Neuraminidase Inhibitor

Indicated for the treatment of uncomplicated acute illness due to influenza infection in adults who have been symptomatic for no more than 2 days

C

There are insufficient human data to determine the risk to a pregnant woman or developing fetus. Studies evaluating the effects on embryo-fetal development in rats and rabbits showed a dose-dependent increase in the rates of minor skeleton abnormalities in exposed offspring. The rate of each abnormality remained within the background rate of occurrence in the species studied. Oseltamivir and its metabolite are excreted in the breast milk of lactating rats. It is unknown if they appear in human milk.

Hypersensitivity to any components of the product

Dosage adjustment is required for creatinine clearance between 10-30 mL/minute, only for Influenza A or B infections; has not been evaluated in prevention of these infections; this medicine is not a substitute for the flu shot. Safe and efficacious use in children (<18 years) has not been established. Also consider primary or concomitant bacterial infections.

1% to 10%:

Central nervous system: Insomnia (1.1%), vertigo (1%)

Gastrointestinal: Nausea (10%), vomiting (9%)

<1%: Anemia, humerus fracture, peritonsillar abscess, pneumonia, pseudomembranous colitis, pyrexia, unstable angina

Single doses of 1000 mg resulted in nausea and vomiting

Cimetidine and amoxicillin have no effect on plasma concentrations. Probenecid increases oseltamivir carboxylate serum concentration by twofold. Dosage adjustments are not required.

Oseltamivir, a prodrug, is hydrolyzed to the active form, oseltamivir carboxylate. It is thought to inhibit influenza virus neuraminidase, with the possibility of alteration of virus particle aggregation and release. In clinical studies of the influenza virus, 1.3% of post-treatment isolates had decreased neuraminidase susceptibility to oseltamivir carboxylate.

Absorption: Well absorbed

Distribution: V_d: 23-26 L (oseltamivir carboxylate)

Protein binding: 3% oseltamivir carboxylate; oseltamivir is 42% bound to human plasma products

Metabolism: Converted by hepatic esterases to the active drug, oseltamivir carboxylate. Neither the parent nor active metabolite has any effect on the P-450 system.

Bioavailability: 75% of the dose reaches the systemic circulation in the active form

Half-life: 6-10 hours (oseltamivir carboxylate); similar in geriatric patients (68-78 years of age)

Elimination: 90% of oseltamivir is metabolized to oseltamivir carboxylate; oseltamivir carboxylate is eliminated entirely by renal excretion

Adults: Oral: 75 mg twice daily initiated within 2 days of onset of symptoms; duration of treatment: 5 days

Prophylaxis (investigational use): 75 mg once daily for duration of exposure period (6 weeks has been used in clinical trials)

Dosage adjustment in renal impairment:

Cl_cr 10-30 mL/minute: Reduce dose to 75 mg once daily for 5 days

Cl_cr <10 mL/minute: Has not been studied

Dosage adjustment in hepatic impairment: Has not been evaluated

Elderly: No adjustments required

Take with or without food; take with food to improve tolerance

No information available to require special precautions

No effects or complications reported

Take within 2 days of flu symptoms (fever, cough, headache, fatigue, muscular weakness, and sore throat). This is not a substitute for the flu shot. Not recommended for pregnant or nursing women. For best results, do not miss doses.

Have patient take with food to decrease the nausea associated with this medicine; administer at breakfast and dinner

Capsule, as phosphate: 75 mg (blister package 10)

Anonymous, "Neuraminidase Inhibitors for Treatment of Influenza A and B Infections," MMWR, 1999, 48(RR-14):1-9.

Bardsley-Elliot A and Noble S, "Oseltamivir," Drugs, 1999, 58(5):851-60.

Hayden FG, Atmar RL, Schilling M, et al, "Use of the Selective Oral Neuraminidase Inhibitor Oseltamivir to Prevent Influenza," N Engl J Med, 1999, 341(18):1387-8.

He G, Massarella J, and Ward P, "Clinical Pharmacokinetics of the Prodrug Oseltamivir and Its Active Metabolite Ro 64-0802," 1999, 37(6):471-84.

JAMA, 1999, 282:1240-6.