1. ANTIFUNGAL AGENTS
By: Mrs. Kalaivani Sathish M. Pharm
Assistant Professor,
PIMS - PANIPAT
Dr Mrs Borkar 1
2. • Fungi are eukaryotic, heterotrophic organisms that
live as saprobes or parasites.
• Complex organisms in comparison to bacteria .
• Have nucleus and well defined nuclear membrane,
and chromosomes.
• Have rigid cell wall composed of chitin (bacterial
cell wall is composed of peptidoglycan)
• Fungal cell membrane contains ergosterol , human
cell mebmrane is composed of cholesterol
• Antibacterial agents are not effective against fungi.
• Fungal infections are also called as mycoses
ANTIFUNGAL AGENTS
Introduction
2Dr Mrs Borkar
3. ANTIFUNGAL AGENTS
• Systemic fungal infections are a major cause of death
in patients whose immune system is compromised
– cancer or its chemotherapy,
– organ transplantation
– HIV-1 infection.
• Superficial infections of the skin and other soft tissue
structures.
• Antifungal agents target
– distinctive components of the fungal cell membrane
– others alter cell wall synthesis
– nucleic acid synthesis
Introduction
3Dr Mrs Borkar
4. • Superficial : Affect skin – mucous membrane
– Tinea versicolor
– Dermatophytes : affect keratin layer of skin, hair, nail.
e.g.tinea pedis, ring worm infection
– Candidiasis : Yeast-like, oral thrush, vulvo-vaginitis , nail
infections.
• Deep Infections :
– Affect internal organs as : lung ,heart , brain leading to
pneumonia , endocarditis , meningitis.
ANTIFUNGAL AGENTS
Types of Fungal Infections
4Dr Mrs Borkar
7. • Antifungal agent with the broadest spectrum of activity
• Produced by Streptomyces nodosus.
• Natural, Amphoteric polyene macrolide –
– Amphoteric = can react as an acid as well as a base
– polyene = many double bonds
– macrolide = containing a large lactone ring
• Heptaene macrolide - large lactone ring with multiple ketone and
hydroxyl group)
• Drug of choice for the vast majority of life-threatening systemic
fungal infections
• Interacts with ergosterols, forms pores that increase membrane
permeability and allow leakage of intracellular ions &
macromolecules from fungal cell ( cell death ).
ANTIFUNGAL AGENTS
Amphotericin B
7Dr Mrs Borkar
8. • Broad range of pathogenic fungi
• Protozoa, Leishmania braziliensis and
Naegleria fowleri
• No antibacterial activity
• Amphotericin A & B are antifungal antibiotics.
• Amphotericin A is not used clinically.
ANTIFUNGAL AGENTS
Amphotericin B
8Dr Mrs Borkar
10. • Poorly absorbed orally, useful for fungal infection of
gastrointestinal tract.
• For systemic infections given as slow I/V infusion.
• Locally used in corneal ulcers, arthritis and candidial
bladder irrigation
• Highly protein bound - > 90%
• Penetration through BBB is poor but increases in inflamed
meninges.
• Excreted slowly via kidneys, traces found in urine for
months after cessation of drugs.
• Half life 15 days
ANTIFUNGAL AGENTS
Amphotericin - ADME
10Dr Mrs Borkar
12. 1. Slow IV infusion for systemic fungal disease.
2. Intrathecal for fungal CNS infections.
3. Topical drops & direct subconjunctival
injection for Mycotic corneal ulcers &
keratitis.
4. Local injection into the joints in fungal
arthritis.
5. Bladder irrigation in Candiduria.
ANTIFUNGAL AGENTS
Routes of Administration
12Dr Mrs Borkar
13. • Packaged in a lipid- associated delivery system
which acts as a reservoir
• Large doses can be administered – 5 times
• Reduces binding to human cell membrane
• Clinically have more efficacy , less nephrotoxicity
• More expensive
ANTIFUNGAL AGENTS
Amphotericin – Liposomal Preparations
13Dr Mrs Borkar
15. • Usual dose is 0.5–0.6 mg/kg, administered in 5% glucose over 4
hours
• Candida esophagitis, Rapidly progressive mucormycosis or invasive
aspergillosis .
• Coccidioides meningitis: Intrathecal infusion ; started with twice
weekly schedule , increased to thrice weekly and continued on twice-
weekly schedule.
• Treatment of cryptococcal meningitis, Severe or rapidly progressing
histoplasmosis, blastomycosis, coccidioidomycosis, penicilliosis
marneffei, invasive aspergillosis, extracutaneous sporotrichosis,
fusariosis, alternariosis, and trichosporonosis.
• Given once weekly to prevent relapse in patients with AIDS who have
been treated successfully for cryptococcosis or histoplasmosis.
ANTIFUNGAL AGENTS
Amphotericin B - Therapeutic Uses and Dosage
15Dr Mrs Borkar
16. • Major acute reaction to intravenous is fever and chills, which
typically end spontaneously in ~30 minutes and often abate with
subsequent infusions.
• Tachypnea and modest hypotension may occur, but true
bronchospasm or anaphylaxis is rare.
• Hypotension and hypoxia in preexisting cardiac or lung disease
• Prophylactic use of IV glucocorticoids decreases reaction
• Transient azotemia occurs in 80% of patients
• Kidney function may be affected if other nephrotoxic agents like
aminoglycoside are used concurrently.
• Administration of 1 L of NS IV prior to amphotericin B administration
is recommended for adults who can tolerate the Na+ load.
• Azotemia occurs less frequently with lipid preparations of
amphotericin, and saline loading is not needed.
ANTIFUNGAL AGENTS
Amphotericin B - Adverse effects
16Dr Mrs Borkar
17. • Hypochromic, normocytic anemia is usual and reverses
slowly following cessation of therapy.
• It is due decreased production of erythropoietin and often
responds to erythropoietin.
• Headache, nausea, vomiting, malaise, weight loss, and
phlebitis at peripheral infusion sites are common.
• Arachnoiditis, manifested by fever and headache, can
occur with intrathecal injection; it may be decreased by
intrathecal administration of 10–15 mg of hydrocortisone.
• Local injections of amphotericin B into a joint or peritoneal
dialysate fluid commonly produce irritation and pain.
ANTIFUNGAL AGENTS
Amphotericin B - Adverse effects
17Dr Mrs Borkar
18. Immediate reactions ( Infusion –related toxicity ).
• Fever, muscle spasm, vomiting ,headache, hypotension.
• Can be avoided by :
– Slowing the infusion
– Decreasing the daily dose
– Premedication with antipyretics, antihistamincs or corticosteroids.
– test dose.
Slower Reactions:
• Most serious is renal toxicity (nearly in all patients ).
• Hypokalemia
• Hypomagnesaemia
• Impaired liver functions
• Anemia, Thrombocytopenia
ANTIFUNGAL AGENTS
Amphotericin B - Adverse effects
18Dr Mrs Borkar
20. • Synthetic, water soluble, fluorinated pyrimidine analog
• Often used in combination with amphotericin B and
Itraconazole
• Spectrum of antigungal activity is considerably less than
that of amphotericin B.
• Amphotericin B increases cell permeability , allowing more
5-FC to penetrate the cell, they are synergistic
• Fungistatic
• Has useful activity against Candida and Cryptococcus.
• Acts by inhibiting synthesis of fungal DNA
ANTIFUNGAL AGENTS
Flucytosine
20Dr Mrs Borkar
21. • Absorbed rapidly and well from the GI tract, widely
distributed
• Minimally bound to plasma proteins.
• Penetrates well into CSF.
• Mainly excreted unchanged through kidney
• Half life drug normally is 3–6 hours but may reach
200 hours in renal failure.
• Dose modification is necessary in renal dysfunction
plasma concentrations should be measured
periodically
• Flucytosine is cleared by hemodialysis and
peritoneal dialysis
ANTIFUNGAL AGENTS
Flucytosine - ADME
21Dr Mrs Borkar
22. • Given orally at 100 mg/kg/day, in 4 divided doses
and is used predominantly in combination with
amphotericin B.
• Severe deep fungal infections as in meningitis
• Cryptococcal meningitis: begin with
amphotericin B plus flucytosine and change to
fluconazole after the patient has improved.
• There is the risk of amphotericin induecd
azotemia and flucytocine dose has to be reduced
in this situation otherwise the combination will
cause bone marrow suppression or colitis
ANTIFUNGAL AGENTS
Flucytosine – Uses
22Dr Mrs Borkar
23. • Hematologic : Leukopenia, thrombocytopenia,
bone marrow depression
• Allergic: Rash, nausea, vomiting, diarrhea, and
enterocolitis
• Hepatic: Elevation in hepatic transaminases but
this reverses when therapy is stopped.
• Toxicity is more frequent in patients with AIDS or
azotemia.
• Alopecia
ANTIFUNGAL AGENTS
Flucytosine – Adverse effects
23Dr Mrs Borkar
24. • Bacterial origin.
• Isolated from Streptomyces noursei in 1950
by Elizabeth Lee Hazen and Rachel Fuller
Brown,.
• Polyene macrolide ,similar in structure &
mechanism to amphotericin B.
• Too toxic for systemic use.
• Used only topically - available as creams,
ointment , suppositories & other
preparations.
ANTIFUNGAL AGENTS
Nystatin/Nysfungin
24Dr Mrs Borkar
25. • Prevent or treat superficial candidiasis of mouth,
esophagus, intestinal tract.
• Oral suspension of 100,000 U/ml 4 times a day and
tablets 500,000 U are used to decrease GIT
colonization with Candida
• Vaginal candidiasis - pessaries used for 2 weeks
• Can be used in combination with antibacterial
agents & corticosteroids
• In Cutaneous infection available in cream, ointment
or powder form and applied 2-3 times a day
ANTIFUNGAL AGENTS
Nystatin/Nysfungin – Clinical uses
25Dr Mrs Borkar
26. • Bivalent chemical group composed of five-membered
organic rings
• Broad spectrum of activity - Antibacterial, antiprotozoal,
anthelminthic and antifungal.
• Group of synthetic fungistatic agents
• Classification: according to the number of nitrogen atoms
attached to the ring
– Imidazoles (2 nitrogen atoms): Ketoconazole,
Miconazole, Econazole, Clotrimazole, Bifonazole
– Triazoles (3 nitrogen atoms): Itraconazole, Fluconazol,
Vorionazole → systemic treatment
ANTIFUNGAL AGENTS
Azole Antifungals
26Dr Mrs Borkar
27. • Cryptococci, Blastomyces, Histoplasma
capsulatum, Coccidioides , Paracoccidioides
brasiliensis, and dermatophytes.
• Aspergillus spp., Scedosporium,
apiospermum (Pseudallescheria boydii),
Fusarium, and Sporothrix schenckii are
intermediate in susceptibility.
• C. krusei and the agents of mucormycosis are
resistant.
ANTIFUNGAL AGENTS
Azole - antifungal activity
27Dr Mrs Borkar
28. • Inhibit the fungal cytochrome
P450 enzyme
• Responsible for converting
lanosterol to ergosterol ( the
main sterol in fungal cell
membrane ).
ANTIFUNGAL AGENTS
Azole Antifungals- Mechanism of Action
28Dr Mrs Borkar
29. • Contain 2 Nitrogen atoms attached to the ring
• Reduce the formation of ergosterol in the cell
membrae which become permeable to cellular
constituents.
• They lack selectivity, and also inhibits human
gonadal and steroid synthesis leading to decreased
testosterone and cortisol production
• Ketoconazole,
• miconazole,
• clotrimazole,
• isoconazole ,
• Tioconazole
ANTIFUNGAL AGENTS
Azole Antifungals- Imidazoles
29Dr Mrs Borkar
31. • Well absorbed orally as acidic environment favors its
dissolution.
• Bioavailability is impaired with food.
• Cola drinks improve its absorption in patients with
achlorhydria.
• Metabolized extensively in liver and inactive products
appear in the feces.
• Moderate hepatic dysfunction has no effect on drug
concentration.
• 84 % is bound to plasma proteins.
• Half life increases with dose
• It does not enter CSF.
ANTIFUNGAL AGENTS
Imidazole – Ketoconazole- ADME
31Dr Mrs Borkar
32. • Inhibits adrenal and gonadal steroids which leads to
menstrual irregularities, loss of libido, impotency and
gynaecomastia in males.
• Efficacy is poor in immunosuppressed patients and
in meningitis.
• Hepatotoxic - rare but may prove fatal.
• Dose dependant nausea, anorexia ,vomiting
• Hair loss
• Fluid retention and hypertension.
• Not used in Pregnancy, lactation ,hepatic dysfunction
ANTIFUNGAL AGENTS
Imidazole – Ketoconazole – Adverse Effects
32Dr Mrs Borkar
33. Decrease in the
ergosterol in the
fungal membrane
By ketoconazle
reduces
the fungicidal
action of
amphotericin
33Dr Mrs Borkar
34. Used topically or systematic (oral route only ) to treat
1. Oral & vaginal candidiasis.
2. Dermatophytosis.
3. Systemic mycoses & mucocutaneous candidiasis.
ANTIFUNGAL AGENTS
Imidazole – Ketoconazole – Clinical uses
34Dr Mrs Borkar
35. Ketoconazole is
not useful for
fungal infections of
UT
as level of parent
drug in urine is
very low
35Dr Mrs Borkar
36. • Bioavailability is low by taking orally.
• Used topically.
• Absorption less than 0.5 % from intact skin, 3-10 %
from vagina
• Activity in vagina remains for 3 days.
• Stigma, erythema, edema, vesication, pruritus,
urticaria mild vaginal burning sensation may occour.
• Cure dermatophytes, cutaneous candidiasis and
vulvovaginal candidiasis
ANTIFUNGAL AGENTS
Imidazole – Clotrimazole
36Dr Mrs Borkar
37. • Damage the fungal cell membrane by inhibiting
enzyme desmethylase
• They are selective
• Penetrate to CNS
• Resistant to degradation
• Cause less endocrine disturbance.
• Fluconazole,
• itraconazole,
• voriconazole
ANTIFUNGAL AGENTS
Azole Antifungals- Triazoles
37Dr Mrs Borkar
38. • It is a synthetic triazole, new drug
• Lacks endocrine side effects of ketoconazole.
• Broad spectrum activity
• Administered orally as well as I/V.
• Food increases its absorption
• Metabolized in liver to active metabolite
• Highly lipid soluble ,well distributed to bone, sputum,
adipose tissues.
• Can not cross BBB
ANTIFUNGAL AGENTS
Azole antifungals – Itraconazole
38Dr Mrs Borkar
39. • Food increases its absorption
• Metabolized in liver extensively
• It is highly lipid soluble and well distributed to
bone, sputum and adipose tissue.
• Highly bound to plasma protein
• Half life is 30-40 hours
• Does not penetrate CSF adequately
• The capsule is better absorbed with food, but the
oral solution is better absorbed in the fasting
state
ANTIFUNGAL AGENTS
Itraconazole- ADME
39Dr Mrs Borkar
40. ANTIFUNGAL AGENTS
Azole antifungals – Itraconazole - Therapeutic Uses
• Available as a capsule and solutions for oral or intravenous
administration
• Oral solution is 60% more bioavailable than the capsules
• IV only in serious infections.
• Dose – Cap 200 to 400 mg/day
• doses exceeding 200 mg/day are given in 2 divided doses
• Loading dose: 200 mg 3 times daily can be given for the first 3
days
• The only agent with significant activity against aspergillus species
• It can safely be administered prophylactically in patients receiving
bone marrow transplants
40Dr Mrs Borkar
41. • Dermatophytoses and onychomycosis.
• Onychomycosis - 200 mg daily after food for 3 months
• For deep mycoses, loading dose of 200 mg three times
daily for 3 days. Thereafter, two 100-mg capsules are given
twice daily with food.
• Histoplasmosis : AIDS-associated histoplasmosis
maintainance therapy - 200 mg once daily
• It easily penetrate CSF and is a drug of choice in
cryptococcal meningitis and coccido mycosis
• Cryptococcosis: 400 mg daily for 8 weeks in meningitis, In
AIDS 200 mg for life.
ANTIFUNGAL AGENTS
Azole antifungals – Itraconazole - Therapeutic Uses
41Dr Mrs Borkar
42. • Itraconazole solution - for oropharyngeal and esophageal
candidiasis.
• Taken fasting in a dose of 100 mg once daily and swished
vigorously in the mouth before swallowing to optimize topical
effect.
• 100 mg of the solution twice a day for 2–4 weeks.
• Candidiasis: 200 mg on 1st day then 100 mg daily for 2 weeks.
• Not effective in aspergillosis.
• Used orally in dermatophytosis & vulvo-vaginal candidiasis.
ANTIFUNGAL AGENTS
Azole antifungals – Itraconazole - Therapeutic Uses
42Dr Mrs Borkar
43. • Interact with many drugs
• Interactions can cause serious toxicity
• Fatal cardiac arrhythmias.
• Congestive heart failure in patients with impaired
ventricular function.
• Hepatic failure and death. If symptoms of hepatotoxicity
occur, the drug should be discontinued and liver function
assessed.
• Anaphylaxis and severe rash have rarely occurred.
ANTIFUNGAL AGENTS
Itraconazole – Adverse Effects
43Dr Mrs Borkar
44. • Relative to capsules, the oral solution of
itraconazole more frequently causes diarrhea,
abdominal cramps, anorexia, and nausea.
• Intravenous itraconazole has all the adverse
effects of capsules but generally is well tolerated.
• Chemical phlebitis: dedicated catheter port is
required,
• Infusion durations >1 hour are recommended.
• Intravenous formulation is contraindicated in
patients with a creatinine clearance <30 mL/min.
ANTIFUNGAL AGENTS
Itraconazole – Adverse Effects
44Dr Mrs Borkar
45. • The adverse effects are related to dose and duration of use
• In the absence of interacting drugs, itraconazole capsules
are well tolerated at 200 mg daily.
• GI distress occurs with use of 300 mg/day or more
• In patients receiving 50–400 mg/day, nausea and vomiting,
hypertriglyceridemia, hypokalemia, elevated serum
aminotransferases, and rash occurred in few patients
• Doses of 300 mg twice daily have led to adrenal
insufficiency, lower limb edema, hypertension, and
rhabdomyolysis
• Doses above 400 mg/day are not recommended for long-
term use
ANTIFUNGAL AGENTS
Itraconazole – Adverse Effects
45Dr Mrs Borkar
46. • It is fluorinated bistriazole.
• The widest therapeutic index of the azoles.
• Excellent bioavailability by oral route.
• Bioavailability not altered by food or gastric acidity
• Not hepatotoxic
• It can safely be administered prophylactically in patients
receiving bone marrow transplants.
• Maximum excretion by kidney
• Half life is 25-30 hours.
ANTIFUNGAL AGENTS
Fluconazole - ADME
47Dr Mrs Borkar
47. • Fluconazole is almost completely absorbed
from the GI tract irrespective of food or gastric
acidity.
• Concentration in plasma is same by oral or I/v
route.
• Only 10% of drug in circulation is protein
bound.
• Readily diffuses into body fluids, including
breast milk, sputum, saliva, and CSF.
ANTIFUNGAL AGENTS
Fluconazole - ADME
48Dr Mrs Borkar
48. • Tablets for oral administration
• Powder for oral suspension
• Intravenous solutions containing 2 mg/mL.
• Dosage is 50–800 mg once daily for oral or
intravenous administration.
• Children are treated with 3–6 mg/kg once
daily
ANTIFUNGAL AGENTS
Fluconazole - Dosage
49Dr Mrs Borkar
49. • Candidiasis - 200 mg on the first day and then 100 mg daily
for at least 2 weeks, in oropharyngeal candidiasis.
• single dose of 150 mg is effective in uncomplicated vaginal
candidiasis.
• 400 mg daily in deep candidiasis in allogeneic bone marrow
transplant recipients
• Systemic fungal infections
– 400-800 mg q24h
– > 800 mg q24h in unstable patient
• Maintenance for cryptococcal meningitis - 400 mg/day, for
the initial 8 weeks in the treatment in AIDS after the
patient has been stabilized with intravenous amphotericin
ANTIFUNGAL AGENTS
Fluconazole - Uses
50Dr Mrs Borkar
50. • Nausea and vomiting at doses >200 mg/day
• Headache, skin rash, abdominal pain, and diarrhea
• Reversible alopecia may occur with prolonged
therapy
• Rare deaths due to hepatic failure or Stevens-
Johnson syndrome have occurred.
• Highly teratogenic: Associated with skeletal and
cardiac deformities in infants born to women taking
high doses during pregnancy and should be avoided
during pregnancy
ANTIFUNGAL AGENTS
Fluconazole – Adverse effects
51Dr Mrs Borkar
51. • Fungistatic in vitro for various species of
dermatophytes.
• Inhibits fungal mitosis
52Dr Mrs Borkar
ANTIFUNGAL AGENTS
Griseofulvin
52. • Entirely local action, no systemic absorption
• Micronized and ultramicronized powders are used to
facilitate dissolution
• Half life in plasma of ~1 day.
• Deposited in keratin precursor cells and persists in keratin
to provide prolonged resistance to fungi.
• The new growth of hair or nails is the first to become free
of disease.
• As the fungus-containing keratin is shed, it is replaced by
normal tissue.
• Griseofulvin is detectable in the stratum corneum within 4–
8 hours of oral administration.
53Dr Mrs Borkar
ANTIFUNGAL AGENTS
Griseofulvin - ADME
53. • Mycotic infections of the hair (tinea capitis)
• Tinea of the hands and beard
• “Athlete’s foot” or epidermophytosis involving
the skin and nails
• Not effective in treatment of subcutaneous or
deep mycoses
54Dr Mrs Borkar
ANTIFUNGAL AGENTS
Griseofulvin - Uses
54. • 5–15 mg/kg for children
• 0.5–1 g for adults in 4 divided doses
• Severe infections: 1.5–2 g daily for short periods
• Best results are obtained
• Treatment must be continued until infected tissue is
replaced by normal hair, skin, or nails, which
requires 1 month for scalp and hair ringworm, 6–9
months for fingernails, and at least a year for
toenails.
55Dr Mrs Borkar
ANTIFUNGAL AGENTS
Griseofulvin - Dosage
55. • Headache, GI symptoms (e.g., nausea, vomiting,
diarrhea, heartburn, flatulence), and rash.
• More serious reactions include hepatotoxicity,
serum sickness reaction, angioedema, and
hematologic effects (e.g., leukopenia, neutropenia,
punctate basophilia, and monocytosis).
• Blood should be checked weekly during treatment.
• Estrogen-like effects have been observed in
children.
56Dr Mrs Borkar
ANTIFUNGAL AGENTS
Griseofulvin – adverse effects
56. • Topical treatment is useful in superficial fungal infections
confined to the stratum corneum, squamous mucosa, or
cornea, including dermatophytosis (ringworm), candidiasis,
tinea versicolor, piedra, tinea nigra, and fungal keratitis.
• Unsuccessful for mycoses of the nails (onychomycosis) and
hair (tinea capitis)
• No place in subcutaneous mycoses, such as sporotrichosis
and chromoblastomycosis.
• Efficacy of topical agents depends not only on the type of
lesion and the mechanism of drug action, but also on the
viscosity, hydrophobicity, and acidity of the formulation.
57Dr Mrs Borkar
ANTIFUNGAL AGENTS
Topical Antifungal Agents
57. • Regardless of formulation, penetration of topical
drugs into hyperkeratotic lesions often is poor.
• Removal of thick, infected keratin may be a useful
adjunct to therapy.
• Preferred formulations are
– Creams
– Solutions
– Powders, whether applied by shake containers or
aerosols, largely are used for the feet and moist
lesions of the groin and other intertriginous areas
58Dr Mrs Borkar
ANTIFUNGAL AGENTS
Topical Antifungal Agents
59. • Used in superficial fungal infections:
– Dermatophytosis ( ring worm)
– Candidiasis
– Fungal keratitis.
• Not effective in mycoses of the nails & hair or
subcutaneous mycoses.
• Preferred formulation for cutaneous application
is cream or solution.
60Dr Mrs Borkar
ANTIFUNGAL AGENTS
Topical Antifungal Agents
60. • Indications for topical use include
– tinea corporis
– tinea pedis
– tinea cruris
– tinea versicolor
– cutaneous candidiasis.
• Agents for topical use should be selected based on cost
and availability.
• They are applied twice daily for 3–6 weeks.
• Preparations for cutaneous use are effective for
61Dr Mrs Borkar
ANTIFUNGAL AGENTS
Topical Antifungal Agents - Azoles
61. • Creams, suppositories, and tablets for vaginal candidiasis
• 5 gm, Used once daily for 1–7 days, preferably at bedtime to
facilitate retention.
• Three vaginal formulations—
– clotrimazole tablets,
– miconazole suppositories,
– Terconazole cream
• Come in both low- and high-dose preparations.
• Shorter duration of therapy is recommended for the higher
doses.
• The action is local and only little is absorbed
• Most common side effect is vaginal burning or itching.
• A male sexual partner may experience mild penile irritation.62Dr Mrs Borkar
ANTIFUNGAL AGENTS
Topical Antifungal Agents – Vaginal Applications