Furosemide

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

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.

Keep container tightly closed in a dry and well-ventilated place.

Furosemide injection should be stored at a temperature of 15-30 °C and protected from light; injections having a yellow color should not be used. Exposure of furosemide tablets to light may cause discoloration; discolored tablets should not be dispensed. Furosemide tablets should be stored and dispensed in well-closed, light-resistant containers at a controlled room temperature of 15-30 °C. ... The 20-mg tablets do not have a specific expiration dating period. Furosemide oral solutions should be stored at 15-30 °C and protected from light and freezing; once opened, unused portions of the oral solution should be discarded after the time period recommended by the manufacturer.

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: Prevent further leakage or spillage if safe to do so. 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.

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

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 scrubber; Contaminated packaging: Dispose of as unused product.

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: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.

Precautions for safe handling: Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.

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.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

Eye/face protection: Safety glasses with side-shields conforming to EN166. 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: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Methotrexate and other drugs that, like Lasix, undergo significant renal tubular secretion may reduce the effect of Lasix. Conversely, Lasix may decrease renal elimination of other drugs that undergo tubular secretion. High-dose treatment of both Lasix and these other drugs may result in elevated serum levels of these drugs and may potentiate their toxicity as well as the toxicity of Lasix.

Phenytoin interferes directly with renal action of Lasix. There is evidence that treatment with phenytoin leads to decreased intestinal absorption of Lasix, and consequently to lower peak serum furosemide concentrations.

Lasix may decrease arterial responsiveness to norepinephrine. However, norepinephrine may still be used effectively.

There is a risk of ototoxic effects if cisplatin and Lasix are given concomitantly. In addition, nephrotoxicity of nephrotoxic drugs such as cisplatin may be enhanced if Lasix is not given in lower doses and with positive fluid balance when used to achieve forced diuresis during cisplatin treatment.

For more Interactions (Complete) data for Furosemide (36 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 110(SRC), determined from a structure estimation method(2), indicates that furosemide is expected to have high mobility in soil(SRC). The pKa of furosemide is 3.9(3), indicating that this compound will exist almost entirely in 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 of the anion from moist soil is not expected because anions do not volatilize(SRC). Furosemide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.1X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Furosemide may biodegrade in soil based upon half-lives of 14-20 days in river sediments(5).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 110(SRC), determined from a structure estimation method(2), indicates that furosemide is expected to adsorb to suspended solids and sediment(SRC). A pKa of 3.9(3) indicates furosemide will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected(SRC). Furosemide is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow of 2.03(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low. Furosemide had a biodegradation half-life of 14-20 days in various river sediments under aerobic conditions; furosemide was degraded at a slower rate under anaerobic conditions(7).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), furosemide, which has an estimated vapor pressure of 3.1X10-11 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 furosemide may be removed from the air by wet and dry deposition(SRC). Furosemide absorbs UV light at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: Furosemide is white or slightly yellow, solid powder or crystals. Furosemide is used to treat edema associated with many diseases (either as the sole drug or as an adjunct to other antihypertensives). HUMAN STUDIES: Overdoses of diuretics are uncommon and infrequently serious. Problems most frequently involve chronic over medication or poor monitoring and/or lack of anticipation of drug interactions or not compensating for concomitant hepatic or renal dysfunction. Main toxic effects are on the kidneys with diuresis of water, sodium, and potassium leading most frequently to a hyponatremic, hypokalemic, and hypochloremic dehydration. More caution is warranted with patients at higher risk for abnormal renal function including patients with any renal disease, diabetes mellitis, and borderline fluid and/or electrolyte status. In a hospital-based study of adverse reactions to medications there was a 21% rate of adverse affects to frusemide with most common ones being hypovolemia, hyperuricemia, and hypokalemia which for the most part were mild, but the rate and severity increased with increasing daily doses. Hypersensitivity reactions such as rash, photosensitivity, thrombocytopenia, and pancreatitis are rare. Life threatening hyperkalemia and reversible renal failure occurred in an elderly male taking captopril concomitantly with furosemide. Acute rhabdomyolysis and myoglobinuria due to hypokalaemia occurred in a 74-year-old male taking furosemide. Severe anaphylactic reaction to furosemide involving urticaria; angioedema and hypotension occurred in an adult 5 minutes after receiving intravenous furosemide. Furosemide abuse (400 mg daily) was associated with severe hyponatremia and central pontine myelinolysis. Self-administration of furosemide over 6 years resulted in calcification of the renal medulla. Nephrocalcinosis and nephrolithiasis occurred in 5 children after treatment with furosemide. It has also reported nephrocalcinosis in premature infants being treated with furosemide. Cholelithiasis in infants was caused by furosemide. Tachycardia was reported following a high dose intravenous regimen using furosemide. Renal calcifications were encountered in premature infants when given furosemide. Furosemide-induced renal calcifications in low birth weight infants may lead to glomerular and tubular dysfunction in the long-term. A concentration-dependent increase in the frequency of chromosomal aberrations was observed in human lymphocytes exposed in vitro to furosemide for 24 and 72 hr. No such effect was detected in the human fibroblast cell line. ANIMAL STUDIES: Chronic administration to rats has caused tubular degeneration in the kidneys. Calcification and damage to the renal parenchyma occurred in a subchronic study in dogs. Developmental studies have been conducted in mice, rats and rabbits. An increase in the incidence and severity of hydronephrosis (distention of the renal pelvis and occasionally the ureters) was seen in a mouse study and one of three rabbit studies. In male mice treated intraperitoneally with furosemide at 0.3-50 mg/kg bw, a non-dose-dependent increase in the percentage of meiotic cells with chromosomal aberrations was observed during the whole spermatogenic cycle. Furosemide was tested over a wide range of doses (0, 100, 333, 1000, 3333, and 10,000 ug/plate) in four Salmonella typhimurium strains (TA98, TA100, TA1535, and TA1537) with and without metabolic activation. Furosemide was negative in these tests and the highest ineffective dose level tested in any Salmonella tester strain was 10,000 ug/plate. Furosemide was reported to induce mutations in L5178Y mouse lymphoma cells in the presence of an exogenous metabolic system only at the highest concentration tested (1500 ug/mL). It was also reported to induce sister chromatid exchange and chromosomal aberrations in Chinese hamster CHO cells at 3750 and 500 ug/mL in the presence and absence of an exogenous metabolic system. Furosemide induced chromosomal damage in Chinese hamster lung fibroblasts in vitro, but only in the absence of an exogenous metabolic system. ECOTOXICITY STUDIES: Furosemide in combination with other drugs found in waste water was genotoxic to zebrafish, and exhibited toxic effects on riverine microbial communities.

/AQUATIC SPECIES/ Over the past few years, the increasing and uncontrolled use of pharmaceutical substances in agriculture, fish farming, human health and in veterinary medicine, together with an improper use of out-of-date medicines, has led to a consequent increase in the environmental problems linked to their disposal. In some Italian waste water treatment plants were found furosemide, a diuretic; ranitidine, an antiulcer drug; bezafibrate, a lipid regulator and ibuprofen, a painkiller. The present paper shows, by means of the synergic application of three tests (the Comet Test, the Diffusion Assay and the RAPD-PCR technique), how the DNA of zebrafish can be damaged after exposure to the above mentioned drugs. The data from the Comet Test, the Diffusion Assay and the RAPD-PCR technique were generally in agreement; these results show that all four drugs are genotoxic.

/AQUATIC SPECIES/ Although pharmaceutical and therapeutic products are widely found in the natural environment, there is limited understanding of their ecological effects. ...Rotating annular bioreactors /were used/ to assess the impact of 10 ug/L of the selected pharmaceuticals ibuprofen, carbamazepine, furosemide, and caffeine on riverine biofilms. After 8 weeks of development, community structure was assessed using in situ microscopic analyses, fluor-conjugated lectin binding, standard plate counts, fluorescent in situ hybridization, carbon utilization spectra, and stable carbon isotope analyses. The biofilm communities varied markedly in architecture although only caffeine treated biofilms were significantly thicker. Cyanobacteria were suppressed by all 4 compounds, whereas the nitrogen containing caffeine, furosemide, and carbamazepine increased algal biomass. Ibuprofen and carbamazepine reduced bacterial biomass, while caffeine and furosemide increased it. Exopolymer content and composition of the biofilms was also influenced. Significant positive and negative effects were observed in carbon utilization spectra. In situ hybridization analyses indicated all treatments significantly decreased the gamma-proteobacterial populations and increased beta-proteobacteria. Ibuprofen in particular increased the alpha-proteobacteria, beta-proteobacteria, cytophaga-flavobacteria, and SRB385 probe positive populations. Caffeine and carbamazepine additions resulted in significant increases in the high GC354c and low GC69a probe positive cells. Live-dead analyses of the biofilms indicated that all treatments influenced the ratio of live-to-dead cells with controls having a ratio of 2.4, carbamazepine and ibuprofen being 3.2 and 3.5, respectively, and furosemide and caffeine being 1.9 and 1.7, respectively. Stable isotope analyses of the biofilms indicated delta 13C values shifted to more negative values relative to control biofilms. This shift may be consistent with proportional loss of cyanobacteria and relative increase in algal biomass rather than incorporation of pharmaceutical carbon into microbial biofilm. Thus, at 10 ug/L levels pharmaceuticals exhibit both nutrient-like and toxic effects on riverine microbial communities.

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/[USEPA; ICSS Dashboard Application; Available from, as of May 1, 2017: http://actor.epa.gov/dashboard/]

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for furosemide is available.[Available from, as of July 26, 2017: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

Samples collected May 18-19 and Oct 19-20, 2009 from a wastewater treatment plant in Los Angeles, CA contained furosemide at mean concentrations of 93 and 57 ng/L, respectively(1). Furosemide was removed 0-17% and 15-62% in samples collected Jan-Mar and Jun-Sep 2004, respectively, from six sewage treatment plants in Italy(2). Furosemide was detected in 100, 96 and 83% of waste water influent, effluent and sludge samples at respective LOQ's of 4.0 ng/L, 2.0 ng/L and 1.0 ng/g, samples were collected from three Spanish treatment plants in eight campaigns over a two year period (July 2007-March 2009)(3). Furosemide was detected in the effluents of waste water treatment plants in Spain at 128-937 ng/L(4).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of furosemide can be estimated to be 110(SRC). According to a classification scheme(2), this estimated Koc value suggests that furosemide is expected to have high mobility in soil. The pKa of furosemide is 3.9(3), indicating that this compound will exist almost entirely in anion form in the environment and anions generally do not adsorb to soils containing organic carbon and clay than their neutral counterparts(4).

/HUMAN EXPOSURE STUDIES/ The pharmacokinetics and pharmacodynamics of the combination of amiloride (2 x 2.5 mg) and long acting furosemide (2 x 10 mg) were compared with amiloride (5 mg) and furosemide (20 mg) in 12 healthy male volunteers aged 26.2 + or - 1.6 yr and weighing 68.8 + or - 6.2 kg, after random order administration. Furosemide and amiloride plasma or urine concn were determined by HPLC with fluorimetric detection. The rate of absorption (tmax = 3 hr) and the bioavailability of the two diuretics were not significantly modified by their combination. Furosemide plasma half life was 2.77 + or - 1.04 hr after the combination treatment and 2.76 + or - 0.98 hr alone, amiloride plasma half life was respectively 15.7 + or - 4.6 hr and 14.6 + or - 3.7 hr. The urinary elimination of furosemide was significantly higher in the 2-4 hr interval in the combination treatment, accompanying its delayed maximum effect of diuresis. A synergistic effect was observed after the combination administration of the two diuretics; between the 2nd and the 8th hour, the sodium elimination was significantly increased (p< 0.01) and the potassium excretion was significantly decreased (p= 0.05). After a single dose, no modification of plasma or erythrocyte magnesium levels was observed. This study shows that the combination of the two drugs entails a synergy of their activities which does not involve pharmacokinetic changes.

/HUMAN EXPOSURE STUDIES/ Interactions between sodium and calcium regulating systems are poorly characterized but clinically important. Parathyroid hormone (PTH) levels are increased shortly after furosemide treatment by an unknown mechanism, and this effect is blunted by the previous administration of a calcimimetic in animal studies. Here, we explored further the possible underlying mechanisms of this observation in a randomized crossover placebo-controlled study performed in 18 human males. Volunteers took either cinacalcet (60 mg) or placebo and received a 20 mg furosemide injection 3 hr later. Plasma samples were collected at 15-min intervals and analyzed for intact PTH, calcium, sodium, potassium, magnesium, phosphate, plasma renin activity (PRA), and aldosterone up to 6 hr after furosemide injection. Urinary electrolyte excretion was also monitored. Subjects under placebo presented a sharp increase in PTH levels after furosemide injection. In the presence of cinacalcet, PTH levels were suppressed and marginal increase of PTH was observed. No significant changes in electrolytes and urinary excretion were identified that could explain the furosemide-induced increase in PTH levels. PRA and aldosterone were stimulated by furosemide injection but were not affected by previous cinacalcet ingestion. Expression of NKCC1, but not NKCC2, was found in parathyroid tissue. In conclusion, our results indicate that furosemide acutely stimulates PTH secretion in the absence of any detectable electrolyte changes in healthy adults. ...

/SIGNS AND SYMPTOMS/ The principal signs and symptoms of overdose with Lasix are dehydration, blood volume reduction, hypotension, electrolyte imbalance, hypokalemia and hypochloremic alkalosis, and are extensions of its diuretic action.

AEROBIC: Furosemide is stated as not readily biodegraded(1). Furosemide had a biodegradation half-life of 14-20 days in various river sediments under aerobic conditions; furosemide was degraded at a slower rate under anaerobic conditions(2). In an Australian sewage treatment plant, 20% of furosemide was removed, 15% was attributed to biodegradation(3).

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including furosemide, 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. Furosemide is included on this list.

Oral dosage form new animal drugs. Furosemide. ... (1) Cattle ... Indications for use. For treatment of physiological parturient edema of the mammary gland and associated structures. Limitations. Treatment not to exceed 48 hours post-parturition. Milk taken during treatment and for 48 hours after the last treatment must not be used for food. Cattle must not be slaughtered for food within 48 hours following last treatment. (2) Dogs ... Indications for use-(A) For treatment of edema (pulmonary congestion, ascites) associated with cardiac insufficiency and acute noninflammatory tissue edema. (B) For treatment of edema (pulmonary congestion, ascites) associated with cardiac insufficiency. (3) Cats ... Indications for use. For treatment of edema (pulmonary congestion, ascites) associated with cardiac insufficiency and acute noninflammatory tissue edema.

Implantation or injectable dosage form new animal drugs. Furosemide. ... (1) Dogs and cats ...Indications for use. For the treatment of edema (pulmonary congestion, ascites) associated with cardiac insufficiency and acute noninflammatory tissue edema. ... (2) Horses ... Indications for use. For the treatment of edema (pulmonary congestion, ascites) associated with cardiac insufficiency, and acute noninflammatory tissue edema. Limitations. Do not use in horses intended for human consumption. ... (3) Cattle ... Indications for use. For the treatment of physiological parturient edema of the mammary gland and associated structures. Limitations. Treatment not to exceed 48 hours post-parturition. Milk taken during treatment and for 48 hours (four milkings) after the last treatment must not be used for food. Cattle must not be slaughtered for food within 48 hours following last treatment.

Diuretics; Sodium Potassium Chloride Symporter Inhibitors

Furosemide has been used empirically and has been legally approved for many years by the US racing industry for the control of exercise-induced pulmonary haemorrhage (EIPH) or bleeding.

MEDICATION (VET)

MEDICATION

Use (kg) in Switzerland (2009): >500

(1976) 1.82X10+3 GRAMS (PRINCPL CUSTMS DISTS)

(1978) 1.25X10+6 GRAMS (PRINCPL CUSTMS DISTS)

(1976) NOT PRODUCED COMMERCIALLY IN US

(1978) NOT PRODUCED COMMERCIALLY IN US

2,4-Dichlorobenzoic acid is heated with chlorosulfonic acid, and the resulting 5-chlorosulfonyl derivative is reacted with concentrated ammonia to convert it to the 5-sulfamoyl analogue (I). Refluxing I with furfurylamine in large excess or in the presence of sodium bicarbonate yields crude furosemide, which is recrystallized from aqueous ethanol.

Produced by treatment of 2,4-dichloro-5-sulfamoylbenzoic acid with excess furfurylamine in the absence of solvent at 120-130 °C.

Preparation: K. Sturm et al., Germany patent 1122541; eidem United States of America patent 3058882 (both 1962 to Hoechst)

Prepared in 85% yield from 2-fluoro-4-chloro-5-sulfamoylbenzoic acid and furfurylamine at 95 °C for 2 hr

Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients

Pharmaceuticals

The first high-ceiling diuretic on the market and is still the most important product in this group.

Furosemide use in horses for /the control of exercise-induced pulmonary haemorrhage (EIPH) or bleeding/ is highly controversial and has been criticized by organizations outside and inside of the racing industry. ... The existing literature references suggest that furosemide has the potential of increasing performance in horses without significantly changing the bleeding status.

Furosemid was on the top ten list of pharmaceuticals used in Denmark in 1995.