral suspension, which when constituted with water as directed contains 6 mg/mL oseltamivir base.
• In addition to the active ingredient, each capsule contains pregelatinized starch, talc, povidone K30, croscarmellose sodium, and sodium stearyl fumarate.
• The 30 mg capsule shell contains gelatin, titanium dioxide, yellow iron oxide, and red iron oxide. The 45 mg capsule shell contains gelatin, titanium dioxide, and black iron oxide. The 75 mg capsule shell contains gelatin, titanium dioxide, yellow iron oxide, black iron oxide, and red iron oxide.
• Each capsule is printed with blue ink, which includes FD&C Blue No. 2 as the colorant. In addition to the active ingredient, the powder for oral suspension contains sorbitol, monosodium citrate, xanthan gum, titanium dioxide, tutti-frutti flavoring, sodium benzoate, and saccharin sodium.
• Oseltamivir phosphate is a white crystalline solid with the chemical name (3R,4R,5S)-4-acetylamino-5-amino-3(1-ethylpropoxy)-1-cyclohexene-1-carboxylic acid, ethyl ester, phosphate. The chemical formula is C16H28N2O4 (free base). The molecular weight is 312.4 for oseltamivir free base and 410.4 for oseltamivir phosphate salt

Pharmacodynamics

There is limited information regarding Oseltamivir Pharmacodynamics in the drug label.

Pharmacokinetics

Absorption and Bioavailability

• Oseltamivir is readily absorbed from the gastrointestinal tract after oral administration of oseltamivir phosphate and is extensively converted predominantly by hepatic esterases to oseltamivir carboxylate.
• At least 75% of an oral dose reaches the systemic circulation as oseltamivir carboxylate. Exposure to oseltamivir is less than 5% of the total exposure after oral dosing.
• Plasma concentrations of oseltamivir carboxylate are proportional to doses up to 500 mg given twice daily.
• Coadministration with food has no significant effect on the peak plasma concentration (551 ng/mL under fasted conditions and 441 ng/mL under fed conditions) and the area under the plasma concentration time curve (6218 ng∙h/mL under fasted conditions and 6069 ng∙h/mL under fed conditions) of oseltamivir carboxylate.

Distribution

• The volume of distribution (Vss) of oseltamivir carboxylate, following intravenous administration in 24 subjects, ranged between 23 and 26 liters.
• The binding of oseltamivir carboxylate to human plasma protein is low (3%).
• The binding of oseltamivir to human plasma protein is 42%, which is insufficient to cause significant displacement-based drug interactions.

Metabolism

• Oseltamivir is extensively converted to oseltamivir carboxylate by esterases located predominantly in the liver. Neither oseltamivir nor oseltamivir carboxylate is a substrate for, or inhibitor of, cytochrome P450 isoforms.

Elimination

• Absorbed oseltamivir is primarily (>90%) eliminated by conversion to oseltamivir carboxylate. Plasma concentrations of oseltamivir declined with a half-life of 1 to 3 hours in most subjects after oral administration.
• Oseltamivir carboxylate is not further metabolized and is eliminated in the urine. Plasma concentrations of oseltamivir carboxylate declined with a half-life of 6 to 10 hours in most subjects after oral administration.
• Oseltamivir carboxylate is eliminated entirely (>99%) by renal excretion. Renal clearance (18.8 L/h) exceeds glomerular filtration rate (7.5 L/h), indicating that tubular secretion occurs in addition to glomerular filtration. Less than 20% of an oral radiolabeled dose is eliminated in feces.

Special Populations

• Renal Impairment

Administration of 100 mg of oseltamivir phosphate twice daily for 5 days to patients with various degrees of renal impairment showed that exposure to oseltamivir carboxylate is inversely proportional to declining renal function.

Hepatic Impairment

• In clinical studies oseltamivir carboxylate exposure was not altered in patients with mild or moderate hepatic impairment.

Pediatric Patients

• The pharmacokinetics of oseltamivir and oseltamivir carboxylate have been evaluated in a single-dose pharmacokinetic study in pediatric patients aged 5 to 16 years (n=18) and in a small number of pediatric patients aged 3 to 12 years (n=5) enrolled in a clinical trial.
• Younger pediatric patients cleared both the prodrug and the active metabolite faster than adult patients resulting in a lower exposure for a given mg/kg dose. For oseltamivir carboxylate, apparent total clearance decreases linearly with increasing age (up to 12 years).
• The pharmacokinetics of oseltamivir in pediatric patients over 12 years of age are similar to those in adult patients.

Geriatric Patients

• Exposure to oseltamivir carboxylate at steady-state was 25% to 35% higher in geriatric patients (age range 65 to 78 years) compared to young adults given comparable doses of oseltamivir. Half-lives observed in the geriatric patients were similar to those seen in young adults.
• Based on drug exposure and tolerability, dose adjustments are not required for geriatric patients for either treatment or prophylaxis.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

• In 2-year carcinogenicity studies in mice and rats given daily oral doses of the prodrug oseltamivir phosphate up to 400 mg/kg and 500 mg/kg, respectively, the prodrug and the active form oseltamivir carboxylate induced no statistically significant increases in tumors over controls.
• The mean maximum daily exposures to the prodrug in mice and rats were approximately 130- and 320-fold, respectively, greater than those in humans at the proposed clinical dose based on AUC comparisons.
• The respective safety margins of the exposures to the active oseltamivir carboxylate were 15- and 50-fold.
• Oseltamivir was found to be non-mutagenic in the Ames test and the human lymphocyte chromosome assay with and without enzymatic activation and negative in the mouse micronucleus test.
• It was found to be positive in a Syrian Hamster Embryo (SHE) cell transformation test. Oseltamivir carboxylate was non-mutagenic in the Ames test and the L5178Y mouse lymphoma assay with and without enzymatic activation and negative in the SHE cell transformation test.
• In a fertility and early embryonic development study in rats, doses of oseltamivir at 50, 250, and 1500 mg/kg/day were administered to females for 2 weeks before mating, during mating and until day 6 of pregnancy. Males were dosed for 4 weeks before mating, during mating, and for 2 weeks after mating. * There were no effects on fertility, mating performance or early embryonic development at any dose level. The highest dose was approximately 100 times the human systemic exposure (AUC0-24h) of oseltamivir carboxylate.
• Animal Toxicology and/or Pharmacology

Single, oral administration of ≥657 mg/kg oseltamivir resulted in toxicity, including death, in juvenile 7 day old rats, but had no effect on adult rats. * No toxicity was observed after repeated administration of up to 500 mg/kg oseltamivir to developing juvenile rats 7 to 21 days old. This 500 mg/kg dose was approximately 280 and 14 times the human systemic exposure (AUC0-24h) of oseltamivir and oseltamivir carboxylate, respectively.

• Clinical relevance of the juvenile rat study finding for young infants is unknown.

Clinical Studies

Treatment of Influenza

Adult Subjects

• Two placebo-controlled double-blind clinical trials were conducted: one in the U.S. and one outside the U.S. Subjects were eligible for these trials if they had fever >100ºF, accompanied by at least one respiratory symptom (cough, nasal symptoms, or sore throat) and at least one systemic symptom (myalgia, chills/sweats, malaise, fatigue, or headache) and influenza virus was known to be circulating in the community.
• In addition, all subjects enrolled in the trials were allowed to take fever-reducing medications.
• Of 1355 subjects enrolled in these two trials, 849 (63%) subjects were influenza-infected (age range 18 to 65 years; median age 34 years; 52% male; 90% Caucasian; 31% smokers). Of the 849 influenza-infected subjects, 95% were infected with influenza A, 3% with influenza B, and 2% with influenza of unknown type.
• TAMIFLU was started within 40 hours of onset of symptoms. Subjects participating in the trials were required to self-assess the influenza-associated symptoms as "none," "mild," "moderate," or "severe."
• Time to improvement was calculated from the time of treatment initiation to the time when all symptoms (nasal congestion, sore throat, cough, aches, fatigue, headaches, and chills/sweats) were assessed as "none" or "mild."
• In both studies, at the recommended dose of TAMIFLU 75 mg twice daily for 5 days, there was a 1.3 day reduction in the median time to improvement in influenza-infected subjects receiving TAMIFLU compared to subjects receiving placebo.
• Subgroup analyses of these studies by gender showed no differences in the treatment effect of TAMIFLU in men and women.
• In the treatment of influenza, no increased efficacy was demonstrated in subjects receiving treatment of 150 mg TAMIFLU twice daily for 5 days.

Geriatric Subjects

• Three double-blind placebo-controlled treatment trials were conducted in subjects ≥65 years of age in three consecutive seasons.
• The enrollment criteria were similar to that of adult trials with the exception of fever being defined as >97.5°F. Of 741 subjects enrolled, 476 (65%) subjects were influenza-infected.
• Of the 476 influenza-infected subjects, 95% were infected with influenza type A and 5% with influenza type B.
• In the pooled analysis, at the recommended dose of TAMIFLU 75 mg twice daily for 5 days, there was a 1-day reduction in the median time to improvement in influenza-infected subjects receiving TAMIFLU compared to those receiving placebo (p=NS). However, the magnitude of treatment effect varied between studies.

Pediatric Subjects

• One double-blind placebo-controlled treatment trial was conducted in pediatric subjects aged 1 to 12 years (median age 5 years), who had fever (>100°F) plus one respiratory symptom (cough or coryza) when influenza virus was known to be circulating in the community.
• Of 698 subjects enrolled in this trial, 452 (65%) were influenza-infected (50% male; 68% Caucasian).
• Of the 452 influenza-infected subjects, 67% were infected with influenza A and 33% with influenza B.
• The primary endpoint in this study was the time to freedom from illness, a composite endpoint that required 4 individual conditions to be met.
• These were: alleviation of cough, alleviation of coryza, resolution of fever, and parental opinion of a return to normal health and activity. TAMIFLU treatment of 2 mg/kg twice daily, started within 48 hours of onset of symptoms, significantly reduced the total composite time to freedom from illness by 1.5 days compared to placebo.
• Subgroup analyses of this study by gender showed no differences in the treatment effect of TAMIFLU in male and female pediatric subjects.

Prophylaxis of Influenza

Adult Subjects

• The efficacy of TAMIFLU in preventing naturally occurring influenza illness has been demonstrated in three seasonal prophylaxis studies and a postexposure prophylaxis study in households.
• The primary efficacy parameter for all these studies was the incidence of laboratory-confirmed clinical influenza.
• Laboratory-confirmed clinical influenza was defined as oral temperature ≥99.0°F/37.2°C plus at least one respiratory symptom (cough, sore throat, nasal congestion) and at least one constitutional symptom (aches and pain, fatigue, headache, chills/sweats), all recorded within 24 hours, plus either a positive virus isolation or a four-fold increase in virus antibody titers from baseline.
• In a pooled analysis of two seasonal prophylaxis studies in healthy unvaccinated adults (aged 13 to 65 years), TAMIFLU 75 mg once daily taken for 42 days during a community outbreak reduced the incidence of laboratory-confirmed clinical influenza from 5% (25/519) for the placebo group to 1% (6/520) for the TAMIFLU group.
• In a seasonal prophylaxis study in elderly residents of skilled nursing homes, TAMIFLU 75 mg once daily taken for 42 days reduced the incidence of laboratory-confirmed clinical influenza from 4% (12/272) for the placebo group to <1% (1/276) for the TAMIFLU group. About 80% of this elderly population were vaccinated, 14% of subjects had chronic airway obstructive disorders, and 43% had cardiac disorders.
• In a study of postexposure prophylaxis in household contacts (aged ≥13 years) of an index case, TAMIFLU 75 mg once daily administered within 2 days of onset of symptoms in the index case and continued for 7 days reduced the incidence of laboratory-confirmed clinical influenza from 12% (24/200) in the placebo group to 1% (2/205) for the TAMIFLU group.
• Index cases did not receive TAMIFLU in the study.

Pediatric Subjects

• The efficacy of TAMIFLU in preventing naturally occurring influenza illness has been demonstrated in a randomized, open-label, postexposure prophylaxis study in households that included children aged 1 to 12 years, both as index cases and as family contacts.
• All index cases in this study received treatment. The primary efficacy parameter for this study was the incidence of laboratory-confirmed clinical influenza in the household.
• Laboratory-confirmed clinical influenza was defined as oral temperature ≥100°F/37.8°C plus cough and/or coryza recorded within 48 hours, plus either a positive virus isolation or a four-fold or greater increase in virus antibody titers from baseline or at illness visits.
• Among household contacts 1 to 12 years of age not already shedding virus at baseline, TAMIFLU for oral suspension 30 mg to 60 mg taken once daily for 10 days reduced the incidence of laboratory-confirmed clinical influenza from 17% (18/106) in the group not receiving prophylaxis to 3% (3/95) in the group receiving prophylaxis.

Immunocompromised Subjects

• A double-blind, placebo-controlled study was conducted for seasonal prophylaxis of influenza in 475 immunocompromised subjects (including 18 pediatric subjects 1 to 12 years of age) who had received solid organ (n=388; liver, kidney, liver and kidney) or hematopoietic stem cell transplants (n=87).
• Median time since transplant for solid organ transplant recipients was 1105 days for the placebo group and 1379 days for the oseltamivir group.
• Median time since transplant for hematopoietic stem cell transplant recipients was 424 days for the placebo group and 367 days for the oseltamivir group.
• Approximately 40% of subjects received influenza vaccine prior to entering the study.
• The primary efficacy endpoint for this study was the incidence of confirmed, clinical influenza, defined as oral temperature >99.0°F/37.2°C plus cough and/or coryza, all recorded within 24 hours, plus either a positive virus culture or a four-fold increase in virus antibody titers from baseline.
• The incidence of confirmed clinical influenza was 3% (7/238) in the group not receiving TAMIFLU compared with 2% (5/237) in the group receiving TAMIFLU; this difference was not statistically significant. A secondary analysis was performed using the same clinical symptoms and RT-PCR for laboratory confirmation of influenza.
• Among subjects who were not already shedding virus at baseline, the incidence of RT-PCR-confirmed clinical influenza was 3% (7/231) in the group not receiving TAMIFLU and <1% (1/232) in the group receiving TAMIFLU.

How Supplied

TAMIFLU Capsules

• 75-mg capsules (75 mg free base equivalent of the phosphate salt): grey/light yellow hard gelatin capsules. "ROCHE" is printed in blue ink on the grey body and "75 mg" is printed in blue ink on the light yellow cap. Available in blister packages of 10 (NDC 42254-001-10).

Storage

Storage

• Store the capsules at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F).
• TAMIFLU for Oral Suspension
• Supplied as a white powder blend in a glass bottle. After constitution, the powder blend produces a white tutti-frutti–flavored oral suspension.
• After constitution with 55 mL of water, each bottle delivers a usable volume of 60 mL of oral suspension equivalent to 360 mg oseltamivir base (6 mg/mL).
• Each bottle is supplied with a bottle adapter and a 10 mL oral dispenser (NDC 0004-0820-09).

Storage

• Store dry powder at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F).
• Store constituted suspension under refrigeration for up to 17 days at 2° to 8°C (36° to 46°F). Do not freeze.
• Alternatively, store constituted suspension for up to 10 days at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F).

Images

Drug Images

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Patient Counseling Information

• Patients and/or caregivers should be advised of the risk of severe allergic reactions (including anaphylaxis) or serious skin reactions and should stop TAMIFLU and seek immediate medical attention if an allergic-like reaction occurs or is suspected.
• Patients and/or caregivers should be advised of the risk of neuropsychiatric events in patients with influenza and should contact their physician if they experience signs of abnormal behavior while receiving TAMIFLU. Their physician will determine if TAMIFLU treatment should be continued.
• Instruct patients to begin treatment with TAMIFLU as soon as possible from the first appearance of flu symptoms. Similarly, prevention should begin as soon as possible after exposure, at the recommendation of a physician.
• Instruct patients to take any missed doses as soon as they remember, except if it is near the next scheduled dose (within 2 hours), and then continue to take TAMIFLU at the usual times.
• TAMIFLU is not a substitute for a flu vaccination. Patients should continue receiving an annual flu vaccination according to guidelines on immunization practices.
• A bottle of TAMIFLU for oral suspension contains approximately 11 g sorbitol. One dose of 75 mg TAMIFLU for oral suspension delivers 2 g sorbitol. For patients with hereditary fructose intolerance, this is above the daily maximum limit of sorbitol and may cause dyspepsia and diarrhea.

Precautions with Alcohol

Alcohol-Oseltamivir interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• TAMIFLU

Look-Alike Drug Names

There is limited information regarding Oseltamivir Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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