These Highlights Do Not Include All The Information Needed To Use Oseltamivir Phosphate Capsules Safely And Effectively. See Full Prescribing Information For Oseltamivir Phosphate Capsules.

Adults and Adolescents (13 years of age and older)

The recommended oral dosage of oseltamivir phosphate capsules for treatment of influenza in adults and adolescents 13 years and older is 75 mg twice daily (one 75 mg capsule or 12.5 mL of oral suspension twice daily) for 5 days.

Storage

Store oseltamivir phosphate capsules at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted to 15°C and 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Preserve in well-closed containers as defined in USP.

Reports of overdoses with oseltamivir phosphate capsules have been received from clinical trials and during postmarketing experience. In the majority of cases reporting overdose, no adverse reactions were reported. Adverse reactions reported following overdose were similar in nature to those observed with therapeutic doses of oseltamivir phosphate capsules  [see Adverse Reactions (6)] .

Oseltamivir phosphate capsules, USP, influenza neuraminidase inhibitor (NAI), are available as:

• Capsules containing 30 mg, 45 mg, or 75 mg of oseltamivir for oral use, in the form of oseltamivir phosphate.

In addition to the active ingredient, croscarmellose sodium, povidone K29/32, pregelatinized starch, sodium stearyl fumarate and talc. The 30 mg capsule shell contains: black iron oxide, gelatin, potassium hydroxide and titanium dioxide. The 45 mg capsule shell contains: FD&C Blue#1 Aluminum Lake, gelatin, iron oxide yellow, and titanium dioxide. The 75 mg capsule shell contains: black iron oxide, brilliant blue FCF – FD&C Blue 1, gelatin, potassium hydroxide, quinoline yellow and titanium dioxide.

Oseltamivir phosphate is a white or almost white powder with the chemical name (3R,4R,5S)-4-acetylamino-5-amino-3(1-ethylpropoxy)-1-cyclohexene-1-carboxylic acid, ethyl ester, phosphate (1:1). The chemical formula is C ₁₆H ₂₈N ₂O ₄(free base). The molecular weight is 312.4 for oseltamivir free base and 410.4 for oseltamivir phosphate salt. The structural formula is as follows:

Oseltamivir phosphate capsules are 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 [see Warnings and Precautions (5.1)] .

The following serious adverse reactions are discussed below and elsewhere in the labeling:

• Serious skin and hypersensitivity reactions [see Warnings and Precautions (5.1)]
• Neuropsychiatric events [see Warnings and Precautions (5.2)]

Live attenuated influenza vaccine (LAIV), intranasal:

Avoid administration of LAIV within 2 weeks before or 48 hours after oseltamivir phosphate capsules use, unless medically indicated. ( 7)

Patients with renal impairment had higher blood levels of oseltamivir carboxylate compared to patients with normal renal function which may increase the risk of oseltamivir phosphate capsules -associated adverse reactions. Therefore, dosage adjustment is recommended for patients with a serum creatinine clearance between 10 and 60 mL/minute and for patients with end-stage renal disease (ESRD) undergoing routine hemodialysis or continuous peritoneal dialysis treatment [see Dosage and Administration (2.4)].  Oseltamivir phosphate capsules are not recommended for patients with ESRD not undergoing dialysis [see Indications and Usage (1.3) and Clinical Pharmacology (12.3)] .

• Oseltamivir phosphate capsules are 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.
• Influenza viruses change over time. Emergence of resistance substitutions could decrease drug effectiveness. Other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs. Prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use oseltamivir phosphate capsules  [see Microbiology (12.4)] .
• Oseltamivir phosphate capsules are not recommended for patients with end-stage renal disease not undergoing dialysis [see Dosage and Administration (2.4) and Use in Specific Populations (8.6)].

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 [see Clinical Pharmacology (12.3)] .

Oseltamivir phosphate capsules are influenza neuraminidase inhibitor (NAI) indicated for:

• Treatment of acute, uncomplicated influenza A and B in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours. ( 1.1)
• Prophylaxis of influenza A and B in patients 1 year and older. ( 1.2)

Limitations of Use:

• Not a substitute for annual influenza vaccination. ( 1.3)
• Consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use. ( 1.3)
• Not recommended for patients with end-stage renal disease not undergoing dialysis. ( 1.3)

Oseltamivir is an antiviral drug with activity against influenza virus [see Microbiology (12.4)].

Oseltamivir phosphate capsules are indicated for the treatment of acute, uncomplicated illness due to influenza A and B infection in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours.

• Serious skin/hypersensitivity reactions such as Stevens-Johnson Syndrome, toxic epidermal necrolysis and erythema multiforme: Discontinue oseltamivir phosphate capsules and initiate appropriate treatment if allergic-like reactions occur or are suspected. ( 5.1)
• Neuropsychiatric events: Patients with influenza, including those receiving oseltamivir phosphate capsules, particularly pediatric patients, may be at an increased risk of confusion or abnormal behavior early in their illness. Monitor for signs of abnormal behavior. ( 5.2)

Treatment of influenza

• Adults and adolescents (13 years and older): 75 mg twice daily for 5 days ( 2.2)
• Pediatric patients 1 to 12 years of age: Based on weight twice daily for 5 days ( 2.2)
• Pediatric patients 2 weeks to less than 1 year of age: 3mg/kg twice daily for 5 days ( 2.2)
• Renally impaired adult patients (creatinine clearance >30-60 mL/min): Reduce to 30 mg twice daily for 5 days ( 2.4)
• Renally impaired adult patients (creatinine clearance >10-30 mL/min): Reduce to 30 mg once daily for 5 days ( 2.4)
• ESRD patients on hemodialysis: Reduce to 30 mg immediately and then 30 mg after every hemodialysis cycle. Treatment duration not to exceed 5 days ( 2.4)
• ESRD patients on CAPD: Reduce to a single 30 mg dose immediately ( 2.4)

Prophylaxis of influenza

• Adults and adolescents (13 years and older): 75 mg once daily for at least 10 days ( 2.3)
  • Community outbreak: 75 mg once daily for up to 6 weeks ( 2.3)
• Pediatric patients 1 to 12 years of age: Based on weight once daily for 10 days ( 2.3)
  • Community outbreak: Based on weight once daily for up to 6 weeks ( 2.3)
• Renally impaired adult patients (creatinine clearance >30-60 mL/min): Reduce to 30 mg once daily ( 2.4)
• Renally impaired adult patients (creatinine clearance >10-30 mL/min): Reduce to 30 mg once every other day ( 2.4)
• ESRD patients on hemodialysis: Reduce to 30 mg immediately and then 30 mg after alternate hemodialysis cycles for the recommended duration of prophylaxis ( 2.4)
• ESRD patients on CAPD: Reduce to 30 mg immediately and then 30 mg once weekly for the recommended duration of prophylaxis ( 2.4)

There have been postmarketing reports of delirium and abnormal behavior leading to injury, and in some cases resulting in fatal outcomes, in patients with influenza who were receiving oseltamivir phosphate capsules  [see Adverse Reactions (6.2)] . Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made but they appear to be uncommon based on oseltamivir phosphate capsules usage data. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of oseltamivir phosphate capsules to these events has not been established. 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. Closely monitor oseltamivir phosphate capsules -treated patients with influenza for signs of abnormal behavior. If neuropsychiatric symptoms occur, evaluate the risks and benefits of continuing oseltamivir phosphate capsules for each patient.

Oseltamivir phosphate capsules are indicated for the prophylaxis of influenza A and B in patients 1 year and older.

Oseltamivir Phosphate Capsules, USP:

• 30-mg (30 mg free base equivalent of the phosphate salt): capsule cap and body are opaque white, cap imprinted “S5” with black ink, body without any print; the contents is white or almost white.
• 45-mg (45 mg free base equivalent of the phosphate salt): capsule cap is buff and printed “S4” with blue ink, body is white and without any imprint; the contents is white or almost white.
• 75-mg (75 mg free base equivalent of the phosphate salt): capsule cap is light green and printed “S2” with black ink, body is white and without any imprint; the contents is white or almost white.

The following adverse reactions have been identified during post-approval use of oseltamivir phosphate capsules. 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 oseltamivir phosphate exposure.

General disorders and administration site conditions: Swelling of the face or tongue, allergy, anaphylactic/anaphylactoid reactions, hypothermia

Skin and subcutaneous tissue disorders: Rash, dermatitis, urticaria, eczema, toxic epidermal necrolysis, Stevens-Johnson Syndrome, erythema multiforme [see Warnings and Precautions (5.1)]

Gastrointestinal Disorders: Gastrointestinal bleeding, hemorrhagic colitis

Cardiac Disorders: Arrhythmia

Hepatobiliary Disorders: Hepatitis, abnormal liver function tests

Nervous System Disorders: Seizure

Metabolism and Nutrition Disorders: Aggravation of diabetes

Psychiatric Disorders: Abnormal behavior, delirium, including symptoms such as hallucinations, agitation, anxiety, altered level of consciousness, confusion, nightmares, delusions [see Warnings and Precautions (5.2)]

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Efficacy of oseltamivir phosphate capsules for the treatment or prophylaxis of influenza has not been established in immunocompromised patients [see Clinical Studies (14.2)] . Safety of oseltamivir phosphate capsules has been demonstrated for up to 12 weeks for prophylaxis of influenza in immunocompromised patients [see Adverse Reactions (6.1)].

There is no evidence for efficacy of oseltamivir phosphate capsules in any illness caused by pathogens other than influenza viruses. Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications during the course of influenza. Oseltamivir phosphate capsules have not been shown to prevent such complications. Prescribers should be alert to the potential for secondary bacterial infections and treat them as appropriate.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Administer oseltamivir phosphate capsules for the treatment of influenza in patients 2 weeks of age or older [see Dosage and Administration (2.2)] or for prophylaxis of influenza in patients 1 year and older [see Dosage and Administration (2.3)] .

The capsules may be taken with or without food; however, tolerability may be enhanced if oseltamivir phosphate capsules are taken with food.

Adjust the oseltamivir phosphate capsules dosage in patients with moderate or severe renal impairment [see Dosage and Administration (2.4)].

For patients who cannot swallow capsules, oseltamivir phosphate for oral suspension is the preferred formulation. When oseltamivir phosphate for oral suspension is not available from wholesaler or the manufacturer, oseltamivir phosphate capsules may be opened and mixed with sweetened liquids such as regular or sugar-free chocolate syrup, corn syrup, caramel topping, or light brown sugar (dissolved in water). During emergency situations and when neither the oral suspension or the age-appropriate strengths of oseltamivir phosphate capsules to mix with sweetened liquids are available, then a pharmacist may prepare an emergency supply of oral suspension from oseltamivir phosphate 75 mg capsules [see Dosage and Administration (2.6)].

Cases of anaphylaxis and serious skin reactions including toxic epidermal necrolysis, Stevens-Johnson Syndrome, and erythema multiforme have been reported in postmarketing experience with oseltamivir phosphate capsules. Stop oseltamivir phosphate capsules and institute appropriate treatment if an allergic-like reaction occurs or is suspected. The use of oseltamivir phosphate capsules is contraindicated in patients with known serious hypersensitivity to oseltamivir phosphate capsules  [see Contraindications (4) and Adverse Reactions (6.2)] .

Efficacy of oseltamivir phosphate capsules in the treatment of influenza in patients with chronic cardiac disease and/or respiratory disease was evaluated in one randomized, placebo-controlled clinical trial. Efficacy in this population, as measured by time to alleviation of all symptoms, was not established, but no new safety signals were identified [ see Clinical Studies (14.1) ].

No clinical trial data are available regarding treatment of influenza in patients with any medical condition sufficiently severe or unstable to be considered at imminent risk of requiring hospitalization.

Table 2 displays the dosage recommendations for the treatment and prophylaxis of influenza in adults with various stages of renal impairment (estimated creatinine clearance of less than or equal to 90 mL per minute). Dosage modifications are recommended in adults with an estimated creatinine clearance less than or equal to 60 mL per minute [see Use in Specific Population (8.6) and Clinical Pharmacology (12.3)] .

Initiate treatment with oseltamivir phosphate capsules within 48 hours of influenza symptom onset.

Initiate post-exposure prophylaxis with oseltamivir phosphate capsules within 48 hours following close contact with an infected individual. Initiate seasonal prophylaxis with oseltamivir phosphate capsules during a community outbreak.

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 recommended 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 in this study was approximately 115 times the human systemic exposure (AUC _0-24h) of oseltamivir carboxylate that occurs after administration of the maximum recommended human dose.

NDC 48972-7899-1

Oseltamivir Phosphate Capsules USP

30 mg

Each capsule contains oseltamivir phosphate equivalent to 30 mg



oseltamivir (free base).

Rx only

10 Capsules

Sunshine Lake Pharma Co., Ltd.

545391443

NDC 48972-7900-1

Oseltamivir Phosphate Capsules USP

45 mg

Each capsule contains oseltamivir phosphate equivalent to 45 mg



oseltamivir (free base).

Rx only

10 Capsules

Sunshine Lake Pharma Co., Ltd.

545391443

NDC 48972-7901-1

Oseltamivir Phosphate Capsules USP

75 mg

Each capsule contains oseltamivir phosphate equivalent to 75 mg



oseltamivir (free base).

Rx only

10 Capsules

Sunshine Lake Pharma Co., Ltd.

545391443

No dose adjustments are needed for either oseltamivir or the concomitant drug when coadministering oseltamivir with amoxicillin, acetaminophen, aspirin, cimetidine, antacids (magnesium and aluminum hydroxides and calcium carbonates), rimantadine, amantadine, or warfarin [see Clinical Pharmacology (12.3)] .

The following directions are provided for use only during emergency situations and when FDA-approved, commercially manufactured oseltamivir phosphate for oral suspension is not available from wholesalers or the manufacturer.

The following emergency preparation instructions will provide one patient with enough oseltamivir phosphate capsules for a 5-day course of treatment of influenza or a 10-day course of prophylaxis of influenza:

Adults and Adolescents (13 years of age and older)

The recommended oral dosage of oseltamivir phosphate capsules for treatment of influenza in adults and adolescents 13 years and older is 75 mg twice daily (one 75 mg capsule or 12.5 mL of oral suspension twice daily) for 5 days.

Storage

Store oseltamivir phosphate capsules at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted to 15°C and 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Preserve in well-closed containers as defined in USP.

Reports of overdoses with oseltamivir phosphate capsules have been received from clinical trials and during postmarketing experience. In the majority of cases reporting overdose, no adverse reactions were reported. Adverse reactions reported following overdose were similar in nature to those observed with therapeutic doses of oseltamivir phosphate capsules  [see Adverse Reactions (6)] .

Oseltamivir phosphate capsules, USP, influenza neuraminidase inhibitor (NAI), are available as:

• Capsules containing 30 mg, 45 mg, or 75 mg of oseltamivir for oral use, in the form of oseltamivir phosphate.

In addition to the active ingredient, croscarmellose sodium, povidone K29/32, pregelatinized starch, sodium stearyl fumarate and talc. The 30 mg capsule shell contains: black iron oxide, gelatin, potassium hydroxide and titanium dioxide. The 45 mg capsule shell contains: FD&C Blue#1 Aluminum Lake, gelatin, iron oxide yellow, and titanium dioxide. The 75 mg capsule shell contains: black iron oxide, brilliant blue FCF – FD&C Blue 1, gelatin, potassium hydroxide, quinoline yellow and titanium dioxide.

Oseltamivir phosphate is a white or almost white powder with the chemical name (3R,4R,5S)-4-acetylamino-5-amino-3(1-ethylpropoxy)-1-cyclohexene-1-carboxylic acid, ethyl ester, phosphate (1:1). The chemical formula is C ₁₆H ₂₈N ₂O ₄(free base). The molecular weight is 312.4 for oseltamivir free base and 410.4 for oseltamivir phosphate salt. The structural formula is as follows:

Oseltamivir phosphate capsules are 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 [see Warnings and Precautions (5.1)] .

The following serious adverse reactions are discussed below and elsewhere in the labeling:

• Serious skin and hypersensitivity reactions [see Warnings and Precautions (5.1)]
• Neuropsychiatric events [see Warnings and Precautions (5.2)]

Live attenuated influenza vaccine (LAIV), intranasal:

Avoid administration of LAIV within 2 weeks before or 48 hours after oseltamivir phosphate capsules use, unless medically indicated. ( 7)

Patients with renal impairment had higher blood levels of oseltamivir carboxylate compared to patients with normal renal function which may increase the risk of oseltamivir phosphate capsules -associated adverse reactions. Therefore, dosage adjustment is recommended for patients with a serum creatinine clearance between 10 and 60 mL/minute and for patients with end-stage renal disease (ESRD) undergoing routine hemodialysis or continuous peritoneal dialysis treatment [see Dosage and Administration (2.4)].  Oseltamivir phosphate capsules are not recommended for patients with ESRD not undergoing dialysis [see Indications and Usage (1.3) and Clinical Pharmacology (12.3)] .

• Oseltamivir phosphate capsules are 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.
• Influenza viruses change over time. Emergence of resistance substitutions could decrease drug effectiveness. Other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs. Prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use oseltamivir phosphate capsules  [see Microbiology (12.4)] .
• Oseltamivir phosphate capsules are not recommended for patients with end-stage renal disease not undergoing dialysis [see Dosage and Administration (2.4) and Use in Specific Populations (8.6)].

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 [see Clinical Pharmacology (12.3)] .

Oseltamivir phosphate capsules are influenza neuraminidase inhibitor (NAI) indicated for:

• Treatment of acute, uncomplicated influenza A and B in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours. ( 1.1)
• Prophylaxis of influenza A and B in patients 1 year and older. ( 1.2)

Limitations of Use:

• Not a substitute for annual influenza vaccination. ( 1.3)
• Consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use. ( 1.3)
• Not recommended for patients with end-stage renal disease not undergoing dialysis. ( 1.3)

Oseltamivir is an antiviral drug with activity against influenza virus [see Microbiology (12.4)].

Oseltamivir phosphate capsules are indicated for the treatment of acute, uncomplicated illness due to influenza A and B infection in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours.

• Serious skin/hypersensitivity reactions such as Stevens-Johnson Syndrome, toxic epidermal necrolysis and erythema multiforme: Discontinue oseltamivir phosphate capsules and initiate appropriate treatment if allergic-like reactions occur or are suspected. ( 5.1)
• Neuropsychiatric events: Patients with influenza, including those receiving oseltamivir phosphate capsules, particularly pediatric patients, may be at an increased risk of confusion or abnormal behavior early in their illness. Monitor for signs of abnormal behavior. ( 5.2)

Treatment of influenza

• Adults and adolescents (13 years and older): 75 mg twice daily for 5 days ( 2.2)
• Pediatric patients 1 to 12 years of age: Based on weight twice daily for 5 days ( 2.2)
• Pediatric patients 2 weeks to less than 1 year of age: 3mg/kg twice daily for 5 days ( 2.2)
• Renally impaired adult patients (creatinine clearance >30-60 mL/min): Reduce to 30 mg twice daily for 5 days ( 2.4)
• Renally impaired adult patients (creatinine clearance >10-30 mL/min): Reduce to 30 mg once daily for 5 days ( 2.4)
• ESRD patients on hemodialysis: Reduce to 30 mg immediately and then 30 mg after every hemodialysis cycle. Treatment duration not to exceed 5 days ( 2.4)
• ESRD patients on CAPD: Reduce to a single 30 mg dose immediately ( 2.4)

Prophylaxis of influenza

• Adults and adolescents (13 years and older): 75 mg once daily for at least 10 days ( 2.3)
  • Community outbreak: 75 mg once daily for up to 6 weeks ( 2.3)
• Pediatric patients 1 to 12 years of age: Based on weight once daily for 10 days ( 2.3)
  • Community outbreak: Based on weight once daily for up to 6 weeks ( 2.3)
• Renally impaired adult patients (creatinine clearance >30-60 mL/min): Reduce to 30 mg once daily ( 2.4)
• Renally impaired adult patients (creatinine clearance >10-30 mL/min): Reduce to 30 mg once every other day ( 2.4)
• ESRD patients on hemodialysis: Reduce to 30 mg immediately and then 30 mg after alternate hemodialysis cycles for the recommended duration of prophylaxis ( 2.4)
• ESRD patients on CAPD: Reduce to 30 mg immediately and then 30 mg once weekly for the recommended duration of prophylaxis ( 2.4)

There have been postmarketing reports of delirium and abnormal behavior leading to injury, and in some cases resulting in fatal outcomes, in patients with influenza who were receiving oseltamivir phosphate capsules  [see Adverse Reactions (6.2)] . Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made but they appear to be uncommon based on oseltamivir phosphate capsules usage data. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of oseltamivir phosphate capsules to these events has not been established. 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. Closely monitor oseltamivir phosphate capsules -treated patients with influenza for signs of abnormal behavior. If neuropsychiatric symptoms occur, evaluate the risks and benefits of continuing oseltamivir phosphate capsules for each patient.

Oseltamivir phosphate capsules are indicated for the prophylaxis of influenza A and B in patients 1 year and older.

Oseltamivir Phosphate Capsules, USP:

• 30-mg (30 mg free base equivalent of the phosphate salt): capsule cap and body are opaque white, cap imprinted “S5” with black ink, body without any print; the contents is white or almost white.
• 45-mg (45 mg free base equivalent of the phosphate salt): capsule cap is buff and printed “S4” with blue ink, body is white and without any imprint; the contents is white or almost white.
• 75-mg (75 mg free base equivalent of the phosphate salt): capsule cap is light green and printed “S2” with black ink, body is white and without any imprint; the contents is white or almost white.

The following adverse reactions have been identified during post-approval use of oseltamivir phosphate capsules. 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 oseltamivir phosphate exposure.

General disorders and administration site conditions: Swelling of the face or tongue, allergy, anaphylactic/anaphylactoid reactions, hypothermia

Skin and subcutaneous tissue disorders: Rash, dermatitis, urticaria, eczema, toxic epidermal necrolysis, Stevens-Johnson Syndrome, erythema multiforme [see Warnings and Precautions (5.1)]

Gastrointestinal Disorders: Gastrointestinal bleeding, hemorrhagic colitis

Cardiac Disorders: Arrhythmia

Hepatobiliary Disorders: Hepatitis, abnormal liver function tests

Nervous System Disorders: Seizure

Metabolism and Nutrition Disorders: Aggravation of diabetes

Psychiatric Disorders: Abnormal behavior, delirium, including symptoms such as hallucinations, agitation, anxiety, altered level of consciousness, confusion, nightmares, delusions [see Warnings and Precautions (5.2)]

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Efficacy of oseltamivir phosphate capsules for the treatment or prophylaxis of influenza has not been established in immunocompromised patients [see Clinical Studies (14.2)] . Safety of oseltamivir phosphate capsules has been demonstrated for up to 12 weeks for prophylaxis of influenza in immunocompromised patients [see Adverse Reactions (6.1)].

There is no evidence for efficacy of oseltamivir phosphate capsules in any illness caused by pathogens other than influenza viruses. Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications during the course of influenza. Oseltamivir phosphate capsules have not been shown to prevent such complications. Prescribers should be alert to the potential for secondary bacterial infections and treat them as appropriate.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Administer oseltamivir phosphate capsules for the treatment of influenza in patients 2 weeks of age or older [see Dosage and Administration (2.2)] or for prophylaxis of influenza in patients 1 year and older [see Dosage and Administration (2.3)] .

The capsules may be taken with or without food; however, tolerability may be enhanced if oseltamivir phosphate capsules are taken with food.

Adjust the oseltamivir phosphate capsules dosage in patients with moderate or severe renal impairment [see Dosage and Administration (2.4)].

For patients who cannot swallow capsules, oseltamivir phosphate for oral suspension is the preferred formulation. When oseltamivir phosphate for oral suspension is not available from wholesaler or the manufacturer, oseltamivir phosphate capsules may be opened and mixed with sweetened liquids such as regular or sugar-free chocolate syrup, corn syrup, caramel topping, or light brown sugar (dissolved in water). During emergency situations and when neither the oral suspension or the age-appropriate strengths of oseltamivir phosphate capsules to mix with sweetened liquids are available, then a pharmacist may prepare an emergency supply of oral suspension from oseltamivir phosphate 75 mg capsules [see Dosage and Administration (2.6)].

Cases of anaphylaxis and serious skin reactions including toxic epidermal necrolysis, Stevens-Johnson Syndrome, and erythema multiforme have been reported in postmarketing experience with oseltamivir phosphate capsules. Stop oseltamivir phosphate capsules and institute appropriate treatment if an allergic-like reaction occurs or is suspected. The use of oseltamivir phosphate capsules is contraindicated in patients with known serious hypersensitivity to oseltamivir phosphate capsules  [see Contraindications (4) and Adverse Reactions (6.2)] .

Efficacy of oseltamivir phosphate capsules in the treatment of influenza in patients with chronic cardiac disease and/or respiratory disease was evaluated in one randomized, placebo-controlled clinical trial. Efficacy in this population, as measured by time to alleviation of all symptoms, was not established, but no new safety signals were identified [ see Clinical Studies (14.1) ].

No clinical trial data are available regarding treatment of influenza in patients with any medical condition sufficiently severe or unstable to be considered at imminent risk of requiring hospitalization.

Table 2 displays the dosage recommendations for the treatment and prophylaxis of influenza in adults with various stages of renal impairment (estimated creatinine clearance of less than or equal to 90 mL per minute). Dosage modifications are recommended in adults with an estimated creatinine clearance less than or equal to 60 mL per minute [see Use in Specific Population (8.6) and Clinical Pharmacology (12.3)] .

Initiate treatment with oseltamivir phosphate capsules within 48 hours of influenza symptom onset.

Initiate post-exposure prophylaxis with oseltamivir phosphate capsules within 48 hours following close contact with an infected individual. Initiate seasonal prophylaxis with oseltamivir phosphate capsules during a community outbreak.

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 recommended 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 in this study was approximately 115 times the human systemic exposure (AUC _0-24h) of oseltamivir carboxylate that occurs after administration of the maximum recommended human dose.

NDC 48972-7899-1

Oseltamivir Phosphate Capsules USP

30 mg

Each capsule contains oseltamivir phosphate equivalent to 30 mg



oseltamivir (free base).

Rx only

10 Capsules

Sunshine Lake Pharma Co., Ltd.

545391443

NDC 48972-7900-1

Oseltamivir Phosphate Capsules USP

45 mg

Each capsule contains oseltamivir phosphate equivalent to 45 mg



oseltamivir (free base).

Rx only

10 Capsules

Sunshine Lake Pharma Co., Ltd.

545391443

NDC 48972-7901-1

Oseltamivir Phosphate Capsules USP

75 mg

Each capsule contains oseltamivir phosphate equivalent to 75 mg



oseltamivir (free base).

Rx only

10 Capsules

Sunshine Lake Pharma Co., Ltd.

545391443

No dose adjustments are needed for either oseltamivir or the concomitant drug when coadministering oseltamivir with amoxicillin, acetaminophen, aspirin, cimetidine, antacids (magnesium and aluminum hydroxides and calcium carbonates), rimantadine, amantadine, or warfarin [see Clinical Pharmacology (12.3)] .

The following directions are provided for use only during emergency situations and when FDA-approved, commercially manufactured oseltamivir phosphate for oral suspension is not available from wholesalers or the manufacturer.

The following emergency preparation instructions will provide one patient with enough oseltamivir phosphate capsules for a 5-day course of treatment of influenza or a 10-day course of prophylaxis of influenza: