Source: Health Products Regulatory Authority (ZA) Revision Year: 2020 Publisher: Strides Pharma SA (Pty) Ltd, 106 16<sup>th</sup> Road, Building 2, Midrand, 1686
Pharmacological classification: A 20.2.8 Antivirals agents.
Pharmacotherapeutic group: Antivirals for systemic use, neuraminidase inhibitors
ATC code: J05AH02
Oseltamivir phosphate is a pro-medicine and selective inhibitor of influenza virus neuraminidase enzymes. Viral neuraminidase is essential for the release of recently formed virus particles from infected cells, and the further spread of infectious virus. The active metabolite of oseltamivir inhibits neuraminidases of influenza viruses of both types A and B. The active metabolite also inhibits influenza virus growth in vitro and inhibits influenza virus replication and pathogenicity in viva. The active metabolite reduces shedding of both influenza A and B virus by inhibiting the release of infectious virus from infected cells.
Not applicable.
Oseltamivir is readily absorbed from the gastrointestinal tract after oral administration of oseltamivir phosphate and is extensively converted predominantly by hepatic esterases to the active metabolite. Plasma concentrations of the active metabolite are measurable within 30 minutes, reach near maximal levels in 2 to 3 hours post dose, and substantially exceed (>20-fold) those of the pro-medicine. At least 75% of an oral dose reaches the systemic circulation as the active metabolite. Plasma concentrations of the active metabolite are proportional to the dose and are unaffected by co-administration with food (see section 4.2).
The mean volume of distribution (Vss) of the active metabolite is approximately 23 litres in humans. The active moiety reaches all key sites of influenza infections as shown by animal studies. The binding of the active metabolite to human plasma protein is negligible (approximately 3%). The binding of the pro-medicine to human plasma protein is 42%. These levels are insufficient to cause significant medicine interactions.
Oseltamivir phosphate is extensively converted to the active metabolite by esterases located predominantly in the liver. Neither oseltamivir nor the active metabolite is substrates for or inhibitors of cytochrome P450 isoforms (see section 4.5).
Absorbed oseltamivir is primarily (>90%) eliminated by conversion to the active metabolite. The active metabolite is not further metabolised and is eliminated in the urine. Peak plasma concentrations of the active metabolite decline with a half-life of 6-10 hours in most subjects. The active metabolite is eliminated entirely (>99%) by renal excretion. Renal clearance (18,8 I/h) exceeds glomerular filtration rate (7,5 I/h) indicating that tubular secretion in addition to glomerular filtration occurs. Less than 20% of an oral radiolabeled dose is eliminated in faeces.
Not applicable.
Not applicable.
Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated-dose toxicity and genotoxicity.
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