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Oseltamivir Phosphate

Pronunciation

Pronunciation: OH-sel-TAM-i-vir FOS-fate
Class: Antiviral agent

Trade Names

Tamiflu
- Capsules, oral 30 mg
- Capsules, oral 45 mg
- Capsules, oral 75 mg
- Powder for oral suspension 6 mg/mL

Pharmacology

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

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Pharmacokinetics

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.

Elimination

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 Function Impairment

Exposure to the active metabolite is inversely proportional to declining renal function.

Hepatic Function Impairment

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 y and younger clear 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 y are similar to adult patients.

Indications and Usage

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

Unlabeled Uses

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 .

Contraindications

Hypersensitivity to oseltamivir or any component of the product.

Dosage and Administration

Influenza Prophylaxis
Adults and Adolescents 13 y and older

PO 75 mg once daily for at least 10 days, starting within 2 days of exposure.

Children 1 to 12 y

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 y and older

PO 75 mg twice daily for 5 days, beginning within 2 days of onset of symptoms.

Children 1 to 12 y of age

Start therapy within 2 days of onset of symptoms.

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

The dosage provided as part of the FDA's Emergency Use Authorization (EUA) of oseltamivir during the 2009 H1N1 influenza public health emergency was as follows. However, the EUA expired on June 23, 2010.

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 dosage 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 y 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.

41 kg or more

PO 75 mg once per day for 10 days.

Younger than 1 y 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

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 y 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.

41 kg or more

PO 75 mg twice daily for 5 days.

Younger than 1 y 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 Advice

  • 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, corn syrup, caramel topping, or light brown sugar dissolved in water).
  • The Institute for Safe Medication Practices recommends that doses of oral suspension be communicated in mg, not by volume.
  • Efficacy has not been established in patients who begin treatment 48 h after onset of symptoms.
  • Shake the oral suspension well before each use. Use within 10 days of preparation.

Storage/Stability

Store capsules and dry powder for oral suspension between 59° and 86°F. Store reconstituted suspension product under refrigeration between 36° and 46°F for up to 17 days. Do not freeze. Alternatively, store reconstituted suspension for up to 10 days between 59° and 86°F.

Drug Interactions

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.

Adverse Reactions

Cardiovascular

Arrhythmia (postmarketing).

CNS

Abnormal behavior, agitation, altered level of consciousness, anxiety, confusion, delirium, delusions, hallucinations, nightmares, seizures (postmarketing).

Dermatologic

Dermatitis, eczema, erythema multiforme, rash, Stevens-Johnson syndrome, TEN, urticaria (postmarketing).

EENT

Ear disorder (2%); conjunctivitis (1%).

GI

Vomiting (15%); nausea (10%); abdominal pain (5%); diarrhea (3%); 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 (1%).

Miscellaneous

Hypothermia (postmarketing).

Precautions

Monitor

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 y.

Elderly

Safety and efficacy have been demonstrated.

Hypersensitivity

Cases of anaphylaxis and serious skin reactions, including erythema multiforme, Stevens-Johnson syndrome, and TEN, have been reported.

Renal Function

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

Bacterial infections

Not established for prophylactic use to prevent complications from serious bacterial infections that may begin with influenza-like symptoms.

High-risk patients

Efficacy in patients with chronic cardiac disease and/or respiratory disease and use in immunocompromised patients have not been established.

Neuropsychiatric events

There have been neurologic and behavioral symptoms including hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes.

Overdosage

Symptoms

Nausea, vomiting.

Patient Information

  • Advise patients to read patient information leaflet before starting therapy.
  • Review dosing schedule and prescribed length of therapy with patients. Caution patients that medication must be started within 48 h of onset of influenza symptoms or exposure to influenza-infected person in order to be effective.
  • Advise patients to take their prescribed dose without regard to meals, but to administer with food if GI upset occurs.
  • Advise patients and/or caregivers using suspension to shake well before measuring dose and to measure and administer dose using supplied dosing dispenser.
  • Advise patients that if a dose is missed to take it as soon as they remember. However, if it is within 2 h of the time for the next dose, advise them to skip the missed dose and take the next dose. Caution patients 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 patients to complete the entire course of therapy, even if they are feeling better.
  • Advise patients that oseltamivir is not a substitute for flu vaccination and to continue to obtain an annual flu vaccination.
  • Advise patients to inform their 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 patients to discontinue therapy and contact their health care provider immediately if experiencing signs or symptoms of an allergic reaction (eg, hives, rash, swelling of throat).
  • Inform patients and/or caregivers of the risk of neuropsychiatric events (eg, hallucinations, delirium) in patients with influenza and advise them to contact their health care provider if they experience signs of abnormal behavior while on therapy.
  • For patients with hereditary fructose intolerance, a bottle of oseltamivir oral suspension contains approximately 11 g of sorbitol (1 dose of 75 mg delivers sorbitol 2 g); this is above the daily maximum limit of sorbitol and may cause dyspepsia and diarrhea.

Copyright © 2009 Wolters Kluwer Health.

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