| GHS 分類 | This chemical does not meet GHS hazard criteria for 1.3% (1 of 76) of reports.DangerH360 (93.4%): May damage fertility or the unborn child [Danger Reproductive toxicity]P203, P280, P318, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 76 reports by companies from 13 notifications to the ECHA C&L Inventory. |
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| 規制情報 | Ramipril: 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. |
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| FDA 要件 | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including ramipril, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
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| Hazard Classes and Categories | Repr. 1B (93.4%) |
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| Hazardous Reactivities and Incompatibilities | Incompatible materials: Strong oxidizing agents. |
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| 消火手順 | Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. |
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| 保管条件 | Store at 20 deg to 25 °C (68 deg to 77 °F).Keep container tightly closed in a dry and well-ventilated place. |
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| 清掃方法 | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid breathing vapors, mist or gas. 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. |
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| 処分方法 | 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 companyContaminated packaging: Dispose of as unused product. |
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| Preventive Measures | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains.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.Precautions for safe handling: Provide appropriate exhaust ventilation at places where dust is formed.Appropriate engineering controls: General industrial hygiene practice.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. |
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| Personal Protective Equipment (PPE) | Eye/face protection: 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: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place.Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). |
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| 相互作用 | In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of non-ateroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors, with angiotensin-converting enzyme (ACE) inhibitors, including ramipril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving ramipril and NSAID therapy. The antihypertensive effect of ACE inhibitors, including ramipril, may be attenuated by NSAIDs.Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithiumtherefore, frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, the risk of lithium toxicity may be increased.Coadministration of ramipril with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients.Patients on diuretics, especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with ramipril. The possibility of hypotensive effects with ramipril can be minimized by either decreasing or discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with ramipril. If this is not possible, reduce the starting dose. |
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| Hepatotoxicity | Ramipril, like other ACE inhibitors, has been associated with a low rate of serum aminotransferase elevations ( |
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| 環境中動態 | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2000(SRC), determined from a structure estimation method(2), indicates that ramipril is expected to have low mobility in soil(SRC). The estimated pKa values of ramipril are 3.74 and 5.15(3), indicating that this compound will exist almost entirely exist in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Ramipril is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.8X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2017).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2000(SRC), determined from a structure estimation method(2), indicates that ramipril is expected to adsorb to suspended solids and sediment(SRC). Estimated pKa values of 3.74 and 5.15(3) indicate ramipril will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 3(SRC), from an estimated log Kow of 3.32(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2017).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ramipril, which has an estimated vapor pressure of 3.8X10-11 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 ramipril may be removed from the air by wet and dry deposition(SRC). Ramipril contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). |
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| 有害作用 | The following adverse reactions have been associated with ramipril administration. |
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| Milk Concentrations | /MILK/ Ingestion of a single 10 mg oral dose of ramipril resulted in undetectable amounts of ramipril and its metabolites in breast milk. |
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| 毒性の概要 | IDENTIFICATION AND USE: Ramipril is a prodrug and has little pharmacologic activity until hydrolyzed in the liver to ramiprilat. It is an angiotensin-converting enzyme (ACE) inhibitor indicated for the treatment of hypertension. It is also used for stable patients with demonstratable congestive heart failure within the first few days of sustaining acute myocardial infarction. HUMAN STUDIES: Rare ACE inhibitor-associated clinical syndrome manifested initially by cholestatic jaundice may occur. It may progress to fulminant hepatic necrosis and is potentially fatal. Patients receiving an ACE inhibitor, including ramipril, who develop jaundice or marked elevations in hepatic enzymes should discontinue the drug and receive appropriate monitoring. Sensitivity reactions, including anaphylactic reactions and angioedema (including laryngeal or tongue edema) are potentially fatal. Head and neck angioedema involving the tongue, glottis, or larynx may cause airway obstruction. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, ramipril should be discontinued and appropriate therapy (e.g., epinephrine) should be initiated immediately. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue ramipril as soon as possible. No mutagenic activity was detected in the unscheduled DNA synthesis in a human cell line. ANIMAL STUDIES: No evidence of a tumorigenic effect was found when ramipril was given by gavage to rats for up to 24 months at doses of up to 500 mg/kg/day or to mice for up to 18 months at doses of up to 1000 mg/kg/day. A study in rats with dosages as great as 500 mg/kg/day did not produce adverse effects on fertility. Kidney organogenesis and functional development continue well into the postnatal period in the rat. A within-litter design was used to characterize renal susceptibility to an ACE inhibitor during the third week of life in rats. There were no treatment-related effects in rats dosed on PND 21. Following dosing on PND 14, dose-related increases were noted in mean serum urea nitrogen and/or creatinine levels on PND 17, but these measures recovered by PND 28. The interim changes were accompanied by macroscopic and microscopic changes in the kidneys on PND 17, including tubular hypoplasia, renal papillary edema, cortical tubular dilatation, hydronephrosis (pelvic dilatation) and tubular basophiliarenal anatomic changes were still evident and more severe on PND 28, 14 days after dosing. No mutagenic activity was detected in the Ames test in bacteria, the micronucleus test in mice or a forward gene-mutation assay in a Chinese hamster ovary cell line.Ramipril overdose can lead to severe hypotension, primarily attributed to vasodilation and effective hypovolemia. A study conducted in 2006 to investigate the effects of ramipril overdose on blood pressure concluded that a drop in blood pressure typically occurs within the first 4 to 4.5 hours after ingestion. Therefore, monitoring the patient for at least 6 hours after the overdose is essential. If the blood pressure remains stable during the first 6 hours after administration, the patient can be considered for discharge. |
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| 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 November 16, 2017: http://actor.epa.gov/dashboard/] |
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| Effluent Concentrations | Ramipril exhibited a 70% removal rate during wastewater treatment at a sewage treatment plant in Dresden, Germany. Influent and effluent sampling was conducted on 10 consecutive days in January/February 2015(1). |
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| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of ramipril can be estimated to be 2000(SRC). According to a classification scheme(2), this estimated Koc value suggests that ramipril is expected to have low mobility in soil. The estimated pKa values of ramipril 3.74 and 5.15(3), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). |
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| Human Toxicity Excerpts | /SIGNS AND SYMPTOMS/ Rare angiotensin-converting enzyme (ACE) inhibitor-associated clinical syndrome manifested initially by cholestatic jaundice may occurmay progress to fulminant hepatic necrosis and is potentially fatal. Patients receiving an ACE inhibitor, including ramipril, who develop jaundice or marked elevations in hepatic enzymes should discontinue the drug and receive appropriate monitoring./SIGNS AND SYMPTOMS/ Like other angiotensin-converting enzyme (ACE) inhibitors, ramipril rarely is associated with hypotension in patients with uncomplicated hypertension. Symptomatic hypotension may occurpatients at particular risk include those with severe volume and/or salt depletion secondary to prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Volume and/or salt depletion should be corrected before starting ramipril therapy. Marked hypotension may occur in patients with heart failure (with or without associated renal impairment), which may be associated with oliguria and/or progressive azotemia and, rarely, acute renal failure and/or death. In patients with heart failure, ramipril therapy should be started under close medical supervision, and patients should be followed closely for at least 2 weeks after initiation of ramipril or diuretic therapy or dosage adjustment of either drug./SIGNS AND SYMPTOMS/ Sensitivity reactions, including anaphylactic reactions and angioedema (including laryngeal or tongue edema) are potentially fatal. Head and neck angioedema involving the tongue, glottis, or larynx may cause airway obstruction. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, ramipril should be discontinued and appropriate therapy (e.g., epinephrine) should be initiated immediately./CASE REPORTS/ ... /The purpose of this study was/ to describe 3 patients who developed hepatitis, with or without jaundice, after receiving ramipril. Medical records and liver biopsies of the 3 patients were reviewed. Clinical, laboratory, and histologic findings were compared with findings in other cases of angiotensin-converting enzyme inhibitor-induced liver injury reported in the literature. The 3 patients were middle-aged men. In 2 patients, jaundice appeared 4 and 8 weeks after starting ramipril. Bilirubin levels peaked at 15.5 and 5 mg/dL, and alkaline phosphatase values peaked at 957 and 507 U/L. Aminotransferase levels were mildly elevated. Endoscopic retrograde cholangiopancreatography and ultrasonography showed no bile duct obstruction. Liver biopsies from the jaundiced patients were similar, with cholestasis, duct necrosis, and extravasation of bile, ductular proliferation, and portal inflammation. Cholestasis improved in 1 patient 6 weeks after stopping ramipril and was prolonged for 14 months in the other, in whom biliary cirrhosis was present on biopsy. The third patient developed hepatitis without jaundice 3 weeks after starting ramiprilsymptoms resolved after stopping the drug. Ramipril-associated liver injury is similar to that seen with other angiotensin-converting enzyme inhibitors, but liver biopsy findings of duct necrosis and extravasation of bile have not been reported previously. Prolonged cholestatic hepatitis and biliary cirrhosis may result from the use of ramipril. Monitoring of liver enzymes is advisable for patients starting on ramipril.For more Human Toxicity Excerpts (Complete) data for Ramipril (9 total), please visit the HSDB record page. |
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| Artificial Pollution Sources | Ramipril's production and administration as a antihypertensive(1) may result in its release to the environment through various waste streams(SRC). |
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| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)RamiprilvLess-DILI-concern7Adverse reactionsDOI:10.1016/j.drudis.2016.02.015 |
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