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Antifungals

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By Iris Dawn Tabangcora, RN

Antifungals are used to treat mycosis, or infections caused by fungi. Fungi are different from bacteria in the sense that their cell walls are made up of chitin and various polysaccharides rendering these organisms resistant to antibiotics.

There is an increased incidence of fungal infections in immunocompromised patients (e.g., patients with AIDS, those taking immunosuppressants like organ transplant recipients, etc.).

Antifungals can be systemic and/or topical.

  • Systemic antifungals are used to treat systemic mycoses and can be toxic to the host and not to be used indiscriminately. It is important to get a culture of the fungus causing the infection to ensure that the right drug is being used so that the patient is not put at additional risk from the toxic adverse effects associated with these drugs.
  • Topical antifungals are used to treat a variety of mycoses of skin and mucous membranes. Some systemic antifungals have topical forms.

Table of Contents

Antifungals: Generic and Brand Names

Here is a table of commonly encountered antifungals, their generic names, and brand names:

  • Systemic Antifungals
    • Azole Antifungals
      • fluconazole (Diflucan)
      • itraconazole (Sporanox)
      • ketoconazole (Nizoral, Xolegel)
      • terbinafine (Lamisil)
      • voriconazole (VFend)
    • Echinocandin Antifungals
      • anidulafungin (Eraxis)
      • caspofungin acetate (Cancidas)
      • micafungin (Mycamine)
    • Other systemic antifungals
      • amphotericin B ( Abelcet, Amphotec)
      • flucytosine (Ancobon)
      • griseofulvin
      • nystatin (Mycostatin, Nilstat)
  • Topical Antifungals
    • Azole Topical Antifungals
      • butoconazole (Gynazole I)
      • clotrimazole (lotrimin, Mycelex)
      • ketoconazole (Extina, Xolegel)
      • miconazole (Monistat, Fungoid)
      • oxiconazole (Oxistat)
      • sertaconazole nitrate (Ertaczo)
      • sulfonazole (Exelderm)
      • terbinafine (Lamisil)
      • terconazole (Terazol)
      • tioconazole (Monistat-1, Vagistat-1)
    • Other topical antifungals
      • ciclopirox (Loprox, Penlac Nail Lacquer)
      • gentian violet
      • naftifine (Naftin)
      • tolnaftate (Aftate, Tinactin)
      • undecylenic acid (Cruex, Desenex)

Azole Antifungals

Azoles are antifungals used to treat systemic and topical fungal infections. They are less-toxic compared to other antifungals but they may also be less effective.   

Therapeutic Action

The desired and beneficial action of azoles is:

  • Either binding to sterols and cause cell death or interfering with cell replication.
  • Ketoconazole, fluconazole, and itraconazole block the activity of a sterol in a fungal wall. Therefore, they may also block the activity of human steroids such as testosterone and cortisol.
  • Posaconazole, a new drug, inhibit the synthesis of ergosterol leading to inability of the fungus to form cell wall.
  • Terbinafine blocks the formation of ergosterol.

Indications

Azoles are indicated for the following medical conditions:

  • Treatment for candidiasis, cryptococcal meningitis, systemic mycoses, aspergillosis, among others.

Here are some important aspects to remember for indication of antifungals in different age groups:

Children

  • This population is more sensitive to the effects of antifungals so more severe adverse reactions may be expected from them.
  • Only fluconazole, ketoconazole, terbinafine, and griseofulvin have established pediatric doses.
  • Topical agents are avoided on open or draining areas to avoid systemic absorption. Also, occlusive dressings, including tight diapers, should be avoided over the affected areas.

Adults

  • This age group widely use over-the-counter antifungals and it should be emphasized to them that antifungals can be very toxic so usage is only justified when causative organism is identified.
  • Pregnant and lactating women should be advised that usage of this drug should only be in situations where the benefits clearly outweigh the risks.
  • As for women of childbearing age, barrier contraceptives should be employed. Lastly, antifungals should not be used over open or draining areas as this can facilitate systemic absorption.

Older adults

  • They are more susceptible to the adverse effects of the drug, especially those with hepatic and renal dysfunction. In such cases, doses are needed to be lowered.

Pharmacokinetics

Here are the characteristic interactions of azoles and the body in terms of absorption, distribution, metabolism, and excretion:

RouteOnsetPeakDuration
OralSlow1-2 h2-4 d
IVRapid1 h2-4 d
Half-life (T1/2)MetabolismExcretion
30 hliverkidney (urine)

Contraindications and Cautions

The following are contraindications and cautions for the use of azoles:

  • Hepatic dysfunction. Ketoconazole, fluconazole, posaconazole, and terbinafine can cause serious hepatic toxicity. Patients are carefully monitored for bone marrow suppression and GI and liver toxicity if using these drugs, particularly posaconazole.
  • Endocrine or fertility problems. Ketoconazole is absolutely contraindicated in patients with this condition because of its effects on these processes. Fluconazole can be the alternative drug but it can cause liver and/or renal toxicity. Caution is exercised.
  • Pregnancy and lactation. Not known whether most azoles cross placenta or enter breastmilk. However, terbinafine is known to do so.
  • Patients taking drugs that can prolong QTc interval. Voriconazole and these drugs can worsen condition and can cause ergotism if taken with ergot alkaloids.

Adverse Effects

Use of azoles may result to these adverse effects:

  • GI: liver toxicity
  • Severe effects on a fetus or a nursing babies

Interactions

The following are drug-drug interactions involved in the use of azoles:

  • Cyclosporine, digoxin, oral hypoglycemics, warfarin, oral anticoagulants, phenytoin: increased serum levels of these drugs when ketoconazole and fluoconazole are also being taken by the patient. The two drugs strongly inhibit CYP450 enzyme system.
  • Statins, triazolam, midazolam, pimozide, dofetilide: serious cardiac effects together with itraconazole
  • Ergot alkaloids: ergotism if taken with posaconazole and voriconazole

Echinocandin Antifungals

Echinocandin antifungals include anidulafungin, caspofungin, and micafungin.

Therapeutic Action

The desired and beneficial action of echinocandin antifungals is:

  • Inhibiting glucan synthesis. Glucan is an enzyme that is present in the fungal cell wall but not in human cell walls. Fungal cell wall cannot be formed if glucan is destroyed.

Indications

Echinocandin antifungals are indicated for the following medical conditions:

  • Treatment of candidemia and other forms of Candida infection
  • Treatment of invasive aspergillosis in patients who do not respond or are intolerant to other therapies
  • Prophylaxis of Candida infections in patients with hematopoietic stem cell transplant

Pharmacokinetics

Here are the characteristic interactions of azoles and the body in terms of absorption, distribution, metabolism, and excretion:

Anidulafungin

RouteOnsetPeakDuration
Anidulafungin IVRapidN/AN/A
Half-life (T1/2)MetabolismExcretion
40-50 hlivercolon (feces)

Caspofungin

RouteOnsetPeakDuration
Caspofungin IVRapidN/AN/A
Half-life (T1/2)MetabolismExcretion
9-11 h, then 6-48 h, then 40-50 hliverkidney (urine)

Micafungin

RouteOnsetPeakDuration
Micafungin IVRapidN/AN/A
Half-life (T1/2)MetabolismExcretion
14-17 hliverkidney (urine)

Contraindications and Cautions

The following are contraindications and cautions for the use of echinocandin antifungals:

  • Anidulafungin. May cross placenta and enter breastmilk. Caution is also used in the presence of hepatic impairment.
  • Caspofungin. It is embryotoxic in animal studies and known to enter breast milk.
  • Micafungin. Should only be used in pregnant and lactating patients if benefits clearly outweigh the risks.

Adverse Effects

Use of echinocandin antifungals may result to these adverse effects:

  • GI: hepatic toxicity
  • Serious hypersensitivity reactions, particularly with micafungin
  • Immunological: bone marrow depression

Interactions

The following is drug-drug interaction involved in the use of echinocandin antifungals:

  • Cyclosporine: concurrent use with caspofungin is contraindicated

Other Antifungal Agents

  • Other antifungal agents include amphotericin B, flucytosine, griseofulvin, and nystatin.  

Therapeutic Action

The desired and beneficial action of other antifungal agents are:

  • Causing fungal cell death (fungicidal) and preventing fungal cell reproduction (fungistatic)
  • Amphotericin B binds to sterols in the fungus cell wall, changing the cell wall permeability. It is a very potent drug with many unpleasant adverse effects.
  • Flucytosine is a less toxic drug that alters the cell membrane of susceptible fungi, causing cell death. Griseofulvin acts in much the same way.
  • Nystatin binds to sterols in the cell wall, changing permeability and allowing cellular component leakage.

Indications

Azoles are indicated for the following medical conditions:

  • Treatment of progressive, potentially fatal infections due to many adverse effects
  • Treatment of systemic infections caused by Candida or Cryptococcus
  • Treatment of variety of tinea infections caused by Trichophyton spp.

Pharmacokinetics

Here are the characteristic interactions of other antifungals and the body in terms of absorption, distribution, metabolism, and excretion:

Amphotericin B and flucytosine

RouteOnsetPeakDuration
Amphotericin B and flucytosine IVRapid2 h for flucytosineN/A
Half-life (T1/2)MetabolismExcretion
24 h, then 15 daysnot well understoodkidney (urine)

Griseofulvin

RouteOnsetPeakDuration
Griseofulvin PON/A4 hN/A
Half-life (T1/2)MetabolismExcretion
24 hliverkidney (urine)

Contraindications and Cautions

The following are contraindications and cautions for the use of other antifungals:

  • Amphotericin B. Successfully used during pregnancy but caution must be used. This is contraindicated during lactation because it can cause potential risk to the neonate.
  • Flucytosine. Extreme caution in patients with renal impairments. Toxicity can occur at 100 mcg/mL.
  • Nystatin. Not be used during pregnancy and for lactating patients because effects are not known.

Adverse Effects

Use of other antifungals may result to these adverse effects:

Interactions

The following are drug-drug interactions involved in the use of other antifungals:

  • Nephrotoxic antibiotics, antineoplastics, cyclosporine, corticosteroids: not combined with amphotericin B because of inreased risk of severe renal toxicity

Nursing Considerations

Here are important nursing considerations when administering systemic antifungals:

Nursing Assessment

These are the important things the nurse should include in conducting assessment, history taking, and examination:

  • Assess for the mentioned cautions and contraindications (e.g. known history of allergy to antifungals, liver and kidney dysfunction, pregnancy and lactation, etc.) to prevent any untoward complications.
  • Perform a thorough physical assessment (other medications taken, orientation and reflexes, skin color and lesions, etc.) to establish baseline data before drug therapy begins, to determine effectiveness of therapy, and to evaluate for occurrence of any adverse effects associated with drug therapy.
  • Obtain a culture of the infected area to make an accurate determination of the type and responsiveness of the fungus.
  • Evaluate renal and hepatic function tests and complete blood count to determine baseline function of these organs and to assess possible toxicity during drug therapy.

Nursing Diagnoses

Here are some of the nursing diagnoses that can be formulated in the use of this drug for therapy:

  • Acute pain related to GI, CNS, and local drug effects
  • Disturbed sensory perception (kinesthetic) related to CNS effects

Implementation with Rationale

These are vital nursing interventions done in patients who are taking systemic antifungals:

  • Check culture and sensitivity reports to ensure that this is the drug of choice for this patient.
  • Ensure that patient receives full course of antifungals as prescribed (may take up to 6 months for chronic infection), to get the full beneficial effects.
  • Monitor IV sites to ensure that phlebitis or infiltration does not occur.
  • Provide safety measures (e.g.side rails and assistance with ambulation, antipyretics for fever and chills, temperature regulation for fever, etc.) to protect the patient if CNS effects (e.g. confusion, disorientation, numbness) occur.
  • Provide small, frequent, nutritious meals if GI upset is severe. Monitor nutritional status and arrange a dietary consultation as needed to ensure nutritional status.
  • Advise patient to report sore throat, unusual bruising or bleeding, or yellowing of eyes and skin, all of which could indicate hepatic toxicity; or severe nausea and vomiting, which could interfere with nutritional state and slow recovery.
  • Educate client on drug therapy to promote understanding and compliance.

Evaluation

Here are aspects of care that should be evaluated to determine effectiveness of drug therapy:

  • Monitor patient response to therapy (resolution of fungal infections).
  • Monitor for adverse effects (e.g. orientation and affect, nutritional state, skin color and lesions, renal and hepatic function, etc).
  • Evaluate patient understanding on drug therapy by asking patient to name the drug, its indication, and adverse effects to watch for.
  • Monitor patient compliance to drug therapy.

Topical Antifungals

  • Topical antifungals are used to treat a variety of mycoses of skin and mucous membranes. Some systemic antifungals have topical forms.
  • Fungi causing these mycoses are called dermatophytes.

Therapeutic Action

The desired and beneficial action of topical antifungals is:

  • Altering the cell permeability of the fungus, causing prevention of replication and fungal death.

Indication

Topical antifungals are indicated for the following medical conditions:

  • Local treatment for mycoses, including tinea infections.

Pharmacokinetics

Topical antifungals are not absorbed systemically. Pharmacokinetics is unknown.

Contraindications and Cautions

The following are contraindications and cautions for the use of topical antifungals:

  • Known allergy to topical antifungals.
  • Econazole can cause intense, local burning, and irritation. Drug should be discontinued upon evidence of these manifestations.
  • Gentian violet stains skin and clothing bright purple. It can also be very toxic so it should be applied near active lesion.
  • Naftifine, oxiconazole, and sertaconazole should not be used for longer than 4 weeks due to the risk of adverse effects and possible emergency of resistant fungal strains. Sulconazole should not be used for longer than 6 weeks for the same reasons.

Adverse Effects

Use of topical antifungals may result to these adverse effects:

  • Local: irritation, burning, rash, swelling
  • GI: nausea, vomiting, hepatic dysfunction (especially when they are taken as suppository or troche)
  • GU: urinary frequency, burning, change in sexual activity (related to local absorption in the vagina)

Nursing Considerations

Here are important nursing considerations when administering topical antifungals:

Nursing Assessment

These are the important things the nurse should include in conducting assessment, history taking, and examination:

  • Assess for the mentioned cautions and contraindications (e.g. known history of allergy to antifungals) to prevent any untoward complications.
  • Perform a thorough physical assessment (other medications taken, skin color, temperature, and lesions, etc.) to establish baseline data before drug therapy begins, to determine effectiveness of therapy, and to evaluate for occurrence of any adverse effects associated with drug therapy.
  • Obtain a culture of the infected area to make an accurate determination of the type and responsiveness of the fungus.

Nursing Diagnoses

Here is the nursing diagnosis that can be formulated in the use of this drug for therapy:

  • Acute pain related to local drug effects

Implementation with Rationale

These are vital nursing interventions done in patients who are taking topical antifungals:

  • Check culture and sensitivity reports to ensure that this is the drug of choice for this patient.
  • Ensure that patient receives full course of antifungals as prescribed to get the full beneficial effects.
  • Instruct patient in the correct method of administration, depending on the route, to improve effectiveness and decrease the risk of adverse effects.
    •  Troches should be dissolved slowly in the mouth.
    •  Vaginal suppositories, creams, and tablets should be inserted high into the vagina with the patient remaining recumbent for at least 10-15 minutes after insertion.
    •  Topical creams and lotions should be gently rubbed into the affected area after it has been cleansed with soap and water and patted dry. Occlusive bandages should be avoided.
  • Advise patient to stop the drug if a severe rash occurs, especially if it is accompanied by blisters or if local irritation and pain are very severe. This development may indicate drug sensitivity or worsening of condition being treated.
  • Educate client on drug therapy to promote understanding and compliance.

Evaluation

Here are aspects of care that should be evaluated to determine effectiveness of drug therapy:

  • Monitor patient response to therapy (resolution of fungal infections).
  • Monitor for adverse effects (e.g. rash, local irritation, burning, etc).
  • Evaluate patient understanding on drug therapy by asking patient to name the drug, its indication, and adverse effects to watch for.
  • Monitor patient compliance to drug therapy.

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References and Sources

References and sources for this pharmacology guide for Antifungals:

  • Karch, A. M., & Karch. (2011). Focus on nursing pharmacology. Wolters Kluwer Health/Lippincott Williams & Wilkins. [Link]
  • Katzung, B. G. (2017). Basic and clinical pharmacology. McGraw-Hill Education.
  • Lehne, R. A., Moore, L. A., Crosby, L. J., & Hamilton, D. B. (2004). Pharmacology for nursing care.
  • Smeltzer, S. C., & Bare, B. G. (1992). Brunner & Suddarth’s textbook of medical-surgical nursing. Philadelphia: JB Lippincott.
Iris Dawn is a nurse writer in her 20s who is on the constant lookout for latest stories about Science. Her interests include Research and Medical-Surgical Nursing. She is currently furthering her studies and is seriously considering being a student as her profession. Life is spoiling her with spaghetti, acoustic playlists, libraries, and the beach.

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