Nystatin

Nystatin oral suspension and tablets should be stored in tight, light-resistant containers at room temperature (eg, 15-30 °C); exposure of the tablets to temperatures exceeding 40 °C and freezing of the oral suspension should be avoided. Nystatin powder should be stored in tight, light-resistant containers and refrigerated at 2-8 °C.

Most nystatin preparations for topical application to the skin should be stored at 15-30 °C and protected from freezing. Mycostatin® vaginal tablets should be stored at 2-15 °C. Nystatin lozenges for oral topical administration should be stored in tight, light-resistant containers and refrigerated at 2-8 °C.

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.

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.

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.

Nystatin interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability. Nystatin exerts its antifungal activity by binding to ergosterol found in fungal cell membranes. Binding to ergosterol causes the formation of pores in the membrane. Potassium and other cellular constituents leak from the pores causing cell death.

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.

/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.

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.

MEDICATION (VET)

MEDICATION

An experimental teratogen. An anti-biotic

Antimycotic polyene antibiotic... for local treatment of vulvovaginal candidiasis (monoliasis).

Medicine (antifungal antibiotics), feed additive

Use (kg; approx.) in Germany (2009): >7500

Vandeputte, US patent 2,832,719 (1958 to Olin Mathieson); Renella, US patent 3,517,100 (1970 to American Cyanamid)

Polyene antifungal antibiotic complex containing 3 biologically active compounds, A1,A2,A3. Produced by Streptomyces noursei, S. aureus and other Streptomyces spp.

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.