HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
Raloxifene
RALOXIFEN · Evista · (6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl)(4-(2-(piperidin-1-yl)ethoxy)phenyl)Methanone · RALOXAFINE · RALOXIFENE · RALOXIFENE-D7 · Raloxifene CRS · LY156758 free base
Identifikatoren & physikalische Daten
| CAS No. | 82640-04-8 |
|---|---|
| Summenformel | C28H27NO4S |
| Durchschnittliche Molmasse | 473,6 g/mol |
| Monoisotopische Masse | 473,16607934 g/mol |
| SMILES | O=C(c1ccc(OCCN2CCCCC2)cc1)c1c(-c2ccc(O)cc2)sc2cc(O)ccc12 |
| InChIKey | GZUITABIAKMVPG-UHFFFAOYSA-N |
| PubChem CID | 5035 |
| ChEMBL | CHEMBL81 |
| ChEBI | CHEBI:8772 |
| EC No. | 686-786-1 |
| DTXSID | DTXSID3023550 |
Chemische & physikalische Eigenschaften
| XLogP | 6,1 |
|---|---|
| Polarare Oberfläche (TPSA) | 98,2 |
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 6 |
| Frei drehbare Bindungen | 7 |
| Schwere Atome | 34 |
| Formalladung | 0 |
| Komplexität | 655 |
| Stoffklassen | Pharmaceutical |
| Arzneimittel | Pharmaceuticals -> Listed in ZINC15 |
| LogP (Verteilungskoeffizient) | 5.24.48 |
| Color/Form | Crystals from acetone |
| Löslichkeit | Insoluble5.12e-04 g/LDMSO: 28 mg/mL, soluble560μg/L at 25℃ |
| Human Drugs | EMA approved medicines: Human medicinePharmaceuticals |
| Endocrine Disruptors | Potential endocrine disrupting compound |
| Schmelzpunkt | 268-272143-147 °CCrystals from methanol/watermp: 258 °CUV max (ethanol): 286 nm (epsilon 32800). Freely soluble in dimethylsulfoxidesparingly soluble in methanolslightly soluble in alcoholvery slightly soluble in water, isopropyl alcohol, octanol. Practically insoluble in ether, ethyl acetate /Raloxifene hydrochloride/143 - 147 °C250-253°C |
| Physical Description | Solid |
| Stability/Shelf Life | Stable under recommended storage conditions. /Raloxifene hydrochloride/ |
| Collision Cross Section | 213.4 Ų [M-H]- [CCS Type: DTBuffer gas: N2Ionization: ESI-Dataset: TOXCASTSource Identifier: DTXSID1034181]212.74 Ų [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards] |
| Siedepunkt | 728.2±60.0 °C(Predicted) |
| Dichte | 1.289±0.06 g/cm3(Predicted) |
| Lagerbedingungen | Desiccate at +4°C |
| pKa (Säurekonstante) | 8.83±0.15(Predicted) |
| Aggregatzustand | solid |
| Farbe | light yellow |
| InChI | InChI=1S/C28H27NO4S/c30-21-8-4-20(5-9-21)28-26(24-13-10-22(31)18-25(24)34-28)27(32)19-6-11-23(12-7-19)33-17-16-29-14-2-1-3-15-29/h4-13,18,30-31H,1-3,14-17H2 |
| InChIKey | GZUITABIAKMVPG-UHFFFAOYSA-N |
| SMILES | C(C1=C(C2=CC=C(O)C=C2)SC2=CC(O)=CC=C21)(C1=CC=C(OCCN2CCCCC2)C=C1)=O |
| LogP (Verteilungskoeffizient) | 6.09 |
| CAS Datenbank | 84449-90-1(CAS DataBase Reference) |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH302 (33.3%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P261, P262, P264, P264+P265, P270, P271, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P316, P317, P318, P319, P321, P330, P332+P317, P337+P317, P361+P364, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 3 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatorische Informationen | Status: Active Update: 28-04-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/33491 |
| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including raloxifene hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Raloxifene hydrochloride/ |
| Toxic Combustion Products | Special hazards arising from the substance or mixture: Carbon oxides, Nitrogen oxides (NOx), Sulfur oxides, Hydrogen chloride gas. /Raloxifene hydrochloride/ |
| Hazard Classes and Categories | Acute Tox. 4 (33.3%) |
| Shipment Methods and Regulations | /PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Methods for transporting hazardous drugs to the health-care setting should be consistent with environmental protection and national or local regulations for transporting hazardous substances. When hazardous drugs are being transported to the home-care setting, appropriate containers (eg, lined cardboard boxes) and procedures should be used to prevent breakage and contain leakage. ... The drugs must be securely capped or sealed and properly packaged and protected during transport to reduce further the chance of breakage and spillage in a public area such as a corridor or elevator. /Antineoplastic agents/ |
| Brandbekämpfungsverfahren | Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. /Raloxifene hydrochloride/Advice for firefighters: Wear self-contained breathing apparatus for fire fighting if necessary. /Raloxifene hydrochloride/ |
| Lagerbedingungen | Store at controlled room temperature, 20 deg to 25 °C (68 deg to 77 °F) [see USP]. The USP defines controlled room temperature as a temperature maintained thermostatically that encompasses the usual and customary working environment of 20 deg to 25 det C (68 deg to 77 °F)that results in a mean kinetic temperature calculated to be not more than 25 °Cand that allows for excursions between 15 deg and 30 °C (59 deg and 86 °F) that are experienced in pharmacies, hospitals, and warehouses.Keep container tightly closed in a dry and well-ventilated place. /Raloxifene hydrochloride/ |
| Reinigungsverfahren | ACCIDENT 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. Methods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal. /Raloxifene hydrochloride//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Spill kits containing all materials needed to clean up spills of hazardous drugs should be assembled or purchased. These kits should be readily available in all areas where hazardous drugs are routinely handled. If hazardous drugs are being prepared or administered in a nonroutine area (home setting or unusual patient-care area), a spill kit should be obtained by the drug handler. The kit should include two pairs of disposable gloves (one outer pair of utility gloves and one inner latex pair)low-permeability, disposable protective garments (coveralls or gown and shoe covers)safety glasses or splash gogglesrespiratorabsorbent, plastic-backed sheets or spill padsdisposable towelingat least 2 sealable thick plastic hazardous waste disposal bags (prelabeled with an appropriate warning label)a disposable scoop for collecting glass fragmentsand a puncture-resistant container for glass fragments. All individuals who routinely handle hazardous drugs must be trained in proper spill management and cleanup procedures. Spills and breakages must be cleaned up immediately according to the following procedures. If the spill is not located in a confined space, the spill area should be identified and other people should be prevented from approaching and spreading the contamination. Wearing protective apparel from the spill kit, workers should remove any broken glass fragments and place them in the puncture-resistant container. Liquids should be absorbed with a spill padpowder should be removed with damp disposable gauze pads or soft toweling. The hazardous material should be completely removed and the area rinsed with water and then cleaned with detergent. The spill cleanup should proceed progressively from areas of lesser to greater contamination. The detergent should be thoroughly rinsed and removed. All contaminated materials should be placed in the disposal bags provided and sealed and transported to a designated containment receptacle. Spills occurring in the biohazard cabinet should be cleaned up immediatelya spill kit should be used if the volume exceeds 150 ml or the contents of one drug vial or ampule. If there is broken glass, utility gloves should be worn to remove it and place it in the puncture-resistant container located in the biohazard cabinet. The biological safety cabinet, including the drain spillage trough, should be thoroughly cleaned. If the spill is not easily and thoroughly contained, the biological safety cabinet should be decontaminated after cleanup. If the spill contaminates the high efficiency particulate air filter, use of the biological safety cabinet should be suspended until the cabinet has been decontaminated and the high efficiency particulate air filter replaced. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ If hazardous drugs are routinely prepared or administered in carpeted areas, special equipment is necessary to remove the spill. Absorbent powder should be substituted for pads or sheets and left in place on the spill for the time recommended by the manufacturer. The powder should then be picked up with a small vacuum unit reserved for hazardous drug cleanup. The carpet should then be cleaned according to usual procedures. The vacuum bag should be removed and discarded or cleaned, and the exterior of the vacuum cleaner should be washed with detergent and rinsed before being covered and stored. The contaminated powder should be discarded into a sealable plastic bag and segregated with other contaminated waste materials. Alternatively, inexpensive wet or dry vacuum units may be purchased for this express use and used with appropriate cleaners. All such units are contaminated, once used, and must be cleaned, stored, and ultimately discarded /properly/ ... The circumstances and handling of spills should be documented. Health-care personnel exposed during spill management should also complete an incident report or exposure form. /Antineoplastic agents/ |
| 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. Contaminated packaging: Dispose of as unused product. /Raloxifene hydrochloride//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All contaminated disposables should be contained in sealable bags for transfer to larger waste containers. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All bottles must be discarded as contaminated waste after decontamination of the biohazard cabinet. All protective apparel (gown, gloves, goggles, and respirator) should be discarded as contaminated waste. /Antineoplastic agents/For more Disposal Methods (Complete) data for Raloxifene (9 total), please visit the HSDB record page. |
| Preventive Measures | ACCIDENT 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. /Raloxifene hydrochloride/Precautions for safe handling: Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection. /Raloxifene hydrochloride/Appropriate engineering controls: General industrial hygiene practice. /Raloxifene hydrochloride/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. /Raloxifene hydrochloride/For more Preventive Measures (Complete) data for Raloxifene (24 total), please visit the HSDB record page. |
| 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). /Raloxifene hydrochloride/Skin protection: Handle with gloves. /Raloxifene hydrochloride/Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place. /Raloxifene hydrochloride/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). /Raloxifene hydrochloride/For more Personal Protective Equipment (PPE) (Complete) data for Raloxifene (9 total), please visit the HSDB record page. |
| Wechselwirkungen | The manufacturer states that concomitant use of systemic estrogens with raloxifene currently is not recommended because of the lack of experience from prospective clinical trials with such use.Concomitant administration of raloxifene and ampicillin results in a 28% decrease in peak plasma concentration and a 14% decrease in the extent of absorption of raloxifene. These changes in raloxifene absorption are consistent with decreased enterohepatic cycling associated with a reduction of enteric bacteria. Because systemic exposure and the elimination rate of raloxifene are not affected, raloxifene may be given concomitantly with ampicillin. In raloxifene-treated women with osteoporosis, concomitant administration of amoxicillin did not affect the plasma concentrations of raloxifene. Raloxifene may be given concomitantly with amoxicillin.While the effect of long-term administration of raloxifene in conjunction with warfarin has not been studied and the drug reportedly does not affect the protein binding of the anticoagulant, concomitant administration of single doses of raloxifene and warfarin has resulted in a 10% decrease in prothrombin time compared with administration of warfarin alone. In raloxifene-treated women with osteoporosis, concomitant administration of warfarin did not affect the plasma concentrations of raloxifene. If the drugs are used concomitantly, the patient and prothrombin time should be monitored closely and the dosage of the anticoagulant adjusted accordingly.Administration of cholestyramine and raloxifene results in a 60% decrease in the absorption and enterohepatic cycling of raloxifene. The manufacturer states that raloxifene should not be administered with cholestyramine. Although not studied specifically, other anion-exchange resins would also be expected to decrease the absorption and enterohepatic cycling of raloxifene.Raloxifene is more than 95% bound to plasma proteins. The manufacturer states that concomitant administration of raloxifene with other highly protein-bound drugs is not expected to affect the plasma concentrations of raloxifene. In raloxifene-treated women with osteoporosis, concomitant administration of other highly protein-bound drugs (eg, gemfibrozil) did not affect the plasma concentrations of raloxifene. Raloxifene reportedly does not affect the protein binding of phenytoin, tamoxifen, or warfarin in vitro. The manufacturer states that caution is advised if raloxifene is used concomitantly with other highly protein-bound drugs such as diazepam, diazoxide, or lidocaine. |
| Unerwünschte Wirkungen | Raloxifene's most common documented adverse effects are hot flashes, flu-like symptoms, muscle spasms, arthralgia, and infection. Less common effects are insomnia, vomiting, sinusitis, deep venous thrombosis, bronchitis, pharyngitis, and breast pain. Raloxifene-treated women reported peripheral edema ( raloxifene 14.1% vs placebo 11.7%), muscle spasms/leg cramps (12.1% vs 8.3% ), hot flashes (7.8% vs 4.7% ), cholelithiasis (3.3% vs 2.6% ), and venous thromboembolic events 2.0% vs 1.4%). |
| Toxizitätsübersicht | IDENTIFICATION AND USE: Raloxifene is used for the treatment and prevention of osteoporosis in postmenopausal women and for the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis. HUMAN STUDIES: No fatalities associated with raloxifene overdose have been reported. In postmarketing reports, adverse reactions were reported in approximately half of the adults who took >/= 180 mg raloxifene HCl and included leg cramps and dizziness. Raloxifene therapy is associated with an increased risk of venous thromboembolic events such as deep-vein thrombosis and pulmonary embolism. Increased risk of death due to stroke occurred in a trial in postmenopausal women with documented coronary heart disease or at increased risk for major coronary events. A few cases of jaw bone osteonecrosis have been associated with raloxifene. Two 18-month-old children each ingested raloxifene HCl 180 mg, symptoms reported included ataxia, dizziness, vomiting, rash, diarrhea, tremor, and flushing, as well as elevation in alkaline phosphatase. Raloxifene may cause fetal toxicity when administered to pregnant women. Effects on reproductive function are expected because raloxifene is an estrogen agonist-antagonist. ANIMAL STUDIES: Mortality was not observed in rats or mice following single oral doses of raloxifene hydrochloride 5000 mg/kg, or in monkeys following single oral doses of raloxifene hydrochloride 1000 mg/kg. In a 21-month carcinogenicity study in mice, there was an increased incidence of ovarian tumors in female mice given oral raloxifene hydrochloride 9-242 mg/kg daily and an increased incidence of testicular interstitial cell tumors, prostatic adenomas, and adenocarcinomas in male mice given raloxifene hydrochloride 41 or 210 mg/kg daily. In studies in rats using raloxifene hydrochloride, doses of 0.1-10 mg/kg during gestation and lactation delayed and disrupted parturition, decreased neonatal survival and altered physical development, sex- and age-specific reductions in growth and changes in pituitary hormone content, and decreased lymphoid compartment size in offspring were observed. Disruption of parturition, which resulted in maternal and progeny morbidity and/or death, was observed in rats given raloxifene hydrochloride 10 mg/kg. While ovarian or vaginal pathology was not observed in adult offspring (4 months of age), uterine hypoplasia and reduced fertility were noted. In reproductive studies in rabbits using raloxifene hydrochloride, doses of 0.1 mg/kg or more resulted in abortion and a low rate of fetal heart anomalies (i.e., ventricular septal defects). In rabbits using raloxifene doses of 10 mg/kg or more (at least 4 times the recommended dose in humans on a mg/sq m basis), hydrocephaly was observed in the fetuses. In female rats, at doses of 0.1 to 10 mg/kg/day, raloxifene disrupted estrous cycles and inhibited ovulation. These effects of raloxifene were reversible. When male and female rats were given daily doses >/=5 mg/kg prior to and during mating, no pregnancies occurred. In reproductive studies in rats using raloxifene hydrochloride doses of 1 mg/kg or more, retardation of fetal development and developmental abnormalities (i.e., wavy ribs, kidney cavitation) were observed. Raloxifene was not mutagenic in in vitro or in vivo studies, including the Ames microbial test with and without metabolic activation, the unscheduled DNA synthesis assay in rat hepatocytes, the mouse lymphoma assay for mammalian cell mutation, the chromosomal aberration assay in Chinese hamster ovary cells, the sister chromatid exchange assay in Chinese hamsters, and the micronucleus test in mice.There is some documentation of increased risk of deep vein thrombosis, embolic cerebrovascular accident, and pulmonary embolism with the usage of this drug. Patients developing new-onset vaginal bleeding require a workup, including an endometrial biopsy and an OB/GYN consultation. There are some reports of an increased risk of death due to a cerebrovascular accident in trials of postmenopausal women with coronary heart disease or with high-risk factors for coronary arterial disease. |
| 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 February 4, 2019: http://actor.epa.gov/dashboard/] |
| Medical Surveillance | /PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ There is no method available for routine monitoring of personnel for evidence of hazardous drug exposure. Tests for the presence of mutagens or chromosomal damage are not drug specific and are of value only in controlled studies. Chemical analysis of urine for the presence of hazardous drugs at the sensitivity level needed to detect occupational exposure is limited to a few drugs and is not yet commercially available. /Antineoplastic agents/ |
| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ Estrogen replacement therapy after menopause reduces the incidence of arterial disease and cerebrovascular events. The reduced incidence also seems to be due to a positive effect of estrogens on brain blood flow as shown by a decrease in the carotid artery pulsatility index. Raloxifene, a second-generation selective estrogen receptor modulator, has aroused considerable interest because of its tissue-specific agonist-antagonist effect on estrogen receptors. However, there have been no studies on the effect of raloxifene on carotid blood flow after menopause. A total of 66 healthy women in postmenopause for more than a year were divided randomly into 2 groups: the first group (n = 33mean age +/- SD, 53.3 +/- 5.2 years) was treated with raloxifene (one 60-mg capsule per day) for 6 months, and the other group (n = 33mean age +/- SD, 51.9 +/- 4 years) was untreated. Doppler ultrasonography was used to measure carotid artery pulsatility index (PI) at the beginning of the study and at 2-month intervals. A reduction in carotid artery PI was observed in all patients receiving raloxifene. No significant changes were observed in the control group. The reduction with respect to baseline values was 6.1%(P <.05) after 2 months, 11.2% (P <.05) after 4 months, and 13.2% (P <.05) after 6 months of therapy. The higher the baseline PI, the greater was its reduction after therapy. After 6 months of therapy, raloxifene induced a reduction in PI similar to that reported after estrogen therapy. The present results further our understanding of the mechanisms by which raloxifene might reduce the incidence of cardiovascular disease in postmenopausal women./SIGNS AND SYMPTOMS/ In postmarketing spontaneous reports, raloxifene overdose has been reported very rarely (less than 1 out of 10,000 [<0.01%] patients treated). The highest overdose has been approximately 1.5 grams. No fatalities associated with raloxifene overdose have been reported. Adverse reactions were reported in approximately half of the adults who took >/=180 mg raloxifene HCl and included leg cramps and dizziness./SIGNS AND SYMPTOMS/ Raloxifene therapy is associated with an increased risk of venous thromboembolic events such as deep-vein thrombosis and pulmonary embolism./SIGNS AND SYMPTOMS/ Increased risk of deep vein thrombosis and pulmonary embolism have been reported with Evista. Women with active or past history of venous thromboembolism should not take Evista. Increased risk of death due to stroke occurred in a trial in postmenopausal women with documented coronary heart disease or at increased risk for major coronary events. Consider risk-benefit balance in women at risk for strokeFor more Human Toxicity Excerpts (Complete) data for Raloxifene (14 total), please visit the HSDB record page. |
| Artificial Pollution Sources | Raloxifene's production and administration as a medication for osteoporosis(1) may result in its release to the environment through various waste streams(SRC). |
| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)raloxifeneDILI NegativeOralDOI:10.1016/j.drudis.2019.09.022 |
| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Acute Exposure/ Mortality was not observed in rats or mice following single oral doses of raloxifene hydrochloride 5000 mg/kg (810 or 405 times, respectively, the recommended human dose on a mg/sq m basis)./LABORATORY ANIMALS: Acute Exposure/ Mortality was not observed in monkeys following single oral doses of raloxifene hydrochloride 1000 mg/kg (80 times the recommended human dose on a mg/sq m basis)./LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Cisplatin induced nephrotoxicity is the chief obstacle in the use of cisplatin as chemotherapeutic agent. However, it remains as most widely employed anticancer agent to treat various solid tumors like head-neck, testicular, ovarian and mammary gland cancer. Raloxifene is claimed to be potent anti-inflammatory as well as anti-cancer agent. The present study was carried out to explore the effect of pre-treatment of raloxifene on cisplatin induced nephrotoxicity and its anti-tumor activity in 7,12 dimethyl benz-[a]-anthracene induced mammary tumor in animal model. Renal damage was accessed by measuring serum level of creatinine, blood urea nitrogen and albumin whereas systemic inflammation was accessed by measuring level of pro-inflammatory cytokines like tumor necrosis factor alpha (TNF-a), interleukin 6 (IL-6), interleukin 10 (IL-10) and nuclear factor kappa B (NFkB). Moreover, assessment of tumor reduction was done by measuring tumor volume and percentage tumor reduction. A single dose of cisplatin (7.5 mg/kg) resulted in significant increase in serum creatinine, blood urea nitrogen, NF-kB, TNF-a and IL-6 levels along with decrease in albumin and IL-10 levels. However, there were no significant changes in raloxifene (8 mg/kg) treated group. Pre-treatment of raloxifene (8 mg/kg) caused marked decrease in serum creatinine, blood urea nitrogen, TNF-a and IL-6 levels whereas increase in albumin and IL-10 levels. However, pre-treatment of raloxifene showed maximum tumor reduction as compared to cisplatin and raloxifene treated groups. The present study demonstrates that raloxifene potentiates anti-tumor activity of cisplatin with simultaneous reduction in its nephrotoxicity, and this effect is attributed to its direct anti-inflammatory activity./LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In a 21-month carcinogenicity study in mice, there was an increased incidence of ovarian tumors (i.e., benign and malignant tumors of granulosa/theca cell origin, benign tumors of epithelial cell origin) in female mice given oral raloxifene hydrochloride 9-242 mg/kg daily (equivalent to systemic exposure of about 0.3-34 times the area under the plasma concentration-time curve [AUC] in women receiving the recommended raloxifene hydrochloride dosage) and an increased incidence of testicular interstitial cell tumors, prostatic adenomas, and adenocarcinomas in male mice given raloxifene hydrochloride 41 or 210 mg/kg daily (4.7 or 24 times the AUC in women).For more Non-Human Toxicity Excerpts (Complete) data for Raloxifene (22 total), please visit the HSDB record page. |
| Populations at Special Risk | Increased risk of deep vein thrombosis and pulmonary embolism have been reported with Evista. Women with active or past history of venous thromboembolism should not take Evista. Increased risk of death due to stroke occurred in a trial in postmenopausal women with documented coronary heart disease or at increased risk for major coronary events. Consider risk-benefit balance in women at risk for strokeRaloxifene is contraindicated in women with active or past episodes of venous thrombosis, including deep-vein thrombosis, pulmonary embolism, or retinal vein thrombosis. Potential therapeutic benefit versus risk should be assessed in women at risk of thromboembolic disease secondary to congestive heart failure, superficial thrombophlebitis, or active malignancy.The manufacturer states that raloxifene should not be used in pediatric patients. |
| Antidote and Emergency Treatment | /SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B//SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). 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 0.9% saline (NS) 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 ... . /Poisons 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 severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/ |
| USGS Health-Based Screening Levels for Evaluating Water-Quality | RaloxifenePharmaceuticalSmith, C.D. and Nowell, L.H., 2024. Health-Based Screening Levels for evaluating water-quality data (3rd ed.). DOI:10.5066/F71C1TWP |
| Wassergefährdungsklasse (WGK) | 3 |
| Zollcode | 29349990 |
| Gefahrstoffdaten | 84449-90-1(Hazardous Substances Data) |
Anwendungen & Verwendung
Verwenden
Raloxifene is a nonsteroidal, selective estrogen receptor modulator (SERM). Antiosteoporotic.