Oseltamivir Phosphate
(Oseltamivir)Oseltamivir Phosphate Prescribing Information
Warnings and Precautions
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
Oseltamivir phosphate capsules are an 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 Treatment of Influenza
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.
- Prophylaxis of influenza A and B in patients 1 year and older. 1.2 Prophylaxis of Influenza
Oseltamivir phosphate capsules are indicated for the prophylaxis of influenza A and B in patients 1 year and older.
- Not a substitute for annual influenza vaccination. 1.3 Limitations of Use
- 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)andUse in Specific Populations (8.6)].
- Consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use. 1.3 Limitations of Use
- 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)andUse in Specific Populations (8.6)].
- Not recommended for patients with end-stage renal disease not undergoing dialysis. 1.3 Limitations of Use
- 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)andUse in Specific Populations (8.6)].
Initiate treatment with oseltamivir phosphate within 48 hours of influenza symptom onset.
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.
Table 1 displays the recommended oral dosage of oseltamivir phosphate capsules for treatment of influenza in pediatric patients 2 weeks of age through 12 years of age and provides information about prescribing the capsule or the formulation for oral suspension.
- Adults and adolescents (13 years and older): 75 mg twice daily for 5 days
- Pediatric patients 1 to 12 years of age: Based on weight twice daily for 5 days
- Pediatric patients 2 weeks to less than 1 year of age: 3 mg/kg twice daily for 5 days
- Renally impaired adult patients (creatinine clearance > 30 to 60 mL/min): Reduce to 30 mg twice daily for 5 days 2.4 Dosage in Patients with Renal Impairment
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)andClinical Pharmacology (12.3)].Table 2 Recommended Dosage Modifications forTreatmentandProphylaxisof Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on DialysisRenal Impairment(Creatinine Clearance)Recommended TreatmentRegimen *Recommended ProphylaxisRegimen * †Mild
(>60 to 90 mL/minute)
75 mg twice daily for 5 days 75 mg once daily Moderate
(>30 to 60 mL/minute)
30 mg twice daily for 5 days 30 mg once daily Severe
(>10 to 30 mL/minute)
30 mg once daily for 5 days 30 mg every other day
ESRD Patients on Hemodialysis
(≤ 10 mL/minute)
30 mg immediately and then 30 mg after every hemodialysis cycle
(treatment duration not to exceed 5 days)
30 mg immediately and then 30 mg after alternate hemodialysis cycles ESRD Patients on Continuous
Ambulatory Peritoneal Dialysis‡
(≤10 mL/minute)
A single 30 mg dose administered
immediately
30 mg immediately and then 30 mg
once weekly
ESRD Patients not on Dialysis Oseltamivir phosphate capsules is not recommended Oseltamivir phosphate capsules is not recommended * Capsules or oral suspension can be used for 30 mg dosing.
† The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients).
‡ Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.
- Renally impaired adult patients (creatinine clearance > 10 to 30 mL/min): Reduce to 30 mg once daily for 5 days 2.4 Dosage in Patients with Renal Impairment
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)andClinical Pharmacology (12.3)].Table 2 Recommended Dosage Modifications forTreatmentandProphylaxisof Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on DialysisRenal Impairment(Creatinine Clearance)Recommended TreatmentRegimen *Recommended ProphylaxisRegimen * †Mild
(>60 to 90 mL/minute)
75 mg twice daily for 5 days 75 mg once daily Moderate
(>30 to 60 mL/minute)
30 mg twice daily for 5 days 30 mg once daily Severe
(>10 to 30 mL/minute)
30 mg once daily for 5 days 30 mg every other day
ESRD Patients on Hemodialysis
(≤ 10 mL/minute)
30 mg immediately and then 30 mg after every hemodialysis cycle
(treatment duration not to exceed 5 days)
30 mg immediately and then 30 mg after alternate hemodialysis cycles ESRD Patients on Continuous
Ambulatory Peritoneal Dialysis‡
(≤10 mL/minute)
A single 30 mg dose administered
immediately
30 mg immediately and then 30 mg
once weekly
ESRD Patients not on Dialysis Oseltamivir phosphate capsules is not recommended Oseltamivir phosphate capsules is not recommended * Capsules or oral suspension can be used for 30 mg dosing.
† The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients).
‡ Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.
- 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 Dosage in Patients with Renal Impairment
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)andClinical Pharmacology (12.3)].Table 2 Recommended Dosage Modifications forTreatmentandProphylaxisof Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on DialysisRenal Impairment(Creatinine Clearance)Recommended TreatmentRegimen *Recommended ProphylaxisRegimen * †Mild
(>60 to 90 mL/minute)
75 mg twice daily for 5 days 75 mg once daily Moderate
(>30 to 60 mL/minute)
30 mg twice daily for 5 days 30 mg once daily Severe
(>10 to 30 mL/minute)
30 mg once daily for 5 days 30 mg every other day
ESRD Patients on Hemodialysis
(≤ 10 mL/minute)
30 mg immediately and then 30 mg after every hemodialysis cycle
(treatment duration not to exceed 5 days)
30 mg immediately and then 30 mg after alternate hemodialysis cycles ESRD Patients on Continuous
Ambulatory Peritoneal Dialysis‡
(≤10 mL/minute)
A single 30 mg dose administered
immediately
30 mg immediately and then 30 mg
once weekly
ESRD Patients not on Dialysis Oseltamivir phosphate capsules is not recommended Oseltamivir phosphate capsules is not recommended * Capsules or oral suspension can be used for 30 mg dosing.
† The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients).
‡ Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.
- ESRD patients on CAPD: Reduce to a single 30 mg dose immediately 2.4 Dosage in Patients with Renal Impairment
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)andClinical Pharmacology (12.3)].Table 2 Recommended Dosage Modifications forTreatmentandProphylaxisof Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on DialysisRenal Impairment(Creatinine Clearance)Recommended TreatmentRegimen *Recommended ProphylaxisRegimen * †Mild
(>60 to 90 mL/minute)
75 mg twice daily for 5 days 75 mg once daily Moderate
(>30 to 60 mL/minute)
30 mg twice daily for 5 days 30 mg once daily Severe
(>10 to 30 mL/minute)
30 mg once daily for 5 days 30 mg every other day
ESRD Patients on Hemodialysis
(≤ 10 mL/minute)
30 mg immediately and then 30 mg after every hemodialysis cycle
(treatment duration not to exceed 5 days)
30 mg immediately and then 30 mg after alternate hemodialysis cycles ESRD Patients on Continuous
Ambulatory Peritoneal Dialysis‡
(≤10 mL/minute)
A single 30 mg dose administered
immediately
30 mg immediately and then 30 mg
once weekly
ESRD Patients not on Dialysis Oseltamivir phosphate capsules is not recommended Oseltamivir phosphate capsules is not recommended * Capsules or oral suspension can be used for 30 mg dosing.
† The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients).
‡ Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.
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.
The recommended dosage of oseltamivir phosphate capsules for prophylaxis of influenza in adults and adolescents 13 years and older is 75 mg orally once daily (one 75 mg capsule or 12.5 mL of oral suspension once daily) for at least 10 days following close contact with an infected individual and up to 6 weeks during a community outbreak. In immunocompromised patients, oseltamivir phosphate capsules may be continued for up to 12 weeks
Table 1 displays the recommended oral dosage of oseltamivir phosphate capsules for prophylaxis of influenza in pediatric patients 1 year to 12 years of age based on body weight and provides information about prescribing the capsule or the formulation for oral suspension. Prophylaxis in pediatric patients is recommended for 10 days following close contact with an infected individual and up to 6 weeks during a community outbreak
Weight | Treatment Dosage for 5 days | Prophylaxis Dosage for 10 days * | Volume of Oral Suspension (6 mg/mL) for each Dose † | Number of Bottles of Oral Suspension to Dispense | Number of Capsules to Dispense (Strength) ‡ |
Patients from 2 Weeks to less than 1 Year of Age | |||||
| Any weight | 3 mg/kg twice daily | Not applicable | 0.5 mL/kg § | 1 bottle | Not applicable |
Patients 1 to 12 Years of Age Based on Body Weight | |||||
| 15 kg or less | 30 mg twice daily | 30 mg once daily | 5 mL | 1 bottle | 10 capsules (30 mg) |
| 15.1 kg to 23 kg | 45 mg twice daily | 45 mg once daily | 7.5 mL | 2 bottles | 10 capsules (45 mg) |
| 23.1 kg to 40 kg | 60 mg twice daily | 60 mg once daily | 10 mL | 2 bottles | 20 capsules (30 mg) |
| 40.1 kg or more | 75 mg twice daily | 75 mg once daily | 12.5 mL | 3 bottles | 10 capsules (75 mg) |
* The recommended duration for post-exposure prophylaxis is 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients). The amount supplied (e.g., number of bottles or capsules) for seasonal prophylaxis may be greater than for post-exposure prophylaxis.
†Use an oral dosing dispensing device that measures the appropriate volume in mL with the oral suspension.
‡Oseltamivir phosphate for oral suspension is the preferred formulation for patients who cannot swallow capsules.
§For patients less than 1 year of age, provide an appropriate dosing device that can accurately measure and administer small volumes.
- Adults and adolescents (13 years and older): 75 mg once daily for at least 10 days
- Community outbreak: 75 mg once daily for up to 6 weeks
- Pediatric patients 1 to 12 years of age: Based on weight once daily for 10 days
- Community outbreak: Based on weight once daily for up to 6 weeks
- Renally impaired adult patients (creatinine clearance > 30 to 60 mL/min): Reduce to 30 mg once daily 2.4 Dosage in Patients with Renal Impairment
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)andClinical Pharmacology (12.3)].Table 2 Recommended Dosage Modifications forTreatmentandProphylaxisof Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on DialysisRenal Impairment(Creatinine Clearance)Recommended TreatmentRegimen *Recommended ProphylaxisRegimen * †Mild
(>60 to 90 mL/minute)
75 mg twice daily for 5 days 75 mg once daily Moderate
(>30 to 60 mL/minute)
30 mg twice daily for 5 days 30 mg once daily Severe
(>10 to 30 mL/minute)
30 mg once daily for 5 days 30 mg every other day
ESRD Patients on Hemodialysis
(≤ 10 mL/minute)
30 mg immediately and then 30 mg after every hemodialysis cycle
(treatment duration not to exceed 5 days)
30 mg immediately and then 30 mg after alternate hemodialysis cycles ESRD Patients on Continuous
Ambulatory Peritoneal Dialysis‡
(≤10 mL/minute)
A single 30 mg dose administered
immediately
30 mg immediately and then 30 mg
once weekly
ESRD Patients not on Dialysis Oseltamivir phosphate capsules is not recommended Oseltamivir phosphate capsules is not recommended * Capsules or oral suspension can be used for 30 mg dosing.
† The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients).
‡ Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.
- Renally impaired adult patients (creatinine clearance > 10 to 30 mL/min): Reduce to 30 mg once every other day 2.4 Dosage in Patients with Renal Impairment
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)andClinical Pharmacology (12.3)].Table 2 Recommended Dosage Modifications forTreatmentandProphylaxisof Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on DialysisRenal Impairment(Creatinine Clearance)Recommended TreatmentRegimen *Recommended ProphylaxisRegimen * †Mild
(>60 to 90 mL/minute)
75 mg twice daily for 5 days 75 mg once daily Moderate
(>30 to 60 mL/minute)
30 mg twice daily for 5 days 30 mg once daily Severe
(>10 to 30 mL/minute)
30 mg once daily for 5 days 30 mg every other day
ESRD Patients on Hemodialysis
(≤ 10 mL/minute)
30 mg immediately and then 30 mg after every hemodialysis cycle
(treatment duration not to exceed 5 days)
30 mg immediately and then 30 mg after alternate hemodialysis cycles ESRD Patients on Continuous
Ambulatory Peritoneal Dialysis‡
(≤10 mL/minute)
A single 30 mg dose administered
immediately
30 mg immediately and then 30 mg
once weekly
ESRD Patients not on Dialysis Oseltamivir phosphate capsules is not recommended Oseltamivir phosphate capsules is not recommended * Capsules or oral suspension can be used for 30 mg dosing.
† The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients).
‡ Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.
- 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 Dosage in Patients with Renal Impairment
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)andClinical Pharmacology (12.3)].Table 2 Recommended Dosage Modifications forTreatmentandProphylaxisof Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on DialysisRenal Impairment(Creatinine Clearance)Recommended TreatmentRegimen *Recommended ProphylaxisRegimen * †Mild
(>60 to 90 mL/minute)
75 mg twice daily for 5 days 75 mg once daily Moderate
(>30 to 60 mL/minute)
30 mg twice daily for 5 days 30 mg once daily Severe
(>10 to 30 mL/minute)
30 mg once daily for 5 days 30 mg every other day
ESRD Patients on Hemodialysis
(≤ 10 mL/minute)
30 mg immediately and then 30 mg after every hemodialysis cycle
(treatment duration not to exceed 5 days)
30 mg immediately and then 30 mg after alternate hemodialysis cycles ESRD Patients on Continuous
Ambulatory Peritoneal Dialysis‡
(≤10 mL/minute)
A single 30 mg dose administered
immediately
30 mg immediately and then 30 mg
once weekly
ESRD Patients not on Dialysis Oseltamivir phosphate capsules is not recommended Oseltamivir phosphate capsules is not recommended * Capsules or oral suspension can be used for 30 mg dosing.
† The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients).
‡ Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.
- ESRD patients on CAPD: Reduce to 30 mg immediately and then 30 mg once weekly for the recommended duration of prophylaxis 2.4 Dosage in Patients with Renal Impairment
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)andClinical Pharmacology (12.3)].Table 2 Recommended Dosage Modifications forTreatmentandProphylaxisof Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on DialysisRenal Impairment(Creatinine Clearance)Recommended TreatmentRegimen *Recommended ProphylaxisRegimen * †Mild
(>60 to 90 mL/minute)
75 mg twice daily for 5 days 75 mg once daily Moderate
(>30 to 60 mL/minute)
30 mg twice daily for 5 days 30 mg once daily Severe
(>10 to 30 mL/minute)
30 mg once daily for 5 days 30 mg every other day
ESRD Patients on Hemodialysis
(≤ 10 mL/minute)
30 mg immediately and then 30 mg after every hemodialysis cycle
(treatment duration not to exceed 5 days)
30 mg immediately and then 30 mg after alternate hemodialysis cycles ESRD Patients on Continuous
Ambulatory Peritoneal Dialysis‡
(≤10 mL/minute)
A single 30 mg dose administered
immediately
30 mg immediately and then 30 mg
once weekly
ESRD Patients not on Dialysis Oseltamivir phosphate capsules is not recommended Oseltamivir phosphate capsules is not recommended * Capsules or oral suspension can be used for 30 mg dosing.
† The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients).
‡ Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.
Oseltamivir Phosphate Capsules, USP:
- 30-mg (30 mg free base equivalent of the phosphate salt): Hard gelatin capsules with yellow ivory opaque cap and yellow ivory opaque body printed “AMNEAL” on cap and “264” on body with blue ink.
- 45-mg (45 mg free base equivalent of the phosphate salt): Hard gelatin capsules with light gray opaque cap and light gray opaque body printed “AMNEAL” on cap and “265” on body with blue ink.
- 75-mg (75 mg free base equivalent of the phosphate salt): Hard gelatin capsules with yellow ivory opaque cap and light gray opaque body printed “AMNEAL” on cap and “266” on body with blue ink.
There are no adequate and well-controlled studies with oseltamivir phosphate in pregnant women to inform a drug associated risk of adverse developmental outcomes. Available published epidemiological data suggest that oseltamivir phosphate, taken in any trimester, is not associated with an increased risk of birth defects. However, these studies individually are limited by small sample sizes, use of different comparison groups, and some lacked information on dose, which preclude a definitive assessment of the risk
Pregnant women are at higher risk of severe complications from influenza, which may lead to adverse pregnancy and/or fetal outcomes including maternal death, still births, birth defects, preterm delivery, low birth weight and small for gestational age.
Published prospective and retrospective observational studies of more than 5,000 women exposed to oseltamivir phosphate during pregnancy, including more than 1,000 women exposed in the first trimester, suggest that the observed rate of congenital malformations was not increased above the rate in the general comparison population, regardless of when therapy was administered during the gestational period. However, individually, none of these studies had adequate sample sizes and some lacked information on dose, which preclude a definitive assessment of the risk.
Oseltamivir was administered orally during organogenesis to pregnant rats (at 50, 250, or 1,500 mg/kg/day on gestation days 6 to 17) and rabbits (at 50, 150, or 500 mg/kg/day on gestation days 6 to 18). In rats, embryofetal effects consisting of an increased incidence of minor skeletal malformations were observed at a maternally toxic dose (1,500 mg/kg/day), resulting in systemic drug exposures (based on AUC for oseltamivir carboxylate) 190 times human exposures at the maximum recommended human dose (MRHD) of oseltamivir phosphate (75 mg twice a day). In the rabbit study, embryofetal effects consisting of an increased incidence of minor skeletal abnormalities and variants were observed at maternally toxic doses (> 150 mg/kg/day) resulting in systemic exposures (based on AUC for oseltamivir carboxylate) ≥ 8 times human exposures at the MRHD of oseltamivir phosphate.
In prenatal and postnatal development studies in rats, oseltamivir was administered orally (at 50, 250, 500, or 1500 mg/kg/day) from organogenesis through late gestation, delivery, and lactation (gestation day 6 to postpartum/lactation day 20). Prolonged parturition duration and reduced offspring viability were observed at a maternally toxic dose (1,500 mg/kg/day). No adverse maternal or offspring effects were observed at doses ≤ 500 mg/kg/day, resulting in systemic drug exposures (based on AUC for oseltamivir carboxylate) 44 times human exposures at the MRHD of oseltamivir phosphate.
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
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. Stop oseltamivir phosphate and institute appropriate treatment if an allergic-like reaction occurs or is suspected. The use of oseltamivir phosphate is contraindicated in patients with known serious hypersensitivity to oseltamivir phosphate