oseltamivir phosphate
Tamiflu

Available forms
Available by prescription only
Capsules: 75 mg
Suspension: 12 mg/ml

Indications and dosages
 Treatment of uncomplicated, acute influenza A and B infection in adults symptomatic for 2 days or less. Adults: 75 mg P.O. b.i.d. for 5 days, beginning within 2 days of symptom onset.
 Treatment of influenza in children age 1 and older. Children who weigh more than 40 kg (88 lb): 75 mg oral suspension P.O. b.i.d.
Children who weigh 24 to 40 kg (53 to 88 lb): 60 mg oral suspension P.O. b.i.d.
Children who weigh 16 to 23 kg (35 to 51 lb): 45 mg oral suspension P.O. b.i.d.
Children who weigh 15 kg (33 lb) or less: 30 mg oral suspension P.O. b.i.d.
≡ Dosage adjustment. For adults with creatinine clearance of less than 30 ml/ minute, 75 mg P.O. once daily for 5 days, beginning within 2 days of symptom onset.
 Prevention of influenza following close contact with infected person. Adults and adolescents age 13 and older: 75 mg P.O. once daily beginning within 2 days of exposure and lasting at least 7 days.
 Prevention of influenza during a community outbreak. Adults and adolescents age 13 and older: 75 mg P.O. once daily for up to 6 weeks.
≡ Dosage adjustment. For patients with creatinine clearance of less than 30 ml/ minute, 75 mg P.O. every other day for 5 days, beginning within 2 days of exposure.

Pharmacodynamics
Antiviral action: Oseltamivir is hydrolyzed in the liver to its active form, oseltamivir carboxylase. Oseltamivir carboxylase inhibits the enzyme neuraminidase in influenza virus particles. This action is thought to inhibit viral replication, possibly by interfering with viral particle aggregation and release from the host cell.

Pharmacokinetics
Absorption: Well absorbed after oral administration. More than 75% of dose reaches the systemic circulation as oseltamivir carboxylase. Peak level of oseltamivir is 65.2 ng/ml whereas that of oseltamivir carboxylase is 348 ng/ml.
Distribution: Serum protein-binding is low for both oseltamivir (42%) and oseltamivir carboxylase (3%). Volume of distribution of oseltamivir carboxylase is 23 to 26 L.
Metabolism: Oseltamivir is extensively metabolized by hepatic esterases to its active component, oseltamivir carboxylase. Oseltamivir is neither a substrate nor an inhibitor of cytochrome P-450 oxidases.
Excretion: Oseltamivir carboxylase is almost entirely eliminated in urine via glomerular filtration and tubular secretion. Less than 20% of oral dose is eliminated in feces.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or its components. Use cautiously in patients with chronic cardiac disease, chronic respiratory disease, or any acute medical illness requiring hospitalization. Efficacy of oseltamivir hasn’t been established in these settings.

Interactions
None reported.

Adverse reactions
CNS: dizziness, insomnia, headache, vertigo, fatigue.
GI: abdominal pain, diarrhea, nausea, vomiting.
Respiratory: bronchitis, cough.

Effects on lab test results
None reported.

Overdose and treatment
Single doses as high as 1,000 mg have been linked to only nausea and vomiting. The entire 5-day course of therapy provides a total dose of 750 mg.

Special considerations
• Oseltamivir doesn’t appear to interfere with normal humoral antibody response to influenza.
• Efficacy of oseltamivir against influenza virus type A and B has been demonstrated in clinical trials. There’s no evidence supporting the use of oseltamivir in the treatment of other viral infections.
• Administration of oseltamivir with meals may alleviate adverse GI effects.
• Nausea and vomiting are the most frequent adverse effects.
• Store drug at 59° to 86° F (15° to 30° C).
Breast-feeding patients
• It isn’t known if drug appears in breast milk. The potential benefits and risks of oseltamivir therapy on the breast-fed infant must be considered.
Pediatric patients
• Safety and efficacy in children haven’t been established.
Geriatric patients
• Dosage reduction isn’t required for elderly patients unless creatinine clearance is less than 30 ml/minute.

Patient education
• Advise patient to call as soon as possible to begin treatment within 2 days of symptom onset.
• Tell patient to complete the full 5 days of treatment, even if he feels better.
• Inform patient that oseltamivir may be taken with or without meals and that nausea or vomiting may be relieved by taking drug with food or milk.
• Advise patient to take a missed dose as soon as possible unless the next dose is due within 2 hours. In that case, tell him to skip the dose.
• Tell patient that drug doesn’t replace the influenza virus vaccine. If patient is at risk for influenza, he should continue to receive the vaccine each fall.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use