Nystatin - Mechanism of action, uses, dosage, side effects and interactions

Contents

What is nystatin?

What is nystatin?

Nystatin is a drug that is used to fight infections which are caused by a fungus, therefore, it is classified as an anti-fungal drug. Nystatin is used for the treatment of fungal infections of the mouth, skin, vagina, and intestinal tract.

It is available in a variety of dosage forms which are used to treat the fungal infections anywhere in the body and is available in the form of a tablet, capsule, liquid and a soft lozenge which are to be taken by mouth.

It is also available in the form of a tablet or a vaginal cream that are inserted directly into the vagina. For application to the skin, the drug is available in the form of a powder, ointment or cream.

Nystatin was originally discovered in 1950 by Rachel Fuller Brown and Elizabeth Lee Hazen. When the drug is administered by the oral route is used primarily to treat yeast infections in the mouth and the stomach.

This is because of the fact that the drug is not absorbed into the bloodstream when given orally due to which it cannot be used to treat the systemic fungal infections in various parts of the body including the skin.

The drug is available under various brand names including Bio-Statin, Mycostatin, and Nilstatetc which are all included in the class of antifungal medications.

Nystatin description, IUPAC name, molecular formula, weight, structure, and drug class

Nystatin belongs to the class of antifungal drugs. The drug is an antimycotic polyene antibiotic which is obtained from Streptomyces noursei. It is a species of bacterium in the genus Streptomyces.

The drug is effective against a variety of molds and yeasts including the Candida species. Nystatin can cause toxicity upon intravenous administration but is not absorbed across intact skin or mucous membranes.

The drug is however considered a safe drug for the treatment of oral o gastrointestinal fungal infections.

Nystatin is available in a variety of dosage forms to treat fungal infections all over the body and in all the available dosage forms, the strength of the drug is 100,000 nystatin units while in a few dosage forms 500,000 nystatin units may also be present.

IUPAC name: (4E,6E,8E,10E,14E,16E,18S,19R,20R,21S,35S)-3-[(2S,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-19,25,27,29,32,33,35,37-octahydroxy-18,20,21-trimethyl-23-oxo-22,39-dioxabicyclo[33.3.1]nonatriaconta-4,6,8,10,14,16-hexaene-38-carboxylic acid

Molecular formula: C47H75NO17

Molecular weight: 926.107 g/mol

Chemical structure:

Drug class: This compound belongs to the class of organic compounds known as aminoglycosides. These are molecules or a portion of a molecule composed of amino-modified sugars.

Nystatin identification and chemistry

Nystatin is usually light yellow in color but the drug may vary from yellow to tan in color. It has a slight odor and the odor is somewhat similar to the odor of cereals.

The drug shows appreciable solubility in water and organic solvents such as methanol and ethylene glycol. It is only sparingly soluble in benzene, toluene, chloroform and ethyl acetate while it is insoluble in ether.

Nystatin is amphoteric and shows optimum stability in a phosphate-citrate buffer at pH of 5.7 however, aqueous and alkaline solutions are unstable. Nystatin is affected by air and moisture and gets deteriorated by exposure to heat, light, moisture or air.

What is the mechanism of action of nystatin?

Nystatin is an antimicrobial agent which is classified as an anti-fungal agent and it primarily acts on the cell membrane of microorganisms.

These agents bind to the sterols which are present in the cell membranes of different microorganisms and hence alter the permeability of the cell membrane resulting in leakage of the intracellular contents and ultimately causing the death of the microbe.

As an anti-fungal agent, it exerts its effect by binding to the sterols in the cell membrane of the microorganisms. It binds specifically with ergosterol which is a sterol and is present in cell surface membrane of fungi.

Nystatin shows activity against fungi and not against bacteria since bacteria do not have sterols in their cell membrane.

Nystatin forms a complex after binding with ergosterol in the fungal cell membrane and as a result of this binding, the membrane loses its ability to act as a selective barrier which causes potassium and other cellular components to leak out of the cell. This results in the death of the fungi and the anti-fungal effect are achieved.

What are nystatin indications?

Nystatin is an anti-fungal medication which is used for the treatment of fungal infections caused primarily by Candida species.

Candida is a form of a yeast which is normally present in the body including the oral cavity and the gastrointestinal tract. However, the yeast does not normally cause infection when the immune system is working properly.

If there is any disturbance in the immune function or even if there is any disturbance in the normal bacterial flora of the gastrointestinal tract then this organism can cause serious infections and in such cases, nystatin is prescribed.

Following are the indications in which nystatin is used:

Oropharyngeal candidiasis
Cutaneous candidiasis
Mucocutaneous candidiasis
Vulvovaginal candidiasis

These are the primary indications for the use of the drug. The drug is also used for the prevention as well as treatment of candida infections of the esophagus, oral cavity, and the intestinal tract.

The suspension form of nystatin is also used for the prophylactic treatment of oral candidiasis in newborns who are born to mothers already suffering from vaginal candidiasis.

Therefore, this drug can also be used for the prophylactic treatment and management of candidal infections.

What are the pharmacokinetics of nystatin?

Nystatin is generally given by various routes. The drug is not given for systemic infections possibly due to the fact that it has shown poor absorption in the gastrointestinal tract and hence have a poor bioavailability.

Even if the drug is given in usual doses, it is not able to achieve detectable blood concentrations. Nystatin also has poor penetration in the eye which means it cannot be used for ophthalmic infections.

Nystatin is not even absorbed if it applied topically to the skin or mucous membranes. There is not even data related to the distribution of the drug since it is not used for systemic infections and has poor absorption through the gut. The drug is excreted in feces in unchanged form.

If a patient is suffering from renal insufficiency, then there are chances that the drug might achieve significant plasma concentration when administered orally.

How should nystatin be used?

Nystatin is available in a wide range of dosage forms which includes tablet, capsules or liquid which are to be administered orally.

Apart from this, a soft lozenge form is also available which is to be dissolved slowly in the mouth which means that lozenge form is also administered orally but this form is not to be chewed or swallowed as the intact drug rather it is kept in the mouth where it dissolves slowly.

Since this drug is used for the treatment of vaginal infections, therefore, it is also available in tablet and cream form which are inserted directly into the vagina.

Lastly, the drug is also available in such dosage forms which are applied topically to the skin which includes powder, ointment, and cream to be applied topically to the skin.

The patient should always follow the directions carefully which are mentioned on the prescription label and if he does not understand something, he should ask that from his doctor or pharmacist.

Nystatin should be used exactly as directed by the doctor or pharmacist. It should not be used more or less than the prescribed amount. It should also not be used more often than that as prescribed by your doctor or pharmacist.

How to use dry powder form of nystatin?

Take about 4 ounces of water and about a ⅛ teaspoonful of dry powder should be added to it. Then it should be stirred well until completely dissolved.
After the powder is completely mixed in the water, the medicine should be taken by dividing the water into several portions. The total amount of water was 4 ounces soon the powder has completely dissolved in it, it should be divided into several portions. The patient should hold each divided portion of the medicine in his mouth or swish it around in his mouth for as long as possible, gargle, and then swallow it. It is to be made sure that the patient uses all of the liquid to get the full dose of the medicine.

How to use lozenge (pastille) form of nystatin?

Nystatin lozenges (pastilles) should be placed in the mouth and sufficient time must be given so that the lozenges can dissolve completely. The process is usually slow and it can take about 15 to 30 minutes for the lozenges to dissolve completely. During this period, the saliva should be swallowed which allows the medicine to move along with the saliva into the gastrointestinal tract. The lozenges should be chewed or swallowed as a whole.
These lozenges should not be given to infants to children up to 5 years of age because they are too small to use the lozenges safely. They might chew the lozenges or even swallow them as a whole which is not recommended.
The patient should continue to use these lozenges for at least 48 hours after the symptoms of mouth infection disappear.

How to use oral liquid form of nystatin?

The medicine sometimes comes in a dropper bottle. Even if nystatin comes in a dropper bottle, it is to be taken by mouth and the markings on the dropper bottle should be used to accurately measure the dose. This allows the patient to take an accurate amount of the dose.
If the patient is using this medicine for an infection in the mouth, then he should take this medicine by placing one-half of the dose in each side of the mouth. The patient should hold this medicine in his mouth or swish it around in his mouth for as long as possible, then gargle and then swallow it.
If the patient is using this medicine for an intestinal infection, then he should just swallow the liquid after measuring an accurate dose from the dropper. In such cases, there is no need to hold the medicine in the mouth or swish it around in the mouth.
The patients should use the medication at least 3 to 5 times a day for mouth infections and should use it for 3 times a day for intestinal infection. In order to mix the medication evenly, the bottle should be shaken properly before each use.

How to use nystatin for topical application?

For skin infections, nystatin skin ointment or cream is usually used several times a day.
Before applying the cream, the area of the skin should be thoroughly cleaned. The patient should apply only a small amount of ointment or cream and then he should gently and thoroughly massage it into his skin. If the medication is to be applied to the face, it should be kept away from the eyes.
For those patients who are using powder which is to be applied on the infected skin, dust the powder on the skin and leave it for some time. If the patient is using the powder for infected feet, he should dust the powder inside his shoes as well as on his feet.

How to use nystatin for vaginal infection?

For vaginal infections, nystatin vaginal tablets or cream are usually used once or twice a day. Those women who are not pregnant, nystatin vaginal tablets are usually used for 2 weeks while those women who are pregnant, these tablets are used for 3 to 6 weeks before delivery.
If the symptoms of the patient improve after using the medication for a few days then the patient should use it. The medication i.e. the vaginal tablets or cream should be inserted high into the vagina. For inserting these tablets into the vagina, a special applicator is provided. This applicator comes with the medicine and special directions which should be followed in order to insert the medicine properly into the vagina. The tablets should be unwrapped just before inserting them.

The patient should carefully read the directions which are provided with the tablets or cream and should follow the following steps:

Fill the special applicator to the level which is indicated on it.
Lie on your back with your knees drawn upward and spread apart.
Gently insert the applicator into your vagina and push the plunger to release the medication.
Withdraw the applicator and wash it with soap and warm water.
Wash your hands promptly to avoid spreading infection.

The patient may use a sanitary napkin while using a vaginal cream as it can leave a stain on the clothes. It is not recommended to use a tampon as it can absorb the drug. The patient should continue to use the vaginal tablet or cream during the treatment even if she gets a period.

What side effects can nystatin cause?

Nystatin is generally well tolerated in the majority of individuals but the drug can cause some serious side effects.

Those patients who are using vaginal tablets or creams or those who are using the drug for topical application can experience some serious side effects including:

Irritation
Itching
Burning

These effects can occur at the site where the drug is applied. Those patients who are using the drug orally can also experience some side effects including:

Nausea
Diarrhea
Stomach pain
Skin rash

The patient should immediately call the doctor if he experiences any of the above side effects upon administration of oral tablets or oral liquid form of nystatin.

Apart from these effects, the drug can also cause some other serious effects which occur rarely in patients but need prompt medical attention if the patient experiences such effects including:

Vomiting
Urticarial
Oral irritation and sensitization
Hypersensitivity reaction
Angioedema
Facial edema
Steven-Johnson syndrome
Tachycardia
Bronchospasm

Nysatin carcinogenesis, mutagenesis, impairment of fertility

No long-term animal studies have been performed to evaluate carcinogenic potential. There also have been no studies to determine mutagenicity or whether this medication affects fertility in males or females.

What is the recommended dosage of nystatin?

In the treatment of thrust (that is oropharyngeal candidiasis):

Via oral route: ( oral suspension is used )

In children, adolescents, and adults:

The dose of nystatin is usually in between 400,000 units to 600,000 units (which is approximately 4 to 6ml) in every dose PO which is swished in the mouth 4 times in a day with regular intervals in between two consecutive swishing.

One dose of nystatin oral suspension should be divided into two portions, using one half of suspension on each side of the mouth.

This treatment procedure should be continued for minimum 2 days until the symptoms have resolved. Recommendations laid in the guidelines show that it can prolong up to 7 to 14 days.

In neonates and infants:

The dose of nystatin for neonates and infants is about 200,000 units ( 2ml ) every dose PO which is placed in the mouth 4 times in a day with regular intervals in between two consecutive placed.

It is advised to not to feed the child for at least 5 to 10 minutes once the treatment procedure with nystatin suspension.

This treatment procedure should be continued for minimum 2 days until the symptoms have resolved. The babies who are HIV infected, it is better to continue the treatment for 7 to 14 days.

In premature neonates:

In premature neonates, the dose of nystatin is decided on the basis of the limited information on the premature and low weight neonates.

About 100,000 units approximately 1ml in each dose is given to premature neonates. The dose is then divided into two portions placing each portion on each side of the mouth.

It is advised to not to feed the child for at least 5 to 10 minutes once the treatment procedure with nystatin suspension. This treatment procedure should be continued for minimum 2 days until the symptoms have resolved.

In the treatment of cutaneous candidiasis or mucocutaneous or for the adjunctive treatment of candidal diaper dermatitis.

Topical application (by using ointments or creams)

In neonates, infants, children, adolescents, and adults:

Nystatin cream or ointment should be only applied to the affected area. On average it should be applied 2 times a day until it has completely healed. For intertriginous areas, a cream is recommended instead of using the ointment.

Topical powder

In neonates, infants, children, adolescents, and adults:

Nystatin powder is applied to the infected area at least two to three times in a single day until the patient has completely healed.

This dosage form is more suited for the treatment when there are moist lesions present in comparison to using creams and ointments.

In the treatment of vulvovaginal candidiasis (VVS)

Intravaginal route (vaginal tablets)

In female adolescents and adults:

In females, approximately 100,000 units which can be equal to 1mg are given to the patient via the vaginal route once a day continuous for 14 days.

According to a report given in the CDC, nystatin is a least preferable antifungal in comparison to other topical azole medicines.

In the treatment of intestinal candidiasis (with or without underlying existence of vulvovaginal candidiasis)

Oral route :

In male and female adults:

The recommended dose of nystatin is 500,000 to 1 million units (tablets and oral suspension) PO three times a day with regular intervals in between them.

This treatment procedure should be continued for a minimum of 2 days after the clinical outcome is obtained in order to prevent the relapse of the infection.

What precautions are needed with nystatin?

You should always tell your doctor or pharmacist if you are allergic to nystatin. You should also tell him if you are allergic to any other medicine or if you have any other type of allergies including food, dyes, preservatives, or animals.

You should always tell your doctor or pharmacist about your medical history especially if you have suffered from or are currently suffering from diseases such as HIV disease, diabetes or kidney disease.

In case you are pregnant or are planning to get pregnant or breastfeeding then you should inform this to your doctor accordingly so that he can adjust the medication accordingly.

Use of nystatin in pregnancy and breastfeeding

Nystatin is included in pregnancy category C by the US Food and Drug Administration. This implies that the drug should be used with caution during pregnancy and should only be prescribed if the benefits of the drug are more than the risks.

There is not enough evidence of the safety of the drug in pregnant women because of the lack of well-controlled studies but still should be used with caution in pregnancy.

The drug is approved for use by nursing mothers since there is no data which suggests that the drug gets excreted into breast milk.

As the drug has very poor systemic absorption upon oral administration, therefore, it is considered that virtually the drug does not enter the bloodstream and as a result is not excreted in breast milk.

Mothers who are breastfeeding their children should be more careful and only apply water-miscible cream or gel preparations topically on the breast since ointments may expose the infant to high levels of paraffin while licking.

Before nursing, any excess cream should be removed from the nipples.

Can I use nysttin eith other antifungals?

Nystatin being an anti-fungal drug, if used in combination with other anti-fungal drugs can result in duplication of the dose and can result in toxicity of the drug.

These drugs included in this class are ketoconazole, econazole, miconazole, oxiconazole, sertaconazole, sulconazole. These all are anti-fungal agents and the concurrent use of these drug with nystatin should be avoided.

Can I use zinc oxide and nystatin together?

Zinc oxide is commonly used for the treatment of skin infections including mild skin irritations and abrasions.

Since nystatin is also used topically for the treatment of skin infections, using the two drugs concurrently can result in the duplication of therapy and this can lead to an overdose of the drug.

For this reason, it is recommended that the two drugs should not be used together especially when applied to the same place.

What are the storage conditions for nystatin?

The oral suspension of nystatin and nystatin tablets must be stored in tight, light-resistant containers and kept at room temperatures ranging in between 15°C to 30°C. Care must be taken to not to expose these formulations at temperatures greater than 40°C and neither should be kept in the refrigerator.
Nystatin powder formulation must be stored in tightly closed light-resistant containers at temperatures between 2°C – 8°C.
Topical preparations of nystatin should not be kept in a refrigerator at a temperature range between 15°C to 30°C. Special care should be done in order to prevent them from freezing.
Nystatin vaginal tablets must be stored at a temperature range of between 2°C – 8°C.

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