Oseltamivir (Oseltamivir phosphate): Uses, Dosage, Side Effects & Warnings

Uses

Oseltamivir phosphate is 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) 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) 1.1 Treatment of Influenza Oseltamivir phosphate is 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. 1.2 Prophylaxis of Influenza Oseltamivir phosphate is indicated for the prophylaxis of influenza A and B in patients 1 year and older. 1.3 Limitations of Use
• Oseltamivir phosphate 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.
• 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 [see Microbiology (12.4) ].
• Oseltamivir phosphate is 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) ].

Dosage and administration

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: 3 mg/kg twice daily for 5 days (2.2)
• Renally impaired adult patients (creatinine clearance >30 to 60 mL/min): Reduce to 30 mg twice daily for 5 days (2.4)
• Renally impaired adult patients (creatinine clearance >10 to 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 to 60 mL/min): Reduce to 30 mg once daily (2.4)
• Renally impaired adult patients (creatinine clearance >10 to 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) 2.1 Dosage and Administration Overview Administer oseltamivir phosphate 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 is taken with food. Adjust the oseltamivir phosphate 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) ]. 2.2 Recommended Dosage for Treatment of Influenza Initiate treatment with oseltamivir phosphate within 48 hours of influenza symptom onset. Adults and Adolescents (13 years of age and older) The recommended oral dosage of oseltamivir phosphate for treatment of influenza in adults and adolescents 13 years and older is 75 mg twice daily (one 75 mg capsule twice daily) for 5 days. Pediatric Patients (2 weeks of age through 12 years of age) Table 1 displays the recommended oral dosage of oseltamivir phosphate 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. 2.3 Recommended Dosage for Prophylaxis of Influenza Initiate post‐exposure prophylaxis with oseltamivir phosphate within 48 hours following close contact with an infected individual. Initiate seasonal prophylaxis with oseltamivir phosphate during a community outbreak. Adults and Adolescents (13 years of age and older) The recommended dosage of oseltamivir phosphate for prophylaxis of influenza in adults and adolescents 13 years and older is 75 mg orally once daily (one 75 mg capsule 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 may be continued for up to 12 weeks [see Use in Specific Populations (8.9) ] . The duration of protection lasts for as long as oseltamivir phosphate dosing is continued. Pediatric Patients (1 year to 12 years of age) Table 1 displays the recommended oral dosage of oseltamivir phosphate 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 [see Use in Specific Populations (8.4) and Clinical Studies (14.2) ]. Table 1 Oseltamivir Phosphate Dosage Recommendations in Pediatric Patients for Treatment and Prophylaxis of Influenza * 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.

Dosage forms and strengths

Oseltamivir Phosphate Capsules, USP:
• 30‐mg (30 mg free base equivalent of the phosphate salt): Light yellow opaque/Light yellow opaque size “4” hard gelatin capsules imprinted with “LL” on cap and “30” on body with blue ink, filled with white to off-white granular powder.
• 45‐mg (45 mg free base equivalent of the phosphate salt): Grey opaque/Grey opaque size “4” hard gelatin capsules imprinted with “LL” on cap and “45” on body with blue ink, filled with white to off-white granular powder.
• 75‐mg (75 mg free base equivalent of the phosphate salt): Light yellow opaque/Grey opaque size “2” hard gelatin capsules imprinted with “LL” on cap and “75” on body with blue ink, filled with white to off-white granular powder.
• Capsules: 30 mg, 45 mg, 75 mg (3)

Contraindications

Oseltamivir phosphate 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 [see Warnings and Precautions (5.1 ) ]. Patients with known serious hypersensitivity to oseltamivir or any of the components of oseltamivir phosphate (4)

Warnings and precautions

• Serious skin/hypersensitivity reactions such as Stevens‐Johnson Syndrome, toxic epidermal necrolysis and erythema multiforme: Discontinue oseltamivir phosphate and initiate appropriate treatment if allergic‐like reactions occur or are suspected. (5.1)
• Neuropsychiatric events: Patients with influenza, including those receiving oseltamivir phosphate, 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) 5.1 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 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 [see Contraindications (4) and Adverse Reactions (6.2) ]. 5.2 Neuropsychiatric Events 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 [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 usage data. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of oseltamivir phosphate 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‐treated patients with influenza for signs of abnormal behavior. If neuropsychiatric symptoms occur, evaluate the risks and benefits of continuing oseltamivir phosphate for each patient. 5.3 Risk of Bacterial Infections There is no evidence for efficacy of oseltamivir phosphate 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 has not been shown to prevent such complications. Prescribers should be alert to the potential for secondary bacterial infections and treat them as appropriate.

Side effects

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) ] Most common adverse reactions (>1% and more common than with placebo):
• Treatment studies – Nausea, vomiting, headache. (6.1)
• Prophylaxis studies – Nausea, vomiting, headache, pain. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Laurus Generics Inc. at 1-833-3-LAURUS (1-833-352-8787) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience 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. Adverse Reactions from Treatment and Prophylaxis Trials in Adult and Adolescent Subjects (13 years of age and older) The overall safety profile of oseltamivir phosphate is based on data from 2,646 adult and adolescent subjects that received the recommended dosage of 75 mg orally twice daily for 5 days for treatment of influenza and 1,943 adult and adolescent subjects that received the recommended dosage of 75 mg orally once daily for up to 6 weeks for prophylaxis of influenza in clinical trials. The most common adverse reactions in the pooled treatment and pooled prophylaxis trials in adults and adolescents are displayed in Table 5. The majority of these adverse reactions were reported on a single occasion, occurred on either the first or second treatment day and resolved spontaneously within 1 to 2 days. This summary includes otherwise healthy adults/adolescents and subjects “at risk” (subjects at higher risk of developing complications associated with influenza, e.g., elderly patients and patients with chronic cardiac or respiratory disease). In general, the safety profile in the subjects “at risk” was qualitatively similar to that in otherwise healthy adults/adolescents. Table 5 Adverse Reactions Occurring in ≥1% of Adults and Adolescents (13 years of age and older) in Treatment and Prophylaxis Trials* * Adverse reactions that occurred in ≥1% of oseltamivir phosphate‐treated adults and adolescents and ≥1% greater in oseltamivir phosphate‐treated subjects compared to placebo‐treated subjects in either the treatment or prophylaxis trials. System Organ Class Adverse Reaction Treatment Trials Prophylaxis Trials Oseltamivir phosphate 75 mg twice daily (n = 2,646) Placebo (n = 1,977) Oseltamivir phosphate 75 mg once daily (n = 1,943) Placebo (n = 1,586) Gastrointestinal Disorders Nausea Vomiting 10 % 8 % 6 % 3% 8 % 2% 4 % 1% Nervous System Disorders Headache General Disorders Pain 2 % <1% 1% <1% 17% 4% 16% 3% Adverse Reactions from Treatment and Prophylaxis Trials in Pediatric Subjects (1 year to 12 years of age) A total of 1,481 pediatric subjects (including otherwise healthy pediatric subjects aged 1 year to 12 years and asthmatic pediatric subjects aged 6 to 12 years) participated in clinical trials of oseltamivir phosphate for the treatment of influenza. A total of 859 pediatric subjects received treatment with oseltamivir phosphate for oral suspension either at a 2 mg per kg twice daily for 5 days or weight‐band dosing. Vomiting was the only adverse reaction reported at a frequency of >1% in subjects receiving oseltamivir phosphate (16%) compared to placebo (8%). Amongst the 148 pediatric subjects aged 1 year to 12 years who received oseltamivir phosphate at doses of 30 to 60 mg once daily for 10 days in a post‐exposure prophylaxis study in household contacts (n = 99), and in a separate 6–week seasonal influenza prophylaxis safety study (n = 49), vomiting was the most frequent adverse reaction (8% on oseltamivir phosphate versus 2% in the no prophylaxis group). Adverse Reactions from Treatment Trials in Pediatric Subjects (2 weeks to less than 1 year of age) Assessment of adverse reactions in pediatric subjects 2 weeks to less than 1 year of age was based on two open‐label studies that included safety data on 135 influenza‐infected subjects 2 weeks to less than 1 year of age (including premature infants at least 36 weeks post conceptional age) exposed to oseltamivir phosphate at doses ranging from 2 to 3.5 mg per kg of the formulation for oral suspension twice daily orally for 5 days. The safety profile of oseltamivir phosphate was similar across the age range studied, with vomiting (9%), diarrhea (7%) and diaper rash (7%) being the most frequently reported adverse reactions, and was generally comparable to that observed in older pediatric and adult subjects. Adverse Reactions from the Prophylaxis Trial in Immunocompromised Subjects In a 12‐week seasonal prophylaxis study in 475 immunocompromised subjects, including 18 pediatric subjects 1 year to 12 years of age, the safety profile in the 238 subjects receiving oseltamivir phosphate 75 mg once daily was consistent with that previously observed in other oseltamivir phosphate prophylaxis clinical trials [see Clinical Studies (14.2) ]. 6.2 Postmarketing Experience The following adverse reactions have been identified during post‐approval use of oseltamivir phosphate. 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.

Drug interactions

Live attenuated influenza vaccine (LAIV), intranasal: Avoid administration of LAIV within 2 weeks before or 48 hours after oseltamivir phosphate use, unless medically indicated. (7) 7.1 Influenza Vaccines Live Attenuated Influenza Vaccine The concurrent use of oseltamivir phosphate with live attenuated influenza vaccine (LAIV) intranasal has not been evaluated. However, because of the potential for oseltamivir phosphate to inhibit replication of live vaccine virus and possibly reduce the efficacy of LAIV, avoid administration of LAIV within 2 weeks before or 48 hours after oseltamivir phosphate administration, unless medically indicated. Inactivated Influenza Vaccine Inactivated influenza vaccine can be administered at any time relative to use of oseltamivir phosphate. 7.2 Drugs Without Clinically Significant Drug Interaction with Oseltamivir Phosphate 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) ].

Use in specific populations

8.1 Pregnancy Risk Summary 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 [see Data and Clinical Pharmacology (12.3) ]. In animal reproduction studies with oseltamivir, no adverse developmental effects were observed at clinically relevant exposures (see Data). 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 to 4% and 15 to 20%, respectively. Clinical Considerations Disease‐Associated Maternal and/or Embryo/Fetal 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. Data Human Data 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. Animal Data 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, embryo‐fetal 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, 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 1,500 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. 8.2 Lactation Risk Summary Based on limited published data, oseltamivir and oseltamivir carboxylate have been shown to be present in human milk at low levels considered unlikely to lead to toxicity in the breastfed infant. Postmarketing experience has not reported any information to suggest serious adverse effects of oseltamivir exposure via breast milk in infants. It is not known if oseltamivir affects human milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for oseltamivir phosphate and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. 8.4 Pediatric Use Treatment of Influenza The safety and efficacy of oseltamivir phosphate for the treatment of influenza in pediatric patients 2 weeks old to 17 years of age has been established [see Dosage and Administration (2.2), Clinical Pharmacology (12.3), and Clinical Studies (14.1) ] and is based on:
• 13 to 17 years of age: Safety and efficacy in adolescent patients 13 to 17 years of age was supported by adequate and well‐controlled trials in adults and adolescents and younger pediatric patients and safety data in adolescents treated with oseltamivir phosphate in a study of treatment and prophylaxis.
• 1 year to 12 years of age: Safety and efficacy in pediatric patients 1 year to 12 years of age was supported by results of one double‐blind, placebo‐controlled trial in 452 pediatric patients with influenza in whom oseltamivir phosphate 2 mg per kg twice daily or placebo was administered within 48 hours of symptom onset [see Clinical Studies (14.1) ]. Additional safety information was provided in a double‐blind, placebo‐controlled trial in pediatric patients 6 to 12 years of age with known asthma. Efficacy could not be established in pediatric patients with asthma.
• 2 weeks to less than 1 year of age: Safety and efficacy in pediatric patients 2 weeks to less than 1 year of age is supported by adequate and well‐controlled trials in adults and older pediatric patients and two open‐label trials of oseltamivir phosphate (2 to 3.5 mg per kg twice daily for 5 days) in 136 pediatric subjects 2 weeks to less than 1 year of age. In these two trials, the oseltamivir plasma concentrations in these subjects were similar to or higher than the oseltamivir plasma concentrations observed in older pediatric subjects and adults [see Clinical Pharmacology (12.3) and Clinical Studies (14.1) ].

Pregnancy

8.1 Pregnancy Risk Summary 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 [see Data and Clinical Pharmacology (12.3) ]. In animal reproduction studies with oseltamivir, no adverse developmental effects were observed at clinically relevant exposures (see Data). 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 to 4% and 15 to 20%, respectively. Clinical Considerations Disease‐Associated Maternal and/or Embryo/Fetal 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. Data Human Data 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. Animal Data 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, embryo‐fetal 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, 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 1,500 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.

Pediatric use

8.4 Pediatric Use Treatment of Influenza The safety and efficacy of oseltamivir phosphate for the treatment of influenza in pediatric patients 2 weeks old to 17 years of age has been established [see Dosage and Administration (2.2), Clinical Pharmacology (12.3), and Clinical Studies (14.1) ] and is based on:
• 13 to 17 years of age: Safety and efficacy in adolescent patients 13 to 17 years of age was supported by adequate and well‐controlled trials in adults and adolescents and younger pediatric patients and safety data in adolescents treated with oseltamivir phosphate in a study of treatment and prophylaxis.
• 1 year to 12 years of age: Safety and efficacy in pediatric patients 1 year to 12 years of age was supported by results of one double‐blind, placebo‐controlled trial in 452 pediatric patients with influenza in whom oseltamivir phosphate 2 mg per kg twice daily or placebo was administered within 48 hours of symptom onset [see Clinical Studies (14.1) ]. Additional safety information was provided in a double‐blind, placebo‐controlled trial in pediatric patients 6 to 12 years of age with known asthma. Efficacy could not be established in pediatric patients with asthma.
• 2 weeks to less than 1 year of age: Safety and efficacy in pediatric patients 2 weeks to less than 1 year of age is supported by adequate and well‐controlled trials in adults and older pediatric patients and two open‐label trials of oseltamivir phosphate (2 to 3.5 mg per kg twice daily for 5 days) in 136 pediatric subjects 2 weeks to less than 1 year of age. In these two trials, the oseltamivir plasma concentrations in these subjects were similar to or higher than the oseltamivir plasma concentrations observed in older pediatric subjects and adults [see Clinical Pharmacology (12.3) and Clinical Studies (14.1) ]. The safety and efficacy of oseltamivir phosphate for treatment of influenza in pediatric patients less than 2 weeks of age have not been established. Prophylaxis of Influenza The safety and efficacy of oseltamivir phosphate for the prophylaxis of influenza in pediatric patients 1 year to 17 years old has been established [see Dosage and Administration (2.3), Clinical Pharmacology (12.3), and Clinical Studies (14.2) ] and is based on:
• 13 to 17 years of age: Prophylaxis in adolescent patients 13 to 17 years of age is supported by one randomized, placebo‐controlled post‐exposure household prophylaxis trial of oseltamivir phosphate 75 mg taken orally once daily for 7 days in household contacts including 207 adolescents [see Clinical Studies (14.2) ].
• 1 year to 12 years of age: Oseltamivir phosphate for prophylaxis in pediatric patients 1 year to 12 years of age is supported by one randomized, open‐label, post‐exposure household prophylaxis trial including pediatric subjects 1 year to 12 years of age who received 30 to 60 mg of oseltamivir phosphate for oral suspension (supplied as powder) taken orally once daily for 10 days [see Clinical Studies (14.2) ]. Additional safety information was provided in a 6‐week seasonal prophylaxis (community outbreak) safety study in 49 patients 1 year to 12 years of age. The safety and efficacy of oseltamivir phosphate for prophylaxis of influenza have not been established for pediatric patients less than 1 year of age.

Geriatric use

8.5 Geriatric Use Treatment of Influenza Of the 4,765 adults in clinical trials of oseltamivir phosphate for the treatment of influenza, 948 (20%) were 65 years and older, while 329 (7%) were 75 years and older. In three double‐blind, placebo‐controlled trials in the treatment of influenza in patients at least 65 years old, that enrolled 741 subjects (374 received placebo and 362 received oseltamivir phosphate), 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 [see Clinical Studies (14.1) ]. Prophylaxis of Influenza Of the 4,603 adults in clinical trials of oseltamivir phosphate for the prophylaxis of influenza, 1,046 (23%) were 65 years and older, while 719 (16%) were 75 years and older. In a randomized, placebo‐controlled trial in elderly residents of nursing homes who took oseltamivir phosphate for up to 42 days for the prophylaxis of influenza (oseltamivir phosphate n=276, placebo n=272), 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 [see Clinical Studies (14.2) ].

Overdosage

Reports of overdoses with oseltamivir phosphate 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 [see Adverse Reactions (6) ].

Description

Oseltamivir phosphate capsules,USP an influenza neuraminidase inhibitor (NAI), is available as:
• Capsules containing 30 mg, 45 mg, or 75 mg of oseltamivir for oral use, in the form of oseltamivir phosphate USP. In addition to the active ingredient, each capsule contains croscarmellose sodium, pregelatinized starch, polyvinylpyrrolidone, sodium stearyl fumarate and talc. The 30 mg capsule shell contains gelatin, iron oxide yellow and titanium dioxide. The 45 mg capsule shell contains gelatin, iron oxide black and titanium dioxide. The 75 mg capsule shell contains gelatin, iron oxide yellow, iron oxide black, and titanium dioxide. Each capsule is printed with blue ink, which includes FD & C Blue # 2 aluminum lake and shellac as the colorant. Oseltamivir phosphate USP, is a White to off-white solid with the chemical name (3 R ,4 R ,5 S )-4-acetylamino-5-amino-3(1-ethylpropoxy)-1-cyclohexene-1-carboxylic acid ethyl ester phosphate (1:1). The chemical formula is C 16 H 28 N 2 O 4 .H 3 PO 4 . The molecular weight is 312.4 for oseltamivir free base and 410.4 for oseltamivir phosphate salt. The structural formula is as follows: Meets USP Dissolution Test 2. oseltamivir-structure

Mechanism of action

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

How supplied

Oseltamivir Phosphate Capsules, USP: 30‐mg capsules (30 mg free base equivalent of the phosphate salt): Light yellow opaque/Light yellow opaque size “4” hard gelatin capsules imprinted with “LL” on cap and “30” on body with blue ink, filled with white to off-white granular powder. Available in blister packages of 10 (42385-985-11) and Unit-of-use-bottles of 100 (42385-985-01). 45‐mg capsules (45 mg free base equivalent of the phosphate salt): Grey opaque/Grey opaque size “4” hard gelatin capsules imprinted with “LL” on cap and “45” on body with blue ink, filled with white to off-white granular powder. Available in blister packages of 10 (42385-986-11) and Unit-of-use-bottles of 100 (42385-986-01). 75‐mg capsules (75 mg free base equivalent of the phosphate salt): Light yellow opaque/Grey opaque size “2” hard gelatin capsules imprinted with “LL” on cap and “75” on body with blue ink, filled with white to off-white granular powder. Available in blister packages of 10 (42385-987-11) and Unit-of-use-bottles of 100 (42385-987-01). Storage Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.]

Patient information

Advise the patient to read the FDA‐approved patient labeling (Patient Information and Instructions for Use). Serious Skin/Hypersensitivity Reactions Advise patients and/or caregivers of the risk of severe allergic reactions (including anaphylaxis) or serious skin reactions. Instruct patients and/or caregiver to stop oseltamivir phosphate and seek immediate medical attention if an allergic‐like reaction occurs or is suspected [ see Warnings and Precautions (5.1) ]. Neuropsychiatric Events Advise patients and/or caregivers of the risk of neuropsychiatric events in oseltamivir phosphate‐treated patients with influenza and instruct patients to contact their physician if they experience signs of abnormal behavior while receiving oseltamivir phosphate [see Warnings and Precautions (5.2) ] . Important Dosing Information Instruct patients to begin treatment with oseltamivir phosphate as soon as possible from the first appearance of flu symptoms, within 48 hours of onset of symptoms. Similarly, instruct patients to start taking oseltamivir phosphate for prevention as soon as possible after exposure [ see Dosage and Administration (2) ]. 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 oseltamivir phosphate at the usual times. Influenza Vaccines Instruct patients that oseltamivir phosphate is not a substitute for receiving an annual flu vaccination. Patients should continue receiving an annual flu vaccination according to guidelines on immunization practices. Because of the potential for oseltamivir phosphate to inhibit replication of live attenuated influenza vaccine (LAIV) and possibly reduce efficacy of LAIV, avoid administration of LAIV within 2 weeks or 48 hours after oseltamivir phosphate administration, unless medically necessary [see Drug Interactions (7.1) ]. The brands listed are trademarks of their respective owners and are not trademarks of Laurus Labs Limited. Manufactured for: Laurus Generics Inc. 400 Connell Drive Suite 5200 Berkeley Heights, NJ 07922 Manufactured by: Laurus Labs Limited Anakapalli-531011 India

Active ingredients

Oseltamivir Phosphate in 9 products

Oseltamivir NDC products (9)

NDC	Strength & form	Labeler	Type
62332-413	Oseltamivir Phosphate 30 mg/1 Capsule	Alembic Pharmaceuticals Inc.	ANDA
62332-414	Oseltamivir Phosphate 45 mg/1 Capsule	Alembic Pharmaceuticals Inc.	ANDA
62332-415	Oseltamivir Phosphate 75 mg/1 Capsule	Alembic Pharmaceuticals Inc.	ANDA
46708-413	Oseltamivir Phosphate 30 mg/1 Capsule	Alembic Pharmaceuticals Limited	ANDA
46708-414	Oseltamivir Phosphate 45 mg/1 Capsule	Alembic Pharmaceuticals Limited	ANDA
46708-415	Oseltamivir Phosphate 75 mg/1 Capsule	Alembic Pharmaceuticals Limited	ANDA
42385-985	Oseltamivir Phosphate 30 mg/1 Capsule	Laurus Labs Limited	ANDA
42385-986	Oseltamivir Phosphate 45 mg/1 Capsule	Laurus Labs Limited	ANDA
42385-987	Oseltamivir Phosphate 75 mg/1 Capsule	Laurus Labs Limited	ANDA

Frequently asked questions

What is Oseltamivir used for?

Oseltamivir phosphate is 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) Limitations of Use : • Not a substitute for annual influenza vaccination. (1.3) • Consider…

What are the side effects of Oseltamivir?

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) ] Most common adverse reactions (>1% and more common than with placebo): • Treatment studies – Nausea, vomiting, headache. (6.1) • Prophylaxis studies – Nausea,… See the full label for the complete list.

Who makes Oseltamivir?

Oseltamivir is listed by 3 labelers in the FDA NDC directory, including Alembic Pharmaceuticals Inc., Alembic Pharmaceuticals Limited, Laurus Labs Limited.