Zanamivir

332.31

332.31

1592732-453-0

L6O3XI777I

DTXSID0023749

C47786

White to off-white powder

J05AH01|J - Antiinfectives for systemic use

2932999000

201

-3.2

white to beige

1.75±0.1 g/cm3(Predicted)

253-255 °C

1.679

H2O: soluble10mg/mL, clear

-20°C Freezer

4.4X10-18 mm Hg at 25 deg C (est)

D20 +40.9° (c = 0.9 in water)

Henry's Law constant = 4.6X10-30 atm-cu m/mol at 25 °C (est)

Colorless crystals /Sesquihydrate/|Hydroxyl radical reaction rate constant = 2.1X10-10 cu cm/molec-sec at 25 °C (est)|Zwitterionic at physiological pH.

NONH for all modes of transport

3

22-36/37/38

26

RA9451000

Xn

P261-P305 + P351 + P338

H302-H315-H319-H335

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl zanamivir, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 40 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

In randomized controlled trials, 2% to 3% of zanamivir recipients developed ALT or AST elevations above twice the upper limit of the normal range, but a similar rate was found in placebo-treated patients. Despite widespread use, there is little evidence that zanamivir when used by inhalation causes liver injury, either in the form of asymptomatic serum enzyme elevations or clinically apparent liver disease. In pilot studies of intravenous zanamivir for severe influenza, serum enzyme elevations have been reported in ~10% of patients, occasionally with jaundice, but the role of zanamivir versus the underlying severe viral infection has not been defined.

Zanamivir is not a substrate nor does it affect cytochrome P450 (CYP) isoenzymes (CYP1A1/2, 2A6, 2C9, 2C18, 2D6, 2E1, and 3A4) in human liver microsomes.

Bronchospasm and decline in lung function have been reported in some patients receiving relenza. Many but not all of these patients had underlying airways disease such as asthma or chronic obstructive pulmonary disease. Because of the risk of serious adverse events and because efficacy has not been demonstrated in this population, /zanamivir/ is not generally recommend for treatment of patients with underlying airways disease.

Zanamivir has limited plasma protein binding (<10%).

While data specific to zanamivir were not located(SRC, 2006), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through subsoils into aquifers(1).

Zanamivir is distributed in the breast milk of rats. It is unknown if zanamivir is distributed in human breast milk.

For the prevention and treatment of influenza A and B.|FDA Label|Dectova is indicated for the treatment of complicated and potentially life-threatening influenza A or B virus infection in adult and paediatric patients (aged ≥6 months) when:The patient's influenza virus is known or suspected to be resistant to anti-influenza medicinal products other than zanamivir, and/orOther anti-viral medicinal products for treatment of influenza, including inhaled zanamivir, are not suitable for the individual patient.Dectova should be used in accordance with official guidance.|Prevention of influenza, Treatment of influenza

Zanamivir is an inhibitor of the influenza neuraminidase enzyme and is given by inhalation as therapy and prophylaxis against influenza A and B. Zanamivir has not been associated with clinically apparent liver injury, at least when given by inhalation.

Antiviral Agents

Antiviral Agents; Enzyme Inhibitors|At this time, CDC recommends the use of oseltamivir or zanamivir for the treatment of infection with swine influenza (H1N1) viruses.|MEDICATION: Antiviral; Influenza viral neuraminidase inhibitor|Zanamivir is indicated for the treatment of uncomplicated acute illness due to influenza A virus in adults and children 7 years and older who have been symptomatic for no more than 2 days. Zanamivir must be started within 48 hours after the onset of influenza symptoms. /Included in US product labeling/|For more Therapeutic Uses (Complete) data for ZANAMIVIR (6 total), please visit the HSDB record page.

Swine influenza (H1N1) viruses contain a unique combination of gene segments that have not been reported previously among swine or human influenza viruses in the US or elsewhere. The H1N1 viruses are resistant to amantadine and rimantadine but not to oseltamivir or zanamivir.|Bronchospasm and decline in lung function have been reported in some patients receiving relenza. Many but not all of these patients had underlying airways disease such as asthma or chronic obstructive pulmonary disease. Because of the risk of serious adverse events and because efficacy has not been demonstrated in this population, /zanamivir/ is not generally recommend for treatment of patients with underlying airways disease. Some patients with serious adverse events during treatment with /zanamivir/ have had fatal outcomes, although causality was difficult to assess. /Zanamivir/ should be discontinued in any patient who develops bronchospasm or decline in respratory function; immediate treatment and hospitalization may be required. Some patients without prior pulmonary disease may also have respiratory abnormalities from acute respiratory infection that could resemble adverse drug reactions or increase patient vulnerability to adverse drug reactions.|FDA Pregnancy Risk Category: B /NO EVIDENCE OF RISK IN HUMANS. Adequate, well controlled studies in pregnant women have not shown increased risk of fetal abnormalities despite adverse findings in animals, or, in the absence of adequate human studies, animal studies show no fetal risk. The chance of fetal harm is remote but remains a possibility./|Adverse effects occurring in 1-3% or more of adults and children 12 years of age or older include diarrhea; nausea; vomiting; nasal signs and symptoms; bronchitis; sinusitis; cough; ear, nose, and throat infections; headache; and dizziness. No adverse effect occurred at an incidence greater than 3%. Adverse effects occurring in up to 5% of children 5-12 years of age include ear, nose, and throat infections; vomiting; nausea; and diarrhea. Some adverse effects may be secondary to lactose vehicle inhalation. Bronchospasm and allergic-like reactions, including oropharyngeal edema and serious rash, have been reported. Unlike amantadine and rimantadine, neuraminidase inhibitors like zanamivir do not appear to adversely affect the CNS.|For more Drug Warnings (Complete) data for ZANAMIVIR (10 total), please visit the HSDB record page.

Resistance to zanamivir has been produced in vitro by serial passage of influenza virus in the presents of increasing concentrations of the drug, and strains of influenza B with in vitro resistance to zanamivir have emerged rarely during therapy with the drug.

Zanamivir, an antiviral agent, is a neuraminidase inhibitor indicated for treatment of uncomplicated acute illness due to influenza A and B virus in adults and pediatric patients 7 years and older who have been symptomatic for no more than 2 days. Zanamivir has also been shown to significantly inhibit the human sialidases NEU3 and NEU2 in the micromolar range (Ki 3.7 +/-0.48 and 12.9+/-0.07 microM, respectively), which could account for some of the rare side effects of zanamivir.

Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. (See all compounds classified as Antiviral Agents.)|Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)

Absolute bioavailability is very low following oral administration (2%). Following oral inhalation, bioavailability is 4% to 17%.|It is excreted unchanged in the urine with excretion of a single dose completed within 24 hours. Unabsorbed drug is excreted in the feces.Zanamivir is renally excreted as unchanged drug.|2.5 - 10.9 L/h [Following oral inhalation 10 mg]|Protein binding: Very low (<10%).|Orally inhaled zanamivir is systemically absorbed, approximately 4% to 17%.|Elimination: Renal: Excreted unchanged in the urine with excretion of a single dose completed within 24 hours. Total clearance ranges from 2.5 to 10.9 L/hr. Fecal: Unabsorbed drug is secreted in the feces.|Time to peak effect: 72 hours.|For more Absorption, Distribution and Excretion (Complete) data for ZANAMIVIR (7 total), please visit the HSDB record page.

Not metabolized|Not metabolized.

2.5-5.1 hours|The serum half-life of zanamivir following administration by oral inhalation ranges from 2.5 to 5.1 hours.

The proposed mechanism of action of zanamivir is via inhibition of influenza virus neuraminidase with the possibility of alteration of virus particle aggregation and release. By binding and inhibiting the neuraminidase protein, the drug renders the influenza virus unable to escape its host cell and infect others.|Zanamivir is a potent selective competitive inhibitor of the influenza virus neuraminidase, an enzyme essential for viral replication. Neuraminidase cleaves terminal sialic acid residues from glycoconjugates to enable the release of virus from infected cells, prevent the formation of viral aggragates after release from host cells, and possibly decrease viral inactivation by respiratory mucous.|Zanamivir is a selective inhibitor of influenza A and B virus neuraminidase, possibly altering particle aggregation and release.

/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/SIGNS AND SYMPTOMS/ Bronchospasm and decline in lung function have been reported in some patients receiving relenza. Many but not all of these patients had underlying airways disease such as asthma or chronic obstructive pulmonary disease. Because of the risk of serious adverse events and because efficacy has not been demonstrated in this population, /zanamivir/ is not generally recommend for treatment of patients with underlying airways disease. Some patients with serious adverse events during treatment with /zanamivir/ have had fatal outcomes, although causality was difficult to assess. /Zanamivir/ should be discontinued in any patient who develops bronchospasm or decline in respratory function; immediate treatment and hospitalization may be required. Some patients without prior pulmonary disease may also have respiratory abnormalities from acute respiratory infection that could resemble adverse drug reactions or increase patient vulnerability to adverse drug reactions.

2,3-Didehydro-2,4-Dideoxy-4-Guanidino-N-Acetyl-D-Neuraminic Acid

Oral Inhalation: Powder for inhalation (contained in Rotadisk foil pack): 5 mg per inhalation Relenza (with Diskhaler), (GlaxoSmithKline).

Human drugs -> Dectova -> EMA Drug Category|Antivirals for systemic use -> Human pharmacotherapeutic group|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients