Niclosamide

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Antibiotics

Pharmaceuticals

PALE, YELLOW CRYSTALS

ALMOST COLORLESS CRYSTALS

A cream-colored or yellowish-white powder

Bright yellow crystalline solid

SPARINGLY SOL IN CHLOROFORM, ETHER, ETHANOL

SOL IN ACETONE

Sol at 20 °C in 150 parts of alcohol

In water = 5-8 mg/L at 20 °C

For more Solubility (Complete) data for NICLOSAMIDE (8 total), please visit the HSDB record page.

Breast Feeding; Lactation; Anti-infective Agents; Antiparasitic Agents; Anthelmintics; Anticestodal Agents; Antinematodal Agents; Molluscacides

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Intestinal anthelminthics

TABLETS ARE SENSITIVE TO MOISTURE.

Decomp more rapidly in the presence of ... UV irradiation.

It is stable to heat and is hydrolysed by concentrated acid or alkali.

164.6 Ų [M-H]- [CCS Type: DT; Buffer gas: N2; Ionization: ESI-; Dataset: TOXCAST; Source Identifier: DTXSID7040362]

168.3 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Hydrolysed in aqueous solution with a decomposition half-life at 20 °C of 7 days (pH 6.9), 18.8 days (pH 13.3). Stable to heat. Decomposes under UV irradiation. Hydrolysed by concentrated acid or alkali.

Decomposes at 208 °C

Its biological effectiveness in water is stable at pH 5-9 and is also largely independent of the concentration of calcium and magnesium ions.

Warning

H400 (96%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

P273, P391, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 75 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Chemical: Benzamide, 5-chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxy-

Niclosamide: Does not have an individual approval but may be used under an appropriate group standard

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Niclosamide tablets. Oral dosage form new animal drugs. Specifications and conditions of use provided for dogs.

Niclosamide. New animal drugs for use in animal feeds. Conditions of use provided for laboratory mice.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Niclosamide is reported to be highly stable to heat but it is hydrolized by strong alkali or acids. Recommendable methods: Incineration & landfill. Peer review: Incinerate niclosamide in a unit with effluent gas scrubbing. (Peer-review conclusions of an IRPTC expert consultation (May 1985))

IT WAS CONCLUDED THAT CARBARYL POTENTIATED TOXICITY OF BAYER 73 TO RAINBOW TROUT BY INCREASING ITS UPTAKE FROM WATER, POSSIBLY BY EFFECTS ON GILL BLOOD FLOW OR PERMEABILITY.

Niclosamide can be admin in conjunction with several other drugs ... The effectiveness of niclosamide for tapeworms of mice is enhanced when it is given in conjunction with cucurbitine or procaine.

... To study the in utero developmental toxicity of these cmpd, pregnant female Wistar Albino rats received 1/50 LD50 of ametryne and niclosamide either individually or in combination on gestational days 5-15 before they were /sacrificed/ on day 20. The results showed neither mortality nor clinical no ... adverse effects in the treated dams throughout the study period. Also, no overt preimplantation losses were noted. ... Corrected maternal wt gain was significantly reduced under the influence of ametryne treatment. Gravid uterine weight and litter size were statistically reduced in dams treated with ametryne or a combination of ametryne and niclosamide. The percentage of postimplantation deaths was significantly raised under the influence of ametryne treatment (21.15%) or the combined treatment (25.45%) compared with 6.48% in untreated rats and 15.6% in niclosamide treated dams. ... Fetal morphological abnormality examination showed a pronounced incr in incidence of malformed fetuses (litters) up to 5.8% (29.4%), 6.48% (33.3%), and 7.9% (33.3%) in ametryne, niclosamide and combination treated groups, respectively, compared with 1.6% (11.1%) in the control group. The most common deformities were skeletal abnormalities in all groups studied, while the ametryne group showed external deformities as well. The results suggest the possibility of embryo/fetotoxicity of ametryne and fetotoxicity of niclosamide, at least at higher doses.

LC50 Gammarus pseudolimnaeus, mature, 2,400 ug/l/96 hr at 21 °C (95% confidence limit 1,800-3,100 ug/l) /wettable powder, 70%, tested in hard water, 272 ppm calcium chloride/

LC50 Orconectes, early instar, 25,000 ug/l/96 hr at 21 °C (95% confidence limit 19,000-33,000 ug/l) /wettable powder, 70%, tested in hard water, 272 ppm calcium carbonate/

LC50 Palaemonetes, mature, 10,000 ug/l/96 hr at 21 °C (95% confidence limit 7,000-15,000 ug/l) /wettable powder, 70%, tested in hard water, 272 ppm calcium carbonate/

LC50 Pteronarcys, second yr class, 200 ug/l/96 hr at 15 °C (95% confidence limit 130-300 ug/l) /wettable powder, 70%/

For more Ecotoxicity Values (Complete) data for NICLOSAMIDE (7 total), please visit the HSDB record page.

AQUATIC FATE: IT...PERSISTS /IN WATER/ FOR SEVERAL MONTHS. /ETHANOLAMINE SALT/

TERRESTRIAL FATE: Based on a recommended classification scheme(1), measured Koc values from 946-1580(2) to 3111(3) (determined in sediment, pH 7.0, 20 °C) indicate that niclosamide will have low to slight mobility in soil(SRC). Results reported for water and sediment samples indicate that both aerobic and anaerobic biodegradation may be major fate processes for this compound in soil(3,SRC). Niclosamide degraded rapidly in pond and river sediments incubated under aerobic, static conditions with half-lives of 1.1 and 3.9 days, respectively(3). Niclosamide's values for vapor pressure(4) and Henry's Law constant(4,5,SRC) indicate that volatilization from dry and moist soil surfaces should not be a major fate process(SRC). Niclosamide will be susceptible to direct photolysis on soil surfaces; degradation was rapid when this compound was exposed to UV light on silica gel TLC plates and on glass slides. Less than 50% niclosamide remained after 24 hours and after 168 hours less than 5% of the parent compound remained(6).

AQUATIC FATE: Intense sunlight, high pH (> 9.0), and the presence of sediment have been shown to reduce the efficacy of niclosamide treatments in water(1). Measured Koc values from 946-1580(2) to 3111(1) (determined in sediment, pH 7.0, 20 °C) indicate that niclosamide will adsorb strongly to suspended solids and sediment in the water column(1,2). Both aerobic and anaerobic biodegradation will be major fate processes for this compound in water(1,SRC). Niclosamide degraded rapidly in pond and river sediments incubated under aerobic, static conditions with half-lives of 1.1 and 3.9 days, respectively(1). Rapid disappearance of niclosamide from water above the sediment was also observed with half-lives of 3.1 and 0.83 days in water above pond and river sediment, respectively(1). 11.3, 7.2, 3.5, and 6.2% of the added 14C-niclosamide was present as CO2 after 32 days for cultures incubated under river sediment/aerobic, river sediment/anaerobic, pond sediment/aerobic, and pond sediment/anaerobic conditions, respectively(1). Aminoniclosamide is the major degradation product under both aerobic and anaerobic conditions(1).

AQUATIC FATE: Niclosamide will not volatilize from water surfaces based on an estimated Henry's Law constant of 6.5X10-10 atm-cu m/mole(SRC), calculated from experimental values for vapor pressure(1) and water solubility(2). An estimated BCF value of 215(3,SRC), from a measured water solubility(2), suggests that niclosamide will bioconcentrate in aquatic organisms(SRC), according to a recommended classification scheme(4). Depuration of 14C-labeled niclosamide in rainbow trout occurred within 72 hours following exposure. Biliary concentration was high, reaching a 10,000:1 bile to water ratio within 24 hours(5). 14C-labeled niclosamide had a half-life of about 150 hours in water when it was exposed to ultraviolet light (>290 nm)(6).

ATMOSPHERIC FATE: According to a suggested classification scheme(1), a measured vapor pressure of 9.9X10-9 mm Hg at 25 °C(2) indicates that niclosamide will exist mainly in the particulate phase in the ambient atmosphere. Particulate-phase niclosamide may be physically removed from the air by dry deposition(SRC). Direct photolysis of niclosamide is indicated by experiments where this compound was spotted onto silica gel plates and exposed to UV light; less than 50% of the parent compound remained after 24 hours(3).

Niclosamide works by killing tapeworms on contact. Adult worms (but not ova) are rapidly killed, presumably due to uncoupling of oxidative phosphorylation or stimulation of ATPase activity. The killed worms are then passed in the stool or sometimes destroyed in the intestine. Niclosamide may work as a molluscicide by binding to and damaging DNA.

The Koc of niclosamide is estimated as approximately 1600(SRC), using a measured water solubility of 6.5 mg/L(1) and a regression-derived equation(2,SRC). According to a recommended classification scheme(3), this estimated Koc value suggests that niclosamide has low mobility in soil(SRC). Adsorption of niclosamide by sediment reached equilibrium after 4-7.5 hours of shaking; an average Koc value of 3111 +/- 1552 was measured using five different sediments (pH range = 6.8-7.8; organic carbon = 1.9-9.2%)(4). Bottom sediment samples from 3 rivers in the Upper Peninsula of Michigan gave Koc values at 20 °C of 3510, 946, 766, and 77.9 at pH 6.5, 7, 8, and 9 for the Cedar River, 1210, 1570, 828, and 234 at the same pH values for the Ford River, and 1920, 1580, 532, and 131 at the same pH values for the Tahquamenon River(5).

Niclosamide is quite free of undesirable effects other than very occasional gastrointestinal upset.

UP TO 10% OF PATIENTS MAY EXPERIENCE...MILD ABDOMINAL PAIN & NAUSEA ON DAY DRUG IS ADMIN.

YOMESAN GIVEN ORALLY TO HUMANS AT 30 MG/KG DID NOT CAUSE FORMATION OF METHEMOGLOBIN.

A transient erythema was the only reaction in 4 of 7 persons when niclosamide was applied to their forearms for 24 hr. 2 of 6 reacted similarly to the ethanolamine salt.

For more Human Toxicity Excerpts (Complete) data for NICLOSAMIDE (10 total), please visit the HSDB record page.

A second order microbial transformation rate constant of 2.0X10-14 L/organism-hr was determined for niclosamide in natural pond water; degradation was via microbially mediated hydrolysis of the amide(1). The biodegradability of niclosamide in soil was reported as extremely low(2). Niclosamide degraded rapidly in both pond and river sediments incubated under static conditions with half-lives of 1.1 and 3.9 days, respectively(3). Rapid disappearance of niclosamide from water above the sediment was also observed with half-lives of 3.1 and 0.83 days in water above pond and river sediment, respectively(3); degradation in autoclaved samples occurred at a very slow rate indicating a dependence on microbial activity. Aminoniclosamide is the major degradation product for this reaction, representing more than 50% of the extractable radioactivity(3). 11.3, 7.2, 3.5, and 6.2% of the added 14C-niclosamide was present as CO2 after 32 days for cultures incubated under river sediment/aerobic, river sediment/anaerobic, pond sediment/aerobic, and pond sediment/anaerobic conditions, respectively; by 93 days, 37.7, 9.0, 6.8, and 8.7% of the total radioactivity for the same cultures was present as CO2(3). Aminoniclosamide was again the major degradation product detected in water and sediment extracts from this experiment; more aminoniclosamide was formed under anaerobic than aerobic conditions, especially during the first 64 days of incubation(3).

An estimated BCF value of 215 was calculated for niclosamide(SRC), using a water solubility of 6.5 mg/l(1) and a recommended regression-derived equation(2). According to a classification scheme(3), this BCF value suggests that bioconcentration in aquatic organisms may be low(SRC). Depuration occurred within 72 hours for rainbow trout exposed to 14C-labeled niclosamide. Biliary concentration was high, reaching a 10,000:1 bile to water ratio in 24 hours. The metabolite formed was the glucuronide(4,5).

The Henry's Law constant for niclosamide is estimated as 6.5X10-10 atm-cu m/mole(SRC) from its experimental values for vapor pressure, 9.9X10-9 mm Hg(1), and water solubility, 6.5 mg/L(2). This value indicates that niclosamide will be essentially nonvolatile from water surfaces(3,SRC). Niclosamide's values for vapor pressure(1) and Henry's Law constant(1,2,SRC) indicate that volatilization from dry and moist soil surfaces should not be a major fate process(SRC).

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Niclosamide tablets. Oral dosage form new animal drugs. Specifications and conditions of use provided for dogs.

Niclosamide. New animal drugs for use in animal feeds. Conditions of use provided for laboratory mice.

P02DA01

P - Antiparasitic products, insecticides and repellents

QP - Antiparasitic products, insecticides and repellents

P02DA01

Niclosamide is an antihelminth used against tapeworm infections. It may act by the uncoupling of the electron transport chain to ATP synthase. The disturbance of this crucial metabolic pathway prevents creation of adenosine tri-phosphate (ATP), an essential molecule that supplies energy for metabolism.

Niclosamide works by killing tapeworms on contact. Adult worms (but not ova) are rapidly killed, presumably due to uncoupling of oxidative phosphorylation or stimulation of ATPase activity. The killed worms are then passed in the stool or sometimes destroyed in the intestine. Niclosamide may work as a molluscicide by binding to and damaging DNA.

Niclosamide has prominent activity against most of the cestodes that infect man; Enterobius (Oxyuris) vermicularis is also susceptible. At low concn, niclosamide stimulates oxygen uptake by Hymenolepis diminuta, but at higher concn respiration is inhibited and glucose uptake is blocked. The principal action of the drug may be to inhibit anaerobic phosphorylation of adenosine diphosphate (ADP) by the mitochondria of the parasite, an energy producing process that is dependent on CO2 fixation ... .

Cestocidal activity is due to inhibition of absorption of glucose by the tapeworm and uncoupling of the oxidative phosphorylation process in the mitochondria of cestodes. Resultant blocking of the Krebs cycle leads to accumulation of lactic acid, which kills the tapeworm. ... overstimulation of adenosine triphosphatase (ATPase) activity of the mitochondria may be related to cestodal action of niclosamide.

ANTHELMINTIC NICLOSAMIDE...REDUCED TO CORRESPONDING AMINO DERIVATIVE BY BOTH MOUSE- & SHEEP-LIVER ENZYME PREPARATIONS & BY ENZYMES FROM CESTODES & NEMATODES. ...NICLOSAMIDE WAS NOT HYDROLYZED EITHER BY MAMMALIAN & HELMINTH ENZYME PREPN OR BY WHOLE HELMINTHS.

In warm-blooded organisms, the nitro group is reduced to an amino group (5,2'-dichloro-4-aminosalicylanilide).

Pregnant rats were treated orally with niclosamide at 1000 mg/kg on day 13, 19, or 20 of gestation, and rats were sacrificed at 4, 8, 16, or 24 hr posttreatment. Highest concentrations of niclosamide and 2,5'-dichloro-4'-aminosalicylanilide were detected in liver and kidney 8 hr after treatment. Niclosamide, but not its amino metabolite, was present in fetuses from rats treated on day 13, whereas both compounds were found in fetuses from rats treated on day 19 or 20. It was suggested that 19- and 20-day-old fetuses, but not 13-day-old fetuses, were able to metabolize niclosamide.

Niclosamide ... is absorbed from the gastrointestinal tract, and mutagenic metabolites are excreted in the free form and as conjugated glucuronides. as in the case of other secondary amides, phase I metabolism of niclosamide may result in hydrolytic cleavage of the amide bond, giving rise to 5-chlorosalicylic acid and 2-chloro-4-nitroaniline. ...

Agents used to treat tapeworm infestations in man or animals.

Substances used in the treatment or control of nematode infestations. They are used also in veterinary practice.

Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics.

Agents destructive to snails and other mollusks.

Niclosamide appears to be minimally absorbed from the gastrointestinal tract—neither the drug nor its metabolites have been recovered from the blood or urine.

VERY LITTLE IS ABSORBED FROM THE GI TRACT ... .

EXPOSING RAINBOW TROUT TO (14)C-BAYER 73 CAUSED BILE TO WATER (14)C RATIO OF 10,000:1. AFTER 24 HR OF EXPOSURE, THIN LAYER CHROMATOGRAPHY OF UNFRACTIONATED BILE FROM FISH SHOWED 1 MAJOR RADIOACTIVE PEAK. UNCHANGED BAYER 73 WAS FOUND IN BILE.

Niclosamide is excreted in feces.

When male and female volunteers each were treated orally with 2000 mg of radiocarbon-labeled niclosamide, between 2 and 25% of the dose was eliminated in the urine over a 4-day period; the remainder was found in the feces. Elimination of niclosamide equivalents was essentially complete after 1-2 days. Maximal niclosamide equivalents in serum ranged from 0.25 to 6.0 ppm; the variation associated with this parameter was attrributed to differential rates of absorption among the individual.

For more Absorption, Distribution and Excretion (Complete) data for NICLOSAMIDE (6 total), please visit the HSDB record page.

MEDICATION

MEDICATION (VET)

MOLLUSCICIDE /ETHANOLAMINE SALT/

Molluscicide with respiratory and stomach action; control of schistosomiasis and fascioliasis in man by control of fresh-water snails which act as intermediate hosts.

Use (kg; approx.) in Germany (2009): >10

For the treatment of tapeworm and intestinal fluke infections: Taenia saginata (Beef Tapeworm), Taenia solium (Pork Tapeworm), Diphyllobothrium latum (Fish Tapeworm), Fasciolopsis buski (large intestinal fluke). Niclosamide is also used as a molluscicide in the control of schistosomiasis.

PHOSPHORUS TRICHLORIDE IS SLOWLY INTRODUCED INTO A BOILING XYLENE SOLN CONTAINING 5-CHLOROSALICYLIC ACID & 2-CHLORO-4-NITROANILINE IN EQUIMOLAR RATIO & HEATING CONTINUED FOR 3 HR. CRYSTALS OF NICLOSAMIDE SEPARATE ON COOLING & ARE RECRYSTALLIZED FROM ETHANOL.

TABLETS: 500 MG. THE TABLETS ALTHOUGH NOT MARKETED IN THE US, MAY BE OBTAINED BY LICENSED PHYSICIANS FROM THE PARASITIC DISEASE DRUG SERVICE, CENTER FOR DISEASE CONTROL, ATLANTA, GA, 30333.

CLONITRALID (FOR 2-HYDROXYETHYLAMMONIUM SALT) FOR PUBLIC HEALTH USE (FED REP GERM). /2-HYDROXYETHYLAMMONIUM SALT/

... EC (250 G AI/L); WP (700 G/KG).

BAYLUSCIDE /ETHANOLAMINE SALT OF NICLOSAMIDE/...WETTABLE POWDER; EMULSIFIABLE CONCENTRATE /ETHANOLAMINE SALT/

For more Formulations/Preparations (Complete) data for NICLOSAMIDE (7 total), please visit the HSDB record page.

... US PATENT ... 3,113,067 ... NICLOSAMIDE IS A POWERFUL MOLLUSCICIDE GIVING A TOTAL KILL OF AUSTRALORBIS GLAB @ 0.3 MG/L; IT IS NON-PHYTOTOXIC @ FIELD CONCN.

BASIC PRODUCER: BAYER AG (FEDERAL REPUBLIC OF GERMANY) (BAYLUSCID) /2-HYDROXYETHYLAMMONIUM SALT/

IT IS EFFECTIVE AGAINST MOST AQUATIC SNAILS @ 0.3-1.0 PPM ... IT HAS THE ADVANTAGE OF CONSIDERABLE SELECTIVITY ... /ETHANOLAMINE SALT/

It is marketed in the USA for use only in dogs and cats among domestic animals ...

For more General Manufacturing Information (Complete) data for NICLOSAMIDE (7 total), please visit the HSDB record page.