A Comprehensive Monograph on Nystatin (DB00646)

1.0 Executive Summary

Nystatin is a polyene macrolide antibiotic with a long-standing history in the management of fungal infections. Discovered in 1950 from the soil bacterium Streptomyces noursei, it was the first agent of its class to be used clinically, establishing a new paradigm for antifungal therapy. Its primary mechanism of action involves binding with high affinity to ergosterol, an essential sterol in the fungal cell membrane. This interaction leads to the formation of transmembrane pores, disrupting membrane integrity and causing the leakage of vital intracellular components, which results in either fungistatic or fungicidal activity, particularly against a broad spectrum of yeasts and fungi, most notably Candida species.

The clinical utility and safety profile of Nystatin are fundamentally defined by its pharmacokinetic properties. When administered orally or topically, it undergoes negligible systemic absorption. This characteristic confines its therapeutic effects to the site of application, making it an exceptionally safe and effective treatment for localized cutaneous, mucocutaneous, and gastrointestinal candidiasis, including oropharyngeal thrush, diaper dermatitis, and intestinal infections. Conversely, this same property, combined with significant systemic toxicity when administered parenterally, renders it unsuitable for the treatment of systemic mycoses.

Available in a variety of formulations—including oral suspensions, tablets, topical creams, ointments, and powders—Nystatin allows for targeted local therapy. Despite the advent of newer, systemically active antifungal agents, Nystatin remains a valuable and widely prescribed medication. Its inclusion on the World Health Organization's List of Essential Medicines underscores its enduring importance in global health as a reliable, low-cost, and safe option for the management of common, non-invasive fungal infections.

2.0 Identification and Physicochemical Profile

The foundational identity of Nystatin is established through a combination of chemical, structural, and physical properties that dictate its formulation, stability, and clinical behavior.

2.1 Chemical and Structural Identity

Nystatin is a well-characterized small molecule classified as a polyene antifungal antibiotic.[1] Its primary identifiers are as follows:

• Generic Name: Nystatin [1]
• DrugBank ID: DB00646 [1]
• CAS Number: 1400-61-9 [3]

The empirical chemical formula for the principal component of Nystatin is C47​H75​NO17​.[1] This corresponds to an average molecular weight of approximately 926.107 g/mol and a monoisotopic mass of 925.503499959 Da.[1] Minor variations in reported molecular weight (e.g., 926.09 g/mol, 926.12 g/mol) exist across different databases, a discrepancy that reflects the nature of the commercial drug substance.[3]

A critical aspect of Nystatin's chemical identity is that it is not a single, pure compound but rather a complex mixture of three closely related, biologically active components: Nystatin A1, Nystatin A2, and Nystatin A3. Nystatin A1 is the main and most abundant component of this complex.[5] These components differ slightly in their structure, such as variations in the stereochemistry of hydroxyl groups or the position of a carbonyl group.[8] This inherent heterogeneity explains the slight variations in reported molecular weights and the multiple complex IUPAC names found in the literature. For practical purposes, "Nystatin" in a pharmaceutical context refers to this standardized complex, with its potency measured in units of activity rather than by mass alone.

The structural complexity of Nystatin A1 is reflected in its formal IUPAC name: $(1S,3R,4R,7R,9R,11R,15S,16R,17R,18S,19E,21E,25E,27E,29E,31E,33R,35S,36R,37S)-33-oxy-1,3,4,7,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,25,27,29,31-hexaene-36-carboxylic acid.[10] The molecule is characterized by a large macrolide ring containing a conjugated tetraene and a diene moiety, attached to the aminoglycoside sugar D-mycosamine.[11]

The drug is known by numerous synonyms, including Nistatina, Nystatine, Nystatinum, and the early developmental name Fungicidin.[1]

2.2 Physical and Chemical Properties

Nystatin presents as a light yellow to yellow-tan fine powder with a characteristic odor described as being suggestive of cereals.[2] It does not have a sharp melting point but instead decomposes gradually at temperatures above 155–160 °C.[2]

Its solubility profile is a defining characteristic. Nystatin is poorly soluble in water, with an aqueous solubility of approximately 360 mg/L at 24 °C.[2] It is also insoluble in nonpolar solvents like ether and chloroform.[2] It exhibits slightly better solubility in lower aliphatic alcohols, such as methanol (11.2 mg/mL) and ethanol (1.2 mg/mL), and is highly soluble in solvents like propylene glycol and dimethylformamide (DMF).[2]

Nystatin is an amphoteric substance, containing both a carboxylic acid group and an amino group, which gives it acidic and basic properties with pKa values of approximately 5.72 and 8.64, respectively.[2]

2.3 Stability and Formulation Considerations

The physicochemical properties of Nystatin directly inform its formulation, clinical application, and storage requirements. The molecule is notably unstable and susceptible to degradation upon exposure to heat, light, moisture, air, and oxygen.[2] This extensive unsaturation within its polyene structure makes it prone to oxidation, which inactivates the drug.[12]

Its stability is also highly dependent on pH. Aqueous suspensions and solutions are unstable, particularly in strongly acidic (pH 2) or alkaline (pH 9) conditions.[2] It exhibits optimal stability in phosphate-citrate buffers at a pH of 5.7.[2]

These stability challenges necessitate specific handling and storage conditions. The pure substance and its formulations must be stored in tightly closed containers, protected from light, and often refrigerated (e.g., -20°C for the pure substance, 2-8°C for some formulations) to maintain potency.[4] Oral suspensions, once opened, should typically not be used beyond 30 days.[15]

The drug's very low aqueous solubility is the primary driver behind its available formulations. It is not formulated as a true aqueous solution for clinical use but rather as a suspension for oral administration or as topical creams, ointments, and powders.[16] This poor solubility is also a key factor contributing to its negligible absorption from the gastrointestinal tract, a pharmacokinetic property that is central to its safety profile and clinical niche.

Property	Description	Reference(s)
DrugBank ID	DB00646	1
CAS Number	1400-61-9	3
Molecular Formula	C47​H75​NO17​	1
Average Mol. Weight	926.107 g/mol	1
Appearance	Light yellow to yellow-tan fine powder	2
Odor	Suggestive of cereals	2
Water Solubility	360 mg/L (at 24 °C); poorly soluble	2
Melting Point	Decomposes >155–160 °C	2
Storage Conditions	Store sealed, protected from heat, light, and moisture; refrigeration often required	4

3.0 Historical Perspective and Biosynthesis

Nystatin holds a significant place in the history of medicine as a pioneering antifungal agent. Its discovery and natural origin are foundational to understanding its chemical class and therapeutic role.

3.1 Discovery and Development

Nystatin was discovered in 1950 by Rachel Fuller Brown and Elizabeth Lee Hazen, two researchers at the New York State Department of Health's Division of Laboratories and Research.[11] Their work marked a major breakthrough, as Nystatin was the first polyene macrolide antifungal to be identified and developed for clinical use, providing a much-needed weapon against previously difficult-to-treat fungal infections.[11]

The name of the drug is a tribute to the institution where this seminal work was conducted, derived from the New York State Department of Health.[11] The discovery was the result of a painstaking screening of hundreds of soil samples for microorganisms with antifungal activity.[17] Industrial-scale production was initiated by Squibb & Sons Co., and the drug was first marketed in 1954 under the brand name Mycostatin.[5] Initial medical approvals were granted around 1954-1955, solidifying its place in the clinical armamentarium.[18]

3.2 Origin and Biosynthetic Pathway

Nystatin is a natural product, a secondary metabolite produced by the soil actinomycete Streptomyces noursei.[1] The specific strain that led to its discovery was isolated from the soil of a dairy farm in Fauquier County, Virginia, belonging to a friend of the researchers named Nourse, after whom the species was named.[11]

Commercial production of Nystatin relies on large-scale fermentation of S. noursei in controlled liquid nutrient media.[21] The antibiotic is primarily intracellular, meaning it is contained within the bacterial cells (mycelium). The recovery process, therefore, involves separating the mycelium from the fermentation broth and then extracting the Nystatin using a water-miscible organic solvent, such as methanol, ethanol, or isopropanol.[20]

The complex chemical structure of Nystatin A1 is assembled through a well-defined biosynthetic pathway. It is a polyketide, synthesized via the polyketide synthase I (PKS I) pathway.[11] Analysis of the Nystatin biosynthetic gene cluster in

S. noursei has identified the requisite enzymatic machinery, including a loading module (nysA), six large PKS modules for assembling the macrolide core (nysB, nysC, nysI, nysJ, nysK), and two thioesterase modules for chain termination (nysK, nysE).[11] After the synthesis of the macrolide ring, the molecule undergoes a series of post-PKS modifications. These are catalyzed by enzymes encoded within the gene cluster, including P450 monooxygenases (nysL, nysN), an aminotransferase (nysDII), and a glycosyltransferase (nysDI), which attaches the crucial D-mycosamine sugar moiety.[11]

The shared biosynthetic origin of Nystatin with other polyene antifungals, most notably Amphotericin B, accounts for their significant structural similarities.[1] Both molecules possess a large macrolide ring with a series of conjugated double bonds and are glycosylated with mycosamine. This structural relationship is the biochemical basis for their shared mechanism of action—binding to ergosterol—and also explains the clinically observed phenomenon of cross-resistance, where fungal strains that develop resistance to Nystatin often exhibit reduced susceptibility to Amphotericin B as well.[19]

4.0 Clinical Pharmacology

The clinical pharmacology of Nystatin is centered on its specific mechanism of action, which confers a potent and selective antifungal effect. Its pharmacodynamic properties, including its spectrum of activity and resistance patterns, further define its therapeutic role.

4.1 Mechanism of Action: The Ergosterol-Binding Ionophore Model

Nystatin's antifungal activity is a direct result of its interaction with the fungal cell membrane. It functions as a channel-forming ionophore, a molecule that can insert itself into a lipid bilayer and create a pathway for ions to cross.[1]

• Primary Target: The specific molecular target for Nystatin is ergosterol, a sterol that is the principal sterol component of fungal cell membranes. Ergosterol is functionally analogous to cholesterol in mammalian cells and is essential for maintaining the structural integrity, fluidity, and function of the fungal membrane.[1]
• Binding and Pore Formation: Nystatin has a high binding affinity for ergosterol. Upon encountering a susceptible fungal cell, Nystatin molecules insert into the membrane and aggregate with ergosterol molecules. It is estimated that a complex of 4 to 12 Nystatin molecules, along with an unknown number of ergosterol molecules, assembles to form a stable, barrel-stave-like pore that spans the entire membrane.[1]
• Disruption of Membrane Integrity: The formation of these aqueous pores fundamentally compromises the membrane's role as a selective barrier. This leads to a rapid and uncontrolled efflux of essential intracellular components, particularly monovalent cations like potassium (K+), and an influx of protons, leading to intracellular acidification.[1] The loss of the electrochemical gradient and vital cellular contents ultimately leads to the cessation of metabolic activity and cell death.[1]

4.2 Secondary Mechanisms and Cellular Effects

In addition to direct pore formation, Nystatin exerts other disruptive effects on the fungal membrane.

• Lipid Peroxidation: The series of conjugated double bonds in Nystatin's polyene structure is capable of abstracting electron density from ergosterol. This can initiate a cascade of lipid peroxidation within the membrane, causing oxidative damage to membrane lipids. This process alters the biophysical properties of the membrane, further disrupting transport functions and contributing significantly to the leakage of potassium ions and rapid cell death.[11]
• Cholesterol Binding and Toxicity: The therapeutic utility of Nystatin is predicated on its selective toxicity. This selectivity arises from its much greater binding affinity for fungal ergosterol compared to its mammalian counterpart, cholesterol.[1] This differential affinity creates a therapeutic window where concentrations effective against fungi have minimal impact on host cells. However, this selectivity is not absolute. Nystatin can bind to cholesterol, albeit with lower affinity. This off-target binding is the molecular basis for its significant systemic toxicity. When Nystatin is administered parenterally and achieves high concentrations in the bloodstream, it can bind to cholesterol in human cell membranes—particularly in the renal tubules—and form pores, leading to the same cytotoxic effects observed in fungi. This explains the severe nephrotoxicity that has precluded its use as a systemic agent.[11]

4.3 Pharmacodynamics: Spectrum of Activity and Resistance

Nystatin exhibits a broad spectrum of antifungal activity, primarily against yeasts and yeast-like fungi. Its action is concentration-dependent; it is generally fungistatic (inhibits growth) at lower concentrations and fungicidal (kills the fungus) at higher concentrations or against highly susceptible organisms.[1]

• Antifungal Spectrum: Nystatin is highly active against most species of Candida, including C. albicans, C. parapsilosis, C. tropicalis, C. guilliermondi, and C. krusei. It is also effective against other pathogenic fungi such as Cryptococcus neoformans, Aspergillus species, Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides immitis.[8] It has no clinically significant activity against bacteria, protozoa, or viruses, as these organisms lack sterols in their cell membranes.[1]
• Resistance Patterns: The development of resistance to Nystatin varies by species. In Candida albicans, the most common cause of candidiasis, acquired resistance is minimal and rarely develops during the course of therapy.[1] However, other Candida species, such as C. tropicalis and C. krusei, can become quite resistant upon exposure to the drug.[19] This resistance is often associated with alterations in the sterol composition of the fungal cell membrane, which reduces the amount of ergosterol available for Nystatin to bind. Because Amphotericin B shares the same target, this mechanism of resistance frequently leads to cross-resistance between the two drugs.[19] This has important clinical implications, as failure of Nystatin therapy in a non- albicans Candida infection may predict a poor response to Amphotericin B.

5.0 Pharmacokinetic Profile: A Non-Systemic Agent

The pharmacokinetic profile of Nystatin is uniquely characterized by its almost complete lack of systemic absorption, which is the single most important factor governing its clinical use, safety, and limitations. The processes of absorption, distribution, metabolism, and excretion (ADME) are all dominated by this fundamental property.

5.1 Absorption and Bioavailability

Following administration by oral or topical routes, systemic absorption of Nystatin is insignificant.[1]

• Oral Administration: When taken orally, either as a suspension or tablet, Nystatin passes through the gastrointestinal tract with virtually no absorption into the bloodstream. Its oral bioavailability is effectively 0%.[1] Consequently, no detectable plasma concentrations are achieved with standard therapeutic doses.[1]
• Topical and Vaginal Administration: Similarly, when applied to intact skin or mucous membranes (including the vagina), Nystatin is not absorbed into the systemic circulation.[1]
• Exceptions to Non-Absorption: While non-absorption is the rule, there are rare circumstances where low but significant plasma concentrations have been occasionally observed. This has been noted in patients with renal insufficiency or in those with severe inflammation or damage to the gastrointestinal tract, which may compromise the integrity of the mucosal barrier.[16]

5.2 Distribution, Metabolism, and Excretion (ADME)

The negligible absorption of Nystatin dictates the remainder of its pharmacokinetic profile.

• Distribution: As the drug does not enter the systemic circulation in meaningful amounts, it does not undergo distribution to body tissues. Its therapeutic action is therefore strictly localized to the surfaces where it is applied: the skin, the oral cavity, and the lumen of the gastrointestinal tract.[1] For the same reason, Nystatin is not subject to plasma protein binding.[1]
• Metabolism: Because it is not systemically available, Nystatin is not metabolized to any appreciable extent by hepatic or other enzymes.[1]
• Excretion: Following oral administration, the vast majority of the dose is excreted unchanged in the feces.[1] Its elimination half-life is therefore not a meaningful pharmacological parameter and is simply dependent on the rate of gastrointestinal transit.[11]

This "non-pharmacokinetic" profile is not a defect but rather the defining characteristic of Nystatin's therapeutic niche. It allows for the delivery of high, effective concentrations of the drug directly to the site of a superficial infection without exposing the rest of the body to the drug, thereby avoiding the systemic toxicity that precludes its parenteral use. This unique ADME profile is the cornerstone of Nystatin's exceptional safety record when used as indicated.

6.0 Therapeutic Applications and Clinical Efficacy

Nystatin is a versatile antifungal agent used for both the treatment and prophylaxis of localized infections caused by susceptible fungi, primarily Candida species. Its utility is maximized through a range of formulations designed for specific anatomical sites.

6.1 Approved Indications and Off-Label Uses

The clinical applications of Nystatin are focused on infections where the drug can be applied directly to the affected area.

• Primary Indications:
• Oropharyngeal Candidiasis (Thrush): Nystatin oral suspension, lozenges, and pastilles are first-line treatments for mild to moderate thrush in both immunocompetent and immunocompromised individuals.[1]
• Intestinal Candidiasis: Oral tablets and powder for suspension are indicated for the treatment of non-esophageal gastrointestinal candidiasis.[1]
• Cutaneous and Mucocutaneous Candidiasis: Topical formulations (cream, ointment, powder) are used to treat a variety of skin infections, including candidal diaper dermatitis, intertrigo (infections in skin folds), and paronychia (infection around the nails).[1]
• Vulvovaginal Candidiasis: Vaginal tablets and topical creams are indicated for the treatment of vaginal yeast infections.[1]
• Prophylactic Use: Oral Nystatin is often used to prevent candidal overgrowth in high-risk populations. This includes patients with HIV/AIDS who have low CD4+ counts, individuals undergoing chemotherapy, and organ transplant recipients on immunosuppressive therapy.[11]
• Off-Label Use: A notable off-label use is the prophylaxis of invasive candidiasis in very low-birth-weight neonates. While some studies have shown efficacy, it is generally considered a second-line option after fluconazole due to concerns about resistance and efficacy in this vulnerable population.[1]
• Combination Products: Nystatin is a common component in multi-ingredient topical products. It is frequently combined with a corticosteroid (e.g., triamcinolone, hydrocortisone) to treat inflamed fungal dermatoses, where the steroid reduces inflammation and the Nystatin treats the underlying infection. It may also be combined with antibacterial agents (e.g., neomycin, gramicidin) for mixed bacterial and fungal skin infections.[1]

Formulation	Strength	Primary Indication(s)	Common Brand Name(s)
Oral Suspension	100,000 units/mL	Oropharyngeal Candidiasis (Thrush)	Mycostatin, Nystan, Nilstat, Nystex 11
Oral Tablets	500,000 units	Intestinal Candidiasis	Mycostatin, Nilstat 16
Topical Cream	100,000 units/g	Cutaneous Candidiasis, Diaper Dermatitis	Mycostatin, Nystex, Pediaderm AF 49
Topical Ointment	100,000 units/g	Cutaneous Candidiasis, Diaper Dermatitis	Mycostatin, Nystex 49
Topical Powder	100,000 units/g	Cutaneous Candidiasis (especially in moist areas)	Nystop, Nyamyc, Klayesta 27
Vaginal Tablets	100,000 units	Vulvovaginal Candidiasis	Mycostatin, Nilstat, Nyaderm 52

6.2 Formulation-Specific Applications and Efficacy

The effectiveness of Nystatin therapy depends heavily on using the correct formulation to ensure adequate contact with the infected site.

• Oral Formulations: For oropharyngeal candidiasis, patients using the oral suspension are instructed to swish the liquid around the mouth for as long as possible before swallowing. This "swish and swallow" technique maximizes the duration of contact between the drug and the oral mucosa, enhancing its local effect.[17] Lozenges and pastilles are designed to dissolve slowly in the mouth, providing prolonged drug delivery.[53]
• Topical Formulations: The choice of topical base is guided by the nature of the skin lesion. Creams are generally preferred for intertriginous areas as they are less occlusive than ointments. For very moist or weeping lesions, the topical powder is most appropriate as it helps to keep the area dry.[25]
• Clinical Efficacy: Nystatin is generally effective for its approved indications, with symptomatic improvement often noted within 24 to 72 hours of starting treatment.[37] However, its efficacy relative to other antifungal classes varies. For oropharyngeal candidiasis, particularly in HIV-infected patients or in cases of moderate-to-severe disease, systemic azoles like fluconazole are often more effective and are recommended as first-line therapy by many clinical guidelines.[16] For mild, uncomplicated cases, Nystatin remains a valid and safe choice.[46]

6.3 Dosage and Administration Guidelines

Nystatin dosage is expressed in USP Nystatin Units, reflecting its biological activity.

• Oropharyngeal Candidiasis:
• Adults and Children: 400,000 to 600,000 units (4 to 6 mL) of the oral suspension administered four times daily. The dose should be divided, with half placed in each side of the mouth.[38]
• Infants: 200,000 units (2 mL) four times daily, administered with a dropper into each side of the mouth. Feeding should be avoided for 5 to 10 minutes after administration to prolong contact time.[38]
• Neonates (Premature/Low Birth Weight): 100,000 units (1 mL) four times daily is often effective.[38]
• Intestinal Candidiasis:
• Adults: 500,000 to 1,000,000 units (1 to 2 tablets) taken three times daily.[27]
• Cutaneous Candidiasis:
• Cream/Ointment: Apply liberally to the affected area two to three times daily.[43]
• Powder: Apply to the affected area two to three times daily. For athlete's foot, the powder should also be dusted into shoes and socks.[43]
• Duration of Therapy: For all indications, treatment should be continued for at least 48 hours after symptoms have resolved and cultures are negative to prevent relapse.[15]

Indication	Patient Population	Formulation	Dosage	Frequency
Oropharyngeal Candidiasis	Adults & Children	Oral Suspension	400,000–600,000 units	4 times daily
	Infants	Oral Suspension	200,000 units	4 times daily
	Neonates (Premature)	Oral Suspension	100,000 units	4 times daily
Intestinal Candidiasis	Adults	Oral Tablets	500,000–1,000,000 units	3 times daily
Cutaneous Candidiasis	All Ages	Cream / Ointment	Apply to affected area	2–3 times daily
	All Ages	Powder	Apply to affected area	2–3 times daily

6.4 Non-Clinical and Research Applications

Beyond its clinical use, Nystatin's unique biophysical properties have made it a valuable tool in scientific research and other fields.

• Cell Biology and Electrophysiology: In the laboratory, Nystatin is used to create "perforated" patch-clamp recordings. When included in the recording pipette, it forms small pores in the patched cell membrane that are permeable only to monovalent ions. This allows for the measurement of electrical currents across the membrane without dialyzing and washing out larger intracellular components like proteins and second messengers, preserving the cell's internal signaling machinery.[11] It is also employed as a specific inhibitor of the lipid raft-caveolae pathway of endocytosis.[11]
• Art Conservation: In a novel application, derivatives of Nystatin have been used to prevent the growth of mold on cultural artifacts. A notable example is its application to protect wood panel paintings that were damaged by flooding during the 1966 Arno River Flood in Florence, Italy.[11]

The evolution of Nystatin's use reflects a broader trend in pharmacology. While the development of newer systemic antifungals has refined its clinical role to a specific niche—primarily for safe, localized therapy—its fundamental mechanism has been repurposed by scientists, giving it a second life as a sophisticated tool for basic research. This dual identity demonstrates the enduring value of a well-understood molecule long after its initial discovery.

7.0 Safety and Toxicology Profile

The safety profile of Nystatin is excellent when used as indicated for topical and oral (non-systemic) therapy. However, it possesses significant intrinsic toxicity that becomes apparent if the drug reaches the systemic circulation. This dichotomy is central to understanding its safe and effective use.

7.1 Adverse Drug Reactions and Side Effects

Adverse effects are generally mild, infrequent, and related to the route of administration.

• Oral Administration: The most common side effects are gastrointestinal in nature, reflecting the drug's local action within the GI tract. These include diarrhea, nausea, vomiting, and abdominal pain or bloating.[11] Oral irritation or sensitization has also been reported.[31]
• Topical Administration: Adverse events are rare, with a reported frequency of less than 0.1%.[19] When they do occur, they are localized to the site of application and may include burning, itching, rash, eczema, or pain.[11]
• Rare but Serious Reactions: Although uncommon, hypersensitivity reactions can occur with any formulation. These may range from a simple rash or urticaria (hives) to more severe reactions. Very rarely, Stevens-Johnson syndrome (SJS), a severe cutaneous adverse reaction, has been reported.[11] Anaphylaxis, characterized by symptoms such as bronchospasm, facial swelling, and tachycardia, is also a rare possibility.[11]

7.2 Contraindications and Precautions

The contraindications for Nystatin are limited, reflecting its poor absorption and localized action.

• Contraindications: The only absolute contraindication is a known history of hypersensitivity (allergy) to Nystatin or any of the excipients in the formulation.[19]
• Precautions:
• The most critical precaution is that standard Nystatin formulations (oral and topical) should not be used for the treatment of systemic mycoses.[1] They are ineffective for this purpose and attempting to achieve systemic levels would require toxic parenteral doses.
• If irritation or sensitization develops at the site of application, treatment should be discontinued.[19]
• If there is a lack of therapeutic response, the diagnosis should be re-confirmed with appropriate microbiological tests (e.g., KOH smears, cultures) to rule out non-susceptible organisms or other conditions.[19]

7.3 Overdose and Acute Toxicity

Overdose with standard Nystatin formulations is of low concern due to its lack of absorption.

• Overdose Symptoms: Oral doses in excess of five million units daily have been reported to cause nausea and gastrointestinal upset, including stomach bloating, pain, and vomiting.[1] There have been no reports of serious systemic toxic effects or superinfections resulting from oral overdose.[1]
• Management: In the event of an overdose, management is supportive. Individuals are advised to contact a poison control center. Given the low risk of systemic toxicity, aggressive interventions are typically not required.[41]
• Acute Toxicity (LD50): Animal studies confirm the low acute toxicity of oral Nystatin. The median lethal dose (LD50​) in rats is approximately 10,000 mg/kg, an extremely high value that underscores its safety upon ingestion.[66]

7.4 Systemic Toxicity and Rationale for Non-Parenteral Use

The safety profile of Nystatin is dichotomous: it is safe when used locally but toxic when administered systemically. This is not a contradiction but a direct consequence of its pharmacology and pharmacokinetics.

• Parenteral Toxicity: Early clinical investigations with intravenous Nystatin revealed severe adverse effects, including chills, fever, nausea, vomiting, and sterile abscesses at injection sites.[12] This significant systemic toxicity has prevented the development and approval of any parenteral formulation for routine clinical use.[1]
• Mechanism of Toxicity: The mechanism of systemic toxicity is the same as its mechanism of antifungal action: binding to sterols and forming pores in cell membranes. When present in the bloodstream, Nystatin binds to cholesterol in human cell membranes, causing cellular damage. This effect is particularly pronounced in the kidneys, leading to nephrotoxicity.[11] The apparent paradox of a drug with a very high oral LD50​ being considered "too toxic" for systemic use is thus resolved. The LD50​ reflects the low hazard of ingestion due to non-absorption, while the preclusion from parenteral use reflects the high hazard of systemic exposure.

8.0 Drug Interaction Profile

The potential for drug-drug interactions with Nystatin is largely dictated by its pharmacokinetic profile. Because it is not systemically absorbed, the risk of systemic pharmacokinetic interactions is minimal to non-existent, whereas local pharmacodynamic interactions within the gastrointestinal tract are possible.

8.1 Pharmacodynamic Interactions

These interactions occur at the site of action, typically within the gastrointestinal lumen for oral formulations.

• Interactions at the Ergosterol Target:
• Other Ergosterol Binders: Co-administration with other polyenes that also bind to ergosterol, such as Amphotericin B, could theoretically lead to competitive or additive effects, though this is not a well-documented clinical issue for orally administered Nystatin.[70]
• Ergosterol Synthesis Inhibitors: Drugs that inhibit the synthesis of ergosterol, such as azole antifungals (e.g., clotrimazole), work by depleting the fungal membrane of Nystatin's target. This could potentially lead to antagonism, reducing Nystatin's efficacy.[70]
• Interaction with Probiotics: A clinically significant interaction exists with yeast-based probiotics, most notably Saccharomyces boulardii. As an antifungal, oral Nystatin will kill the live yeast in the probiotic preparation, rendering it ineffective. Therefore, concurrent use should be avoided.[27]

8.2 Pharmacokinetic Interactions

While extensive theoretical interactions can be predicted from in vitro data, these are generally not observed in clinical practice.

• Clinical Observation: Due to its negligible absorption from the GI tract, Nystatin does not reach systemic circulation in sufficient concentrations to interact with metabolic enzymes (e.g., cytochrome P450) or systemic drug transporters. As a result, most clinical resources state that there are no significant drug-drug interactions with Nystatin.[17]
• Theoretical Transporter Inhibition: Despite the lack of clinical interactions, specialized pharmacological databases, based on in vitro assays, report that Nystatin is an inhibitor of the hepatic uptake transporters SLCO1B1 and SLCO1B3.[70] These transporters are responsible for moving a wide array of drugs from the blood into the liver for metabolism and elimination, including statins (e.g., atorvastatin), bosentan, cyclosporine, and erythromycin.[1] Inhibition of these transporters would be expected to increase the plasma concentrations of their substrates, potentially leading to toxicity.

The apparent discrepancy between the extensive list of potential in vitro interactions and the clinical reality of a drug with very few interactions is resolved by its pharmacokinetics. For Nystatin to inhibit hepatic transporters in vivo, it would first need to be absorbed from the gut and reach the liver via the portal circulation in sufficient concentrations. Since this does not occur, the potential for these pharmacokinetic interactions is not clinically realized. This is a critical point of clarification for prescribers: the risk of systemic drug interactions with standard oral or topical Nystatin is negligible.

9.0 Use in Special Populations

The safety and efficacy of Nystatin have been evaluated in various special populations, with recommendations guided by its localized action and minimal systemic exposure.

9.1 Pregnancy and Lactation

Nystatin is generally considered safe for use during pregnancy and lactation due to its lack of systemic absorption.

• Pregnancy: The U.S. Food and Drug Administration (FDA) has assigned different pregnancy categories to Nystatin formulations, a distinction that appears to be based on the volume of available clinical data rather than a difference in inherent risk.
• FDA Pregnancy Category A: Nystatin vaginal tablets are assigned to Category A, indicating that adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus.[73] This is likely due to the extensive use and study of these products for treating vaginal candidiasis, which is common during pregnancy.[75]
• FDA Pregnancy Category C: Oral and topical formulations of Nystatin are assigned to Category C. This category indicates that animal reproduction studies have either shown an adverse effect on the fetus and there are no adequate studies in humans, or that studies in animals and humans are not available.[31]

Despite the Category C designation for oral and topical forms, their use is widely considered safe during pregnancy when clinically indicated, as the negligible absorption is expected to prevent any significant fetal exposure.11

• Lactation: Nystatin is considered compatible with breastfeeding.[77] The drug is not absorbed systemically by the mother and is therefore not expected to be excreted into breast milk in any significant amount.[78] When used topically to treat candidiasis of the breast or nipples, it is recommended to use a water-miscible cream (which is easier to wash off) rather than an ointment. Any residual medication should be gently wiped from the nipple area before nursing to minimize direct infant ingestion.[77]

9.2 Pediatric Use

Nystatin is widely used and considered safe and effective in all pediatric age groups, from premature neonates to adolescents.

• Safety and Efficacy: Clinical experience has established its utility and safety in children.[19]
• Formulation and Administration: The oral suspension is the preferred formulation for infants and young children (up to 5 years of age) who cannot safely use lozenges or tablets.[53] For oral thrush in infants, the suspension is typically administered with a dropper, placing half the dose in each side of the mouth to ensure broad distribution over the mucosal surfaces.[38]
• Dosing: Dosages are carefully tailored to the specific pediatric age group, with lower doses recommended for premature and low-birth-weight neonates (see Section 6.3).[38]
• Clinical Research: While Nystatin is standard of care for neonatal thrush and is used off-label for prophylaxis in high-risk neonates, some experts have called for more robust clinical trials to better define its role and efficacy for prophylaxis in older pediatric patient groups, such as those with cystic fibrosis or congenital heart disease.[84]

9.3 Geriatric Use

Nystatin is commonly prescribed for older adults, particularly for the treatment of oropharyngeal candidiasis, which can be prevalent in this population, especially among denture wearers.[11]

• Safety and Dosing: There is no specific information to suggest that geriatric patients respond differently or experience different side effects compared to younger adults.[43] No age-specific dosage adjustments are generally required. However, dedicated clinical studies in the elderly are limited, and it is noted that a greater sensitivity in some older individuals cannot be entirely ruled out.[19]

10.0 Regulatory and Commercial Landscape

Nystatin's long history and established efficacy have secured its place as a globally recognized and regulated medication. Its commercial profile is characteristic of a mature, off-patent drug that is essential for treating common infections.

10.1 Regulatory Approvals

Nystatin is approved for use by major regulatory agencies worldwide.

• U.S. Food and Drug Administration (FDA): Nystatin has been in clinical use in the United States since the 1950s. Its initial approval predates the modern drug approval framework, and its formal approval date is often cited as "Prior to January 1, 1982".[88] Since then, numerous generic versions have been approved through the Abbreviated New Drug Application (ANDA) process. For example, an ANDA for a generic Nystatin Oral Suspension was approved on June 25, 1998.[89]
• European Medicines Agency (EMA) and National Agencies: Nystatin is widely approved across Europe. The approval process for generic products often relies on referencing a long-established innovator product. For instance, Nystimex, an oral suspension, was approved in 2015 through a Decentralised Procedure with Sweden as the Reference Member State, using Mycostatin (authorized in Sweden since 1973) as the reference product.[91] National agencies, such as the Danish Medicines Agency, also list multiple approved Nystatin-containing products.[92]
• World Health Organization (WHO): Nystatin is included on the WHO's List of Essential Medicines, a designation reserved for medications considered to be the most effective and safe to meet the most important needs in a health system. This highlights its fundamental importance in global public health.[11]

10.2 Major Manufacturers and Global Brand Names

As a widely used, off-patent drug, Nystatin is produced by a large and diverse group of pharmaceutical manufacturers and marketed under an extensive number of brand names.

• Major Manufacturers: The production of Nystatin, both as an active pharmaceutical ingredient (API) and as finished dosage forms, is a global enterprise. Key manufacturers include Antibiotice, which is a world-leading producer of the Nystatin API, AdvaCare Pharma, Teva Pharmaceuticals, Bayer, Taro Pharmaceuticals, and many others in the United States, Europe, and Asia.[93]
• Brand Names: The commercial landscape is populated by hundreds of brand names worldwide.
• Common Innovator and Generic Names: In North America and other regions, common brand names include Mycostatin, Nilstat, Nystop, Nyaderm, and Nyamyc.[1]
• International Brand Names: The global market features a vast array of brands, many of which are combination products. The table below provides a representative sample of this diversity.

The market profile of Nystatin is a classic example of a mature, essential medicine. Its off-patent status has fostered intense generic competition, ensuring its affordability and widespread availability. Its established safety and efficacy for common superficial infections make it an ideal candidate for low-cost production and for inclusion in combination therapies that address both infection and inflammation (e.g., with corticosteroids). This robust, high-volume market, supported by its status as a WHO Essential Medicine, confirms Nystatin's enduring role as a foundational antifungal agent in global healthcare.

Brand Name	Country/Region	Additional Active Ingredient(s)
Nystan	United Kingdom	None
Biofanal	Germany	None
Candio-Hermal	Germany, Austria	None
Flagystatin	Canada, Argentina, Philippines	Metronidazole
Kenacomb	Australia, New Zealand	Triamcinolone, Neomycin, Gramicidin
Viaderm-K.C.	Canada	Triamcinolone, Neomycin, Gramicidin
Polygynax	France, South Korea, Mexico	Neomycin, Polymyxin B
Macmiror Complex	Italy, Turkey, Poland	Nifuratel
Timodine	United Kingdom	Hydrocortisone, Dimeticone, Benzalkonium
Trimovate	United Kingdom	Clobetasone, Oxytetracycline

This table provides a representative sample of international brand names and is not exhaustive. Data compiled from.[40]

Works cited

1. Nystatin: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed September 1, 2025, https://go.drugbank.com/drugs/DB00646
2. Nystatin powder - PubChem, accessed September 1, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/nystatin
3. Nystatin | CAS 1400-61-9 | SCBT - Santa Cruz Biotechnology, accessed September 1, 2025, https://www.scbt.com/p/nystatin-1400-61-9
4. CAS 1400-61-9 Nystatin - Alfa Chemistry, accessed September 1, 2025, https://www.alfa-chemistry.com/product/nystatin-cas-1400-61-9-290198.html
5. Nystatin | 1400-61-9 - ChemicalBook, accessed September 1, 2025, https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0463474.htm
6. CAS RN | 1400-61-9 - Thermo Fisher Scientific, accessed September 1, 2025, https://www.thermofisher.com/search/cas/1400-61-9
7. Nystatin - LKT Labs, accessed September 1, 2025, https://lktlabs.com/product/nystatin/
8. Redalyc.Physical and chemical analysis of commercial nystatin, accessed September 1, 2025, https://www.redalyc.org/pdf/3072/307228854010.pdf
9. CHEBI:7660 - nystatin - EMBL-EBI, accessed September 1, 2025, https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7660
10. Nystatin A1 | C47H75NO17 | CID 11286230 - PubChem, accessed September 1, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/Nystatin-A1
11. Nystatin - Wikipedia, accessed September 1, 2025, https://en.wikipedia.org/wiki/Nystatin
12. Nystatin, accessed September 1, 2025, https://www.karger.com/Article/Pdf/219536
13. PRESCRIBING INFORMATION INCLUDING PATIENT MEDICATION INFORMATION Prpms-NYSTATIN SUSPENSION Nystatin Oral Suspension, USP 100,0 - Pharmascience, accessed September 1, 2025, https://www.pharmascience.com/wp-content/uploads/2023/07/pms-Nystatin-Suspension-pm-en-live-2022-10-05.pdf
14. CAS No : 1400-61-9| Chemical Name : Nystatin | Pharmaffiliates, accessed September 1, 2025, https://pharmaffiliates.com/en/1400-61-9-nystatin-pa1467000.html
15. PrJAMP-Nystatin Oral Suspension USP, accessed September 1, 2025, https://pdf.hres.ca/dpd_pm/00078902.PDF
16. Nystatin - LiverTox - NCBI Bookshelf, accessed September 1, 2025, https://www.ncbi.nlm.nih.gov/books/NBK548581/
17. NYSTATIN | Journal of Prescribing Practice - MAG Online Library, accessed September 1, 2025, https://www.magonlinelibrary.com/doi/10.12968/jprp.2022.4.1.8
18. Nystatin - Drug Targets, Indications, Patents - Patsnap Synapse, accessed September 1, 2025, https://synapse.patsnap.com/drug/0b263f7df68245d582c110a079878f36
19. Nystatin Powder: Package Insert / Prescribing Information - Drugs.com, accessed September 1, 2025, https://www.drugs.com/pro/nystatin-powder.html
20. US2797183A - Nystatin and method of producing it - Google Patents, accessed September 1, 2025, https://patents.google.com/patent/US2797183A/en
21. GB796512A - Process for recovering an antibiotic nystatin - Google Patents, accessed September 1, 2025, https://patents.google.com/patent/GB796512A/en
22. The influence of carbon sources and morphology on nystatin production by Streptomyces noursei - PubMed, accessed September 1, 2025, https://pubmed.ncbi.nlm.nih.gov/11911923/
23. Nystatin Production by a Local Streptmyces sp. Isolated from Egyptian Soil - ResearchGate, accessed September 1, 2025, https://www.researchgate.net/publication/314838501_Nystatin_Production_by_a_Local_Streptmyces_sp_Isolated_from_Egyptian_Soil
24. CN103755758A - Preparation method of nystatin - Google Patents, accessed September 1, 2025, https://patents.google.com/patent/CN103755758A/en
25. 4165adea-6467-4085-9cbf-aedff4baeae6.xml - accessdata.fda.gov, accessed September 1, 2025, https://www.accessdata.fda.gov/spl/data/4165adea-6467-4085-9cbf-aedff4baeae6/4165adea-6467-4085-9cbf-aedff4baeae6.xml
26. What is the clinical significance of Nystatin (antifungal medication) to human health?, accessed September 1, 2025, https://www.droracle.ai/articles/26631/what-is-the-significance-of-nystatin-to-health
27. Mycostatin, Nilstat (nystatin) dosing, indications, interactions, adverse effects, and more, accessed September 1, 2025, https://reference.medscape.com/drug/mycostatin-nilstat-nystatin-342594
28. In Vitro Pharmacodynamic Characteristics of Nystatin Including Time-Kill and Postantifungal Effect | Antimicrobial Agents and Chemotherapy - ASM Journals, accessed September 1, 2025, https://journals.asm.org/doi/10.1128/aac.44.10.2887-2890.2000
29. In Vitro Pharmacodynamic Characteristics of Nystatin Including Time-Kill and Postantifungal Effect - PMC, accessed September 1, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC90172/
30. Comparison of In Vitro Antifungal Activities of Free and Liposome-Encapsulated Nystatin with Those of Four Amphotericin B Formulations | Antimicrobial Agents and Chemotherapy - ASM Journals, accessed September 1, 2025, https://journals.asm.org/doi/10.1128/aac.42.6.1412
31. Nystatin Tablets: Package Insert / Prescribing Information - Drugs.com, accessed September 1, 2025, https://www.drugs.com/pro/nystatin-tablets.html
32. Nystatin Oral Suspension USP [100,000 units per mL] - DailyMed, accessed September 1, 2025, https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=cc3516cd-985c-489f-b4a1-8477876c5a97
33. Nystatin - FPnotebook, accessed September 1, 2025, https://fpnotebook.com/ID/Pharm/Nystn.htm
34. Nystatin - Bionity, accessed September 1, 2025, https://www.bionity.com/en/encyclopedia/Nystatin.html
35. Nystatin : Indications, Uses, Dosage, Drugs Interactions, Side effects - Medical Dialogues, accessed September 1, 2025, https://medicaldialogues.in/generics/nystatin-2725304
36. Nystatin | Davis's Drug Guide for Rehabilitation Professionals, accessed September 1, 2025, https://fadavispt.mhmedical.com/content.aspx?bookid=1873§ionid=139020232
37. Mycostatin topical, Pediaderm AF (nystatin topical) dosing, indications, interactions, adverse effects, and more - Medscape Reference, accessed September 1, 2025, https://reference.medscape.com/drug/nystatin-topical-343490
38. Nystatin Oral Suspension (Nystatin (oral)): Side Effects, Uses, Dosage, Interactions, Warnings - RxList, accessed September 1, 2025, https://www.rxlist.com/nystatin-oral-suspension-drug.htm
39. [Intestinal excretion of nystatin during and after oral administration to newborn infants at risk], accessed September 1, 2025, https://pubmed.ncbi.nlm.nih.gov/2038352/
40. About nystatin - NHS, accessed September 1, 2025, https://www.nhs.uk/medicines/nystatin/about-nystatin/
41. Nystatin Tablets - Cleveland Clinic, accessed September 1, 2025, https://my.clevelandclinic.org/health/drugs/19582-nystatin-tablets
42. Nystatin - brand name list from Drugs.com, accessed September 1, 2025, https://www.drugs.com/ingredient/nystatin.html
43. Nystatin (topical route) - Side effects & dosage - Mayo Clinic, accessed September 1, 2025, https://www.mayoclinic.org/drugs-supplements/nystatin-topical-route/description/drg-20065134
44. www.mayoclinic.org, accessed September 1, 2025, https://www.mayoclinic.org/drugs-supplements/nystatin-vaginal-route/description/drg-20065120#:~:text=Nystatin%20belongs%20to%20the%20group,only%20with%20your%20doctor's%20prescription.
45. Full article: Efficacy of nystatin for the treatment of oral candidiasis: a systematic review and meta-analysis - Taylor & Francis Online, accessed September 1, 2025, https://www.tandfonline.com/doi/full/10.2147/DDDT.S100795
46. Nystatin Monograph for Professionals - Drugs.com, accessed September 1, 2025, https://www.drugs.com/monograph/nystatin.html
47. Mycostatin - Drug Summary, accessed September 1, 2025, https://www.pdr.net/drug-summary/Nystatin-Oral-Suspension-nystatin-3439
48. Nystatin: Side Effects, Uses, Dosage, Interactions, Warnings - RxList, accessed September 1, 2025, https://www.rxlist.com/nystatin/generic-drug.htm
49. Nystatin Topical Cream: Uses & Side Effects - Cleveland Clinic, accessed September 1, 2025, https://my.clevelandclinic.org/health/drugs/19293-nystatin-cream-or-ointment
50. Nystatin (Nystop, Nyamyc): Uses, Side Effects, Tips & More - GoodRx, accessed September 1, 2025, https://www.goodrx.com/nystatin/what-is
51. Nystatin Topical Forms: Side Effects, Uses, Dosage, and More, accessed September 1, 2025, https://www.healthline.com/health/drugs/nystatin-topical-forms
52. Nystatin (vaginal route) - Side effects & dosage - Mayo Clinic, accessed September 1, 2025, https://www.mayoclinic.org/drugs-supplements/nystatin-vaginal-route/description/drg-20065120
53. Nystatin (oral route) - Side effects & dosage - Mayo Clinic, accessed September 1, 2025, https://www.mayoclinic.org/drugs-supplements/nystatin-oral-route/description/drg-20065146
54. NYSTATIN oral - MSF Medical Guidelines, accessed September 1, 2025, https://medicalguidelines.msf.org/en/viewport/EssDr/english/nystatin-oral-16684364.html
55. Nystatin Effectiveness in Oral Candidiasis Treatment: A Systematic Review & Meta-Analysis of Clinical Trials - PMC - PubMed Central, accessed September 1, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9697841/
56. Nystatin Dosage Guide + Max Dose, Adjustments - Drugs.com, accessed September 1, 2025, https://www.drugs.com/dosage/nystatin.html
57. Label: NYSTATIN tablet, film coated - DailyMed, accessed September 1, 2025, https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=f03b294d-10cd-4bba-92c8-42ae9b110cd0
58. Nystatin: MedlinePlus Drug Information, accessed September 1, 2025, https://medlineplus.gov/druginfo/meds/a682758.html
59. Nystatin Cream: Package Insert / Prescribing Information - Drugs.com, accessed September 1, 2025, https://www.drugs.com/pro/nystatin-cream.html
60. Nystatin Cream (Nystatin Cream, Ointment): Side Effects, Uses, Dosage, Interactions, Warnings - RxList, accessed September 1, 2025, https://www.rxlist.com/nystatin-cream-drug.htm
61. Nystatin topical (Mycostatin, Nystop): Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD, accessed September 1, 2025, https://www.webmd.com/drugs/2/drug-8684-612/nystatin-topical/nystatin-topical/details
62. Side effects of nystatin - NHS, accessed September 1, 2025, https://www.nhs.uk/medicines/nystatin/side-effects-of-nystatin/
63. NYSTATIN suspension - DailyMed, accessed September 1, 2025, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9954118e-abe6-4388-98c9-4473d39b2e28&audience=consumer
64. https://nctr\-crs.fda.gov/fdalabel/services/spl/set\-ids/f7a98d15\-ce46\-4358\-ac6e\-d10afa4d34c2/spl\-doc, accessed September 1, 2025, https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/f7a98d15-ce46-4358-ac6e-d10afa4d34c2/spl-doc
65. Nystatin Topical: MedlinePlus Drug Information, accessed September 1, 2025, https://medlineplus.gov/druginfo/meds/a618065.html
66. 1. CHEMICAL PRODUCT AND COMPANY IDENTIFICATION - Grove Medical, accessed September 1, 2025, https://www.grovemedical.com/Customer/grmein/Customerpages/specpages/11-5113_SDS.pdf
67. SAFETY DATA SHEET - Sigma-Aldrich, accessed September 1, 2025, https://www.sigmaaldrich.com/US/en/sds/sigma/n3503
68. SAFETY DATA SHEET - LGC Standards, accessed September 1, 2025, https://assets.lgcstandards.com/sys-master%2Fpdfs%2Fhce%2Fh4c%2F10603771985950%2FSDS_DRE-C15661000_ST-WB-MSDS-5429593-1-1-1.PDF
69. Safety Data Sheet - MP Biomedicals, accessed September 1, 2025, https://www.mpbio.com/media/document/infor/1/9/4/5/3/4/MP_MSDS_194534_US_EN.pdf
70. Showing BioInteractions for Nystatin (DB00646) | DrugBank Online, accessed September 1, 2025, https://go.drugbank.com/drugs/DB00646/biointeractions
71. Nystatin Interactions Checker - Drugs.com, accessed September 1, 2025, https://www.drugs.com/drug-interactions/nystatin.html
72. Taking or using nystatin with other medicines and herbal supplements - NHS, accessed September 1, 2025, https://www.nhs.uk/medicines/nystatin/taking-or-using-nystatin-with-other-medicines-and-herbal-supplements/
73. Nystatin topical Use During Pregnancy | Drugs.com, accessed September 1, 2025, https://www.drugs.com/pregnancy/nystatin-topical.html
74. www.drugs.com, accessed September 1, 2025, https://www.drugs.com/pregnancy/nystatin-topical.html#:~:text=Nystatin%20topical%20cream%2C%20ointment%2C%20and,studies%20have%20not%20been%20reported.
75. Vaginal yeast infections during pregnancy - PMC, accessed September 1, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC2654841/
76. Nystatin Use During Pregnancy - Drugs.com, accessed September 1, 2025, https://www.drugs.com/pregnancy/nystatin.html
77. Pregnancy, breastfeeding and fertility while taking or using nystatin ..., accessed September 1, 2025, https://www.nhs.uk/medicines/nystatin/pregnancy-breastfeeding-and-fertility-while-taking-or-using-nystatin/
78. Nystatin - Drugs and Lactation Database (LactMed®) - NCBI Bookshelf, accessed September 1, 2025, https://www.ncbi.nlm.nih.gov/books/NBK501241/
79. Who can and cannot take or use nystatin - NHS, accessed September 1, 2025, https://www.nhs.uk/medicines/nystatin/who-can-and-cannot-take-or-use-nystatin/
80. Fungal infections and Breastfeeding, accessed September 1, 2025, https://www.breastfeedingnetwork.org.uk/factsheet/fungal-infections-and-breastfeeding/
81. nystatin, accessed September 1, 2025, https://www.glowm.com/resources/glowm/cd/pages/drugs/n037.html
82. Pediatric Nystatin (Mycostatin®, Nilstat®) Antifungal Treatment, accessed September 1, 2025, https://www.chp.edu/our-services/transplant/liver/education/medications/nystatin-mycostatin-nilstat
83. Nystatin (Oral) | Drug Lookup | Pediatric Care Online | American ..., accessed September 1, 2025, https://publications.aap.org/pediatriccare/drug-monograph/18/5935/Nystatin-Oral
84. Oral nystatin prophylaxis to prevent systemic fungal infection in very low birth weight preterm infants: a randomized controlled trial - PMC - PubMed Central, accessed September 1, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC7164192/
85. Nystatin is commonly prescribed as prophylaxis in children beyond the neonatal age, accessed September 1, 2025, https://pubmed.ncbi.nlm.nih.gov/36610724/
86. Nystatin Effectiveness in Oral Candidiasis Treatment: A Systematic Review & Meta-Analysis of Clinical Trials - MDPI, accessed September 1, 2025, https://www.mdpi.com/2075-1729/12/11/1677
87. What is the recommended dose and frequency of Nystatin (antifungal medication)?, accessed September 1, 2025, https://www.droracle.ai/articles/4805/nystatin-dose-and-frequency-
88. Nystatin - Drug Usage Statistics, ClinCalc DrugStats Database, accessed September 1, 2025, https://clincalc.com/drugstats/Drugs/Nystatin
89. Drug Approval Package: Nystatin NDA #64-142 - accessdata.fda.gov, accessed September 1, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/64142.cfm
90. Approval Package for - accessdata.fda.gov, accessed September 1, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/64142ap_appltr_prntlbl_chemr.pdf
91. Public Assessment Report Scientific discussion Nystimex (nystatin ..., accessed September 1, 2025, https://docetp.mpa.se/LMF/Nystimex%20oral%20suspension%20ENG%20PAR_09001bee807a5ffa.pdf
92. Medicines authorised with a summary of the risk management plan (sRMP), accessed September 1, 2025, https://laegemiddelstyrelsen.dk/en/licensing/licensing-of-medicines/medicines-authorised-with-a-summary-of-the-risk-management-plan?letter=N&subletter=v-z
93. Generic NYSTATIN INN equivalents, pharmaceutical patent ..., accessed September 1, 2025, https://www.drugpatentwatch.com/p/generic/nystatin
94. Nystatin Tablets – Manufacturer - AdvaCare Pharma, accessed September 1, 2025, https://www.advacarepharma.com/en/pharmaceuticals/nystatin-tablets
95. Nystatin - Antibiotice, accessed September 1, 2025, https://www.antibiotice.ro/en/partners/nystatin/
96. Nystatin | Manufacturers | Suppliers | India - Manus Aktteva Biopharma LLP, accessed September 1, 2025, https://www.manusaktteva.com/api/Nystatin
97. Nystatin API Suppliers - Find All GMP Manufacturers - Pharmaoffer.com, accessed September 1, 2025, https://pharmaoffer.com/api-excipient-supplier/antimycotics/nystatin
98. Nystatin (International database) - Drugs.com, accessed September 1, 2025, https://www.drugs.com/international/nystatin.html