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Amoxicillin
amoxycillin · AMOXYCILLIN TRIHYDRATE · Augmentin · Amoxicilline · amoxil · AMOXICILIN TRIHYDRATE · AMOXICILLIN USP(CRM STANDARD) · 4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylicacid,6-((amino(4-hydroxyphenyl)
Identifikatoren & physikalische Daten
| CAS No. | 26787-78-0 |
|---|---|
| Summenformel | C16H19N3O5S |
| Durchschnittliche Molmasse | 365,4 g/mol |
| Monoisotopische Masse | 365,10454189 g/mol |
| SMILES | CC1(C)S[C@@H]2[C@H](NC(=O)[C@H](N)c3ccc(O)cc3)C(=O)N2[C@H]1C(=O)O |
| InChIKey | LSQZJLSUYDQPKJ-NJBDSQKTSA-N |
| PubChem CID | 33613 |
| ChEMBL | CHEMBL1082 |
| ChEBI | CHEBI:2676 |
| EC No. | 248-003-8 |
| DTXSID | DTXSID3037044 |
| Lokaler Name | Amoxicillin |
Chemische & physikalische Eigenschaften
| XLogP | -2 |
|---|---|
| Polarare Oberfläche (TPSA) | 158 |
| H-Brücken-Donoren | 4 |
| H-Brücken-Akzeptoren | 7 |
| Frei drehbare Bindungen | 4 |
| Schwere Atome | 25 |
| Formalladung | 0 |
| Komplexität | 590 |
| LogP (Verteilungskoeffizient) | 0.87log Kow = 0.87 |
| Geruch | Penicillin-type odor |
| Geschmack | Bitter tasting |
| Color/Form | Crystals from water |
| Löslichkeit | Soluble in water1 g sol in about 370 mL water, about 2000 mL alc, about 290 mL phosphate buffer (1%, ph 7), about 330 mL methanol9.58e-01 g/L10.7 [ug/mL] (The mean of the results at pH 7.4)4g/L at 25℃ |
| Siedepunkt | 743.2743.2±60.0 °C(Predicted) |
| Schmelzpunkt | 194194 °C140 °C |
| Optical Rotation | Specific optical rotation: +248 deg to +268 deg |
| Caco2 Permeability | -6.1 |
| Physical Description | Off-white solid[HSDB] |
| Stability/Shelf Life | Stable under recommended storage conditions.Following reconstitution, amoxicillin oral suspensions should preferably be refrigerated at 2-8 °C, but refrigeration is not necessary and the suspension are stable for 14 days at room temp or 2-8 °C |
| Dissociation Constants | 2.6 |
| Dichte | 1.54±0.1 g/cm3(Predicted) |
| Dampfdruck | 0Pa at 25℃ |
| Lagerbedingungen | 2-8°C |
| pKa (Säurekonstante) | pKa 2.4 (Uncertain) |
| Aggregatzustand | solid |
| Farbe | Light yellow |
| Merck | 13,582 |
| BRN | 7507120 |
| BCS Class | 1,3 |
| Stabilität | Stable. Incompatible with strong oxidizing agents. |
| InChI | 1S/C16H19N3O5S/c1-16(2)11(15(23)24)19-13(22)10(14(19)25-16)18-12(21)9(17)7-3-5-8(20)6-4-7/h3-6,9-11,14,20H,17H2,1-2H3,(H,18,21)(H,23,24)/t9-,10-,11+,14-/m1/s1 |
| InChIKey | LSQZJLSUYDQPKJ-UWFZAAFLSA-N |
| SMILES | CC1(C)S[C@@H]2[C@H](NC(=O)[C@H](N)c3ccc(O)cc3)C(=O)N2[C@H]1C(O)=O |
| LogP (Verteilungskoeffizient) | 0.87 at 25℃ |
| CAS Datenbank | 26787-78-0(CAS DataBase Reference) |
| EPA chemische Informationen | 4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-, (2S,5R,6R)- (26787-78-0) |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]H334 (98.3%): May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]P233, P260, P261, P271, P272, P280, P284, P302+P352, P304+P340, P321, P333+P317, P342+P316, P362+P364, P403, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 59 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website. |
|---|---|
| Regulatorische Informationen | Status: Active Update: 14-10-2020 https://echa.europa.eu/registration-dossier/-/registered-dossier/12616Amoxicillin: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right. |
| Weitere Sicherheitsinformationen | IMAP assessments - 4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[[amino(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-, [2S-[2.alpha.,5.alpha.,6.beta.(S*)]]-: Environment tier I assessmentIMAP assessments - 4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[[amino(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-, [2S-[2.alpha.,5.alpha.,6.beta.(S*)]]-: Human health tier I assessment |
| Gefahrenübersicht | Occupational asthma confirmed in a pharmaceutical worker[Malo] Causes contact urticaria[Kanerva, p. 219] |
| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including amoxicillin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Amoxicillin trihydrate is included on this list. /Amoxicillin trihydrate/Oral Dosage Form New Animal Drugs. ... Indications for use /in dogs/. Treatment of infections of the respiratory tract (tonsillitis, tracheobronchitis), genitourinary tract (cystitis), gastrointestinal tract (bacterial gastroenteritis), and soft tissues (abscesses, lacerations, wounds), caused by susceptible strains of Staphylococcus aureus, Streptococcus spp., Escherichia coli, Proteus mirabilis, and bacterial dermatitis caused by S. aureus, Streptococcus spp., and P. mirabilis. ... Indications for use /in cats/. Treatment of infections caused by susceptible organisms as follows: upper respiratory tract due to S. aureus, Streptococcus spp., and E. coligenitourinary tract (cystitis) due to S. aureus, Streptococcus spp., E. coli, and P. mirabilisgastrointestinal tract due to E. coliand skin and soft tissue (abscesses, lacerations, and wounds) due to S. aureus, Streptococcus spp., E. coli, and Pasteurella multocida. ... Federal law restricts this drug to use by or on the order of a licensed veterinarian. /Amoxicillin trihydrate film-coated tablets/Oral Dosage Form New Animal Drugs. ... Indications for use /in dogs/: Treatment of infections caused by susceptible strains of organisms as follows: respiratory tract (tonsillitis, tracheobronchitis) caused by Staphylococcus aureus, Streptococcus spp., Escherichia coli, and Proteus mirabilisgenitourinary tract (cystitis) caused by S. aureus, Streptococcus spp., E. coli, and P. mirabilisgastrointestinal tract (bacterial gastroenteritis) caused by S. aureus, Streptococcus spp., E. coli, and P. mirabilisbacterial dermatitis caused by S. aureus, Streptococcus spp., and P. mirabilisand soft tissues (abscesses, lacerations, and wounds) caused by S. aureus, Streptococcus spp., E. coli, and P. mirabilis. ... Indications for use /in cats/: Treatment of infections caused by susceptible strains of organisms as follows: upper respiratory tract due to Staphylococcus spp., Streptococcus spp., Haemophilus spp., E. coli, Pasteurella spp., and P. mirabilisgenitourinary tract (cystitis) due to S. aureus, Streptococcus spp., E. coli, P. mirabilis, and Corynebacterium spp.gastrointestinal tract due to E. coli, Proteus spp., Staphylococcus spp., and Streptococcus spp.skin and soft tissue (abscesses, lacerations, and wounds) due to Staphylococcus spp., Streptococcus spp., E. coli, and Pasteurella multocida. ... Indications for use /in dogs/: Treatment of bacterial dermatitis due to S. aureus, Streptococcus spp., Staphylococcus spp., and E. coli, and soft tissue infections (abscesses, wounds, lacerations) due to S. aureus, Streptococcus spp., E. coli, P. mirabilis and Staphylococcus spp. Limitations. Federal law restricts this drug to use by or on the order of a licensed veterinarian. /Amoxicillin trihydrate for oral suspension/For more FDA Requirements (Complete) data for AMOXICILLIN (13 total), please visit the HSDB record page. |
| Toxic Combustion Products | Special hazards arising from the substance or mixture: Carbon oxides, nitrogen oxides (NOx), sulfur oxides |
| Hazard Classes and Categories | Skin Sens. 1 (100%)Resp. Sens. 1 (98.3%) |
| Hazardous Reactivities and Incompatibilities | Incompatible materials: Oxidizing agents. |
| Brandbekämpfungsverfahren | Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary. |
| Lagerbedingungen | Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature 2 - 8 °C.Amoxicillin capsules, 125- and 250-mg chewable tablets, and powder for oral suspension should be stored in tight containers at 20 °C or loweramoxicillin 200- and 400-mg chewable tablets and amoxicillin film-coated tablets should be stored in tight containers at 25 °C or lower. |
| Reinigungsverfahren | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. |
| Entsorgungsverfahren | SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubberContaminated packaging: Dispose of as unused product. |
| Preventive Measures | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains.Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker. |
| Allowable Tolerances | A tolerance of 0.01 part per million is established for negligible residues of amoxicillin in milk and in the uncooked edible tissues of cattle. |
| Personal Protective Equipment (PPE) | Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).Skin protection: Handle with gloves.Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). |
| Körperbelastung | It has been reported that 60% of amoxicillin ingested is excreted in urine from the human body(1). |
| Wechselwirkungen | Amoxicillin may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.Concomitant use of penicillins (e.g., amoxicillin, carbenicillin) may decrease renal clearance of methotrexate, presumably by inhibiting renal tubular secretion of the drug. Increased serum concentrations of methotrexate, resulting in GI or hematologic toxicity, have been reported in patients receiving concomitant administration of low- or high-dose methotrexate therapy with penicillins. Patients receiving methotrexate and penicillins concomitantly should be monitored carefully.Chloramphenicol, macrolides, sulfonamides, and tetracyclines may interfere with the bactericidal effects of penicillin. This has been demonstrated in vitrohowever, the clinical significance of this interaction is not well documented.Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use of amoxicillin and probenecid may result in increased and prolonged blood levels of amoxicillin.For more Interactions (Complete) data for AMOXICILLIN (7 total), please visit the HSDB record page. |
| Hepatotoxicity | Rare instances of idiosyncratic liver injury have been reported in persons receiving the aminopenicillins including amoxicillin. Cases are characterized by a short latency period of a few days to as long as two weeks. The onset of liver injury can occur after the antibiotic is stopped. The serum enzyme pattern associated with aminopenicillin liver injury has included a hepatocellular pattern with marked elevations in ALT and AST, and minimal elevations in alkaline phosphatase and rapid recovery after withdrawal. In addition, cholestatic forms of hepatic injury with marked alkaline phosphatase elevations (as also seen with penicillin-induced liver injury) have also been described, some of which have been associated with prolonged cholestasis (Case 1). The onset of hepatic injury may be accompanied by signs or symptoms of hypersensitivity such as eosinophilia, rash and arthralgias, and in some cases is accompanied by toxic epidermal necrolysis or Stevens Johnson syndrome.Much more common than liver injury from amoxicillin alone is the typically cholestatic hepatitis that occurs after treatment with the combination of amoxicillin and clavulanate. Indeed, this combination is currently the most common cause of idiosyncratic acute liver injury in the United States, Europe and Australia. The injury, however, is usually attributed to the clavulanate rather than amoxicillin. The clinical features are similar but perhaps not completely the same. In cases of liver injury seeming due to amoxicillin, an extra effort should be made to make sure that it was not amoxicillin-clavulanate [Augmentin] that was taken.Likelihood score: B (highly likely but rare cause of clinically apparent liver injury). |
| Ökotoxizitätswerte | EC50Species: Microcystis aeruginosa (Blue-Green Algae) exponential growth phase, nonaxenic, 2X10+6 cells/mLConditions: freshwater, static, 21 °C, pH 7.9Concentration: 3.7 ug/L for 7 daysEffect: population, increased chlorophyll A concentration />99.9% purity/Species: Anabaena sp. (Blue-Green Algae) PCC 7120, strain CPB4337Conditions: freshwater, static, 28 °CConcentration: 56300 ug/L for 72 hrEffect: population, decreased population growth rate /> or =90% purity/Species: Pseudokirchneriella subcapitata (Green Algae)Conditions: freshwater, static, 22 °CConcentration: >1500000 ug/L for 72 hrSpecies: Danio rerio (Zebra Danio) embryo, newly fertilized eggsConditions: freshwater, static, 27 °C, pH 7.5Concentration: 132400 ug/L for 48 hrEffect: increased hatch mortality /formulation/For more Ecotoxicity Values (Complete) data for AMOXICILLIN (11 total), please visit the HSDB record page. |
| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 100(SRC), determined from a structure estimation method(2), indicates that amoxicillin is expected to have high mobility in soil(SRC). Volatilization of amoxicillin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.5X10-21 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Amoxicillin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.7X10-17 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Using the Closed Bottle test, amoxicillin, present at 3.27 mg/L, was not biodegraded(4), suggesting that biodegradation is not an important environmental fate process in soil(SRC).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 100(SRC), determined from a structure estimation method(2), indicates that amoxicillin is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.5X10-21 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow of 0.87(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Using the Closed Bottle test, amoxicillin, present at 3.27 mg/L, was not biodegraded(7), suggesting that biodegradation is not an important environmental fate process in water(SRC). Using the Zahn-Wellens test in combination with HPLC-UV-VIS, 94% loss was observed. This complete mineralization was attributed to hydrolysis(7).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), amoxicillin, which has an estimated vapor pressure of 4.7X10-17 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase amoxicillin may be removed from the air by wet and dry deposition(SRC). Amoxicillin contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). |
| Unerwünschte Wirkungen | Asthma - Reversible bronchoconstriction (narrowing of bronchioles) initiated by the inhalation of irritating or allergenic agents.Common Adverse Drug ReactionsAlthough generally well-tolerated, amoxicillin may lead to common gastrointestinal symptoms, including nausea, vomiting, and diarrhea. Additional adverse drug reactions associated with amoxicillin are listed below.Superinfections: Mucocutaneous candidiasis and Clostridium difficile–associated diarrhea (CDAD) are potential adverse effects of amoxicillin. Notably, individuals taking amoxicillin may experience less diarrhea than those taking ampicillin due to better absorption in the gut.Nephrotoxicity: Amoxicillin may cause crystalluria and interstitial nephritis.Hypersensitivity reactions: Amoxicillin has the potential to cause hypersensitivity reactions categorized as type I, II, III, or IV. Differentiating between a type-I and type-IV reaction is crucial due to varying danger levels. A type-I hypersensitivity reaction involves an IgE-mediated response in sensitized patients, inducing widespread histamine release, resulting in an urticarial-like pruritic rash or severe anaphylaxis. In contrast, a type-IV hypersensitivity reaction is not mediated by histamine release and typically presents as a more papular or morbilliform rash, often without itching. Notably, almost all patients receiving amoxicillin inadvertently for infectious mononucleosis may develop a maculopapular rash attributed to a type IV–mediated hypersensitivity reaction. Notably, reactions of this type are not associated with anaphylaxis.Hepatotoxicity: Cases of idiosyncratic liver injury have been reported in individuals receiving amoxicillin. The associated serum enzyme pattern reveals a hepatocellular pattern characterized by significant elevations in aspartate transaminase (AST) and alanine transaminase (ALT), with minimal increases in alkaline phosphatase. Most patients experience rapid recovery upon withdrawal of amoxicillin. The cause of liver injury associated with amoxicillin use is attributed to hypersensitivity. Although rare, cases of acute liver failure and vanishing bile duct syndrome have been reported. Corticosteroids are often used to treat allergic reactions caused by penicillin-related immunoallergic hepatitis, which is a rare cause of clinically apparent liver injury, with a likelihood score of B.Postmarketing Adverse Drug ReactionsGastrointestinal: Gastrointestinal effects may include black hairy tongue, pseudomembranous colitis, and hemorrhagic colitis.Neurological: Neurological effects may encompass reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, and aseptic meningitis.Hematological: Hematological effects may include hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and neutropenia.Dermatological: Dermatological effects may manifest as serum sickness-like reactions, erythematous maculopapular rashes, exfoliative dermatitis, toxic epidermal necrolysis, and hypersensitivity vasculitis.Drug-Drug Interactions* Concomitant use of probenecid diminishes the renal tubular secretion of amoxicillin, leading to increased and prolonged amoxicillin blood levels.* Amoxicillin can induce abnormal prolongation of prothrombin time (increased INR) in patients taking oral anticoagulants, requiring meticulous monitoring and potential dosage adjustments for anticoagulation.* Concurrent administration of amoxicillin and allopurinol increases the incidence of rashes compared to amoxicillin alone.* Amoxicillin may alter intestinal flora, leading to reduced estrogen reabsorption and potentially diminishing the efficacy of combined oral estrogen or progesterone contraceptives.* Chloramphenicol, macrolides, sulfonamides, and tetracyclines can interfere with the bactericidal effects of penicillin, although the clinical significance of this interaction is not extensively documented. In general, clinicians are advised to avoid combining bacteriostatic and bactericidal drugs.* Intravesical BCG therapy should not be administered concomitantly with antibiotics, including amoxicillin, to mitigate the potential risk of interference with the clinical response to intravesical BCG.Drug-Laboratory Test InteractionsHigh urine concentrations of amoxicillin can cause false-positive reactions in urine glucose tests using certain detection methods. Clinicians should consider using alternative enzymatic glucose oxidase-based tests. |
| Milk Concentrations | Because amoxicillin is distributed into milk and may lead to sensitization of infants, the drug should be used with caution in nursing women. Because of its general safety in infants, the CDC states that amoxicillin is an option for anti-infective prophylaxis in breast-feeding women when Bacillus anthracis is known to be penicillin susceptible and there is no contraindication to maternal amoxicillin use. |
| Toxizitätsübersicht | IDENTIFICATION AND USE: Amoxicillin is a semi-synthetic antibiotic related to penicillin. HUMAN EXPOSURE AND TOXICITY: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy including amoxicillin. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before initiating therapy with amoxicillin, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, amoxicillin should be discontinued and appropriate therapy instituted. There was no evidence of any association between use of these drugs and the incidence or type of congenital malformation. There was no association with use of these drugs and intrauterine growth retardation or perinatal death, but there was a significant difference in the rate of prematurity in the users (8.9%) compared with nonusers (6.5%). ANIMAL STUDIES: Reproduction studies have been performed in mice and rats at doses up to 2000 mg/kg. There was no evidence of harm to the fetus due to amoxicillin. However, 100 ug/mL amoxicillin altered rat renal development in vitro. Prolonged use of amoxicillin might have a negative effect on bone formation around implants. Studies to detect mutagenic potential of amoxicillin alone have not been conductedhowever, the following information is available from tests on a 4:1 mixture of amoxicillin and potassium clavulanate. Amoxicillin and potassium clavulanate was non-mutagenic in the Ames bacterial mutation assay, and the yeast gene conversion assay. Amoxicillin and potaA prospective study of 51 pediatric patients at a poison control center suggested that amoxicillin overdoses of less than 250 mg/kg are not associated with significant clinical symptoms, as per the FDA product labeling.Signs and Symptoms of Overdose* Interstitial nephritis leading to oliguric renal failure has been reported in a small number of patients following overdosage with amoxicillin.* Crystalluria leading to renal failure has been reported in both adult and pediatric patients following amoxicillin overdosage.Management of Overdose* In case of amoxicillin overdose, clinicians should discontinue amoxicillin therapy and provide supportive care to patients.* Clinicians should maintain the patient's airway, breathing, and circulation.* Healthcare providers should ensure the patient maintains adequate fluid intake to mitigate the risk of amoxicillin crystalluria.* Renal impairment appears to be reversible with the cessation of drug administration.* Amoxicillin may be removed from circulation by hemodialysis.* Individuals should contact a poison control center at 1-800-222-1222 for updated information about an amoxicillin overdose. |
| Ökotoxizitätsauszüge | /AQUATIC SPECIES/ Amoxicillin (AMX) is one of the most commonly prescribed antibiotics around the world due to its broad-spectrum activity against different bacterial strains as well as its use as a growth promoter in animal husbandry. Although residues of this antibacterial agent have been found in water bodies in diverse countries, there is not enough information on its potential toxicity to aquatic organisms such as the common carp Cyprinus carpio. This study aimed to evaluate AMX-induced oxidative stress in brain, gill, liver and kidney of C. carpio. Carp were exposed to three different concentrations of AMX (10 ng/L, 10 ug/L, 10 mg/L) for 12, 24, 48, 72, and 96 hr, and the following biomarkers were evaluated: lipid peroxidation (LPX), hydroperoxide content (HPC), protein carbonyl content (PCC) and activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Amoxicillin and its main degradation product amoxicilloic acid (AMA) were determined by high performance liquid chromatography coupled with electrochemical detection and UV detection (HPLC-EC-UV). Significant increases in LPX, HPC, and PCC (P<0.05) were found in all study organs, particularly kidney, as well as significant changes in antioxidant enzymes activity. Amoxicilloic acid in water is concluded to induce oxidative stress in C. carpio, this damage being highest in kidney. The biomarkers used are effective for the assessment of the environmental impact of this agent on aquatic species.[Elizalde-Velazquez A et alEnviron Toxicol/AQUATIC SPECIES/ Antibiotics have been widely used in human and veterinary medicine to treat or prevent diseases. Residues of antibiotics have been found in aquatic environments, but their effects on fish have been not properly investigated. This work aimed to assess the sub-lethal effects of oxytetracycline and amoxicillin on zebrafish development and biomarkers. Embryos and adults were exposed during 96 hr to amoxicillin and oxytetracycline following OECD guidelines. Tissues of adults and pools of embryos were used for catalase, glutathione-S-transferases and lactate dehydrogenase determinations. Amoxicillin caused premature hatching (48 hr-EC50=132.4 mg/L) whereas oxytetracycline cause delayed hatching of embryos (72 hr-EC50=127.6 mg/L). Moreover, both antibiotics inhibited catalase and induced glutathione-S-transferases in zebrafish adults. However, only oxytetracycline induced lactate dehydrogenase. Short-term effects of antibiotics were observed at high doses (mg/l) indicating that physiological impairment in fish populations is unlike to occur. However, effects of chronic exposures to low doses of ABs must be investigated./AQUATIC SPECIES/ Pharmaceuticals are found in the aquatic environment but their potential effects on non-target species like fish remain unknown. This in vitro study is a first approach in the toxicity assessment of human drugs on fish. Nine pharmaceuticals were tested on two fish hepatocyte models: primary cultures of rainbow trout hepatocytes (PRTH) and PLHC-1 fish cell line. Cell viability, interaction with cytochrome P450 1A (CYP1A) enzyme and oxidative stress were assessed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrasodium bromide tetrazolium (MTT), 7-ethoxyresorufin-o-deethylase (EROD) and dichlorofluorescein (DCFH-DA) assays, respectively. The tested drugs were clofibrate (CF), fenofibrate (FF), carbamazepine (CBZ), fluoxetine (FX), diclofenac (DiCF), propranolol (POH), sulfamethoxazole (SFX), amoxicillin (AMX) and gadolinium chloride (GdCl(3)). All substances were cytotoxic, except AMX at concentration up to 500 uM. The calculated MTT EC(50) values ranged from 2 uM (CF) to 651 uM (CBZ) in PLHC-1, and from 53 uM (FF) to 962 uM (GdCl(3)) in PRTH. CF, FF, and FX were the most cytotoxic drugs and induced oxidative stress before being cytotoxic. Compared to hepatocytes from human and dog, fish hepatocytes seemed to be more susceptible to the peroxisome proliferators (PPs) CF and FF. In PLHC-1 cells none of the tested drugs induced the EROD activity whereas POH appeared as a weak EROD inducer in PRTH. Moreover, in PRTH, SFX, DiCF, CBZ and to a lesser extend, FF and CF inhibited the basal EROD activity at clearly sublethal concentrations which may be of concern at the biological and chemical levels in a multipollution context./AQUATIC SPECIES/ In aquaculture, disinfection of facilities, prevention of fish diseases, and stimulation of fish growth are priority goals and the most important sources of toxic substances to the environment, together with excretory products from fish. In the present study, embryos of two species of sea urchin (Paracentrotus lividus and Arbacia lixula) were exposed to serial dilutions of six antibiotics (amoxicillin (AMOX), ampicillin, flumequine (FLU), oxytetracycline (OTC), streptomycin (ST), and sulfadiazine [SFD]) and two disinfectants (sodium hypochlorite (NaClO) and formaldehyde [CH(2)O]). Alterations in larval development were studied, and the effective concentrations (ECs) were calculated to evaluate the toxicity of the substances. Both species showed similar sensitivities to all substances tested. Disinfectants (EC(50) = 1.78 and 1.79 mg/L for CH(2)OEC(50) = 10.15 and 11.1 mg/L for NaClO) were found to be more toxic than antibiotics. AMOX, OTC, and ST caused <20% of alterations, even at the highest concentrations tested. FLU was the most toxic to P. lividus (EC(50) = 31.0 mg/L) and SFD to A. lixula (EC(50) = 12.7 mg/L). The sea urchin bioassay should be considered within toxicity assessment-monitoring plans because of the sensitivity of larvae to disinfectants. |
| Plant Concentrations | Amoxicillin, present at 1 mg/kg soil, was not detected in carrots and lettuce grown on light loamy sand soil (90.14% sand, 6.26% silt, 3.60% clay, pH 6.3, 0.4% organic carbonChurch Warsop, Nottinghamshire, UK collected in summer 2004)the study simulated soil treated with manure from animals administered veterinary medicines(1). |
| Ongoing Test Status | EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPAICSS Dashboard ApplicationAvailable from, as of October 28, 2016: http://actor.epa.gov/dashboard/] |
| Effluent Concentrations | Based on an annual consumption of 198,086.80 kg/yr, the estimated amoxycillin elimination from primary and secondary treatment processes was 0.27 and 88%, respectively, from wastewater facilities in Spain in 2009, giving a predicted environmental occurrence of 326.70 ng/L. A measured value of 40 ng/L was reported for an unspecified aquatic environment(1). Amoxicillin was not detected in effluent or industrial wastewater samples from The Netherlands tested in 2002(2). The median influent and effluent loads of six wastewater treatment plants in Italy were 13 mg/day/1000 inhabitants and not detected, respectively, sampled in winter and summer 2004(3). The compound was present at a median concentration of 4.7 ng/L in effluent from 9 sewage treatment plants in Italy(4). |
| Wassergefährdungsklasse (WGK) | 2 |
| Zollcode | 29411000 |
| RTECS-Nr. | XH8300000 |
| R-Sätze (R) | 42/43 |
| Gefahrensymbole | Xn,Xi |
| Sicherheitshinweise (S) | 22-36/37 |
| Lagerklasse | 11 - Combustible Solids |
| Gefahrstoffdaten | 26787-78-0(Hazardous Substances Data) |
| Gefahrenklasse | Resp. Sens. 1Skin Sens. 1 |
Anwendungen & Verwendung
Verwenden
Antibacterial;Bacterial transpeptidase inhibitor