Pronunciation
(OH-sel-TAM-i-vir FOS-fate)

Med Watch Safty Alert:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanM...

Trade Name(s)
• Tamiflu

Class
• Antiviral agent

Treatment of uncomplicated acute illness caused by influenza infection in patients 1 yr of age and older who have been symptomatic for 2 days or less; prophylaxis of influenza in patients 1 yr of age and older.

Unlabeled Use(s):H1N1 Influenza A (Swine Flu)
For treatment and chemoprophylaxis of H1N1 influenza A (swine flu) virus infection. This includes patients with confirmed, probable, or suspected H1N1 influenza A (swine flu) virus infection and their close contacts. For more information, refer to the CDC guidelines at http://www.cdc.gov/h1n1flu/recommendations.htm .

Standard considerations.

Influenza Prophylaxis
Adults and Adolescents 13 yr of age and older - PO 75 mg once daily for at least 10 days, starting within 2 days of exposure.
Children 1 yr of age to younger than 13 yr of age - Start therapy within 2 days of exposure.
15 kg or less - PO 30 mg once daily for 10 days.
16 to 23 kg - PO 45 mg once daily for 10 days.
24 to 40 kg - PO 60 mg once daily for 10 days.
More than 40 kg - PO 75 mg once daily for 10 days.
Renal function impairment (CrCl 10 to 30 mL/min) - PO 75 mg every other day or 30 mg every day for 10 days.

Influenza Treatment
Adults and Adolescents 13 yr of age and older - PO 75 mg twice daily for 5 days, beginning within 2 days of onset of symptoms.
Children 1 yr of age to younger than 13 yr of age - 15 kg or less - PO 30 mg twice daily for 5 days.
16 to 23 kg - PO 45 mg twice daily for 5 days.
24 to 40 kg - PO 60 mg twice daily for 5 days.
More than 40 kg - PO 75 mg twice daily for 5 days.
Renal function impairment (CrCl 10 to 30 mL/min) - PO 75 mg once daily for 5 days.


Off-Label Dosing
• Prophylaxis of H1N1 Influenza A (Swine Flu)
Adults - PO 75 mg once daily for at least 10 days following close contact with an infected individual as recommended by the CDC. Therapy should begin within 2 days of exposure. The recommended dose for prophylaxis during a community outbreak of influenza is 75 mg once daily. Safety and efficacy have been demonstrated for up to 6 wk. For more information, refer to the CDC guidelines at http://www.cdc.gov/h1n1flu/recommendations.htm .
Children - For more information, refer to the CDC guidelines at http://www.cdc.gov/h1n1flu/recommendations.htm .
1 yr of age and older - 15 kg or less - PO 30 mg once per day for 10 days.
16 to 23 kg - PO 45 mg once per day for 10 days.
24 to 40 kg - PO 60 mg once per day for 10 days.
More than 40 kg - PO 75 mg once per day for 10 days.
Younger than 1 yr of age - 6 to 11 mo of age - PO 25 mg once daily for 10 days.
3 to 5 mo of age - PO 20 mg once daily for 10 days.
Younger than 3 mo of age - Not recommended unless situation judged critical because there are limited data on use in this age group.
• Treatment of H1N1 Influenza A (Swine Flu)
Adults - PO 75 mg twice daily for 5 days. Treatment should begin within 2 days of onset of influenza symptoms. For more information, refer to the CDC guidelines at http://www.cdc.gov/h1n1flu/recommendations.htm .
Children - For more information on dosing recommendations, refer to http://www.cdc.gov/h1n1flu/recommendations.htm .
1 yr of age and older - 15 kg or less - PO 30 mg twice daily for 5 days.
16 to 23 kg - PO 45 mg twice daily for 5 days.
24 to 40 kg - PO 60 mg twice daily for 5 days.
More than 40 kg - PO 75 mg twice daily for 5 days.
Younger than 1 yr of age - 6 to 11 mo of age - PO 25 mg twice daily for 5 days.
3 to 5 mo of age - PO 20 mg twice daily for 5 days.
Younger than 3 mo of age - PO 12 mg twice daily for 5 days.
General Administration

• May be taken with or without food. Tolerability may be enhanced if taken with food.

• For patients who cannot swallow capsules, if the oral suspension is not available, the capsules may be opened and mixed with sweetened liquids (eg, regular or sugar-free chocolate syrup).

• Efficacy has not been established in patients who begin treatment 40 h after onset of symptoms.

• Efficacy of repeated treatment or prophylaxis courses has not been studied.

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

• Shake the oral suspension well before each use. Use within 10 days of preparation.

Storage
Store capsules and dry powder for oral suspension at 59° to 86°F. Store reconstituted suspension product under refrigeration at 36° to 46°F. Do not freeze pharmacy compound suspension. May be stored for 35 days in a refrigerator or 5 days at 77°F.

Tamiflu

Capsules

• 30 mg

• 45 mg

• 75 mg

Powder for oral suspension

• 12 mg/mL

Live vaccines: Because of potential interference between these products, avoid administration of live attenuated influenza vaccine within 2 wk before or 48 h after oseltamivir.

Probenecid: Coadministration results in 2-fold increase in exposure to oseltamivir carboxylate.

cardiovascular: Arrhythmia (postmarketing).

cns: Headache (18%); fatigue (8%); dizziness (2%); insomnia, vertigo (1%); abnormal behavior, agitation, anxiety, confusion, delirium, delusions, hallucinations, nightmares, seizures (postmarketing).

dermatologic: Dermatitis (1%); eczema, erythema multiforme, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria (postmarketing).

eent: Otitis media (9%); asthma (aggravated) (3%); ear disorder (2%); conjunctivitis, tempanic membrane disorder (1%).

gi: Vomiting (15%); diarrhea, nausea (10%); abdominal pain (5%); GI bleeding, hemorrhagic colitis (postmarketing).

hepatic: Abnormal LFTs, hepatitis (postmarketing).

hypersensitivity: Allergy, anaphylatic/anaphylactoid reactions, swelling of the face or tongue (postmarketing).

metabolic-nutritional: Aggravation of diabetes (postmarketing).

respiratory: Epistaxis (3%); bronchitis cough, pneumonia, sinusitis (2%).

miscellaneous: Lymphadenopathy (1%).

Monitoring: There have been reports of self-injury and delirium, primarily in children. Monitor for signs of abnormal behavior throughout the treatment period.

Pregnancy: Category C .

Lactation: Undetermined.

Children: Safety and efficacy not established in children younger than 1 yr of age.

Elderly: Safety and efficacy have been demonstrated.

Renal function impairment: Dosage adjustment is recommended in patients with a serum CrCl less than 30 mL/min.

Neuropsychiatric events: There have been neurologic and behavioral symptoms that included hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes.

Repeated courses: Safety and efficacy not established.

Inhibition of influenza virus neuraminidase, with possible alteration of virus particle aggregation and release.

Absorption:
Readily absorbed from GI tract. C _max for oseltamivir is 65.2 ng/mL. C _max for metabolite is 348 ng/mL. AUC _(0-12h) for oseltamivir is 112 ng•h/mL. AUC _(0-12h) for metabolite is 2,719 ng•h/mL.

Distribution:
At least 75% of the dose reaches systemic circulation as oseltamivir carboxylate (bioavailability). The Vd is 23 to 26 L (metabolite); 3% is protein bound (metabolite); 42% is protein bound (parent drug).

Metabolism:
Converted to active oseltamivir carboxylate by esterases located predominantly in the liver.

Excretion:
The half-life is 6 to 10 h for the metabolite. The half-life for the parent drug is 1 to 3 h. More than 90% of oseltamivir is metabolized to oseltamivir carboxylate, which is entirely (more than 99%) eliminated by renal excretion. Less than 20% of the oral dose is eliminated through feces.

Special Populations:
renal - Exposure to the active metabolite is inversely proportional to declining renal function.

Hepatic - Exposure to the active metabolite is not altered in patients with mild to moderate hepatic function impairment. Safety and efficacy in patients with severe hepatic function impairment have not been evaluated.

Elderly - Exposure to the active metabolite at steady state was 25% to 35% higher in elderly patients. Dosage adjustments are not required.

Children - Children 12 yr of age and younger clear both the prodrug and active metabolite faster than adult patients, resulting in a lower exposure to a given mg/kg dose. The pharmacokinetics of the prodrug in patients older than 12 yr of age are similar to adult patients.

Nausea, vomiting.

• Advise patient to read patient information leaflet before starting therapy.

• Review dosing schedule and prescribed length of therapy with patient. Caution patient that medication must be started within 40 h of onset of influenza symptoms or exposure to influenza-infected person in order to be effective.

• Advise patient to take prescribed dose without regard to meals, but to administer with food if GI upset occurs.

• Advise patient or caregiver using suspension to shake well before measuring dose and to measure and administer dose using supplied dosing dispenser.

• Advise patient that if a dose is missed to take as soon as remembered. However, if it is within 2 h of the time for the next dose, skip the missed dose and take the next dose. Caution patient not to take 2 doses at the same time to catch up.

• Review other modalities for alleviating influenza symptoms (eg, hydration, OTC antipyretics and analgesics, rest).

• Remind patient to complete entire course of therapy, even if feeling better.

• Advise patient that oseltamivir is not a substitute for flu vaccination and to continue to obtain an annual flu vaccination.

• Advise patient to inform health care provider if flu symptoms do not appear to be improving or are getting worse, or if new symptoms develop during or after treatment.

• Instruct patient to discontinue therapy and contact health care provider immediately if experiencing signs or symptoms of an allergic reaction (eg, hives, rash, swelling of throat).