Basic Profile / Key Facts
Drug Category
- Antiviral Agents
- Enzyme Inhibitors
Dosage Forms
- Capsule containing 75 mg oseltamivir for oral use and as a powder for oral suspension (which when constituted with water as directed contains 12 mg/mL oseltamivir base)
Indications
For the treatment of uncomplicated acute illness due to influenza infection in patients 1 year and older who have been symptomatic for no more than 2 days. Also for the prophylaxis of influenza in adult patients and adolescents 13 years and older.
Pharmacology
Oseltamivir is an antiviral drug, a neuraminidase inhibitor used in the treatment and prophylaxis of both influenza A and influenza B. Oseltamivir is a prodrug (usually administered as phosphate), it is hydrolysed hepatically to the active metabolite, the free carboxylate of oseltamivir (GS4071). Like zanamivir, oseltamivir acts as a transition-state analogue inhibitor of influenza neuraminidase.
Mechanism of Action
Oseltamivir is an ethyl ester prodrug requiring ester hydrolysis for conversion to the active form, oseltamivir carboxylate. The proposed mechanism of action of oseltamivir is inhibition of influenza virus neuraminidase with the possibility of alteration of virus particle aggregation and release.
Absorption
Readily absorbed from the gastrointestinal tract after oral administration with a bioavailability of 75%.
Toxicity
At present, there has been no experience with overdose. Single doses of up to 1000 mg of oseltamivir have been associated with nausea and/or vomiting. Mean LD (intravenous, mouse) = 100 mg/kg.
Biotrnasformation / Drug Metabolism
Extensively converted to oseltamivir carboxylate by esterases located predominantly in the liver. Neither oseltamivir nor oseltamivir carboxylate is a substrate for, or inhibitor of, cytochrome P450 isoforms. At least 75% of an oral dose reaches the systemic circulation as oseltamivir carboxylate.
Contraindications
TAMIFLU is contraindicated in patients with known hypersensitivity to any of the components of the product.
Drug Interactions
Information derived from pharmacology and pharmacokinetic studies of oseltamivir suggests that clinically
significant drug interactions are unlikely.
Oseltamivir is extensively converted to oseltamivir carboxylate by esterases, located predominantly in the liver.
Drug interactions involving competition for esterases have not been extensively reported in literature. Low protein
binding of oseltamivir and oseltamivir carboxylate suggests that the probability of drug displacement interactions is
low.
In vitro studies demonstrate that neither oseltamivir nor oseltamivir carboxylate is a good substrate for P450
mixed-function oxidases or for glucuronyl transferases.
Cimetidine, a non-specific inhibitor of cytochrome P450 isoforms and competitor for renal tubular secretion of
basic or cationic drugs, has no effect on plasma levels of oseltamivir or oseltamivir carboxylate.
Clinically important drug interactions involving competition for renal tubular secretion are unlikely due to the
known safety margin for most of these drugs, the elimination characteristics of oseltamivir carboxylate (glomerular
filtration and anionic tubular secretion) and the excretion capacity of these pathways. Coadministration of
probenecid results in an approximate twofold increase in exposure to oseltamivir carboxylate due to a decrease in
active anionic tubular secretion in the kidney. However, due to the safety margin of oseltamivir carboxylate, no dose
adjustments are required when coadministering with probenecid.
Coadministration with amoxicillin does not alter plasma levels of either compound, indicating that competition for
the anionic secretion pathway is weak.
In six subjects, multiple doses of oseltamivir did not affect the single-dose pharmacokinetics of
acetaminophen.
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