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)


• Prophylaxis of influenza A and B in patients 1 year and older. (1.2)

• 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)

• 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)

Oseltamivir Phosphate Capsules, USP:

• 30-mg (30 mg free base equivalent of the phosphate salt): size “4” hard gelatin capsules with ivory opaque body imprinted with “NP070” in blue ink and ivory opaque cap with “30 mg” in blue ink.

• 45-mg (45 mg free base equivalent of the phosphate salt): size “4” hard gelatin capsules with white opaque body imprinted with “NP071” in blue ink and white opaque cap with “45 mg” in blue ink.

• 75-mg (75 mg free base equivalent of the phosphate salt): size “2” hard gelatin capsules with white opaque body imprinted with “NP072” in blue ink and white opaque cap with “75 mg” in 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

The background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage is 2‐4% and 15‐20%, respectively.

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 1500 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, embryo‐fetal effects consisting of an increased incidence of minor skeletal malformations were observed at a maternally toxic dose (1500 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, embryo‐fetal 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 (1500 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.

• 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)