Nystatin

926.09

276.208923

215-749-0

DTXSID4040688

Light yellow powder|Yellow to tan powder

A - Alimentary tract and metabolism|D - Dermatologicals|G - Genito urinary system and sex hormones

38210000

327.45000

6.14

yellow suspension

0.9±0.1 g/cm3

44-46 °C

400.2±14.0 °C at 760 mmHg

297.0±15.2 °C

1.504

H2O: insoluble

−20°C

8.7X10-7 mm Hg at 25 °C (est)

LD50 i.p. in mice: ~200 mg/kg (Seneca)

D25 -10° (glacial acetic acid); +21° (pyridine); +12° (DMF); -7° (0.1N HCl in methanol)

Odor suggestive of cereals

Amphoteric

Henry's Law constant = 2.0X10-7 atm-cu m/mol at 25 °C (est)

Gradually decomp above 160 °C without melting by 250 °C; activity not diminished by blood or serum; exhibits strong reducing properties|Aq soln are stable for 10 minutes on heating to 100 °C at pH 7.0; stable in moderately alkaline media, but labile at pH 9 and pH 2|Heat, light, and oxygen accelerate decomp|Hygroscopic|For more Other Experimental Properties (Complete) data for NYSTATIN (7 total), please visit the HSDB record page.

3

NONH for all modes of transport

3

11-34

22-24/25-45-36/37/39-26-16

RF5950000

F,C

Solutions and aqueous suspensions begin to lose activity soon after preparation. Aqueous suspensions are stable for 10 minutes on heating to 100 °C at pH 7; also stable in moderately alkaline media, but labile at pH 9 and pH 2. Heat, light, and oxygen accelerate decomposition.

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.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl nystatin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.|Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: nystatin is included in topical antifungal drug products.|A tolerance of zero is established for residues of nystatin in or on eggs and the uncooked edible tissues of swine and poultry.|New animal drugs for use in animal feeds. Requirement of a medicated feed mill license. Nystatin is included on this list.|For more FDA Requirements (Complete) data for NYSTATIN (7 total), please visit the HSDB record page.

|Danger|H300 (50%): Fatal if swallowed [Danger Acute toxicity, oral]|P260, P261, P264, P270, P271, P301+P310, P304+P340, P312, P314, P321, P330, P403+P233, P405, and P501|Aggregated GHS information provided by 7 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Nystatin therapy has been associated with a low rate of serum enzyme abnormalities, although it has been difficult to attribute these elevations to nystatin. Despite its use for several decades, there have been no convincing cases of acute hepatic injury linked to nystatin therapy. While nystatin is usually is not normally absorbed, low concentrations may enter the circulation in patients with inflammation and damage to the gastrointestinal tract. Nevertheless, nystatin is considered very safe and is unlikely to cause hepatic injury.

LD50 Mouse ip 200 mg/kg

Nystatin is produced from Streptomyces noursei, S. aureus, and other Streptomyces species(1).

Nystatin's production and use as an antibiotic, experimental teratogen(1), feed additive(2), and a veterinarian medication(3) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 170(SRC), determined from a water solubility of 3.60X10+2 mg/L(2) and a regression-derived equation(3), indicates that nystatin is expected to have moderate mobility in soil(SRC). Volatilization of nystatin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.0X10-7 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Nystatin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.68X10-7 mm Hg(SRC), determined from a fragment constant method(5). A 4% degradation in 28 days using the Closed Bottle test(6) indicates that biodegradation is not an important environmental fate process in soil.|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 170(SRC), determined from a water solubility of 3.60X10+2 mg/L(2) and a regression-derived equation(3), indicates that nystatin is expected to adsorb slightly to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.0X10-7 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 22(SRC), from its water solubility and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). A 4% degradation in 28 days using the Closed Bottle test(7) indicates that biodegradation is not an important environmental fate process in water.|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), nystatin, which has an estimated vapor pressure of 8.7X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere.Vapor-phase nystatin is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 1.5 hours(SRC), calculated from its rate constant of 2.5X10-10 cu cm/molec-sec at 25 °C(SRC), that was derived using a structure estimation method(3). Vapor-phase nystatin is degraded in the atmosphere by reaction with ozone(SRC); the half-life for this reaction in air is estimated to be 2.6 hours(SRC), calculated from its rate constant of 1.1X10-16 cu cm/molec-sec at 25 °C(SRC), that was derived using a structure estimation method(4). Particulate-phase nystatin may be removed from the air by wet or dry deposition(SRC). The rate of nystatin decomposition is affected by light(5) and therefore the compound may be susceptible to direct photolysis by sunlight.

The rate constant for the vapor-phase reaction of nystatin with photochemically-produced hydroxyl radicals has been estimated as 2.5X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1.5 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of nystatin with ozone has been estimated as 1.1X10-16 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2.6 hours at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2). Nystatin is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). The rate of nystatin decomposition is affected by light(4) and therefore the compound may be susceptible to direct photolysis by sunlight.

An estimated BCF of 22 was calculated for nystatin(SRC), using a water solubility of 3.60X10+2 mg/L(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low provided the compound is not metabolized by the organism(SRC).

The Koc of nystatin is estimated as 170(SRC), using a water solubility of 3.60X10+2 mg/L at 25 °C(1)and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that nystatin is expected to have moderate mobility in soil.

The Henry's Law constant for nystatin is estimated as 2.0X10-10 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that nystatin is expected to be essentially nonvolatile from water surfaces(2). Nystatin's Henry's Law constant indicates that it will be essentially nonvolatile from moist soil surfaces(SRC). Nystatin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.7X10-7 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to nystatin may occur through inhalation and dermal contact with this compound at workplaces where nystatin is produced or used. The general population may be exposed to nystatin via use of antimicrobial products containing nystatin. (SRC)

Nystatin is a topical and oral antifungal agent with activity against many species of yeast and candida albicans, which is used largely to treat skin and oropharyngeal candidiasis. Nystatin is not absorbed orally and has not been linked to drug induced liver injury.

Antifungal Agents

Antibiotics, Antifungal; Antibiotics, Macrolide; Ionophores|MEDICATION (VET):Antifungal; growth promotant|MEDICATION (VET): /Used in treatment of/ intestinal mycosis due to Candida albicans in poultry; occasionally orally in cats and dogs in suspected Candida intestinal overgrowth following antibiotic therapy, and also topically ... as cream or ointment on skin lesions ...|Nystatin vaginal tablets are used as lozenges to treat oropharyngeal candidiasis since their slow dissolution rate provides prolonged oral contact. /NOT included in US product labeling/|For more Therapeutic Uses (Complete) data for NYSTATIN (9 total), please visit the HSDB record page.

Since it is not known whether nystatin is distributed into human milk, the drug should be used with caution in nursing women.|Adverse effects occur infrequently with oral nystatin therapy. Mild and transitory nausea, vomiting, GI distress, and diarrhea have occurred; high oral doses (e.g., greater than 5 million units daily) are most likely to produce these adverse GI effects. Hypersensitivity reactions have been reported very rarely.|Patients should be instructed to contact their physician if symptoms of irritation or sensitization occur during nystatin therapy. Patients should be warned against interrupting or discontinuing vaginal nystatin therapy during a prescribed regimen, even during menstruation or if symptomatic relief occurs after only a few days of therapy, unless otherwise instructed by their physician. Patients should be advised that adjunctive measures such as therapeutic douches are not necessary and may be inadvisable during vaginal nystatin therapy; however, cleansing douches may be used in nonpregnant women, if desired, for aesthetic effect.|Adverse reactions to topically applied nystatin are very infrequent, even during prolonged use. Irritation has occurred rarely. Hypersensitivity reactions to nystatin have been reported only rarely; however, preservatives (eg, ethylenediamine, parabens, thimerosal) in some of the formulations are associated with a high incidence of contact dermatitis. An acneiform eruption has occurred rarely following topical application of nystatin and triamcinolone acetonide.|For more Drug Warnings (Complete) data for NYSTATIN (9 total), please visit the HSDB record page.

Candida rarely become resistant to nystatin in vivo. When resistant strains appear, they frequently also are resistant to other polyene antifungal antibiotics. Nystatin is not active against bacteria, protozoa, or viruses.

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)|Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. (See all compounds classified as Antifungal Agents.)|Chemical agents that increase the permeability of biological or artificial lipid membranes to specific ions. Most ionophores are relatively small organic molecules that act as mobile carriers within membranes or coalesce to form ion permeable channels across membranes. Many are antibiotics, and many act as uncoupling agents by short-circuiting the proton gradient across mitochondrial membranes. (See all compounds classified as Ionophores.)

Nystatin penetrates eye poorly.|Nystatin is poorly absorbed from the GI tract, and detectable blood concentrations are not obtained after usual doses. Following oral administration, nystatin is excreted almost entirely in feces as unchanged drug.|In healthy individuals, mean salivary nystatin concentrations in excess of those required in vitro for growth inhibition of clinically important Candida persist for approximately 2 hours after the beginning of oral dissolution of two nystatin lozenges (400,000 units) administered simultaneously.|Not absorbed following topical application to intact skin or mucous membranes.|For more Absorption, Distribution and Excretion (Complete) data for NYSTATIN (6 total), please visit the HSDB record page.

Nystatin exerts its antifungal activity by binding to sterols in the fungal cell membrane. The drug is not active against organisms (e.g., bacteria) that do not contain sterols in their cell membrane. As a result of this binding, the membrane is no longer able to function as a selective barrier, and potassium and other cellular constituents are lost.|... /Antimicrobial/ agents that act directly on the cell membrane of the microorganism, affecting permeability and leading to leakage of intracellular compounds; these include ... the polyene antifungal agents nystatin ... which bind to cell-wall sterols ...

/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 /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's 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 or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/CASE REPORTS/ ...Few cases of local allergic reactions have been reported.|/EPIDEMIOLOGY STUDIES/ Prescription frequencies in the first trimester were compared for miconazole, clotrimazole, nystatin, candicidin, aminacrine compounds, and metronidazole before deliveries involving congenital anomalies versus those not linked to congenital anomalies. Prescriptions before spontaneous abortions were compared with those in the first trimester of deliveries and with those before legal abortions. No statistically significant association was observed with any of these agents for the overall frequency of birth defects or for specific birth defects analyzed (cardiovascular defects, oral clefts, and spina bifida). Two hundred fifty miconazole exposures among 4264 spontaneous abortions, compared with 2236 in the first trimester of 55,736 deliveries, provided an estimated relative risk of 1.4 (95% confidence limits 1.2-1.5). One hundred twelve treatments with clotrimazole among the spontaneous abortions, compared with 1086 among the deliveries, provided a relative risk of 1.4 (95% confidence limits 1.1-1.6). In contrast, large numbers of exposures to nystatin and aminacrine compounds did not show this association, suggesting that spontaneous abortions are caused by the imidazole agents miconazole and clotrimazole rather than the condition being treated. Because many associations were examined without previous hypotheses, and because the data were inadequate to show an elevated risk for clotrimazole when comparing spontaneous with legal abortion exposures, these findings are considered to be a signal for further studies rather than definitive in themselves.

Fungicidin

Tablets, dragees, lozenges, suspensions, drops, ointments, powders, gels, creams, ovulas, and vaginal tablets of different concentrations. There are also formulations available in combination with antibiotics and/or steroids such as tetracycline, neomycin, gramicidin, and cortisone. Dosages are often expressed in IE (100 000 IE = 22.73 mg nystatin A1).|Trade Names: Adiclair (Ardeypharm), Biofanal (Pfleger), Candex (Dome), Candio-Hermal (Hermal, Merck), Canstat (Lederle), Diastatin (Pfizer), Fungicidin (Spofa), Fungireduct (Azupharma), Herniocid (Mayrhofer), Korostatin (Holland-Rantos), Lederlind (Lederle), Lystin (Mekim), Mikostatin (Squibb), Moronal (Heyden, Squibb), Multilind (Bristol-Myers Squibb, Fair), Mycostatin (Bristol-Myers Squibb, Heyden, Sanofi Winthrop, Westwood-Squibb), Mykinac (NMC), MycoPosterine N (Kade), Mykundex (Jossa), Nadostine (Pan-Well), Nilstat (Lederle), Nyaderm (Taro), Nysert (Norwich Eaton), Nystacid (Farmos Group), Nystaderm (Dermapharm), Nysta-Dome (Dome), Nystan (Squibb), Nystat-Rx (Pharma-Tek), Nystavescent (Squibb), Nystex (Savage), Oranyst (Taro), O-V Statin (Squibb), Restatin (Remedica), Rivostatin (Rivopharm) Stereomycin (Medica).|Nystatin is commercially available as a cream, ointment, or powder for topical application to the skin; as a powder for oral suspension, oral suspension, or film-coated tablets for oral administration; as oral lozenges for oral topical administration; and as tablets for intravaginal administration.|Oral: For suspension 50 million units Nystatin Powder, Paddock Nystat-Rx, (Pharma-Tek); 150 million units Nystatin Powder, Paddock Nystat-Rx, (Pharma-Tek); 500 million units Nystatin Powder, Paddock Nystat-Rx, (Pharma-Tek); 1 billion units Nystat-Rx, (Pharma-Tek); 2 billion units Nystatin Powder, (Paddock); 5 billion units Nystatin Powder, (Paddock). Oral: Suspension: 100,000 units/mL Mycostatin ( with =1% alcohol parabens and sucrose 50%), (Bristol-Myers Squibb). Oral: Tablets, film-coated 500,000 units Mycostatin Filmlok ( with povidone), (Bristol-Myers Squibb)

Nystatin is now known to be a mixture but composition has not been completely elucidated. Nystatin A [34786-70-4] C47-H75-N-O17 is closely related to Amphotericin B. Each is a macrocyclic lactone containing a ketal ring, an all-trans polyene system, and a mycosamine (3-amino-3-deoxyrhamnose) moiety.|/Used/ mostly as antifungal feed additive in control or treatment of crop ... US feed additive regulations use 2,800 units/mg. ... US regulations established zero tolerance for its residue in or on uncooked tissues or by-products (including eggs) of treated animals or poultry if used for human consumption.|Used as food additive permitted in feed and drinking water of animals and ... also permitted in food for human consumption.|Nystatin was found in the mycelium of Streptomyces noursei in 1950 and produced on an industrial scale by Squibb & Sons Co. in 1954. This antibiotic was used orally and topically as the first clinically applied polyene macrolide with antifungal properties.

UV spectrophotometric procedure for determination of nystatin during stability studies is briefly described.|A flow microcalorimetric procedure has been developed for bioassay of nystatin. It is assayed by monitoring its effect on respiring culture of saccharomyces cerevisiae.|It is concluded that the newer methods of assay are as reproducible & reliable as agar diffusion & turbidimetric methods & that they are generally more sensitive.|Method: AOAC 974.48; Procedure: microbiological method; Analyte: nystatin; Matrix: feeds; Detection Limit: not provided.|For more Analytic Laboratory Methods (Complete) data for NYSTATIN (12 total), please visit the HSDB record page.

Analyte: nystatin; matrix: cerebral spinal fluid; procedure: high-performance liquid chromatography with ultraviolet detection at 410 nm

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients|Veterinary Drug -> ANTIFUNGAL_AGENT; -> JECFA Functional Classes

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