Anti-Fungal Agents

Drug MOA Indication ADRs

Amphotericin B
 - potent and broad spectrum - fungicidal effects at lower sporadic - IV adminsteration: causes chills, rigors,
(IV) antifungal agent
doses
nausea, headache (steroids and NSAIDS
- Binds ergosterol cell membrane to - Fungistatic since it sticks around for a bit
can be used to ↓ symptoms)
create pores→ ↑permeability → - Severe systemic mycoses
 (hypersensitivity reactions can occur -
fungicidal/-static effects (progressive + 
 give them steroids)

potentially fatal)
- Phelbitis can occur if admistration site is
- Slightly more Selective against not changed frequently

ergosterol (than cholestrol) - Nephrotoxicity prominent and extensive

( high dosage- permanent toxicity)
(minimized by infusion of saline prior to
drug dosage)

- Renal fx (creatinine) needs to be

monitored- make sure pts is hydrated

- Hypokalemia (replace K+ as part of

infusion preload)

Ketoconazole
- Inhibits ergosterol synthesis - safer oral alternative to ampho B
- N/V (reduced with intake of food)

- azoles: 3 groups resulting in leaky fungal cell - Drug response is slow —> useful for - Topical application is associated with few
of chemical membrane 
 long term chronic infections and less for systemic side effects but may cause
groupings: - fungistatic but fungicidal at acute, severe infections
burning, itching and irritation at site of
imidazoles, higher doses
- human cell steroid synthesis has caused application

triazoles, thiazole - Resistance is rare

gynecomastia and impotence due to - Systemic effects of oral agents may
- Txlast for months inhibition of testosterone synthesis and cause some GI distress

menstrual irregularities due to estradiol - These agents may elevate warfarin blood
synthesis inhibition.
levels by inhibiting hepatic metabolism –
- azoles: broad spectrum and useful for monitor INR, increased risk of bleeding.

systemic and/or superficial mycoses

- Onchymycosis therapy: (e.g.
- Onchomycosis therapy: extended daily ketoconazole or itraconazole)-
oral therapy; 1 week to 12 mos
hepatotoxicity of ketoconazole limits
extended use

Fluconazole Topical ADRs minimal


(burning/irritation)

Itraconazole (or 

Ketoconazole) Systemic (GI distress)
Miconazole

Clotrimazole

Griseofulvin 
 Deposits in keratin & Inhibits fungal PO for Superficial mycoses 
 - decreases warfarin efficacy through
(PO) mitosis (esp. tinea capitis) induction of hepativ metabolism- may
decrease INR

Nystatin Topical/PO 
 Intestinal candidiasis & mucosal candida N/V/D

Polyene Abx 
 infx 

(binds sterols in membrane→leaking) (ie oral thrush)

Tolnaftate - agents applied topically for superficial

mycoses
Undecylenic acid

Echinocandins (‘-fungin’)
Drug MOA Indication ADRs

Anidulafungin (IV admin)



- inhibits the creation of glucan in combined use of caspofungin and
the fungal cell wall by inhibiting cyclosporine augments liver enzymes more

1,3-β-D glucan synthase

than with cyclosporine alone. Combination
treatment is only indicated if benefit
outweighs risk

Caspofungin

Micafungin

Terbinafine directly inhibit squalene epoxidase Onychomycosis (PO) combo tx w/ azole

causing squalene to accumulate in
with tx lasting 6-12 weeks (adherence issue
fungi to toxic levels • inhibit with pts)

ergosterol synthesis


Naftifine Superficial dermatophytes (topical)

Systemic Mycoses “Mainstay”

- valuable class Tx drugs due to
of antifungals
- Opportunistic (immunocompromised hosts, Onchomycosis (nail infx) = Terbinafine + Azole (ie itraconazole)
oral availability and high penetration;
mainly)
for 6-12+ weeks
topical versions available

• Candidiasis
• Griseofulvin (6-12mo) = O.G. tx

• Aspergillosis
• ≠topical tx, which won’t reach nail bed

• Cryptococcosis

• Mucormycosis
Invasive Candida = Echinocandins

- Non-Opportunistic (in any host) Oral thrush = Nystatin or Clotrimazole (topicals)

• Sporotrichosis
• May need oral fluconazole or ketoconazole

• Blastomycosis
(ie in immunocompromised pt)
• Histoplasmosis

• Coccidioidomycosis

Most Antifungal agents are CYP3A4 inhibitors

- caution indicated for pts receiving concurrent drug

therapy where CYP3A4 is prominent drug
metabolism pathway

Ergosterol: 3 double bonds and tertiary methyl

group

- similar to cholestrol, part of fungal cell membrane

- Ergosterol is the primary target for antifungals—> so

the drugs used are inhibiting enzymes and pathways
that lead to ergosterol

Sites of drug action

Drug Contraindications Notes

Amphotericin B
 - resistance is low

(IV) - IV for deep mycotic

(systemic) infections
(infusions are slow
(over 2-4 hours)

- Pts receiving this

drug should be
hospitalized or at
least closely
supervised

Ketoconazole
- - PO with excellent
- azoles: 3 groups peripheral
of chemical distributions

groupings: - Poor distribution to

imidazoles, CNS

triazoles, thiazole - Entirely hepatically

metabolized (do LFT
to monitor Liver)-
monitor before,
monthly and after

- Because of the
compartments that
the fungi tend to
exist is difficultto get
drugs into those
compartment, thats
why tx last for a long
time. When we get
to oncomyses, toe
nails grow slowly, so
we need to get
meds into the toe
nail bed

Fluconazole

Itraconazole (or
Ketoconazole)

Miconazole

Clotrimazole

Griseofulvin 
 Treatment may last

(PO) from 3 weeks to a year
(toenails).

oral griseofulvin for

6-12 months was the
mainstay against
dermatophytic

onychomycosis.

Nystatin

Tolnaftate Not effective

against candida
Undecylenic acid
Drug Contraindications Notes

Anidulafungin PK: anidulafungin

significantly differs
from the others in that
it undergoes chemical
degradation to inactive
forms at body pH and

temperature. Because
it does not rely on
hepatic metabolism or
renal excretion, the
drug is relatively safe
for use in patients with
hepatic or renal
dysfunction

Caspofungin - caspofungin also

undergoes chemical
degradation, its
primary mode of
metabolism is through
slow peptide
hydrolysis and N-
acetylation in liver;
reduced dosage
should be considered
in hepatic impairment

Micafungin

Terbinafine

Naftifine
Table 1