This chemical does not meet GHS hazard criteria for 2.5% (1 of 40) of reports.
Warning
H302 (97.5%): Harmful if swallowed [Warning Acute toxicity, oral]
P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 40 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Warning
危険有害性情報
FDA Requirements · 1 件
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.
Hazard Classes and Categories · 2 件
Acute Tox. 4 (97.5%)
Acute Tox. 4 (100%)
安全と保護具
Disposal Methods · 1 件
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.
毒性情報
化学と産業
薬理情報
ATC Code · 2 件
J - Antiinfectives for systemic use
QJ - Antiinfectives for systemic use
Protein BindingZanamivir has limited plasma protein binding (<10%).
Pharmacodynamics · 1 件
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.
Mechanism of Action · 3 件
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.
Biological Half-Life · 2 件
2.5-5.1 hours
The serum half-life of zanamivir following administration by oral inhalation ranges from 2.5 to 5.1 hours.
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.
Hepatotoxicity · 1 件
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.
Milk ConcentrationsZanamivir is distributed in the breast milk of rats. It is unknown if zanamivir is distributed in human breast milk.
Human Toxicity Excerpts · 1 件
/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.
Drug Induced Liver Injury · 5 件
Drug-Induced Liver Injury Severity and Toxicity (DILIst)
Zanamivir
DILI Negative
Oral; Respiratory (inhalation)
DOI:10.1016/j.drudis.2019.09.022
Non-Human Toxicity Excerpts · 5 件
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In 2-year carcinogenicity studies conducted in rats and mice using a powder formulation administered through inhalation, zanamivir induced no statistically significant increases in tumors over controls. The maximum daily exposures in rats and mice were approximately 23 to 25 and 20 to 22 times, respectively, greater than those in humans at the proposed clinical dose based on AUC comparisons.
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ An increase in lymphoma incidence over controls was seen male rats given a high dose (30 to 50 mg/kg/day); there was no dose relationship.
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Embryo/fetal development studies were conducted in rats (dosed from days 6 to 15 of pregnancy) and rabbits (dosed from days 7 to 19 of pregnancy) using the same IV doses. Pre- and post-natal developmental studies were performed in rats (dosed from day 16 of pregnancy until litter day 21 to 23). In all studies, intravenous (1, 9, and 90 mg/kg/day) instead of the inhalational route of drug administration was used. No malformations, maternal toxicity, or embryotoxicity were observed in pregnant rats or rabbits and their fetuses. Because of insufficient blood sampling timepoints in both rat and rabbit reproductive toxicity studies, AUC values were not available. However, in a subchronic study in rats at the 90-mg/kg/day IV dose, the AUC values were greater than 300 times the human exposure at the proposed clinical dose.
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ An additional embryo/fetal study, in a different strain of rat, was conducted using subcutaneous administration of zanamivir, 3 times daily, at doses of 1, 9, or 80 mg/kg during days 7 to 17 of pregnancy. There was an increase in the incidence rates of a variety of minor skeleton alterations and variants in the exposed offspring in this study. Based on AUC measurements, the high dose in the study produced an exposure greater than 1,000 times the human exposure at the proposed clinical dose. However, the individual incidence rate of each skeletal alteration or variant, in most instances, remained within the background rates of the historical occurrence in the strain studied.
/GENOTOXICITY/ Zanamivir was not mutagenic in in vitro and in vivo genotoxicity assays which included bacterial mutation assays in S. typhimurium and E. coli , mammalian mutation assays in mouse lymphoma, chromosomal aberration assays in human peripheral blood lymphocytes, and the in vivo mouse bone marrow micronucleus assay.
Populations at Special Risk · 1 件
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.
Environmental Water Concentrations · 1 件
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).
Antidote and Emergency Treatment · 2 件
/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/
Effects During Pregnancy and Lactation◉ Summary of Use during Lactation
法規制情報
FDA Requirements · 1 件
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.
安全データ
wgk
3
rtecs
RA9451000
hs_code
2932999000
risk_code
22-36/37/38
hazard_code
Xn
safety_code
26
Hazard Classifications
Acute Tox. 4 OralEye Irrit. 2Skin Irrit. 2STOT SE 3
ストレージクラス
11 - Combustible Solids
有毒物質データの
139110-80-8(Hazardous Substances Data)
Established Pharmacologic Class [EPC] - Neuraminidase Inhibitor
Mechanisms of Action [MoA] - Neuraminidase Inhibitors
Zanamivir is a Neuraminidase Inhibitor. The mechanism of action of zanamivir is as a Neuraminidase Inhibitor.
ZANAMIVIR
MeSH Pharmacological Classification · 2 件
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Absorption, Distribution and Excretion · 6 件
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.
Cellular LocationsCytoplasm
用途と製造
Uses · 3 件
Antiviral
Medication
Antiviral Agents; Enzyme Inhibitors
Methods of ManufacturingL. M. von Itzstein et al., WO 91 16320; eidem, US patent 5360817 (1991, 1994 both to Biota)
Formulations/PreparationsOral Inhalation: Powder for inhalation (contained in Rotadisk foil pack): 5 mg per inhalation Relenza (with Diskhaler), (GlaxoSmithKline).
説明Zanamivir was launched as Relenza in Australia for treatment of human influenza A and B virus infections. Zanamivir (4-guanidino-Neu5Ac2en) can be obtained by several similar ways, for instance in seven step synthesis starting from N-acetyI-D-neuraminic acid. Mechanistically, Zanamivir is a potent and specific inhibitor of neuraminidase (or sialidase), a key viral surface glycohydrolase essential for viral replication and disease progression by catalyzing the cleavage of terminal sialic acid residues from the glycoprotein. The in vitro activity of Zanamivir against a wide variety of influenza A and B strains was demonstrated in different model systems; its activity against clinically relevant isolates of influenza virus, with IC50 values ranging from 0.005 to 15 pM was superior to those of amantadine and rimantadine.
使用ZANAMIVIR HYDRATE is a sialic acid analog that inhibits neuraminidase release of newly replicated influenza virus particles. It has been shown to selectively inhibit the growth of influenza A and B viruses in plaque reduction assays with IC50 values ranging from 5 to 14 nM and to directly inhibit influenza A and B virus neuraminidases with IC50 values ranging from 0.6 to 7.9 nM in vitro. The efficacy and tolerabilbity of zanamivir has also been established in clinical trial.[Cayman Chemical]
一般的な説明Zanamivir is identical to 2-deoxy-2,3-dehydro-N-acetylneuraminic acid except that itpossesses a guanidino group at position 4 instead of a hydroxylgroup. At positions 119 and 227 of the receptor site,there exist glutamic acid residues. Zanamivir has beenshown to form a salt bridge with the guanidine and Glu-119and a charge transfer interaction with Glu-227. These interactionsincrease the interaction strength with the enzymeand create an excellent competitive inhibitor and an effectiveantiviral agent for influenza types A and B.Human studies have shown that zanamivir is effectivewhen administered before or after exposure to the influenzavirus. If administered before exposure to the virus, the drugreduced viral propagation, infectivity, and disease symptoms.If administered after exposure, the drug reduces propagation,viral titer, and illness. Zanamivir is marketed as a dry powderfor oral inhalation. It is used in adolescents and adults who have been exposed and are symptomatic for not more than 2days. Zanamivir is also indicated for prophylactically treatingfamily members of a person who has developed influenza.
