Oseltamivir Chemical Properties

Melting point:

107-108 °C

Boiling point:

473.3±45.0 °C(Predicted)

Density 

1.08±0.1 g/cm3(Predicted)

storage temp. 

2-8°C(protect from light)

solubility 

Chloroform (Sparingly), DMSO (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly)

form 

Solid

pka

7.7 (25°); 6.6 (70°)

color 

Off-White to Pale Beige

Stability:

Hygroscopic

CAS DataBase Reference

196618-13-0

EPA Substance Registry System

1-Cyclohexene-1-carboxylic acid, 4-(acetylamino)-5-amino-3-(1-ethylpropoxy)-, ethyl ester, (3R,4R,5S)- (196618-13-0)

Safety Information

Hazardous Substances Data

196618-13-0(Hazardous Substances Data)

Oseltamivir Usage And Synthesis

Description

Oseltamivir is a drug that suppresses the action of influenza A, influenza B, and H1N1 influenza viruses in children and adults. Oseltamivir is administered for the treatment of influenza (flu) for people who are above the age of 2 weeks and have been experiencing flu-like symptoms for less than two days. Oseltamivir may also be prescribed for people who are above 1-year-old as a protective measure to prevent them from contracting influenza due to exposure to the virus without necessarily having indicated any symptoms of infection. The drug may not treat common cold. Oseltamivir goes by the brand name Tamiflu.

Indications

Oseltamivir is prescribed for the treatment of mild or severe illness that results from infection with influenza A or B virus for patients above the age of 2 weeks, and have been experiencing flu-like symptoms for less than 48 hours. The drug is also used for preventive treatment against influenza amongst adolescents above 13 years and adults.

Contraindications

Oseltamivir is contraindicated in patients who may be hypersensitive to the medication or any of the ingredients in its formulation.

Dosage

For best results, Oseltamivir should be administered orally at least within two days of the onset of symptoms or exposure to influenza. The recommended dosage for treatment in adults with influenza is 74mg taken twice per day for 5 days.
In children, the recommended dosage should be 30-75mg (for children between 15kg and 40kg) take twice per day for 5 days, where dosing also depends on the body weight of the patient. For children who are 2 weeks old but <1 year, 3mg/kg should be administered orally two times per day.
For flu prevention in adults, 75mg of Oseltamivir should be administered on a daily basis for 10 days, whereas in children, 30-75mg should be given once per day for 10 days.

Interactions

Drug interactions may influence the effectiveness of certain medications and may increase the risk of exposure to adverse side effects hence the need to consult a doctor with the list of other medications that one might be taking while getting a prescription for Oseltamivir.
A patient should notify their healthcare provider if they have received any nasal flu vaccines within 2 weeks before the administration of the first dose of Oseltamivir.
This drug may reduce protection against flu if the vaccine has been administered through the nose. One should wait for 2 weeks after the treatment with Oseltamivir before nasal administration of the flu vaccine.

Mechanism of Action

The drug is an ethyl ester prodrug that necessitates hydrolysis for modification into the radical form, Oseltamivir carboxylate. The suggested mechanism of action of the drug is suppression of the influenza virus neuraminidase, which increases the probability of modification of the virus molecule, amalgamation and release.
Oseltamivir inhibits the spread of the influenza virus by preventing the action of neuraminidase, the enzyme that allows the spread of the virus from infected cells to those that are not infected. Oseltamivir inhibits the intercellular proliferation of the virus hence the duration and symptoms associated with influenza are also reduced. The length of the presenting symptoms may be reduced by one and a half days if treatment is initiated within 2 days at the onset of the flu symptoms.

Pharmacodynamics

Oseltamivir is an antiviral medication, a neuraminidase suppressor that is used in prophylaxis and treatment of influenza A and B viruses. It is a prodrug that is prescribed as a phosphate, which is hydrolyzed hepatically into the radical metabolite, the unbound carboxylate of the drug (GS4071). Oseltamivir functions as a transitional analog suppressor of influenza neuraminidase.

Elimination

Upon primary absorption, >90% of Oseltamivir is eliminated by transformation into Oseltamivir carboxylate. The converted form of the drug does not undergo further metabolism, and it is excreted in urine. A significant portion, >99% of the Oseltamivir carboxylate is expelled from the body by renal excretion.

Side Effects

Common side effects associated with Oseltamivir include dizziness, headache, abdominal pain, bronchitis, diarrhea, vomiting, and nausea. Taking Oseltamivir after meals may help in reducing nausea. Other adverse side effects may include exacerbation of diabetes, behavioral disturbances, seizures, skin reactions, and allergic reactions.
A patient may need to seek emergency help if they are using Oseltamivir and they experience hallucinations, unusual behavior, shaking/tremors, and sudden confusion.
One should also consult their doctor if they are experiencing signs of an allergic reaction to the drug which may include hives, swelling in the throat or the face, difficulties in breathing, severe skin reactions such as a purple or red skin rash, sore throat, skin pain, peeling, burning eyes, and blistering.

Originator

Tamiflu,Hoffmann-La Roche Inc

Uses

Oseltamivir is an orally active inhibitor of influenza virus neuraminidase; converted in vivo to the active acid metabolite. An antiviral drug. It is a COVID19-related research product.

Indications

Oseltamivir phosphate (Tamiflu) is the ethyl ester prodrug of oseltamivir carboxylate, an analogue of neuraminic (sialic) acid that is a reversible competitive antagonist of influenza A and B neuraminidase.Influenza virus resistant to oseltamivir has not been found in naturally acquired isolates but has been isolated from influenza patients who have undergone treatment with this drug.These resistant strains contain mutations in the active site of neuraminidase and are generally less virulent and infective than nonresistant virus. In vitro passage of influenza virus in the presence of oseltamivir carboxylate can produce mutations in hemagglutinin that decrease the overall dependence of viral replication on neuraminidase; however, the clinical relevance of this resistance mechanism is unknown.

Definition

ChEBI: A cyclohexenecarboxylate ester that is the ethyl ester of oseltamivir acid. An antiviral prodrug (it is hydrolysed to the active free carboxylic acid in the liver), it is used to slow the spread of influenza.

Therapeutic Function

Antiviral

Antimicrobial activity

Oseltamivir is active against influenza A and B, but no other virus.

Acquired resistance

Mutations in the neuraminidase (H274Y) have been detected in treated patients with seasonal H1N1 infection. Cross-resistance with zanamivir has been described in vitro.

Pharmaceutical Applications

A selective neuraminidase inhibitor, formulated as the phosphate salt of the ethyl ester for oral administration.

Pharmacokinetics

Oral absorption: c. 75%
C_max 75 mg oral: 0.35–0.55 mg/L after 4 h
Plasma half-life: 7–9 h
Plasma protein binding: Not known
The ethyl ester prodrug is hydrolyzed by hepatic esterases to release the active compound, oseltamivir carboxylate. Drug is excreted in the urine as the carboxylate derivative.

Clinical Use

Treatment and prevention of susceptible influenza A (H3N2) and B infections in adults and young children

Clinical Use

Oseltamivir is approved for the treatment of uncomplicated acute influenza in patients aged 1 year and older. It decreases the duration of illness by 1 to 1.5 days when treatment is initiated within 48 hours of the onset of symptoms. Oseltamivir is also indicated for the prophylaxis of influenza in individuals aged 13 and older. It reduces infection rates to approximately 10 to 25% of that found in untreated populations; however, it is not intended to substitute for the early vaccination recommended by the CDC. Oseltamivir can be used as postexposure prophylaxis in household contacts of infected patients, with infection rates of treated patients around 10% of placebo control levels.

Side effects

The most frequently reported adverse effects of oseltamivir are nausea and vomiting.These events are usually mild to moderate, occur during the first 1 to 2 days of treatment, and can be lessened by taking the drug with food. Bronchitis, insomnia, and vertigo may also occur. Oseltamivir may not be indicated for use in certain individuals. Its efficacy in patients with chronic cardiac or respiratory disease has not been established. In clinical trials, no difference in the incidence of complications was seen between treatment and control groups. The efficacy of oseltamivir has not been demonstrated in immunocompromised patients, patients who begin treatment after 40 hours of symptoms, or patients given repeated prophylactic courses of therapy. Dosage adjustment is recommended for individuals with renal insufficiency; the drug’s safety in patients with hepatic insufficiency is unknown.

Side effects

Adverse events relate to the gastrointestinal tract; the most common is nausea with or without vomiting in 10% of patients. Food alleviates side effects.

Metabolism

Oseltamivir is a prodrug; it is extensively metabolised by esterases in the liver to the active carboxylate metabolite.
Oseltamivir carboxylate is not further metabolised and is eliminated entirely by renal excretion. Renal clearance exceeds glomerular filtration rate indicating that tubular secretion occurs in addition to glomerular filtration. Less than 20% of an oral radiolabelled dose is eliminated in faeces.

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